Hairy cell leukemia (HCL) is an indolent B-cell neoplasm that strongly
expresses CD20. Despite initial very high response rates with cladribine
(Leustatin), many patients ultimately relapse.
From January 2000 to February 2001, 16 patients (15 male, 1 female) with HCL,
with a median age of 57 years (range: 38-81 years), having relapsed after
prior treatment with cladribine, were treated with rituximab (Rituxan) at 375
mg/m² weekly × 4. All patients had received at least one prior course of
cladribine (median: 44 months from last cladribine; range: 19-119 months),
eight patients received two prior courses of cladribine, five patients received
interferon, and two patients had undergone splenectomy.
A total of 15 patients are currently evaluable for response, with at least a
6-month follow-up. Three patients (20%) achieved complete remissions, defined as
the absence of hairy cells in the peripheral blood and bone marrow with the
following peripheral blood parameters: ³ 1.5 × 109 neutrophils/mL, hemoglobin
concentration ³ 12 g/dL, and ³ 100,000 platelets/mL. One patient (7%) had
minimal residual disease as evidenced by positive staining on DBA.44 and CD20
without morphologic evidence of HCL by light microscopy. One patient (7%)
achieved a partial response, defined as at least 50% improvement in all
cytopenias with at least a 50% reduction of hairy cells from the peripheral
blood and bone marrow. Thus, 5 of 15 (33%) patients achieved a response. At a
median follow-up of 12 months (range: 9-20 months), no responders had
relapsed. Three patients (20%) achieved hematologic improvement without
sufficient reduction in marrow HCL cells to qualify as a response; both lasted
less than 3 months in duration.
The only grade 3/4 toxicities demonstrated were culture-negative febrile
neutropenia, transient and reversible disseminated intravascular coagulation
related to rituximab administration, and a diverticular abscess. Of 10 patients
who failed to respond, 6 subsequently received other treatments: 3 were
retreated with cladribine, 2 underwent splenectomy, and 1 received pentostatin
(Nipent). All six patients treated after rituximab achieved hematologic
improvements, although no bone marrow follow-up data are presently available.
CONCLUSION: Rituximab, administered at this dose and schedule, has only
modest activity in cladribine-failed HCL patients when compared to other agents
active in this disease.