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....

References

Ruiz-Arguelles GJ, Cantu-Rodriquez OG, Gomez-Almaguer F, et al. Hairy cell leukemia is infrequent in Mexico and has a geographic distribution. Am JHematol 52(4) 316-318, 1995 Aug. 2. Staines A, Cartwright RA Hairy cell leukemia Descriptive epidemiology and a case study. Br J Hematol 85(4) 714-717, 1993 Dec. 3. Au WY, Kwong YL, Ma SK, et al. Hairy cell leukemia in Hong Kong Chinese a 12-year retrospective survey. Hematol Oncol 18(4) 155-159, 2000 Dec. 4. Kristinsson Sy, Vidarsson B, Agnarsson...

Comparisons Of Allo Sct Versus Auto Sct Follicular

There are few trials prospectively designed to compare allo SCT versus auto SCT for follicular NHL patients. Table 65.7 illustrates the results using myeloablative preparative regimens for allo SCT as compared to auto SCT for use in follicular NHL.16 35-37 Again, most series are small in size except for communications from registry analyses, such as the recent report by van Besien et al.16 Treatment-related mortalities for allo SCT are approximately 30 , nearly a log-fold higher compared to...

Response Criteria

The National Cancer Institute-Working Group (NCI-WG) and the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) independently proposed criteria for assessing response in patients with chronic lympho-cytic leukemia (CLL) (Table 25.1), the NCI proposal having gained wider acceptance and being the one usually employed.12 These criteria have proved to be extremely useful to conduct and compare trials, thereby contributing to progress in CLL therapy. Nevertheless, these proposals were...

Radiation therapy alone

Staging laparotomy was part of the standard work up of patients with HL in the 1960s and 1970s, in part due to a lack of effective radiological techniques to evaluate abdominal and pelvic lymphadenopathy. Most patients therefore underwent pathologic staging. In contrast, at the present time few patients undergo pathologic staging. Computerized tomography and positron emission tomography (PET scanning) have lead to the common practice of clinical staging. With this evolution, some of the data...

Prognostic Factors

While the presence of the t(15 17) or PML-RARA fusion confers an overall good prognosis to APL patients, there nevertheless exists a subset of APL patients who are at high risk of relapse or death despite best available therapy. In 2000, Spanish (PETHEMA Programa de 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...

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....

Primary Cerebral Lymphoma

Primary CNS lymphoma (PCL) is defined as an NHL that is confined to the craniospinal axis without systemic involvement. This diagnosis is rare in immunocompetent patients but occurs more frequently in patients with both congenital and acquired immunodeficiency. AIDS-related PCL occurs equally frequently across all ages and transmission risk groups, and the tumors are high-grade B-cell diffuse large cell or immunoblastic NHLs. The presence of Epstein-Barr virus (EBV) is a universal feature of...

Recommended Treatment Approach For Early Stage Mycosis Fungoides

Nonrandomized clinical trials have not suggested that any one skin-directed therapy is preferable. Treatment choice should be made with the patient's preference and practitioner's skill in mind. Our philosophy regarding the management of patients is to maximize benefits while minimizing side effects. Therefore, we advocate the use of topical monotherapy. If patients fail to respond, we switch to a different topical therapy. Our first-line treatment for early stage patients is PUVA or NB-UVB...

Blood And Bone Marrow Changes

Anemia is present in 60-80 of patients at presentation.1-5 It is usually mild to moderate in severity and is normocytic, normochromic in morphology. The anemia has the characteristics of anemia of chronic inflammation (formerly anemia of chronic disease) with low serum iron, decreased transferrin saturation, and elevated ferritin. The reticulocyte count is low, reflecting a hypoproliferative state. A bone marrow examination commonly reveals erythroid hypoplasia and a varying degree of myeloma...

Tcell Phenotype

The T-cell phenotype is an important adverse prognostic factor all by itself. Except for CD30+ anaplastic large T-cell lymphomas, patients with T-cell lymphomas have significantly lower response rates and shorter disease-free and overall survival results than do those with B-cell lymphomas.222380 Gisselbrecht et al.22 showed that patients with non-ALCL T-cell tumors have more disseminated disease, B symptoms, bone marrow involvement, hepatosplenomegaly, and skin involvement than do those with...

Histone Deacetylase Inhibitors

Chromatin remodeling is part of the epigenetic changes seen during neoplastic transformation. While promoter hypermethylation is associated with silencing of tumor suppressor genes, it is not the only modification that controls chromatin condensation and promoter activity. Posttranslational modifications, such as acetyla-tion, methylation, and phosphorylation of histone proteins comprising the chromatin nucleosomes, are responsible for formation of complexes that control gene expression....

Quality Of Life

Measured by an instrument such as the FACT Questionnaire. Clinically useful improvement in specific domains Physical Functional Emotional Social Spiritual (Improvements must last at least 2 months in the absence of ongoing cytotoxic therapy.)b Hematologic improvement should be described by the number of individual, positively affected cell lines (e.g. HI-E HI-E + HI-N HI-E + HI-P + HI-N). Major response For patients with pretreatment hemoglobin less than 11 g dL, greater than 2 g dL increase in...

Clinical Trials

Remission induction therapy for older adults with AML is no panacea, with 5-year survival rates resembling those of patients with advanced lung cancer.2 It is thus reasonable to consider investigational agents for older AML patients up front, particularly as these patients have a disease that resembles the advanced MDS or secondary AML.22 88 Potential targets for antileukemia therapy are explained in more detail in Chapter 9. They include specific signaling molecules required for the...

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...

Tcell Recognition Of

As noted previously, the principal function of HLA molecules is to acquire peptide fragments and to interact with effector T cells or NK cells. Peptide fragments bound by HLA molecules are found in a cleft whose walls are formed by more or less parallel alpha helices that sit atop a floor formed by p-pleated sheets (Figure 93.5). In class I molecules, six pockets are formed that accommodate side chains of the bound peptides.2025 Most of the highly polymorphic amino acid positions can be...

Collection

Optimal yield of mononuclear cells remains a critical factor in UCB collection. A suitable UCB unit has been defined as a volume of at least 40 ml (excluding anticoagulant) and a total nucleated cell (TNC) count of 6 X 10.814 Factors associated with improved UCB harvest include fewer previous births, larger infant size, greater gestational age, longer umbilical cord, and larger placenta.1516 Two methods of UCB collection exist in utero and ex utero. In utero collection is initiated within...

Solid Tumors Incidence And Risk Factors

The risk of solid tumors after treatment of lymphoma is most established in Hodgkin's lymphoma. However, as therapies for NHL improve and result in more survivors, it is expected that risks and risk factors for the development of solid tumors in this setting will be similar to those in Hodgkin's lymphoma. In the modern Hodgkin's lymphoma therapeutic era (post-mechlorethamine), lung and breast cancer, often appearing 15 or more years after completion of lymphoma therapy, have emerged as the most...

Splenectomy

The definition of remission in a malignancy is established in order to distinguish the effectiveness of different treatment options and determine whether treatment has an impact on survival and quality of life. The development of these definitions for HCL has paralleled the improved management of this disease. For many years, the major treatment for patients with HCL was splenectomy.5 Splenectomy was undertaken either due to pain and discomfort secondary to an enlarged spleen or for the...

Thyroid And Gonadal Dysfunction

Subclinical and clinical thyroid disease is common after treatment of HL. In a series of 151 patients, 26 cases of subclinical, 12 cases of manifest clinical hypothyroidism, and 2 cases of hyperthyroidism were documented.14 Thyroid dysfunction was more frequent in patients who underwent mantle or neck radiotherapy. Hypothyroidism was often revealed after the sixth year of follow-up. A high incidence of thy-roiditis was also reported in this group of patients. Annual monitoring of thyroid...

Demethylating Agents

DNA methylation is a normal mechanism of gene expression regulation, and abnormal DNA methyla-tion patterns that can interfere with the expression of genes used for growth, differentiation, and survival are seen in MDS. It has been known for some time that hypomethylating drugs can promote in vitro cellular differentiation,50 and that this occurs at doses much lower than those needed for maximal cytotoxic effect. The clinical trials using the DNA demethylating agents 5-azacytidine (azacitidine,...

Immune Stimulation And Myeloma Chronic infections and eczema

Many medical conditions associated with chronic stimulation of the immune system, such as repeated infections, allergic conditions, or autoimmune disease, have been reported to increase the risk of MM. In a case-control study, past history was abstracted from medical records for leukemia, n 299 non-Hodgkin's lymphoma (NHL), n 100 and MM, n 175 patients, and matched with 787 controls. Prior histories of eczema and musculoskeletal conditions were associated with higher risk for MM with no role...

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...

Activated Signalling Components

A number of signaling components are now known to be activated in HCs. The so-far identified activation signals and their likely mutual relationships are summarized in Table 29.4. Some of these signals are transient and clearly originate from cell stimulation by components of the in vivo microenvironment, but some persist in vitro, suggesting that they are truly constitutive. It is, however, not yet clear which of these constitutive signals is a direct consequence of the still unknown oncogenic...

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...

Immunoglobulin Measurements

Serum protein electrophoresis is required for detecting monoclonal Ig. Cellulose acetate or agarose gel elec-trophoresis is commonly used. The latter was shown to be more sensitive.110 A monoclonal immunoglobulin (M spike) is identified as a discrete, homogeneous band on electrophoresis or as spikes in the 7, p, or a2 region of the densitometer tracing. Two M proteins may occur rarely (biclonal gammopathy). Immunofixation is then used to determine the isotype of the paraprotein, using specific...

Radioimmunotherapy RIT

Two radioimmunoconjugates are currently commercially available Y-90 ibritumomab tiuxetan (Zevalin) and I-131 tositumomab (Bexxar). The clinical trials thus far conducted with radioimmunoconjugates have demonstrated greater activity than their cold antibody, and are useful in patients who have relapsed after or who are refractory to rituximab. 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...

Chronic Myeloid Leukemia

Grade 3 or 4 neutropenia had been observed in 13 patients with chronic myelogenous leukemia (CML), treated on a phase III randomized trial with imatinib. Imatinib does not affect the Philadelphia chromosome negative normal hematopoietic progenitors, and while G-CSF and GM-CSF have been tested without adverse consequences in a phase II trial of this agent, the standard recommendation is to withhold and subsequently restart the therapy, rather than prescribing growth factors.26

Androgens

Androgens have been beneficial for the treatment of MMM-associated anemia. Various androgen formulations have been used in MMM patients, including nan-drolone,29 oxymetholone, and danazol.3031 Doses of danazol in the range of 600-800 mg day led to responses in four out of seven patients (treated from 3 to 6 months) with MMM anemia in a report by Cervantes et al.30 In this study, responders had either previously been splenectomized, or had only modest splenomegaly. In addition, it has been...

Maternal Physiologic Changes With Pregnancy

Several normal adaptive changes occur in the hemato-logic environment during pregnancy. Plasma volume increases by about 50 with only a 20-50 rise in red cell mass, resulting in a normocytic anemia.6 Inadequate hematopoiesis can result if iron and folate stores are not supplemented in advance. The normocytic anemia often becomes microcytic if iron metabolism cannot keep pace with fetal demand despite supplementation. Leukocytosis occurs during pregnancy, most likely due to increased levels of...

Antithrombotic therapy

Low-dose aspirin, 80-100 mg daily, seems reasonable to recommend, in addition to cytoreduction, for patients who have a prior history of thrombosis or cardiovascular disease.9 In addition, aspirin is effective for the treatment of erythromelalgia and other microvas-cular, neurologic, and ocular disturbances. 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,...

Survival

Survival in symptomatic patients without treatment is estimated to be between 6 and 18 months, and with appropriate therapy > 10 years. However, the mean survival is influenced by the age at diagnosis. Thus, younger patients diagnosed and managed appropriately can have longer survivals. The main causes of death are thrombosis (29 ), hematologic malignancies in those treated in previous eras with alkylating agents (23 ), nonhematologic malignancies (16 ), hemorrhage (7 ), and myelofibrosis...

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...

Info

These include age > 60 years, tumor stage, B symptoms, serum LDH level, and the presence of more than one extranodal site of involvement. The IPI is essentially a scoring system in which these five clinical features are tallied to categorize patients into one of four prognostic groups that correlate with both relapse-free survival (RFS) and overall survival (OS) (Table 54.2). Moreover, patients with low-risk disease consistently attain complete response more frequently than the...

Introduction

Myelodysplastic syndrome (MDS) is not a single disease, but rather a group of disorders affecting the bone marrow. Therefore, no single approach is likely to be of universal benefit to all patients. In fact, one way to consider the complexity of MDS is to think of it as being to the bone marrow what pneumonia is to the lungs the response of an organ to a variety of assaults, such as aging, toxic exposure, infections, and autoimmunity. Among infections of the lungs alone, pneumonia could be the...

Morphology

Until recently, ALL was classified based on morphology and cytochemistry according to the French-American-British (FAB) schema, which includes three major subtypes L1, L2, and L3.1 However, recent studies have failed to show prognostic significance of the L1 and L2 categories, and their designation has not had a high reproducibility rate among morphologists. Based on these findings, and as a result of improved understanding of the biology of these disorders, the 2001 World Health Organization...

Therapeutic Challenges

Some challenges have been encountered with radioim-munoconjugates as well. Tumor bulk, location, and burden vary greatly among patients and can significantly affect the distribution of the drug. Complex and meticulous dosimetry studies using trace-labeled radioimmunoconjugates must be conducted with each patient prior to initiating therapy. This determines where the highest concentration of radiation will be delivered ideally, tumor sites receive the largest dose, while healthy organ and tissue...

Criteria For Diagnosis

The National Cancer Institute (NCI) sponsored a working group in 1988 that developed criteria and guidelines for clinical protocols, as well as general-practice recommendations for patients with CLL.3 In 1996, the criteria and guidelines were revised to those in current use.4 These guidelines importantly include indications for treatment and criteria for evaluating response to treatment. The diagnosis of CLL requires a sustained absolute lymphocytosis of greater than 5000 lymphocytes L. This...

Adoptive Immunotherapy

Khatri et al. demonstrated the striking temporal relationship between the endogenous expansion of a TCR Vfi-restricted, CD3+CD8+ population of MHC class I-restricted CTL and the regression of a monoclonal PTLD in a HSCT recipient. Unfortunately, the delay in recovery of such immune surveillance against transformed EBV-positive B cells results in the development of potentially fatal PTLD. T-cell immunotherapy has been reported to be efficacious in the management of PTLD in this setting.39...

Allogeneic Sct In

Various therapeutic options exist for the management of a newly diagnosed patient with MDS. In addition to the subtype and IPSS score at diagnosis, the age and performance status of the patient are important determinants of feasible therapeutic options. In spite of significant improvements in supportive care and the increasing therapeutic options that are available (Chapter 44 and 48), an allogeneic SCT remains the only option that has curative potential, leading to the recommendation that all...

Treatment Approaches

Prognosis remains poor in MCL, and patients who respond to treatment usually relapse. There is currently no standard treatment for the disease. Conventional treatment of MCL results in response rates of 20-60 . The disease invariably recurs and the median survival in this disease is approximately 3 years. Therapeutic options are continually being refined as the clinical methods of classifying MCL evolve and as the biology elucidates the histologic and cytogenetic characteristics of MCL...

Selfantigens For Immunotherapy Of

Proteinase 3, a serine protease stored in azurophilic granules, is a differentiation antigen associated with myeloid granule formation and is overexpressed in a variety of myeloid leukemia types, including CML cells. Therefore, it has been considered a possible target antigen for specific active immunotherapy. CTLs specific for an HLA-A2.1-restricted nonpolymorphic peptide (PR1) derived from proteinase 3 have shown HLA-restricted cytotoxicity, and selectively inhibit CML progenitors over normal...

Gcsfgmcsf

Since the two growth factors mobilize different cells, concurrent or sequential administration of these growth factors may be synergistic. Spitzer et al.30 conducted a randomized study comparing G-CSF plus GM-CSF each at 5 g kg per day with G-CSF 10 g kg per day for stem cell mobilization in 50 patients with lymphoma and solid tumors. There were no statistically significant differences in either the CD34+ cell yield or the rate of hematopoietic recovery between the two groups. Winter et al.31...

Extramedullary Plasmacytoma

Primary extramedullary plasmacytoma occurs rarely and involves most commonly the upper air passages and paranasal sinuses (90 ), though a variety of organ involvement has been reported.105 The clinical manifestations depend on the sites of involvement. In the head and neck region, painless or painful mass may be the first sign. Nasal obstruction, discharge, epistaxis, hoarseness, or hemoptysis may occur. Less commonly involved sites include lung, GI tract, lymph nodes, and the thyroid gland....

Relapse

The relapse rate following IS therapy may be substantial. For ATG CsA, it may be as high as 35 in 7 years.1281 In general, relapse has a good prognosis and survival of relapsed patients is not significantly shortened.81 Patients with falling blood counts can receive a trial of CsA. If unsuccessful in rescuing the counts, a repeated course of ATG should be given. The response rates are likely comparable to those seen in the initial course of ATG. In some instances, rabbit ATG can be used instead...

Clinical Features In

Patients usually present with symptoms secondary to cytopenias, as the leukemia suppresses normal hematopoiesis. Patients may have pallor, fatigue, and shortness of breath secondary to anemia bleeding, bruising, and ecchymoses secondary to thrombocy-topenia coagulation defects and infections secondary to neutropenia.3 Fifteen to twenty percent of patients will present with fevers, which can result from infection or from the leukemia itself.4 Fewer than 20 of patients will have bone pain.4

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...

Inhibitors Of The Downstream Pathways Ras signaling

Activation of the Ras signaling pathway is essential for BCR ABL function. After BCR ABL has activated Ras, Ras requires several additional posttranslational modifications, including prenylation. Prenylation involves adding a lipid anchor to the target protein, which 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...

Radiolabeled Antibodies

Another targeting strategy for NHL has been the use of radioimmunoconjugates. Radiolabeled antibodies are capable of delivering a radiation dose to neighboring cells while minimizing doses to nonmalignant tissues. Low-dose-rate radiation continues to expose cells to radiation even after initial exposure, resulting in accumulation of cell damage leading to apoptosis in cells that may have been effectively repaired after more conventional high-dose-rate radiation. Two radioimmunoconjugates...

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...

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...

Cml Treated With Interferon

As interferon became the treatment of choice, the validity of the Sokal system came into question. To address the question of prognostic factors in patients treated with interferon, Hasford et al. analyzed data on 1303 patients aged 10-85 years and treated with interferon.15 This analysis identified age, spleen size, percentages of circulating blasts, basophils, and eosinophils, as well as platelet counts as significant prognostic factors. The resulting Hasford score was then validated on 322...

Molecular Anatomy Of The Bcrabl Fusion

The breakpoints in ABL are spread over a large genomic region and may occur 5' of ABL exon Ib, between ABL exons Ia and II or, most frequently, between the two alternative first ABL exons (Figure 17.2) (reviewed in Ref. 36). Despite this variation, the ABL portion in the fusion mRNA and protein is usually constant, encompassing ABL exons 2-11. This is thought to be the result of posttranscriptional processing of the primary transcript. In contrast, the breakpoints in BCR localize to three...

Irradiation Of Blood Components

TA-GVHD is a rare, potentially lethal disorder caused by the engraftment and proliferation of donor lymphocytes in the transfusion recipient.3667 Viable donor lymphocytes in the transfused blood component recognize the HLA antigens of the recipient and mount an immune response. TA-GVHD was first reported almost four decades ago and, to date, over 200 cases of TA-GVHD have been reported. The true incidence is unknown, as it is thought that many patients with TA-GVHD go unrecognized and...

Other Potential Nosocomial Exposures

One of the best-known pathogens to be transmitted through hospital water sources is Legionella.40 Hospitals vary in their Legionella incidence, and infection control and surveillance measures differ from one institution to another. Copper-silver ionization systems have been described as the most effective way to control potential sources.40 Hospital visitors should not be permitted to visit if they have any fever or respiratory illness. Visitors should wash their hands before and after leaving...

Lenalidomide Cc5013 Revlimid

Lenalidomide is a member of a class of thalidomide analogues called immunmodulatory drugs, or IMiDs. In vitro, lenalidomide modulates cytokine production and T-lymphocyte stimulation at least 100 times more potently than thalidomide.118, 119 Phase I trials in relapsed-refractory patients using doses ranging from 5 mg day to 50 mg day have shown response rates of 40-71 , even in patients previously treated with thalidomide.120, 121 The toxicity profile of lenalidomide is very different than that...

Overexpression Of The Baalc Gene

The BAALC gene, mapped to band 8q22.3, encodes a protein with no homology to any known proteins or functional domains. BAALC is expressed mainly in neu-roectoderm-derived tissues and hematopoietic precursors, with no expression in mature BM or blood mononuclear cells.65 High expression of BAALC mRNA in circulating blasts is an independent adverse prognostic factor in uniformly treated adults younger than 60 years with de novo AML and normal cytogenetics.1920 In another, smaller study, high...

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...

Supportive Care

Many patients with MDS require close monitoring only during the early phase of their disease. However, once patients become symptomatic from cytopenias, the timely use of supportive care measures can impact significantly on their quality of life (QOL). Supportive care measures generally consist of packed red blood cell (PRBC) transfusions to treat or prevent the symptoms and physiologic consequences of anemia, antibiotics to treat or prevent infection, and platelet transfusions to prevent or...

Gmcsf

GM-CSF is a multilineage CSF because it stimulates the proliferation and differentiation of HPCs into neu- trophil, eosinophil, and monocyte colonies. GM-CSF functions in conjunction with other cytokines, ery-thropoietin and IL-3, to promote the proliferation and differentiation of erythroid and megakaryocytic progenitors, respectively. Administration of GM-CSF not only increases the number of monocytes but also increases the function of monocytes and macrophages including oxidative metabolism,...

Nodular sclerosis Hodgkins lymphoma

The nodular sclerosis subtype accounts for 70 of classical HL.13 This subtype is morphologically characterized by collagen bands that surround Hodgkin's or Reed-Sternberg cells. NS HL equally affects males and females and the median age at diagnosis is 28 years. At diagnosis, most patients present with stage II disease, with mediastinal involvement noted in 80 of patients, bulky disease (see Diagnostic Evaluation section for definition of bulky disease) in 54 , and splenic or lung involvement...

Microbiology

Table 99.2 summarizes the common pathogens encountered during the preengraftment period. The most common portals of entry for bacterial infection during this period include central venous catheters and mucositis of the mouth and gut arising from the preparative regimen. Thus, not surprisingly, bacterial pathogens such as viridans streptococci and Gramnegative bacilli from the mouth and gastrointestinal tract, respectively, and skin organisms such as coagulase negative staphylococci are the most...

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...

Chemotherapy Plus Growth Factors For Stem Cell Mobilization

Although chemotherapy alone can produce increases in progenitors in PB, multiple phase II studies have shown that the addition of growth factors such as G-CSF and GM-CSF to myelosuppressive chemotherapy enhances mobilization and allows for more progenitors to be collected with fewer apheresis procedures while reducing myelotoxicity. Siena et al.37 reported that after highdose CY, an approximately 30-fold expansion of CFU-GM numbers was observed. This increase was further magnified, to over 100...

Descriptive Epidemiology

HL is an uncommon cancer, with approximately 8000 new cases diagnosed in the United States annually.5 Several large epidemiologic reports have noted that males have a slightly higher incidence of HL than do females that whites are at higher risk than are blacks and that HL seems to be more common in patients of higher socioeconomic class than in those of lower socioeconomic class.6-11 HL is associated with a bimodal age-specific incidence distribution. The first peak occurs in early adulthood,...

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...

Hemorrhagic Cystitis

Hemorrhagic cystitis after transplant may be caused by cyclophosphamide or ifosfamide. The nonenzymatic metabolite of these agents, acrolein, causes hyperemia and ulceration of the bladder mucosa, resulting in hemorrhage and focal necrosis. Previously treatment with busulfan appears to increase the risk of hemorrhagic cystitis.114 Prophylaxis includes hyperhydration with forced diuresis, bladder irrigation, or mesna. There is no clear preferred strategy. Randomized studies comparing one...

Presentation

Most patients with AA present with symptoms of anemia or bleeding due to deficient red blood cell and platelet production. Infection associated with low neutrophil numbers is not a common initial presentation. Often, AA is uncovered incidentally patients may remain asymptomatic for a long time due to the latent onset of anemia. Consequently, the latency period and the onset of the disease are difficult to determine. In some cases, when AA is discovered early, a follow-up blood examination will...

Vinca Alkaloids

Vincristine, vinblastine, vindesine, vinorelbine The vincas are natural compounds originally derived from the periwinkle plant. Two of these compounds, vincristine and vinblastine, are usedin the treatment of a variety of hematological malignancies, including lymphocytic leukemia, lymphoma, Hodgkin's disease, and myeloma. Vinca alkaloids are known as spindle poisons, because of their ability to inhibit the assembly of microtubules. This targeting of microtubules is thought to be one of the most...

Nonmyeloablative Transplantation

Similar to the situation in ALL, nonmyeloablative transplantation for AML has been shown to reduce transplant-related morbidity and mortality, mainly by reducing the incidence of serious complications in the immediate posttransplant period. Here as well, the GVL reaction is an important component of therapy. The Spanish Group for Hematopoietic Transplantation demonstrated a significant improvement in outcome for patients who developed grade II-IV acute GVHD in comparison with patients who...

Polycythemia Vera

The dominant feature of polycythemia vera (PV), also termed polcythemia rubra vera or primary proliferative polycythemia, is the excessive production of erythrocytes frequently accompanied by increases in other hematopoietic lineages. To achieve a diagnosis of PV it is important to exclude potential causes of a secondary erythrocytosis. Clinical evaluation, pathology, cytogenetics, and the determination of erythropoietin levels or demonstration of spontaneous erythroid colonies are all...

Making The Diagnosis

Although the complete blood count and bone marrow findings in CML cases may be classic, less marked phe-notypic presentations may mimic other myeloprolifera-tive diseases, especially AMM. The diagnosis rests on the demonstration of the Ph chromosome in the bone marrow, the (9 22) translocation in the marrow or peripheral blood by FISH (fluorescent in situ hybridization) studies, or by reverse transcriptase analysis by polymerase chain reaction (RT-PCR) of the marrow or blood for the molecular...

Age At Diagnosis

Most clinical trials5-9 have noted a marked difference in both complete remission (CR) rate and DFS in ALL patients, depending on patient age. Both comorbid medical conditions resulting in increased toxicity of induction and postremission therapy and the presence of higher risk biologic features contribute to the adverse prognosis of older adults with ALL. DFS is consistently less than 20 in patients older than 60 years. Shorter remission duration in older adults is also a consequence of the...

Classification Of Aa Based On Etiology And Pathophysiologic Mechanisms

AA may have diverse causes that allow for clinically useful classification (Table 41.1). While iatrogenic AA is uncommon, it can be easily recognized. The most common is the idiopathic form of AA, and most parts of this chapter deal with this classical AA entity. Congenital bone marrow failure syndromes can evolve to AA they will not be discussed in detail here. Drugs and chemicals have been implicated as etiologic agents in AA for many decades. Benzene has served as a model chemical implicated...

Biology Of

An observation made years ago is that CLL B cells isolated from the peripheral blood undergo rapid apopto-sis in vitro. The rate of apoptosis varies substantially, but there appears to be no simple correlation between rates of apoptosis in vitro and clinical outcome. A similar rapid rate of in vitro apoptosis is also observed in B cells derived from involved lymph nodes in patients with follicular lymphoma. As both populations express large amounts of BCL2 protein, these data may indicate that...

Leptomeningeal Lymphoma

Leptomeningeal involvement is seen in about 15 of patients diagnosed with PCNSL. The presentation is commonly clinically silent and only detectable by cytological examination of the CSF. Less frequently, there can be overt cranial nerve or nerve root symptoms that are easily visible as gadolinium enhancement of the leptomeninges on MRI examination. Leptomeningeal disease is usually present with intracerebral involvement, but in 1-2 of cases it is the sole site of PCNSL. The treatment depends on...

Comprehensive Treatment Strategy For

The clinical problems that MDS patients experience can be broken down into three basic categories. While anemia is the major problem for some patients, others have potentially life-threatening neutropenia or throm-bocytopenia. Patients in both categories may be at high risk for developing AML. These scenarios are discussed below. 1. Anemia only These patients often have relatively good-risk disease, and are most suitable for low-intensity approaches or supportive care alone. rHuEPO should be...

Chemotherapy Regimens Mopp and MOPP derivatives

The dosage, schedule, and frequency of MOPP chemotherapy are described in Table 73.6. Patients receive four drugs over a 2-week interval followed by a 2-week recovery period. A total of 4 weeks constitutes one cycle of treatment. Most patients receive six cycles. Historically, the dose of vincristine used in MOPP frequently exceeded the currently recognized dosage limit of 2 mg. Two updated mature studies with 1045 and 14 years46 follow-up, respectively, showed that 66 of patients have remained...

Imatinib Meslate In Accelerated And Blastphase

Although it is unlikely that patients, nowadays, will enter blastic or accelerated phase without having received prior treatment with imatinib, it is worthwhile to review the results of imatinib therapy in ima-tinib-naive patients for historical interest, as well as to gain some understanding of the role of bcr abl in the growth and proliferation of CML cells during transformation to the blast phase. The clinical development of imatinib mesylate followed the traditional development of cytotoxic...

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...

Nhl

Bartholomew's34 NHL 27 330 72 months Older patient age St. Bartholomew's34 NHL 27 330 72 months Older patient age MD Anderson37 NHL 22 493 21 months TBI conditioning MD Anderson37 NHL 22 493 21 months TBI conditioning Beth Israel Brigham38 NHL and HL 6 300 47 months Prior XRT Beth Israel Brigham38 NHL and HL 6 300 47 months Prior XRT

Mantle Cell Lymphoma

General Mantle cell lymphoma (MCL) represents approximately 6 of lymphomas.1 It generally presents in middle-aged to older adults with a median age of approximately 60 and a male predominance. Stage 3 or 4 involvement is common at presentation and bone marrow involvement is seen in more than half the patients at presentation. Although nodal disease is most common, primarily extranodal disease involving Waldeyer's ring or the gastrointestinal tract does occur.5 Pathology Nodular, mantle zone,...

Myeloablative Peripheral Blood Stem Cell Transplantation

Use of allogeneic PBSCs has increased over the last several years. PBSC transplantation results in more rapid engraftment and requires shorter hospital stays than does SCT.32 Relatively few myeloablative allogeneic PBSC transplants have been performed to date in patients with multiple myeloma. In one small study, 10 patients received granulocyte colony-stimulating factor mobilized PBSCs (median of 9.7 X 108 mononuclear cells kg and 14.3 X 106 CD34+ cells kg) from HLA-iden-tical siblings.33...

Nam H Dang and Fredrick Hagemeister

T-cell lymphoid malignancies are a heterogeneous group of relatively rare diseases that are defined as distinct entities by a constellation of laboratory and clinical characteristics, including morphologic features, immunophenotypes, genetic abnormalities, clinical manifestations, and responses to treatment. The mature T- and natural killer (NK)-neoplasms as defined by the World Health Association (WHO) classification account for approximately 10 of all lymphoid malignancies.1 However, the...

Stem Cell Transplatation

The results, techniques, and practical aspects of SCT will be described in detail in Chapter 37. However, some important aspects of SCT in CML and its integration with other treatment options are discussed here. First, SCT may be curative for a significant fraction of eligible patients who receive a transplant from a human leukocyte antigen (HLA)-identical sibling. Unfortunately, because of the requirements for age, adequate organ function and performance status, and availability of donor, only...

Treatment Of Relapsed And Refractory Dlbcl

More than half of all DLBCL patients initially entering remission with combination chemotherapy will relapse. The standard treatment approach for such patients is to deliver salvage chemotherapy followed by consolidative autologous stem cell transplantation in patients demonstrating chemosensitivity.71a Patients with chemorefractory disease and patients relapsing following an autologous stem cell transplant have an overall poor prognosis and should be considered for allogeneic stem cell...

Ovarian Tissue Cryopreservation

Ovarian tissue banking in humans is being considered to restore fertility in patients who lose ovarian function because of chemotherapy or radiotherapy.56 Ovarian tissue cryopreservation and transplantation was first examined in rodent studies and then in sheep and human ovarian xenograft studies.57 However, no pregnancies have been reported in humans from the use of cryopreserved ovarian tissue. Although promising, there is a theoretical risk that malignant stem cells will be reimplanted along...

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 patients into risk categories that predict survival in...

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...

Os

N 52 low 15 prior auto SCT (29 ) N 62 intermediate high 32 prior auto SCT (52 ) N 22 mantle cell 8 prior auto SCT (36 ) overall PFS 54 at 2 years 13 at 2 years Poor outcome in chemoresistant and non-low grade NHL N 21 intermediate high N 7 low 11 prior auto SCT 17 ablative and 11 nonablative 7 in CCR from prior auto SCT N 10 intermediate high N 10 low PFS, progression-free survival OS, overall survival CR, complete remission CCR, coutinuous complete remission. PFS, progression-free survival OS,...

Arginine Butyrate

Arginine butyrate and other histone deacetylase inhibitors induce the activity of certain genes. Exposure of EBV-positive tumor cells to butyrate results in robust induction of herpesvirus in immediate-early and early (lytic) genes, including thymidine kinase (TK), and a modest induction of lytic replication. There is now extensive experience in the administration of arginine butyrate over extended periods of time to adults and children with sickle cell anemia or P-thalassemia to...

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...

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...

Incidence And Risk Factors

The incidence of PTLD varies depending on the type of transplant, recipient age, and type of immunosuppres-sion used (Tables 62.1 and 62.2). The incidence of PTLD is 4 times higher in pediatric than in adult transplant recipients.16 In SOT recipients, the incidence of PTLD varies with the type of allograft 19 of intestinal transplants, 2-10 of heart transplants, 5-9 of heart-lung transplants, 2-8 of liver transplants, and 1-10 of renal transplants.16 Additional risk factors for PTLD in SOT...

Longterm Complications

The initial concern for patients treated with the purine nucleosides was for an increased risk of infection and the development of second malignancies due to the profound long-term suppression of CD4 and CD8 lym-phocytes.27 28 However, a significant increase in infections is not seen in patients who have responded to treatment and have normal neutrophil counts. In our series, during the 7-year median follow-up, only herpes zoster was seen in remission patients.24 A variety of second...

Epidemiology

CLL is the most common adult form of leukemia in Western society. According to a recent analysis of the Surveillance Epidemiology and End Results database,1 the annual overall age-adjusted incidence in the United States between 1997 and 2001 was 3.5 100,000 people 5.0 100,000 for males and 2.5 100,000 for females. This is a disease of older adults with distinct and unique clinical characteristics and concerns. The majority of individuals are diagnosed when over 65 years of age, and the...

Gcsfscf

SCF is an early acting hematopoietic factor that displays pronounced synergies with other hematopoietic growth factors such as GM-CSF, G-CSF, erythropoietin, IL-3, and IL-6 to stimulate proliferation of erythroid, megakaryocytic, granulocytic, and mast and basophil progenitor cells. The SCF receptor (c-kit) is present on many tissues of neuroectodermal, epithelial, and hematopoietic origin. In patients with stage II III breast cancer with no previous chemotherapy, Glaspy et al.32 showed that...

Recommended Treatment Approach For Primary Cutaneous Bcell Lymphoma

The clinical course and prognosis of CBCL is excellent and significantly differs from systemic lymphomas. Our approach to treatment strategies depends on the number and localization of lesions and the patient's age and health condition. The tox-icity of treatment should not outweigh the cosmetic and functional disability of the disease. We prefer initial observation for patients with unifocal or mul-tifocal lesions. If cosmetic consequences are a concern, we use local therapies such as...

Haploidentical HLAmismatched related donors

Related donors sharing one HLA haplotype, but with a greater level of HLA disparity have also been used.48-50,79,81,83,84,90 The greater level of disparity is associated with increased engraftment failure, GVHD, and transplant-related mortality (TRM).76,87,91 Drobyski and colleagues83 found that matched, unrelated-donor transplants had better outcomes than related donors, with more than one HLA mismatch for class I (A,B) or class II (DRB1*,DQB1*). Improved results may be obtained with more...

Aml With Rearrangements Of Band 11q23 And The Mll Gene

This category represents approximately 4 of cases of adult AML, but rearrangements involving band 11q23 and the MLL gene (also known as ALL1, HRX, and HTRX) are three to four times more common in children with AML, being especially frequent among infants aged 12 months or less, 43-58 of whom carry an 11q23 MLL abnormality.13 At both the cytogenetic and molecular genetic level, AML with the 11q23 MLL rearrangements is extremely heterogeneous. Well over 30 different balanced chromosome...