Interferon

When splenectomy was used commonly as a first-line treatment approach to HCL, one of every two to three patients relapsed following the procedure. Other chemotherapeutic agents were tried with limited suc-cess.45-47 The demonstration of activity of interferon-a against hairy cell leukemia was viewed as a significant advance, as it was the first agent that could partially eradicate the hairy cell population from the bone marrow, thus eventually changing the response criteria. However, much like splenectomy, interferon-a is only rarely indicated in the current approach to initial management, and only under certain clinical circumstances.

The first experience with interferon in hairy cell leukemia was reported in 1984 by Quesada et al.48 They treated seven patients with partially purified human interferon and showed a dramatic improvement in all blood counts within a 2- to 3-month period. Once recombinant interferon became available, Golomb et al. treated 69 patients with interferon a-2b at 2 X 106 U/m2 subcutaneously three times weekly for a year.49-51 Interferon-a demonstrated an ORR of 91% with 13% of the patients achieving a CR, defined as <5% of hairy cells in the bone marrow and normalization of peripheral blood counts. Relapses were uncommon during therapy and for the first 6-9 months thereafter. Median actuarial failure-free survival was 25.4 months.

Interferon a-2a (Roferon-A, Roche, Nutley, NJ) has also been studied in hairy cell leukemia. Quesada et al.52 treated 25 patients with 3 X106 U/m2 of interferon a-2a daily for 4-6 months, followed by three times a week for a year. They documented a response rate of 87%, with 30% of the patients exhibiting a CR. Median time to remission was 3.5 months. Discontinuation of the treatment resulted in clinical relapse in 33% of the patients.

Numerous other trials have shown comparable results (see Table 31.4). Response rates range from 43% to 100%, the majority of which are partial. Hematologic changes follow a well-described pattern. Platelet counts increase first, often as early as 2 weeks into therapy, reaching a normal value by approximately 1.5-2 months. During the first 2 months of treatment there is a notable decrease in the white count and hemoglobin.53 Full granulocytic response is usually delayed until 3-5 months. Hemoglobin response lags behind, with responses still seen as far as 9 months into the therapy.58 59 In general, treatment naive patients exhibit higher response rates. In addition to improving peripheral blood counts, interferon-a also reduces splenomegaly size. Interferon-a is effective in patients with an intact spleen as well as in splenectomized patients.

Neither the optimal dose nor the optimal duration of interferon therapy has been clearly established. Standard regimens include either interferon a-2b (Intron A) 2 X 106 U/m2 subcutaneously three times per week for a year or interferon a-2a (Roferon-A) 3 X 106 U/m2 daily for 4-6 months, followed by three times a week a for a year.

Despite impressive ORRs, between 33% and 86% patients relapse at a median of 6-30 months (see Table

With long-term follow-up, an increased incidence of second malignancies has been noted following interferon-a treatment.65 After a median follow-up of 91 months, 13 patients (19%) developed a second malignancy. Six were hematopoietic and seven adeno-carcinomas. The excess frequency was 4.33 compared

Table 31.3 Splenectomy in the treatment of hairy cell leukemia

Response

Number of duration

Results of interferon therapy in patients with hairy cell leukemia

Author

Type of interferon

Dose and schedule

Number of subjects

CR (%)

PR (%)

Duration (month) of response

Quesada48 Jacobs53

Interferon alpha-N1 Interferon alpha-2b

3 X 106U daily 2 X 106 U/m2, three times weekly

0 0

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