Immunosuppressive total lymphoid irradiation-based reconditioning regimens enable engraftment after graft rejection or graft failure in patients treated with allogeneic hematopoietic stem cell transplantation.
OBJECTIVE
To retrospectively evaluate the efficacy of total lymphoid irradiation (TLI)-based reconditioning regimens in patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation.


METHODS
The results of 14 patients (7 adults and 7 children) with a variety of hematologic malignant diseases treated with a TLI-based reconditioning regimen with 7-Gy single-dose application plus anti-T-lymphocyte antibody OKT3 (n = 11) and/or antithymocyte globulin (n = 7)/fludarabine (n = 9), followed by an infusion of peripheral blood stem cells (n = 13) or bone marrow stem cells (n = 1) from related or unrelated donors, were retrospectively analyzed.


RESULTS
Of the 14 recipients, the data from 11 were evaluable for engraftment after TLI-based reconditioning because 3 adults died early (at Day 2, 5, and 15) after the second transplantation of infectious complications. Engraftment in 4 adults was seen after a median of 12 days (range, 10-18) and occurred after a median of 10 days (range, 9-32) in the 7 children. TLI-based reconditioning was well-tolerated with no severe toxicity. The median overall survival and disease-free survival for the whole cohort was 140 days (range, 5-1,268). After a median follow-up of 681 days, the disease-free survival and overall survival rate was 85.7% and 85.7%, respectively, in the children. Despite engraftment in the 4 remaining adults, 1 died of fatal graft-vs.-host disease, 1 of infectious complications, 1 of disease relapse, and 1 of acute respiratory distress syndrome.


CONCLUSIONS
In patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation, TLI-based reconditioning regimens allow sustained engraftment, paralleled by a favorable toxicity profile, potentially leading to long-term survival.
Heinzelmann
Frank
F
Department of Radiation Oncology, University of Tuebingen, Tuebingen, Germany.
Lang
Peter J
PJ
Ottinger
Hellmut
H
Faul
Christoph
C
Bethge
Wolfgang
W
Handgretinger
Rupert
R
Bamberg
Michael
M
Belka
Claus
C
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000379:methods; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D006084:Graft Rejection / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015182:Lymphatic Irradiation / Q000379:methods* / Q000401:mortality; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods; D011014:Pneumonia / Q000209:etiology; D019233:Retreatment / Q000379:methods; D012189:Retrospective Studies; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods* / Q000401:mortality; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D014740:Vidarabine; C024352:fludarabine