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Blood, 15 January 2001, Vol. 97, No. 2, pp. 383-387
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
The number of donor CD3+ cells is the most important
factor for graft failure after allogeneic transplantation of
CD34+ selected cells from peripheral blood from
HLA-identical siblings
Alvaro Urbano-Ispizua,
Ciril Rozman,
Pedro Pimentel,
Carlos Solano,
Javier de la Rubia,
Salut Brunet,
Jaime Pérez-Oteiza,
Christelle Ferrá,
Javier Zuazu,
Dolores Caballero,
Alzira Carvalhais,
Jose Luis Díez,
Ildefonso Espigado,
Carmen Martínez,
Fernando Campilho,
Miguel Angel Sanz,
Jorge Sierra,
Javier García-Conde, and
Emilio Montserrat for the Spanish Group for Allogeneic Peripheral Blood
Transplantation
From the Institute of Hematology and Oncology,
Department of Hematology, Hospital Clínic, University of
Barcelona, Barcelona, Spain; Instituto Português de
Oncologia-Centro do Porto, Oporto, Portugal; Hospital Clínico,
Valencia, Spain; Hospital La Fe, Valencia, Spain; Hospital Sant Pau,
Barcelona, Spain; Hospital Ramón y Cajal, Madrid, Spain; Hospital
Duran i Reynals, Barcelona, Spain; Hospital Vall d'Hebron, Barcelona,
Spain; Hospital Clínico, Salamanca, Spain; Hospital Gregorio
Marañón, Madrid, Spain; and Hospital Virgen del
Rocío, Sevilla, Spain.
This study analyzed the characteristics of 257 HLA-identical
sibling transplants of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells depleted of T cells by
CD34+ positive selection (allo-PBT/CD34+) for
their effect on the incidence of graft failure. Twenty-four patients
developed graft failure (actuarial probability, 11%; 95% confidence
interval, 7.1-14.9). Prognostic factors considered were sex and age of
donor and recipient, donor-recipient blood group compatibility,
diagnosis, disease status at transplant, conditioning regimen,
cytomegalovirus serology, number of CD34+ and
CD3+ cells infused, and cryopreservation. The major factor
associated with graft failure was the number of CD3+ cells
in the inoculum. Twenty-three of 155 patients receiving a T-cell dose
in the graft less than or equal to 0.2 × 106/kg
experienced graft failure, compared with only one of 102 patients receiving more than 0.2 × 106/kg (actuarial probability
18% vs 1%, respectively; P = .0001). The actuarial
probability of graft failure progressively increased as the number of
CD3+ cells in the graft decreased, which was determined by
grouping the number of CD3+ cells in quartiles (log-rank
P = .03; log-rank for trend P = .003). In
the multivariate analysis by the proportional hazard method, 2 covariates entered into regression at a significant level:
CD3+ cells less than or equal to
0.2 × 106/kg (risk ratio = 17;
P < .0001), and patients with chronic myelogenous leukemia (CML) conditioned with busulphan-based regimens (risk ratio = 4.8; P = .001). From these results it appears
that the number of CD3+ cells in the inoculum with a
threshold of 0.2 × 106/kg or lessis the most critical
factor in maintaining a sustained engraftment in
allo-PBT/CD34+ from HLA-identical siblings. In addition,
for patients with CML receiving 0.2 × 106/kg or less
CD3+ cells, total body irradiation might be better than
busulphan-based regimens.
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