Allogeneic Hematopoietic Cell Transplantation Is an Effective Treatment for Blastic Plasmacytoid Dendritic Cell Neoplasm in First Complete Remission: Systematic Review and Meta-analysis

Introduction

It is common practice to refer patients to transplantation centers for allogeneic hematopoietic cell transplantation (allo-HCT) for blastic plasmacytoid dendritic-cell neoplasm (BPDCN) despite lack of randomized controlled trials. We performed a systematic review to assess the totality of evidence pertaining to the efficacy of allo-HCT in BPDCN.

Integrating Genomics in Myelodysplastic Syndrome to Predict Outcomes After Allogeneic Hematopoietic Cell Transplantation

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic neoplastic disorders most commonly occurring in the elderly population; MDS has a tendency to progress to acute leukemia. Although epigenetic therapies have improved the outcomes of MDS patients, allogeneic hematopoietic cell transplantation remains the only curative option. Molecular characterization of MDS using next-generation sequencing has expanded not only the knowledge on MDS but also the depth of understanding of evolution and contribution of recurrent somatic mutations in precursor conditions. Rapidly evolving genomic information on MDS may provide clinicians with better risk stratification tools and may also aid in supplying useful information to allow comprehensive therapeutic decision making for MDS patients. In this concise review, we summarize the current knowledge and understanding of recurrent somatic mutations in MDS and discuss salient genomic information predicting response and influencing therapeutic outcomes in the context of allogeneic hematopoietic cell transplantation, as well as the potential application of these findings into future clinical practice.     

Allogeneic Hematopoietic Cell Transplantation for Richter Syndrome: A Single-Center Experience

Background

Recent studies have shown dismal outcomes when chronic lymphocytic leukemia progresses to Richter syndrome after patients receive ibrutinib, with a median overall survival ranging from 2.6 to 3.5 months. Published data on efficacy of allogeneic hematopoietic cell transplantation in Richter syndrome are limited to single-center case series and registry data.

Donor Age and Non-Relapse Mortality: Study of Their Association after HLA-Matched Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome

The purpose of this retrospective study was to study the correlation between donor age (DA) and non-relapse mortality (NRM) and relapse incidence (RI) among patients treated with allogeneic hematopoietic cell transplantation (aHCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in a single Canadian center. Data from 125 consecutive patients transplanted with a matched related or unrelated donor between 2015 and 2020 were analyzed using multivariable models. After a median follow-up of 2.8 years, the cumulative incidences of NRM and relapse were 19% and 35% at 5 years. Despite being independently associated with NRM and relapse-free survival (RFS), DA was not associated with RI. The independent determinants of NRM in addition to DA were patient age and hematopoietic cell transplantation comorbidity index (HCT-CI), independently of donor kinship. The effect of DA on NRM was found to be significantly increased over the age of 50 years. DA was not associated with incidence of acute graft-versus-host disease (aGVHD) but showed an association with the occurrence of chronic GVHD (cGVHD). In conclusion, younger donors should be favored to limit NRM and increase RFS in HLA-matched aHCT. The etiological mechanisms behind the association of DA with higher NRM remain to be elucidated.     

On Behalf of the SFGM-TC: Retrospective Comparison of Reduced and Higher Intensity Conditioning for High-Risk Myelodysplastic Syndrome Treated With Allogeneic Stem-Cell Transplantation

BackgroundAllogeneic hematopoietic stem-cell transplantation (allo-HSCT) remains the best curative option for high-risk myelodysplastic syndrome . We retrospectively compared patient outcomes after allo-HSCT according to the intensity of the conditioning regimen.Patients and MethodsThree conditioning regimens were compared in 427 patients allografted for high-risk myelodysplastic syndrome: reduced-intensity conditioning (RIC), fludarabine (150-160 mg/m²) and busulfan (6.4 mg/kg); sequential FLAMSA-RIC, fludarabine, amsacrine, and aracytine followed by RIC; and myeloablative with reduced toxicity (RTC), fludarabine and busulfan (9.6 mg/kg or 12.8 mg/kg).ResultsThe patients in the 3 conditioning groups were different in regards to the number of treatment lines (P< .001), percentage of blasts in bone marrow (P< .001), and disease status at transplantation (P< .001). No significant differences in outcomes (overall survival, progression-free survival, nonrelapse mortality, relapse incidence, and graft versus host disease relapse-free survival) were observed between the 3 groups. Using propensity score analysis to overcome baseline imbalances, we compared 70 patients receiving FLAMSA-RIC to 260 patients receiving RIC, and compared 83 patients receiving RTC to 252 patients receiving RIC. The only factor influencing overall and progression-free survival was cytogenetic risk at transplantation. After the covariate adjustment using propensity score to reduce baseline imbalances, the only factor influencing overall and progression-free survival was still cytogenetic risk at transplantation.ConclusionOverall survival appears to be similar with the 3 conditioning regimens. The only factor influencing survival is cytogenetic risk at transplantation, suggesting that new promising drugs in the conditioning and/or early interventions after transplantation are needed to improve outcomes in these patients.