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The effect of graft purging with 4-hydroperoxycyclophosphamide in autologous bone marrow transplantation for acute myelogenous leukemia. Exp Hematol 2001 Nov;29(11):1336-46 PMID: 11698130

Pubmed ID

11698130

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.

Author List

Miller CB, Rowlings PA, Zhang MJ, Jones RJ, Piantadosi S, Keating A, Armitage JO, Calderwood S, Harris RE, Klein JP, Lazarus HM, Linker CA, Sobocinski KA, Weisdorf D, Horowitz MM

Authors

Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin
Mei-Jie Zhang PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acute Disease
Adolescent
Adult
Americas
Bone Marrow Purging
Bone Marrow Transplantation
Child
Child, Preschool
Cyclophosphamide
Disease-Free Survival
Female
Graft Survival
Humans
Infant
Leukemia, Myeloid
Life Tables
Male
Middle Aged
Prognosis
Proportional Hazards Models
Registries
Remission Induction
Retrospective Studies
Risk
Survival Analysis
Transplantation, Autologous
Treatment Outcome
jenkins-FCD Prod-296 4db9d02597e0a2e889e230f853b641c12f1c3ee3