Related and unrelated nonmyeloablative hematopoietic stem cell transplantation for malignant diseases.
Patients with advanced hematological malignancies ineligible for conventional myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) due to advanced age or medical contraindications were enrolled in multi-center study to investigate the safety and efficacy of nonmyeloablative HSCT using a 2 Gy total body irradi ation (TBI)-based regimen. A total of 192 patients (median age 55) were treated with HLA-matched sibling peripheral blood stem cell (PBSC) grafts, and 63 patients (median age 53) received a 10 of 10 HLA-antigen matched unrelated donor (URD) HSCT (PBSC graft, n = 48; marrow graft, n = 15). Diagnoses included multiple myeloma (n = 61), myelodysplastic syndrome (n = 55), chronic myeloid leukemia (n = 31), non-Hodgkin lymphoma (n = 31), acute myeloid leukemia (n = 28), chronic lymphocytic leukemia (n = 24), Hodgkin Disease (n = 14). The conditioning regimen was fludarabine 30 mg/m2/d x 3 days and 2 Gy TBI. Ninety-five related HSCT patients received 2 Gy TBI without fludarabine. Postgrafting immunosuppression was combined mycophenolate mofetil an cyclosporine. Transplants were well tolerated with a median of 0 days of hospitalization in the first 60 days for eligible patients. For related HSCT recipients, median follow-up was 289 (100-1,188) days. Nonfatal graft rejection occurred in 6.8%. Of those with sustained engraftment, graft-versus-host disease (GVHD) occurred in 49% (33% grade II, 11% grade III, 5% grade IV). Day-100 non-relapse mortality was 6%. Overall, 59% (114/192) of patients were alive. The relapse/disease progression mortality was 18%, and non-relapse mortality was 22%. The projecte 2-year survival and progression-free survival were 50% and 40%. For the URD HSCT recipients, median follow-up was 190 (100-468) days. Graft rejection occurred in 27% (17/63) of patients, mostly in recipients of marrow grafts (9/15). Acute GVHD occurred in 63% (50% grade II, 13% grade III) of 46 engrafted patients. Chronic GVHD requiring therapy occurred in 50% of patients. Of the 63 URD HSCT patients, 54% were alive, 37% in CR, 3% PR, and 14% with disease progression or relapse. Related and unrelated nonmyeloablative HSCT is feasible and potentially curative in patients with advanced hematological malignancies who have no other treatment options.
Georges
George E
GE
Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, USA.
Maris
Michael
M
Sandmaier
Brenda M
BM
Malone
David G
DG
Feinstein
Lyle
L
Niederweiser
Dietger
D
Shizuru
Judith A
JA
McSweeney
Peter A
PA
Chauncey
Thomas R
TR
Agura
Edward
E
Little
Marie-Trse
MT
Sahebi
Firoozeh
F
Hegenbart
Ute
U
Pulsipher
Michael A
MA
Bruno
Benedetto
B
Forman
Stephen
S
Woolfrey
Ann E
AE
Radich
Jerald P
JP
Blume
Karl G
KG
Storb
Rainer
R
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D016572:Cyclosporine / Q000008:administration & dosage; D018572:Disease-Free Survival; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D014181:Transplantation Immunology; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014916:Whole-Body Irradiation
D016572:Cyclosporine; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine