Interferon is effective in hairy‐cell leukaemia

Abstract

Seventeen patients with hairy-cell leukaemia (HCL) and peripheral cytopenias were given human lymphoblastoid interferon (Wellferon), 3 megaunits daily or 6 megaunits on alternate days intramuscularly, for 4-24 weeks. Twelve of the patients had undergone splenectomy, three had no palpable spleen and had therefore not been offered surgery, and two patients with substantial splenomegaly were given interferon (IFN) as treatment of first choice. Toxic effects were minor except in one patient who experienced a severe form of somnolence syndrome. In all patients hairy cells (HCs) were cleared from the blood and platelet and Hb levels improved in 2-14 weeks. Neutrophils were improved in 14/17 of the patients. In the two patients with splenomegaly, the spleen became impalpable after 5-8 weeks therapy, and haematological improvement occurred at 12-14 weeks. HC infiltration of the marrow was reduced in all patients, but was complete (less than 5%) in only two, both of whom had impalpable spleens. Immunological surface-marker studies confirmed that light-chain-restricted B cells disappeared from the blood in parallel with the clearance of morphological HCs. There was no evidence of HC maturation and no increase in phenotypic NK cells. T cells were moderately reduced and the relatively greater reduction of Leu 2a+ suppressor cells resulted in increased Leu 3a+/2a+ helper/suppressor ratios in 11/17 of the patients. Early experience in the six patients who have stopped IFN suggests that, after an initial further increase in Hb and neutrophil levels, HCs gradually return with slow deterioration of haematological parameters. Interferon is now the treatment of choice for patients becoming cytopenic post-splenectomy or for patients without splenomegaly. IFN is effective first-line therapy in patients with splenomegaly, but further work is needed to establish whether the agent should replace splenectomy in such patients. Some form of maintenance or re-treatment therapy will probably be necessary.

Response of hairy cells to IFN-α involves induction of apoptosis through autocrine TNF-α and protection by adhesion

“…Although these proteins are present in the circulation in soluble form, they are abundant in tissues as part of the insoluble ECM of bone marrow and splenic red pulp where HCs accumulate and from where these cells disappear much more slowly during IFN-␣ therapy. 8 We therefore propose that integrin receptor cross-linking by HC adhesion to ECM is responsible for the persistence of malignant cells in these organs during IFN-␣ therapy long after they have disappeared from the blood.…”

“…In contrast, the malignant cells remain in spleen and bone marrow for much longer periods and may not become completely eliminated from these tissues. 8 Previous studies of the effects of IFN-␣ have shown that this cytokine increases autocrine TNF-␣ production and inhibits HC proliferation in response to cell stimulation. 3 However, these observations do not explain the therapeutic effects of IFN-␣, because TNF-␣ is described as an autocrine rescue factor for HCs 9 and because HCL is a disease of prolonged cell survival rather than of increased proliferation.…”

Which Role for Rituximab in Hairy Cell Leukemia? Reflections on Six Cases

“…The treatment of relapsed or refractory HCL has not been standardized. The therapeutic options usually include splenectomy [23], IFN-α [24,25] and repeat treatment with PA [26]. Repeat treatment with PA induces in 70–90% remissions, but the responses are usually of shorter duration.…”

Rituximab in relapsed or refractory hairy cell leukemia

“…Relapses were frequent after cessation of therapy. [5][6][7][8] The activity of nucleoside analogs in HCL was demonstrated, and treatment with a single course of 2-chlorodeoxyadenosine (2-CdA) produced complete remission (CR) rates of 80% to 90%. [9][10][11][12][13][14][15] Responses after 2-CdA were durable, with reported relapse-free survival rates ranging from 70% to 85% at 4 to 5 years.…”