Consequences of Chemotherapy Induced Myelosuppression In Patients with Chronic Lymphocytic Leukemia (CLL)

Abstract 4637

Purine analogs, including fludarabine and pentostatin, are frequently used as first-line agents once therapy of CLL commences. However, as a result of such treatment, approximately 20% of patients become myelosuppressed to the extent that a full course of therapy cannot be given. Myelosuppression was defined as absolute neutrophil count < 1500/uL and/or platelets < 100,000 for two consecutive laboratory findings, occurring anytime from the initiation of purine analog chemotherapy until one month following last cycle of chemotherapy. We sought to determine the consequences of such myelosuppression by retrospective analysis of all patients with CLL undergoing initial treatment that included purine analogs between 2003 and 2008 at the Cleveland Clinic. We identified 45 patients meeting these criteria. The median age at treatment was 63 (range 41 to 82) and all met standard criteria for the diagnosis and treatment of CLL. Of these 45 patients, 19 could not complete all 6 cycles of planned treatment. Of these 45 patients, 9 (20% of the 45 patients analyzed) could not complete treatment due to persisting myelosuppression. The clinical characteristics of these 9 patients are compared to the other 36 patients in the table.

We attempted to correlate CD38 and Zap-70 expression with pre-treatment risk factors (age, Rai stage, and performance status), but found no association, except in the case of CD38 positivity in relation to PS ≥ 1 (p = 0.04). Cytogenetics were unknown for a majority of patients and therefore were not analyzed. The 9 patients remained myelosuppressed for a median of 10 months (range 2 to 41), and 6 of these 9 patients were platelet transfusion dependent at some point (compared to 1 of 36 patients of the non-myelosuppressed group, p <0.001). Of the 9 myelosuppressed patients, 6 recovered hematopoiesis after a median of 11 months (range 7–41), 4 relapsed with CLL after a median of 29 months (range 12 – 51), and 4 died. Of the 4 who died, 2 died while remaining myelosuppressed. Our data corroborates the findings of others that approximately 20% of patients treated with purine analogs will experience enough myelosuppression to reduce the number of cycles that can be delivered. Although we could not identify many significant pre-treatment predictors of such myelosuppression, we did observe that some patients remained myelosuppressed for long periods of time, often with adverse consequences, including transfusion dependence, relapse, and death. Efforts to avoid prolonged myelosuppression by better patient selection and strict attention to recommendations for dose reductions, rather than dose delays, may lessen the incidence of such consequences.