title: Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors.
abstract: We enrolled 30 patients on a prospective phase II trial utilizing a total body irradiation (TBI)-based myeloablative preparative regimen (fludarabine 30 mg/m2/day × 3 days and TBI 150 cGy twice per day on day -4 to -1 [total dose 1200 cGy]) followed by infusion of unmanipulated peripheral blood stem cells from a haploidentical family donor (haplo). Postgrafting immunosuppression consisted of cyclophosphamide 50 mg/kg/day on days 3 and 4, mycophenolate mofetil through day 35, and tacrolimus through day 180. Median patient age was 46.5 years (range, 24 to 60). Transplantation diagnosis included acute myelogenous leukemia (n = 16), acute lymphoblastic leukemia (n = 6), chronic myelogenous leukemia (n = 5), myelodysplastic syndrome (n = 1), and non-Hodgkin's lymphoma (n = 2). Using the Dana Farber/Center for International Blood and Marrow Transplant Research/Disease Risk Index (DRI), patients were classified as low (n = 4), intermediate (n = 12), high (n = 11), and very high (n = 3) risk. All patients engrafted with a median time to neutrophil and platelet recovery of 16 and 25 days, respectively. All evaluable patients achieved sustained complete donor T cell and myeloid chimerism by day +30. Acute graft-versus-host disease (GVHD) grades II to IV and III and IV was seen in 43% and 23%, respectively. The cumulative incidence of chronic GVHD was 56% (severe in 10%). After a median follow-up of 24 months, the estimated 2-year overall survival (OS), disease-free survival (DFS), nonrelapse mortality, and relapse rate were 78%, 73%, 3%, and 24%, respectively. Two-year DFS and relapse rate in patients with low/intermediate risk disease was 100% and 0%, respectively, compared with 39% and 53% for patients with high/very high risk disease. When compared with a contemporaneously treated cohort of patients at our institution receiving myeloablative HLA-matched unrelated donor (MUD) transplantation (acute myelogenous leukemia [n = 17], acute lymphoblastic leukemia [n = 15], chronic myelogenous leukemia [n = 7], myelodysplastic syndrome [n = 7], non-Hodgkin lymphoma [n = 1], chronic lymphoblastic leukemia [n = 1]), outcomes were statistically similar, with 2-yr OS and DFS being 78% and 73%, respectively after haplo transplantation versus 71% and 64%, respectively, after MUD transplantation. In patients with DRI low/intermediate risk disease, 2-yr DFS was superior after haplo compared with MUD transplantations (100% versus 74%, P = .032), whereas there was no difference in DFS in patients with high/very high risk disease (39% versus 37% for haplo and MUD respectively, P = .821). Grade II to IV acute GVHD was seen less often after haplo compared with MUD transplantation (43% versus 63%, P = .049), as was moderate-to-severe chronic GVHD (22% versus 58%, P = .003). Myeloablative haplo transplantation using this regimen is a valid option for patients with advanced hematologic malignancies who lack timely access to a conventional donor. Outcomes appear at least equivalent to those seen in contemporaneous patients who underwent transplantation from MUD.
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia. Electronic address: ssolomon@bmtga.com.
authors: Scott R
authors: SR
authors: Solomon
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia.
authors: Connie A
authors: CA
authors: Sizemore
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia.
authors: Melissa
authors: M
authors: Sanacore
authors: Department of Mathematics and Statistics, Georgia State University, Atlanta, Georgia.
authors: Xu
authors: X
authors: Zhang
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia.
authors: Stacey
authors: S
authors: Brown
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia.
authors: H Kent
authors: HK
authors: Holland
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia.
authors: Lawrence E
authors: LE
authors: Morris
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia.
authors: Asad
authors: A
authors: Bashey
mesh_terms: D000208:Acute Disease; D000328:Adult; D002908:Chronic Disease; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D011446:Prospective Studies; D012008:Recurrence; D012306:Risk; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use; D019172:Transplantation Conditioning; D014185:Transplantation, Isogeneic; D061349:Unrelated Donors; D014916:Whole-Body Irradiation
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: Haploidentical; Myeloablative; Peripheral blood stem cells; Stem cell transplantation; Total body irradiation