Cytarabine Consolidation Research Articles

Autologous peripheral blood progenitor cell transplantation mobilized with high-dose cytarabine in acute myeloid leukemia in first complete remission

The aim of this study was to increase disease-free survival (DFS) in AML in CR1 using a high-dose cytarabine consolidation plus G-CSF as in vivo purging and mobilization of CD34+ cells before ablative therapy and peripheral blood autograft. Fifty-six consecutive AML patients (pts) (including 11 children < 15 years), with a median age of 32 years, were analyzed. After achievement of CR with cytarabine-mitoxantrone (7 + 3) in adults and a BFM-like protocol in children, pts were intensified with cytarabine 2 g/m2 x six doses plus mitoxantrone for adults, or, 3 g/m2 x six doses plus etoposide for children, followed by G-CSF 5 micrograms/kg SC daily. The ablative regimens used were busulfan and cyclophosphamide (Bu/Cy) in standard-risk pts plus etoposide (2400 mg/m2) for high-risk pts. For the 54 pts who underwent autologous transplant, the median time to reach > 1.0 x 10(9)/l neutrophils was 13 days (8-48), and to reach platelets > 25 x 10(9)/l 32 days (8-364), and the median numbers of red blood cell and platelet units transfused were 3 and 5, respectively. Six pts had treatment-related deaths (11%). The disease-free survival and overall survival at 30 months (mos) for the 56 eligible pts were 61% and 62%, respectively. Only two relapses were observed after 21 mos, while there were 12 relapses within 12 mos. The above treatment results in a similar DFS rate as does rescue with bone marrow cells, with faster neutrophil and platelet recovery.

Long-Term Outcome of High-Dose Cytarabine-Based Consolidation Chemotherapy for Older Patients with Acute Myelogenous Leukemia

Despite reports of improved response and leukemia-free survival for adults with acute myelogenous leukemia, advanced age remains a significant adverse prognostic factor for both response to induction therapy and prolonged leukemia-free survival. In addition to a high incidence of treatment-related complications, older patients may have other disease characteristics which predict for brief remission duration despite intensive consolidation chemotherapy. We analyzed the long-term results of high-dose cytarabine-anthracycline consolidation chemotherapy in older patients and examined the effect of major prognostic factors including a history of myelodysplasia, increased age, and cytogenetics. One hundred and ten patients age ± 60 with newly diagnosed acute myelogenous leukemia were enrolled on three sequential studies conducted from 1982 to 1996. Fifty-six patients (51%) achieved a complete remission and were eligible for high-dose cytarabine-based consolidation chemotherapy administered in two to three courses.After a median follow-up of surviving patients for seventeen months, twelve patients remain alive with eleven in continued remission. Median remission duration for all eligible patients is nine months and the actuarial leukemia-free survival is 14 ± 10%. Toxicity of consolidation therapy included treatment-related death in six patients and serious neurotoxicity in five. When compared to younger patients, patients over age 60 sustained a much higher risk of relapse despite successfully completing intensive consolidation therapy, regardless of whether other adverse prognostic features were present.Advanced age in acute myelogenous leukemia is associated with a significantly higher risk of relapse unmodified by the presence or absence of other adverse disease characteristics. Although older patients tolerated intensive therapy designed to address the high risk of relapse, there was no apparent benefit of high-dose cytarabine consolidation alone as post-remission treatment for acute myelogenous leukemia in this population.

Treatment of acute leukemia in adults.

The goal of therapy for young adults with de novo acute myeloid leukemia is cure. Seventy percent or more of young adults achieve initial remission, and 30% to 40% of adults receiving postremission chemotherapy appear to remain in remission. High-dose cytarabine consolidation therapy appears particularly effective. However, with current approaches, only 20% of young adults are cured. New approaches are needed to increase the cure rate substantially, and autologous bone marrow transplantation appears to be the most promising treatment modality in acute myeloid leukemia. Improved preparative regimens and purging techniques may be critical factors in determining the effectiveness of autologous bone marrow transplantation. In adult acute lymphoblastic leukemia, very high remission rates are now being reported with intensive multiagent induction therapy, and approximately one third of young adults with this disease are cured with current intensive chemotherapy approaches. The role and optimal methods of bone marrow transplantation for acute lymphoblastic leukemia are under investigation.

Recombinant interferon alfa given before and in combination with standard chemotherapy in children with acute lymphoblastic leukemia in first marrow relapse: a Pediatric Oncology Group pilot study.

Recombinant interferon alfa (rIFN-alpha) was given to 31 children with acute lymphoblastic leukemia (ALL) in first on-therapy marrow relapse as the sole treatment (30 megaunits/m2/d intravenously x 10 days) before standard four-drug reinduction and during multiagent continuation therapy (30 megaunits/m2 subcutaneously x 3 consecutive days every 3 weeks). After 10 days of rIFN-alpha, there were two partial remissions (PRs); seven additional patients had either greater than or equal to 25% reduction in the percentage of marrow blast cells or hypoplastic marrow. Two patients had progressive disease with an increase in leukocyte counts. All patients experienced influenza-like symptoms, and there were isolated instances of severe abdominal pain and personality change. Dose-limiting toxicity comprised grade III/IV transaminase elevation (two patients) and syncope with personality change (one patient). Twenty-three of 31 children (74%) subsequently achieved marrow remission using standard agents. One patient was taken off study during teniposide (VM-26) and cytarabine (ara-C) consolidation due to toxicity. Continuation therapy including rIFN-alpha pulse was well tolerated in the remaining children; only one patient required rIFN-alpha dosage reduction (for CNS toxicity). rIFN-alpha toxicity did not necessitate reductions in doses of standard chemotherapy agents or significant delays in therapy. Five patients remain in remission at 26+ to 36+ months; 13 patients relapsed in marrow, one in the meninges (7 months), and one in meninges, mediastinum, and lymph nodes (2 months). Two children were removed from study for marrow transplant. In summary, high-dose rIFN-alpha alone had a modest antileukemic effect. In contrast to the clinical experience with combined rIFN-alpha and chemotherapy in adults, rIFN-alpha given in a pulse-like manner throughout continuation therapy did not compromise the intensity of the standard chemotherapy regimen.