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.
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.
Blum
W
W
Department of Internal Medicine, Division of Oncology, Section of Bone Marrow Transplantation and Leukemia, St. Louis Children's Hospital, St. Louis, Missouri 63110-1093, USA. wblum@im.wustl.edu
Brown
R
R
Lin
H S
HS
Zehnbauer
B
B
Khoury
H
H
Goodnough
L T
LT
Westervelt
P
P
Vij
R
R
DiPersio
J
J
Adkins
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000633:toxicity; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D006648:Histocompatibility; D006801:Humans; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D011829:Radiation Dosage; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects* / Q000401:mortality
D003520:Cyclophosphamide