Reduced intensity allogeneic umbilical cord blood transplantation in children and adolescent recipients with malignant and non-malignant diseases.
There is a significant amount of morbidity and mortality following myeloablative umbilical cord blood transplantation (UCBT). Reduced intensity (RI) conditioning offers an alternative to myeloablative conditioning before UCBT. We investigated RI-UCBT in 21 children and adolescents with malignant (n=14), and non-malignant diseases (n=7). RI conditioning consisted of fludarabine (150-180 mg/m2) with either busulfan (< or = 8 mg/kg)+rabbit antithymocyte globulin (R-ATG; n=16) or cyclophosphamide+R-ATG+/-etoposide (n=5). Human leukocyte antigen match: 4/6 (n=13), 5/6 (n=5) and 6/6 (n=3). The median total nucleated cell and CD34+ cell dose per kilogram were 3.58 x 10(7) and 2.54 x 10(5), respectively. The median time for neutrophil and platelet engraftment was 17.5 and 52 days, respectively. There were six primary graft failures (chronic myelogenous leukemia (CML), beta-thalassemia, hemophagocytic lymphohistiocytosis (HLH) and myelodysplastic syndrome (MDS)). The probability of developing grade II to grade IV acute graft-versus-host disease (GVHD) and chronic GVHD was 28.6 and 16.7%, respectively. Incidence of transplant-related mortality (TRM) was 14%. The 5 years overall survival (OS) in all patients was 59.8%. The 5 years OS for patients with average versus poor-risk malignancy was 77.8 versus 22.2% (P=0.03). RI-UCBT may result in graft failure in specific high-risk chemo-naïve patients (CML, beta-thalassemia, HLH and MDS), but in more heavily pretreated pediatric and adolescent recipients results in rapid engraftment and may be associated with decreased severe GVHD and TRM.
Department of Pediatrics, Columbia University, New York, NY 10032, USA.
M B
MB
Bradley
P
P
Satwani
L
L
Baldinger
E
E
Morris
C
C
van de Ven
G
G
Del Toro
J
J
Garvin
D
D
George
M
M
Bhatia
E
E
Roman
L A
LA
Baxter-Lowe
J
J
Schwartz
E
E
Qualter
R
R
Hawks
K
K
Wolownik
S
S
Foley
O
O
Militano
J
J
Leclere
Y-K
YK
Cheung
M S
MS
Cairo
D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005312:Fetal Blood / Q000166:cytology*; D006086:Graft vs Host Disease / Q000517:prevention & control; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D019520:Living Donors; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000628:therapy; D009369:Neoplasms / Q000401:mortality / Q000628:therapy*; D018579:Patient Selection; D011994:Recombinant Proteins; D016019:Survival Analysis; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D017211:Treatment Failure; D016896:Treatment Outcome; D017086:beta-Thalassemia / Q000401:mortality / Q000628:therapy
D018952:Antigens, CD34; D007155:Immunologic Factors; D011994:Recombinant Proteins; C081222:sargramostim; D016178:Granulocyte-Macrophage Colony-Stimulating Factor