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.
Bradley
M B
MB
Department of Pediatrics, Columbia University, New York, NY 10032, USA.
Satwani
P
P
Baldinger
L
L
Morris
E
E
van de Ven
C
C
Del Toro
G
G
Garvin
J
J
George
D
D
Bhatia
M
M
Roman
E
E
Baxter-Lowe
L A
LA
Schwartz
J
J
Qualter
E
E
Hawks
R
R
Wolownik
K
K
Foley
S
S
Militano
O
O
Leclere
J
J
Cheung
Y-K
YK
Cairo
M S
MS
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