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


CONCLUSIONS
Grafts purged with 4HC are associated with higher leukemia-free survival after autologous bone marrow transplants for AML.
Miller
C B
CB
The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rowlings
P A
PA
Zhang
M J
MJ
Jones
R J
RJ
Piantadosi
S
S
Keating
A
A
Armitage
J O
JO
Calderwood
S
S
Harris
R E
RE
Klein
J P
JP
Lazarus
H M
HM
Linker
C A
CA
Sobocinski
K A
KA
Weisdorf
D
D
Horowitz
M M
MM
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000569:Americas / Q000453:epidemiology; D016465:Bone Marrow Purging / Q000379:methods*; D016026:Bone Marrow Transplantation / Q000379:methods* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries; D012074:Remission Induction; D012189:Retrospective Studies; D012306:Risk; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D003520:Cyclophosphamide; C011272:perfosfamide