By Dr. Farhad Ravandi
M. D. Anderson Cancer Center
Hairy cell leukemia (HCL) is an indolent lymphoid malignancy characterized by infiltration of the bone marrow, liver, spleen and occasionally lymph nodes with malignant B-cells with cytoplasmic hair-like projections. The disease generally presents with significant spleen enlargement, and low blood count usually resulting in infectious complications. Similar to CLL, patients often experience a long disease course and continue to relapse after purine analogs and alkylating agents.
Purine analogs such as 2-chlorodeoxyadenosine (2-CDA or cladribine) and 2-deoxycoformycin (DCF or pentostatin) have been used successfully to treat patients with HCL. Overall response (OR) rates ranging from 75% to 100% after a single course of cladribine have been reported. However, responses are not universal and a significant proportion of patients relapse. Similarly, not all HCL patients respond to pentostatin. Those patients that achieve responses often ultimately relapse.
There is a definite relapse rate associated with therapy of HCL with both cladribine and pentostatin and the relapse-free survival does not appear to achieve a plateau. This is somewhat reminiscent of other chronic lymphoid diseases such as follicular lymphoma and CLL where despite a long disease course patients continue to relapse after nucleoside analog and alkylating agent therapy. Both response rate and duration improve significantly after the addition of monoclonal antibodies such as rituximab to the regimens used to treat patients with lymphoproliferative disorders. Recently, a number of reports have demonstrated the efficacy of rituximab in treating patients with relapsed HCL. The target of rituximab, the pan-B cell antigen CD20, is brightly expressed on the surface of hairy cells. Dr. Nieva (Scripps) and colleagues reported their experience in 24 patients with HCL after failing cladribine therapy. Rituximab was administered at 375 mg/m2 once weekly for 4 weeks. They reported a CR rate of 13% and a PR rate of 13% for an OR of 25%. No unusual toxicity was reported. Similarly, Dr. Lauria (Siena, Italy) and colleagues treated 10 patients with relapsed/progressed HCL with a similar regimen of rituximab and reported 1 CR and 4 PR (OR 50%). In the study by Dr. Hagberg (Uppsala, Sweeden) and colleagues 11 patients with HCL (including 3 previously untreated patients) were treated with rituximab 375 mg/m2 weekly for 4 weeks. They reported an OR rate of 64% with 6 CRs and 1 PR (including 1 CR in the untreated patients). At M. D. Anderson Cancer center, we are using an extended -dosing regimen of rituximab 375 mg/m2 weekly for 8 doses, 15 patients with relapsed/refractory HCL were treated. A higher response rate of 80% including 8 (52%) CR and 2 (13%) CR with residual marrow disease and 2 (13%) PR was observed using this extended course regimen.
Rituximab has been successfully combined with nucleoside analog based chemotherapy in the treatment of other indolent lymphoproliferative disorders. This has been generally well tolerated with no serious side effects. Based on the reported safety of rituximab and cladribine and the lack of overlapping toxicity, and in attempt to improve the rate and durability of responses, we have initiated a phase II study of cladribine followed by rituximab in patients with newly diagnosed or relapsed/refractory HCL. Cladribine 5.6 mg/m2 will be administered by continuous infusion daily for 5 days. This will be followed by 8 weekly doses of rituximab 375 mg/m2 starting on day 28. Studies for minimal residual disease by immunophenotyping will be performed on patients achieving CR at the completion of cladribine and then after completion of the 8 week course of rituximab. Patients will receive the first dose of each agent (Cladribine and Rituximab) at MD Anderson Cancer Center but the subsequent doses may be administered by the local treating oncologists. The early results in 12 patients are encouraging with few side effects and a 100% response rate. For further information please contact Farhad Ravandi, MD at 713-745-0394.