Monica Bocchia

Fludarabine in patients with advanced and/or resistant B-chronic lymphocytic leukemia

Abstract:  In this study, we evaluated the efficacy of fludarabine (FLU), an adenine nucleoside analogue, in 35 previously treated patients with advanced and progressed B‐cell chronic lymphocytic leukemia (B‐CLL) and in 6 at diagnosis. All patients were treated at a dose of 25 mg/m2 per day for 5 consecutive days (mean number of courses was 5, with a range from 4 to 6). The majority of patients experienced a beneficial effect on hematological parameters. In particular, a remarkable reduction of lymphocyte count together with an increase of neutrophils and platelets was observed. The overall response rate was 42% with 1 complete response and 16 partial responses. Ten patients achieved minor responses and the remaining 14 showed no benefit from treatment. An increased response rate was achieved in 6 untreated patients who showed an overall response rate of 67% (4/6). The major complications observed were neutropenia (66%) and febrile episodes (44%) that were generally infection‐related and were fatal in 3 cases. Because we were dealing with patients whose disease was advanced and/or resistant to treatment, the overall results may be considered encouraging with acceptable toxic reactions not superior to those frequently observed with polychemotherapy.

Relationship between immunological phenotype and hematological response to α-IFN treatment in 35 patients with hairy cell leukemia

Abstract: During the past 6 years, clinical trials employing α‐interferon (α‐IFN) in hairy cell leukemia (HCL) have shown dramatic improvement in the management of this disease. Complete remissions (CR), however, are relatively rare (10–15%) and a minority of patients (10–25%) do not respond adequately to α‐IFN. The possibility that the poor response to α‐IFN treatment could be related to a peculiar immunological phenotype of the hairy cell (HC) was investigated in this study. The results demonstrated that, in the majority of patients who failed to respond to α‐IFN, HC showed an immunological phenotype characterized by positivity with the CD5 monoclonal antibody which is usually absent on HC and characteristically expressed on B‐chronic lymphocytic leukemia cells. In fact, among the 10 HCL patients who presented with this phenotype, only 5 partial remissions (PR) and 5 minor responses (MR) were achieved, as opposed to the 3 complete remissions (CR), 19 PR and 3 MR observed in the 25 CD5‐negative patients. The possibility that a more extensive immunological analysis of HCL patients at diagnosis may be predictive of the response to IFN treatment is postulated.

CEOP regimen in the treatment of advanced low-grade non-Hodgkin's lymphomas: preliminary report.

Between March 1987 and December 1988, 30 previously untreated patients with low-grade non-Hodgkins lymphomas (NHL), according to the Kiel classification, were treated by a combination of therapy including cyclophosphamide, epirubicin, vincristine, and prednisone (CEOP). Eighteen patients (60%) achieved a complete pathologic remission, and 8 patients (26.6%) had a partial response with a reduction of more than 50% of tumor-related manifestations. Four patients (13.4%) were primary resistant to CEOP. The overall survival was 96.6% with a median follow-up of 25 months from the diagnosis; none of the patients who achieved complete response relapsed at a median follow-up of 21 months from the completion of treatment. Clinical and hematologic toxicities were irrelevant. This regimen was effective in inducing a good remission rate of low-grade NHL, but a longer follow-up for definitive conclusions is warranted.

Comparison of Low-Dose versus Standard-Dose Alpha-Interferon Regimen in the Hairy Cell Leukemia Treatment

In a randomized clinical trial, the effects of standard doses of alpha-interferon (alpha-IFN) compared with the effects of half of these doses were evaluated in patients with hairy cell leukemia. There were 14 patients treated with standard-dose (3 MU/day i.m. for 6 months, then 3 MU three times/week for a further 6 months) and 10 patients with low-dose alpha-IFN (1.5 MU/day with the same schedule and for the same period). The overall response rate, the quality, and the duration of response were rather similar in both groups. The rapidity of response in normalizing the peripheral blood counts was similar, even increased in low-dose-treated patients, consisting mainly in clearing the number of circulating hairy cells (p less than 0.03). Finally, the toxic effects of both regimens were minimal but less evident in patients treated with low-dose alpha-IFN. Despite the small number of patients, on the basis of this report, we can confirm that 1.5 MU/day of alpha-IFN is an adequate treatment for patients with hairy cell leukemia.

Immunotherapy of Chronic Myeloid Leukemia

Immunotherapy utilizing anti-granulocyte antibodies naked provides an effective means of treating chronic myelogenous leukemia (CML). Such antibodies can be administered alone or in combination with other treatments, such as an immunoconjugate or chemotherapy. There is provided a effective treatment method for treating CML in either manner, typically associated toxic side effects in cancer therapy is avoided. Immunotherapy disclosed, when inducer to induce the expression of antigens not minimally appear in the myeloblast surface is co-administered, it is also effective in the treatment of acute myeloid leukemia (AML).