Higher doses of CD34+ peripheral blood stem cells are associated with increased mortality from chronic graft-versus-host disease after allogeneic HLA-identical sibling transplantation.
Allogeneic peripheral blood stem cell transplantation (PBSCT) has emerged as an alternative to bone marrow transplantation. PBSCT can be associated with a higher incidence of chronic graft-versus-host disease (cGVHD). In this study, we investigated whether there was a correlation between the composition of PBSC grafts (CD34+ and CD3+ cells) and hematological recovery, GVHD, relapse, and relapse-free survival (RFS) after myeloablative HLA-identical sibling PBSCT. The evolution of 100 acute or chronic leukemia patients was analyzed. Neither hematological recovery, acute or cGVHD, nor relapse, was significantly associated with CD3+ cell dose. Increasing CD34+ stem cells was associated with faster neutrophil (P=0.03) and platelet (P=0.007) recovery. Moreover, 47 of the 78 patients evaluable for cGVHD (60%; 95% CI, 49-71%) developed extensive cGVHD. The probability of extensive cGVHD at 4 years was 34% (95% CI, 21-47%) in patients receiving a 'low' CD34+ cell dose (<8.3 x 10(6)/kg), as compared to 62% (95% CI, 48-76%) in patients receiving a 'high' CD34+ cell dose (>8.3 x 10(6)/kg) (P=0.01). At a median follow-up of 59 months, this has not translated into a difference in relapse. In patients evaluable for cGVHD, RFS was significantly higher in patients receiving a 'low' CD34+ cell dose as compared to those receiving a 'high' CD34+ cell dose (P=0.04). This difference was mainly because of a significantly higher cGVHD-associated mortality (P=0.01). Efforts to accelerate engraftment by increasing CD34+ cell dose must be counterbalanced with the risk of detrimental cGVHD.
Institut Paoli-Calmettes, Marseille, France.
M
M
Mohty
K
K
Bilger
E
E
Jourdan
M
M
Kuentz
M
M
Michallet
J H
JH
Bourhis
N
N
Milpied
L
L
Sutton
J P
JP
Jouet
M
M
Attal
P
P
Bordigoni
J Y
JY
Cahn
A
A
Sadoun
N
N
Ifrah
D
D
Guyotat
C
C
Faucher
N
N
Fegueux
J
J
Reiffers
D
D
Maraninchi
D
D
Blaise
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism*; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality* / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006680:HLA Antigens / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization; D006650:Histocompatibility Testing; D006801:Humans; D007239:Infections / Q000209:etiology / Q000276:immunology; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation / Q000401:mortality*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D035781:Siblings; D015996:Survival Rate; D014019:Tissue Donors; D014185:Transplantation, Isogeneic / Q000276:immunology / Q000401:mortality; D016896:Treatment Outcome
D018952:Antigens, CD34; D006680:HLA Antigens; D016179:Granulocyte Colony-Stimulating Factor