Haploidentical transplantation with post‐transplant cyclophosphamide versus single cord blood transplantation for myelodysplastic syndrome: A retrospective study from the Adult Myelodysplastic Syndrome Working Group of the Japanese Society for Transplantation and Cellular Therapy (JSTCT)

Abstract

Myelodysplastic syndrome (MDS) is a heterogenous group of hematological disorders characterized by dysplastic morphology, peripheral blood cytopenia, and the risk of progression to acute myeloid leukemia (AML). Several therapeutic approaches have been attempted for MDS, including erythroid stimulating agents, immunosuppression, low-dose or intensive chemotherapy, hypomethylating agents, and allogeneic hematopoietic cell transplantation (HCT). Although allogeneic HCT is the only potential curative treatment option for MDS, donor searches are less likely to identify a matched sibling donor (MSD) in patients with MDS, because MDS is predominantly a disease of the elderly, and sibling donors are also likely to be an elderly person.Alternative HLA mismatched donors, such as a haploidentical related donor 1,2 or unrelated cord blood (CB), 2-4 could also be considered for MDS patients who lack an HLA-matched related or unrelated donor. Although haploidentical HCT has historically been limited by significant graft-versus-host disease (GVHD) and graft failure, these problems have been overcome by the use of post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis, resulting in a drastic expansion of PTCy-haplo HCT in recent years. 5 Among MDS patients, PTCy as GVHD prophylaxis has improved transplant outcomes. 1 The main limitations of CBT for adults have been the higher incidence of graft failure and early non-relapse mortality (NRM). However, our recent studies showed that neutrophil engraftment and NRM have significantly improved after CBT in adults. 6 Several studies demonstrated comparable or better survival for haplo-HCT than CBT in adult patients with heterogenous hematological malignancies. 7-10 However, comparative data for PTCy-haplo HCT and CBT have been limited solely to adult patients with MDS. 2 Therefore, we retrospectively compared the outcomes of PTCy-haplo HCT versus single-unit CBT in adult patients with MDS using the Japanese database.Included in this study were patients aged 16 years or older with MDS who underwent haploidentical related HCT or single-unit unrelated CBT as the first allogeneic HCT between 2014 and 2020 in Japan. Details for other methods are provided in the supplemental methods.

Single‐unit unrelated cord blood transplantation versus HLA‐matched sibling transplantation in adults with advanced myelodysplastic syndrome: A registry‐based study from the adult MDS working group of the Japanese society for transplantation and cellular therapy

“…11,[44][45][46] Our previous study demonstrated comparable survival rates between haploidentical-related donor transplants and CBT in adult patients with MDS. 11 Donor selection might therefore be dependent not only on donor availability, patient and disease circumstances but also on physician and center preference. Third, our findings should be interpreted cautiously when extended to other racial cohorts, because CBT in Japan has several distinctive traits, including the use of single-unit UCB for adults, more flexible selection criteria for UCB units, and a broader indication for advanced disease.…”

“…Thus, selection bias and the center effect could have affected the results of our study. Second, the use of post‐transplant cyclophosphamide as GVHD prophylaxis has led to a significant increase in haploidentical‐related donor transplants for various hematological diseases, including MDS 11,44–46 . Our previous study demonstrated comparable survival rates between haploidentical‐related donor transplants and CBT in adult patients with MDS 11 .…”

“…Second, the use of post‐transplant cyclophosphamide as GVHD prophylaxis has led to a significant increase in haploidentical‐related donor transplants for various hematological diseases, including MDS 11,44–46 . Our previous study demonstrated comparable survival rates between haploidentical‐related donor transplants and CBT in adult patients with MDS 11 . Donor selection might therefore be dependent not only on donor availability, patient and disease circumstances but also on physician and center preference.…”

“…Unrelated cord blood (UCB) is an alternative donor option for adult patients with MDS who require prompt allogeneic HCT without an MSD or matched unrelated donor (MUD). [3][4][5][6][7][8][9][10][11][12] The advancement of UCB transplantation (CBT) procedures has contributed to the recent improvement in engraftment and early mortality, 13 which were the main limitations of CBT in adults. These improvements have resulted in a drastic expansion of CBT for MDS in recent years.…”

Progress in survival following three decades of allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: A real‐world registry study in Japan

“…The marked increase in the number of UBMT and UCBT in our MSDs. 14 Furthermore, rapid availability is the most important benefit for alternative HLA mismatched donors, such as unrelated cord blood or a haploidentical related donor, 15,16 for MDS patients, because some patients needed an urgent allogeneic HCT (Figure S3B). This ease of donor availability could extend access to allogeneic HCT for MDS because the identification of an MSD can be limited for patients with MDS, particularly in the elderly.…”