title: The Addition of Low-Dose Total Body Irradiation to Fludarabine and Melphalan Conditioning in Haplocord Transplantation for High-Risk Hematological Malignancies.
abstract: BACKGROUND
  Preliminary evidence indicates that the addition of low-dose total body irradiation (TBI) (2-4 Gy) to reduced intensity conditioning may reduce the rate of relapse in allogeneic stem cell transplants. In very high-risk patients receiving combination haploidentical single-unit cord blood transplants, we have added 4 Gy TBI to the widely used fludarabine, melphalan conditioning regimen, in hopes of reducing relapse and decreasing graft rejection.
  
  
  METHODS
  We retrospectively reviewed the posttransplant outcomes of patients who underwent haplocord stem cell transplant between May 2013 and March 2015 and who received fludarabine 30 mg/m day (D)-7 to -3, melphalan 140 mg/m D-2, and 2 Gy TBI D-4 and -3.
  
  
  RESULTS
  All 25 patients achieved primary neutrophil engraftment after a median of 12 days. The median time to platelet engraftment was 27 days. The cumulative incidence of nonrelapse mortality was 16% by D+100 and 33% by 1 year. The cumulative incidence of grade III to IV acute graft-versus-host disease was 36% by D+100. The CIR was 13% by D+100 and 29% by 1 year. The estimated 1-year overall survival and progression-free survival were 40% and 37%, respectively. In a subgroup analysis, we compared the outcome of 13 acute myeloid leukemia patients receiving this conditioning regimen with age and disease risk index-matched acute myeloid leukemia patients receiving fludarabine-melphalan without TBI. The TBI group had lower incidence of relapse at 1 year (15% vs 54%, P = 0.05).
  
  
  CONCLUSIONS
  Overall, combination fludarabine-melphalan with low-dose TBI after haplocord stem cell transplant assures good engraftment and leads to acceptable toxicity and disease control in the setting of high risk, heavily pretreated patients. These findings warrant further investigation at a larger-scale, prospective level.
authors.affiliation: 1 Department of Hematology/Oncology, Weill Cornell Medicine, New York, NY. 2 Department of Radiation Oncology, Weill Cornell Medicine, New York, NY.
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Choe
authors.forename: Usama
authors.initials: U
authors.lastname: Gergis
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Mayer
authors.forename: Himanshu
authors.initials: H
authors.lastname: Nagar
authors.forename: Adrienne A
authors.initials: AA
authors.lastname: Phillips
authors.forename: Tsiporah B
authors.initials: TB
authors.lastname: Shore
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Smith
authors.forename: Koen
authors.initials: K
authors.lastname: van Besien
mesh_terms: D000328:Adult; D000368:Aged; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D011829:Radiation Dosage; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D016896:Treatment Outcome; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014916:Whole-Body Irradiation / Q000009:adverse effects / Q000401:mortality; D055815:Young Adult
chemical_list: D019653:Myeloablative Agonists; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan