A prospective randomized study of alpha-2b interferon plus hydroxyurea or cytarabine for patients with early chronic phase chronic myelogenous leukemia: the International Oncology Study Group CML1 study.

A prospective randomized international study of 143 patients showed no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy. Combinations of alpha-interferon (INF) and chemotherapeutic agents are currently first-line therapy for the majority of patients with chronic myeloid leukemia (CML). The International Oncology Study Group conducted a prospective randomized study comparing INF combined with hydroxyurea or cytarabine. The primary study aim was to compare the survival durations in these patient cohorts. Patients with early chronic phase CML were randomized to receive INF 5 million units (Mu) given five times per week subcutaneously plus hydroxyurea or cytarabine as required to achieve a complete hematologic response and to maintain a WBC count between 2x10(9)/L and 10x10(9)/L and a platelet count between 75x10(9)/L and 100x10(9)/L. Therapy continued as tolerated unless progressive or blast phase disease occurred. At 36 months, the actuarial survival rate was equivalent in both groups: HI group (79 patients) survival was 85% (95% CI, 68-100%), as compared to 95% (95% CI, 79-100%) in the CI group (64 patients). In conclusion if seems that there is no apparent early survival advantage conferred by combining cytarabine, rather than hydroxyurea, with INF as first-line CML therapy.

Cyclophosphamide, etoposide, vincristine, adriamycin, and dexamethasone (CEVAD) regimen in refractory multiple myeloma: an International Oncology Study Group (IOSG) phase II protocol.

A 4- day continuous intravenous (CIV) infusion of vincristine and doxorubicin with high-dose dexamethasone (VAD) regimen is a standard refractory multiple myeloma (MM) regimen. A Phase II study of a CEVAD regimen, i.e., VAD plus etoposide administered as a 96-hr continuous infusion, was carried out with IV bolus cyclophosphamide. Thirty-six patients were treated on study and received a total of 114 cycles of CEVAD: median 2 cycles (range 1-8). No patient achieved a CR. The overall rate of PR was 15/36 (42%). Patients achieved maximal response after a median of 4 (range 3-6) courses. PR rates were 40% (4/10) in patients with primary refractory disease, 48% (11/23) in patients with secondary refractory disease, 31% (6/19) in patients who had failed previous VAD therapy, and 50% (7/14) in patients receiving 2nd or subsequent relapse therapy. Three patients died during their initial cycle of therapy from rapidly progressive disease and sepsis. Overall median survival was 24 weeks with a 1-year survival of 33.3% ¿95% confidence interval of 20-46%¿. Myelosuppression was the most frequent adverse event with NCI grade 2 neutropenia and/or thrombocytopenia in 15% of first cycles, grade 3 in 20%, and grade 4 in 65%. Two-thirds of patients had at least one episode of grade 3 or 4 sepsis. In 15% of septic episodes positive blood cultures were obtained. Overt cardiotoxicity was seen in two patients. CEVAD as used in this study was not more effective than VAD in terms of overall response rate or survival.

Hypereosinophilia Progressing to Granulocytic Sarcoma and Acute Myelocytic Leukemia with Trisomy 8: A Case Report and Review of the Literature.

Conditions associated with increased peripheral blood and bone marrow eosinophil count may be reactive, clonal or idiopathic. Clonal eosinophilic disorders are characterized by increased production of eosinophils alongside a clone of malignant cells. In these patients, the eosinophils can either be demonstrated as being part of the malignant clone or produced as a result of cytokine production by the malignant clone. Criteria for the diagnosis of idiopathic hypereosinophilic syndrome (HES) include the exclusion of other known causes of hypereosinophilia. A few patients with the initial diagnosis of HES develop clonal disorders manifested by granulocytic sarcoma or acute leukemia. We report a patient with a nine year history of HES before progressing to chloroma and acute leukemia. Cytogenetic studies on the bone marrow specimen revealed trisomy 8. This report and others in the literature support the concept that at least some cases of HES are as yet unidentified clonal diseases. Cytogenetic studies are therefore recommended at diagnosis and during the follow up of patients with HES.

HTLV-1 and Adult T-Cell Leukemia/Lymphoma: A Review.

Infection with the human T-lymphotropic virus type 1 (HTLV-1) has been shown to be fundamental to the etiology of Adult T-cell Leukemia/Lymphoma (ATL). The disease is endemic in specific geographic areas but is increasingly reported from non-endemic regions. With increasing number of patients with this entity, the diversity in the clinical features has become apparent. In the past treatment strategies using combination chemotherapy have been unsatisfactory, but more recent trials using adenosine analouges, interferons, and combination of interferons and AZT have shown promise. With increased understanding of the etiology and molecular basis of the disease more effective therapies can be anticipated.

Heterogeneity of amphetamine response in depressed patients.

There is considerable diversity of opinion as to the nature of the response of depressed patients to amphetamine infusion. The authors report on the clinical response of 18 endogenously depressed patients to double-blind, intravenous administration of amphetamine or saline. Although the drug produced activation, mood elevation, and recall of emotionally charged material in the group as a whole, there was considerable heterogeneity of response as well as a tendency for response dimensions to vary independently of one another. The heterogeneity of clinical response may be associated with differences in underlying clinical, biological, and genetic variables in affectively ill patients.