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Background: Aplastic anaemia is a rare bone marrow failure syndrome and is defined by pancytopenia associated with a hypo-cellular bone marrow with no increase in reticulin and in the absence of any abnormal infiltrate. The objective of the study was to determine the frequency of Aldehyde Dehydrogenase type 2 (ALDH2) deficiency in patients with Aplastic Anaemia and investigate its correlation with patient and disease characteristics. It was a descriptive cross-sectional study conducted at Armed Forces Bone Marrow Transplant Centre Rawalpindi from 01-08-2022-01-02-2023, over a period of 6 months. Methods: A total of 56 patients who were diagnosed with aplastic anaemia during this period, fulfilling inclusion criteria were enrolled. Patients were genotyped as GG (homozygous) and GA (heterozygous). GG had normal ALDH2, while GA were patients with ALDH2 deficiency. Data was collected on the patient's demographics, type and severity of anaemia, type of hematopoietic stem cell transplant (HSCT) and frequency of ALDH2 deficiency. Results were analyzed for ALDH2 deficiency and its correlation with patient and disease characteristics was investigated. Results: A total of 56 patients were included in the study. The median age of the patients was 28 years (20-39). According to the type of aplastic anaemia, 2 (3.6%) had Fanconi anaemia and 54 (96.4%) had acquired aplastic anaemia. In our study, 18 (32.1%) patients had undergone HSCT while the remaining 38 (67.9%) could not undergo HSCT. The frequency of the presence of ALDH2 deficiency was 2 (3.6%). There was no statistically significant correlation between the frequency of ALDH2 deficiency with variables like gender, age distribution, type of aplastic anaemia, the severity of aplastic anaemia and hematopoietic stem cell transplant. Conclusion: We concluded from our study the frequency of ALDH2 was rare in patients with aplastic anaemia. There was no statistically significant co-relation between the frequency of ALDH2 deficiency with variables like gender, age distribution, type of aplastic anaemia, the severity of aplastic anaemia and hematopoietic stem cell transplant. [ABSTRACT FROM AUTHOR]

Purpose: COVID-19 infection resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began to spread across the globe in early 2020. Patients with hematologic malignancies are supposed to have an increased risk of mortality from coronavirus disease of 2019 (COVID-19) infection. From Pakistan, we report the analysis of the outcome and interaction between patient demographics and tumor subtype and COVID-19 infection and hematological malignancy. Patients and methods: This multicenter, retrospective study included adult patients with a history of histologically proven hematological malignancies who were tested positive for COVID-19 via PCR presented at the oncology department of 5 tertiary care hospitals in Pakistan from February to August 2020. A patient with any known hematological malignancy who was positive for COVID-19 on RT-PCR, was included in the study. Chi-square test and Cox-regression hazard regression model was applied considering p ≤ 0.05 significant. Results: A total of 107 patients with hematological malignancies were diagnosed with COVID-19, out of which 82 (76.64%) were alive, and 25 (23.36%) were dead. The significant hematological malignancy was B-cell Lymphoma in dead 4 (16.00%) and alive group 21 (25.61%), respectively. The majority of the patients in both the dead and alive group were on active treatment for hematological malignancy while they came positive for COVID-19 [21 (84.00%) & 48 (58.54%) p 0.020]. All patients in the dead group were admitted to the hospital 25 (100.00%), and among these, 14 (56.00%) were admitted in ICU with a median 11 (6–16.5) number of days. Among those who had contact exposure, the hazard of survival or death in patients with hematological malignancies and COVID-19 positive was 2.18 (CI: 1.90–4.44) times and 3.10 (CI: 2.73–4.60) times in patients with travel history compared to no exposure history (p 0.001). Conclusion: Taken together, this data supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality resulting from COVID-19 infection. [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: Prevalence of aplastic anemia (AA) is high in the Asian population. This study was done to explore the etiology and association of AA with various socio-economic and environmental factors. Study design and setting: Study included 1324 consecutive AA cases registered at Armed Forces Bone Marrow Transplant Centre Rawalpindi, Pakistan, from March 2001 to August 2016. The study questionnaire was completed through an interview. It included patients' socio-demographic details, personal and family medical history, environmental attributes and clinico-hematological features. Results: The median age of patients was 20 years, 997 were male and 327 female. Distribution of non-severe, severe and very severe AA was 230 (17.4%); 598 (45.2%) and 496 (37.4%), respectively. The majority of patients were from low (n = 761, 57.5%) or middle socioeconomic class (n = 543, 41%). Consanguinity among patients (n = 806, 61%) was slightly higher than the national statistics. History of chemical exposures included fertilizers (n = 116, 8.7%), pesticides (n = 56, 4.2%) and industrial chemicals (n = 37, 2.8%). PNH clone was found in 63 of AA patients. After excluding 298 patients undergoing HSCT and 660 deaths/lost to follow-up, disease evolution was observed in 38(10.4%) patients out of 366 evaluable patients. These included PNH = 18, MDS = 11 and AML = 9. Discussion: Due to lack of funding and adequate human resource at the center, age and sex-matched controls could not be included. Other limitations were a lack of molecular testing to exclude the possibility of inherited bone marrow failure syndromes on a genetic basis. Conclusion: Younger age, male predominance and higher consanguinity point toward genetic factors in AA etiology among the South Asian population. [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]

Summary: 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), β-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 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. [Copyright &y& Elsevier]

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma encountered by hematopathologists and oncologists. Management guidelines for DLBCL are developed and published by countries with high income and do not cater for practical challenges faced in resource-constrained settings. This report by a multidisciplinary panel of experts from Pakistan is on behalf of three major national cancer societies: Society of Medical Oncology Pakistan, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology. The aim is to develop a practical and standardized guideline for managing DLBCL in Pakistan, keeping in view local challenges, which are similar across most of the low- and middle-income countries across the globe. Modified Delphi methodology was used to develop consensus guidelines. Guidelines questions were drafted, and meetings were convened by a steering committee to develop initial recommendations on the basis of local challenges and review of the literature. A consensus panel reviewed the initial draft recommendations and rated the guidelines on a five-point Likert scale; recommendations achieving more than 75% consensus were accepted. Resource grouping initially suggested by Breast Health Global Initiative was applied for resource stratification into basic, limited, and enhanced resource settings. The panel generated consensus ratings for 35 questions of interest and concluded that diagnosis and treatment recommendations in resource-constrained settings need to be based on available resources and management expertise., Competing Interests: Munira MoosajeeTravel, Accommodations, Expenses: Roche Kamran RashidHonoraria: Roche/GenentechSpeakers' Bureau: Roche/Genentech, Lilly MedicalTravel, Accommodations, Expenses: Roche Usman AhmadHonoraria: RocheTravel, Accommodations, Expenses: RocheNo other potential conflicts of interest were reported.

Management of rare hematological disorders pose unique diagnostic and therapeutic challenges due to unusual occurrence and limited treatment options. We retrospectively identified 45 patients receiving matched related donor transplant for rare hematological disorders from 2006 to 2019. Patients were divided into two groups (1) malignant and (2) non malignant. The malignant disorder group included four patients while the nonmalignant group included 41 patients divided into immune dysregulation (n = 23), bone marrow failure (n = 10), metabolic (n = 5), and bleeding diathesis (n = 3). Twenty-six (57.8%) patients received myeloablative conditioning (MAC) and 16 (35.6%) received reduced intensity conditioning (RIC), while 3 (6.6%) patients with severe combined immunodeficiency received stem cell infusion alone without conditioning. The cumulative incidence (CI) of grade II-IV acute GVHD (aGVHD) was 39.1% (n = 18) and chronic GVHD (cGVHD) 15.2% (n = 7). There was no primary graft failure while CI of secondary graft failure was 9%. Overall survival (OS) and disease-free survival (DFS) was 82.2% and 77.8% respectively. Group wise OS was 75% in the malignant group, 82.6% in the immune dysregulation group, 80% in patients with metabolic disorders and bone marrow failure, while 100% in patients with bleeding diathesis. This retrospective analysis shows that hematopoietic stem cell transplant can be a feasible treatment option for rare hematological disorders.

Objective: To analyze factors associated with survival, rejection and graft versus host disease in aplastic anaemia patients undergoing allogeneic haematopoietic stem cell transplantation (SCT) from HLA matched sibling donors., Study Design: Analytical study., Place and Duration of Study: Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from July 2001 to June 2010., Methodology: Consecutive aplastic anaemia (AA) patients undergoing haematopoietic stem cell transplantation from HLA-matched sibling donors at this centre were included in this study. Potential factors affecting overall survival, rejection, disease-free survival and graft versus host disease were analyzed. Survival analysis was done by Kaplan-Meier method. Cox regression model was applied for multivariate analysis., Results: Ninety male and thirty-five female patients with AA were included in the study. Median age was 18 years. Conditioning regimens used were cyclophosphamide (Cy) plus antilymphocyte globulin (ALG) or antithymocyte globulin (ATG), fludarabine (FLU) +Cy+ATG, Campath 1-H +Cy in 89, 30 and 6 cases respectively. GVHD prophylaxis used was ciclosporin (CSA) plus prednisolone and short methotrexate in 81 while 44 received CSA plus prednisolone. At a median follow-up of 1185 days OS and DFS were 84% and 78% respectively. Factors associated with better OS were male sex, Flu/Cy/ATG conditioning and use of bone marrow as stem cell source., Conclusion: Flu/Cy/ATG conditioning regimen, bone marrow as stem cell source and CSA, prednisolone and short methotrexate regimen were associated with better survival in AA.

Objective: To evaluate the outcome in denovo AML patients treated with different remission induction and consolidation chemotherapy regimens in our population., Methods: A retrospective study on acute myeloid leukaemia (AML) patients was carried out at Armed Forces Bone Marrow Transplant Centre Rawalpindi Pakistan between July 2001 and June 2006. During 5 years period 46 patients received treatment for AML at our centre. Twenty nine patients were males and 17 were females. Median age of patients was 21 years (range: 7-56 years). These 46 patients were categorized into two groups on the basis of type of leukaemia and chemotherapy given. In group-I 40 patients (group Ia: 23 patients of M1-M6, less M3 group Ib: 17 patients of AML M3) received anthracycline and cytarabin based chemotherapy. In group-II, six patients (AML- M3) received all trans retinoic acid (ATRA) based chemotherapy., Results: In group Ia, out of 23 patients, 14 patients (60.8%) achieved complete remission (CR) after remission induction chemotherapy, 10 patients remained in CR after 3rd and 4th consolidation. Eleven patients died and five patients relapsed during treatment and follow up. In this group overall CR, relapse rate (RR) and mortality was 30.4% (7/23), 21.7% (5/23) & 48% (11/23) respectively. In group Ib out of 17 patients, 9 patients (53%) achieved CR after remission induction. Eleven patients died during treatment while one patient relapsed in this group. Overall CR, RR & mortality was 29.4% (5/17), 6% (1/17) & 55% (11/17) respectively. In group II all patients achieved CR (100%) after 1st course of chemotherapy. Two of these patients unfortunately died of uncontrolled sepsis during 1st consolidation, while remaining 4 patients 66.6% are on maintenance chemotherapy and are still in CR., Conclusion: Overall CR, RR and mortality in all groups was 35% (16/46), 13% (6/46) and 52% (24/46) respectively at a median follow-up of 36 + 8 months. Survival in AML-M3 patients treated with ATRA based chemotherapy is significantly superior than anthracycline based chemotherapy (66.6% vs. 29.4%). Infection and chemotherapy toxicity being major causes of mortality.