Reduced-intensity conditioning followed by related allografts in hematologic malignancies: long-term outcomes most successful in indolent and aggressive non-Hodgkin lymphomas.
Reduced-intensity conditioning (RIC) extends the curative potential of allogeneic hematopoietic cell transplantation (HCT) to patients with hematologic malignancies unable to withstand myeloablative conditioning. We prospectively analyzed the outcomes of 123 patients (median age, 57 years; range, 23-70 years) with hematologic malignancies treated with a uniform RIC regimen of cyclophosphamide, fludarabine, and total-body irradiation (200 cGy) with or without antithymocyte globulin followed by related donor allogeneic HCT at the University of Minnesota between 2002 and 2008. The cohort included 45 patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), 27 with aggressive non-Hodgkin lymphoma (NHL), 8 with indolent NHL, 10 with Hodgkin lymphoma (HL), 10 with myeloma, and 23 with acute lymphocytic leukemia, chronic myelogenous leukemia, other leukemias, or myeloproliferative disorders. The probability of 4-year overall survival was 73% for patients with indolent NHL, 58% for those with aggressive NHL, 67% for those with HL, 30% for those with AML/MDS, and only 10% for those with myeloma. Corresponding outcomes for relapse in these patients were 0%, 32%, 50%, 33%, and 38%, and those for progression-free survival were 73%, 45%, 27%, 27%, and 10%. The incidence of treatment-related mortality was 14% at day +100 and 22% at 1 year. The incidence of grade II-IV acute graft-versus-host disease was 38% at day +100, and that of chronic graft-versus-host disease was 50% at 2 years. Multivariate analysis revealed superior overall survival and progression-free survival in patients with both indolent and aggressive NHL compared with those with AML/MDS, HL, or myeloma. Worse 1-year treatment-related mortality was observed in patients with a Hematopoietic Cell Transplantation Comorbidity Index score ≥ 3 and in cytomegalovirus-seropositive recipients. These results suggest that (1) RIC conditioning was well tolerated by an older, heavily pretreated population; (2) patients with indolent and aggressive NHL respond well to RIC conditioning, highlighting the importance of the graft-versus-lymphoma effect; and (3) additional peri-transplantation manipulations are needed to improve outcomes for patients with AML/MDS or myeloma receiving RIC conditioning before HCT.
Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN 55455, USA. ewarlick@umn.edu
Erica D
ED
Warlick
Marcie
M
Tomblyn
Qing
Q
Cao
Todd
T
Defor
Bruce R
BR
Blazar
Margaret
M
Macmillan
Michael
M
Verneris
John
J
Wagner
Kathryn
K
Dusenbery
Mukta
M
Aurora
Veronika
V
Bachanova
Claudio
C
Brunstein
Linda
L
Burns
Sarah
S
Cooley
Dan
D
Kaufman
Navneet S
NS
Majhail
Brian
B
McClune
Philip
P
McGlave
Jeffrey
J
Miller
Betul
B
Oran
Arne
A
Slungaard
Gregory
G
Vercellotti
Daniel J
DJ
Weisdorf
D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D020350:Graft vs Tumor Effect; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000601:surgery*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000601:surgery; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods* / Q000706:statistics & numerical data; D011446:Prospective Studies; D012008:Recurrence; D015996:Survival Rate; D013601:T-Lymphocytes; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation; D055815:Young Adult
D000961:Antilymphocyte Serum; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine