Low-dose (550 cGy), single-exposure total body irradiation and cyclophosphamide: Consistent, durable engraftment of related-donor peripheral blood stem cells with low treatment-related mortality and fatal organ toxicity

William Blum, R. Brown, H. S. Lin, B. Zehnbauer, H. Khoury, L. T. Goodnough, P. Westervelt, R. Vij, J. DiPersion, D. Adkins

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23 Scopus citations

Abstract

On the basis of observations of dog models and from earlier studies with humans, we hypothesized that a low-dose (550 cGy) TBI-based conditioning regimen would result in sustained engraftment of HLA-matched sibling peripheral blood stem cells (PBSC) with low treatment-related mortality (TRM) and low serious organ toxicity if the TBI was given as a single dose and at a high dose rate. The regimen included 550 cGy TBI administered as a single dose at 30 cGy/min and cyclophosphamide. Cyclosporine was given as GVHD prophylaxis. Twenty-seven good-risk (acute leukemia in first remission and chronic-phase chronic myelogenous leukemia) and 53 poor-risk (other) patients were accrued. Complete donor engraftment occurred in 93% to 100% of evaluable patients at each scheduled assessment and was durable through 4 years. Mixed chimerism (50% to 98% donor) was observed in 9 patients (11%). Without further intervention, all patients had complete donor engraftment on subsequent assessments. Graft failure did not occur. TRM through at least 2 years was 7% in the good-risk and 19% in the poor-risk diagnostic groups. Grade 4 (fatal) organ toxicity occurred in only 2 patients (2.5%). Other causes of TRM included infection and GVHD. Median follow-up for the surviving patients was 1234 days (range, 780-1632 days). Current status includes 39 patients (49%) alive and in complete remission, 2 alive in relapse, and 39 dead. Relapse occurred in 15% of the good-risk group and 45% of the poor-risk group. The Kaplan-Meier estimates of 3-year disease-free and overall survival of the good-risk group were 77% and 85%, respectively, and of the poor-risk group were 34% and 36%, respectively. Low-dose (550 cGy), single-exposure TBI given at a high dose rate with cyclophosphamide resulted in consistent durable engraftment of HLA-matched sibling PBSC with a low risk of fatal organ toxicity and TRM.

Original languageEnglish
Pages (from-to)608-618
Number of pages11
JournalBiology of Blood and Marrow Transplantation
Volume8
Issue number11
DOIs
StatePublished - 2002

Keywords

  • HLA-matched
  • Organ toxicity
  • Peripheral blood stem cells
  • Total body irradiation

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