Immunosuppressive total lymphoid irradiation-based reconditioning regimens enable engraftment after graft rejection or graft failure in patients treated with allogeneic hematopoietic stem cell transplantation

Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):523-8. doi: 10.1016/j.ijrobp.2007.06.037. Epub 2007 Sep 14.

Abstract

Purpose: 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 and materials: 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.

Publication types

  • Evaluation Study

MeSH terms

  • Adolescent
  • Adult
  • Antilymphocyte Serum / therapeutic use
  • Bone Marrow Transplantation / methods
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Graft Rejection / prevention & control
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / surgery*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Lymphatic Irradiation / methods*
  • Lymphatic Irradiation / mortality
  • Middle Aged
  • Muromonab-CD3 / therapeutic use
  • Peripheral Blood Stem Cell Transplantation / methods
  • Pneumonia / etiology
  • Retreatment / methods
  • Retrospective Studies
  • Survival Rate
  • Transplantation Conditioning / methods*
  • Transplantation Conditioning / mortality
  • Transplantation, Homologous
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents
  • Muromonab-CD3
  • Vidarabine
  • fludarabine