Haploidentical transplantation in children with unmanipulated peripheral blood stem cell graft: The need to look beyond post‐transplantation cyclophosphamide in younger children

Abstract

Haploidentical transplantation with PTCY following marrow or PBSC graft has been associated with low incidence of GVHD in adults with similar data lacking in children. We report on the outcome of 25 patients <20 yr of age (median age 12 yr), undergoing a haploidentical PBSC transplantation for both malignant and non-malignant disorders. Engraftment was prompt and sustained. Cumulative incidences of acute GVHD and chronic GVHD were 40.3% and 16.7%, respectively. On subgroup analysis, it was evident that acute GVHD developed in 80% of patients <10 yr compared to only 13.3% in those between 10 and 20 yr [log-rank p = 0.001], despite similar graft composition with significantly higher NRM (60% vs. 0%; p = 0.001). The FFS was 63.5%; (79% in >10 yr and 40% in <10 yr, p = 0.01). Our data suggest that PTCY-based haploidentical PBSC transplantation is feasible in older children, but results in early and severe alloreactivity in younger children. These findings, despite being counterintuitive, could be explained by the variable metabolism of CY and oral mycophenolate in younger children indicating that PTCY-based approach as used in adults might not be adequate for younger children.

Higher CD45RA+ Regulatory T Cells in the Graft Improves Outcome in Younger Patients Undergoing T Cell–Replete Haploidentical Transplantation: Where Donor Age Matters

“…Finally, we had modified the original PTCy protocol to incorporate CTLA4Ig in sequential doses for younger patients to reduce the incidence of EA as reported in our earlier studies [2,3]. We had demonstrated in a pilot study in children with SAA that the incidence of both GVHD and PTHPS was markedly reduced when CTLA4Ig was combined with PTCy and sirolimus, compared with the cohort of SAA who received PTCy with cyclosporine A and mycophenolate mofetil [16].…”

“…Based on the encouraging results witnessed in adults, we had extended PTCy-based haploidentical HSCT to the pediatric age group. We had reported a high incidence of both acute graft-versus host disease (GVHD) [2] and post-transplantation hemophagocytic syndrome (PTHPS) without an infectious trigger [3], occurring within 35 days of HSCT in younger children undergoing PTCybased haploidentical bone marrow transplantation. Both were associated with very high mortality.…”

“…Both were associated with very high mortality. We postulated that this might be due to age-dependent differences in metabolism of Cy and mycophenolate mofetil [2].…”

Acute GvHD prophylaxis with posttransplant cyclophosphamide after hematopoietic stem cell transplantation (HSCT) for non-malignant disorders

“…Allo-HSCT from a nonrelated donor or partially compatible haploidentical donor exhibit comparable survival parameters for the patients with non-malignant disorders. Under these conditions, the PtCy-based GHD prophylaxis provides good control of evolving aGVHD [8]. A higher risk of non-engraftment in cases of haploidentical donorship could be decreased due to myeloablative conditioning regimens.…”

“…PtCy prophylaxis was applied in all these cases showing its clinical efficiency. This approach has additional benefits when applying peripheral blood stem cells as a source of transplant [8,12].…”