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Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3323-3327
Effect of nucleated marrow cell dose on relapse and survival
in identical twin bone marrow transplants for leukemia
A. John Barrett,
Olle Ringdén,
Mei-Jie Zhang,
Asad Bashey,
Jean-Yves Cahn,
Mitchell
S. Cairo,
Robert Peter Gale,
Alois Gratwohl,
Franco Locatelli,
Rodrigo Martino,
Kirk R. Schultz,
Pierre Tiberghien, and
the
GVHD/GVL Working Committee of the International Bone Marrow
Transplant Registry
From the International Bone Marrow Transplant Registry, Health
Policy Institute, Medical College of Wisconsin, Milwaukee, WI;
Hematology Branch, National Heart, Lung and Blood Institute, National
Institutes of Health, Bethesda, MD; Department of
Transplantation Surgery, Huddinge University Hospital, Huddinge,
Sweden; Department of Hematology/Oncology, University of California,
San Diego, CA; Service d'Hematologie, Hôpital Minjoz, France;
Department of Pediatrics, Georgetown University Medical Center,
Washington, DC; Center for Advanced Studies in Leukemia, Los Angeles,
CA; Department of Hematology, Kantonsspital, Basel, Switzerland;
University of Pavia, Pavia, Italy; Servicio de Hematologia Clinica,
Hospital de Sant Pau, Barcelona, Spain; Department of Pediatrics,
University of British Columbia, Vancouver, BC, Canada; and Cell and
Gene Therapy Unit, Etablissement de Transfusion Sanguine de
Franche-Comte, Bescancon, France. A complete list of the members of
the GVHD/GVL Working Committee of the International Bone Marrow
Transplant Registry appears at the end of this article.
The impact of cell dose (number of nucleated donor cells per
kilogram recipient weight) on transplantation outcome is controversial and may differ for allogeneic and identical twin (syngeneic) bone marrow transplants. We studied the association between cell dose and
outcome in 100 unmanipulated identical twin bone marrow
transplantations for leukemia, reported to the International Bone
Marrow Transplant Registry between 1985 and 1994, using Cox
proportional hazards regression for multivariate analyses. Cell doses
ranged from 0.3 to 7.4 × 108 nucleated cells/kg
(median, 3.0 × 108cells/kg). Median follow-up was 75 months. Five-year cumulative incidences of transplant-related mortality
with high (more than 3 × 108 cells/kg) versus low (less
than or equal to 3 × 108 cells/kg) cell doses were
2% (95% confidence interval [CI], 0% to 8%) versus 10%
(95% CI, 4% to 20%), respectively. Five-year probabilities of
leukemia-free survival were 53% (95% CI, 39% to 67%) and 37% (95%
CI, 23% to 52%), respectively. In multivariate analysis, among
patients surviving in remission at least 9 months after
transplantation, those receiving high cell doses were at significantly
lower risk for treatment failure (relapse or death) than those
receiving low cell doses (RR, 0.27; 95% CI, 0.12 to 0.6;
P = .001). Lower treatment failure resulted from fewer
relapses in the high cell dose group (RR for relapse, 0.28; 95% CI,
1.2 to 0.66; P = .003). These findings suggest that
outcomes after syngeneic bone marrow transplantation could be improved
by transplanting more than 3 × 108 nucleated cells per
kilogram. The benefit of high cell dose on relapse may represent a
delayed graft-versus-leukemia effect.
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