Allogeneic hematopoietic cell transplantation from alternative donors in children with myelodysplastic syndrome: is that an alternative?

Allogeneic hematopoietic cell transplantation (HCT) in children with myelodysplastic syndrome (MDS) remains a challenge due to the toxic conditioning regimens administered to minimize the risk of relapse in the HLA-matched or of graft rejection in the HLA-mismatched settings. In the absence of matched sibling donors, alternative donors such as unrelated and/or partially matched family sources remain risky, yet the only available, options. Herein we report the results of HCT from alternative donors in 14 children with different subtypes of MDS (juvenile myelomonocytic leukemia [JMML] n = 9; myelodysplastic syndrome [MDS] refractory anemia n = 3; MDS refractory anemia with excess of blasts in transformation n = 2) transplanted at our institution. The median time from diagnosis to HCT was 9 months (range 4 to 90 months). The variety of HCT types included: unrelated peripheral blood progenitor cell transplantation (PBPCT) (n = 2), partially matched family donor T-cell-repleted BMT/PBPCT (n = 6), and haploidentical T-cell-depleted PBPCT (n = 6). Five of 14 patients remain alive at 7 to 37 months posttransplant (including two patients after partially matched family donor BMT, two patients after haploidentical T-cell-depleted-PBPCT, and one after unrelated-PBPCT, respectively). The major complications were: primary graft failure in the haploidentical T-cell-depleted-setting or graft-versus-host disease (GvHD) in T-cell-repleted partially matched family or unrelated settings, respectively. Despite the high transplant-related mortality rate in this series, allogeneic HCT from alternative donors remains an interesting solution for children with MDS who lack matched sibling donors. Due to improved immune reconstitution, despite an increased risk of GvHD, T-cell-repleted transplants from single HLA-mismatched family donors remain a valuable option for children without matched donors. Splenectomy prior to HCT may positively affect the posttransplant course in patients with overt splenomegaly for example those afflicted with JMML.