Outcome e ricostituzione immunitaria post-trapianto nella popolazione giovane adulta e pediatrica affetta da leucemia acuta dopo trapianto di midollo osseo da donatore incompatibile sottoposto a ex vivo T-alfa/beta/CD19 deplezione

Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-haploidentical relative (haplo-HSCT) is a suitable option for children/young adults with acute leukemia (AL) either relapsed or at high-risk of treatment failure and in urgent need of an allograft. A novel method of graft manipulation based on the selective, negative depletion of αβ T and B cells has been recently developed. In the present study, enrolled and analyzed are 111 children with AL, with a median age of 10 years (range 0.9-22.2) transplanted between September 2011 and May 2018. Eighty-two (74%) and 29 (26%) patients had acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), respectively; all children were transplanted in complete morphological remission and received a fully myeloablative preparative regimen. The donor was mainly chosen according to immunological criteria, giving priority to NK-cell alloreactivity, KIR B haplotype, higher B-content score and size of NK alloreactive subset. They received Anti-Thymocyte Globulin (ATG) prior to HSCT to prevent GvHD and no patient was given any post-transplant pharmacological GvHD prophylaxis. With a median follow-up 47 months (range: 2 months – 7.7 years), the 5-year probability of overall survival was above 70% for both AML and ALL patients. The cumulative incidence of grade I-II acute GvHD was 25% (95% confidence interval, CI, 17-33), with skin GvHD being the most frequent organ involved, and no patient developed grade III/IV aGvHD. Four out of 91 patients at risk developed chronic GvHD, in all cases of limited severity, with a cumulative incidence of 5%. Six patients died for transplant-related complications, this resulting into a 5-year cumulative incidence of transplant-related mortality (TRM) of 6% (95% CI, 2-11) while the 5-year cumulative incidence of relapse was 24% (95% CI, 16-33) at a median time of 186 days (range 60-1012) after transplantation. The 5-year probability of LFS in children with ALL and AML was 69% (95% CI, 57-79) and 73% (95% CI, 52-86), respectively., and the use of total body irradiation (TBI) during the preparative regimen was associated with better patient’s outcome, since it protected against the risk of leukemia recurrence [18% (95% CI, 10-28) vs. 45% (95% CI, 22-66) in patients who did or did not receive TBI, respectively, p