Results of Haploidentical Allogeneic Haematopoietic Stem-Cell Transplantation in Patients with Acute Leukaemia: A Single Centre Experience

Background: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a potentially curative treatment for a variety of hematologic malignancies and nonmalignant hematologic disorders. However, only about a third of candidates for allo-HSCT have HLA-matched siblings. For patients who lack HLA-matched siblings, partially HLA-mismatched (haploidentical) related donors are good alternative sources of stem cells for allo-HSCT.  In this retrospective, single center study we evaluated safety and efficacy of haploidentical allo-HSCT compared to those of HLA-matched allo-HSCT in patients with acute leukemia.

Methods: A total of 94 acute leukemia patients with a mean age of 37 years who underwent allo-HSCT between June 2010 and November 2012 were analyzed. All patients received Cyclophosphamide (Cy) 50 mg/kg i.v. on days +3 and +4. Pharmacologic prophylaxis of GvHD with cyclosporine-A (CsA) and mycophenolate mofetil (MMF) was not initiated until day +5 to avoid blocking Cy-induced tolerance. All patients received CsA which was initiated at a dose of 400 mg/day, and then adjusted according to the plasma levels. If there was no GvHD, it was tapered off by day +180. In addition to CsA, all haploidentical allo-HSCT recipients received MMF until day +35 at a dose of 1 gr/day.

Results: There were no significant differences in age, sex, type of acute leukemia, disease status up-front HSCT, or transplant characteristics between the groups except a higher median number of stem cells infused in haploidentical group (p=0.002). The median follow-up was 194 (range 88-372) days for haploidentical group and 210 (range 105-417) days for HLA-matched group. 98% of the patients engrafted. The median time to neutrophil and thrombocyte engraftments were significantly longer in the haploidentical group compared to the HLA-matched group (neutrophil engraftment; 20 days vs 16 days, respectively, p= 0.006) (thrombocyte engraftment; 18 days vs 16 days, respectively, p=0.015). The incidence of acute GvHD >= 2 was 56% in haploidentical group and 19% in HLA-matched group (p=0.001). The incidence of documented viral infections was significantly higher in the haploidentical group compared to the HLA-matched group (42% vs 11%, respectively, p=0.001). The relapse rates as well as the overall mortality rates (at 100 days and 1 year) were not significantly different between the two groups.

Conclusion: Our results suggest that haploidentical allo-HSCT is a safe treatment modality in patients with acute leukemia who lack HLA-matched siblings. The major problems are seems to be viral infections and acute GvHD. Future challenges remain in improving post-transplant immune reconstitution and finding the best approach to reduce the incidence and severity of GvHD and infections, while preserving graft-versus-leukemia effect to prevent the recurrence of the underlying disease.