Chronic Lymphocytic Leukaemia: Proposals for a Revised Prognostic Staging System

Binet, Jacques‐Louis; Catovsky, Daniel; Chandra, Pradeep; Dighiero, Guillaume; Montserrat, Emilio; R., K.; Sawitsky, Arthur

doi:10.1111/j.1365-2141.1981.tb02727.x

Cited by 203 publications

(35 citation statements)

References 12 publications

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“…The disease may be characterized by a rather indolent course with good long-term prognosis in the absence of therapeutic intervention, or it may take on an accelerated course requiring treatment immediately. 1,2 However, patients with early stage disease may sometimes progress more rapidly than would be expected on the basis of their clinical stage. Identification of other prognostic factors such as ␤ 2 -microglobulin and soluble CD23 has allowed a better stratification of early-stage disease patients, but whether initiation of treatment based on these parameters changes outcome favorably or delays progression is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Expression profile of 11 proteins and their prognostic significance in patients with chronic lymphocytic leukemia (CLL)

et al. 2002

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It has been suggested that the expansion of the leukemic cells in chronic lymphocytic leukemia (CLL) is due to dysregulation of pathways of programmed cell death (apoptosis) rather than cell proliferation, although differences may exist in early vs late and treated vs untreated patients. In the present study, we analyzed the expression of 11 proteins in CLL cells that are implicated in the control of apoptosis, proliferation, and differentiation, and correlated this expression profile with survival. Using a quantitative solid-phase radioimmunoassay (RIA), we measured the cellular protein levels of Bcl-2, cyclin D1, PCNA, ATM, Fas, Bax, retinoic acid receptor alpha (RAR␣), retinoic acid receptor beta (RXR␤), Flt1, VEGF, and cellular ␤ 2 -microglobulin in 230 samples of CLL. Univariate analysis using the Cox proportional hazard model showed a correlation with survival of only the following proteins: Bcl-2 (P Ͻ 0.001), cyclin D1 (P = 0.027), Fas (P = 0.055), PCNA (P Ͻ 0.001), and ATM (P = 0.028). In a multivariate analysis using classification and regression tree analysis (CART), five groups of patients (nodes) could be generated with significant differences of survival expectation (P Ͻ 0.0001) based on levels of expression of the above proteins. Based on CART analysis, Bcl-2 levels emerge as the most important protein in predicting survival between all 11 proteins studied. Patients with marked elevation in Bcl-2 levels had the worst outcome while patients with intermediate levels, but with high levels of PCNA and cyclin D1 or abnormal ATM expression had intermediate survival. These data indicate that intracellular levels of proteins such as Bcl-2, ATM, cyclin D1, and PCNA can be used as markers to predict clinical behavior and survival in patients with CLL. The pathways in which these proteins are involved may also represent possible targets for future therapeutic trials in CLL.

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Section: Introductionmentioning

confidence: 99%

Expression profile of 11 proteins and their prognostic significance in patients with chronic lymphocytic leukemia (CLL)

et al. 2002

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“…7 The IW on CLL developed an integrated staging system in 1981 (Table 5). 8 T-cell function may be impaired, especially in patients with advanced disease, although the T cells are not derived from the malignant clone. The CD4/CD8 ratio is decreased due to an increased number of T-suppressor cells.…”

Section: Stagingmentioning

confidence: 99%

Chronic leukemias

Morrison

1994

CA: A Cancer Journal for Clinicians

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“…Clinical staging systems, introduced almost three decades ago by Rai et al 47 and Binet et al, 48 have been effective in classifying patients with CLL into broad prognostic groups.…”

Section: Prognostic Factors In Cllmentioning

confidence: 99%

Stem cell transplantation for chronic lymphocytic leukemia: should not more patients get a transplant?

Jabbour

Keating

Champlin³

et al. 2004

Bone Marrow Transplant

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Summary:Novel therapeutic approaches with conventional chemotherapy and monoclonal antibody combinations have improved the complete remission rates in chronic lymphocytic leukemia. However, cure remains elusive, particularly in fludarabine-refractory patients, whose prognosis remains poor. Autologous stem cell transplantation (SCT) has been explored for such patients, lengthening the time to treatment failure in selected patients, but there is little hope that it will improve the cure rate. The strategy is particularly ineffective in patients with poor biological prognostic factors, such as abnormal cytogenetics and unmutated immunoglobulin heavy-chain variable region. Allogeneic SCT remains the only curative approach, producing an extended disease-free survival in 25-60%, mainly via the graft-versus-leukemia effect. The treatment-related mortality with such an approach has been significant, however, with a 30-40% risk of death within 100 days of the transplant. Nonmyeloablative (NMA) conditioning regimens may produce high response rates and lower morbidity, especially for patients with chemosensitive disease. Randomized trials designed according to the new biologic prognostic parameters described in chronic lymphocytic leukemia are required to better define the role of NMA SCT in the near future.

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Chronic Lymphocytic Leukaemia: Proposals for a Revised Prognostic Staging System

Cited by 203 publications

References 12 publications

Expression profile of 11 proteins and their prognostic significance in patients with chronic lymphocytic leukemia (CLL)

Expression profile of 11 proteins and their prognostic significance in patients with chronic lymphocytic leukemia (CLL)

Chronic leukemias

Stem cell transplantation for chronic lymphocytic leukemia: should not more patients get a transplant?

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