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Blood, 15 October 2000, Vol. 96, No. 8, pp. 2703-2711
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Analysis of engraftment, graft-versus-host disease, and immune
recovery following unrelated donor cord blood transplantation
Blythe G. Thomson,
Kent A. Robertson,
Darla Gowan,
Doug Heilman,
Hal E. Broxmeyer,
David Emanuel,
Patricia Kotylo,
Zacharie Brahmi, and
Franklin
O. Smith
From the Stem Cell Transplantation Program,
Department of Pediatric Hematology/ Oncology; Herman B. Wells Center
for Pediatric Research; Department of Biostatistics; Department of
Microbiology and Immunology; Department of Medicine; Department of
Pathology; and Walther Oncology Center, Indiana University School of
Medicine; and the Walther Cancer Institute, Indianapolis, IN.
Unrelated cord blood (UCB) is being used as a source of alternative
hematopoietic stem cells for transplantation with increasing frequency.
From November 1994 to February 1999, 30 UCB transplant procedures were
performed for both malignant and nonmalignant diseases in 27 children,
aged 0.4 to 17.1 years. Patients received either HLA-matched (n = 3)
or 1- or 2-antigen-mismatched (n = 27) UCB following 1 of 2 standardized preparative and graft-versus-host disease regimens
(hyperfractionated total body irradiation, cyclophosphamide, and
antithymocyte globulin [ATG] with cyclosporine A and methotrexate; or
busulfan, melphalan, and ATG with cyclosporine A and prednisone). The
median time to neutrophil and platelet engraftment was 27 days (12-60 days) and 75 days (33-158 days) posttransplantation, respectively. No
correlation was noted between neutrophil and platelet engraftment and
nucleated cells per kilogram, CD34+ cells per kilogram
infused, or cytomegalovirus status of recipient. The cumulative
probability of acute grade 2 or greater graft-versus-host disease
(GVHD) was 37.2%, and of grade 3 or greater GVHD was 8.8%. No
patients developed chronic GVHD. CD4, CD19, and natural killer cell
recovery was achieved at a median of 12, 6, and 2 months, respectively.
CD8 recovery was delayed at a median of 9 months. Normal mitogen
response was achieved at 6 to 9 months. The probability of survival,
disease-free survival, and event-free survival at 1 year was 52.3%
(34.1%-70.5%), 54.7% (34.5%-74.9%) and 49.6% (29.9%-69.4%),
respectively. This series of 30 UCB transplants suggests that although
CD8 cell recovery is delayed, the pattern of immune reconstitution with
UCB is similar to that reported for other stem cell sources.
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