Influence of bone marrow graft lymphocyte subsets on outcome after HLA-identical sibling transplants.
OBJECTIVE
The aim of this study was to analyze bone marrow lymphocyte subsets and CD34 cell dose and their influence on the outcomes of bone marrow transplantation.


METHODS
Forty-eight patients (median age 30 years, range 5-54) receiving HLA-identical sibling bone marrow transplantation for hematologic malignancies were analyzed.


RESULTS
Median number (range) of nucleated cells and CD34+ cells infused were 2.4 (0.4-6.0) x 10(8)/kg and 3.5 (0.5-13.0) x 10(6)/kg, respectively. Probability of neutrophil recovery was 97%. In a multivariate analysis, time to neutrophil recovery was shortened when a higher number of CD3/CD8 cells was infused (> or =1.0 x 10(7)/kg) (hazard ratio [HR] = 2.13, p = 0.018); when the patient was female or had negative cytomegalovirus serology (HR = 2.03, p = 0.03; HR = 0.41, p = 0.009; respectively). The incidence of grade II to IV acute graft-vs-host disease (GVHD) was 47%. Infusion of >1 x 10(7) CD4 infused/kg increased the risk of acute GVHD (HR = 2.86, p = 0.03). Nineteen of 40 patients at risk experienced chronic GVHD, the risk of which was increased by diagnosis of chronic leukemia (p = 0.03), <2.0 x 10(8) nucleated cells infused/kg (p = 0.05), and a low number of all lymphocyte subsets, except CD19. Estimated 3-year survival rate was 54%. Risk of death was increased in patients receiving <3.5 x 10(6)CD34 infused/kg (HR = 0.37, p = 0.02). Only six patients relapsed.


CONCLUSIONS
A high cell dose of CD3/CD8 is associated with faster neutrophil recovery, whereas a high cell dose of CD4+ cells increases the incidence of acute GVHD. A high number of nucleated cells and CD34+ cells infused was associated with decreased risk of chronic GVHD and improved survival, respectively.
Rocha
V
V
Bone Marrow Transplant Unit, Saint Louis Hospital, 1, av. Claude Vellefaux, 75475 Paris, Cedex 10, France. vrocha@cbtg.com
Carmagnat
M V
MV
Chevret
S
S
Flinois
O
O
Bittencourt
H
H
Esperou
H
H
Garnier
F
F
Ribaud
P
P
Devergie
A
A
Socié
G
G
Dal'Cortivo
L
L
Marolleau
J P
JP
Charron
D
D
Gluckman
E
E
Rabian
C
C
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D016026:Bone Marrow Transplantation / Q000401:mortality; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000637:transplantation; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D015897:Comorbidity; D003586:Cytomegalovirus Infections / Q000453:epidemiology; D005260:Female; D005602:France / Q000453:epidemiology; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D007958:Leukocyte Count; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D009679:Nuclear Family; D012306:Risk; D016019:Survival Analysis; D014019:Tissue Donors; D014184:Transplantation, Homologous
D018952:Antigens, CD34; D017252:CD3 Complex