Continuous and differential improvement in worldwide access to hematopoietic cell transplantation: activity has doubled in a decade with a notable increase in unrelated and non-identical related donors.

Promoting access to and excellence in hematopoietic cell transplantation (HCT) by collecting and disseminating data on global HCT activities is one of the principal activities of the Worldwide Network for Blood and Marrow Transplantation, a non-Governmental organization in working relations with the World Health Organization. HCT activities are recorded annually by member societies, national registries and individual centers including indication, donor type (allogeneic/autologous), donor match and stem cell source (bone marrow/peripheral blood stem cells/cord blood). In 2018, 1,768 HCT teams in 89 countries (six WHO regions) reported 93,105 (48,680 autologous and 44,425 allogeneic) HCT. Major indications were plasma cell disorders and lymphoma for autologous, and acute leukemias and MDS/MPN for allogeneic HCT. HCT number increased from 48,709 in 2007. Notable increases were seen for autoimmune diseases in autologous and hemoglobinopathies in allogeneic HCT. The number of allogeneic HCT more than doubled with significant changes in donor match. While HCT from HLA identical siblings has seen only limited growth, HCT from non-identical related donors showed significant increase worldwide. Strongest correlation between economic growth indicator of gross national income/capita and HCT activity/ten million population was observed for autologous HCT (r=0.79). HCT from unrelated donors showed strong correlation (r=0.68), but only moderate correlation (r=0.51) was detected from related donors. The use of HCT doubled in about a decade worldwide at different speed and with significant changes regarding donor match as a sign of improved access to HCT worldwide. Although narrowing, significant gaps remain between developing and non-developing countries.

Post-transplantation Cyclophosphamide-based Graft-versus-host-disease Prophylaxis Compared to Methotrexate-cyclosporine a in Matched-related Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND AND OBJECTIVES: Post-transplant cyclophosphamide (PTCy) has shown promising results with low rates of severe graft-versus-host-disease (GVHD), either alone or combined with conventional immunosuppression (CIS). However, studies comparing PTCy with CIS as a GVHD prophylaxis are scarce. The study aimed to determine the rates of GVHD and survival outcomes for patients undergoing peripheral blood stem cell transplant (PBSCT) from HLA-matched related donors (MRD) receiving PTCy-based GVHD prophylaxis and compare these outcomes with those of patients receiving methotrexate (MTX) and cyclosporine-A (CsA) as a GVHD prophylaxis. PATIENTS AND METHODS: Seventy-five patients with advanced hematologic malignancies who underwent MRD allogeneic hematopoietic cell transplantation (allo-HCT) were analyzed prospectively. These patients received PTCy and CSA as a GVHD prophylaxis (therapeutic group) and their outcomes were compared with those of 75 retrospectively collected patients who received methotrexate and CsA as a GVHD prophylaxis (historical group) from the same two transplant centers. RESULTS: The median recipient age was significantly lower in the MTX/CsA group at 28 years compared to 34 years in the PTCy/CSA group. Peripheral blood was the only graft source used. All patients had a complete MRD, with two patients having a one-antigen mismatched related donor within the PTCy/CsA group. The 1-year cumulative incidence (CI) of chronic GVHD was 13.4% with PTCy/CsA and 38.6% with MTX/CsA (P = .001). Acute GVHD CI across all grades did not differ between the groups, with 10.7% for PTCy/CsA and 14.7% for MTX/CsA (P = .46). At two years, the overall survival (OS) (54.4% vs 67.2%, P = 0.282), disease-free survival (DFS) (54.1% vs 66.1%, P = 0.358), relapse rates (27.4% vs 20.1%, P = 0.245), and non-relapse mortality (NRM) (29.3% vs 25%, P = 0.904) did not differ between PTCy/CsA and MTX/CsA, respectively. CONCLUSION: PTCy-based GVHD prophylaxis in MRD transplant is feasible and leads to lower chronic GVHD rates without causing a significantly different risk of relapse or survival than MTX/CsA. More extensive studies are needed to confirm our results.

Allogeneic hematopoietic stem cell transplantation for non-malignant hematological disorders.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a geno-identical matched sibling (MSD) is one of the most successful therapies in patients with non-malignant hematological disorders. This study included 273 patients with severe aplastic anemia (SAA), 152 patients with B-Thalassemia major (BTM), 31 patients with Fanconi's anemia (FA), 20 patients with congenital immunodeficiency diseases (ID), and 13 patients with inherited metabolic disorders (IMD) allografted from a MSD. In SAA, the 8-year overall survival (OS) of the whole group patients was 74%. OS was significantly better in patients conditioned with fludarabine and cyclophosphamide (Flu/Cy) than in those who received cyclophosphamide and antithymocyte globulin (Cy/ATG) (p = 0.021). Acute graft-versus-host disease (aGVHD) grade II-IV occurred in 15% while chronic GVHD (cGVHD) occurred in 28%. In BTM, the 12-year disease-free survival (DFS) of the whole group of BTM patients was 72.4%. DFS was 74% for peripheral blood stem cell (PBSC) group compared to 64% in the BM stem cell group. The incidence of graft rejection was significantly lower in patients who received PBSC than in those who received BM (9% vs 25%) (p = 0.036). AGVHD grade II-IV and cGVHD occurred in 15% and 12% of the whole group of BTM patients respectively. In FA, the 5-year OS was 64.5%. Graft rejection occurred in 10% of patients. Grade II-IV aGVHD occurred in 16% while cGVHD occurred in 4%. In ID, the 5-year OS was 62%. Graft rejection occurred in two (10%) patients. Three patients (15%) developed grade II-IV aGVHD, 2 of them progressed to secondary cGVHD. In IMD, OS was 46% at 5 years. Graft rejection occurred in 8% of patients. AGVHD grade II-IV occurred in 15% while cGVHD occurred in 14%. In conclusion, Allo-HSCT provides a higher DFS rate over conventional therapies for patients with non-malignant hematological disorders with prolonged survival.