Advances in therapy for hairy cell leukemia

Abstract

Background. Hairy cell leukemia (HCL) is a chronic B‐cell malignancy, typically seen in middle‐aged men, characterized by pancytopenia, splenomegaly, immunologic abnormalities, and morphologically typical neoplastic mononuclear cells in the blood, bone marrow, liver, spleen, and other tissues. Diagnosis is confirmed by demonstration of hairy cells in biopsy specimens from the bone marrow or spleen or in peripheral blood. The natural history of this lymphoproliferative disorder varies. Patients may die early during the initial phase of therapy; others may require no therapy; and for some, splenectomy alone, without further treatment, may suffice for many years. Recently, the nucleosides pentostatin (2′‐deoxycoformycin) (DCF) and 2′‐chlorodeoxyadenosine (2‐CdA) have been shown to produce greater numbers of durable complete remissions with curative potential in patients with HCL. The treatment options, with emphasis on major therapeutic advances with alpha‐interferon, DCF, and 2‐CdA, are reviewed in this article. Methods. Studies on HCL published from 1958 to 1992 were reviewed using the Cancerline and Medline retrieval systems and other bibliographies. Results. Management of HCL has changed in the last decade as a result of three new effective agents: alpha‐interferon, DCF, and 2‐CdA. DCF has produced an overall response rate of 86% and a complete remission rate of 62%. 2‐CdA has yielded an overall response rate of 95% and a complete remission rate of 82%. Alpha‐interferon has given an overall response rate of 82% and a complete remission rate of 8%. Other agents with limited activities include chlorambucil, cyclophosphamide, cytarabine, vincristine, doxorubicin, and zorubicin hydrochloride. The effects of lithium carbonate, immunotherapy, splenic irradiation, androgens, and leukaphoresis are minimal and transient. Conclusions. Modern management of HCL with 2‐CdA and DCF is now potentially curative rather than palliative in some patients; however, the optimal therapeutic approach remains uncertain. Alpha‐interferon has been approved by the Food and Drug Administration as the first‐line drug therapy, followed by DCF in non‐responding patients. 2‐CdA remains an experimental therapy, but its higher response rate and ease of administration may make it the first‐line treatment of choice. Additional research into the biology of HCL and further clinical trials are needed to determine the optimal treatment strategy for this disorder. Therefore, the best therapeutic approach at the current time is to include patients with HCL in ongoing clinical trials.Cancer 1993; 72:5–16.

Similarities between the sensitivity to 2-chlorodeoxyadenosine of lymphocytes from CLL patients and bryostatin 1-treated WSU-CLL cells: an infrared spectroscopic study

“…The sequential use of Bryo 1 (100 nM) followed by 2-CdA (12 mM) resulted in complete growth inhibition of WSU-CLL cells (Fig. 5), which further supports the hypothesis that Bryo 1 induces differentiation of CLL to a hairy cell stage that renders them more susceptible to 2-CdA, a drug active in treating de novo HCL [20]. The similar IR spectra of 2-CdAsensitive CLL cells and Bryo 1-treated WSU-CLL cells would then suggest that there exists a similar mechanism for drug resistance in the two groups.…”

Ex vivo evidence of lymphocyte apoptosis in hairy cell leukemia, induced by 2-chlorodeoxyadenosine treatment

“…The therapeutic potential of 2-CdA was first reported in 1987 [16][17][18]. Given the high overall response rate of 95% and a complete remission rate of 82%, obtained with a 7-day course of intravenous cladribine, this drug has emerged as the treatment of choice for patients with HCL [1,6,10]. The efficacy of 2-CdA treatment was confirmed in independent cooperative studies [19,20].…”

Hairy cell leukemia

“…Apart from its use in splenic rupture, it can still be considered for patients with pure "splenic" HCL who have a normal marrow or for those patients with pancytopenia related to hypersplenism. However, the standard treatment is now with the nucleoside analogs or interferon(IFN)-alfa, and with their development came the need for more rigorous definitions of response [1,8]. By consensus, a complete response (CR) is defined as normalization of the peripheral blood counts (hemoglobin > 120 g/L, platelets > 100 x 10 9 /L, and neutrophils > 1.5 x 10 9 /L) with less than 5% hairy cells in the marrow [8].…”

“…However, the standard treatment is now with the nucleoside analogs or interferon(IFN)-alfa, and with their development came the need for more rigorous definitions of response [1,8]. By consensus, a complete response (CR) is defined as normalization of the peripheral blood counts (hemoglobin > 120 g/L, platelets > 100 x 10 9 /L, and neutrophils > 1.5 x 10 9 /L) with less than 5% hairy cells in the marrow [8]. A partial response (PR) is defined as the normalization of peripheral blood counts and the persistence of more than 5% of hairy cells in the marrow; however, treatment must have produced a greater than 50% fall in the marrow hairy cell infiltration.…”

“…The first active agent for HCL, interferon-alfa, can produce a CR in approximately 10% of HCL patients and a PR in the majority of remaining patients [1, [8][9][10][11][12][13] ( Table 1). Treatment can cause flulike symptoms with initiation of therapy as well as mild myelosuppression, but severe toxicity is uncommon.…”