Defects in Cellular Immunity

Infections associated with impaired cellular immunity such as tuberculosis, cryptococcosis, listeriosis, and herpes zoster have been reported in CLL patients even before intensive therapy was available and before techniques were available to identify specific components of cellular immunity. Prominent among these abnormalities are decreased concentrations of circulating CD4+ lymphocytes, which may occur secondary to the disease process but are a significant consequence of therapy with purine...

Second Era 19241973 Initial Clinical Investigations Into CLL 221 Major Contributors

In the first era, CLL was separated from leukemia, and its separation from lymphomas was initiated. The second era, between 1924 and 1973, was marked by significant contributions to our understanding of the natural history of the disease, the diagnosis, and (as poor as they were) the various treatments for this disease. It should be noted that chronic leukemia was often the subject of a given report and that both forms (myelogenous and lymphocytic) were studied. Just before...

References

Cronkite ER, et al. Clinical staging of chronic lymphocytic leukemia. Blood 1975 46 219-234. 2. Binet, J-L, Leporier M, Dighiero G, et al. A clinical staging system for chronic lymphocytic leukemia. Cancer 1977 40 855-864. 3. Ashby W. Determination of the length of life of transfused blood corpuscles in man. J Exp Med 1919 29 267-281. 4. Berlin R. Red cell survival studies in normal and leukaemic subjects latent hemolytic syndrome in leukaemia with splenomegaly nature of...

Ataxia Telangiectasia Gene and Risk of CLL

The genetic basis of CLL is largely unknown. Probably for technical reasons, cytogenetic abnormalities appear to be less frequent in CLL than in many other hematological malignancies although the use of techniques such as in situ hybridization, comparative genomic hybridization, and others has significantly increased the proportion of cases with cytogenetic abnormalities (16). A number of chromosome breakage syndromes have been known for many years to be associated with an increased risk of...

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....

First Era 18451924 Recognition of CLL As a Distinct Entity

The reports of Rai 2 , Galton 3 , Gunz 4 , Hamblin 5 , Piller 6 , and Videbaek 7 are useful in reconstructing this early historical period. Gunz 4 attributes the first accurate description of a case of leukemia to Dr. Velpeau, who in 1827 8 described a 63-yr-old florist and lemonade seller Monsieur Vernis, who had abandoned himself to the abuse of spirituous liquor and women 8 . Hamblin 5 shed further light on this subject by noting that in this profession and in his former job as a florist,...

Treatment of Indolent CLL

It is not clear whether early therapy benefits patients with indolent CLL. This form of the disease includes patients with a median age of 64 yr displaying a survival greater than 10 yr. In indolent CLL, Chlorambucil CB given daily or intermittently, alone or combined with corticosteroids, is the most commonly used drug. It often provides a period of relief from any symptoms, even in advanced disease. However, there has been much uncertainty as to whether such chemotherapy should be started...

Staging Systems 31 Rai et al

In 1975, my colleagues and I KRR proposed a system of clinical staging, stratifying CLL patients into five stages 5 Table 1 . The criteria of our staging system were based on Galton and Dameshek's postulate that CLL is characterized by a continuous accumulation of immu-nologically inert lymphocytes thus, with increasing tumor burden, clinical disease would progress from observable enlarged lymphoid masses, with relatively preserved marrow function in early stages, to severely impaired marrow...

Treatment of Smoldering CLL

The French group proposed a classification that segregated stage A into A' and A'' 11,15,23 . Criteria for A' were hemoglobin level higher than 120 g L and lymphocyte count lower than 30,000 mm3 and for A'' they were hemoglobin under 120 g L and or lymphocyte count higher than 30,000 mm3. The survival of these two groups was clearly different, with a 5-yr survival of 82 in the A' group and 62 in the A'' group. Interestingly, the survival of the A' group was very close to that of a sex- and...

Chromosome Abnormalities In

With proper mitogen stimulation in vitro in dedicated laboratories, most CLL samples present mitotic cells, and clonal chromosome abnormalities are found in about one-half of the cases studied 5,6 . In more than one-half of cases with clonal abnormalities, there is only one single chromosome aberration, and in one-fourth of those with clonal abnormalities there are complex From Contemporary Hematology Chronic Lymphocytic Leukemia Molecular Genetics, Biology, Diagnosis, and Management Edited by...

IgVH Mutations

CLL has long been considered a homogeneous disease of CD5 B-cells, which are pregerminal cells that have not been exposed to antigenic stimulation. In 1999, two different groups reported an important breakthrough in CLL 29,88 . These groups clearly showed that the mutational status of the somatic mutations of the variable region of the immunoglobulin genes IgVH correlates with different disease subsets. Thus, those patients with unmutated IgVH genes have a poorer prognosis than those displaying...

Immunophenotypic Characteristics of Leukemic BCells in CLPD Other Than CLL

Among the B-CLPD, CLL is the most common disease, its differential diagnosis from other leukemic B-cell CLPD being a constant challenge. Typically, CLL exhibits a highly characteristic phenotype, different from that found in other B-CLPD 44-48 , including weak expression of CD22, CD20 FMC7, CD79b and sIg, together with a relatively high reactivity for the CD5 and CD23 antigens for more details, see Chapter 7 . In the last decade, scoring systems based on the above mentioned markers 46,48 have...

Immunophenotypic Characteristics of Normal Mature BCells

Many studies have been reported, in which the phenotypic features of normal, mature PB 25,28,31 , and or BM B-cells 32-36 have been analyzed. These studies systematically show that virtually all PB and a substantial part of BM B-cells are mature sIg lymphocytes. Most of these correspond to naive sIgM sIgD 80-90 and, to a lesser extent 10-15 , immature sIgM B-lymphocytes 37-43 . In contrast, sIgM , sIgG , or sIgA memory B-cells only represent a minor fraction of the total sIg lymphocytes lt 10...

Clinical Stage

The clinical staging systems independently developed by Rai et al. 3 and Binet et al. 4 in the early 1980s, which are based on easily obtainable biological and clinical parameters, are extremely useful for assessing prognosis in patients with CLL. These staging systems not only facilitate the treatment of patients according to individual prognosis, but also make it possible to conduct and compare trials based on the risk of disease. Rai's stages were further classified as low Rai stage 0 ,...

Hairy Cell Leukemia

HCL was initially described in 1958 under the term leukemic reticulosis 59 . Because of the unique morphologic features of the leukemic B-cells, with their highly characteristic hairy cytoplasmic projections, the term hairy cell leukemia was finally accepted in 1966 60 . HCL Immunophenotypic Patterns of the Most Common Leukemic B-Cell Chronic Lymphoproliferative Disorders Other Than CLL CD19 CD22 CD20 FMC7 CD5 CD10 CD23 CD79b sIg CD103 CD11c CD43 CD24 HC2 CD25 CD38 - weak - - weak - - weak -...

Atypical CLL

Atypical CLL aCLL is an ill-defined term applied to cases that mimic CLL but do not have the classical morphological or immunophenotypic features. Uniformly accepted criteria for aCLL do not exist. Historically the term aCLL has been used primarily for lymphocytosis with morphologically atypical cells lymphoplasmacytoid features, irregular clefted nuclei 13 . Numerous studies have attempted to correlate the morphological definition of aCLL with immunophenotype 7,14,15 , but these studies have...

Lymphocyte Proliferation and Cell Cycle Regulation

CLL is a human malignancy caused principally by defects that prevent programmed cell death rather than by alterations in cell cycle regulation. In the vast majority of patients, CLL cells are predominantly G0 quiescent cells that gradually accumulate in the patient's body, not because they are dividing more rapidly than normal, but because they are surviving too long. Several methods have been used to evaluate tumor cell proliferation and to correlate kinetic cellular parameters with clinical...

Trisomy

The first nonrandom chromosome abnormality discovered in CLL was trisomy 12 12 7 , which is found in about one-third of those who show clonal abnormalities, i.e., about 17 of all patients Fig. 1 . Using FISH analysis, a somewhat higher percentage is achieved 8 about 24 of over 600 CLL patients studied showed evidence of trisomy 12 for review, see ref. 9 , whereas 16 had 12 in the German FISH study 10 . Half of all patients with trisomy 12 have no additional abnormality, and although 12 may...