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Highlights • Haplo-HSCT achieved outcome comparable with MUD-HSCT in SAA young patients. • Haplo-HSCT had a high risk of grades II to IV aGVHD. Graphical Abstract The present study retrospectively analyzed the outcomes of 89 young patients with acquired severe aplastic anemia (SAA) who underwent unmanipulated alternative hematopoietic stem cell transplantation (HSCT) between September 2012 and September 2016 at our single center. Forty-one patients received haploidentical (haplo-) donors and 48 patients matched unrelated donors (MUDs) for HSCT. No significant differences were observed between haplo-HSCT and MUD HSCT cohorts in 3-year overall survival (P =.210), disease-free survival (P =.127), and graft-versus-host disease–free failure-free survival (P =.976). Haplo-HSCT, as salvage therapy, achieved similar outcomes as MUD HSCT in young SAA patients, thereby rendering it an effective and safe option for young SAA patients. Unlabelled image Abstract Salvage haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is considered in patients with severe aplastic anemia (SAA) if a matched unrelated donor (MUD) is unavailable. However, studies on haplo- and MUD transplantation in SAA are lacking. The present study retrospectively analyzed the outcomes of 89 young SAA patients who underwent unmanipulated alternative HSCT between September 2012 and September 2016 at our single center. Forty-one patients received haploidentical donors and forty-eight patients MUDs for HSCT. Most were heavily transfused and refractory to previous immunotherapy. The median durations for myeloid engraftment in the haplo- and MUD cohorts were 14 (range, 10 to 21) and 13 (range, 10 to 18) days, respectively. Compared with the MUD cohort, haplo-HSCT cohorts had an increased cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV (43.9% ± 7.8% versus 12.5% ± 4.8%, P =.001) and grades III to IV (21.1% ± 6.7% versus 6.6% ± 3.7%, P =.045) and similar limited chronic GVHD (47.7% ± 8.5% versus 38.5% ± 7.3%, P =.129) and extensive chronic GVHD (12.1% ± 6.8% versus 9.1% ± 4.3%, P =.198). The median follow-up time of the surviving patients was 26 months (range, 6 to 45). No significant differences were observed between haplo-HSCT and MUD HSCT cohorts in 3-year overall survival (80.3% ± 5.1% versus 89.6% ± 7.0%, P =.210), disease-free survival (76.4% ± 5.1% versus 89.4% ± 7.7%, P =.127), and GVHD-free failure-free survival (79.0% ± 8.6% versus 71.6% ± 9.3%, P =.976). Thus, haplo-HSCT, as salvage therapy, achieved similar outcomes as MUD HSCT in young SAA patients, thereby rendering it as an effective and safe option for SAA. [ABSTRACT FROM AUTHOR]

Background Transfusion support in haematopoietic stem cell transplantation (HSCT) can be very demanding and challenging. The conditioning regimen, stem cell dose, donor type, presence of GvHD, infection all influence transfusion therapy in haematopoietic stem cell transplantation (HSCT). We retrospectively analysed the first 100 days transfusion requirements among HSCT recipients with haematological as well as non-haematological malignancies in our centre. Materials and Methods Transfusion data were retrieved for 100 patients who had undergone HSCT over a period of two years. The HSCT recipients were divided into three groups: autologous, allogenic and haplo-identical. Allogenic group was subdivided into matched related donor (MRD) and matched unrelated donor (MUD). The allo and haplo groups were then classified on the basis of the ABO compatibility as major, minor, bi-directional and compatible. We analysed the mean requirement of blood components (RBC, RDP, SDP and FFP) within the first 100 days of HSCT in each category. Results and Discussion Haematologic malignancies constituted 97% of the indications for HSCT. Allo-HSCT constituted 50% of the HSCT, of which 92% were MRD. Auto and haplo-HSCT constituted 40% and 10% respectively. Mean requirement for all products – RBC, SDP, RDP and FFP – was highest in the haplo category, followed by the allo category and then the auto HSCT category. The mean product requirement in the MUD category was significantly higher than in the MRD category (p < 0.05). The mean product requirement in the major and bidirectional ABO incompatible group was significantly higher as compared to the minor and ABO compatible group (p < 0.05). Hence our data may help transfusion medicine specialists to understand the transfusion requirement in stem cell transplant settings from developing countries like India. The average number of blood donors required for each group of stem cell transplant patients can also be roughly predicted from this study. [ABSTRACT FROM AUTHOR]

While allogeneic hematopoietic stem cell transplantations have a curative potential, several patients with hematologic malignancies cannot avail themselves of this therapeutic option due to lack of matched donor availability. Although HLA-haploidentical transplantations were previously associated with poor outcomes, recent evidence with use of post transplantation cyclophosphamide indicate improved safety and efficacy. The following paper discusses the most recent developments in this area. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic cell transplantation (HCT) from a matched related donor (MRD) is the preferred therapy for many adults with acute leukemia. Yet most patients do not have matched siblings, and the numbers who do will continue to drop as the average number of children per couple in the United States continues to decline. Recent reports show little difference in the outcomes of matched related and matched unrelated transplants for acute leukemia. Additionally, survival rates at 3–5 years after transplant appear to be generally similar following matched related, matched unrelated, single antigen mismatched unrelated, double cord blood and, perhaps even after haplo-identical transplants. Nevertheless, there are differences between stem cell sources that should be considered in the choice of donor. The following review provides some perspective on the identification of the best stem cell sources for patients who do not have matches within their families. [ABSTRACT FROM AUTHOR]

Outcome differences by donor type for allogeneic hematopoietic stem cell transplantation vary based on disease and recipient age. The following paper summarizes analyses of transplant outcome among adults with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who received transplants from HLA-identical siblings, fully (8/8) matched unrelated donors (MUD), or mismatched (7/8) unrelated donors. The paper also reviews transplantation outcomes for children with leukemia who had genotypically matched sibling donors, mismatched (7/8) or phenotypically matched related donors or matched (8/8) unrelated donors. Morbidity is higher after unrelated donor vs HLA-matched sibling transplants due to higher rates of acute graft-vs-host disease (GVHD). However, survival is similar or within 10%–15% with all studies donor type, with disease-specific differences probably reflecting differences in underlying population risk for treatment-related mortality. [Copyright &y& Elsevier]

Excessive adverse events were encountered in a Phase I/II study of cyclophosphamide (CY) dose deescalation in a fludarabine-based conditioning regimen for bone marrow transplantation from unrelated donors in patients with severe aplastic anemia. All patients received fixed doses of antithymocyte globulin, fludarabine, and low-dose total body irradiation. The starting CY dose was 150 mg/kg, with deescalation to 100 mg/kg, 50 mg/kg, or 0 mg/kg. CY dose level 0 mg/kg was closed due to graft failure in 3 of 3 patients. CY dose level 150 mg/kg was closed due to excessive organ toxicity (n = 6) or viral pneumonia (n = 1), resulting in the death of 7 of 14 patients. CY dose levels 50 and 100 mg/kg remain open. Thus, CY at doses of 150 mg/kg in combination with total body irradiation (2 Gy), fludarabine (120 mg/m2), and antithymocyte globulin was associated with excessive organ toxicity. [ABSTRACT FROM AUTHOR]

Although bone marrow transplantation has resulted in life-saving T-cell reconstitution in infants with severe combined immunodeficiency (SCID), correction of B-cell function has been more problematic. This review examines B-cell reconstitution results presented in 19 reports from the United States and Europe on posttransplantation immune reconstitution in patients with SCID over the past 2 decades. The analysis considered whether pretransplantation conditioning regimens were used, the overall survival rate, the percentage with donor B-cell chimerism, the percentage with B-cell function, and the percentage of survivors requiring immunoglobulin replacement. The survival rates were higher at those centers that did not use pretransplantation conditioning or posttransplantation graft-versus-host disease prophylaxis. The percentage of survivors with B-cell chimerism, function, or both was higher and the percentage requiring immunoglobulin replacement was lower at those centers that used pretransplantation conditioning. However, there were substantial numbers of patients requiring immunoglobulin replacement at all centers. Thus pretransplantation conditioning does not guarantee that B-cell function will develop. Because most infants with SCID either present with serious infections or are given diagnoses as newborns, one must decide whether there is justification for using agents that compromise innate immunity and have intrinsic toxicities to gain B-cell immune reconstitution. [Copyright &y& Elsevier]

The large MRC/ECOG adult acute lymphoblastic leukemia (ALL) study establishes the value of sibling donor allogeneic transplant in standard-risk patients demonstrating superior outcome to conventional chemotherapy. The small but significant number of patients having matched unrelated donor (MUD) transplants on this study protocol appear to do well, and may establish the value of such an approach for those without a sibling. Reduced-intensity conditioning (RIC) conditioning might begin to address the transplant-related mortality problems of the older patients. The youngest adults may not need a transplant at all. If they are now treated on pediatric chemotherapy protocols, their outcome appears to improve significantly. The MRC/ECOG study, the emerging MUD and RIC data all help establish allogeneic transplant more widely in this disease. [Copyright &y& Elsevier]

Abstract: Despite the increasing use of peripheral blood progenitor cells (PBPC) instead of bone marrow (BM) for allogeneic hematopoietic stem cell transplantation (allo HSCT) from human leukocyte antigen (HLA)-matched unrelated donors in children, the relative benefits and risks of both stem cell sources in the pediatric setting remain largely unknown. Recently, the only larger study comparing the value of the 2 stem cell sources in a young patient group was confined to transplantation from HLA-identical sibling donors in older children and adolescents with acute leukemia. Based on the paucity of data in pediatric HLA-matched unrelated donor transplantation, we analyzed the outcome of 23 BM and 38 PBPC transplantations performed at our center. Neutrophil and platelet engraftment were achieved significantly faster in PBPC compared to BM recipients (18 versus 22 days and 26 versus 33 days; P < .001 and P = .03) whereas the risk for grade II-IV acute graft-versus-host disease (aGVHD) (62% versus 55%; P = .53) and chronic GVHD (cGVHD 65% versus 59%; P = .54) was comparable. As overall survival (OS; PBPC versus BM: 47.5% ± 8.6% versus 51.8% ± 10.5%; P = .88) and relapse-free survival (43.3% ± 8.3% versus 51.8% ± 10.5%; P = .60) are without detectable difference, PBPC and BM appear both as a valid stem cell source for HLA-matched unrelated donor transplantation in children with hematologic malignancies. [Copyright &y& Elsevier]