Retransplantation with stem cells from mismatched related donors after graft rejection in pediatric patients.
Graft failure is a life-threatening complication after transplantation of hematopoietic stem cells. We report a cohort of 11 pediatric patients with leukemias (n=8) and severe aplastic anemia (n=3) who experienced graft rejection after myeloablative transplantation from mismatched related donors (n=6) or after cord blood or matched unrelated donor transplantation (n=5). In the latter, the original donor was not available anymore. All patients were re-transplanted with CD34(+) selected or CD3/CD19 depleted stem cells from a second, haploidentical donor. Median time span from diagnosis of rejection to second transplant was 9 days. Reconditioning regimens comprised total lymphoid irradiation, thiotepa, fludarabine, ATG/OKT3 and were well tolerated. A median number of 23.5x10(6)/kg stem cells with 95,000/kg residual T-cells were infused. Sustained engraftment of neutrophiles/platelets and complete donor chimerism was achieved in all patients (ANC>500/microl: 9 (11-32) days). No GvHD>grade II was observed. 8/11 patients are disease free (median follow up 1.9 years; 1 year-EFS=72%). Causes of death were: pneumonitis, infection, relapse. Thus, haploidentical transplantation represents a realistic option to rescue patients with graft failure within a short time span, for whom a second donation from the original donor is not available. The use of different donors may contribute to avoid a second rejection.
Lang
Peter
P
Department of Pediatric Oncology, University Children's Hospital, Eberhard Karl's University, Tübingen, Hoppe Seyler Strasse 1, 72076 Tübingen, Germany. prlang@med.uni-tuebingen.de
Mueller
Ingo
I
Greil
Johann
J
Bader
Peter
P
Schumm
Michael
M
Pfeiffer
Matthias
M
Hoelle
Walter
W
Klingebiel
Thomas
T
Heinzelmann
Frank
F
Belka
Claus
C
Schlegel
Paul G
PG
Kremens
Bernhard
B
Woessmann
Wilhelm
W
Handgretinger
Rupert
R
D000293:Adolescent; D000328:Adult; D002423:Cause of Death; D002452:Cell Count; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D006084:Graft Rejection; D006085:Graft Survival; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility; D006801:Humans; D047589:Leukocyte Reduction Procedures; D012086:Reoperation; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous