32
M. L. Torrey et al.
Figure 2. The Scripps Clinic treatment algorithm for relapsed/refractory hairy cell leukemia [13].
neutropenia, and thrombocytopenia, occur in a significant number of patients. Anemia is much less common [12]. Attempts to reduce the infectious risk from neutropenic fevers with the adjunctive use of granulocyte-colony stimulating factor (G-CSF) did not reduce the incidence of fever or hospitalizations, so is not routinely administered [4]. Cladribine also produced a protracted suppression of the CD4 and CD8 T-lymphocyte populations, explaining the risk for delayed opportunistic infections [12]. Cladri- bine’s direct incorporation into DNA and its associated immunosuppression might also explain the slight increased risk of second malignancies [8]. Analysis of purine analog-treated patients noted a slight increase in the observed-to-expected incidence of secondary malignancies when compared to the National Cancer Institute’s Surveillance, Epidemiol- ogy and End Results (NCI SEER) database, but this finding may also simply reflect the known risk of secondary malignancies associated with lymphopro- liferative disorders in general, as is true for chronic lymphocytic leukemia.
Conclusions
The emergence of the purine nucleoside analogs has dramatically altered the natural history of HCL. Pentostatin and cladribine are both effec- tive agents. Based on a single, brief, well- tolerated treatment course, cladribine is generally now accepted as front-line therapy in HCL. At the time of relapse, readministration of cladribine or alternative therapies, such as pentostatin or biologics, may be appropriate. The clinical benefit of eliminating MRD is unknown, and therefore more aggressive front-line therapies remain in- vestigational.
Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at
www.informahealthcare.com/lal.
References
1. Else M, Dearden C, Matutes E, et al. Long-term follow up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis. Br J Haematol 2009;145:733–740.
2. Saven A, Burian C, Koziol JA, et al. Long-term follow-up of patients with hairy cell leukemia after cladribine treatment. Blood 1998;92:1918–1926.
3. Sigal, D, Sharpe R, Burian C, Saven A. Very long-term eradication of minimal residual disease in patients with hairy cell leukemia after a single course of cladribine. Blood 2010;115:1893–1896.
4. Saven A. Hairy cell leukemia. In: Lichtman MA, Kipps TJ, Kaushansky K, et al., editors. Williams Hematology. 7th ed. New York: McGraw-Hill; 2006. pp 1385–1393.
5. Carson DA, Wasson DB, Kaye J, et al. Deoxycytidine kinase- mediated toxicity of deoxyadenosine analogs toward malignant human lymphoblasts in vitro and toward murine L1210 leukemia in vivo. Proc Natl Acad Sci USA 1980;77:6865– 6869.
6. Beutler E. Cladribine (2-chlorodeoxyadenosine). Lancet 1992;340:952–956.
7. Piro LD, Carrera CJ, Carson DA, et al. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2- chlorodeoxyadenosine. N Engl J Med 1990;322:1117–1121.
8. Goodman GR, Burian C, Koziol JA, et al. Extended follow-up of patients with hairy cell leukemia after treatment with cladribine. J Clin Oncol 2003;21:891–896.
9. Dearden CE, Matutes, E, Hilditch BL, et al. Long-term follow- up of patients with hairy cell leukemia after treatment with pentostatin or cladribine. Br J Haematol 1999;106:515–519.
10. Wheaton S, Tallman MS, Hakimian D, et al. Minimal residual disease may predict bone marrow relapse in patients with hairy cell leukemia treated with 2-chlorodeoxyadenosine. Blood 1996;87:1556–1560.
11. Ellison DJ, Sharpe RW, Robbins BA, et al. Immunomorpho- logic analysis of bone marrow biopsies after treatment with 2- chlorodeoxyadenosine for hairy cell leuekmia. Blood 1994;84:4310–4315.
12. Sigal D, Miller H, Schram E, Saven A. Beyond hairy cell: the activity of cladribine in other hematologic malignancies. Blood 2010;116:2884–2896.
13. Huynh E, Sigal D, Saven A. Cladribine in the treatment of hairy cell leukemia: initial and subsequent results. Leuk Lymphoma 2009;50(Suppl. 1):12–17.
14. Estey EH, Kurzrock R, Kantarjian HM, et al. Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA). Blood 1992;79:882–887.
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