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Aplastic anemia is a relatively rare but potentially fatal disorder, with a reported higher incidence in developing countries in comparison to the West. There are significant variations in epidemiological as well as etiological factors of bone marrow failure syndromes in the developing countries in comparison to the developed world. Furthermore, the management of bone marrow failure syndromes in resource constraint settings has significant challenges including delayed diagnosis and referral, limited accessibility to healthcare facilities, treatment modalities as well as limitations related to patients who require allogeneic stem cell transplantation. Here we will provide a review of the available evidence related to specific issues of aplastic anemia in the developing countries and we summarize suggested recommendations from the Eastern Mediterranean blood and bone marrow transplantation (EMBMT) group and the severe aplastic anemia working party of the European Society of blood and marrow transplantation (SAAWP of EBMT) related to the diagnosis and therapeutic options in countries with restricted resources.

Objective: To determine the effect of high altitude on frequency and risk factors of venous thrombosis inindividuals ascending to high altitude Study Design: Cross-sectional analytical study. Place and Duration of Study: Armed Forces Bone Marrow Transplant Centre, Combined Military HospitalSkardu, from Apr 2015 to Aug 2018. Methodology: High Altitude was taken as height equal to or more than 8000 feet. Polycythemia as hemoglobin>16.5 g/dl OR hematocrit >49%. Medical records of all patients evacuated from high altitude through CombinedMilitary Hospital Skardu were analyzed retrospectively. A proforma was designed to include necessary variables. Results: We evaluated medical records of 539 individuals and found frequency of 86 (15.9%) for venous thromboembolism (VTE) at high altitude. Cerebral venous sinus thrombosis (CVST) was most common thrombotic complication seen in 39 patients (46%). Majority of thrombotic episodes occurred at >18000 feet (likelihood ratio (LR) 5.99, p-value 0.009). Majority of thrombotic episodes 34 (39%) occurred within first 45 days of ascent to high altitude. Thrombosis was linked to smoking 47 (55%) (likelihood ratio 21.3 and p-value

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.

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.

Mesenchymal stromal cells (MSCs) have emerged as a promising candidate for the treatment of steroid-refractory graft-versus-host disease (GVHD). In this uncontrolled, pilot clinical study, we report safety and efficacy of allogeneic bone marrow MSCs administered intravenously to steroid-refractory GVHD patients. A total of 33 MSC infusions were given to 10 patients suffering from acute GVHD (n = 3), chronic GVHD (n = 5), and overlap syndrome (n = 2). Eight out of ten patients are alive after a median follow-up of 11 months with five having sustained complete remission (CR). Three patients with partial response received further doses to sustain the response. One of them died of lung infection while others are still alive. One out of the two non-responding patients died after 17 days of MSC therapy due to advanced liver GVHD while the other is having a stable disease course. The overall and GVHD-free survival was 80% and 50%, respectively. The patients developed no complication or toxicity related to MSC infusion. Luminex analysis revealed a modest drop after MSC infusion in pro-inflammatory cytokines like TNFα, IL-1β, and IL-6 whereas serum IL-10 levels were slightly raised. Allogeneic donor-derived bone marrow mesenchymal stromal cell therapy is a safe and feasible treatment for steroid-refractory GVHD patients (NCT02824653). We report the safety and efficacy of allogeneic bone marrow mesenchymal stromal cell therapy in 10 patients suffering from steroid-resistant graft-versus-host disease. Eight out of ten patients are alive after a median follow-up of 11 months with five having sustained CR. The response rate was better in acute GVHD patients compared to chronic GVHD patients. MSC therapy within 20 days of steroid-refractory acute GVHD resulted in sustained CR. Initial and sustained response was superior in pediatric patients compared to adults. The Luminex analysis showed a modest decrease in pro-inflammatory cytokines in those responding to MSC therapy.

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 factor...

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.

The World Health Organization-designated Eastern Mediterranean region (EMRO) consists of 22 countries in North Africa and Western Asia with a collective population of over 679 million. The area comprises some of the wealthiest countries per capita income and some of the poorest. The population structure is also unique and contrasts with western countries, with a much younger population. The region sits in the heart of the thalassemia belt. Many countries have a significant prevalence of sickle cell disease, and cancer is on the rise in the region. Therefore, the strategic priorities for the growth and development of hematopoietic stem cell transplantation (HSCT) differ from country to country based on resources, healthcare challenges, and prevalent infrastructure. Thirty-one reporting teams to the Eastern Mediterranean Blood and Marrow Transplantation Group have active HSCT programs in 12 countries; allogeneic transplants outnumber autologous transplants, and the proportion of allotransplants for non-malignant conditions is higher in the EMRO region than in Western Europe and North America. The vast majority (99%) of allotransplants are from matched related donors. Matched unrelated donors and other alternate donor transplants are underutilized. The chance of finding a matched related donor for allografts is higher, with a significant chance of finding matched donors among non-sibling related donors. Reasons for relatively lower rates of transplants compared with other countries are multifactorial. Capacity building, development of newer centers, innovative funding, and better utilization of information technology are required to make transplantation as an accessible modality to more patients. Cost-effectiveness and cost-containment, regulation, and ensuring quality will all be priorities in planning HSCT development in the region.

Introduction Allogeneic hematopoietic stem cell transplant (HSCT) is the standard treatment for patients younger than 40 years with Severe and Very Severe Aplastic Anemia (AA) who have a Matched Related Donor (MRD). For patients lacking a MRD, treatment options include immunosuppressive therapy (IST), matched unrelated donor (MUD) or alternate donor (haploidentical/cord blood) transplant. Pakistan has a population of around 23 million but there is no donor registry for MUD transplants and horse antithyomcyte globulin (hATG) is not available. Over past decade, results of haploidentical transplants have improved remarkably with use of post-transplant cyclophosphamide. However, most of these protocols incorporate total body irradiation (TBI) to improve engraftment and reduce graft failure. TBI is not available in most of the transplant centres across Pakistan. We have developed a novel TBI free conditioning regimen (NCT03955601) for haploidentical HSCT in acquired AA patients lacking a MRD. Materials and Methods We conducted a prospective, single centre, interventional trial (NCT03955601) using novel TBI free conditioning at AF bone marrow transplant centre (AFBMTC)/ National institute of blood and marrow transplant (NIBMT) for patients with acquired severe and very severe AA. Between July 2018 and March 2020, a total of 10 patients received related haploidentical transplant.Study inclusion criteria was diagnosis of severe and very severe AA, patients of both genders, age 2-60 years, Karnofsky performance status>70%. Exclusion criteria was presence of donor specific antibodies (DSA), inherited bone marrow failure syndrome, prior HSCT and severe sepsis. Conditioning regimen used was Fludarabine (Flu) 30 mg/m2 IV daily from day -7 to -3, Cyclophosphamide (Cy) 14.5 mg/kg IV daily on day -6 and -5 , rabbit Antithymocyte globulin (rATG) 5 mg /kg/day from day -6 to day-3; Busulphan (Bu) IV 3.2 mg per kg/day in 04 divided doses on day -3 and day-2, Granulocyte Colony Stimulating factor (GCSF) primed Bone marrow harvest (BMH) and/or PBSC graft on day 0 and day +1 respectively. Graft versus host disease (GVHD) prophylaxis used was post-transplant cyclophosphamide (PTCy) administered at a dose of 50mg/kg/day given daily on days +3 and +5 post-transplant, cyclosporine (CsA) from day +5 and mycophenolate mofetil (MMF) from day+5 to +35. Primary outcome measure was overall survival (OS) while secondary outcome measures included graft failure, treatment related mortality (TRM), disease free survival (DFS), GVHD free relapse free survival (GRFS), acute and chronic GVHD. Results: Ten patients were transplanted, 5 (50%) female and 5 (50%) male (table 1). Median age was 15.5 years (range 5-41 years). Median duration from diagnosis to transplant was 14 months (range 4-51 months). One patient received ATG prior to transplant. Median number of red cell concentrate (RCC) transfusions before transplant were 27 (8-90) and platelet transfusions 100(6-150). Median donor age was 23 years (10-41 years). Donor-recipient major ABO mismatch was present in 2(20%) while four (40%) had minor ABO mismatch. Primed bone marrow harvest (BMH) was used in 3(30%) while primed BM+PBSC was given in 7(70%) patients. Median CD34 dose given was 8 x 106/kg (range 5.1-16). Seven patients (70%) achieved sustained neutrophil engraftment. One patient had primary graft failure, one patient secondary graft failure at day 35 due to Cytomegalovirus infection and one patient (currently day +118) is having poor graft function. Acute skin GVHD stage-2 developed in 1 patient which settled with topical steroids. None of the patient developed chronic GVHD. Cytomegalovirus reactivation was documented in 8 (80%) patients. All donors and recipients were CMV seropositive pre-transplant. One patient (female, 20 years) had primary graft failure and died on day +31 with sepsis and multiorgan dysfunction syndrome (MODS). One patient (female, 14 years) had secondary graft failure due to CMV infection and died on day +44 with intracranial hemorrhage. Conditioning regimen was well tolerated without any treatment related morbidly and mortality. Median follow-up of study was 13 months (range 4-22 months). Overall survival of study cohort is 80%, DFS 70% and GRFS 70%. Conclusion: Our study shows that for countries lacking TBI, use of FluCAB-Prime protocol is feasible and is associated with low rates of acute and chronic GVHD. Disclosures No relevant conflicts of interest to declare.

Objective: To determine the frequency and pattern of dermatological manifestationsin patients receiving interferon and ribavarin for hepatitis C. Patients & Methods: The studywas conducted in the Dermatology out patients department (OPD) of Dow University HospitalKarachi from April –November 2013.Patients diagnosed with hepatitis C who received interferona(3 MIU subcutaneously thrice weekly) plus ribavirin (1200 mg daily for 24 weeks).Detailedhistory and dermatological examination including mucous membrane,hair and nails wasperformed initially and then monthly for six months and findings were recorded. Results: Atotal of 109 patients were included in the study.Frequency of various skin diseases in thesepatients werepruritis 44(40.36%), transient alopecia 14(12.84%),generalized morbiliform rashin 22 (20.18%),photosensitivity in 8(7.33%), secondary hyperpigmentation in 17(15.59%)patients.Lichen Planus was observed in 6 (5.50%) patients while brittle nails were seen in 5(4.58%), glossitis in 4(3.66%),chelitis in 8(7.33%)and generalized exfoliating dermatitis in9(8.25%) patients.Apthous ulceration was observed in 7 (6.42%) patients. Conclusions: HCVand its treatment with interferon plus ribavirin is associated with significant dermatologicalcomplications. Physicians should be aware of these side effects and patients should becounseled before starting treatment.

Objectives: The objective of this study is to determine the frequency of Occulthepatitis B virus (DNA) in cases of chronic hepatitis C in a tertiary care hospital of Karachi.Study Design: Cross sectional study. Setting: Medical Department of Abbasi ShaheedHospital and Karachi Medical and Dental College after permission of ethical committee.Period: 15 December 2015 to 15 December 2016. Methods: Patients greater than 18 years ofage of either sex were included while those with positive HBsAg, history of alcoholism, bloodtransfusion, intravenous drug abuse and hemodialysis were excluded. After informed consentblood samples were collected and evaluated for HBV DNA by performing qualitative PCR. Datawas analyzed on SPSS version 16.0.p value of

Post‐transplant lymphoproliferative disorder (PTLD) is rarely reported in matched sibling donor (MSD) transplants of aplastic anemia (AA), and occurrence of Hodgkin lymphoma in this subgroup is extremely uncommon. Our patient, a 7‐year‐old girl, underwent MSD transplant for AA and developed EBV‐driven Hodgkin lymphoma after tapering of immunosuppression. Post‐transplant lymphoproliferative disorders (PTLDs) represent heterogenous groups of clonal disorders occurring after solid organ and hematopoietic stem cell transplantation. Most of PTLDs are EBV driven and have a frequency of 3.2% in stem cell transplant recipients and 1.1% in matched sibling donor (MSD) transplants.1 Risk factors of PTLD include unrelated donor and haploidentical transplants, use of T‐cell depleting conditioning and higher recipient age. The underlying mechanism is failure of newly instituted donor immune system to control EBV‐infected host cells due to profound T‐cell immune suppression. Epstein‐Barr Virus (EBV) DNA monitoring is done in these high‐risk patients to detect reactivation of EBV and institution of pre‐emptive measures like reduction of immunosuppression and treatment with rituximab. There are only few case reports of PTLD in patients of AA undergoing MSD transplant2 but to our knowledge this is first reported case of EBV‐driven Hodgkin lymphoma occurring after tapering of immunosuppression in patient undergoing MSD HSCT for AA.

Purpose: To provide evidence-based recommendations for health care professionals on diagnosis and management of diffuse large B cell lymphoma (DLBCL) in resource constraint settings with variable and often limited access to standard of care and advanced diagnostic and therapeutic facilities. Methods: Modified Delphi methodology[1] was used to generate consensus by experts of three major cancer societies of Pakistan; namely Society of Medical Oncology Pakistan (SMOP), Pakistan Society of Hematology (PSH) and Pakistan Society of Clinical Oncology (PSCO). Guidelines questions were drafted and meetings were convened by steering committee to develop initial recommendations based on local challenges and review of the literature. Consensus panel reviewed the initial draft recommendations and rated the guidelines on five-point Likert scale; recommendations achieving more than 75% consensus were accepted. Resource grouping initially suggested by Breast Health Global Initiative[2] was applied for resource stratification into basic, core and enhanced resource settings. Results: The expert panel advised use of limited immunohistochemistry (IHC) including CD20, CD3 and Ki67% for initial diagnosis in core (limited) resource settings and extended panel in enhanced resources. Cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) with or without rituximab (as per resource setting) remains the standard first line treatment while second line treatment should be offered based on resource availability and patient related factors. Both intra thecal and high dose methotrexate can be used for CNS prophylaxis. Recommendations by guideline committee are listed in Table 1. Conclusion: Diagnosis and treatment recommendations in resource constraint settings should be developed based on available diagnostic, therapeutic resources and management expertise. References: Niederberger, M. and J.J.F.i.p.h. Spranger, Delphi Technique in Health Sciences: A Map. 2020. 8: p. 457.Eniu, A., et al., Guideline implementation for breast healthcare in low-and middle-Income countries: Treatment resource allocation. 2008. 113(S8): p. 2269-2281. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). It causes end-organ disease, multi-organ dysfunction syndrome, graft failure, increased susceptibility to infections and GVHD. According to the published western data greatest risk of CMV infection is the seropositivity of the recipient, however, in a high endemic population where seropositivity is up to 100%, risk factors for CMV reactivation are different and are analyzed in this study. Methods: It is a prospective descriptive study performed at Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan from January 2017 to March 2020. Consecutive patients who underwent allogeneic HSCT during this period were enrolled. All patients were prospectively monitored for CMV reactivation by weekly or two weekly CMV DNA quantitative PCR, from engraftment till day 100 post-transplant. CMV infection was diagnosed on detection of more than 200 copies/ml on PCR. Threshold for starting preemptive antiviral therapy was kept at 2000 copies/ml. Patients with past history of CMV infection, those who expired before day 14 post-transplant or those with less than 70% of required CMV tests were not included in the study. Factors associated with CMV reactivation, outcome of antiviral therapy and effect of CMV on post-transplant survival were studied. Results: Out of 319 transplants during this period, 230 patients fulfilled the inclusion criteria. Of these, 197 were HLA matched sibling, 18 were matched family donor and 15 were haploidentical transplants. There were 163 males and 67 females. Median age at transplant was 9.5 years (0.5-53). Eighty-three transplants were done in thalassemia, 55 in aplastic anemia, 14 in Fanconi anemia, 27 in acute leukemias, 8 in CML, 9 in MDS, 12 in HLH and 22 in other hematological disorders. All the patients and donor were CMV IgG seropositive when tested before transplantation. CMV reactivation was seen in 152 out of 230 patients (66.1%). Of 152, 95 patients had CMV viral load more than 2000 copies/ml and required antiviral treatment. Median time to reactivation since transplant was 35 days (13-90). In multivariate analysis using binary regression, risk factors for high viral load CMV reactivation included steroid administration (p=0.009), recipient age less than 10 years (p=0.003) and haploidentical transplant (p=0.048). No statistically significant association was found with the use of ATG, GVHD, underlying disease, ABO blood group or gender mismatch. Survival analysis using cox regression showed significant impact of high viral load CMV reactivation on post-transplant survival. Event-free survival (EFS) with and without CMV reactivation was 70.5 % and 89.7% respectively (p=0.004) and overall survival (OS) was 80.0 % and 97.4 % with and without CMV reactivation respectively (p=0.002). Valganciclovir was given in 89 patients and 6patients were treated with ganciclovir. Mean time to clear viremia was 19.8±9 days. Myelosuppression was seen in 41% of patients treated with valganciclovir. Renal impairment was seen in 25% of patients treated with valganciclovir. One patient had resistant disease. One patient had CMV pneumonia and she recovered. One patient died of suspected CMV pneumonia Conclusion: CMV reactivation was seen in 66.1% of the transplant recipients, this is higher compared to the western world due to high CMV seropositivity is this region. Steroids administration in post-transplant period significantly increase the risk of CMV reactivation. Preemptive therapy with valganciclovir effectively treats CMV reactivation. Viral threshold for treatment should be decided considering the regional endemicity. CMV adversely effects the transplant outcome in terms of EFS and OS. Disclosures No relevant conflicts of interest to declare.

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.

Aplastic anemia (AA) is the most serious non-malignant blood disorder in Pakistan, ranked second in prevalence, after thalassemia. We investigated various epidemiological, clinical, and genetic factors of AA in a Pakistani cohort of 214 patients reporting at our hospital between June 2014 and December 2015. A control group of 214 healthy subjects was included for comparison of epidemiological and clinical features. Epidemiological data revealed 2.75-fold higher frequency of AA among males. A single peak of disease onset was observed between ages 10 and 29 years followed by a steady decline. AA was strongly associated with lower socioeconomic profile, rural residence, and high rate of consanguineous marriages. Serum granulocyte colony-stimulating factor and thrombopoietin levels were significantly elevated in AA patients, compared to healthy controls (P

Objectives: To assess the efficacy of intra-lesional triamcinolone in for thetreatment of Post Herpetic Neuralgia. Study Design: Prospective interventional study. Setting:Dermatology Department of Dow University Hospital. Period: July 2014 to June 2015. Patientsand Methods: Twenty nine patients with diagnosis of Post Herpetic Neuralgia were includedafter taking written and informed consent. An insulin syringe was used for the injections andthe medicines were injected intralesionally. The mixture contained 30/70% of triamcinolone toxylocaine ratio for local infiltration in post herpetic scars. Pain relief assessment was done withthe help of visual analogue scale (VAS) after two months. Mean pain score before therapy andafter therapy was compared with one sample student t test. Results: Out of total 29 patients 14were male and 15 were females. The mean age ±SD was found to be 45.9± 15.4 years. Themost common region involved was Chest. The mean ±SD duration of Symptoms was 5.58 ±1.80 weeks. The mean pain score before therapy was 6.86 ± 1.66 which after one month oftherapy reduced to 3.72 ± 1.86. The reduction in pain was statistically significant (p

A 33-year male with history of penetrating trauma to left upper chest in 2006, presented through Medical unit to Radiology Department with complain of hemoptysis. Chest X-ray showed a soft tissue lesion in left upper lobe with a linear metallic foreign body. Contrast enhanced CT scan of chest and later CTA was performed which showed a saccular aneurysm arising from mediastinal part of left common aortic artery surrounded by thrombosis with a cylindrical linear metallic foreign body. He was planned for endovascular repair with stenting which he could not afford due to financial constraints. He is currently on conservative follow up. Vascular lesions can be serious complications resulting from blunt or penetrating trauma, when presenting with hemoptysis due to pseudaoneurysms formation even after so many years of trauma.

Dengue fever is a fatal infection affecting the lives of the patients and this study was designed to further explore its pathological effects. A total of 200 consecutives of dengue viral infection were included in this prospective descriptive study conducted at the Department of Pathology, University of Veterinary and Animal Sciences, Lahore from October, 2009 to September, 2010. A special proforma was designed to collect all the relevant clinical information from each patient. All the strip positive cases of dengue virus were further confirmed by performing IgM capture ELISA and then analyzed for hepatic impairment through liver function tests including serum bilirubin, serum alkaline phosphatase, serum ALT and AST. The results were then gathered and analyzed. The already existing liver diseases like hepatitis A, B, C, E and inherited liver disorders were not included in the study. Total number of patients included in study with Dengue IgM +ve were 200. Out of 200 cases 130 were male and 70 were females. The patients were categorized into two classes according to severity of sign symptoms like puerperal rash on the body. The classes are dengue fever (DF) and dengue hemorrhagic fever (DHF). The total number of DF cases was 28.50% (57/200) and number of DHF cases was 71.50% (143/200). The patients of DHF group were found to have more liver derangement that is 90.20% (128/200) while the patients belonging to DF group were at a less risk for impairment of liver function that is 9.80% (15/200). The patients with dengue hemorrhagic fever are more prone to have liver enzyme derangement and it has a direct relation with the titer IgM in the body of patients infected with dengue virus. The liver enzyme which are found to be more raised are serum ALT and AST while serum alkaline phosphatase and serum bilirubin are not markedly raised.

Primary myelofibrosis (PMF) is a clonal, BCR-ABL1 negative myeloproliferative neoplasm characterised by splenomegaly, leukoerythroblastic peripheral blood picture and bone marrow fibrosis. Different cytogentic abnormalities are documented in PMF which have impact on clinical outcome and overall survival. Del 5q31 is documented in only 0.8% of PMF patients and is associated with poor outcome and increased risk of progression to acute leukemia. Anemia with del 5q responds frequently to lenalidomide treatment. We are reporting case of a middle-aged male who presented with constitutional symptoms, myelofibrosis; and calreticulin type 2 mutation was present. His cytogenetics showed del 5q positivity. He was started on lenalidomide but developed toxic epidermal necrolysis, resultantly lenalidomide was stopped. Skin eruptions are a known entity in patients with lenalidomide therapy; but to date, there is no reported case of lenalidomide induced toxic epidermal necrolysis (TEN) in patients with myelofibrosis.

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.

Objective: To determine the frequency of various neurological and psychiatric symptoms associated with B12 deficiency.Study design: Observational and descriptive study. Place and duration of study: The study was conducted on patients presenting to theneurology clinics and inpatients who were admitted through the emergency department at Aga khan University Hospital Karachi, from 1stJuly 2011 to March 2012. Subjects and methods: 150 patients of either gender and age more than 18 years. Detailed history was takenfrom all the patients with special regard to anemia. Inclusion criteria were that patients above 18 years of age of either sex with low serumB12 levels. Patients having any type of neurological tumors, major ischemic stroke, major intracranial haemorrhage, patients onneuroleptic medications and any evidence of toxin induced neuropathy were excluded. All patients underwent for specific investigationcomplete blood count, serum B12 levels (derived by Radio Assay method (RIA). Further investigations Nerve Conduction Studies /Electromyography and CT Scan / Magnetic resonance Imaging of the Brain / spinal cord were carried out as and when required,depending on the clinical scenario. Results: There were 69 (46%) males and 81(54%) females. Female to male ratio was 1:0.8. The ageranged between 18 to 90 years with the mean age of 45.7+ 5.6. Out of 150 patients 107 patients (71.3 %) had severe vitamin B 12deficiency while 43 (28.7%) had mild to moderate deficiency. Neurological manifestations which were observed included; Memory wasimpaired in 13 (8.7%) of the patients. Dysarthia, along with other cerebellar signs (Nystagmus and dysdiadochokinesia) was present in9 patients (6%). 4 patients (2.7%) sought medical attention regarding their abnormal gait and their neurological examination revealedextensor planter responses and hyperreflexia. Cranial nerve examination revealed Anosmia in 2 (1.3%) and upper motor neuron facialweakness in 1 (0.66%) patients. Motor weakness was found in 2 patients (1. 3%), and spasticity in 2 (1.3%) patients. 5 patients (3.3%)had sensory complains and were found to have impaired pain and touch perception. Proximal muscle weakness in one patient whileanother patient had asymmetric muscle weakness and rest of the patients had normal muscle power. None of the patient had autonomicdysfunction. In six neuropsychiatric problems were commonly seen in vitamin B 12 deficient people. In these patients depression wasobserved in 16%, agitation 12.7 %, memory impairment 8.7%, cerebellar signs and dysarthria 6%, sensory symptoms 3.3% and gaitabnormality and hyperreflexia and extensor planters 2.7 %. Conclusions: Various Neuropsychiatric problems are associated with vitaminB 12 deficiency and the most common Neuropsychiatric illness found in these patients were depression, agitation, and memoryimpairment.

Background There is very little information about the quality of life (QOL) of stroke survivors in LMIC countries with underdeveloped non communicable health infrastructures, who bear two thirds of the global stroke burden. Methodology We used a sequential mix methods approach. First, a quantitative analytical cross-sectional study was conducted on 700 participants, who constituted 350 stroke survivor and their caregiver dyads. QOL of stroke survivor was assessed via Stroke Specific Quality of Life Scale (SSQOLS) whereas QOL of caregivers was assessed through RAND-36. In addition; we assessed complications, psychosocial and functional disability of stroke survivors. Following this quantitative survey, caregivers were qualitatively interviewed to uncover contextually relevant themes that would evade quantitative surveys. Multiple linear regression technique was applied to report adjusted β-coefficients with 95% C.I. Results The QOL study was conducted from January 2014 till June 2014, in two large private and public centers. At each center, 175 dyads were interviewed to ensure representativeness. Median age of stroke survivors was 59(17) years, 68% were male, 60% reported depression and 70% suffered post-stroke complications. The mean SSQOLS score was 164.18 ± 32.30. In the final model severe functional disability [adjβ -33.77(-52.44, -15.22)], depression [adjβ-23.74(-30.61,-16.82)], hospital admissions [adjβ-5.51(-9.23,-1.92)] and severe neurologic pain [adjβ -12.41(-20.10,-4.77)] negatively impacted QOL of stroke survivors (P

Objective: To compare outcome, disease-free survival and rejection in aplastic anaemia patients receiving: (A) ALG or ATG plus cyclophosphamide (CY) 200 mg/Kg ; (B) Fludarabine 120 mg/m2, ATG plus CY 300 mg/m2 and (C) Fludarabine 120 mg/m2, ATG plus CY 120 mg/Kg conditioning regimens. Patients & Methods: The study included 202 consecutive aplastic anaemia patients undergoing hematopoietic stem cell transplantation from HLA matched sibling donors at this centre from July 2001 to April 2014. Overall 122 had very severe aplastic anemia, 76 severe and 4 non-severe aplastic anemia. Group A, B and C were compared for outcome, disease free survival and rejection. The stem cell source was bone marrow (39.6%); PBSC (7.9%) or both bone marrow plus PBSC (51.5%). GVHD prophylaxis consisted of cyclosporine (51% cases) and cyclosporine plus methotrexate (45.5% case). Chi-square test was used to compare categorical variables. Two way ANOVA was used to compare group means. Kaplan Meier survival curves with log rank test was applied to compare the groups for survival analysis. Results: Group A included 99, group B 72 and group C 31 patients. Male to female ratio was 76/23 in group A; 56/16 in group B and 22/9 in group C. Median age of patients in group A, B and C were 16, 22 and 18 years respectively (p=0.001). At a median follow up of 1267 days the overall and disease free survival were 76.7% and 68.7% in group A, 70.8% and 69.4% in group B, 67.7% and 54.8% in group C (p=0.350, and p=0.412 respectively). The rejection rate was 11.1%, 9.7% and 35.5% in group A, B and C respectively (p=0.001). Frequency of chronic GVHD was 10%, 8% and 35.5 in respective groups (p Conclusion: Conditioning regimens using ALG or ATG with Cy 200 mg/kg; and Fludarabine 120 mg/m2, ATG plus Cy 120 mg/kg give comparable results while the regimen using Fludarabine 120 mg/m2, ATG plus Cy 300 mg/m2 is associated with high rejection rate and inferior survival in aplastic anemia following allogeneic stem cell transplantation. Disclosures No relevant conflicts of interest to declare.

Introduction Tyrosine kinase inhibitors (TKIs) have largely replaced allogeneic hematopoietic stem cell transplantation (HSCT) as first line treatment option in chronic phase chronic myeloid leukemia (CML) yet due to the need for continued administration the cost becomes prohibitive in majority of patients without any health insurance coverage. Therefore allogeneic stem cell transplant remains a reasonable treatment option for such patients especially in resource constrained countries. It is also useful treatment modality in children, CML in accelerated phase and in patients intolerant to TKIs. We report results of 64 consecutive patients undergoing HLA matched sibling allo HSCT at our center from April 2002 to September 2012. Methods Patients with Philadelphia positive CML were categorized into standard and high risk based on age >40 years, disease duration > 12 month from diagnosis to transplant and accelerated phase. Conditioning regimens used were oral busulphan 16 mg/kg plus cyclophosphamide 200 mg/kg (Bu16/Cy200), Bu16/Cy120, Bu16/Cy120/Etoposide30 and Bu16/Cy120/ATG. Source of stem cell was peripheral blood stem cells (PBSC) or bone marrow (BM) infusion. GVHD prophylaxis consisted of ciclosporin, short methotrexate (10 mg/m2 on day +1, 8 mg/m2 on day +3 & 6) ± prednisolone. Statistical calculations included Fisher’s exact test, Kaplan-Meier for survival analysis, and Cox regression for multivariate analysis. Results Median age of the patients was 28 years (range 7 – 54). Female donor to male recipient was seen in 12 cases while 20 patients had major blood group mismatch. Forty seven patients were standard risk while 17 were categorized as high risk. Bu16/Cy120 was the most common conditioning regimen given in 34 cases followed by Bu16/Cy200 in 19 cases. Fifty four patients received PBSC while BM was given in 8 cases. Grade I/II acute GVHD was seen in one-third of the cases while 7 (11%) had grade III/IV GVHD. Extensive chronic GVHD was seen in 10 (16%) cases while 12 (19%) patients had limited chronic GVHD. Complications observed were hemorrhagic cystitis (7), VOD (4), CMV infection (2) and septicemia (3). Five (8%) patients had disease relapse. The overall survival was 70.3% (median 1627 days) while disease free survival was 62.5% (median 1547 days). Nineteen patients died of various complications like extensive GVHD (n=5), septicemia (n=3), VOD (n=3), CMV infection (n=3) and disseminated aspergillosis (n==2). A significant difference was observed among patients bearing standard risk compared with those in high risk group in terms of overall survival (79% versus 47% , p=0.013), disease free survival (72% versus 35%, p=0.031) and incidence of acute GVHD (34% versus 71%, p=0.01) in univariate analysis. Age >40 year was the only factor associated with adverse outcome in multivariate Cox-regression model. Conclusions Early allogeneic HSCT in CML patients Disclosures: No relevant conflicts of interest to declare.

Allogeneic stem cell transplantation (SCT) from HLA matched sibling donor is the standard treatment option in younger patients with severe aplastic anaemia (SAA). In the current study outcome of 70 patients with SAA undergoing allogeneic SCT at our institution from July 2001 to June 2007 is presented. Median follow up time was 727 days (range 100–2187). Three patients received 2nd SCT due to graft failure or rejection so actual number of SCT in the patients was 73. Median age of the patients was 16 years (range 5–38), 55 males, and 15 females. Seventeen had major ABO mismatch while sex mismatch in the form of female donor to male patient was present in 23 cases, 7 had both major ABO and sex mismatch. Sixty four patients were CMV positive while 6 had CMV negative status. Conditioning regimens included; cyclophosphamide (Cy) 200 mg/kg with either antilymphocyte globulin (ALG) 45 mg/kg (n=33) or antithymocyte globulin (rabbit ATG) 11.25 mg/kg (n=26); Cy plus Campath 100 mg (n=6), fludarabine 150 mg/m2 plus Cy 300 mg/m2 and ATG (n=8). All patient undergoing 2nd transplant received conditioning with Cy, fludarabine and ATG. GVHD prophylaxis was given with cyclosporin (CSA) plus prednisolone (41) with or without short course of methotrexate (29). Patients received PBSC (10) or bone marrow (12) alone or both (48). Mean mononuclear and CD34+ cell doses were 5.59 x 108/Kg and 4.8 x 106/Kg respectively. Median time to neutrophil recovery was 11 days (range 7–24). Neutropenic fever was seen in 60% cases, with mean duration of fever being 8 days. In majority (66%) no focus of infection could be found. Various isolates included gram negative rods (n=6), staphylococcus (n=2) and fungi (n=5). Other post-transplant infections were tuberculosis (n=2), herpes zoster (n=2) and transfusion associated falciparum malaria (n=2). Post-BMT non-infectious complications included acute GVHD (24%), chronic GVHD (08%), hemorrhagic cystitis (14%), seizures (5%), and VOD (3%). Graft rejection and primary graft failure was seen in 3 and 2 cases respectively. Three of them received 2nd transplant and had successful recovery while the other 2 died of septicemia. Six patients died during peri-transplant period, 3 at day 100, and 8 beyond day 100. One patient died of unrelated cause at 2 years post-transplant. Main causes of death were septicemia (n=4), conditioning regimen toxicity (n=3), VOD (n=2), GVHD (n=2) and disseminated aspergillosis (n=2). The overall and disease free survival was 76%. In univariate analysis using Logrank and Wilcoxon test factors correlated with better survival were patient’s age

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 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.