Craig C. Childs

Fludarabine: a new agent with marked cytoreductive activity in untreated chronic lymphocytic leukemia.

Thirty-three patients with chronic lymphocytic leukemia (CLL) with advanced Rai stage (III-IV) or progressive Rai stage (0-II) disease were treated with fludarabine as a single agent. Eleven patients (33%) obtained a complete remission (CR), 13 (39%) a clinical CR with residual nodules as the only evidence of disease (nodular partial remission [PR]), and two patients (6%) achieved a PR for a total response rate of 79%. Response was rapid, usually occurring after three to six courses of treatment. The major morbidity was infection. Febrile episodes occurred in 13% of the courses (pneumonia 6%, minor infection 4%, and transient fever of undocumented cause 3%). Fludarabine appears to be the most cytoreductive single agent so far studied in CLL.

Efficacy of fludarabine, a new adenine nucleoside analogue, in patients with prolymphocytic leukemia and the prolymphocytoid variant of chronic lymphocytic leukemia

PURPOSE To describe the results of fludarabine therapy in patients with prolymphocytic leukemia (PLL) and the prolymphocytoid variant of chronic lymphocytic leukemia (CLL-Pro). PATIENTS AND METHODS Seventeen patients with a diagnosis of PLL or CLL-Pro received fludarabine 30 mg/m2 over 30 minutes daily for 5 days every 4 weeks alone (12 patients), or with prednisone (five patients). Previously defined criteria for response were used. Differences in response rates according to various characteristics were evaluated by chi-square test. RESULTS Three patients (18%) achieved complete remission, and three (18%) had a partial remission, for an overall response rate of 35%. Responses were durable and occurred in all involved organ sites. Lower response rates were observed in patients with anemia, thrombocytopenia, advanced Rai stages, and primary resistance to prior therapy. Toxicities were minimal except for febrile episodes associated with therapy. CONCLUSION Fludarabine has shown encouraging results in these patients and deserves further investigation in combination with other active agents, and in the setting of front-line therapy.

Therapy of lymphoid and undifferentiated chronic myelogenous leukemia in blast crisis with continuous vincristine and Adriamycin infusions plus high-dose decadron

Thirty patients with Philadelphia chromosome‐positive lymphoid (20 patients) or undifferentiated (ten patients) chronic myelogenous leukemia in blast crisis were treated with 0.4 mg of vincristine by continuous intravenous infusion (CIV) daily for 4 days; (doxorubicin) 12 mg/m2 of Adriamycin (Adria Laboratories, Columbus, OH) by continuous intravenous infusion daily for 4 days; and 40 mg of decadron daily on days 1 through 4,9 through 12, and 17 through 20 (VAD). Course 2 was given starting on day 24 with the addition of cyclophosphamide 1 g/m2. Overall nine patients achieved complete remission (30%) and three attained a partial remission (10%), for an overall response rate of 40%. Four patients expired during induction whereas 14 had resistant disease. Response rate was significantly higher for patients with lymphoid compared to undifferentiated morphology (55% versus 10% P = 0.05). In lymphoid blast crisis, Calla‐positive disease was associated with a higher response rate compared to Calla‐negative disease (75% versus 25%; P = 0.08). Eleven patients developed infections, and seven had fever without documented infections. The median overall survival was 29 weeks. Median survival was 43 weeks for patients achieving complete remission and 20 weeks for those with resistant disease. Remission duration was 39 weeks. After primary and salvage therapy, nine patients are alive, six of them in continuous remission for 19+ to 112+ weeks. The authors conclude that VAD chemotherapy is an effective regimen with acceptable toxicity in patients with lymphoid blast crisis especially those with Calla‐positive disease. Alternate induction regimens for undifferentiated disease and for maintenance therapy are currently being investigated.

8;20 Chromosomal translocation in a case of acute leukemia: Cytogenetic, immunophenotypic, ultrastructural, and molecular characteristics

An 8;20 chromosomal translocation was observed in the leukemia cells of a 3-year-old girl. To our knowledge, this is the first report of this translocation in de novo acute leukemia. This chromosomal defect was present in the leukemia cells at diagnosis and also at relapse, but remission bone marrow cells had the 46,XX karyotype. By morphologic and cytochemical criteria the leukemia was myeloid but these features were more lymphoid when the leukemia recurred. However, the immunophenotype was consistent with myeloid leukemia and did not change at relapse. No evidence for either immunoglobulin or TCR gene rearrangement was observed.