title: A two-step approach to myeloablative haploidentical transplantation: low nonrelapse mortality and high survival confirmed in patients with earlier stage disease.
abstract: Haploidentical hematopoietic stem cell transplantation (HSCT) is an attractive alternative donor option based on the rapid availability of an acceptable donor for most patients and decreased cost compared with costs of other alternative donor strategies. The safety of haploidentical HSCT has increased in recent years, making it ethically feasible to offer to patients with earlier stage disease. We developed a 2-step approach to haploidentical HSCT that separates the lymphoid and myeloid portions of the graft, allowing fixed T cell dosing to improve consistency in outcome comparisons. In the initial 2-step trial, the subset of patients without morphologic disease at HSCT had high rates of disease-free survival. To confirm these results, 28 additional patients without evidence of their disease were treated and are now 15 to 45 (median, 31) months past HSCT. To date, the 2-year cumulative incidence of nonrelapse mortality is 3.6%, with only 1 patient dying of nonrelapse causes, confirming the safety of this approach. Based on low regimen toxicity, the probabilities of disease-free and overall survival at 2 years are 74% and 77%, respectively, consistent with the findings in the initial trial and supporting the use of this approach in earlier stage patients lacking a matched related donor.
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: dolores.grosso@jefferson.edu.
authors.forename: Dolores
authors.initials: D
authors.lastname: Grosso
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Sameh
authors.initials: S
authors.lastname: Gaballa
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Onder
authors.initials: O
authors.lastname: Alpdogan
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Matthew
authors.initials: M
authors.lastname: Carabasi
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Joanne
authors.initials: J
authors.lastname: Filicko-O'Hara
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Margaret
authors.initials: M
authors.lastname: Kasner
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Martinez-Outschoorn
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: John L
authors.initials: JL
authors.lastname: Wagner
authors.affiliation: Department of Pharmacy, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: William
authors.initials: W
authors.lastname: O'Hara
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Shannon
authors.initials: S
authors.lastname: Rudolph
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Inna
authors.initials: I
authors.lastname: Chervoneva
authors.affiliation: Tissue Typing Laboratory, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Beth
authors.initials: B
authors.lastname: Colombe
authors.affiliation: Clinical Laboratory for Cellular Therapy, Thomas Jefferson Hospital, Philadelphia, Pennsylvania.
authors.forename: Patricia Cornett
authors.initials: PC
authors.lastname: Farley
authors.affiliation: Department of Infectious Diseases, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Flomenberg
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Manish
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Wenyin
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Mark
authors.initials: M
authors.lastname: Weiss
authors.affiliation: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Neal
authors.initials: N
authors.lastname: Flomenberg
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D018572:Disease-Free Survival; D005260:Female; D019337:Hematologic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015996:Survival Rate; D014019:Tissue Donors
keywords: Disease-free survival; Donor availability; Haploidentical stem cell transplantation; Nonrelapse mortality; T cell dosing