Cost-effectiveness of pentostatin compared with cladribine in the management of hairy cell leukemia in the United Kingdom.
ABSTRACT This article assesses the cost-effectiveness of pentostatin compared with cladribine in the management of hairy cell leukemia (HCL) in the United Kingdom.
A systematic literature search for papers on HCL was performed using MEDLINE, EMBASE, Current Contents, NHS Economic Evaluation Database, and the Cochrane computerized database. Search terms were HCL plus 1 of the following: incidence, prevalence, epidemiology, cladribine, interferon, pentostatin, rituximab, splenectomy, utility, quality of life, cost-effectiveness, cost-utility, resource utilization, economic, or cost. Published clinical outcomes and estimates of health care resource use obtained from 10 consultant hematologists across the United Kingdom were used to construct a 5-year Markov model depicting the current management of HCL in the United Kingdom. Utilities for health states in the model were obtained from the general public using standard gamble, time tradeoff, and visual analog scale techniques. The model was used to consider the decision by a clinician to initially treat an HCL patient with either pentostatin or cladribine and to estimate the relative cost-effectiveness of pentostatin over 5 years (at 2007/2008 prices) from the perspective of the UK's National Health Service (NHS).
According to the model, 64% of all pentostatin-treated patients are expected to be in relapse-free remission at 5 years compared with 49% of cladribine-treated patients (P = 0.04). Repeat treatment of initial partial responders, nonresponders, and those who relapse during the 5 years is expected to result in complete remission in 92% of pentostatintreated patients and 90% of cladribine-treated patients at 5 years. Using pentostatin instead of cladribine is expected to lead to a minimal cost increase (from 21,325 pounds to 21,609 pounds) and an improvement in health status (from 3.64 to 3.77 quality-adjusted life-years [QALYs]) over 5 years. Hence, the cost per QALY gained from using pentostatin is expected to be 5000 pounds. Moreover, pentostatin has a 0.90 probability of being cost-effective for a threshold of 20,000 pounds per QALY. Accordingly, using pentostatin as a first-line treatment for patients with HCL is an effective use of NHS resources.
Based on current practice, this model predicts that pentostatin is a cost-effective treatment compared with cladribine in the management of HCL from the perspective of the UK's NHS.
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ABSTRACT: Hairy cell leukemia (HCL) is an uncommon, indolent, chronic B-cell lymphoproliferative disorder involving the marrow and spleen. Therapy for HCL includes splenectomy, interferon alfa-2a and alfa-2b, pentostatin, and cladribine. The purpose of this article was to report the extended follow-up of HCL patients treated with cladribine. Two hundred nine patients with HCL who were treated with cladribine had at least 7 years of follow-up. A course of cladribine constituted a 7-day continuous intravenous infusion at a dose of 0.1 mg/kg/d. Of the 207 assessable patients who had at least 7 years of follow-up, 196 (95%) achieved a complete response (CR) and 11 (5%) achieved a partial response (PR) after a single course of cladribine (overall response rate, 100%). The median first-response duration for all responders was 98 months. Seventy-six patients (37%) experienced relapse after their first course of cladribine. The median time to first relapse for all responders was 42 months. Time to treatment failure of CRs compared with PRs was statistically significant (P <.0005). The overall survival rate was 97% recorded at 108 months. Forty-seven patients developed 58 second malignancies. The observed-to-expected ratio for second malignancies was 2.03 (95% confidence interval, 1.49 to 2.71). These results confirm previous observations that single courses of cladribine administered to patients with HCL induce high response rates, the majority of which are CRs. Most patients enjoy long-lasting complete remissions, and those patients who experience relapse can be successfully re-treated with cladribine.Journal of Clinical Oncology 03/2003; 21(5):891-6. DOI:10.1200/JCO.2003.05.093 · 17.88 Impact Factor
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ABSTRACT: Between January 1991 and December 1997, 103 patients, 97 with typical hairy cell leukemia (HCL) and 6 with HCL-variant (HCL-V) were treated with 2-chlorodeoxyadenosine (2-CdA) given as 2-h infusion for 5 consecutive d at a daily dose 0.12 mg/kg. To our knowledge this is the largest cohort of HCL patients treated with this type of regimen. Median follow-up amounted to 36 months. Fifty-six of 97 patients with typical HCL were newly diagnosed and 41 were relapsed after previous treatment. Splenectomy as a first-line therapy was performed in 23 patients and 18 remaining patients received prednisone, chlorambucil or interferon-alpha (IFN-alpha) alone or in combinations. Seventy-five (77.3%) patients entered CR and 18 (18.6%) achieved PR, giving an overall response rate of 95.9%. The mean time of first CR duration amounting to 32 months (range 3-72) did not correlate to the number of 2-CdA cycles. 2-CdA was equally effective in treatment of newly diagnosed patients and patients who relapsed after previous therapeutic procedures. Relapse of the disease occurred in 20 of 75 patients who achieved CR after 2-CdA and was usually manifested by very discrete changes in peripheral blood counts (neutropenia and/or relative lymphocytosis). The mean progression-free survival (PFS) time in this group was 37.4 (range 10-66) months. Ten of 20 relapsed patients were retreated with 2-CdA given an identical course to the first one. Seven patients entered second CR lasting 19+ (range 8-47) months and 3 experienced PR. This confirms the previous observations that 2-CdA gives no resistance to leukemic clone. Ten remaining patients have not required retreatment so far and remain in a good clinical and hematological state. The results of HCL-V treatment with 2-CdA were poor. Only 2 patients achieved PR and 4 patients did not respond to this drug. Seven patients (5 with typical HCL and 2 with HCL-V) died, 3 of causes unrelated to the disease. Second neoplasms were noted in 5 patients. 2-CdA-related side effects resulted mainly from myelosuppression and infectious complications. In conclusion we confirm the effectiveness of 2-CdA in inducing CR in patients with typical HCL, but this drug is unable to completely eradicate the leukemic clone which results in the relapse of the disease. The real incidence of the relapse rate may be underestimated unless bone marrow biopsy is performed. The results of our study indicate that a 2-h infusion of 2-CdA in HCL patients is at least as effective as a 24-h infusion but more convenient to the patients, and may be given on an outpatient basis.European Journal Of Haematology 02/1999; 62(1):49-56. DOI:10.1111/j.1600-0609.1999.tb01114.x · 2.41 Impact Factor
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ABSTRACT: To assess the activity and toxicity of 2-chlorodeoxyadenosine (cladribine, CDA) given by subcutaneous bolus injections to patients with hairy cell leukemia (HCL). Sixty-two eligible patients with classic or prolymphocytic HCL (33 non-pretreated patients, 15 patients with relapse after previous treatment, and 14 patients with progressive disease during a treatment other than CDA) were treated with CDA 0.14 mg/kg/day by subcutaneous bolus injections for five consecutive days. Response status was repeatedly assessed according to the Consensus Resolution criteria. Complete and partial remissions were seen in 47 (76%) and 13 (21%) patients, respectively, for a response rate of 97%. All responses were achieved with a single treatment course. Most responses occurred early (i.e. within 10 weeks) after start of CDA therapy, but response quality improved during weeks and even months after treatment completion. The median time to treatment failure for all patients was 38 months. Leukopenia was the main toxicity. Granulocyte nadir (median 0.2 x 10(9)/l) was strongly associated with the incidence of infections (P = 0.0013). Non-specific lymphopenia occurred early after CDA treatment, and normal lymphocytes recovered slowly over several months. No significant associations were found between infections and nadir count of lymphocytes or any lymphocyte subpopulation. No opportunistic infections were observed. One course of CDA given by subcutaneous bolus injections is very effective in HCL. The subcutaneous administration is more convenient for patients and care providers, and has a similar toxicity profile to continuous intravenous infusion. The subcutaneous administration of CDA is a substantial improvement and should be offered to every patient with HCL requiring treatment with CDA.Annals of Oncology 11/2002; 13(10):1641-9. DOI:10.1093/annonc/mdf272 · 6.58 Impact Factor