Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation.
OBJECTIVE
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.


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%).


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.
Bacigalupo
Andrea
A
Dipartimento di Emato-Oncologia, Ospedale San Martino, Genoa, Italy. andrea.bacigalupo@hsanmartino.it <andrea.bacigalupo@hsanmartino.it>
Sormani
Maria Pia
MP
Lamparelli
Teresa
T
Gualandi
Francesca
F
Occhini
Domenico
D
Bregante
Stefania
S
Raiola
Anna Maria
AM
di Grazia
Carmen
C
Dominietto
Alida
A
Tedone
Elisabetta
E
Piaggio
Giovanna
G
Podesta
Marina
M
Bruno
Barbara
B
Oneto
Rosi
R
Lombardi
Anna
A
Frassoni
Francesco
F
Rolla
Davide
D
Rollandi
Gianandrea
G
Viscoli
Claudio
C
Ferro
Carlo
C
Garbarino
Lucia
L
Van Lint
Maria Teresa
MT
D000206:Actuarial Analysis; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000401:mortality* / Q000706:statistics & numerical data; D002423:Cause of Death; D003131:Combined Modality Therapy; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000601:surgery*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality / Q000706:statistics & numerical data; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D017053:Infection Control; D007239:Infections / Q000209:etiology / Q000401:mortality; D007938:Leukemia / Q000188:drug therapy / Q000401:mortality / Q000601:surgery; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality / Q000706:statistics & numerical data; D011292:Premedication; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality; D014184:Transplantation, Homologous / Q000379:methods / Q000401:mortality* / Q000706:statistics & numerical data; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D007166:Immunosuppressive Agents