HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies.
A hematopoietic cell transplantation (HCT) approach was developed for elderly or ill patients with hematologic malignancies that employed nonmyeloablative conditioning to avoid common regimen-related toxicities and relied on graft-versus-tumor effects for control of malignancy. Eighty-nine patients, median age 53 years, were given fludarabine (90 mg/m2) and 2 Gy total body irradiation. Marrow (n = 18) or granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral blood mononuclear cells (G-PBMCs; n = 71) were transplanted from unrelated donors matched for human leukocyte antigen A (HLA-A), -B, -C antigens and -DRB1 and -DQB1 alleles. Postgrafting immunosuppression included mycophenolate mofetil and cyclosporine. Donor T-cell chimerism was higher for G-PBMCs compared with marrow recipients. Durable engraftment was observed in 85% of G-PBMCs and 56% of marrow recipients. Cumulative probabilities of grade II, III, and IV acute graft-versus-host disease (GVHD) were 42%, 8%, and 2%, respectively. Nonrelapse mortality at day 100 and at 1 year was 11% and 16%, respectively. One-year overall survivals and progression-free survivals were 52% and 38%, respectively. G-PBMC recipients had improved survival (57% vs 33%) and progression-free survival (44% vs 17%) compared with marrow recipients. HLA-matched unrelated donor HCT after nonmyeloablative conditioning is feasible in patients ineligible for conventional HCT. G-PBMCs conferred higher donor T-cell chimerism, greater durable engraftment, and better progression-free and overall survivals compared with marrow.
Maris
Michael B
MB
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D1-100, PO Box 19024, Seattle, WA 98109-1024. mmaris@fhcrc.org
Niederwieser
Dietger
D
Sandmaier
Brenda M
BM
Storer
Barry
B
Stuart
Monic
M
Maloney
David
D
Petersdorf
Effie
E
McSweeney
Peter
P
Pulsipher
Michael
M
Woolfrey
Ann
A
Chauncey
Thomas
T
Agura
Ed
E
Heimfeld
Shelly
S
Slattery
John
J
Hegenbart
Ute
U
Anasetti
Claudio
C
Blume
Karl
K
Storb
Rainer
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015994:Incidence; D007938:Leukemia / Q000401:mortality* / Q000628:therapy*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000401:mortality / Q000628:therapy; D015479:Leukemia, Myelomonocytic, Acute / Q000401:mortality / Q000628:therapy; D017710:Lymphocyte Transfusion; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy; D009173:Mycophenolic Acid / Q000493:pharmacokinetics; D009196:Myeloproliferative Disorders / Q000401:mortality / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy; D015996:Survival Rate; D014019:Tissue Donors; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014916:Whole-Body Irradiation
D000903:Antibiotics, Antineoplastic; D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine