Comparison of methodologies for the detection of BRAF mutations in bone marrow trephine specimens.

AIMS: BRAF V600E detection assists in the diagnosis of hairy cell leukaemia (HCL); however, testing practices vary. We evaluated the clinical utility of 5 BRAF mutation testing strategies for use on bone marrow trephines (BMT). METHODS: 11 HCL, 5 HCL 'mimic', 2 treated HCL and 10 normal BMT specimens were tested for mutant BRAF, comparing Sanger sequencing, pyrosequencing, amplicon-based next generation sequencing (NGS), automated (Idylla) PCR and immunohistochemistry (IHC). RESULTS: PCR and IHC were cheaper and identified V600E in 100 % of HCL cases. Pyrosequencing detected the mutation in 91%, NGS in 55% of cases and Sanger sequencing in 27%. All assays gave wild-type BRAF results in HCL mimics and normal BMT samples. CONCLUSIONS: PCR and IHC were most sensitive and cost-effective, but these have limited scope for multiplexing and are likely to be replaced by NGS gene panels or whole genome sequencing in the medium to long term.

Cost-effectiveness of pentostatin compared with cladribine in the management of hairy cell leukemia in the United Kingdom.

OBJECTIVE: This article assesses the cost-effectiveness of pentostatin compared with cladribine in the management of hairy cell leukemia (HCL) in the United Kingdom. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Changes in finances, insurance, employment, and lifestyle among persons diagnosed with hairy cell leukemia.

BACKGROUND: While being cured of cancer generally leads to a life expectancy similar to that of the general population, the extent to which other aspects of life are affected is unknown. To address these concerns, patients with hairy cell leukemia, a cancer with a very high cure rate, were queried about employment, insurance, finances, and lifestyle during and following their treatment. METHODS: Study participants (n = 31) ranging in age from 24 to 73 years at the time of diagnosis (median, 49 years) were surveyed regarding changes in health and life insurance, employment, out-of-pocket medical costs, exercise, diet, and use of mental and alternative health services that occurred during or following hairy cell leukemia treatment. RESULTS: Following a diagnosis of hairy cell leukemia, 61.3% of the respondents paid for some aspect of medical care in spite of having health insurance coverage at the time of diagnosis. Four respondents (12.9%) could not obtain health insurance following treatment, and the occupational choices of several individuals or their spouses were based in large part on a desire to obtain or maintain comprehensive health insurance. Of the 13 individuals who attempted to purchase life insurance, 10 had difficulty obtaining a policy or were denied coverage. Lifestyle changes were noted by 40% to 60% of respondents, and included reports of more frequent exercise, adoption of a healthier diet, and having a greater appreciation for life, loved ones, and physical health. CONCLUSIONS: While hairy cell leukemia is a highly curable malignancy, cancer survivors' lives and lifestyles are altered substantially after receiving treatment for the illness.

Cost-benefit analysis of interferon alfa-2b in treatment of hairy cell leukemia.

The clinical benefits as well as the cost benefits of use of recombinant interferon (IFN) alfa-2b instead of conventional chemotherapy (primarily chlorambucil) for progressive hairy cell leukemia were assessed retrospectively on the basis of 12 months of clinical data from 128 patients treated with IFN alfa-2b. Data from 71 matched historical control patients who had received conventional treatment were used for survival analysis. Hematologic response (reversal of cytopenias) was achieved by 18% of the control patients versus 73% of the IFN-treated patients. This response was associated with virtual elimination of the need for transfusions and splenectomy as well as dramatic decreases in the frequency of fatal infections (22.5% vs. 1.6%) and the 12-month mortality rate (28% vs. 3.1%). Direct costs per patient per year for medical care (transfusions, antibiotic treatment, splenectomy, and chemotherapy) of those receiving IFN alfa-2b were 2.8-fold lower than costs for medical care of control patients ($5,027 vs. $14,046). Indirect costs, which reflect the present value of future earnings lost due to premature death, were 13.3-fold lower for IFN-treated patients than for control patients ($4,771 vs. $63,507). Our analysis demonstrates that IFN alfa-2b offers substantial clinical and cost advantages to patients with hairy cell leukemia and that the introduction of this therapy using novel biotechnology furthers the health care community's commitment to cost containment.