Canadian multicenter pilot trial of haploidentical donor transplantation Academic Article uri icon

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abstract

  • BACKGROUND: Canadian multicenter pilot study of haploidentical donor. AIMS: 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

  • Walker, Irwin Ronald
  • Shehata, Nadine
  • Cantin, Guy
  • Couture, Felix
  • Dhédin, Nathalie
  • Barty, Rebecca
  • Foley, Ronan
  • Sutherland, Robert D
  • Sigouin, Christopher
  • Schultz, Kirk R
  • Mitchell, David

publication date

  • November 2004