Chinese Remedies for Low Platelet Count

Conquer Low Platelets

Alternative And Natural Therapies For Itp (idiopathic Thrombocytopenia Purpura). Live Free From Itp. Complete Program To Increase Platelets. This Is What You Will Learn With this Guide: The Two Herbs That can help bring up your platelets. The Two Vitamins needed to keep those platelets from dropping. What foods may cause your platelets to drop. How science has confirmed the benefits of these herbs in their use with low platelets. Why your doctor may not know about these natural alternatives and how you can assist him in helping you. Different tests that naturopathic doctors do to determine your real state of health that may reverse the course of your body drastically. Understand some of the reasons why people develop low platelets. Discover how your digestive tract may be the culprit to your low platelet level problems. How you can prevent the most drastic step a splenectomy. How you can restore your health so that you dont need any more dangerous drugs. Get your life back and stop ending up in the hospital all the time. Learn why your immune system is attacking your platelets and how to calm it down. Learn what over the counter medications to stay away from if you have low platelets Read more...

Conquer Low Platelets Overview

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Thrombocytopenia

Hematologic malignancies frequently present with symptoms due to absolute and or functional thrombocytopenia. Currently, platelet transfusion remains the only proven method leading to rapid rise in platelet counts. The exact role and optimal dosing of the only approved platelet-lineage specific agent, IL-11, either in the prevention of the need for platelet transfusion or as a facilitator of platelet recovery, is unclear.89 Advanced clinical studies of thrombopoietin-like agents in patients with autoimmune thrombocytope-nia are in progress .

Laboratory Abnormalities In Hyperleukocytosis

Pseudohyperkalemia can be present in patients with a high white blood count secondary to breakdown of white cells in vitro with subsequent release of potas-sium.2 Other spurious laboratory data that can be seen in association with hyperleukocytosis include a falsely elevated platelet count (secondary to white cell fragments), pseudohypoxemia (secondary to oxygen consumption by leukocyte cells), falsely prolonged coagulation tests, and pseudohypoglycemia.421-24 Pseudohypoxemia and pseudohypoglycemia can be avoided by placing samples on ice and performing tests immediately.4,14

With Antithrombotic And Antiplatelet Drugs

A number of factors may contribute to limited efficacy of UFH. These include the need for antithrombin for its action, and reduced effectiveness of the heparin-antithrombin complex in the presence of fibrin monomers. The release of platelet factor 4 in response to heparin may also contribute to reactivating acute ischemia. Other limitations of UFH are the need for continuous infusions and difficulty in achieving target activated partial throm-boplastin times, because of wide variation in antithrombotic response. Heparin-induced thrombocytopenia occurs in 1-3 of patients (35). to plasma proteins and endothelial cells. This leads to a more predictable antithrombotic dose-response relationship, and eliminates the need for routine laboratory monitoring of the anticoagulant effect. The long half-life of about 4 h after subcutaneous injections enables once or twice daily subcutaneous injection. LMWHs have an increase in minor (cutaneous) bleeding compared to UFH, but have the distinct...

Novel Treatment Approaches

Investigators from Shanghai52 53 have recently reported results in 61 newly diagnosed APL patients who received induction therapy with combined ATRA (25 mg m2 day) plus arsenic trioxide (0.16 mg kg day). All patients subsequently received three courses of consolidation chemotherapy, and five cycles of maintenance with sequential ATRA, arsenic, and 6-MP and MTX. Among the 61 patients, 58 (95.1 ) entered CR at a median of 26 days and, with a follow up of 20-39 months, all of them were relapse free.52 Similar results, at least for induction, have been reported by Wang et al.,54 with a CR rate in 80 newly diagnosed patients treated with low-dose ATRA plus arsenic of 92.5 there were two early deaths (2.5 ), and four cases of resistant leukemia, but no data were presented on long-term outcomes. Estey et al.34 have treated 44 newly diagnosed APL patients with ATRA (45 mg m2 day) plus arsenic trioxide (0.15 mg kg day) added at day 10 (with addition of one dose of gemtuzumab ozogamicin if the...

Tiziana Lazzarotto Maria Paola Landini

Purpura, hepatomegaly, splenomegaly, pneumonia and encephalitis. Mild clinical manifestations usually include liver problems with hepatosplenomegaly (60 of cases) and thrombocytopenia (53-77 of cases), and around half the babies present delayed intrauterine growth with low birth weight (Ramsay et al., 1991 Boppana et al., 1992). Structural abnormalities mainly affect the central nervous system (ventriculomegaly, intracranial calcifications and cerebral atrophy), whereas other organs are seldom involved. Associated visual impairment and hearing loss have also been reported and CMV has been implicated in non-immunological hydrops (Inoue et al., 2001).

Definition Of Remission

Absence of a unique phenotype by flow cytometry identical to what appeared in the initial specimen Absolute neutrophil count < 1000 granulocytes mm3 Platelet count > 100,000 mm3 platelet counts, and was used first on a broad scale in studies that led to the eventual approval by the Food and Drug Administration for gemtuzumab ozogamicin.1617 This category was developed for patients who fulfilled the requirements of a morphologic CR, but with residual neutropenia or thrombocytopenia. These patients do not seem to enjoy the same survival as those who enter a full morphologic CR.

Fields Of Expertise Within Toxicology

Hematotoxicity is another area of active investigation. Benzene is an excellent example of the extremes that can be caused by substances that are toxic to the bone marrow. Chronic exposure to benzene can cause either leukemia, or bone marrow injury that can lead to aplastic anemia 6,7 . Agranulocytosis and aplastic anemia are infrequent but deadly toxic effects of several drugs. Anemias related to deficiencies of each of the formed elements of the blood also are known, and some of these are toxicological in origin. For example, thrombocytopenia is an established and potentially deadly adverse effect of heparin, though the etiology may be immunological 8 .

Management Of Myelosuppression

Probably the most common adverse event with imatinib is myelosuppres-sion. Grade 3 or higher neutropenia (i.e., neutrophils < 1 X 109 L) occurs in up to 35-45 of patients, and thrombocytopenia in 20-25 .26'28'32'51'52 Severe anemia is less common, occurring in 5-10 of the patients. All of these are more common in patients who have failed prior therapies (e.g., IFN-a), and are dose-related, occurring more frequently among patients treated with higher doses. Patients who develop grade 3 or higher neutropenia or thrombocy-topenia may have a lower probability of achieving a cytogenetic response. The adverse prognosis is particularly noticeable among patients whose myelosup-pression lasts longer than 2 weeks.5153 This has been attributed to a decreased dose intensity, as the current recommendation is to interrupt therapy in patients who develop this degree of myelosuppres-sion and reduce the doses for those who take more than 2 weeks to recover.54 To...

Imatinib Meslate In Accelerated And Blastphase

Blood or marrow, or a platelet count less than 100 X 103 L unrelated to anticancer therapy. Patients were treated with 400 or 600 mg of imatinib daily. Overall, 69 of the patients achieved a sustained hematologic response, 34 complete, and the rest either achieved a blast percentage in the marrow under 5 with incomplete peripheral blood recovery (marrow response) or a return to a second chronic phase (no criteria for accelerated disease as defined above). The rate of complete cytogenetic response was 17 , and the 1-year progression-free and overall survival was 59 and 74 , respectively. Patients treated with 600 mg compared to 400 mg realized greater benefit with a higher overall cytogenetic responses (28 vs 16 ) and better progression-free and overall 1-year survival rates (67 and 78 vs 44 and 65 ), with no significant increases in toxicity.

Cytarabinebased Combination Regimens

The largest series incorporating AML-type chemotherapy in patients with myeloid blast phase (blast count > 30 ) involved 162 patients treated at MD Anderson Cancer Center over an 11-year period from 1986 to 1997.23 Ninety patients received intensive combination chemotherapy, largely high-dose cytarabine-based. Overall, 28 of the patients responded to treatment, with CHR in 8 of the patients, and an additional 7 achieving all criteria for CHR, but with incomplete platelet count recovery. In addition, 11 of the patients achieved a return to chronic phase, and 2 of the patients were termed a partial response. The duration of response was approximately 4 months, which corresponded with survival as well. In a series of patients treated at the Karolinska Hospital in Sweden,24 47 of 83 patients with accelerated or myeloid blast-phase disease, treated with an anthracycline cytarabine-based regimen, achieved a return to chronic phase, the definition of which was less stringent than the MD...

Cml Treated With Hydroxyurea Or Busulfan

A large study of patients treated mostly with hydrox-yurea was the basis for the first widely recognized prognostic scoring system. Sokal et al. performed a multiple regression analysis of 625 chronic-phase patients aged 5-45 years and identified age, spleen size, hematocrit, platelet count, and the percentage of circulating blast cells as significant prognostic factors.14 The Sokal scoring system devised by this analysis classifies

Inhibitors Of The Downstream Pathways Ras signaling

Facilitates binding of this protein to cellular membranes, allowing them to function as intermediates in the process(es) of signal transduction. In the Ras pathway, prenylation is catalyzed by farnesyl protein transferase the farnesyl transferase inhibitors (FTIs) interfere with this step by inhibiting this enzyme. Given the central role that the ras oncogene plays in controlling cellular metabolism, multiple FTI compounds are currently being developed and tested across a wide range of hematologic malignancies. A phase I II study of tipifarnib, an FTI, in patients with a spectrum of myeloproliferative disorders reported preliminary results in 23 patients.34 Tipifarnib was administered at a dose of 300 mg p.o. b.i.d. for 21 days every 4 weeks. Clinical WBC responses normalization of WBC, complete remission (CR) or > 50 WBC count reduction, partial remission were seen in 5 of 21 (24 ) evaluable patients. No cytogenetic responses were seen in six evaluable patients. Grade 2 anemia and...

Clinical Presentation

The clinical presentation of CLL patients is diverse, with variability in presenting symptoms, physical examination findings, and laboratory test results. As noted above, patients often present without any symptoms, and the diagnosis is made on the basis of an elevated absolute lymphocyte count found on routine complete blood count (CBC). Less commonly, patients present with nontender lymphadenopathy, and are noted to have an elevated blood lymphocyte count on further evaluation. Some patients present with concomitant illnesses such as infection or chronic rhinitis, or less commonly, autoimmune phenomena such as autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia purpura (ITP).

Criteria For Diagnosis

Nation is most helpful in evaluating response to treatment and is required to confirm complete remission. A bone marrow aspirate and biopsy are also useful in evaluating patients with thrombocytopenia to differentiate between an autoimmune process and lack of platelet production due to CLL marrow infiltration.

Role Of Other Diseaserelated Complications

CLL patients are known to be at an increased risk of developing autoimmune hematologic complications. The most frequent among these is Coombs positivity with or without resulting autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Pure red cell aplasia (PRCA) is a relatively rare complication, while immune neutropenia is extremely rare in CLL. When AIHA, ITP, or PRCA occur even in a patient who has not received any prior cytotoxic therapy, we consider these complications indications for instituting therapy.

Diagnosis Symptoms and Clinical Signs

Mon symptoms and physical findings result from anemia, thrombocytopenia, and neutropenia, and include pallor and fatigue, anorexia, petechiae, purpura, bleeding, and infection. Occurrence of initial hyperleukocy-tosis (white blood cell count> 100,000 l) did not vary significantly in the different age groups. Initial involvement of the central nervous system (CNS) is seen less often in adolescents ( 10 ) and in children aged 213 years ( 8 ) than in infants ( 17 ) with AML (data not available for young adults, who rarely get diagnostic lumbar puncture). Infiltration of the skin, especially in monocytic leukemias, is also most frequent ( 20 ) in young children (< 2 years) and rarely seen in older children and adolescents. Likewise, leukemic infiltrations of the periosteum and bone occur more often in young children than in adolescents.

Asad Ansaria Adriana Weinbergb

A cohort of 277 children from birth through 2 years with weekly testing of saliva for HHV-6. HHV-6 has also been associated with myelodysplastic syndrome, hemophagocytic syndrome, infectious mononucleosis, thrombocytopenia with and without purpura and in more rare instances, dilated cardiomyopathy and acute lymphadenitis including Rosai-Dorfman diseases (a rare, benign, pediatric lymphadenopathy) (Levine et al., 1992 Saijo et al, 1995 Syruckova et al., 1996 Yoshikawa et al., 2001 Hashimoto et al., 2002 Maric et al., 2004 Kagialis-Girard et al., 2005). Recently, a case of acute respiratory distress syndrome secondary to HHV-6 pneumonia has been described in an immunocompetent young female (Merk et al., 2005). HHV-6 has also been implicated in chronic fatigue syndrome without clear proof. first-line antiviral for now. The use of these antivirals may be limited by their adverse effects including dose-dependent neutropenia and thrombocytopenia with ganciclovir, and nephrotoxicity with...

Polyclonal Bcell Lymphoproliferative Disorder

An entity called polyclonal hairy B-cell lymphoprolifer-ative disorder (HBLD) has been described in Japan.7273 All of the patients were females, had splenomegaly and minimal or no lymphadenopathy persistent lympho-cytosis was noted in all the patients, some having anemia and thrombocytopenia. Abnormal lymphocytes present in the peripheral blood and bone marrow had round nuclei and abundant pale cytoplasm with long microvilli and prominent membranous ruffles. They expressed CD5- CD10- CD11c+ CD19+ CD20+ CD23 - by flow cytometry studies. Although these findings were similar to those of HCL, the surface marker of the kappa and lambda chains was unbiased and studies of immunoglobulin gene rearrangements and expressions showed a polyclonal proliferation of B cells.73

Indications For Treatment

Hairy cell leukemia is an indolent lymphoproliferative disorder, which, prior to the advent of successful systemic therapy, had a median survival of 53 months. Approximately 10 of the patients diagnosed with this disorder never require therapy. This population is characterized by older age, smaller spleen size, and minimal circulating hairy cells.1 The following criteria, though not validated, are commonly accepted as appropriate indications for therapy neutropenia characterized by an absolute neutrophil count (ANC) < 1 X 109 L, anemia with a hemoglobin < 10 g dL, or thrombocytopenia < (50-100) X109 L, recurrent serious infections, or symptomatic splenomegaly. Much less commonly, bulky or painful lymphadenopathy, constitutional symptoms including fevers, chills, sweats, or weight loss, vasculitis, bone involvement, or leukocytosis with a high proportion of circulating hairy cells (white cell count > 20 X 109 L) are also indications for treatment. Bone marrow involvement, no...

Targeting Cd52 On Hcl Cells With Alemtuzumab

CD52 is a 12-amino-acid glycoprotein that is present on lymphocytes at up to 450,000 sites cell.48'49 It is also present on monocytes, macrophages, eosinophils, and the male reproductive tract.5051 Quigley et al. at the Scripps Clinic recently reported that in nine cases of classic HCL and one of HCLv, all patients expressed CD52 on 92-100 of the HCL cells.52 Fietz et al. reported recently that a patient with HCL and shortlived or poor responses to cladribine, interferon, splenectomy, and rituximab had hematologic benefit with alemtuzumab.53 The patient tolerated rituximab more poorly than alemtuzumab because of an allergic reaction to the former. With both mAbs, the patient had an improvement in thrombocytopenia, but failed to reverse blood transfusion dependence.

Responses To Lmb2 In Hcl Patients

All four patients with HCL, who had failed at least cladribine and interferon, had major responses.69 Patient 30 see Figure 33.2(a) prior to treatment had pancytopenia, with a pretransfusion hemoglobin as low as 8.5 g dL, a platelet count of 47,000 mm3, an absolute neutrophil count (ANC) of 360 mm3, and an enlarged spleen and precarinal lymph nodes. The pan-cytopenia resolved with elimination of the tumor cells. The hairy cell count of 478 L decreased > 90 from just one dose of LMB-2, as assessed on day 3. By day 8, the HCL count had decreased by > 99 , and was cleared following cycle 2. Flow cytometry is able to quantify HCL cells making up < 0.01 of the lymphocytes. The CR in patient 30 was associated with resolution of baseline splenomegaly and precarinal adenopa-thy, and transfusion independence. Recovery of normal counts is shown in Figure 33.2(a), with the platelet count first to recover, improving from a pre-treatment baseline of 53,000-133,000 L by day 22.

Risk Of Fetalneonatal Infection

Since the institution, about 30 years ago, of the recommendation for passive immunization of exposed newborns with VZIG as soon as possible after birth, it is rare for a newborn infant to die of disseminated varicella. Before VZIG became available, one study suggested a 20 fatality rate when the mother had onset of rash less than 4 days and up to 2 days after onset of rash at delivery (13). Infants in whom varicella is fatal often have a disseminated infection with pneumonia, extensive hemorrhagic skin vesicles, hepatitis, and thrombocytopenia. Mothers whose onset of rash is more than 48 hours after delivery may transmit varicella to their babies, but the disease is usually not severe because they transfer antibodies as well (7).

Induction chemotherapy and organ preservation

At the University of Chicago we continue to minimize the degree of surgery that must be undertaken. Review of our previous combined chemoradiation trials concluded that locoregional control was increased at the expense of the development of distant disease. Based on this premise, we have incorporated intensive concomitant chemoradiotherapy as the primary treatment modality in locoregionally advanced stage III, IV HNC to address both locoregional control and distant disease. Recent emphasis on potential benefits of chemoprevention provided the impetus for a phase II trial of the combination regimen of cisplatin (100 mg m2) every 28 d (cycles 1, 3, and 5), and continuous infusion 5-FU (800 mg m2, d 1-5), hydroxyurea (1000 mg BID for 11 doses), twice-daily radiotherapy (1.5 Gy d, d 1-5) every other week one cycle was equivalent to 14 d (68). Patients were then given granulocyte colony-stimulating factor (5 g kg) on d 7-13. Stage III patients were only eligible if the primary tumor...

Comprehensive Treatment Strategy For

Neutropenia thrombocytopenia Patients with mild to moderate, uncomplicated neutropenia and or thrombocytopenia can often be observed however, such patients should be evaluated on an individual basis. Patients with life-threatening neutropenia or throm-bocytopenia warrant active treatment and not simply supportive care (such as platelet transfusions and antibiotics), even though some such patients may be assigned to a low-risk IPSS subcategory. 5-Azacytidine can induce trilineage responses and along with decitabine (an investigational agent in phase III testing) can induce rapid and impressive improvements in peripheral blood counts. Patients with severe cytopenias (even without an increase in bone marrow (BM) blasts) should be considered for allo-geneic stem cell transplantation before they have life-threatening infectious or bleeding complications. Whether patients with cytopenias and no increase in BM blasts will have superior outcomes with reduced intensity stem cell...

Toxicity and biologic effect of il2

Tion of treatment and are mainly related to the capillary-leak syndrome (61-63). More common side effects may include a fever, nausea, diarrhea, cutaneous rashes, pruritus, increases in liver and renal parameters, fluid retention, weight gain, hypotension, confusion, and cardiac arrhythmias (62). All patients show some degree of hepatomegaly and or splenomegaly and variable leukocytosis. The major side effects, although potentially lethal, usually disappear after discontinuation of IL-2 treatment and their duration can be shortened by corticosteroids. High-dose IL-2 (> 8 x 106 m2 d) treatment is usually administered under close supervision in the hospital for no more than 4-5 d due to its toxicity. The leukocyte differential count is affected by IL-2 and varies throughout the regimen. IL-2 infusion is accompanied by neutrophilia and increased circulating eosinophils. After discontinuation of IL-2, a rebound lymphocytosis, with an increase in large granular lymphocytes, can be noted....

Scoring systems without karyotype analyses

Table 43.3 shows the main prognostic scoring systems proposed for MDS that do not include cytoge-netic factors. The Bournemouth score was the first proposed scoring system. Patients were assigned to one of three risk groups based on the number of cytopenias present and the proportion of blasts in the BM.53 The main criticism of this system is the emphasis on blood cytopenias in relation to the proportion of blasts in the BM.7 The scoring system proposed by the Spanish group uses the proportion of BM blasts, platelet count, and age.7 This system is easy to use and has been demonstrated to predict survival in

Histone Deacetylase Inhibitors

Butyrate is an acetylating agent that has been used to induce expression of fetal hemoglobin in sickle cell anemia and thalassemia, but proved unsuccessful for the treatment of AML in phase II trials.11 Sodium phenylbu-tyrate (PB), a derivative thought to be deliverable in oral form, has been shown to induce histone acetylation, p21 expression, G1 cell-cycle arrest, and apoptosis in vitro.12 In a trial conducted by Gore et al.,13 PB was given for 7 28 or 21 28 days to MDS and AML patients, with improvement in thrombocytopenia and neutrope-nia seen in a small number of patients. A dose-limiting toxicity of reversible encephalopathy was due to accumulation of phenylacetate. Currently, oral forms of PB are being investigated. Valproic acid, an oral antiepilep-tic agent, SAHA (suberoylanilide hydroxamic acid), and FK 228 (with FDA approval for cutaneous T-cell lymphoma) are newer HDAC inhibitors currently undergoing clinical trials.

Growth Kinetics of CLL in the Blood

Using flow cytometry, high numbers of circulating lymphocytes in S phase had a shorter therapy-free and total survival compared with those with fewer S-phase cells (65). Also, Orfao et al. (66) showed that a high absolute count of circulating S-phase leukocytes was associated with a higher incidence of hepatosplenomegaly, anemia, and thrombocytopenia, a higher number of lymphocytes in blood and bone marrow, advanced clinical stages, lower serum IgG and IgM, and poorer survival. Moreover, the fraction of circulating Ki-67-labeled cells in CLL correlated with the proportion of prolymphocytes and was higher in resistant CLL than in indolent cases (67). Even high proliferative in vitro responses to B-cell mitogens were significantly associated with poor survival, whereas unstimulated thymidine uptake did not predict outcome (62). Studies of lymphocyte doubling time (LDT) confirmed the above data. LDT is defined as the period needed for the peripheral lymphocyte count to double the...

Clinical Development Of Dasatinib In Chronic Myeloid Leukemia

84 patients (40 in CP, 11 in AP, 23 in myeloid BP, and 10 with Ph+ ALL) received dasatinib 15 to 240 mg daily (29). A CHR was achieved in 37 (93 ) patients in CP and a major cytogenetic response (MCyR) in 18 (45 ), including a CCyR in 14 (35 ). Major hematologic responses were observed in 31 (70 ) of 44 patients with AP, BP, or Ph+ ALL, and MCyR were achieved in 27 , 35 , and 80 of patients in AP, BP, and Ph+ ALL, respectively. Responses were maintained in 95 of patients with CP and in 82 of patients with AP after a median follow-up of more than 12 and 5 months, respectively. However, only one (10 ) patient with Ph+ ALL remained relapse-free after a median follow-up of four months (29). Overall, therapy with dasatinib therapy was well tolerated. The most frequently described toxicities were myelosuppression, gastrointestinal, and fluid retention syndromes. Grade 3-4 neutropenia or thrombocytopenia was observed in 45 and 35 of patients treated in CP and in 89 and 80 of those with AP,...

Making The Diagnosis

The platelet count of reactive thrombocytosis accompanying inflammation, bleeding, cancer, or infection is rarely elevated to the degree seen in ET. A Serum, fer-retin level is helpful in excluding iron deficiency (bleeding as a cause of thrombocytosis). Thrombosis never occurs in secondary thrombocytosis. All patients considered to have ET should have cytogenetic or molecular studies performed to exclude CML, a disease that can present in a patient with an increased platelet count and only a modest elevation of the WBC. For patients with borderline or moderately elevated RBC values, a Cr51 RBC mass study is mandatory to exclude PV. JAK2

Antithrombotic therapy

In patients with PV who continue to have thrombotic or vascular symptoms, despite aspirin and good control of the hematocrit and platelet count with phlebotomy and myelosuppression, clopidogrel 75 mg daily or ticlopi-dine 250 mg orally twice daily should be considered.14

Laboratory Findings

Laboratory findings include platelet count in the range of 450,000-1,000,000 mm3, leukocytosis, basophilia, and the presence of megathrombocytes in the peripheral smear. Marrow cellularity is increased in 90 of the patients, with bizarre megakaryocytes with nuclear pleomorphisms and clustering of megakaryocytes. Enlargement of megakaryocytes with multilobulated nuclei, and their tendency to cluster in small groups along sinuses, is the hallmark of ET.21 The bone marrow may also appear normal. Bleeding times are prolonged in 10-20 of the patients. Platelet aggregation studies are frequently abnormal, most often demonstrating impaired aggregation in response to epinephrine, ADP, and collagen, but not to arachidonic acid and ristocetin.22 Laboratory features of acquired von Willebrand syndrome (simulating type II vW factor deficiency) are associated with a platelet count > 1000 X 109 L. An enhanced throm-botic risk in ET patients has been associated with a reduction in the...

Leukemic Transformation Of

Clinically heralded by organomegaly, worsening constitutional symptoms, anemia, thrombocytopenia, and leukocytosis. At the diagnosis of MMM, these patients had frequently presented with typical disease-related features, but about half had an increase in circulating myeloblasts. All episodes of LT were acute myeloid leukemia, with all French-American-British subtypes represented except M3. Additionally, 91 of patients displayed an abnormal karyotype. LT from MMM was usually fatal, with 89 patients (98 ) having expired of disease or therapy a median of 2.6 months (range 0-24.2) after LT. Supportive care alone or noninduction chemotherapy had similar outcomes in 48 patients and 19 patients, respectively (median survival < 3 months in both groups). Induction chemotherapy in 24 patients (26 ) had a 33 mortality with no complete remissions achieved median survival 3.4 months (range 0.9-24.3) . However, a subset of patients (n 10 41 ) reverted their marrow to a chronic phase of MMM after...

Established singleagent oral chemotherapy

In patients who have CMML with a significant myelo-proliferative component, high WBC count, or organomegaly, treatment with single-agent chemotherapy has been the standard of care. Oral agents such as busulfan, 6-mercaptopurine, hydroxyurea, and oral etoposide have been used empirically with some success, but a prospective randomized study conclusively determined the superiority of hydroxyurea over etopo-side in terms of overall survival in patients with mostly advanced proliferative disease (i.e., splenomegaly, mild thrombocytopenia, and increased bone marrow blasts) 24 months for hydroxyurea versus 9 months for etoposide.10 This is the only prospective randomized study to date that has compared two treatment regimens in patients with CMML. Although neither regimen induced complete remission (CR) or affected the natural history of the disease, the results supported the idea of using hydroxyurea plus supportive care as the standard-of-care arm in any future randomized trials. No...

Platinoid Mechanism and Toxicity Platinoid Overdose Management

CNS Seizures, encephalopathy, heavy-metal induced sensory peripheral neuropathy-axonopathy, retinal toxicity, reduced color vision, ototoxicity (high-frequency). Renal Distal tubular necrosis with subsequent acute renal failure (ARF). Bone marrow Myelosuppression anemia, thrombocytopenia.

Diagnostic And Treatment Paradigms

For the remaining cases which fulfill the original criteria for HES,78 the WHO criteria,76 and other criteria,77 79 further screening should include complete bone marrow examination, including histologic examination, karyotype analysis, FIP1L1-PDGFRa by PCR or FISH, and documentation of disease and eosinophil clonality by FISH or molecular methods. Abnormal T-lymphocyte subsets may be identified immunophenotypically as immature T cells (CD3+, CD4 , and CD8) or aberrant T cells (CD3 and CD4+),80'81 with or without rearrangement of T-cell receptor genes.80-83 The usefulness of determining interleukin 5 (IL-5) and other cytokines plasma concentrations is unknown. Association of eosinophilia with systemic mastocytosis84,85 supports the determination of plasma tryptase concentrations. Assessment of splenomegaly, hepatomegaly, abnormal marrow function (e.g., anemia, thrombocytopenia, marrow fibrosis, and dysplasia), and elevated plasma concentrations of tryptase helps define...

Splenic Marginal Zone Lymphoma

The constituent cells of SMZL bear only passing resemblance to splenic marginal zone cells and do not share their immunophenotype.31 Patients typically present with splenomegaly often accompanied by anemia and thrombocytopenia. Peripheral blood involvement is often, but not always, present and in some of these cases the circulating neoplastic lymphocytes have a villous appearance. These cases were previously termed splenic lymphoma with villous lymphocytes.32 The use of this somewhat imprecise term will not only fail to include those cases without circulating villous lymphocytes but, more importantly, tends to include other cases of B-cell lymphoma with peripheral blood spillover since the cells of various lymphomas may sometimes adopt a villous appearance, either real or artifactual, in the peripheral blood. This is an important consideration since SMZL tends to respond favorably to splenectomy alone in contrast to its poor response to chemotherapy.33

Radioimmunotherapy RIT

Y-90 ibritumomab tiuexetan Y-90 ibritumomab tiuxe-tan has a murine rituximab conjugated to the iso-tope.80 The Y-90 ibritumomab tiuxetan regimen takes about 8 days to administer. On the first day, a dose of cold rituximab at 250 mg m2 is administered to bind nontumor CD20 sites and to facilitate better biodistribution. Because Y-90 is a beta emitter, it cannot be used for imaging thus, indium-111 -labeled ibritu-momab is substituted for biodistribution studies performed at days 2-3, and if needed, 6-7 to ensure appropriate localization of the isotope. On days 7-8, another low dose of cold antibody is delivered followed by 0.4 mCi kg of Y-90 ibritumomab tiuxetan (not to exceed 32 mCi) for patients with platelet counts of at least 150,000 mm3. The dose is reduced to 0.3 mCi in patients with a platelet count of 100-149,000 mm3.81

Clinical Staging and Immune Cytopenias

Patients with anemia and or thrombocytopenia of immune origin, rather than secondary to marrow infiltration by CLL B-lymphocytes, were not considered a separate prognostic group in any of the staging systems. It has been suggested by some investigators that CLL patients who have anemia and or thrombocytopenia of immune origin seem to have a better clinical outcome, compared with those who have anemia and or thrombocytopenia owing to bone marrow infiltration (23,24). Data from a large number of patients would be required to reach a definitive conclusion. Some investigators have suggested classifying these patients as stage C or Rai stage III or IV, immune (25).

Treatment Of Relapsed And Refractory Dlbcl

Famide, and also because they are excellent stem cell mobilizing regimens.7273 Overall response rates are over 60 , although the complete response rate is only 24 .73 The major advantage to improving salvage regimens is to demonstrate chemosensitivity, since this is arguably the most crucial characteristic-determining outcome following autologous stem cell transplantation in aggressive lymphomas. Of the ifosfamide-based salvage regimens for aggressive lymphomas, extensive data have been published on the ICE (ifosfamide, car-boplatin, etoposide) regimen developed at the Memorial Sloan Kettering Cancer Center (MSKCC).73-78 In an initial publication, investigators at MSKCC treated 163 consecutive transplant-eligible patients with relapsed or refractory aggressive NHL with 3 cycles of the ICE regimen. The overall response rate was 66 , allowing 89 of patients to proceed to a planned autologous stem cell transplant. There was minimal nonhematologic toxicity, although a third of patients...

Evaluation Of The Neonate

Minimum laboratory evaluation should include a complete blood cell count and lumbar puncture, as well as bacterial cultures of blood, urine, and cerebrospinal fluid to rule out bacterial infection. Cerebrospinal fluid analysis, in both nonpoliovirus EV and poliovirus infections, may show a pleocytosis suggestive of viral meningitis (usually < 500 white blood cells mm3). Occasionally, the cerebrospinal fluid profile may mimic that of bacterial meningitis, with up to several thousand white blood cells cubic millimeter. A neutrophil predominance is frequently present, and in a minority, increased protein or decreased glucose levels may occur. Conversely, cerebrospinal fluid may be positive by culture or PCR despite a normal cytologic and chemical profile (33,36,37). Central nervous system imaging should be considered if an infant is very lethargic or has focal neurological findings or if there is a neurological deterioration in the presence of significant thrombocytopenia or...

Tyrosine Kinase Inhibitors

From the dose-finding study, complete hematologic responses occurred in almost all patients in chronic phase treated at doses of 300 mg and higher and cytogenetic responses were seen once this dose level was reached. In addition, pharmacokinetic data showed that this dose level achieved in vivo concentrations approaching the predicted in vitro IC90 for cellular proliferation of 1 M (62). Finally, an analysis of white blood and platelet count responses over time suggested that doses of 400 to 600 mg were on the plateau of a dose-response curve, indicating that this dose range would be an efficacious dose for phase II testing. However, in the dose-escalation study, an MTD of STI571 was never reached (60). Although traditional drug development uses dose escalation until an MTD is established, with molecularly targeted therapies, this may not be an appropriate endpoint. A more appropriate endpoint may be the dose that achieves molecular target inhibition. Therefore, in the case of STI571...

Clinical features

Most patients are over 50 with a similar incidence in males and females.87 The disease usually presents with massive splenogamy, which produces abdominal discomfort and pain. Diagnosis is often made at splenectomy performed to establish the cause of unexplained spleen enlargement. B symptoms are present in 25-60 of cases anemia, thrombocytopenia, or leukocytosis are reported in approximately 25 of cases. Autoimmune hemolytic anemia is not uncommon, being found in up to 15 of patients. Splenic hilar lymph nodes appear to be involved in about 25 of cases, but peripheral lymph node involvement is typically absent. Approximately 30 of cases have liver involvement.106-110 Nearly all patients have bone marrow involvement, often accompanied by involvement of peripheral blood (defined as the presence of absolute lymphocytosis of more than 5 ).109 Because of the high frequency of bone marrow or liver involvement, about 95 of cases are classified as Ann Arbor stage IV. Serum paraproteinemia is...

Treatment of Advanced CLL

On the basis of these results (observed in a previous interim analysis held in September 1996), it was decided to discontinue accrual in this group. As expected, median survival was better for stage B (81 mo) than for stage C patients (60 mo). Causes of death were related to CLL in 75 of cases, and overall survival did not differ among the three arms (67, 70, and 69 mo in the ChOP, CAP, and FDB groups, respectively). Incidences of infections (< 5 ) and autoimmune hemolytic anemia (< 2 ) during the six courses were similar in the randomized groups, whereas FDB, compared with ChOP and CAP, induced more frequent protracted thrombocytopenia (p 0.003) and less frequent nausea vomiting (p 0.003) and hair loss (p < 0.0001). For patients with stage B and C CLL, first-line FDB and ChOP regimens both provided similar overall survival and response rates at closing and better results than CAP. However, there was an increase in clinical remission rate and a trend toward a better tolerance of...

Clinical Features Of Hivassociated Castlemans Disease

In general, MCD presents in the fourth or fifth decade of life but occurs earlier in people who are HIV positive. Patients often present with generalized malaise, night sweats, rigors, fever, anorexia, and weight loss. On examination, they have multiple lymphadenopa-thy, hepatosplenomegaly, ascites, edema, and effusions both pulmonary and pericardial. Laboratory investigations may reveal thrombocytopenia, anemia, hypoalbuminemia, and hypergammaglobulinemia. The systemic symptoms are attributed to IL-6 and can be severe enough to cause pancytopenia, organ failure, particularly respiratory and renal, as well as shock, requiring admission into intensive care units. HIV-infected patients with MCD have a greater preponderance for pulmonary complications. MCD is more likely to lead to neuropathic complications than does locally confined Castleman's disease. Patients can develop polyneuropathies, leptomeningeal and CNS infiltration, as well as myasthenia gravis.114 The polyneuropathy is a...

Treatment Of Hivassociated Castlemans Disease

Splenectomy, in addition to establishing the histologic diagnosis, may have a therapeutic benefit as a debulking procedure, as some of the hematologic sequelae such as thrombocytopenia and anemia may in part be due to splenomegaly. Following splenectomy, there is often resolution of the constitutive symptoms but this may be short lived, and some form of maintenance therapy is needed to prevent relapse.115

Irinotecan hydrochloride

Irinotecan hydrochloride (CPT-11), a camptothecin derivative, is a prodrug that is converted to the active compound SN-38, which in turn inhibits topoisomerase I. CPT-11 was evaluated in a phase II study involving 13 patients (3 acute and 10 lymphoma) with relapsed or refractory ATL.111 Median age was 63 years (range 44-78 years). The OR rate was 38.5 (CR 7.7 PR 30.8 ) with a median response duration of 31 days. All responders had lymphoma subtype. Grade 3 or 4 toxicities included leukopenia (66.7 ), thrombocytopenia (41.7 ), anemia (33.3 ), and diarrhea (46.2 ). One treatment-related death occurred.

Purine Analog Based Combination Chemotherapy

Two small phase I studies of the combination of fludarabine and chlorambucil were conducted by Elias et al. (63) and Weiss et al. (64). Both demonstrated clinical activity, but the treatment was limited by significant myelosuppression, especially thrombocytopenia. Another study reported on continuous-infusion cisplatin (although not a classical alkylating agent, this drug also produces DNA crosslinks) and fludarabine plus cytarabine in 26 patients. Patients had received extensive prior treatment for CLL, and most of them were refractory to fludarabine. Responses were seen in 19 of the patients, myelosuppression was reported in more than half of the patients treated, and a high incidence of infectious complications was noted (65). The same three-agent regimen is under investigation in chemotherapy-naive patients. Wierda et al. (79) reported results in 135 patients the overall response rate was 95 , complete responses were seen in 63 , and molecular remissions were demonstrated in 31 of...

Radiolabeled Antibodies

90Y-ibritumomab tiuxetan was FDA approved in the United States at a dose of 0.4 mCi kg, with a dose reduction to 0.3 mCi kg in patients with low platelets (100,000-150,000 mL).22 Unlike 131I tositumomab, 90Y-ibritumomab tiuxetan does not require individualized dosimetry. Witzig et al. reported the superiority of 90Y-ibritumomab tiuxetan versus rituximab in 143 patients with CD20-positive relapsed or refractory low-grade, follicular, or transformed NHL who had received a median of two previous chemotherapies and half of whom were refractory to their last ther-apy.33 The response rates of 90Y-ibritumomab tiuxetan versus rituximab were 80 versus 56 , respectively (p 0.002), and complete responses were seen in 30 versus 14 (p 0.04), respectively. Overall response favored the follicular lymphoma subgroup with a response rate of 86 . The time to progression estimates were similar at 11.2 months in the 90Y-ibritumomab Combined safety data from 349 patients treated on this and four other...

Clinical Manifestations Of Dengue Infection

Dengue fever is characterized by sudden onset of fever, frontal headache, retro-orbital pain, general malaise, generalized myalgias and arthralgias, nausea, vomiting, and rash. One characteristic feature of dengue fever is the severity of body pain, which can be incapacitating and explains why the disease is sometimes called breakbone fever. Other nonspecific symptoms may be present, such as anorexia, mild conjunctival injection, diarrhea, pruritus, and changes in taste sensation. Leukopenia and thrombocytopenia are frequent, and liver enzymes may be mildly elevated. The febrile period lasts 5-7 days, but the patient may remain symptomatic for several more days. The disappearance of fever correlates with the disappearance of viremia. Convalescence may be marked by a period of lassitude. There have been reports of severe depression after the acute period of illness (4,5). Skin eruptions may be more common in primary infections (6). The rash may be present in different ways, including...

Dengue Infection In The Pregnant Woman

Tations, and one case developed DHF also complicated by severe preeclampsia (25). In 1999, Carles also reported four mothers in French Guiana with dengue infection within 1 week of delivery (26). Although low platelet counts were reported, no hemorrhagic complication was recorded. Reports of dengue infections have come from Guadeloupe (one mother developed severe thrombocytopenia, giving birth via cesarean section, and the other had preterm labor mothers and infants recovered without complications) and from Thailand (thrombocytopenia with and without hemorrhagic complications) (27-29). In a review of laboratory-positive cases of mother-infant pairs in Puerto Rico from 1994 to 2003, four cases of maternal-fetal transmission were documented. All mothers were positive for anti-dengue IgM antibody, and infants were diagnosed by virus isolation, polymerase chain reaction, or anti-dengue IgM detection (CDC, unpublished data, 2003). In three of the four cases, the disease in the mother was...

Paraneoplastic syndromes

Classical HL is associated with the overexpression of a variety of cytokines and their receptors on Hodgkin's or Reed-Sternberg cells and in the surrounding inflammatory infiltrate. These cytokines, including interleukin 2 (IL-2), IL-5, IL-6, IL-7, IL-9, IL-10, IL-13, transforming growth factor p (TGFp), and lympho-toxin A (LT-A), may be responsible for the systemic symptoms of HL and for the rare paraneoplastic syndromes associated with HL. Nephrotic syndrome, idiopathic thrombocytopenia purpura, autoimmune hemolytic anemia, and cerebellar degeneration ataxia have all been reported in patients with HL.14-18 Typically, nephrotic syndrome or neurologic symptoms precede a diagnosis of HL or herald a relapse, although occasionally high-dose steroids used to treat many of these syndromes may contribute to a delay in diagnosis.14,16 Idiopathic thrombocytopenia has been described in patients preceding the diagnosis of HL, at the time of relapse, and in patients in clinical remis-

Laboratory Evaluation Of The Mother And The Newborn

The laboratory evaluation of both mother and newborn with a suspected case of dengue must include a variety of diagnostic tests, including specific tests for dengue. A complete blood cell count (CBC) with differential should be ordered for evaluation of the WBC count, hemoglobin and hematocrit levels. Serial CBCs are needed during the first days of illness to evaluate the disease progression, especially for hemoconcentra-tion, an important marker of increased capillary permeability. Serial platelet count measurements are also needed. A continuous, marked decline in platelet level could be the first sign of the development of DHF.

Fractionation and Fragmentation of Heparin

The development of fractions (naturally depolymerized forms) and fragments (chemically or enzymatically depolymerized forms) of heparin added a new dimension in the prophylactic and therapeutic use of heparin. With these more defined materials, efforts were aimed at finding a safer antithrombotic agent that would effectively prevent venous thrombosis, yet would have a lower bleeding risk and a decreased incidence of heparin-induced thrombocytopenia (HIT).

Radiolabeled Monoclonal Antibodies

Lym-1 has been conjugated to 131I in order to effect targeted delivery of this radioactive isotope to tumor cells of B-cell origin. Although 131I-Lym-1 has been tested primarily in patients with advanced NHL, the antibody has been given to several patients with B-CLL. Twenty-five patients with previously treated, advanced B-NHL and five patients with relapsed B-CLL were treated with fractionated, low-dose 131I-Lym-1, with a goal of 300 mCi per patient (122). Thirty percent of patients developed HAMAs, but only three patients had therapy interrupted as a result. Four of the five CLL patients responded (80 ). The same group also reported that patients who responded to 131I-Lym-1 therapy enjoyed improved survival (84 vs 22 wk) (123). Radiation dosimetry studies revealed a lower tumor radiation dose and a higher liver radiation exposure in CLL patients, compared with NHL patients, resulting in a lower therapeutic index for patients with CLL (124). Toxicity was acceptable, and the...

Chemotherapy in advanced disease

Responses in patients with visceral metastatic disease (33,34). This regimen is currently being tested in a phase III trial in patients with advanced disease vs standard-dose M-VAC by the Eastern Cooperative Oncology Group. Gemcitabine + cisplatin had similar response rates of 50 in phase II trials (35,36), but have demonstrated marked myelosuppression and are somewhat less attractive because of the requirement to utilize a nephrotoxic drug such as cisplatin. Nevertheless, a phase III trial of gemcitabine + cisplatin vs M-VAC has been completed, and showed an identical response rate and survival when compared to M-VAC, no differences in QOL assessments, and with less neutropenia and neutropenic fever, but more anemia and thrombocytopenia (37). Thus, several new regimens have shown equivalent efficacy to older regimens, but with significantly less toxicity. Additional trials attempting to increase the efficacy of these regimens are underway.

Blood And Bone Marrow Changes

Leukopenia and thrombocytopenia occur in 10-15 of patients at diagnosis. In some, thrombocytosis develops, presumably from the thrombopoietic effect of IL-6.1'221 This occurs more often in patients with osteosclerotic myeloma. Occasional plasma cells or plasmacytoid lymphocytes can be seen in the peripheral blood smear. A marked increase in plasma cells, 20 of leukocytes or > 2000 L, is seen in rare cases of primary plasma cell leukemia and more commonly in the terminal phase of myeloma.22

Depsipeptide FR901228 or FK228

Preclinical studies have shown improved tolerability and antitumor activity, with an intermittent dosing schedule as the result of the ability to administer higher doses, with shorter infusions found to induce less toxicity 124 . In the initial study, dose limiting toxicities (DLTs) included nausea and vomiting, thrombocytopenia and cardiac arrhythmia with atrial fibrillation. Because cardiac toxicity had been predicted from preclinical studies (myocardial hemorrhage and ischemia) patients were treated under continuous cardiac monitoring. This and a further study 125 showed no clinically significant cardiac adverse effects were observed, although subtle EKG changes were reported (QTc interval prolongation, ST segment and T wave changes). Toxicities observed included nausea vomiting, thrombocytopenia, fatigue and hypophos-photemia.

ICSO Supported Reperfusion

Details on feasibility, safety and effectiveness of ICSO in acute myocardial infarction were provided by Komamura and Kodama.68 Twelve ICSO treated patients with primary transmural acute myocardial infarction (9 anterior, one lateral and 2 inferior AMI) as well as 22 unsupported anterior AMI patients had successful intracoronary thrombolysis with urokinase. A 7F balloon catheter was inserted into the coronary sinus (for right or left circumflex occlusions) of the GCV (for LAD occlusions), and a 1 hr ICSO treatment (10 sec coronary sinus occlusions, 5 sec release periods) was initiated just before the lytic treatment. With ICSO occlusions, mean coronary sinus pressure rose from 8.3 to 38.1 mm Hg. There were no adverse effects on hemo-dynamics, no serious ventricular arrhythmias, no hemolysis or fall in platelet counts. There was no difference in LV function, but the ICSO group exhibited fewer abnormally contracting segments than the control group. In the whole ICSO group, no...

Influence of chemoradiation on acute and late complications of treatment

The acute morbidity of chemoradiation is almost always greater than that of radiation therapy alone. With cisplatin, upper-gastrointestinal-tract symptoms occur in addition to the lower-gastrointestinal-tract symptoms usually seen with pelvic irradiation. Although cisplatin has relatively modest hematologic toxicity, only about half of patients are able to complete the full six courses of weekly cisplatin or the full three courses of the RTOG regimen (18). An effort should be made to manage the dose and timing of chemotherapy to minimize the risk of severe neutropenia or thrombocytopenia, which could delay brachytherapy. Fluorouracil may increase the severity of acute lower-gastrointestinal-tract symptoms, particularly diarrhea, although grade 4 acute complications are still uncommon.

Lenalidomide Cc5013 Revlimid

Is very different than that of thalidomide, with thrombocytopenia and neutropenia predominating, and essentially no sedation, constipation, or neuropathy. The response rate among 34 patients with newly diagnosed MM treated with lenalidomide 25 mg daily for 21 out of every 28 days with pulse dexamethasone (40 mg day on days 1-4, 9-12, 17-20) was 91 (CR 6 ).122 ECOG has completed accrual to a large randomized study of lenalidomide with two different doses of dexamethasone, and the Southwest Oncology Group is currently conducting a 500-person randomized, double-blinded study comparing dexamethasone to dexamethasone plus lenalidomide (LD). The results of these two studies will establish whether LD could be an appropriate front-line regimen for patients with MM.

Precautions and contraindications Table 261

Contraindications to participation in exercise programs for adults with cancer have been published but are not necessarily based on sound research 19, 27 . Precautions have included uncontrolled and unstable cardiac disease, certain metastatic lesions, and recent intracranial hemorrhage or deep-vein thrombosis with pulmonary embolism. Other recommendations include the avoidance of the following high-intensity activities if the hemoglobin level is less than 80 g l, activities that present a risk of bacterial infection if the absolute neutrophil count is less than 0.5x109 l , contact sports or high-impact activities that pose a risk of bleeding if the platelet count is less than 50x109 l 19 , and power weight lifting if cardiomyopathy is a risk factor 29 .

Platelet Interactions

Fondaparinux does not induce in vitro platelet aggregation or activation in the presence of heparin antibody obtained from patients clinically diagnosed with HIT (154,160-162). However, data from the clinical trials in orthopedic surgery reveal that platelet counts < 100,000 xl_1 do occur with fondaparinux treatment. In the fondaparinux groups 2.7 and 4.9 of patients vs 3.7 and 5.3 of patients treated with enoxaparin developed thrombocytopenia (147,148).

Proteasome Inhibitor Bortezomib

Seven patients (4 ) had a CR, and 12 (6 ) had a near-CR (NCR) (myeloma protein undetectable by electrophoresis but immunofixation positive). An additional 34 patients (18 ) achieved a PR, and 14 (7 ) others an MR.24 The median time to disease progression for bortezomib as a single agent was 7 months, compared with 3 months that was reported for the patients' previous therapy (P 0.01). In a landmark analysis, patients who achieved a CR or PR by the end of the second cycle survived significantly longer than those achieving other types of responses. Additional clinical benefits observed in these patients included increases in hemoglobin levels and platelet counts, resulting in a reduction in transfusion requirements. Moreover, levels of unaffected immunoglobu-lins improved. The factors that predicted poor response to bortezomib were older age (> 65 years) and > 50 plasma cells in the bone marrow. In this bortezomib trial, serum -microglobulin level, number or type of...

Clinical Trials of Fondaparinux

Fondaparinux (GlaxoSmithKline) has been evaluated in several clinical trials for the prevention of venous thromboembolism in patients undergoing major orthopedic surgery (148-151,175,176). Approval was obtained for use in hip fracture, hip replacement, and knee replacement surgeries (177). Dosing of fondaparinux is once daily at 2.5 mg s.c. to be started not before 6-8 h after surgery to avoid unwanted bleeding. Patients with low body weight and renal insufficiency require dose adjustment. Overall, there was no reduction in the bleeding risk compared to enoxaparin. Monitoring is not recommended. However, it is advised to closely monitor any thrombocytopenia under fondaparinux treatment. If the platelet count falls to < 100,000 pi-1 fondaparinux should be discontinued, and it should be used with caution in patients with a history of HIT.

Background results of chemotherapy alone in acute promyelocytic leukemia

Age older than 50 yr (9), hyperleukocytosis at diagnosis (5), microgranular APL variant, severe bleeding at diagnosis, and or major thrombocytopenia were associated with a higher risk of early death in newly diagnosed patients with APL treated with chemotherapy alone. Shorter remissions were seen in patients with hyperleukocytosis (3) and in patients with microgranular APL variant (9).

Lincoff AM Bittl JA Harrington RA et al for the Replace2 Investigators Reference

Fundamentally, heparin is not a particularly good anti-thrombin. Also, despite their efficacy, the high cost of GP IIb IIIa inhibitors and the risk of increased bleeding have limited their widespread use to approximately 50-60 of patients undergoing PCI. The REPLACE-2 trial established bivalirudin as an excellent replacement for heparin during PCI. In lower-risk patients, substitution of bivalirudin for GP IIb IIIa inhibitors would result in lower rates of bleeding along with cost savings without compromising efficacy. Notably, bivalirudin has not been proven in higher-risk patients, including acute coronary syndrome patients and ST-elevation MI. Nonetheless, bivalirudin is an obvious choice for a PCI patient with heparin-induced thrombocytopenia or who is at high risk for bleeding complications.

Guidelines For The Diagnosis Of Congenital Toxoplasmosis In A Neonate Or Young Infant

Laboratory Complete blood cell count with differential and platelet count serum quanti tative immunoglobulins liver function tests, including 7GTP and bilirubin urinalysis, serum creatinine CSF cell count protein and glucose Radiologic Brain computed tomographic scan with and without contrast chest x-ray

Laboratory Diagnosis Of Congenital Toxoplasmosis

All neonates suspected of having a congenital infection should have a complete blood cell count (20), including a platelet count to screen for thrombocytopenia (40,41) and eosinophilia (42) (although the latter has not been a common finding in many infected infants), and liver function tests. A lumbar puncture should be done to determine if there is a disproportional increase in cerebrospinal fluid (CSF) protein relative to the degree of pleocytosis (25,43,44) and a computed axial tomographic scan of the brain with contrast to detect diffuse cerebral calcifications (27). Every infant suspected to be congenitally infected (especially those who are asymptomatic) should have a thorough ophthalmologic examination to detect any ocular complications (i.e., chorioretinitis) (Table 1) (1).

YIbritumomab Tiuxetan

Preliminary results of a prospective study on treatment of CBCL showed complete response in eight of nine treated patients while one patient had progressive disease (Duvic et al. 2005). In the follow-up phase, one patient had a relapse after 6 months while seven out of nine patients remained in remission. Reported side effects were a decrease in ECOG status from 0 to 2 or 3 and a weight loss in 33 of patients. Haematological toxicities (thrombopenia, lymphopenia and anaemia) resolved after 12 weeks. Adverse events, recorded in studies treating non-Hodgkin's lymphoma, were infusion-related side effects such as fever, nausea, chills and flu-like-symptoms. The myelosuppressive effects of 90Y-ibritumo-mab tiuxetan are observed 4-8 weeks after administration. Of observed grade 4 haematological toxicities, neutropenias were the most common, in 30 of patients on average, with thrombocytopenia and anaemia occurring in 10 and 3 , respectively. It is noteworthy that neutropenia and...

Prognostic Relapse Factors

Pretreatment factors include high WBC counts in all reports (Table 1) (5), even if, as seen in previous section, results of the European APL group suggest that maintenance treatment may particularly reduce the risk of relapse in this population (20). Most of the other risk factors described, including morphologic M3 variant, low platelet count, CD34 or CD2 expression on blast surface, presence of the short isoform (S isoform or bcr3) and possibly the rare bcr2 (or V) breakpoint in PML-RARa, as compared to bcr1 (or L breakpoint), are generally correlated to high WBC counts (35,36). On the other hand, a metaanalysis of Gimema and Pethema protocols in APL, which both included maintenance with ATRA and low-dose chemotherapy, showed that WBC and platelet counts had independent prognostic value for relapse. Disease-free survival (DFS) at 4 yr was 98 in patients with platelets > 50,000 mm3, 90 in patients with platelets < 50,000 mm3 but WBC < 10,000 mm3, and only 68 in patients with...

Treatment of Autoimmunity in CLL

Autoimmune Thrombocytopenia There are no reported clinical trials of therapy in CLL-associated ITP, and it is wise to follow the Clinical Guidelines of the American Society of Hematology (131) for the treatment of ITP and treat the CLL independently as required. These recommend that asymptomatic thrombocytopenia should only be treated when the platelet count is less than 30 x 109 L. Hospitalization should be confined to patients with mucous membrane or other severe bleeding. Conventional-dose oral prednisolone is the treatment of choice for those who need any treatment, (those with severe bleeding or a platelet count less than 30 x 109 L). The severity of hemolysis or thrombocytopenia following fludarabine is often extreme, and it may be fatal. It is important not to stint on transfusions of red cells or platelets. Immunosuppression is a hazard in these patients, and further immunosuppressive treatment will intensify the risk of infection. When treatment with steroids fails,...

The Concept of Hypersplenism

The anemia of hypersplenism has two causes. There is an expansion of the total plasma volume as well as a pooling of red cells. In very large spleens, up to 40 of red cells may be sequestered there (141,142). The neutropenia of hypersplenism is usually only moderate and asymptomatic. It is caused by an increase in the marginated pool, some of which may be located within the spleen (143,144). On the other hand, the thrombocytopenia of hypersplenism is caused by splenic pooling (144,145). In massively enlarged spleens, up to 90 of platelets can be sequestered there. Nevertheless, the splenic transit time for platelets remains normal at about 10 min, and the splenic platelets remain part of the exchangeable pool (145).

Therapeutic Challenges

Adverse effects The major adverse effect associated with ibritumomab tiuxetan is myelosuppression, consisting mainly of neutropenia and thrombocytopenia.45 46 Because of this, several parameters must be met before patients can be treated with this agent. Qualifications for therapy include < 25 lymphoma involvement of bone marrow, platelet count > 100,000 cells mm3, and no history of hypocellular marrow or failed stem cell collection.28 The average time to neutrophil nadir is 62 days, while platelets typically nadir around day 53. Cells recover after approximately 22-35 days.43 Additional adverse effects include those seen with other anti-CD20 agents, such as fever, hypotension, chills, skin rash, and rarely nausea and vomiting.45 individuals because of fluctuating clearance rates of the compound.1 The major dose-limiting toxicity of 131I tositumomab is myelosuppression, similar to that seen with 90Y ibritumomab. Therefore, patients must have < 25 lymphoma involvement of bone...

Irradiation Of Blood Components

Pancytopenia (particularly leukope-nia and thrombocytopenia) develops late in the course (median 16 days).67 68 Infection or hemorrhage are the most common causes of death, occurring within 3 weeks of onset.67 68 Treatment is rarely effective, and the mortality rate is > 90 .67 68 In our institution, as in many others, patients with hematologic malignancies, as well as those who have undergone stem cell transplantation, routinely receive irradiated blood products from the time of initial diagnosis.

Maternal Physiologic Changes With Pregnancy

Leukocytosis occurs during pregnancy, most likely due to increased levels of endogenous steroids. By the third trimester, white blood cell (WBC) may reach as high as 12,000 L and up to 20,000-30,000 L during labor.7 Platelet counts in the low normal range may be seen during gestation (gestational thrombocytopenia).6 Immune thrombocytopenic purpura occurs more often in young women any platelet count that acutely drops or is less than 50,000 L must be investigated.

Wiskott Aldrich Syndrome

Variable degrees of T and B cell immunodeficiency occur in certain congenital diseases with a wide spectrum of abnormalities involving multiple organ systems. One such disorder is Wiskott-Aldrich syndrome, an X-linked disease characterized by eczema, thrombocytopenia (reduced blood platelets), and susceptibility to bacterial infection. Some of the abnormalities in this disorder can be traced to defective T cell activation, although intrinsic loss of B cell function also contributes to the pathogen-esis. In the initial stages of the disease, lymphocyte numbers are normal, and the principal defect is an inability to produce antibodies in response to T cell-independent polysaccharide antigens, because of which these patients are especially susceptible to infections with encapsulated bacteria. The lymphocytes (and platelets) are smaller than normal. With increasing age, the patients show reduced numbers of lymphocytes and more severe immunodeficiency. The defective gene responsible for...

Hematologic Syndromes

Warm autoimmune hemolytic anemia (AIHA) and occasionally cold antibody-mediated hemolysis is seen most commonly in association with CLL,92 but 3-5 patients with NHL 93 and 1-2 with HD also develop this complication.94 Fludarabine associated hemolytic anemia is also observed in patients with CLL and occasionally in NHL. In a study of patients with NHL, AIHA was associated with female sex, poorer response rate to treatment, a higher incidence of monoclonal gam-mopathy, and inferior overall survival when compared to patients without AIHA.93 AIHA associated with lymphoma usually parallels the disease course and sometimes heralds the onset of relapsing disease. In contrast, autoimmune thrombocytopenia is seen more commonly with HD than with NHL. Unlike AIHA, when ITP recurs, it is seldom associated with a relapse. Treatment is the same as for de novo cases, and accompanies therapy for the underlying malignancy.

PI3KPKB Pathway Modulators with Unknown Mechanism of Action

Of PKB (IC50 < 0.5 M) and induces apoptosis in human tumor cells with elevated levels of PKB, it does not inhibit the kinase activity of recombinant myr-PKB , PI3K, or PDK1. In vivo antitumor activity (tumor growth inhibition > 80 ) against a panel of s.c. human tumors xenografts (e.g., OV-CAR3, OVAR8, and PANC1) with aberrant PKB activation was observed when triciribine was administered i.p at 1 mg kg day. Ex vivo analyses of tumor samples showed that the compound blocks PKB phosphorylation at Thr308 and Ser473 without affecting protein content. At the therapeutic dose, the compound did not affect body weight and glucose levels in plasma. The compound fulfilled the preclinical requirements and entered Phase I clinical trials a few years ago. Hepatotoxicity, hypertriglyceridimia, thrombocytopenia, hypocalcemia, and hyperglycemia have been reported as the most common side effects, and, due to its side effects at high doses, the compound has been limited in the clinic. Phase II...

Agnogenic Myeloid Metaplasia Ammmyelofibrosis With Myeloid Metaplasia

The hemoglobin ranges between 9 and 13 g dL. The WBC count is elevated in about half of the patients, normal in one third, and low in the remainder. Examination of the peripheral blood smear discloses a shift toward granulocytic immaturity, including a few myeloblasts and promyelocytes. Significant changes in the RBCs include variation in size and shape and teardrop-shaped forms (though teardrop forms are not specific for AMM). Large fragments and clumps of megakaryocytes and large platelets may be seen. Nucleated RBCs are noted in advanced cases. The platelet count may be increased, normal, or low, depending upon the stage of disease.

Malignant BCells CD5CD19

The malignant B-CLL B-cell has been well characterized by surface immunophenotype. This latter feature gives us a potential clue as to its origin and functional capacity. In addition to the common B-cell antigens CD19, CD20, and CD21, these malignant cells have been demonstrated to express CD5 and variable amounts of surface-bound immunoglobulin (sIg). In normal hosts, CD5+ B-cells occur at the edge of germinal centers in the mantle zone of lymphoid follicles (14) and are found in cord blood. This latter marker on the malignant B-CLL clone may provide insight into the level of arrest in development of the monoclonal CLL B-cell. The faint expression of sIgs on the B-CLL B-cells is also common to normal B-cells at the edge of germinal centers. The sIgs in B-CLL are usually IgM and or IgD, and rarely IgG or IgA (15). The sIgs often have reactivity for multiple self-antigens (polyreactive autoantibodies) with low avidity and frequently behave like rheumatoid factor (9). Up to 25 of...

Semaxanib SU5416 SU6668 and Sunitinib SU11248

But there were mild-moderate side effects included nausea, diarrhea and fatigue. Median time on study was 13 weeks (range 2-86 weeks), and no maximal tolerated dose (MTD) was reached. In a dose-escalation pharmacological study, SU6668 was administered at 100 or 200 mg kg to 16 patients with advanced solid tumors. No significant toxicities were observed. SU6668 was extensively bound to plasma proteins. A three-times daily dose regime suggested an MTD of 100 mg kg when administered with food. Half-life was 3.6 h. A dose of 300 mg kg administered with food was well tolerated among 35 patients, with adverse effects including fatigue and joint pains. DLT was 400 and 800 mg kg with grade III thrombocytopenia. Four patients had stable disease for more than 6 months. Phase I data were presented at the 39th ASCO meeting, June 2003. A group of 24 patients with advanced solid tumors were given between 200 and 500 mg kg day of SU6668 for 28 days. Grade I and II toxicities were edema, nausea,...

Second Era 19241973 Initial Clinical Investigations Into CLL 221 Major Contributors

In the first comprehensive report on CLL in 1924, Minot (Fig. 11) and Isaacs (23) compared their series of 92 CLL patients with 84 CLL patients reported by Ward. Figures 12 and 13 are extracted from their report. They showed that most cases of CLL occurred at 45-54 yr of age. The male female ratio was 3 1, symptoms were usually present 9 mo before the patient presented, and another 6 mo more was required to confirm the diagnosis. Minot and Isaacs (23) further report on 50 patients who received irradiation and 30 patients who did not and who served as controls. The source of irradiation was radium, administered over the lymph nodes and spleen. They noted that there was no difference in the duration of life span for the two groups 3.45 yr (40 mo). We have taken the liberty of using their data to draw Fig. 14. However, they did note that individual patients did benefit if the irradiation was given at 1 or more years prior to death. Although there seemed to...

Clinical Trials

In the setting of a poor functional age, serious comor-bid medical conditions, and particularly patient preference, less intensive chemotherapy or aggressive supportive care may be more appropriate treatment options. Drugs such as hydroxyurea (generally given in doses of 500-3000 mg day, adjusted to the degree of leukocytosis and or treatment-related thrombocytopenia) and low-dose ara-C (at a dose of 10 mg m2) are well tolerated and will reduce leukocytosis for a period of time, though neither will impact survival.96 We use the phrase aggressive supportive care to emphasize that symptoms will be treated vigorously and to distinguish this modality from hospice. Blood and platelet transfusions should be administered to alleviate symptoms stemming from anemia and thrombocytopenia, and antibiotics initiated when appropriate. In addition, integrative therapies such as Reike, therapeutic touch, and herbal medicines may be used by the willing patient. These latter interventions often can be...

Prognostic Factors

Estudio y Tratamien to de las Hemopatias Malignas) and Italian (GIMEMA Gruppo Italiano Malattie Emato logiche dell' adulto) APL investigators defined low-, intermediate-, and high-risk subgroups of APL patients based on presenting white blood cell (WBC) and platelet counts (low risk WBC count < 10,000 L and platelet count > 40,000 L intermediate risk WBC count < 10,000 L and platelet count < 40,000 L high risk WBC count > 10,000 L).4 Based on the above analysis, as well as on data from numerous other groups, it is now well known and accepted that APL patients who present with WBC counts of more than 10,000 L have a high risk of treatment failure, due both to an increased incidence of deaths during induction and to a higher risk of relapse. Specific genetic findings, such as the bcr-3 PML breakpoint5 and internal tandem duplication (ITD) of the FLT3 gene,6-9 as well as microgranular morphology, are associated with high WBC count, but have not, in general, been found to have...

The Role Of Arac

While ara-C has historically been relegated to a minor role in the treatment of APL,57 more recent data suggest that certain patients, particularly those with high-risk APL, may derive considerable benefit from the addition of ara-C to their treatment. The German AML Cooperative Group,2425 which uses high-dose ara-C during induction, is one of the only groups to report essentially equivalent outcomes in patients with high and low WBC counts, suggesting that high-dose ara-C overcomes the negative prognostic impact of high WBC count. In the recently reported AIDA 2000 trial,26 intensification of consolidation therapy with ATRA and ara-C in high-risk patients led to a cumulative incidence of relapse of 2 , well below the 29 relapse rate seen in the earlier AIDA 0493 trial, and significantly below the 9 relapse rate noted in intermediate-risk patients consolidated with anthracyclines and ATRA alone. Finally, the European APL Group20 has reported preliminary results of a randomized trial...

Toxicities

Myelosuppression occurred in all patients, and 97 and 99 of patients showed grade 3 to 4 neutropenia and thrombopenia, respectively. Secondary complications of severe (grades 3 and 4) infections (27 ) and bleeding (14 ) were seen. The median time to recovery of neutrophils to more than 500 L was 42 d from the first dose of gemtuzumab ozogamicin for remission patients. The median time to recovery of platelets to 25,000 L was 36 d and 75 d from the first dose of gemtuzumab ozogamicin for patients achieving a complete remission (CR) or complete remission, except for incomplete platelet recovery (CRp), respectively. Transient myelosuppression was expected, because normal committed myeloid precursors express CD33 (28). The duration of myelosuppression was not significantly different from that seen with high-dose cytarabine salvage regimens (29).

Disease Presentation

Patients with acute lymphoblastic leukemia (ALL) present with signs and symptoms related to impaired hematopoiesis from progressively worsening bone marrow involvement. Anemia may result in fatigue, light-headedness, dyspnea, and pallor. Patients with thrombocytopenia may develop petechiae, purpura, and hemorrhage. Fevers and infections also commonly occur due to neutropenia. Approximately one-third of patients have been reported to have infections, hemorrhage, or constitutional symptoms at the time of diagnosis.1-3 Clinical characteristics for patients presenting with ALL are given in Table 12.1. Thrombocytopenia is also commonly observed at the time of diagnosis. Kantarjian et al. noted that 74

Morphologic Cr

Morphologic CR without complete recovery of platelet count is not considered a category of CR in AML patients.1 The same is true for ALL patients. Time to platelet recovery seems to predict outcome of patients with de novo ALL who have achieved CR.5 In one study, patients who did not achieve platelet recovery by day 48 had a significantly worse outcome than those who achieved platelet recovery by day 12. Therefore, in ALL, morphologic CR without platelet count recovery (> 100 X 109 L) should not be regarded as CR.

Congenital Infection

Thrombocytopenia (< 100 x 103 mm3) 77 thrombocytopenia (< 100,000 mm3), atypical lymphocytosis, hemolytic anemia, and elevated cerebrospinal (CSF) fluid protein (> 120 mg dL). Elevations of serum transaminases and direct bilirubin are present in the immediate newborn period and peak during the second week of life (77). However, hyperbilirubinemia and liver function abnormalities often persist beyond the neonatal period, resolving over a few months (77). Thus, invasive procedures such as liver biopsy are not justified on the basis of persistent liver function abnormalities in infants with symptomatic congenital CMV infection. Thrombocytopenia is noted in the first few days of life in the majority of infants. The platelet count nadir occurs in the second week of life and normalizes in most patients by the third week of life. CSF abnormalities, especially elevated protein (> 120 mg dL) appear to correlate with clinical indicators of CNS damage (78). About 70 of infants with...

Acute toxicity

The major acute toxicity of 2-CdA is myelosuppression. In their long-term follow-up study, investigators at Scripps Clinic noted a 16 incidence of Grade 3 and a 71 incidence of Grade 4 neutropenia in the first 135 consecutive treated patients.5 Ten percent had Grade 3 and 10 had Grade 4 thrombocytopenia. Grade 3 anemia occurred in 20 and Grade 4 in 2 . Forty-two percent developed neutropenic fever, though in only 13 , was an infection documented. Of these, the most common infecting organism was Staphylococcus, usually associated with the indwelling intravenous catheter. Although there were several oral herpetic infections and acute dermatomal herpes reactivations, no fungal infections were found. This high rate of neutropenia with culture negative neutropenic fever was also noted at similar rates in other single-institution series with 2-CdA. Despite the frequency of myelosuppression, additional acute toxicities were uncommon. There were no significant rates of nausea, vomiting,...

Splenectomy

Splenectomy was the treatment of choice for hairy cell leukemia before the introduction of effective cyto-toxic therapies. In the majority of cases, the peripheral blood counts responded favorably and patients survived for years after the operation, often without additional therapy. Splenectomy removes splenic sequestration of blood elements, thereby alleviating pancytopenia. However, in situations in which pancytopenia is secondary to bone marrow infiltration by hairy cells, splenectomy is less beneficial. CR, defined as hemoglobin greater than 11.0 g dL, granulocyte count greater than 1000 mm3, and a platelet count greater than 100,000 mm3 (Catovsky criteria), has been reported in 40-67 of patients (see Table 31.3). Improvement in at least one cytopenia is seen in up to 90 of patients. The most common hematologic parameter to improve postsplenectomy is the platelet count, often seen within days of the surgery. Patients who achieve a CR have improved survival compared to partial...

Taxanes

As a single agent in the setting of locoregional, recurrent, and metastatic disease, docetaxel is also tolerated fairly well with leukopenia as the primary dose-limiting tox-icity (39). Response rates have been favorable at approx 42 when administered docetaxel (100 mg m2) every 21 d. Hesse et al. reported on significant toxicities encountered in a phase I study of concomitant taxotere (initial dose 15 mg m2) conventional radiation therapy (70 Gy) grade 3 4 radiation dermatitis, neuropathy, and thrombocytopenia at dose level 1 (40). Of five evaluable patients three patients achieved a CR and one patient achieved a PR. Based on the severity of these toxicities, this treatment schedule was not pursued further.

Ifna therapy of cml

Complete hematologic response (CHR) Normal white blood cell count (WBC) (< 10.000 1) Normal platelet count (< 450,000 l) Normal differential (no immature cells) Disappearance of all symptoms and signs of CML The optimal dose of IFN-a is still a matter of dabate. Usually, a dose of 5 x 106 IU m2 is recommended (38). However, in the long run, the IFN-a dose must be adjusted once the WBC decreases to below 2000 l or the platelet count to below 50,000 l. The goal should be to decrease the WBC to a level of 2000 to 4000 l and to achieve a complete hematologic remission. For this

Diagnostic Dilemmas

Certain patients with MDS may present with unusual or uncharacteristic features and represent a diagnostic challenge. These cases usually represent a small but difficult subset of patients in which to confidently establish the diagnosis. Patients may present with isolated thrombocytopenia that may antedate the diagnosis of MDS by months or years.59 The bone marrow may reveal increased megakaryocytes, and an antiplatelet antibody may be identified in the serum. However, as noted above, this may be seen in conjunction with MDS, and may not represent a true case of immune thrombocytopenic purpura (ITP). Often, treatments typically used for ITP are ineffective. In these patients, careful examination of peripheral blood and bone marrow morphology may reveal the correct diagnosis. As in other patients in whom establishment of a diagnosis may be problematic, cytoge-netic analysis may be helpful in leading to the correct diagnosis of MDS. Finding a cytogenetic abnormality frequently...

Supportive Care

Platelet transfusions are used to prevent or treat bleeding due to severe thrombocytopenia or platelet dysfunction. Assuming normal platelet function, prophylactic transfusions are generally reserved for patients with a platelet count of < 10,000 L. Patients with evidence of significant platelet dysfunction should be evaluated on a case-by-case basis. Otherwise, thrombocy-topenic MDS patients who are not bleeding can be observed if they have no other risk factors for significant bleeding. For patients undergoing active therapy for MDS, it may be desirable to maintain a platelet count of > 20,000 L during periods of reversible, treatment-related myelosuppression. A diagnosis of immunemediated thrombocytopenia (ITP) should be considered in thrombocytopenic patients, as ITP and other autoimmune phenomenas are associated with MDS.5 Potent thrombopoietic agents, however, are not currently available. Interleukin-11 has been tested in thrombocy-topenic MDS patients, but its safety and...

Demethylating Agents

Low-dose 5-azacytidine was first used to treat MDS by the Cancer and Leukemia Group B (CALGB) in the 1980s. Small studies evaluated 5-azacytidine at a dose of 75 mg m2 day by either continuous intravenous infusion or subcutaneous injection for 7 days each month and found a 49 or 50 response rate, respectively both showed a complete remission (CR) rate of 12 .5152 In a subsequent, multicenter, randomized, phase III trial, 191 patients with MDS of all subtypes were randomized to receive either 5-azacytidine given subcutaneously at a dose of 75 mg m2 day for 7 days per month with supportive care, or supportive care alone.53 Patients on the supportive care arm were permitted to crossover to the 5-azacytidine arm after 4 months for worsening disease or persistent severe cytopenias. The overall response rate (CR + PR) on the 5-azacytidine arm was 23 (7 CR), with a median response duration of 15 months and a median time on treatment of 9.1 months. Hematologic improvement was seen in 37 of...

Presentation

Figure 41.3 Bone marrow finding in AA. (a) Peripheral blood smear from a patient with aplastic anemia demonstrates severe pancytopenia with normocytic to slightly macrocytic anemia, neutropenia, and thrombocytopenia (peripheral blood, Wright-Giemsa stain, original magnification X 100). (b) Bone marrow touch imprints may be helpful in excluding mimics of aplastic anemia, such as hairy cell leukemia, which can result in a dry tap. This low-power image of a touch imprint reflects the overall hypocellularity encountered in aplastic anemia (bone marrow biopsy touch imprint, Wright-Giemsa stain, original magnification X 10). (c) Bone marrow biopsy in aplastic anemia illustrates severe panhypoplasia with only rare scattered lymphocytes and plasma cells (bone marrow core biopsy, hematoxylin-eosin stain, original magnification X40). (d) Because marrow cellularity may vary geographically within the biopsy, with the area immediately subjacent to the cortex often being hypocellular, it is...

Quality Of Life

Major response For patients with a pretreatment platelet count less than 100 000 mm3, an absolute increase of 30 000 mm3 or more for platelet transfusion-dependent patiens, stabilization of platelet count and platelet transfusion independence. Minor response For patients with a pretreatment platelet count less than 100 000 mm3, a 50 or more increase in platelet count with a net increase greater than 10 000 mm3 but less than 30 000 mm3.

Thalidomide

A phase II trial was conducted at Rush University Medical Center in which 83 MDS patients of all subtypes were given thalidomide 100 mg once a day escalating to a target dose of 400 mg a day.44 The overall response rate was 19 . Fifty-one patients were evaluable at 12 weeks, of whom 16 (almost 30 ) had an erythroid response using the IWG criteria, 2 3 of which were major responses, most of those becoming transfusion independent or achieving a > 50 reduction in transfusion requirements. Improvement in thrombocytopenia or neutropenia was less significant. The most common reason patients were unable to complete the trial was due to toxicities, namely neuropathy, constipation, fatigue, and fluid retention at a dose beyond 200 mg a day. For 10 of the 16 responders, the median time to response was 16-20 weeks, and the majority of responders had lower risk disease refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS), or a low or int-1 IPSS.

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