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Objective: To describe our experience of post-transplant infections in allogeneic stem cell transplants at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan., Methods: From July 2001 to September 2006, patients with malignant and non-malignant hematological disorders having human leukocyte antigen (HLA)-matched sibling donors were selected for transplant. Pre-transplant infection surveillance was carried out, and strict prophylaxis against infection was observed. After admission to the hospital, patients were kept in protective isolation rooms, equipped with a HEPA filter positive-pressure laminar airflow ventilation system. Bone marrow and/or peripheral blood stem cells were used as the stem cell source. Cyclosporin and prednisolone were used as prophylaxis against graft-versus-host disease (GVHD). The engraftment was monitored with cytogenetic/molecular analysis and change of blood group. Survival was calculated from the date of transplant to death or last follow-up., Results: One hundred and fifty-four patients received allogeneic stem cell transplants from HLA-matched siblings for various hematological disorders at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan between July 2001 and September 2006. Indications for transplant included aplastic anemia (n=66), beta-thalassemia major (n=40), chronic myeloid leukemia (n=33), acute leukemia (n=8), and miscellaneous disorders (n=7). One hundred and twenty patients were male and 34 were female. The median age of the patient cohort was 14 years (range 1 1/4-54 years). One hundred and thirty-six patients and 135 donors were cytomegalovirus (CMV) IgG-positive. One hundred and forty patients (90.9%) developed febrile episodes in different phases of post-transplant recovery. Infective organisms were isolated in 150 microbiological culture specimens out of 651 specimens from different sites of infections (23.0% culture positivity). Post-transplant infections were confirmed in 120 patients (77.9%) on the basis of clinical assessment and microbiological, virological, and histopathological examination. Mortality related to infections was 13.0%. Fatal infections included CMV disease (100% mortality, 6/6), disseminated aspergillosis (66.7% mortality, 4/6), pseudomonas septicemia (42.9% mortality, 9/21), and tuberculosis (25% mortality, 1/4)., Conclusions: More than 90% of our patients developed febrile episodes with relatively low culture yield. The majority of infections were treated effectively, however CMV, aspergillosis, and pseudomonas infections remained problematic with high mortality.

Neurological complications are quite frequent in stem cell transplant (SCT) recipients. Major causes are conditioning regimen toxicity, metabolic and electrolyte disturbances, viral infections and cyclosporine related toxicity. Cyclosporine induced neurotoxicity is a well documented complication in stem cell transplant recipients. These patients usually present with seizures which are easily controlled with anti-convulsants and by reducing/withholding the drug. However uncontrolled seizures requiring ventilatory support are rarely reported. Here we present a case report of cyclosporine induced uncontrolled seizures in a young female after allogeneic SCT which was unresponsive to anti-convulsive therapy but was successfully treated with mechanical ventilatory support.

Mycobacterium tuberculosis is a serious, but rare infectious complication after allogeneic bone marrow transplantation. Tuberculosis is a major problem in South East Asia, particularly in India and Pakistan. We describe here infection due to mycobacterium tuberculosis in four patients after allogeneic stem cell transplantation (Allo SCT). The diagnosis was made on the bases of clinical findings, sputum / blood / pleural and pericardial fluids / broncho alveolar lavage (BAL) and tissue biopsy examination. Anti tuberculosis therapy (ATT) was started immediately after diagnosis. Three patients responded to antituberculosis therapy, where as one patient developed severe infective respiratory complications and died at six months post transplant. Mycobacterial infection should be considered in patients post allo SCT with unexplained fever, cough or pleuritic chest pain. These patients at diagnosis should be promptly treated with ATT.

Deep vein thrombosis (DVT) is a rare post transplant multifactorial disease and often results from a combination of risk factors causing venous stasis. Venography and doppler ultrasound are reliable and accurate procedures for detecting venous thrombosis. Once DVT has been established, these patients should be treated with anticoagulants at least for a limited duration particularly in high risk post transplant patients with previous episodes of thrombotic events. We report here a case of a 7 years old boy with B-thalassaemia major, who developed deep vein thrombosis at 04 month post SCT. He was treated with low molecular weight heparin and oral warfarin sodium and INR was stabilized between 2.5 - 3.0. Two months later, he presented with bleeding diathesis and died intracranial haemorrhage. Excessive unchecked anticoagulation was the cause of death. It is recommended that patients on anticoagulation therapy require strict monitoring with PT/INR to avoid bleeding complications related to unchecked over anticoagulation.

Hemophagocytic Lymphohistiocytosis (HLH) is a rare disorder of immune dysregulation characterized by fever, cytopenias, and splenomegaly. Its primary form poses a therapeutic challenge due to its high fatality when left untreated. We retrospectively analyzed 28 patients who underwent related-donor allogeneic stem cell transplant for primary HLH from 2010 to 2021. Among them were 10 cases of familial HLH, 8 cases of Griscelli syndrome type 2, and 1 case each with PRF1 and STX11 mutations. All the patients underwent transplants with reduced-intensity or myeloablative conditioning and 26 of them achieved neutrophil engraftment at a median of day + 14. The donors were either fully matched (68%) or haploidentical (32%). With a median follow-up of 1 year, overall survival was 68% (n = 19) and disease-free survival was 64.4% (n = 18). OS was better in patients transplanted with a sibling donor (compared to parent donor), who achieved complete donor chimerism, and those transplanted early in the course of the disease (diagnosis to transplant duration less than 6 months). [ABSTRACT FROM AUTHOR]

Objectives: Hepatic Veno occlusive disease (VOD), also known as sinusoidal obstruction syndrome (VOD/SOS), is a post-transplant life threatening complication. In this study, we aimed to discuss the incidence, management and outcome of VOD in post allogenic transplant patients of beta thalassemia major (BTM). Methods: A prospective study was conducted in Armed Forces Bone Marrow Transplant Center, between 2001-2022. A total of 385 fully Human Leucocyte Antigen (HLA) matched BTM patients, with Ursodeoxycholic acid for prophylaxis, were included in the study. Incidence of VOD was calculated through cumulative incidence estimates. Chi square test and Mann Whitney test were used to compare discrete and continuous variables respectively. VOD was diagnosed and graded according to European Society for Blood and Marrow Transplantation EBMT Pediatric diagnostic criteria. Risk factors for VOD were grouped as recipient, transplant and donor related. Univariate analysis was performed by log-rank test. All patients who developed VOD were managed primarily with fluid restriction and strict input output monitoring. Statistical analyses were performed using SPSS v 25.0. Results: Out of 385 transplant patients, forty developed VOD. Median time from date of transplant till onset of VOD was 14 days (range 6-30). Cumulative incidence of all grade VOD was 10.39% (95% CI, 7-14). Eleven out of 40 patients who developed VOD died. Cumulative incidence of Transplant related mortality (TRM) for patients with and VOD was 20.5% (95% CI, 16.6-25.1) vs 27.5% (95% CI, 16.1-42) (p value 0.318) respectively. Among risk factors, age of recipient and fibrosis (p value of 0.04 and 0.000 respectively) were found to be significantly associated with VOD. Conclusions: Careful selection of transplant candidates before transplant can help reduce the incidence of VOD. [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]

• High-risk aplastic anemia (AA) is associated with inferior overall survival (OS) and disease-free survival (DFS) when conventional cyclophosphamide-based conditioning is used. • Fludarabine-based conditioning is well tolerated, with lower rates of rejection and excellent long-term survival in these high-risk aplastic anemia patients. • High-risk factors identified in our study were prior hematopoietic stem cell transplant (HSCT), age ≥ 20 years, disease duration > 3 months, RBC transfusions > 20, and random platelet transfusions > 50. • Cyclosporine alone as GVHD prophylaxis and marrow source stem cells as graft source are preferable options. • A randomized trial of fludarabine-based versus conventional cyclophosphamide-containing conditioning would be helpful in establishing a standard of care conditioning regimen in high-risk AA patients. Despite excellent transplant outcomes of aplastic anemia (AA) in developed countries, management in developing countries is challenging because of delay in the diagnosis, use of family donors for transfusions, and higher infection risk pretransplant. These factors can lead to allo-immunization, increased risk of graft failure, graft-versus-host disease (GVHD), and transplant-related mortality, leading to unfavorable outcomes. Conventional cyclophosphamide (Cy) and antithymocyte globulin (ATG) are associated with inferior overall survival in such high-risk patients. We conducted single-center retrospective analysis of high-risk AA patients (N = 147) enrolled consecutively and undergoing matched related donor transplant from March 2002 through October 2018. We included high-risk AA patients receiving fludarabine (Flu)-based conditioning. Median patient age was 20 years (range, 3 to 52). The median time from diagnosis to transplant was 11 months (range, 3 to 63). High-risk features included age ≥ 20 years in 55.8% of patients (n = 82), disease duration more than 3 months in 95 % (n = 140), RBC concentrates transfusions > 20 in 79.6% (n = 117), random donor platelet transfusion > 50 in 64.6% of patients (n = 95), and second hematopoietic stem cell transplant (HSCT) in 7.4% (11). We divided patients into 2 groups based on different conditioning regimens. Flu group 1 (Flu1) received Flu 120 to 150 mg/m2, Cy 120 to 200 mg/kg, and ATG 20 mg/kg, and Flu group 2 (Flu2) was given Flu 150 mg/m2, Cy 300 mg/m2, and ATG 20 mg/kg. Bone marrow stem cells were used as graft source in 97% of patients (n = 144) (alone in 52% and with peripheral blood stem cells in 45%). Cyclosporine alone was used for GVHD prophylaxis in 75% (n = 110) and cyclosporine plus methotrexate in 25% (n = 37). Median total nucleated cell dose was 5 × 108/kg. Median days for neutrophil engraftment was 13 (range, 10 to 20) and platelet engraftment 20 (range, 14 to 43). Day 100 mortality was 7.5% (n = 11). Sustained successful engraftment was achieved in 87.8% of patients (n = 129). Most graft failures (40%) occurred in Flu2 conditioning (P =.000) and in patients with >2 risk factors (P =.000). Overall incidence of acute and chronic GVHD was 11.6% (n = 17) and 12.9% (n = 19), respectively, in Flu1 and Flu2 groups. Overall survival (OS), disease-free survival (DFS), and GVHD-free relapse-free survival (GRFS) was 83.7%, 78.2%, and 70.7%, respectively. A trend toward improved OS was observed in patients receiving Flu1 conditioning but was statistically nonsignificant (P =.256), whereas DFS and GRFS were significantly better in Flu1 versus Flu2 (P =.004 and.001, respectively). When stratified per number of risk factors (age > 20, RBC concentrate > 20 or platelet > 50 random, duration > 3 months, previous HSCT), OS and DFS decreased significantly with increasing number of risk factors (P =.000 and.001, respectively). Patients are able to tolerate Flu-based conditioning well with lower rates of rejection and excellent long-term survival in high-risk AA patients. Cyclosporine alone as GVHD prophylaxis and marrow source stem cells as graft source are preferable options. Use of Flu plus low-dose Cy conditioning is associated with inferior survival outcomes. A randomized trial of Flu-based versus conventional Cy-containing conditioning would be helpful in establishing a standard of care conditioning regimen in high-risk AA patients. [ABSTRACT FROM AUTHOR]

Treatment options for newly diagnosed aplastic anemia (AA) patient includes upfront allogeneic hematopoietic stem cell transplant (HSCT) or immunosuppressive therapy (IST). With recent advances in supportive care, conditioning regimens and post-transplant immunosuppression the overall survival for HSCT approaches 70–90%. Transplant eligibility needs to be assessed considering age, comorbidities, donor availability and probability of response to immunosuppressive therapy (IST). Upfront HSCT should be offered to children and young adults with matched related donor (MRD). Upfront HSCT may also be offered to children and young adults with rapidly available matched unrelated donor (MUD) who require urgent HSCT. Bone marrow (BM) graft source and cyclosporine (CsA) plus methotrexate (MTX) as graft versus host disease (GVHD) prophylaxis are preferable when using anti-thymocyte globulin (ATG) based conditioning regimens. Alemtuzumab is an acceptable alternative to ATG and is used with CsA alone and with either BM or peripheral blood stem cells (PBSC). Cyclophosphamide (CY) plus ATG conditioning is preferable for patients receiving MRD transplant, while Fludarabine (Flu) based conditioning is reserved for older adults, those with risk factors of graft failure and those receiving MUD HSCT. For haploidentical transplant, use of low dose radiotherapy and post-transplant cyclophosphamide has resulted in a marked reduction in graft failure and GVHD. • Transplant outcomes for aplastic anemia continues to improve with time, overall survival after MUD and Haploidentical transplant is now approaching MRD HSCT. • Bone marrow graft source and cyclosporine plus methotrexate GVHD prophylaxis are preferable. • Cyclophosphamide plus ATG conditioning is preferable for younger patients receiving MRD transplant, while Fludarabine based conditioning is reserved for older adults, with risk factors for graft failure and those receiving MUD HSCT. [ABSTRACT FROM AUTHOR]