Comparison of Steady-State Bone Marrow and GCSF-Primed Stem Cell Sources Used in Allogeneic Hematopoietic Stem Cell Transplantation.

OBJECTIVE: To compare donor graft characteristics and clinical outcomes in recipients of allogeneic heamatopoietic stem cell transplantation (HSCT) using GCSF primed bone marrow (GBM) and steady-state bone marrow (SBM) as stem cell sources. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Clinical Haematology, Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, from August 2018 to October 2020. METHODOLOGY: Eighty patients undergoing allogeneic HSCT were analysed. Among these, forty each received GBM and SBM from HLA identical siblings. Graft characteristics, such as total nucleated cells, CD34+ cell yield; clinical outcomes such as neutrophil and platelet engraftment, primary and secondary graft failure (GF), as well as the frequency of acute and chronic graft versus host disease (GvHD), were recorded and compared using the t-test, with significance at p <0.05. RESULTS: A statistically significant difference was observed in CD34+ dose with median dose 7.68 (p=0.002) but not in TNC dose with meadin dose 5 (p=0.86). Neutrophil engraftment occurred much more quickly with median of 13.43 days in the GBM than SBM group (p=0.025). While no statistically significant difference (p=0.89) in platelet engraftment was reported in both SBM and GBM. At the same time, patients with both GBM and SBM transplants showed a comparable ratio of acute to chronic GvHD and primary to secondary GF. CONCLUSION: GBM is associated with better CD34+ stem cell yield and quicker neutrophil engraftment in clinical outcomes. KEY WORDS: Granulocyte colony-stimulating factor, Bone marrow, Hematopoietic stem cell transplantation.

Haematopoietic Stem Cell Transplantation (HSCT) for Primary Immune System Disorders in Children: A Single Centre Experience.

OBJECTIVE: To determine the outcomes of allogeneic HSCT in children with primary immune system disorders (PID). STUDY DESIGN: Descriptive Cross-sectional study. Place and Duration of the Study: Armed Forces bone marrow transplant centre / National Institute of Bone Marrow Transplant (AFBMTC / NIBMT), Rawalpindi, Pakistan, from October 2012 to December 2021. METHODOLOGY: Data of all cases undergoing HSCT for immune system disorders were analysed for variables affecting outcome and overall survival in the first 180 days after allogeneic HSCT. All patients presenting to AFBMTC / NIBMT with PID, age <12 years. Patients with organ dysfunction secondary to repeated infections were excluded from the study. Data of all patients and their donors undergoing HSCT for immune system disorders were analysed for variables affecting outcome and overall survival in the first 180 days after allogeneic bone marrow transplant. Neutrophil engraftment was defined as absolute neutrophil count ≥0.5 × 109/L for 3 consecutive days, while platelet engraftment as platelet count ≥20 × 109/L without platelet transfusion for one week. Overall survival (OS) was taken as time from the date of HSCT till day + 180 post-transplant. RESULTS: A total of 42children including 29 boys and 13 girls underwent HSCT for PID. The mean age was 2.1±2.8 years. Underlying diagnosis was haemophagocytic lymphohistiocytosis (HLH), severe immune deficiency (SCID), leukocyte adhesion defect (LAD), X-linked agammaglobulinemia, chronic granulomatous disease (CGD) and Job's syndrome in 18 (42.9%), 16 (38.1%), 3(7.1%), 2 (4.8%), 2 (4.8%) and 1 (2.4%) patients respectively. Thirty-one (73.8%) children had fully HLA-matched donors while 11 (26.2%) had haplo-matched donors. Major immediate post-transplant complications were febrile neutropenia, mucositis and SOS/VOD in 31 (73.8%), 9 (21.4%) and 4 (10.0%) cases, respectively. Eight (19.0%) had CMV reactivation, acute GVHD was seen in 17 (40.4%) cases, while 1 (2.3%) case had chronic GVHD. Twelve (28.6%) patients died, out of which 5 had graft failure, 3 had VOD, 2 had pneumonia, 1 had severe GVHD, and 1 died due to seizures. Overall survival (OS) in this study was 71.4% with survival reaching up to 80.6% in fully matched HSCT. CONCLUSION: HLH and SCID were the commonest immune disorders requiring HSCT. Graft failure leading to neutropenic sepsis was the commonest cause of mortality. OS was better in fully matched HSCT as compared to haplo-identical HSCT. KEY WORDS: Immune deficiency, Severe combined immunodeficiency, Haematopoietic stem cell transplantation.

Treatment Outcomes Of Patients With Hairy Cell Leukaemia; A 16-Year Experience At A Tertiary Care Center In Pakistan.

BACKGROUND: Hairy cell leukaemia (HCL) is an uncommon neoplasm of mature B-lymphoid cells which is characterized by cytopenias, commonly of all three cell lines, with typical hairy cells on peripheral smear and/or bone marrow along with organomegaly. Objective was to document the outcomes of HCL patients treated at a tertiary care hospital in Pakistan. METHODS: Medical records of patients from 2004 to 2020 were reviewed and data was collected to assess patient's demographics, symptomatology, remission rate and overall survival. The record flies of all patients presenting to AFBMTC with HCL were included in the study. The record file with insufficient data were excluded. RESULTS: 26 patients with a mean age of 48.12±11.43 years were diagnosed with HCL and treated at AFBMTC. Out of these, 23 (88.4%) were male and 03 (11.5%) females. The main presenting complaints were generalized body aches (34.6%), fever (15.4%), incidental finding of cytopenias (11.5%) and abdominal discomfort (26.9%). Splenomegaly was found in 76.92% while hepatomegaly was found in 46.15% of patients. A total of 12 (46.15%) patients received Cladribine (either intravenous or subcutaneous) and splenectomy was done in 7 (26.92%) as 1st line treatment. Eleven patients out of 12 (83.33%) who received Cladribine and 05 (71.42%) patients out of seven who underwent splenectomy; achieved complete remission (CR) after 1 st line of treatment. One patient received Cladribine as 1st line of treatment but did not respond and CHOP regimen was given as second line. Out of the 26 patients, 5 patients (19.23%) relapsed at a median interval of 5.83±6.6 years. Two patients received Cladribine + Rituximab while 03 patients received cladribine as their salvage therapy. Disease free survival (DFS) of 71.4% among the patients underwent splenectomy while 75.0% among the patients received Cladribine. DFS for combination therapy (included CHOP and CVP) was 66.7% while OS was calculated among patients who received cladribine, splenectomy and combination chemotherapy as 100%, 85.7%, 66.7% respectively. CONCLUSIONS: Cladribine has a significant efficacy and encouraging acute and long-term benefits when administered to patients with HCL. A single course of cladribine was able to induce CR in a vast majority of patients. At a median follow up of 4.6 years the OS was 100% with cladribine and 85% with splenectomy. Those who relapsed were successfully retreated with cladribine + Rituximab.

Association of GSTM1 and GSTT1 deletion polymorphisms with Pakistani aplastic anemia patients and controls and meta-analysis.

Interaction of environmental and genetic elements plays a vital role in the pathogenesis of aplastic anemia (AA). Glutathione S-transferase (GST) is a key detoxifying enzyme. Absence or low levels of this enzyme may genetically predispose individuals to AA. GST genes GSTM1 and GSTT1 are polymorphic. The aim of this study was to screen Pakistani AA patients and controls for GSTM1 deletion GSTM0 and GSTT1 deletion GSTT0 and perform meta-analysis using our data and other published data regarding these polymorphisms. DNA samples from 137 patients and 220 controls were screened using multiplex polymerase chain reaction. GSTM0 emerged as susceptible genotype for AA in Pakistan with a percentage frequency of 49.6 % as compared to 30 % in controls with odds ratio (OR) of 2.25, 95 % confidence interval (CI) of 1.4-3.5 and corrected p = 0.006. The meta-analysis showed a significant association between the null genotype GSTT0 and AA in overall analysis with OR of 1.47, 95 % CI of 1.01-2.13 and p value of 0.04 in random effects model. Studies like these could play a role in understanding the underlying path in AA pathogenesis and therefore can help in designing means for prevention, diagnose and treatment.