For a concise review article on the treatment of hairy cell leukaemia with cladribine, please refer to:
Belani, R. and A. Saven. 2006. "Cladribine in hairy cell leukemia." Hematol Oncol Clin North Am 20(5):1109-1123 (available free to NSW CIAP users)r
Various methods of administration of cladribine in hairy cell leukaemia have been investigated. The most reported method is a single course of a seven day continuous IV infusion of 0.1mg /kg /day.rrr Alternative methods have shown to be efficacious and safe, including IV infusion over 2 hours of 0.14 mg/kg /day for five days,r weekly 2 hour IV infusion of 0.15 mg/kg for six weeksr and subcutaneous bolus administration of 0.085 mg /kg /day for seven days.r
Hoffman et alr analysed the initial and long term outcomes after treatment of patients with active hairy cell leukaemia with a single cycle of cladribine. 49 patients were treated with cladribine 0.1 mg /kg /day by continuous IV infusion for a total of seven days. With a median follow-up of more than four years, 80% continued in remission. Only two deaths occurred. A CD25-negative phenotype may predict for a poorer response to cladribine. Patients who relapse may be retreated with cladribine, but subsequent remissions may be of shorter duration.
Liliemark et alr studied the bioavailability of cladribine by treating 10 patients with alternate days of IV infusion (2 hours) or SC cladribine at a dose of 0.14 mg/kg/day. It was concluded that the bioavailability of SC cladribine was 100% (SC route gives a high peak concentration of short duration with AUC identical to that of IV) and no local toxicity was noted.
Juliusson et alr conducted a study with 73 patients with hairy cell leukaemia. Patients received subcutaneous cladribine 0.085 mg /kg /day for 7 days. 81% achieved a CR after 1 or 2 courses and 13% had a PR. There were no relapses after 20 months. Neutropenic sepsis requiring antibiotics occurred in 38% of patients and no toxicity was observed at the injection site.
Rituximab use in relapsed/refractory Hairy Cell Leukaemia
There are some studies that recommend the use of Rituximab (R) in hairy cell leukaemia (HCL), in combination with purine analogue (PA), to attain a deeper remission than otherwise would be attained by PA alone.
In a large long term follow up case series by Else et al,r 233 patients were followed for a median duration of 16 years, and the complete response rates to PA alone in the relapse setting ranged from 50-69%, whereas in combination with Rituximab the CR rate was 92%. In return, the achievement of CR was associated with superior relapse-free survival.
Similar results were seen by Leclerc et al,r whereby in the relapse setting use of Rituximab plus PA achieved a CR of 86%. It is worth noting that Rituximab monotherapy has consistently inferior outcomes compared to R plus PA, and should only be considered if there is contraindication to the use if PA.
The French Society of haematology (FSH) has made a cautious recommendation for the use of R plus PA in the relapsed setting (described as "non-validated treatment regimens" since there have been no consensus practice in terms of whether Rituximab 375 mg/m2 x 4 doses would be administered concurrently with or sequentially to PA.)
Rituximab may be available through PBS subsidy under the context of "relapsed or refractory low grade B cell NHL".
In Hoffman et alr at three months 76% achieved CR and 24% achieved PR with an OS of 100%. With a median follow up of 55 months, relapse free survival is 80% and OS of 95%.The CD25-negative phenotypes had only partial remissions and all relapsed. Eight patients were retreated with cladribine and all achieved at least partial remission.
From Hoffman et alr a single course of cladribine was associated with significant acute myelosuppression. Median nadir was 0.7 x 109/ L. 47% required short admission to hospital for grade 3/4 neutropenia and fever which was invariably culture negative. The median platelet nadir was 55 x 109/ L with no significant episodes of bleeding. There were five cases of development of second malignancies which occurred in four patients.r