Early allogeneic blood stem cell transplantation after modified conditioning therapy during marrow aplasia: stable remission in high-risk acute myeloid leukemia.

Two patients with high-risk acute myeloid leukemia (AML) whose bone marrow aspirates showed more than 25% blasts between 2 and 4 weeks after the first induction chemotherapy immediately received modified conditioning therapy with intravenous busulfan at 50% of the usual dose and fludarabine, before hematologic recovery occurred. Unmanipulated G-CSF mobilized peripheral blood stem cells from an HLA-identical sibling donor were transfused and haematopoietic recovery was achieved in both recipients. Both of them are in continuing hematological remission with full donor chimerism 12 and 22 months after transplantation. Early treatment intensification with allogeneic cell therapy during marrow aplasia might cure high-risk AML patients who are unlikely to achieve remission with conventional chemotherapy protocols.

Low-dose fludarabine and cyclophosphamide in elderly patients with B-cell chronic lymphocytic leukemia refractory to conventional therapy.

BACKGROUND AND OBJECTIVES: In recent years fludarabine alone or in combination with other drugs has been reported to be effective in the treatment of B-cell chronic lymphocytic leukemia (B-CLL), both as first line and salvage therapy. Among the different combination regimens, the association of fludarabine and cyclophosphamide has shown a considerable therapeutic efficacy, although a relevant number of infectious complications have been described, particularly in elderly patients. The aim of this work was to evaluate the efficacy, the toxicity, and the incidence of infectious episodes of a regimen combining lower doses of fludarabine and cyclophosphamide in elderly patients with B-CLL refractory to conventional therapy. DESIGN AND METHODS: Twenty patients with progressive B-CLL with a median age of 75 years (4 in stage B and 16 in stage C) and refractory to conventional therapy were enrolled in this study. The combination regimen was as follows: fludarabine 15 mg/m2/day i.v. [max 25 mg] and cyclophosphamide 200 mg/m2/day i.v. for four days. RESULTS: All patients enrolled were evaluable for response. Three out of 20 (15%) patients achieved a complete remission (CR), 14/20 (70%) a partial response (PR) with an overall response rate (CR+PR) of 85%, according to National Cancer Institute-Working Group response criteria. Three patients were considered resistant. In four out of 20 patients (20%), a severe neutropenia (neutrophils < 0.5x10(9)/L) occurred and one of them developed an infectious complication which required treatment with systemic antibiotics and granulocyte colony- stimulating factor (G-CSF). Non-hematologic toxicity was negligible in all patients but one, who despite a adequate therapy with allopurinol and hydration, experienced a tumor lysis syndrome with transient but severe renal impairment. INTERPRETATION AND CONCLUSIONS: The association of low-dose fludarabine and cyclophosphamide appeared to be effective in this subset of B-CLL patients, reproducing a similar overall response rate obtained with other fludarabine-based combination therapies. In addition, in this group of elderly patients, toxic side effects were negligible and infectious complications remarkably low.

Long-term follow-up after fludarabine treatment in pretreated patients with chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: A study update to assess long-term survival following fludarabine salvage treatment in previously treated patients with chronic lymphocytic lymphoma (CLL). DESIGN AND METHODS: From September 1992 to December 1995, 74 patients with advanced, relapsing B-cell CLL were enrolled in the study. Fludarabine was given for 5 consecutive days at the dose of 25 mg/m2/day in a 30 min infusion. Treatment was repeated every 28 days for a maximum of 6 courses.E RESULTS. Nineteen (26%) patients achieved a complete response (CR) and 20 (27%) patients had a partial response (PR), giving an overall response rate of 53%. The median overall survival was 68 months, and there was a strong negative correlation with the number of previous treatments. The median time to progression was 18 months for patients who achieved a CR and 12 months for those with a PR. INTERPRETATION AND CONCLUSIONS: The results obtained with fludarabine alone in this subset of CLL patients indicate the existence of a conspicuous disease-free survival period. This time window could be used to consolidate the initial response with either biological approaches or high-dose therapeutic strategies such as autologous bone marrow transplantation, with the aim of eventual eradication of the disease.