New Haploidentical HCT Approach Produces Similar Outcomes to HLA-Identical HCT in Children with Acute Leukemia

According to results published in Blood, young patients with acute leukemia who require an HCT but lack a suitable HLA-matched donor can safely receive HCT from an HLA-haploidentical donor, without raising the risks of GVHD or non-relapse mortality (NRM).

Researchers, led by Franco Locatelli, MD, from the Department of Pediatric Hematology and Oncology at Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Pediatrico Bambino Gesù in Rome, Italy, developed a new method of HLA-haploidentical, using graft manipulation to selectively deplete αβ T and B cells – which are largely responsible for the development of GVHD and post-transplant lymphoproliferative disease, respectively. Based on the results, this method “represents a competitive alternative for children with acute leukemia who are in need of urgent allograft.”

The researchers prospectively enrolled 80 children <21 years (median age = 9.7 years; range = 0.9-20.9 years) with acute lymphocytic leukemia (ALL; n=56; 70%) or acute myeloid leukemia (AML; n=24; 30%) who received a first allograft at their facility between September 2011 and September 2014.

All patients received a pre-transplant myeloablative conditioning regimen, and those older than age three with ALL or very high-risk AML (defined as those with cytogenetic/molecular features predicting high risk of relapse) also received total body irradiation (TBI). To prevent GVHD and graft rejection, the researchers administered anti-T lymphocyte globulin (12 mg/kg five to three days prior to HCT). Patients also received rituximab 200 mg/m2 one day prior to HCT.

Patients received the allograft from either their mother (n=46; 57%) or father (n=34; 43%).

Two patients did not engraft. Among those who did, the median time to neutrophil engraftment was 13 days (range = 9-19 days) and the median time to platelet engraftment was 11 days (range = 8-20 days).

No patients received post-HCT GVHD prophylaxis, and 30 percent of patients (n=24) experienced grade 1/2 skin-only acute GVHD. Four patients died because of HCT-related causes, including idiopathic pneumonitis (n=2), disseminated adenovirus infection after graft failure (n=1), and cardiac insufficiency (n=1); all the fatal events occurred within 100 days following HCT. One of the deceased patients had received TBI.

After a median follow-up of 46 months (range = 26-60 months), 19 patients (24%) relapsed after a median of 6.3 months (range = 2-22 months), with 15 relapses occurring during the first year after HCT. The five-year cumulative incidence of NRM was 5 percent (95% CI 2-13).

The five-year overall survival was 72 percent (95% CI 62-82), and the five-year leukemia-free survival was 71 percent (95% CI 61-81). Fifty-eight patients (72%) were alive at follow-up, 57 of whom were in continuous complete response; the remaining patient had relapsed disease.

When the researchers compared the results in this study population with a cohort of children with acute leukemia who received HCT from an HLA-identical sibling (n=41) or 10/10 allelic-matched unrelated donor (n=51) during the same time period, they found similar results between the haploidentical and HLA-matched cohorts.

Notably, patients receiving HLA-haploidentical HCT had a lower incidence of grade 3/4 acute GVHD (p<0.01), visceral GVHD (p<0.01), and chronic GVHD (p=0.03). However, this did not translate to a significant difference in GVHD-specific death.

“Haploidentical HCT offers the opportunity to transplant virtually every child in need of an allograft, with an expected outcome comparable to that obtained when the donor is an HLA-matched sibling or an allelic-matched volunteer,” the authors concluded.

The study is limited by its single-center design. Dr. Locatelli also noted that “this transplantation option cannot be offered to children who are either orphaned or adopted,” which slightly limits its applicability.

The authors reported no relevant conflicts of interest.

Source: Locatelli F, Merli P, Pagliara D, et al. Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion. Blood. 2017 June 6. [Epub ahead of print]