Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia.
OBJECTIVE
Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning regimens imposes prohibitively high risks of morbidity and mortality for patients with high-risk acute myeloid leukemia (AML) who are older or have comorbid conditions. Here, we examined outcomes after nonmyeloablative allogeneic HCT in such patients.


METHODS
Two hundred seventy-four patients (median age, 60 years) with de novo or secondary AML underwent allogeneic HCT from related (n = 118) or unrelated donors (n = 156) after conditioning with 2 Gy of total-body irradiation (TBI) with or without fludarabine. A calcineurin inhibitor and mycophenolate mofetil were used for postgrafting immunosuppression.


RESULTS
With a median follow-up of 38 months in surviving patients, the estimated overall survival at 5 years was 33%. The estimated 5-year relapse/progression and nonrelapse mortality rates were 42% and 26%, respectively. The cumulative incidences of grades 2, 3, and 4 acute graft-versus-host disease (GVHD) were 38%, 9%, and 5%, respectively. The cumulative incidence of chronic GVHD at 5 years was 44%. Patients in first and second complete remission had better survival rates than patients with more advanced disease (37% and 34% v 18%, respectively). Patients with HLA-matched related or unrelated donors had similar survivals. Unfavorable cytogenetic risk status was associated with increased relapse and subsequent mortality. Chronic GVHD was associated with lower relapse risk.


CONCLUSIONS
Allogeneic HCT from related or unrelated donors after conditioning with low-dose TBI and fludarabine, relying almost exclusively on graft-versus-leukemia effects, can result in long-term remissions in older or medically infirm patients with AML.
Gyurkocza
Boglarka
B
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA
Storb
Rainer
R
Storer
Barry E
BE
Chauncey
Thomas R
TR
Lange
Thoralf
T
Shizuru
Judith A
JA
Langston
Amelia A
AA
Pulsipher
Michael A
MA
Bredeson
Christopher N
CN
Maziarz
Richard T
RT
Bruno
Benedetto
B
Petersen
Finn B
FB
Maris
Michael B
MB
Agura
Edward
E
Yeager
Andrew
A
Bethge
Wolfgang
W
Sahebi
Firoozeh
F
Appelbaum
Frederick R
FR
Maloney
David G
DG
Sandmaier
Brenda M
BM
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult