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BACKGROUND: This study aimed to determine the association of single-nucleotide polymorphisms (SNPs) of interleukin-6 (IL-6) gene with the survival and disease status of patients after allogeneic hematopoietic stem cell transplantation. MATERIALS AND METHODS: It was a prospective cohort study of total 102 participants, 51 patients along with their donors who had human leukocyte antigen-identical-matched allogeneic hematopoietic stem cell transplantation (aHSCT). Their pretransplant and posttransplant blood samples were collected for extraction of DNA for genotyping by sequence-specific primers polymerase chain reaction and gel electrophoresis followed by sequencing. The pre- and posttransplant levels of IL-6 were measured using enzyme-linked immunosorbent assay technique. RESULTS: The mean age of our patients was 19.83 ± 12.5 years having males 65 (63.7%) and females 37 (36.3%). The frequency of −174G/C SNP among acute graft-versus-host disease (aGVHD) group was GG = 53.8%, GC = 34.6%, and CC = 11.5%, and for −597G/A SNP, it was GG = 69.2%, GA = 15.4%, and AA = 15.4%. Our results showed that the presence of G allele in both homozygous and heterozygous forms was associated with increased aGVHD incidence, while the homozygous CC and AA mutant genotypes correlated with the lowest number of cases of aGVHD. The polymorphism −597G/A was significantly associated with the incidence of aGVHD with P = 0.04. The GG genotype in −174G/C and −597G/A was found to be significantly associated with aGVHD with P < 0.0001. High serum levels of IL-6 pre- and posttransplant were found to be significantly associated with the incidence of aGVHD with P < 0.0001. CONCLUSION: We concluded that the two SNPs − 174G/C and − 597G/A in the promoter region of IL-6 gene present either in donors or recipients predisposed to increase the risk of development of aGVHD following aHSCT. Their evaluation in our transplant setting may help in the risk stratification of transplant recipients early in time and predict the onset of aGVHD and mortality. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic stem cell transplantation (HSCT) is therapeutic option for many blood diseases. It has increased risk of complications with incompatible pair. The objective of this study was to determine the frequency of complications in ABO-incompatible HSCT in Pakistan. Materials & Methods: This cross-sectional study was conducted at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from 11th August 2018 till 31st March 2021. A sample of 73 ABO-incompatible HSCT patients was selected. Variables were sex, age groups, acute & delayed hemolysis, pure red cell aplasia and acute GvHD. All variables being categorical were described by count and percentage with 80%CI. Complications in sample vs. population were compared through chi-square goodness of fit test. RESULTS: Seventy three patients with ABO-incompatible HSCT included 52 (71.23%) men & 21 (28.77%) women, and 49 (67.12%) in age group ≤14 years & 24 (32.88%) in ≥15 years. Out of 73 patients, eight (10.96%) had acute hemolysis, 26 (35.62%) had delayed hemolysis, four (5.84%) had pure red cell aplasia and 34 (46.58%) had acute GvHD. The observed prevalence in sample was similar to population for acute (p=.46893) and delayed hemolysis (p=.30759) and acute GvHD (p=.55841), while it was different for pure red cell aplasia (p=.00006). CONCLUSION: Most common complication in our study was acute GvHD, followed by delayed hemolysis, acute hemolysis & pure red cell aplasia. The observed prevalence in sample was similar to population for acute & delayed hemolysis and acute GvHD, while it was different for pure red cell aplasia. [ABSTRACT FROM AUTHOR]

Objective: To determine the treatment outcome of Hematopoietic stem cell transplantation in Fanconi Anemia. Study Design: Case series. Place and Duration of Study: Armed Forces Bone Marrow Transplant Center, Rawalpindi, from Jan 2001 to Jun 2018. Methodology: Data of all Fanconi anemia patients who had fully HLA matched bone marrow transplant during this period was analysed for variables affecting the outcome in terms of overall survival. Those fanconi anemia patients who had myelodysplastic changes or acute myeloid leukemia were excluded. Results: Total 27 patients underwent fully HLA matched allogeneic bone marrow transplant for Fanconi Anemia. Mean age of patients at transplant was 12.12 ± 5.16 years. All patients at transplant were in aplastic phase. Conditioning was done with fludarabine 120mg/m2, ATG 20 mg/kg and Cyclophosphamide at a dose of 20-40 mg/kg. Mean time to neutrophil engraftment was 12.3 ± 2.92days and for platelets 20 ± 10.3 days. Major posttransplant complications were neutropenic fever in 26 (96%), hypertension in 18 (66.6%), mucositis in 12 (44.4%), azotaemia in 8 (29.6%), gut toxicity in 7 (25.9%) and haemorrhagic cystitis in 5 (18.5%) patients. Four patients (14.8%) had acute graft versus host disease while 7 (26%) patients had chronic GVHD. Overall survival at 6 months, 1, 5 and 8 years was 67%, 63%, 59% and 55% respectively. While overall survival in patients transplanted at younger age (<11 years) was 81.8% compared to 37.5% in older age group (>11years) and was statistically significant (p-value = 0.03). Conclusion: Our study demonstrated survival difference in Fanconi anaemia patients when transplanted at younger age and conditioning with cyclophosphamide 30 mg/kg, fludarabine 120mg/m2 and thymoglobulin 10mg/kg as an acceptable conditioning protocol. [ABSTRACT FROM AUTHOR]

• Graft-versus-host disease (GVHD) often leads to post-transplant morbidity and mortality and can severely compromise quality of life. • Cyclosporine combined with short-course methotrexate is considered standard-of-care GVHD prophylaxis for patients with severe aplastic anemia who undergo transplantation using cyclophosphamide (Cy) plus anti-thymocyte globulin (ATG) conditioning. • Single-agent cyclosporine is a feasible option for GVHD prophylaxis in matched related donor hematopoietic stem cell transplantation using fludarabine-Cy-ATG conditioning and is associated with very low rates of acute and chronic GVHD. Cyclosporine (CsA) combined with short-course methotrexate is considered standard-of-care graft-versus-host disease (GVHD) prophylaxis for patients with severe aplastic anemia (AA) who undergo transplantation using cyclophosphamide (Cy) plus anti-thymocyte globulin (ATG) conditioning. However, there is no consensus on optimal post-transplant GVHD prophylaxis for patients undergoing matched related donor (MRD) transplantation using fludarabine (Flu)-based conditioning. We conducted a single-center retrospective analysis of patients with acquired AA (n = 106) undergoing MRD transplantation from July 2007 through January 2019. All patients received Flu-Cy-ATG conditioning and single-agent CsA as GVHD prophylaxis. Median age of the study cohort was 20 years (range, 3 to 52) and male to female ratio was 3.8:1. Median time from diagnosis to transplant was 11.5 months (range, 2.8 to 62). Graft source was bone marrow harvest in 71 (68%), combined bone marrow and peripheral blood stem cells in 34 (31%), and peripheral blood alone in 1 (1%) patient. Cumulative incidence of neutrophil engraftment at day 28 was 93.4% (95% confidence interval [CI], 87.3% to 97.1%) while that of platelet engraftment at day 100 was 90.5% (95% CI, 84% to 96%). Cumulative incidence of primary graft failure at day 28 was 6.6% (95% CI, 4% to 8%) while secondary graft failure occurred at a median of 190 days (range, 90 to 415) at a cumulative incidence of 3.7% (95% CI, 2% to 5%). Cumulative incidence of grade II to IV acute GVHD at day 100 was 3.8% (95% CI, 1.4% to 9.9%), while a 1-year probability of chronic GVHD was calculated as 7.5% (95% CI, 2.6% to 15%). Median follow-up post-transplant was 61 months (range, 6 to 144). Overall survival was 84.9%, disease-free survival was 80.2%, and GVHD-free relapse-free survival was 76.3%. This study indicates that single-agent cyclosporine is a feasible option for GVHD prophylaxis in MRD hematopoietic stem cell transplantation using Flu-Cy-ATG conditioning and is associated with very low rates of acute and chronic GVHD. [ABSTRACT FROM AUTHOR]

Use of haploidentical (haplo) donors for hematopoietic cell transplantation (HCT) has significantly increased in the last decade. The major advantage with this strategy is universal availability and faster acquisition of the donor, along with affordability and provision of immunotherapy in post-transplantation period. Historically, haplo-HCT was associated with compromised outcomes because of high rates of graft-versus-host disease and graft failure, but after the development of a post-transplantation high-dose cyclophosphamide strategy, which results in selective T-cell depletion, these issues have been addressed to a large extent. Nevertheless, graft failure, high treatment-related mortality due to graft-versus-host disease, infections, delayed immune reconstitution, and disease relapse remain significant concerns. As the experience with haplo-HCTs grows, the clinical outcomes are becoming more at par with those seen with fully matched unrelated donor allogeneic HCTs. [ABSTRACT FROM AUTHOR]