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survival over 15 years. In this study, 42% of patients died from unrelated causes. However, the median survival of patients with HCL-V is significantly shorter than that of patients with HCL-C. The therapeutic approach to HCL-V is still
debated. Various treatment approaches active in HCL-C achieve partial or no response in HCL-V, and remission is usually shorter than in HCL-C. In addition, HCL-V seems to be resistant to ther- apeutic modalities usually highly effective in the treatment of HCL-C, such as interferon a (IFN-a) and purine nucleoside analogs (PNAs). Currently, principles of therapy of this rare disease derive from uncontrolled single institutional studies, or even single case reports [1,4]. For these reasons, the outcome of therapy is unsatisfactory, with no standard therapy established.
Splenectomy
Good clinical and hematological responses after splenectomy have been observed in 13 out of 19 patients (74%) with HCL-V, reported by Matutes et al. [3]. The median response duration was 4 years
(1–10þ). These data suggest that splenectomy should be considered as the treatment of choice in HCL-V because it corrects cytopenias and removes a significant bulk of disease [4]. Some authors suggest that previous splenectomy may improve the response to chlorambucil and PNAs in patients with HCL-V. Splenic irradiation may also be useful in some patients with HCL-V, especially in elderly patients with massive splenomegaly and poor performance status.
Trteatment Splenectomy
Cladribine Pentostatin
Fludarabine Interferon a
Rituximab
No of patients
Overall response
Complete response Response duration
19 74% 0% Median 4 years 21 48% 10% 8–127 months
24 55% 4% 15–69þmonths 4 21 Interferon
All seven patients with HCL-V treated with IFN-a by Sainati et al. showed no objective response [5]. In the group of 14 patients treated with IFN-a reported by Matutes et al. only two (14%) of them achieved a temporary partial response [3]. This may relate to a low number of IFN-a receptors, which are abundant in typical HCL.
Purine nucleoside analogs
The results of treatment of HCL-V with PNAs are poor. In our study, cladribine (2-CdA) was given in 2 h infusions for 5 days in a daily dose of 0.12 mg/kg. The mean number of 2-CdA cycles was 3.5 [6]. Four of six patients did not respond to 2-CdA treatment and only two entered a partial response (PR) lasting
for 60þand 29þmonths, respectively. Subse- quently, one of them had a splenectomy and another received 2-CdA courses every 6–12 months as maintenance therapy. Palomera et al. reported three patients with HCL-V who were treated with 2-CdA at a daily dosage of 0.1 mg/kg by continuous intravenous infusion for 7 days [7]. One of them had been previously treated with splenectomy and IFN-a and two patients were untreated. The patients received from one to three 2-CdA courses. Two PRs and one complete response (CR) were achieved
lasting from 15þto 127þmonths. These reports indicate that 2-CdA is significantly less active in HCL-V than in HCL-C. An analysis of 19 cases published so far shows a response rate of 55%, including only two CRs (Table I) [8].
Table I. Tharepies used in hairy cell leukemia variant (details available in [8]). Comments
Splenectomy or splenic irradiation should be considered if splenomegaly is a major symptom
Responses are mainly partial after more than one course. Maintenance treatment required in the majority of patients
Patients with HCL-V treated with pentostatin have a poorer clinical outcome and a lower response rate than those of patients with HCL-C
50% 0% 18 months, 30 months Data limited to four patients. Similar activity to 2-CdA and pentostatin
9.5% 0% 12 months 6 100% 100% 4–19þmonths
Alemtuzumab 2 100% 50% NR BL22
Most patients with HCL-V are resistant to IFN-a
Rituximab is a promising therapy for patients with HCL-V, and can be combined with 2-CdA. Further clinical studies are required before rituximab can be considered as front-line therapy for HCL-V
Single case reports suggest that alemtuzumab is an active agent in HCL-V even relapsing after rituximab
3 100% 100% 8–13þmonths
Results suggest that BL22 may be a very effective agent in the treatment of refractory HCL-V
HCL-V, hairy cell leukemia variant; HCL-C, classic HCL; 2-CdA, cladribine; IFN-a, interferon a; NR, not reported.
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