The effect of graft purging with 4-hydroperoxycyclophosphamide in autologous bone marrow transplantation for acute myelogenous leukemia.

Abstract

BACKGROUND:

Autologous bone marrow transplantation is an important therapy for patients with acute myelogenous leukemia (AML). However, leukemia in the graft may contribute to posttransplant relapse. Treatment of the graft with 4-hydroperoxycyclophosphamide (4HC) is sometimes used to decrease numbers of infused leukemia cells (4HC purging). No large controlled trials evaluating efficacy and toxicity of 4HC purging are reported.

METHODS:

We studied 294 patients reported to the Autologous Blood and Marrow Registry receiving either a 4HC-purged (n = 211) or unpurged (n = 83) autograft for AML in first (n = 209) or second (n = 85) remission. Analyses were restricted to patients transplanted less than 6 months after achieving remission. Using Cox proportional hazards regression, we compared time to treatment failure (death or relapse, inverse of leukemia-free survival) after 4HC-purged vs unpurged transplants while controlling for important prognostic factors.

RESULTS:

Median duration of posttransplant neutropenia was 40 (range, 10-200) days after 4HC-purged transplants and 29 (9-97) days after unpurged transplants (p < 0.01). Transplant-related mortality was similar in the two groups. In multivariate analysis, patients receiving 4HC-purged transplants had lower risks of treatment failure than those receiving unpurged transplants (relative risk, 0.69, p = 0.12 in the first posttransplant year; relative risk, 0.28, p < 0.0001 thereafter). Adjusted three-year probabilities of leukemia-free survival (95% confidence interval) were 56% (47-64%) and 31% (18-45%) after 4HC-purged and unpurged transplants in first remission, respectively. Corresponding probabilities in second remission were 39% (25-53%) and 10% (1-29%).

CONCLUSION:

Grafts purged with 4HC are associated with higher leukemia-free survival after autologous bone marrow transplants for AML.

• Authors: C B Miller, P A Rowlings, M J Zhang, R J Jones, S Piantadosi, A Keating, J O Armitage, S Calderwood, R E Harris, J P Klein, H M Lazarus, C A Linker, K A Sobocinski, D Weisdorf, M M Horowitz
• Journal: Experimental hematology (Exp Hematol) Vol. 29 Issue 11 Pg. 1336-46 (Nov 2001) ISSN: 0301-472X [Print] Netherlands
• PMID: 11698130 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cyclophosphamide
• perfosfamide

Topics

• Acute Disease
• Adolescent
• Adult
• Americas (epidemiology)
• Bone Marrow Purging (methods)
• Bone Marrow Transplantation (methods, mortality)
• Child
• Child, Preschool
• Cyclophosphamide (analogs & derivatives)
• Disease-Free Survival
• Female
• Graft Survival
• Humans
• Infant
• Leukemia, Myeloid (mortality, pathology, therapy)
• Life Tables
• Male
• Middle Aged
• Prognosis
• Proportional Hazards Models
• Registries
• Remission Induction
• Retrospective Studies
• Risk
• Survival Analysis
• Transplantation, Autologous
• Treatment Outcome