Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies

Blood. 2002 Jan 1;99(1):75-82. doi: 10.1182/blood.v99.1.75.


A reduced-intensity conditioning regimen was investigated in 45 patients with hematologic malignancies who were considered poor candidates for conventional myeloablative regimens. Median patient age was 49 years. Twenty-six patients previously failed autologous transplantation, and 18 patients had a refractory disease at the time of transplantation. In order to decrease nonrelapse mortality, and enhance the graft-versus-tumor effect, a program was designed in which a reduced conditioning with thiotepa, fludarabine, and cyclophosphamide was associated with programmed reinfusions of donor lymphocytes for patients without graft-versus-host disease (GVHD), not achieving clinical and molecular remission after transplantation. GVHD prophylaxis consisted of cyclosporine A and methotrexate. Seventeen patients received marrow cells and 28 received mobilized hematopoietic cells. All patients engrafted. The probability of grades II-IV and III-IV acute GVHD were 47% and 13%, respectively. The probability of nonrelapse mortality, progression-free survival, and overall survival were 13%, 57%, and 53%, respectively. Thirteen patients in complete remission had a polymerase chain reaction marker for minimal disease monitoring; 10 achieved molecular remission after transplantation. Nine patients received donor lymphocytes: one patient with mantle cell lymphoma had a minimal response, one patient with refractory anemia with excess of blasts in transformation achieved complete remission, and 7 patients did not respond. At a median follow-up of 385 days (range, 24 to 820 days), 25 patients (55%) were alive in complete remission. Although longer follow-up is needed to evaluate the long-term outcome, the study shows that this regimen is associated with a durable engraftment, has a low nonrelapse mortality rate, and can induce clinical and molecular remissions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anemia, Refractory, with Excess of Blasts / therapy
  • Cyclophosphamide / administration & dosage
  • Cyclosporine / therapeutic use
  • Female
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / prevention & control
  • Graft vs Tumor Effect
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Lymphocyte Transfusion
  • Lymphoma, Mantle-Cell / therapy
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Neoplasm, Residual / diagnosis
  • Neoplasm, Residual / genetics
  • Polymerase Chain Reaction
  • Recurrence
  • Remission Induction
  • Survival Rate
  • Thiotepa / administration & dosage
  • Transplantation Chimera
  • Transplantation Conditioning* / methods*
  • Transplantation, Homologous
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives*


  • Cyclosporine
  • Cyclophosphamide
  • Thiotepa
  • Vidarabine
  • fludarabine
  • Methotrexate