title: Canadian multicenter pilot trial of haploidentical donor transplantation.
abstract: BACKGROUND
  Canadian multicenter pilot study of haploidentical donor.
  
  
  OBJECTIVE
  To assess (1) ability to collect suitable graft (CD34+ > or = 5 x 10(6)/kg and CD3 < 1 x 10(5)/kg recipient body weight), (2) toxicity, (3) survival to day +100. ELIGIBILITY: All hematological malignancies and ages; accrual to end after 20 transplants of patients with AML in remission and age less than 55 years.
  
  
  METHODS
  Preparation: Modified Perugia regimen, chemotherapy alone; melphalan 140 mg/m2 day -9, thiotepa 10 mg/kg day -7, fludarabine 40 mg/m2 days -7 to -3, and ATG (Thymoglobulin, Sangstat) days -6 to -2 (total 10.5 mg/kg). Infection prophylaxis: Ganciclovir (GC) 5 mg/kg days 5-20 then x5/week until day +100 then x3/week until 210 (subjects 1-3), foscarnet (FC) 90 mg/kg days 4-21 then short course pre-emptive GC or FC (subjects 4-11); fluconazole; cotrimoxazole. Donors: G-CSF 16 microg/kg daily x5 until second pheresis day. T-cell depletion: CliniMACS (MiltenyiBiotec).
  
  
  RESULTS
  Eleven patients with AML have been transplanted from four centers, eight female, three male, median age 34 (range 19-60). Disease status, first CR 1/11, second CR 4/11, third CR1/11, relapse 5/11. Graft CD34+ > or = 5 x 10(6)/kg was achieved in all cases, median 13.72 x 10(6)/kg (Q1, Q3: 8.26, 17.72; min 5.59, max 22.22), and CD3+ was < 1 x 10(5)/kg in all cases, median of 0.49 x 10(4)/kg (Q1, Q3: 0.30, 2.20; min 0.22, max 4.10). Ten of the 11 patients have died, median survival 103.5 days (Q1, Q3: 61.0, 151.0; min 0, max 290.0). Survival to day +100 6/11 (55%). Four patients died of leukemic relapse, six of infection. Of six patients dying of infection, CMV was a definite cause in four. Of four dying with relapse, CMV was significant in one. Engraftment was assessed in 10 patients who survived >0 days. Granulocyte engraftment (> 0.5 x 10(9)/l) was achieved in all patients, median 11.5 days (Q1, Q3: 10, 17; min 8, max 70). Platelet engraftment (> 20 x 10(9)/l) was achieved in 8 of 10 patients, median 15 days (Q1, Q3: 9, 16; min 9, max 97). The two platelet non-engrafters died on days +45 and +61. Toxicity was low, with one toxic death (day 0), and the Bearman organ toxicity gradings were < or = grade 2 in all other patients. There were no instances of graft-vs.-host disease or graft rejection.
  
  
  CONCLUSIONS
  The problems of graft-vs.-host disease and graft rejection have been removed as barriers to haploidentical transplantation but the slow immune reconstitution limits its general application. Late referrals contribute to a high relapse rate and have delayed an optimal evaluation of the procedure.
authors.affiliation: McMaster University, Hamilton, Ontario, Canada. walkeri@mcmaster.ca
authors.forename: Irwin
authors.initials: I
authors.lastname: Walker
authors.forename: Nadine
authors.initials: N
authors.lastname: Shehata
authors.forename: Guy
authors.initials: G
authors.lastname: Cantin
authors.forename: Felix
authors.initials: F
authors.lastname: Couture
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dhédin
authors.forename: Rebecca
authors.initials: R
authors.lastname: Barty
authors.forename: Ronan
authors.initials: R
authors.lastname: Foley
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sutherland
authors.forename: Christopher
authors.initials: C
authors.lastname: Sigouin
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Schultz
authors.forename: David
authors.initials: D
authors.lastname: Mitchell
mesh_terms: D000328:Adult; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D006239:Haplotypes; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous