Challenges of fracture risk assessment in Asian and Black women.

OBJECTIVES: Bone mineral density (BMD) and fracture risk calculators (eg, the Fracture Risk Assessment Tool [FRAX]) guide primary prevention care in postmenopausal women. BMD scores use non-Hispanic White (NHW) reference data for T-score classification, whereas FRAX incorporates BMD, clinical risk factors, and population differences when calculating risk. This study compares findings among Asian, Black, and NHW women who underwent osteoporosis screening in a US health care system. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Asian, Black, and NHW women aged 65 to 75 years who underwent BMD testing (with no recent fracture, osteoporosis therapy, metastatic cancer, multiple myeloma, metabolic bone disorders, or kidney replacement therapy) were compared across the following measures: femoral neck BMD (FN-BMD) T-score (normal ≥ -1, osteoporosis ≤ -2.5), high FRAX 10-year hip fracture risk (FRAX-Hip ≥ 3%), FRAX risk factors, and diabetes status. RESULTS: Among 3640 Asian women, 23.8% had osteoporosis and 8.7% had FRAX-Hip scores of at least 3% (34.5% among those with osteoporosis). Among 11,711 NHW women, 12.3% had osteoporosis and 17.2% had FRAX-Hip scores of at least 3% (84.8% among those with osteoporosis). Among 1711 Black women, 68.1% had normal FN-BMD, 4.1% had BMD-defined osteoporosis, and 1.8% had FRAX-Hip scores of at least 3% (32.4% among those with osteoporosis). Fracture risk factors differed by group. Diabetes was 2-fold more prevalent in Black and Asian (35% and 36%, respectively) vs NHW (16%) women. CONCLUSIONS: A large subset of Asian women have discordant BMD and FRAX scores, presenting challenges in osteoporosis management. Furthermore, FN-BMD and especially FRAX scores identified few Black women at high fracture risk warranting treatment. Studies should examine whether fracture risk assessment can be optimized in understudied racial minority populations, particularly when findings are discordant.

Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY.

Background: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. Methods: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. Findings: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79-4.91; p < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49-2.11; p < 0.001/OR = 1.89; 95% CI = 1.6-2.24; p < 0.001).CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36-2.41; p < 0.001/OR = 2.11; 95% CI = 1.12-3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08-0.33; p < 0.001).Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001). Interpretation: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS. Funding: AbbVie, and EU/EFPIAInnovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026.

Oral Mucositis in Patients Undergoing Hematopoietic Stem Cell Transplantation.

OBJECTIVE: To determine the factors affecting the frequency and severity of oral mucositis are following hematopoietic stem cell transplantation. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Armed Forces Bone Marrow Transplant Centre Rawalpindi, from September 2020 to February 2022. METHODOLOGY: Patients who underwent allogenic stem cell transplantation were enrolled. Patients were analysed based on history and examination for oral mucositis (OM) as per the WHO mucositis scale, from the start of conditioning chemotherapy till discharge, total duration of mucositis and type of medication were noted. Its association with risk factors like age, gender, conditioning chemotherapy, methotrexate (MTX) for GVHD prophylaxis, and prior history of irradiation was determined. RESULTS: Mean age of the 72 transplant recipients was 21.9 ± 14 years, with 48 males and 24 females. The common underlying diseases were beta-thalassemia major (30.6%, n=22), acute lymphoblastic leukaemia (n=15, 20.8%), aplastic anaemia (n=10, 13.9%), and multiple myeloma (n=8, 11.1%). The frequency of mucositis in those aged under 15 years was 79.3% (n=23) and in those older than 15 years was 74.4% (n=32). Frequency of mucositis was statistically significant in patients who received myeloablative conditioning regimen (85% vs. 20%, p <0.01), and who had prophylactic. MTX (91% vs. 48%, p<0.01) and who had prior craniospinal (CSI) radiation (100% vs. 70.2%, p=0.01). There was no statistical significance between stem cell dose (CD34/TNC) and mucositis. Severity of mucositis was significantly greater in Allogenic vs. auto HSCT (p=0.04). All the patients with mucositis required analgesics for pain management. CONCLUSION: Oral mucositis is a common but potentially debilitating complication of stem cell transplant, requiring opioid analgesia in a significant number of cases. Myeloablative conditioning, prophylactic MTX, and prior CSI are significantly associated with mucositis in transplant patients. KEY WORDS: Hematopoietic stem cell transplantation (HSCT), Oral Mucositis, Myeloablative conditioning, Methotrexate, Analgesia.

Cytomegalovirus Infection Post-Allogeneic Stem Cell Transplantation: Experience from a Country with High Seropositivity.

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Limited data are available from developing countries regarding the frequency of CMV infection and treatment outcomes. We enrolled 230 consecutive patients undergoing allogeneic HSCT for various hematologic disorders at the Armed Forces Bone Marrow Transplant Center/National Institute of Blood And Marrow Transplant between February 2017 and December 202. CMV reactivation post-HSCT was monitored weekly starting at day +30 and continuing until day +100, and preemptive antiviral therapy was administered to prevent CMV disease in all HSCT recipients with ≥2000 CMV copies/mL. The median age of the study cohort was 9.5 years (range, .6 to 53 years), and the male:female ratio was 2.4:1. The most frequent indication for HSCT was beta thalassemia major (36.1%), followed by aplastic anemia (23.9%). Malignant disorders constituted 20% of all the patients. Pretransplantation CMV seropositivity was 99.1% for the recipients and 99.5% for the donors. CMV infection was seen in 66.1% of the patients, and the median time to CMV DNAemia was 36 days (range, 12 to 95 days). Preemptive antiviral therapy was administered to 140 patients with a CMV viral load ≥2000 copies/mL (61%). In multivariate analysis, patient age >12 years, steroid administration, and use of mycophenolate mofetil with or without post-transplantation cyclophosphamide was associated with the greatest probability of CMV reactivation. Overall survival was 97.4% in patients without CMV reactivation, compared to 80.3% in those with CMV reactivation (P = .001). Event-free survival was 78.7% in the total study cohort, including 89.7% for patients without CMV reactivation and 73% for patients with CMV reactivation (P = .003). Our study is the first from this region to explore the frequency of CMV seropositivity and CMV infection, risk factors for CMV reactivation, and outcomes of antiviral therapy in HSCT recipients.

To determine the frequency of aldehyde dehydrogenase type 2 (aldh2) deficiency in aplastic anaemia: A single center experience from pakistan.

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 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 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. CONCLUSIONS: We concluded from our study the frequency of ALDH2 was rare in patients with aplastic anaemia. 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.

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.

Stem Cell Transplantation in Glanzmann's Thrombasthenia: A Report of Two Adult Patients.

Glanzmann's thrombasthenia (GT) is an autosomal recessive bleeding disorder characterised by mucocutaneous bleeding. At molecular level, defect in platelet receptor glycoprotein (GP) IIb/IIIa leads to defective platelet aggregation. Anti-fibrinolytic agents, platelet transfusions, and factor rVIIa are used for prophylaxis before invasive procedures and treatment of bleeding events. Allogeneic stem cell transplant is the only curative option. Here, we report cases of two adult male patients who underwent matched sibling donor stem cell transplantation for GT with recurrent bleeding requiring platelet and red cell transfusions. Both showed marked improvement in quality of life. To conclude, stem cell transplant is a viable treatment option for severe, difficult-to-control cases of GT. Key Words: Platelet disorders, Hematopoietic stem cell transplantation, Thrombasthenia.

Response To Immunosuppressive Therapy In Patients Of Acquired Aplastic Anaemia: A Single Center Experience From A Developing Country.

Background: Aplastic Anaemia (AA) is characterized by pancytopenia and hypocellular marrow. Immunosuppressive therapy (IST) SHOWS impressive haematological response; however, risk of relapse and clonal evolution persists. The objective of the study is to assess response to IST in patients with aplastic anaemia. Methods: A retrospective single centre study at AFBMTC / NIBMT for patients of acquired AA was conducted from January 2005 to December 2019.Inclusion criteria included diagnosed cases of acquired AA receiving IST for at least 12 weeks and age >2 years. IST included cyclosporine (CsA) alone, CsA + androgens, CsA + rabbit anti thymocyte globulin (rATG), CsA + horse anti thymocyte globulin (hATG). Primary outcome measure was response to IST; secondary outcome measure was overall survival (OS). Results: A total of 513 patients received IST. Median age was 23 years (range 2-97 years). In study cohort, 155 (30.2%) patients responded to the IST, 63 (12.3%) achieved complete response (CR) while 92 (17.9%) achieved partial response (PR). The ORR of CsA in NSAA, SAA and VSAA was 52.6%, 28.10% and 10% respectively; whereas ORR of CsA + rATG in NSAA, SAA and VSAA was 50%, 35.1% and 22.5% respectively. OS was 38% at a median follow up of 36 months. There was a significant difference in the survival distributions of different treatment modalities (p=0.016). Median survival time 60 months (CsA), 9 months (CsA+ androgens) and 39 months (CsA+ rATG/hATG.) . Conclusion: In resource constrained settings, single agent CsA remains a reasonable alternative with modest activity and acceptable side effect profile.

Role of Ruxolitinib in Steroid-Refractory Graft versus Host Disease in Patients Undergoing Allogeneic Stem Cell Transplant.

The objective of this study was to evaluate the role of Ruxolitinib in steroid-refractory graft versus host disease. This retrospective descriptive study was conducted from January 2018 to December 2021. A total of 157 patients underwent allogeneic stem cell transplants during the study period. Of these, 20 patients having steroid-refractory GVHD treated with Ruxolitinib were selected for the study. The primary endpoint was the overall response rate to Ruxolitinib measured at 4 weeks and 24 weeks for acute and chronic GVHD, respectively. The secondary endpoints were overall survival and failure-free survival. Of these 20 patients, 7 (35%) had acute GVHD, and 13 (65%) had chronic GVHD. Of acute GVHD, 2 (10%) had grade II, 4 (20%) had grade III, and 1 (5%) had grade IV acute GVHD. Of 13 patients with chronic GVHD, 7 (35%) had moderate and 6 (30%) had severe chronic GVHD. In steroid-refractory acute GVHD, the overall response rate to Ruxolitinib was 85.7%, and in chronic GVHD, it was 84.6%. The failure-free survival was 80% and overall survival was 85%. Adverse events of any grade occurred in 16 (80%) patients with grade III/IV adverse events in 4 (20%) patients only. The study showed that Ruxolitinib is a safe and effective second-line therapy for acute and chronic steroid-refractory GVHD. Key Words: Ruxolitinib, GVHD, Allogeneic stem cell transplant.

Genome-wide CRISPR screen identifies PRC2 and KMT2D-COMPASS as regulators of distinct EMT trajectories that contribute differentially to metastasis.

Epithelial-mesenchymal transition (EMT) programs operate within carcinoma cells, where they generate phenotypes associated with malignant progression. In their various manifestations, EMT programs enable epithelial cells to enter into a series of intermediate states arrayed along the E-M phenotypic spectrum. At present, we lack a coherent understanding of how carcinoma cells control their entrance into and continued residence in these various states, and which of these states favour the process of metastasis. Here we characterize a layer of EMT-regulating machinery that governs E-M plasticity (EMP). This machinery consists of two chromatin-modifying complexes, PRC2 and KMT2D-COMPASS, which operate as critical regulators to maintain a stable epithelial state. Interestingly, loss of these two complexes unlocks two distinct EMT trajectories. Dysfunction of PRC2, but not KMT2D-COMPASS, yields a quasi-mesenchymal state that is associated with highly metastatic capabilities and poor survival of patients with breast cancer, suggesting that great caution should be applied when PRC2 inhibitors are evaluated clinically in certain patient cohorts. These observations identify epigenetic factors that regulate EMP, determine specific intermediate EMT states and, as a direct consequence, govern the metastatic ability of carcinoma cells.

Factors That Affect Patient Attrition in Buprenorphine Treatment for Opioid Use Disorder: A Retrospective Real-World Study Using Electronic Health Records.

PURPOSE: To describe attrition patterns of opioid use disorder (OUD) patients treated with buprenorphine (BUP) and to assess how clinical, sociodemographic, or BUP medication dosing features are associated with attrition. PATIENTS AND METHODS: Electronic health records of adults (16+ year-olds) with OUD treated with BUP from 23 different substance use or mental health care programs across 11 US states were examined for one year following BUP initiation in inpatient (IP), intensive outpatient (IOP), or outpatient (OP) settings. Treatment attrition was declared at >37 days following the last recorded visit. Survival analyses and predictive modelling were used. RESULTS: Retention was consistently 2-3 times higher following BUP initiation in OP (n = 2409) than in IP/IOP (n = 2749) settings after 2 (50% vs 25%), 6 (27% vs 9%) and 12 months (14% vs 4%). Retention was higher for females, whites (vs blacks), and those with less severe OUD, better global function, or not using non-psychotropic medications. Comorbid substance use, other psychiatric disorders, and the number of psychotropic medications were variously related to retention depending on the setting in which BUP was initiated. Predictive modelling revealed that a higher global assessment of functioning and a smaller OUD severity based on the Clinical Global Impression - Severity led to longer retentions, a higher initial BUP dose led to higher retention in a few cases, an OP setting of BUP initiation led to longer retentions, and a lower total number of psychotropic and non-psychotropic medications led to longer retentions. These were the most important parameters in the model, which identified 75.2% of patients who left BUP treatment within three months post-initiation, with a precision of 90.5%. CONCLUSION: Of all the OUD patients who began BUP, 50-75% left treatment within three months, and most could be accurately identified. This could facilitate patient-centered management to better retain OUD patients in BUP treatment.

Allogeneic hematopoietic stem cell transplant in rare hematologic disorders: a single center experience from Pakistan.

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.

Allogeneic hematopoietic stem cell transplantation in aplastic anemia: current indications and transplant strategies.

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.

Single-Agent Cyclosporine for Graft-versus-Host Disease Prophylaxis in Patients with Acquired Aplastic Anemia Receiving Fludarabine-Based Conditioning.

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.

Comparison Of Positivity Of Tuberculin Skin Test With Diagnostic Bcg In Children Suffering From Tuberculosis.

BACKGROUND: Tuberculosis is major public health problem in Pakistan and it is often unrecognized cause of morbidity and mortality in children living in endemic areas. Children with age less than 5 years, and especially those who are immune compromised, are at higher risk of developing tuberculosis following exposure. Tuberculosis in children is usually difficult to diagnose compare to adult patients due to its atypical presentation. Tuberculin skin test and Bacille Calmette-Guerin (BCG) are widely used as diagnostic tests for tuberculosis. It was a Cross sectional study carried out from May 2017 to Nov 2018 in the department of Paediatrics, Ayub Teaching Hospital Abbottabad.. METHODS: Both BCG and tuberculin skin test were performed at the same time by the same doctor. Personal data like age, gender and address, type of tuberculosis, positivity of tuberculin skin test and positivity of diagnostic BCG were recorded. The induration was read 48- 72 hours after administration. RESULTS: As per frequencies and percentages for positivity of tuberculin skin, 51 (67.10%) patients showed positivity for tuberculin skin while 71 (93.42%) patients showed positive results via BCG Test. CONCLUSIONS: In paediatric age group, diagnostic BCG test has got better diagnostic value over Tuberculin Skin Test in diagnosis of tuberculosis.

Epidemiology of aplastic anemia: a study of 1324 cases.

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.

Comparison of Conventional Cyclophosphamide versus Fludarabine-Based Conditioning in High-Risk Aplastic Anemia Patients Undergoing Matched-Related Donor Transplantation.

Allogeneic stem cell transplant for high-risk aplastic anemia (AA) yields inferior results using conventional cyclophosphamide (CY)-based conditioning. The use of fludarabine (Flu)-based regimens has resulted in improved outcomes in high-risk patients. Limited data are available comparing these two conditioning regimens in such patients. We retrospectively analyzed 192 high-risk patients undergoing matched-related donor transplantation from July 2001 to December 2018. The median age was 19.5 (2-52) years. Patients were divided into 2 groups, Cy200 anti-thymocyte globulin (ATG)20 (Gp1 n = 79) or Flu120-150 Cy120-160 ATG20 (Gp2 n = 113). The risk of graft failure was significantly higher in Gp1, and the majority occurred in patients with >2 risk factors (p = 0.02). The incidence of grade II-IV acute graft versus host disease (GVHD) and chronic GVHD was not significantly different between the two groups. The overall survival (OS) of the study cohort was 81.3 %, disease-free survival (DFS) 76.6 % and GVHD-free relapse-free survival (GRFS) was 64.1%. DFS and GRFS were significantly higher in Gp2 as compared to Gp1: DFS 84.1% versus 68.4 % (p = 0.02), GRFS 77.9% versus 54.4% (p = 0.01), respectively. We conclude that Flu-based conditioning is associated with superior OS, DFS and GRFS as compared to the conventional Cy-based regimen in high-risk AA.