Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation

Haematologica. 2004 Oct;89(10):1238-47.

Abstract

Background and objectives: Transplant-related mortality (TRM) following allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to be related to disease stage, duratiion of disease and type of donor. Furthermore, the outcome of transplants performed in the 1990s appears to be better than that of transplants done in the previous decade. The aims of this study were to determine whether these relationships still hold and whether the outcome of transplants is continuing to improve.

Design and methods: We analyzed 1180 consecutive patients with leukemia (n=979) or other hematologic malignancies (n=201) undergoing HSCT in 4 time periods: before 1990, 1991-1995, 1996-2000, and 2001-2002. Changes during these eras include increasing patient age, more unrelated transplants, more patients with advanced disease, different graft-versus-host disease (GvHD) prophylaxis, and different management of infections.

Results: The actuarial 2-year transplant-related mortality (TRM) differed significantly between the transplant eras (p<0.001) with a significant interaction with disease phase (p=0.018). In patients in first remission (n=585) TRM was 34%, 25%, 21% and 6% in the four transplant eras. The reduction in TRM was less evident in patients in second remission (n=284) (37%, 35%, 30%, 25%) and absent in relapsed patients (n=311) (TRM=45%, 41%, 29%, 51%). This is a consequence of reductions in GvHD, infections and multiorgan failure among patients in remission but not among those who relapse. The actuarial 2-year survival has improved significantly in patients in first remission (54%, 66%, 72%, 78%) but not in those in second remission (38%, 46%, 52%,45%), or relapsed patients (31%, 25%, 36%, 21%).

Interpretation and conclusions: In conclusion, TRM has been significantly reduced in first remission patients, suggesting an allograft should be considered in this phase, when appropriate, without delay. There has been no improvement in survival for patients beyond first remission, due to persisting high risk of infections and organ toxicity, a possible consequence of prolonged pre-transplant chemotherapy and neutropenia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actuarial Analysis
  • Adult
  • Anti-Infective Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow Transplantation / mortality*
  • Bone Marrow Transplantation / statistics & numerical data
  • Cause of Death
  • Combined Modality Therapy
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / surgery*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Hematopoietic Stem Cell Transplantation / statistics & numerical data
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Infection Control
  • Infections / etiology
  • Infections / mortality
  • Leukemia / drug therapy
  • Leukemia / mortality
  • Leukemia / surgery
  • Lung Diseases, Interstitial / etiology
  • Lung Diseases, Interstitial / mortality
  • Male
  • Middle Aged
  • Multiple Organ Failure
  • Neutropenia / chemically induced
  • Neutropenia / complications
  • Peripheral Blood Stem Cell Transplantation / adverse effects
  • Peripheral Blood Stem Cell Transplantation / methods
  • Peripheral Blood Stem Cell Transplantation / mortality
  • Peripheral Blood Stem Cell Transplantation / statistics & numerical data
  • Premedication
  • Remission Induction
  • Retrospective Studies
  • Salvage Therapy
  • Survival Analysis
  • Transplantation Conditioning / methods
  • Transplantation Conditioning / mortality
  • Transplantation, Homologous / methods
  • Transplantation, Homologous / mortality*
  • Transplantation, Homologous / statistics & numerical data
  • Treatment Outcome

Substances

  • Anti-Infective Agents
  • Immunosuppressive Agents