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We present a case report of a 62-year-old male, treated for kappa light chain multiple myeloma with chemotherapy followed by autologous stem cell transplant (ASCT) in 2014. He has been in complete remission for 4 years. In 2018, he was evaluated for hypercreatinemia and acute kidney injury(AKI) with a suspicion of disease relapse; he underwent evaluation with bone marrow aspiration cytology which showed no evidence of relapse. However, careful cytogenetic analyses showed IgH amplification (14q32) which probably was the cause for AKI in the absence of any structural abnormality in the kidney. Heavy chain deposition leads to AKI in multiple myeloma, and its association with IgH amplification leading to AKI is reported here. Though heavy chain deposition leading to AKI is common, IgH amplification at chromosome level is the first case observed.

Chronic myeloid leukemia (CML) patients with complex chromosomal translocations as well as non-compliant CML patients often demonstrate short-lived responses and poor outcomes on the current therapeutic regimes using Imatinib and its variants. It has been derived so far that leukemic stem cells (LSCs) are responsible for Imatinib resistance and CML progression. Sonic hedgehog (Shh) signaling has been implicated in proliferation of this Imatinib-resistant CD34(+) LSCs. Our work here identifies the molecular mechanism of Shh-mediated mutation-independent Imatinib resistance that is most relevant for treating CML-variants and non-compliant patients. Our results elucidate that while Shh can impart stemness, it also upregulates expression of anti-apoptotic protein—Bcl2. It is the upregulation of Bcl2 that is involved in conferring Imatinib resistance to the CD34(+) LSCs. Sub-toxic doses of Bcl2 inhibitor or Shh inhibitor (<

Determination of the magnitude of body iron stores helps to identify individuals at risk of iron-induced organ damage in Thalassemia patients. The most direct clinical method of measuring liver iron concentration (LIC) is through chemical analysis of needle biopsy specimens. Here we present a noninvasive method for the measurement of LIC in vivo using magnetic resonance imaging (MRI). Twenty-three pediatric Thalassemia major patients undergoing bone marrow transplantation at our centre were studied. All 23 patients had MRI T2* and R2* decay time for evaluation of LIC on a 1.5 Tesla MRI system followed by liver tissue biopsy for the assessment of iron concentration using an atomic absorption spectrometry. Simultaneously, serum ferritin levels were measured by enzymatic assay. We have correlated biopsy LIC with liver T2* and serum ferritin values with liver R2*. Of the 23 patients 11 were males, the mean age was 8.3 ± 3.7 years. The study results showed a significant correlation between biopsy LIC and liver T2* MRI (r = 0.768; p

Aim: To evaluate the safety and efficacy of 10% intravenous immunoglobulin (IVIG; Flebogamma® 10% DIF) in individuals with chronic immune thrombocytopenic purpura (ITP). Patients & methods: Patients aged 3–70 years, diagnosed with chronic ITP, received 1 g/kg IVIG over two consecutive days. Results: 64 evaluable patients (51 adults, 13 children) with chronic ITP received IVIG. The primary efficacy end point (increased platelet counts from ≤20 × 109/l to ≥50 × 109/l by day 8) was achieved by 81.3% of patients; mean time to response was 1.7 days (all responders). Adverse events, mostly mild or moderate, were reported in 59 patients (92.2%). Conclusion: Flebogamma® 10% DIF administered over two consecutive days was safe and effective in adults and children with chronic ITP.

Background: It is well known that anemia and red cell turn over affects the HbA1c value. Iron deficiency anemia increases the HbA1c and haemolytic anemia lowers it. However, the cut-off of haemoglobin (Hb) or red-cell indices when the HbA1c value becomes unreliable is not known. Aim: We sought to find out values of HbA1c and red-cell indices where there is considerable discordance between HbA1c and plasma glucose (PG) values in the diagnosis of diabetes (DM) and pre-diabetes (Pre-DM) making HbA1c values unreliable. Methods: A cross-sectional study of 237 non-diabetic subjects who attended our out-patient division of preventive health check-up clinics, between November 2016 and December 2017. Data was collected only from relatively healthy subjects who had voluntarily opted for undergoing a preventative health check-up (including a diabetes screening). Patients were classified as concordant (fasting and 2-hr post meal glucose values are in agreement with HbA1c) and discordant (values are not in agreement with HbA1c). Results: A total of 237 patients (73% males) with mean age was 47.2±9.7 years (range 25-75) were included in the study. The HbA1c definition group had more diagnosis of DM (153 vs 96) and but lesser numbers of pre-DM (66 vs 102) compared to the PG group. Out of 237 patients, 133 (56%) showed concordance and 104 (44%) were discordant. The FPG, 2h-PPBG and HbA1c are significantly higher in the concordant group. The Hb value and MCV were significantly higher (p7% (20%). While no single Hb or MCV value could predict discordance, a RDW value >17 was consistently associated with discordance across all the HbA1c strata. Conclusion: A HbA1c below 7% is significantly influenced by red-cell turn over indices and clinicians need to perform additional testing using plasma glucose levels to confirm the presence of diabetes or pre-diabetes. In patients whose RDW >17, HbA1c should be replaced by 75gm OGTT as a test of choice for diagnosis of diabetes or pre-diabetes.

Background: The impact of COVID-19 pandemic has been highly heterogeneous across the globe and different regions within the country. The differences in the outcome of these patients is related to their demographic profile, genetics, socio-economic conditions, and government health policies. Prior to the COVID-19 pandemic, the Healthcare Access and Quality (HAQ) Index for hematological malignancies (HAQ index Methods: Ten tertiary referral hospitals across India reported the demographic, clinical, laboratory, treatment, and outcomes of COVID-19 infection in patients with hematological malignancies. The registry was retrospective from March 21, 2020, and prospective from November 1, 2020, till March 20, 2021. Risk factors associated with severity and mortality were evaluated using the penalised logistic regression and Cox proportional hazards model. Findings: Data from 565 patients was included in this study. Among these, 429 (76%) patients were hospitalized, 186 (33%) patients had moderate/severe COVID-19.There were 116 (20.5%) non-survivors at a mean follow up of 147 (95% CI : 142-153) days. Age >60 years (HR 2·55, 1·23 - 5·27), diagnosis of acute myeloid leukemia (HR 2·85, 1·58 - 5·13), interruption or alteration of anticancer therapy (HR 2·78, 1·65 - 4·68), and post hematopoietic cell transplant status (HR 3·68, 1·82 - 7·45) predicted mortality. In contrast, increasing age [20-40 years (OR 2·54, 1·32 - 4·90), 41-60 years (OR 3·51, 1·84 - 6·71), >60 years (OR 6·04, 3·01 - 12·10), comorbidities such as diabetes mellitus (OR 1·89, 1·18 - 3·04), hypertension (OR 1·94, 1·17 - 3·19), diagnosis of AML (OR 3·70, 2·06 - 6·67), indolent non-hodgkin lymphoma (OR 3·20, 1·68 - 6·09), multiple myeloma (OR 2·88, 1·64 - 5·05), malignancy not being in remission (OR 1·71, 1·12 - 2·60)were significantly associated with severe COVID-19 on univariate analysis. Of these, only increasing age [20-40 years (OR 2·60 (1·31 - 5·15), 40-60 years (OR 3·44, 1.60 - 7·41), more than 60 years (OR 5·70, 2·43 - 13·35)] , AML (OR 2·73, 1·45 - 5·12), and malignancy not being in remission (OR 1·85, 1·18 - 2·89) were significantly associated with severe COVID-19 on multivariable analysis Conclusion: The overall mortality from COVID-19 infection of the entire cohort was 20.5%; the mortality was 46.2% in patients who had moderate to severe disease COVID-19 illness. Similar to previous studies, age, diagnosis of acute myeloid leukemia and a post stem cell transplant status was associated with mortality. In addition, interruption or de-escalation of anticancer therapy during Covid-19 infection was identified as an important factor associated with higher mortality on follow up in the current study. References 1. Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016. Lancet (London, England)2018; 391(10136): 2236-71.Lee AJX, Purshouse K. COVID-19 and cancer registries: learning from the first peak of the SARS-CoV-2 pandemic. Br J Cancer 2021; 124(11): 1777-84. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is classed as group 4 in the present classification of pulmonary hypertension. The pathophysiology of CTEPH is complex, mainly is a consequence of prior acute pulmonary embolism with failure of thrombi to resolve and the recent recognition of added small vessel changes which impacts long-term outcomes even after surgical management. The role of thrombophilia testing in this condition has been debated. Hence, we here analyzed the utility of thrombophilia testing in CTEPH from a center in a developing country. Methods This is a single institution (Narayana Health City, Bangalore); retrospective study including patients ≥ 18 years of age who underwent thrombophilia workup in a diagnosis of CTEPH from January 2019 till July 2021. Tests done to evaluate thrombophilia included factor V Leiden; prothrombin F20210A mutation; MTHFR gene mutation; Protein C, S, and antithrombin deficiency; lupus anticoagulant, anti-beta2 glycoprotein I (IgM and IgG) and anticardiolipin antibody (IgM and IgG); hyperhomocysteinemia and anti-nuclear antibody testing (ANA-IF). The study was approved by the ethics committee of the institute and was carried out in accordance with the principles of the declaration of Helsinki. Results and discussion The study included 56 patients with a median age of 37 years (range 23-50), and 36 (64%) were males. Patients with recurrent venous thrombosis included 37 (66%), with the majority having thrombosis at 2 sites (53%; 22 patients with associated deep vein thrombosis). A family history of thrombosis was present in 4 patients. The majority of patients received vitamin K antagonists (76%), with the rest receiving direct oral anticoagulants (DOAC). Among the tests sent for acquired thrombophilia, ANA-IF and antiphospholipid antibody (APLA) were most frequently evaluated (94%). ANA-IF and APLA tests were positive in 5.6% and 30.1%, respectively. Among the APLA tests, Anti-beta2 glycoprotein I (IgM or IgG) was the most commonly detected antibody (13/46), followed by anticardiolipin antibody (IgG or IgM) (9/43) and lupus anticoagulant (7/40). Double and triple positive APLA were present in 3 and 4 patients, respectively. Homocysteine levels were high in 93.7% though only 16 patients were tested in this cohort. Among the tests for inherited thrombophilia, genetic tests (factor V Leiden, prothrombin F20210A mutation, and MTHFR gene mutation) were tested in only ~50%. Twenty-three percent were positive for heterozygous MTHFR followed by MTHFR compound heterozygous (10%) and heterozygous factor V Leiden heterozygous (10%). Antithrombin III, protein C, and S were tested in ~30% of patients. Antithrombin III was low in only 1 patient, with protein C and S assays being normal in all the patients. The cost analysis was calculated, showed a median of $364 (₹ 27,055) was spent per person on thrombophilia workup. The median cost incurred per patient for inherited thrombophilia workup was $232 (₹ 17,300) and for acquired thrombophilia was $132 (₹ 9814), respectively. Conclusion This single-institution study on thrombophilia workup in CTEPH patients reveals that APLA was the most commonly performed test with high positivity rates of 30.1%. Among the inherited thrombophilia, the positivity rate of MTHFR mutation was highest (33.3%), with other tests having a low positivity rate (0-10%). Hence, we would recommend APLA testing in all patients with CTEPH considering its high positivity and clinical utility. Testing for other thrombophilias should be pursued judiciously especially in economically restrictive settings. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The impact of ABO mismatch has been studied on various hematopoietic cell transplant (HCT) outcomes, including neutrophil and platelet engraftment, pure red cell aplasia, acute and chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), and overall survival (OS). Yet conflicting results have been reported. However, the impact of ABO mismatch on transplant outcomes with various graft types has not been carefully investigated. We analyzed the impact of various graft sources and type of ABO mismatch on transplant outcomes for 1502 patients who underwent HCT at the University of Minnesota between 2000 and 2014: 312 receiving marrow (BM), 475 filgrastim-mobilized blood (peripheral blood stem cell [PBSC]), and 715 umbilical cord blood (UCB) grafts. Neutrophil engraftment by day 28 was marginally less frequent in the bidirectional ABO mismatched transplants receiving UCB, whereas ABO matching had no influence on engraftment in the BM or PBSC cohorts. ABO mismatch led to no significant differences in platelet engraftment irrespective of stem cell source. We observed a modest but not significantly lower incidence of grades II/IV acute GVHD in the bidirectional ABO mismatched transplants in the UCB and the PBSC cohorts but not in the BM group. We found a higher incidence of chronic GVHD in the PBSC group, but it was not significantly lower in the minor ABO mismatched transplants. The incidence of chronic GVHD was similar in the major ABO mismatched transplants receiving BM. We found no significant difference in the OS and NRM between ABO matched and ABO mismatched transplants within each of the 3 graft source groups. Multivariable analysis adjusting for other relevant factors confirmed that ABO match status did not significantly influence the outcomes of either engraftment, acute or chronic GVHD or NRM. We conclude that ABO mismatch does not influence the outcomes of allogeneic HCT, regardless of stem cell source.

Introduction Multiple myeloma (MM) is a malignancy involving terminally differentiated plasma cells. Its incidence in India is about 0.7/1,00,000 population amounting to about 6,800 new cases a year A number of genomic aberrations are associated with MM, most of which confer prognostic significance. Cytogenetic abnormalities are a part of R-ISS score for prognostication which stratifies presence of del(17p), t(4;14) or t(14;16) as stage 3, mSMART is another risk stratification tool which divides MM into high risk and standard risk groups based on genetic aberrations. Hence it is evident that determining the genetic abnormality in MM is important. however, due to limited resources genetic testing is not routinely done and the data in the Indian population is limited. Objective: To estimate the prevalence of molecular cytogenetic abnormalities by Fluorescent in situ hybridization (FISH) analysis in patients with MM and to assess the co-relation with response to induction chemotherapy, relapse and overall survival. Material and Methods: 64 patients were included from January 2016 to December 2019 and followed up till June 2020. Interphase FISH study was performed either at diagnosis or at relapse, on bone marrow aspirate with panel of probes consisting of CKS1B (1q21-22), CDKN2C (1p32.3), D13S319 (13q14.2/13q34), IGH (14q32.33), p53 (17p13.1) and trisomy (5p15/9q22/15q22) (trisomies are considered as hyperdiploidy in this study). Plasma cell purification techniques were not applied prior to FISH analysis. Patients were divided into 2 risk groups; 1) high risk group with presence of del17p, del13q, amplification 1q, del1p and two or more aberrations with either of these and 2) standard risk group with presence of hyperdiploidy or no genetic abnormality. There was no difference in chemotherapy regimen between the 2 groups; 46 (71.8%) received bortezomib-thalidomide-dexamethasone, 10 (15.6%) received bortezomib-cyclophosphamide-dexamethasone, 2(3.1%) received bortezomib-lenalidomide-dexamethasone, 1(1.5%) received daratumumab-bortezomib-dexamethasone and 5(7.8%) received 2 drug chemotherapy. Patients who did not complete minimum follow up of 6 months either due to death or lost to follow up were excluded from the study. Institutional Ethics Committee's approval was taken. Results: Mean age of the population was 60.33 years and male to female ratio was 1.65. 46.87%, 28.13% and 25% of the study population were in the age group of ≤ 60, 61 - 65 and ≥66 years respectively. 12.3%, 43.8% and 43.8% were in R ISS stage 1, 2 and 3 respectively. FISH analysis was done on 61 out of 64 patients (remaining 3 were excluded due to hemodilute bone marrow sample). 22 (36.1%) patients had abnormal genetic aberration on FISH analysis with 10 (16.39%) having two or more abnormalities. The frequency of genetic aberrations was as follows; amplification 1q (13/61, 21.31%), del13q (9/61, 14.75%), hyperdiploidy (7/61, 11.47%), del17p (4/61, 6.55%), IgH rearrangement (3/61, 4.91%), and del1p (1/61, 1.6%). All 3 patients with IgH rearrangement had associated one or more high-risk genetic aberration and hence were included in high risk group. 31.1% of the patients were high risk and 68.9% were standard risk. The response to induction chemotherapy, incidence of relapse, time to 1st relapse and total number of relapses are shown in (table;1) and there was no significant difference between high risk and standard risk group. Overall survival in standard risk group at 2 and 5 years was 89.6% ± 5.8% and 78.6% ± 13.9% and in high risk group was 60.7% ± 13.2% and 29.5% ± 23.1% respectively (p value: 0.762). Overall survival was significantly lower in age group ≥66 years as compared to age group ≤ 60 years and 61 - 65 years (p value 0.001) and it was also significantly lower in R ISS stage 3 as compared to R ISS stage 1 and 2 (p value 0.006). Conclusion: More than one third patients of MM (36.1%) showed genetic abnormality, amplification 1q being the most frequent. Overall survival was significantly lower in older age group and R ISS stage 3 patients. Response to induction chemotherapy and relapse rate were similar in high and standard risk groups. Although overall survival was lower in high risk group, it was statistically not significant. This study highlights the importance of FISH analysis for disease stratification and prognostication which should be routinely practiced. Disclosures No relevant conflicts of interest to declare.

Background Allogenic hematopoietic stem cell transplantation (allo-HSCT) is one of the best therapies for acute myeloid leukemia (AML) and a proven post-remission therapy for intermediate and high-risk AML. The best HSCT source seems to be a matched sibling donor (MSD), but in the absence of one, a readily available haplo-identical donor provides an equally high cure rate. This is of relevance in a developing country like India as the cost of an unrelated donor is usually unaffordable. We present our experience from a single centre. Methods We analysed retrospective data of 122 AML patients who have undergone HSCT between Jan-2012 to Jun-2019 at our centre. Fludarabine + Busulfan or Fludarabine + Melphalan based conditioning regimen were used in MSD transplant and John Hopkins's protocol was followed in haploidentical HSCT. Cyclosporine + methotrexate was used as GVHD prophylaxis in MSD and unrelated donor group and cyclophosphamide + tacrolimus + mycophenolate was used for haploidentical post-transplant. Day 100 Survival, overall survival, incidence of GVHD and CMV reactivation was computed. Results Out of 122 patients, 69 (56.6%) were males, the mean age was 29.05±20.13 (range, 1 -74) years. Peripheral blood stem cell (99%) was the predominant graft source with majority of matched sibling donor (MSD; 54.1%) compared to Haplo-identical donors (30%). Figure 1 shows the demographic and clinical details of the study patients. The incidence of acute GVHD (40.9% vs 32.6%; p=0.372) and chronic GVHD (16.7% vs 15.2%; p=0.837) are similar in MSD and Haplo transplantation. There were 25 (38%) deaths in MSD and 23 (50%) deaths haplo-identical transplantation (p=0.245). The day-100 survival and overall survival function is significantly better in MSD transplantation (p Conclusion Our study showed comparable outcomes in MSD and Haplo-identical transplant with respect to incidence of GVHD and mortality. However, the survival function is better with MSD transplantation. Haplo-identical transplant is a feasible option in case of non-availability of MSD, due to ease of donor availability and strong motivation from the family donor to donate the stem cells.

Background Hematopoietic stem cell transplant (HSCT) is widely used as a gene replacement therapy in Thalassemia patients for decades. Survival probabilities after HSCT have increased considerably with advancements in graft versus host disease (GVHD) preventive strategies and conditioning regimens. Here we report our HSCT experience in patients with Thalassemia major, with different graft sources, in terms of transplant outcomes such as neutrophil and platelet engraftment, acute and chronic graft versus host disease (GVHD), thalassemia free survival and overall survival. Methods We analysed the data of 164 Thalassemia patients who have undergone HSCT between Jan-2012 to Jun-2019 at our centre. We evaluated the demographic and clinical characteristics of patients, graft source on the HSCT outcomes, such as engraftment, graft versus host disease, day-100 survival, thalassemia-free survival and overall survival. Results Out of 164 patients, 100 (61%) were males, the mean age was 9.47±4.41 (range, 1 -24) years. Peripheral blood stem cell (50%) and bone marrow (47%) are the respective graft sources with predominant matched sibling donor transplants (60.4%). One third of the patients received Fludarabine/Busulfan/Cyclophosphamide based conditioning regimen. Twenty-eight percent of the patients developed acute GVHD (grades I-IV) and 7.3% developed chronic GVHD. The average time to neutrophil engraftment was 14 (range, 8-24) days and platelet engraftment was 18 (range, 8-72) days. The average time to neutrophil engraftment and platelets engraftment did not significantly differ between the HLA-donor type (Figure 1). There were 26 deaths (15.9%) and 7 (4.3%) graft rejections during the follow-up. Infections are the major cause of deaths. The day 100 survival was 89%, the overall survival was 84% and the thalassemia free survival was 74.4%. Conclusion HSCT with various preparative regimens, GVHD preventive strategies, and varied graft sources is certainly a unique curative option for the Thalassemia major patients in the developing world. The survival after HSCT in Thalassemia patients are similar regardless of stem cell source, donor-HLA type (Figure 2) and GVHD (Figure 3). However, the incidence of GVHD is more with matched unrelated donors.

We performed a prospective multi-centre observational study to understand the incidence of IFI in patients with AML in India with use of anti-fungal prophylaxis. All patients with AML receiving either induction chemotherapy or salvage chemotherapy between November 2014 and February 2016 were included in this prospective observational study from 10 Indian centres. IFI was defined as per the revised EORTC-MSG criteria. Data on type of chemotherapy used, type of anti-fungal prophylaxis used, time to neutrophil recovery, incidence of IFI and survival were collected. Two hundred patients (118 male and 82 females) with a median age of 35 years (range: 2–66) were recruited. One hundred and eighty-six (93%) had newly diagnosed acute myeloid leukemia (AML) while 14 (7%) had relapsed disease. IFI occurred in 53 patients (26.5%) with proven or probable IFI occurring in 17 (8.5%). Use of posaconazole prophylaxis (p = 0.027) was the only factor found to be associated with a reduced incidence of IFI. The overall survival (OS) at 6 weeks and 3 months respectively was similar among patients who had IFI (83.0 ± 5.2%; 81.0 ± 5.4%) as compared to those without IFI (84.4 + 3.0%; 81.4 ± 3.2%). This prospective study reveals a high incidence of IFI in patients undergoing chemotherapy for AML in India. The use of posaconazole prophylaxis was associated with a significantly lower incidence of IFI. Optimal strategies to prevent IFI need to be studied.

This article summarises the main highlights of the abstracts presented at the annual meeting of American Society of Transplantation and Cellular Therapy (ASTCT). The highlights of ASTCT meeting were organised by iNDUS BMT group in Chennai, India. The purpose of the highlight meeting was to educate the students about the latest research in the field of hematopoietic stem cell transplantation and its applicability for the developing country perspective.

Aims SARS-CoV-2, an infectious agent behind the ongoing COVID-19 pandemic, induces high levels of cytokines such as IL-1, IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ etc in infected individuals that play a role in the underlying patho-physiology. Nonetheless, exact association and contribution of every cytokine towards COVID-19 pathology remains poorly understood. Delineation of the roles of cytokines during COVID-19 holds the key to efficient patient management in clinics. This study performed a comprehensive meta-analysis to establish association between induced cytokines and COVID-19 disease severity to help in prognosis and clinical care. Main methods Scientific literature was searched to identify 13 cytokines (IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-17, TNF-α and IFN-γ) from 18 clinical studies. Standardized mean difference (SMD) for selected 6 cytokines IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ between severe and non-severe COVID-19 patient groups were summarized using random effects model. A classifier was built using logistic regression model with cytokines having significant SMD as covariates. Key findings Out of the 13 cytokines, IL-6 and IL-10 showed statistically significant SMD across studies synthesized. Classifier with mean values of both IL-6 and IL-10 as covariates performed well with accuracy of ~92% that was significantly higher than accuracy reported in literature with IL-6 and IL-10 as individual covariates. Significance Simple panel proposed by us with only two cytokine markers can be used as predictors for fast diagnosis of patients with higher risk of COVID-19 disease deterioration and thus can be managed well for a favourable prognosis., COVID-19, Meta-Analysis, Cytokines, Logistic Models.

INTRODUCTION Acute Graft-versus-host disease (aGVHD) is a common complication of allogeneic hematopoietic cell transplantation (HCT), affecting about 50% of transplants. Grading of aGVHD can serve a variety of purposes, including retrospective assessment of peak severity, real-time assessment of severity at prespecified time points, and determination of the need for treatment. But several problems hamper the application of grading systems to predict outcomes among patients with aGVHD: (1) Assignment of a peak GVHD score is done retrospectively; clinicians cannot use the current grading system for peak score in real-time1. (2) The systems do not account for the time to the response after treatment1. (3) Assignment of grade IV GVHD is often used to indicate that GVHD caused a death, irrespective of the severity. In this situation, the grading reflects the outcome and cannot be used to predict the outcome1. Recently serum biomarkers have emerged as an additional potential measurement of acute GVHD severity. The Mount Sinai Acute GVHD International Consortium (MAGIC) Group, has validated MAGIC algorithm probability (MAP) that combines two GI biomarkers (ST2 and REG3α) into a single value. The MAP predicts response to treatment, GVHD severity. But in resource-limited settings, like transplant centers in India lack testing features. In this study we have developed a risk scoring based on clinical and easily available biochemical parameters to predict the severity of aGVHD. AIMS AND OBJECTIVES To predict the aGVHD severity at the onset based on risk factor score. To assess the steroid response in different risk groups MATERIAL AND METHODS The study included patients who underwent allogeneic HCT at Narayana hrudayalaya hospital, between January 2015 and April 2020 and developed acute GVHD within 100 days of transplant. After taking institutional ethics committee approval, data were collected from medical records. Baseline patient characteristics are mentioned in table 1. The following parameters were analyzed as risk factors for the development of severe GVHD (MAGIC grade 3 and 4): 1. Age >18 yrs, 2. MDR organisms in baseline stool culture, 3. HCT comorbidity index >1, 4. Peripheral blood as a source of stem cells, 5. Female to male transplants, 6. Myeloablative regimens, 7. Suboptimal GVHD prophylaxis, 8. CD34 dose > 6 x 106/kg, 9. Grade 3/4 mucositis 10. Early-onset GVHD (within 28 days), 11. Albumin level at the onset of GVHD, 12. Albumin drop from baseline3, and 13. Bloodstream infection. Risk factors with a p-value of 8). The following outcomes were assessed in each group; severity of GVHD (Grade I/II vs Grade III/IV) and response to steroids. RESULTS Out of 148 patients, 35.5% of Group 1, 56.5% of Group 2 patients and 85.5% of Group 3 patients developed Grade 3 or 4 GVHD respectively (P-value 8 to predict Grade 3/4 GVHD is 85.4%, negative predictive value is 50.6%, sensitivity is 50.5%, and specificity is 85.5%. From Group 1 and 2, only 30% of patients were steroid non responders, while 55.3% of Group 3 patients are steroid non responders (P-value - 0.04). CONCLUSION Traditional GVHD scoring systems reflect the outcome and cannot be used to predict the outcome. Various biomarker-based scoring systems are helpful in this situation, but in resource-limited settings, it might not be easily feasible. Clinical scoring systems like risk factor-based scoring systems are very helpful, which can predict the severe GVHD at early time points leading to management decisions such as upfront initiation of aggressive treatments and earlier introduction of second-line agents. References Leisenring WM, et al. An acute graft-versus-host disease activity index to predict survival after hematopoietic cell transplantation with myeloablative conditioning regimens. Blood. 2006;108(2):749-55. 2.Rashidi A, et al. Peritransplant Serum Albumin Decline Predicts Subsequent Severe Acute Graft-versus-Host Disease after Mucotoxic Myeloablative Conditioning. Biol Blood Marrow Transplant. 2016;22(6):1137-41. Disclosures No relevant conflicts of interest to declare.

BACKGROUND : Clinical Phenotype and outcomes of patients with Acute myeloid leukemia (AML) in the Indian subcontinent differs from published literature. A younger age at diagnosis and higher induction mortality complicate AML management in India(1). Metaphase Karyotyping represents the backbone of prognostication and risk stratification in AML. Optimal treatment strategies for the cohort of Cytogenetically normal AML are still under evaluation. Applications of Next generation Sequencing (NGS) techniques in AML have unravelled the genetic heterogeneity of this disease. Whole genome sequencing has identified many novel mutations leading to tremendous improvements in diagnosis and risk stratification. Development of therapies targeting these genetic alterations is enabling a gradual shift from non-specific approaches to personalised therapy tailored to an individual patient's genome. This will undoubtedly translate to better clinical outcomes for this disease, with otherwise poor prognosis. Whole genome sequencing is still in a nascent stage in Indian settings with no published literature on genomics in AML till date. We aimed to study the genomic landscape of AML in the Indian population and to co-relate this with clinical outcomes over the course of 1 year. METHODS: We recruited 34 newly diagnosed patients with AML who presented to our Centre (Mazumdar Shaw Medical Centre, Narayana Health City, Bangalore, India) between November 2017 and May 2018. Clinical and laboratory details of all patients were recorded. Bone marrow and paired peripheral blood samples were drawn before initiating therapy. Whole genome sequencing and Exome capture was done for each sample using Ilumina HiSeq platform. Patients were risk stratified as per ELN 2017 and treated as per NCCN guidelines. Patients were followed up prospectively for one year from initial diagnosis. Genetic results were stratified according to gene function and analysed with respect to predefined clinical outcomes (remission status post induction, relapse rates, progression free and overall survival). RESULTS: Amongst the 34 study participants, 5 patients failed QC during sequencing and were de-recruited. Hence 29 patients were available for final analysis. Median age of patients was 42 years with 13 patients (44.8%) less than 40 years of age.18 patients (60%) had normal cytogenetics at baseline.17 patients (58%) were classified as intermediate risk and 6 patients each as Standard and high risk, as per ELN 2017. 22 patients (79.3%) patients received standard Induction chemotherapy (3+7 regimen) while 6 patients received hypomethylating agents. Overall CR rate following induction at Day 28 was 50% and Induction mortality was 21.42%. 6 patients underwent an Allogenic Stem cell transplant. A total of 96 mutations (47 driver and 49 VUS mutations) in 123 genes were identified. The average number of Driver mutations was 1.48 per patient. IDH genes were the most frequently mutated Driver genes followed by FLT3 mutations. Frequency of NPM1 mutations was significantly low (17.25%). Highest frequency of VUS mutations was seen in the ETV6, ATM and CBLC genes. Highest frequency of somatic mutations were identified in the genes encoding for myeloid transcription factors and DNA methylation. Average driver mutations showed significant co-relation to Age (> 60 years) and high burden of Bone marrow blasts (>30%). An updated risk stratification incorporating mutation analysis findings resulted in re-stratification of 8 intermediate risk patients into high risk. 2 patients with detectable FLT3 ITD mutation by NGS were negative by PCR. Choice of consolidation therapy and Driver mutation status were found to show statistically significant association with both Event free survival and Overall survival at 1 year. Increased driver mutation burden was associated with increased refractoriness to chemotherapy and poor EFS and OS. Mutations in Tumour suppressor genes, were associated with suboptimal treatment outcomes and poor survival. CONCLUSIONS Genomic landscape of AML in Indian patients shows significant differences from published literature. This may hold clues to the differing biological characteristics of AML seen in this population. Genome based risk stratification and tailored therapy needs to be adapted into the management of AML. This data provides valuable insights into developing therapeutic strategies for Indian patients. Disclosures No relevant conflicts of interest to declare.

Heparin-induced thrombocytopenia (HIT) is a drug-induced thrombocytopenia that results in thrombotic complications rather than bleeding.In many countries like India, the availability of functional assay for diagnosing HIT is unavailable. But with the utility of scoring systems the probability of HIT can be assessed and can guide the intervention required. Presently there are two well characterised and easily calculated scoring systems, which are the commonly used 4T scoring system and newly designed HEP score, to overcome some of the limitations of 4T`s scoring system. The 4Ts score has a negative predictive value (NPV) approaching 100%, but is limited by modest positive predictive value (PPV) and significant inter-observer variability.In this study we are comparing the two scoring systems and their relevance in the Indian scenario in patients undergoing cardiac intervention, receiving heparin. METHODS: - We recruited 100 patients with suspected HIT, for whom antibody testing was orderedat our centre (Narayana Health City, Bangalore, India) between November 2017 and May 2018. - Data were collected at baseline diagnosis in the form of clinical and laboratory data. 4T`s score and the HEP score was calculated based on the above details before the availability of antibody test. - HIT antibody testing was done using ID-PaGIA Heparin/pF4 Antibody Test Kit with control. In this 10 millilitre of serum is pippeted into the upper chamber of the appropriate microtube. Incubate the ID card at room temperature for 5mins at room temperature (18-25oc). Later centrifuge the ID-card for 10mins in the ID-centrifuge then read and records the results. - Patients were followed up daily till the discharge and complete blood picture including WBC count, development of any adverse effects including renal failure, sepsis, intra-arterial device insertion, bleeding was noted. - Area under the curve (AUC) for the receiver operating curve (ROC) of HEP and 4T scores was calculated and p value was obtained based on these curves. RESULTS: - 37 patients were HIT antibody positive out of 100 patients with suspected HIT from a patient population of 26430, who received heparin. The overall incidence of HIT in our institute is 0.14% (37/26430). - Out of the 100 suspected patients 37 were proven to have HIT by using ID-PaGIA Heparin/PF4 rapid gel agglutination assay. In this series, 91% patients had undergone cardiothoracic surgery forming the majority. Two-thirds of the study population was in the age group (41-70years). Males (61%) are more in the study than females (39%).The percentage of HIT positivity was more in females (43.5) than males (32.7%). - In 87 patients who received UFH, who presented with thrombocytopenia during their perioperative period, 30 were proven to have HIT (34.4%).We also observed during that the total leucocyte count at the nadir of platelet was higher in thr HIT positive group. However, it was not statistically significant (p-0.283) - Out of 100 patients with suspected HIT 49% expired. Of the 37 cases proven to have HIT 20 patients expired (54%). There was no statistically significant association between the occurrence of HIT and mortality ( p-value =0.438). - In this study, the areas under the curve for predicting HIT by 4T score was more than HEP score (0.754 and 0.66) with P value-0.093. As the HEP score was not superior to 4T score we have evaluated 2 subgroup analysis. - Among 36 subjects with the intra-arterial device (included in HEP score), 12 were positive for HIT (33.3%). Area under the Curve for the 4T score (0.698) was higher than that for HEP score (0.599) although the difference was not statistically significant(p-0.3906) - In this study, the incidence of renal replacement therapy (not included in HEP score)was 43%. In this patient population, 46% (n=20) are HIT positive. Among subjects on RRT, 4T score (814) had higher Area under the curve compared to HEP score (0.607) in the diagnosis of HIT positivity and the difference was statistically significant (p value 0.035). CONCLUSION The newly diagnosed HEP scoring system, which includes additional causes of thrombocytopenia was not superior to the 4T's score in this study. The inclusion of intra-arterial device in the HEP score did not make a difference in prediction of HIT. Conversely the 4T score was superior to HEP score in the evaluation of the subset of patients on renal replacement therapy, a significant cause of thrombocytopenia, which was not included in the scoring system. Disclosures No relevant conflicts of interest to declare.

Summary Background For patients who do not have a suitable human leukocyte antigen (HLA)-matched family donor, unrelated donor registries of adult volunteers and banked umbilical cord blood (UCB) units provide the potential for successful haemopoietic stem-cell transplantation. The size and genetic composition of such registries determines the proportion of patients who will be able to find a suitable match. We aimed to assess the proportion of positive matches for Indian patients. Methods Using HLA data from ten existing donor and UCB registries and clinical transplant centres in India, we built population-based genetic models for 14 Indian regions to model Indian registry growth to predict the likelihood of identifying a suitable donor—either an adult donor or UCB—for Indian patients. We computed ranking tables of the top ten haplotypes in each regional group and compared these with four US samples from the National Marrow Donor Program (NMDP) registry. Findings The mean proportion of individuals who would have a 10/10 adult donor match within India ranged from 14·4% with a registry size of 25 000 to 60·6% with a registry size of 1 000 000. Only when donor registries increased to 250 000 did the match rate within India exceed that found by searching the US-NMDP registry combined with an Indian registry of 25 000 donors. The proportion of matches increased logarithmically with increased registry size ( R 2 =0·993). For a UCB registry size of 25 000, 96·4% of individuals would find a 4/6 match; however, only 18·3% would have a 6/6 match. Interpretation Serial match modelling and follow-up comparisons can identify the relative and progressively greater value of an India-based donor registry and UCB banking network to serve the Indian population. Understanding regional HLA haplotype diversity could guide registry growth and maximise benefit to patients. Similar modelling could guide planning for the needs of other ethnically distinct populations. Funding University of Minnesota and the Indian Council for Medical Research.

Management of acute myeloid leukemia (AML) in India remains a challenge. A major constraint is the cost of therapy. In a predominantly self paying system the majority of patients will not have the resources to manage a subsequent relapse. Hence, the choice of consolidation therapy has to be carefully considered to balance cost and efficacy. An allogeneic SCT (alloSCT) with a reduced intensity conditioning regimen (RIC) in first remission (CR1) is an attractive option to fulfill these requirements of relatively low cost without compromising efficacy. The need for consolidation chemotherapy prior to offering a RIC alloSCT for AML CR1 remains controversial. To evaluate these aspects we undertook a retrospective analysis of patients with AML CR1 who received a RIC alloSCT from multiple centers in India. Conventional criteria were used for definition of conditioning regimens to be considered RIC (CIBMTR). Data from 8 centers in India was collected between 2005 and 2013. A total of 138 patients fulfilled the criteria of AML CR1 having received an alloSCT with a RIC regimen. The median age was 34 years (range: 2 – 63) and 60% were males. The median time from diagnosis of AML to transplant was 99 days (range: 41 – 504). 123 (89%) were HLA matched related donors, 3 (2.1%) were MUD transplants and the rest were HLA mismatched related donors. The majority by cytogenetics (n=115) were intermediate risk (76%) followed by high risk (23%). 70 (51%) received chemotherapy consolidation prior to transplant, 61 (44%) did not and data was not available in 7 (5%). 68% of those that received consolidation received intermediate or low dose cytosine based regimens. 129 (94%) were CMV serology positive pre-transplant. Fludarabine with melphalan (140mg/m2) (128{93%}) was the most commonly used regimen and cyclosporine with short course low dose methotrexate (126{91%}) the most commonly used GVHD prophylaxis regime. All patients received a PBSC graft with a median CD34 cell dose of 9.1x106/kg (range: 1.3 – 43). With the exception of one, all patients engrafted. The median time to ANC >500/mm3 was 13 days (range: 7 – 22) and platelet count of >20,000/mm3 was 15 days (range: 0-33). Of those that engrafted, 97% achieved complete chimerism at one month post transplant (data not available in 4). Post transplant CMV reactivation was seen in 32% and a fungal infection (possible, probable or definitive) in 13%. Acute GVHD Grade 2-4 was seen in 29% and of patients evaluated 62% had chronic GVHD, the majority of these being limited (61%). The 100 day treatment related mortality (TRM) was 7.5% and the one year TRM was 25.6%. At a median follow up of 24 months the 5 year EFS and OS was 64.0±5.07 (Figure 1A) and 71.1±4.0 respectively. The 5 year cumulative incidence of relapse was 21.8% (Figure 1A). The baseline characteristics as mentioned above were not significantly different between the group that received consolidation and the group that did not. The use of consolidation therapy prior to alloSCT did not have a significant impact on EFS or OS (Figure 1B). On univariate analysis the factors that adversely impacted EFS were mismatched non sibling family donor (RR 8.1; P-value 0.001), CMV reactivation (RR 2.6; P-value 0.001), fungal infection post transplant (RR 6.8; P-value 0.000) and acute GVHD (RR 2.1; P-value 0.02). On a forward stepwise multivariate analysis adjusting for these and other conventional risk factors only CMV reactivation (RR 2.0; 95% CI 1.03-3.87; P-value 0.042) and fungal infection (RR 7.1; 95%CI 3.154-16.12; P-value 0.000) retained their adverse impact. There was no correlation between CMV reactivation and relapse of disease post transplant. The mean costs of induction chemotherapy for these patients was US$ 9239±3596 (n=74), for consolidation chemotherapy it was 5007±3490 (n=21) and for alloSCT it was 18138±13826 (n=118; costing up to 1 year post transplant). Induction chemotherapy followed by HLA matched RIC alloSCT is likely to be a cost effective and affordable treatment option for young adults with AML in CR1in an Indian context. With an average gross net income in India of US$3500/year (http://indiabudget.nic.in) the limitation still remains the cost of treatment and number of centers that can offer this therapy. Figure 1 Figure 1. Disclosures Srivastava: Octapharma: Consultancy, Other. Off Label Use: Bortezomib in the treatment of acute promyelocytic leukemia.

In spite of the modern day innovations, managing severe Haemophilia patients with inhibitors continues to be a challenge. The management of patients with severe haemophilia with inhibitors who are undergoing major surgeries like open heart surgery is technically demanding, fraught with peri-operative complications and needs a multidisciplinary approach. We describe a young man with severe haemophilia with low titre inhibitors who underwent a successful open heart surgery and aortic valve replacement, supported only with bolus doses of Factor VIII and tranexamic acid without any complications.

To confirm the safety and efficacy of an indigenous equine antithymocyte globulin (eATG) along with cyclosporine in Indian subjects with acquired aplastic anaemia. Subjects >2 years old with acquired aplastic anaemia were enrolled at six hospitals between April 2011 and February 2013, after approval from respective Ethics Committees. Equine ATG at a dose of 40 mg/kg/day was infused for 4 days. Efficacy analysis defined a priori, was in subjects, who had completed eATG treatment and followed-up on day 90 and/or 180. Complete response (CR) was defined as—transfusion independent, haemoglobin ≥11 g/dL, absolute neutrophil count (ANC) >1.5 109/L and platelet ≥150 109/L; partial response (PR) was transfusion independent, haemoglobin ≥8 g/dL, ANC >0.5 109/L and platelet ≥20 109/L; non responders were transfusion dependent. Lymphocyte subsets (CD 2, 3, 4 and 8) in the blood were tested on days 0 (pre eATG infusion), 3, 5, 7, 14 and 21 after eATG. Of the 30 subjects (two children

Acquired haemophilia is a very rare condition, occurring in less than 2 per million populations. This condition is caused commonly by acquired antibodies against factor VIII and rarely by antibodies against factor IX. Here we describe an extremely rare presentation of idiopathic acquired haemophilia in an otherwise healthy male patient, caused by simultaneous occurrence of circulating antibodies against both factor VIII and IX.

Acquired Aplastic anemia (AA) is a bone marrow failure syndrome characterized by pancytopenia and marrow hypoplasia, and is mediated by immune destruction of hematopoietic stem cells. Mutations in several genes including telomerase, a ribonucleoprotein enzyme complex, consisting of a reverse transcriptase enzyme (TERT), an RNA template (TERC), and several stabilizing proteins, and the associated shelterin complexes have been found in both congenital and idiopathic AA. In particular, several TERT and TERC mutations reduce telomerase activity in vitro and accelerate telomere attrition in vivo. Shortened telomeres have been observed in a third of idiopathic AA patients, but only 10% of these patients have mutations in genes of the telomerase complex. We have recently demonstrated that in addition to keeping telomeres from shortening, telomerase directly regulates transcriptional programs of developmentally relevant genes (Ghosh et al, Nat Cell Biol, 2012, 14, 1270). We postulate that changes in expression of telomerase associated genes, specifically TERT, contribute to the etiology of aplastic anemia. In an effort to better understand the molecular and clinical correlates of this disease, 24 idiopathic AA patient samples were collected at a tertiary medical center in Bangalore, India. Following informed consent, we performed RT-PCR analysis on harvested RNA from each patient and measured levels of TERT expression compared to that of normal controls (n=6). An 8 fold reduction in TERT expression was observed in 17/24 patients, while 7/24 patients maintained normal TERT expression. In general, TERT-low patients were younger in age (mean age 29y) compared with the TERT-normal patients (mean age 40y). TERT-low patients were more likely to have severe aplastic anemia (SAA) leading to higher mortality and poorer response to therapy, with 6/17 patients dying and 4/17 not responding to ATG therapy. Targeted panel sequencing of the 24 samples on an Illumina platform revealed that while TERT-normal patients had no mutations in genes associated with the telomerase/shelterin complex, TERT-low patients carried predicted pathogenic variants in TERT, TEP1, TINF2, NBN, TPP1, HSP90A and POT1 genes, all associated with the telomerase complex. Somatic gene variants were also identified in other AA associated genes, PRF1 and CDAN1, in the TERT-low cohort. In addition, novel predicted pathogenic mutations associated with the shelterin complex were found in two TERT-low patients in the TNKS gene. We also detected mutations in TET2, BCORL1, FLT-3, MLP and BRAF genes in TERT-low patients. Mutations in these genes are associated with clonal evolution, disease progression and poor prognosis. Our observations were further illustrated in a single patient where normal TERT expression was noted at initial clinical presentation. ATG therapy led to CR, but the patient returned within a year and succumbed to E.coli related sepsis. At that stage he had low TERT expression, suggesting that TERT expression can change as the disease progresses. Taken together, our data support the hypothesis that loss of TERT expression correlates with disease severity and poor prognosis. Our observations further suggest that preliminary and periodic evaluation of TERT expression levels in AA patients is likely to serve as a predictor of disease severity and influence the choice of therapy. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION EGFR (epidermal growth factor receptor) is important for the proliferation of stem cells across the body including the hematopoietic niche. However, the role of EGFR in aplastic anemia and subsequent responses to standard-of-care therapy is unknown.TWIST is a basic helix-loop-helix transcription factor recently found to regulate the hematopoietic stem cell (HSC) niche. The HSC niche is important for treatment of aplastic anemia. Telomerase and associated gene mutations have been reported in aplastic anemia, but these mutations are not present in all subjects and hence the cellular mechanisms of therapeutic responses observed is not explained by deregulated telomerase or associated genes. OBJECTIVE: To investigate the utility of measuring gene expression levels of EGFR and TWIST on the clinical response to immunosuppressive therapy in acquired Aplastic anemia patients without mutations in telomerase gene. METHODS: This was a single institution analysis of patients with acquired Aplastic anemia, in the age group of 16 to 60 years, who were treated with immunosuppressive therapy between June 2014 to December 2015. 15 patients who did not have homozygous TERT (telomerase catalytic subunit) or DKC (Dyskeratosiscongenita) mutations as determined by sequencing were included in this study. Diagnosis of Aplastic anemia was established with bone marrow aspiration and biopsy with normal cytogenetics. PNH was ruled out in all patients. 7 patients had very severe aplasticanemia (VSAA) and 8 had severe aplastic anemia. There were 11 males and 4 females.Following informed consent, we performed RT-PCR analysis on harvested RNA from each patient and measured levels of TWIST and EGFR expression compared to that of normal samples (n=6).15 patients underwent immunosuppressive therapy with horse ATG at 40mg/kg/day for 4 days followed by oral cyclosporine for at least 3 months. Clinical response was assessed at 3 months and 6 months post ATG administration. Total RNA from healthy donors (6) were used to establish normal baseline gene expression values. RESULTS: Out of the 15 patients that received ATG infusion, 10 patients (66%) had an 8-fold reduced expression of EGFR and TWIST compared to normal control. We grouped the study subjectsintoEGFR/TWIST-low (C1) and EGFR/TWIST-normal(C2). C1 subjects were younger in age (average age 29) compared with C2 (average age 40) andwere more likely to be diagnosed with a more severe form of the disease (VSAA). In the C1 group, all patients responded well to treatment with 4 (80%) patients achieving CR and 1 patient achieving a partial response. In C2, 8 (80%) patients showed no response, with 2 patients showing a partial response at the end of 6 months. CONCLUSION: Our data suggests that EGFR and TWIST may have significant impact on the ability of the hematopoietic stem cell niche to respond to immunosuppressive therapy in aplastic anemia, particularly in the absence of telomerase mutations. Therefore, low expression levels of EGFR/TWIST at diagnosis in may be useful in predicting response to immunosupressive therapy and thereby influence treatment decisions in aplastic anemia patients. Disclosures No relevant conflicts of interest to declare.

Granulocytic sarcoma in a patient with acute promyelocytic leukemia (APML) has been described often in the relapse setting, however primary presentation of APML as granulocytic sarcoma is rare. We present a case of a 29 year old male who was evaluated for thrombocytopenia with haematochezia and a diagnosis of acute promyelocytic leukemia was established after the colonic biopsy was reported as a granulocytic sarcoma.

Introduction: Allogeneic stem cell transplantation (SCT) is the only curative therapy currently available for patients with thalassemia major (TM). In developing countries, the significant delay that often occurs between diagnosis and SCT for a variety of reasons and the inadequate transfusion-chelation that most patients can access, leads to greater liver damage and advanced risk status for SCT in most of these patients. This study was therefore aimed at evaluating the outcome of SCT among a large cohort of these patients in India. Methodology: Data on the clinical profile and outcome after allogeneic SCT carried out for patients with TM was collected from the participating centers. All patients transplanted between January 2000 and June 2014 with matched related (MRD) or unrelated donors (MUD) were included in the analysis. Conditioning regimen was based on Bu/Cy (busulfan and cyclophosphamide, ± ATG) or Treo/Thio/Flu (treosulfan, thiotepa and fludarabine) in the vast majority of patients. Graft versus host disease (GVHD) prophylaxis consisted predominantly of cyclosporine and short course methotrexate. Data was collected from prospectively maintained standardized institutional individual medical records and analyzed with the SPSS software version 16.0 Results: Five hundred and ninety six patients [356 males and 240 females] with a median age of 7 years (range: 1 - 25) underwent allogeneic SCT during the study period. There were 560 (94.0%) children aged ≤ 15 years, while 36 (6.0%) were aged >15 years at the time of SCT. Majority of the patients belonged to Pesaro class 3 (n=310; 52.0%), while 219 to class 2 (36.7%) and 67 to class 1 (11.2%). Among the 226/310 patients in Class 3, 126 (55.8%) belonged to the Vellore high risk category (age >7 years and liver size >5cms). Conditioning regimen was based on Bu/Cy (±ATG) in 315 patients (52.9%) while in 278 (46.6%) patients it was based on Treo/Thio/Flu. There was a MRD for 564 patients (94.6%) while 32 (5.4%) received the graft from MUDs. Of the total of 596 patients, 568 (95.3%) engrafted by day +28. 22 patients (3.6%) had early mortality by day +15, 23 (3.9%) more by day +28, and another 50 (8.4%) by day +100. Graft rejection was noted in a total of 38 patients (6.4%), 6 of whom were before day +28. The overall incidence of acute GVHD was 195/568 (34.3%) with grade II-IV in 25.2% (n=143) and grade III-IV was seen in 9.2% (n=52). Chronic GVHD, which was limited in most patients, was seen in 91/501 patients (18.2%) of evaluable patients. At a mean follow up of 11 years (range: 0 -14 years), the overall survival (OS) and event free survival (EFS) for the entire group are 78.9%±1.9% and 72.8%±2.1%. A total of 119 (19.9%) of patients expired - 58 (48.7%) of whom were due to infections while regimen related toxicity lead to death in 23 (19.3%), GVHD in 10 (8.4%) and 28 (23.5%) died due to other causes. The OS and EFS for the different risk categories were the following: class 1 (95.5%±2.5%, 92.5%±3.2%), class 2 (82.0%±2.6%, 75.9%±2.9%) and class 3 (72.5%±3.6%, 65.6%±3.6%), (p=0.001 and p=0.000, respectively). The OS and EFS among those with grade II to IV GVHD was 76.1%±3.6 and 75.4±3.6% while among those with grade III/IV GVHD was 40.4%±6.8, respectively. We compared the outcome in patients who received Bu/Cy based conditioning (n=315; 52.9%) with those receiving Treo/Thio/Flu based conditioning (n=278; 46.6%). In terms of their baseline characteristics, there were greater number of older and class 3 patients in the latter group. (Table 1) While the OS was comparable in the two groups, the EFS was higher among those receiving Treo/Thio/Flu with Class 3 disease (72.3±3.2% vs 58.8±4.9%; p=0.045). (Fig.1) This result was more pronounced among those with Vellore high risk class 3 disease (70.6%±5.0% vs 46.3±7.6%; p=0.010). (Fig.2) Conclusion: The majority of patients with thalassemia major undergoing SCT in India are in the higher risk categories. The overall outcome of SCT among these patients is comparable with those reported in the literature. Treosulfan based conditioning regimen has improved outcome significantly among the high risk patients. Table 1. Bu/Cy(n=315)N (%) Treo/Thio/Flu(n=278)N (%) P value Age 15 309 (98.1)6 (1.9) 248 (89.2)30 (10.8) 0.000 Risk groupClass 1Class 2Class 3 35 (11.1)164 (52.1)116 (36.8) 32 (11.5)54 (19.4)192 (69.1) 0.000 Class 3 HRClass 3 LR 43 (57.3)32 (42.7) 82 (54.7)68 (45.3) 0.776 Disclosures No relevant conflicts of interest to declare.

Introduction: Allogeneic stem cell transplantation (SCT) is the best form of therapy for a young patient (< 50 years) with severe aplastic anaemia. In developing countries, there is a big time interval between diagnosis and SCT leading to increased transfusions and increased risk of infections, both of which adversely affects transplant outcome. This retrospective analysis is aimed at studying the outcomes of SCT among Indian patients with aplastic anaemia. Methodology: The Indian Stem cell transplant registry (ISCTR) is a group of transplant physicians representing about 30 active transplant centres in India. This retrospective analysis was done on data reported on 634 patients by 20 centres who reported outcomes of SCT for aplastic anaemia. Data was collected from individual medical records and databases. Analysis was done using SPSS software version 16.0 Results: Six hundred and thirty four patients [445 males and 189 females] with a median age of 21 years (range: 2 - 65) underwent allogeneic SCT between 1990 and March 2015. There were 209 children (age < 15 years). The median time from diagnosis to SCT was 5 months (range: 1 - 120) while the median number of transfusions was 20 (range: 1 - 150). All donors were HLA identical sibling or family donors; matched unrelated and haplo-identical donor transplants were excluded from this analysis. Conditioning regimen was Cyclophosphamide based (Cy/ Cy+ ATG/ Cy+ TBI/TLI) in 78 patients (12.3%) while majority received Fludarabine with Cyclophosphamide (n = 481; 75.8%) and 75 received other conditioning regimens (Flu/TBI, Flu/Bu, Bu/Cy etc). Graft source was bone marrow [BM] in 124 (19.5%) and peripheral blood stem cells in 510 patients (80.5%). Graft versus host disease (GVHD) prophylaxis predominantly consisted of Cyclosporine and methotrexate in 543 patients (85.6%). Engraftment was seen in 572 patients (90.4%) while 19 (2.9%) had primary graft failure and 43 (6.7%) expired prior to engraftment due to infection or bleeding. The median time to neutrophil engraftment was 13 days (range: 8 - 21) while platelet engraftment occurred at 13 days (range: 5 - 37). Grade II - IV acute GVHD occurred in 29.3% while grade III-IV was seen in 14.1%. Chronic GVHD was seen in 41% of evaluable patients which was limited in most patients. At a median follow up of 43 months (range: 1 - 264), 431 patients are alive. The 5 yr OS for the entire group is 66.3 + 2.0%. The OS was higher in children compared to adults (73.4 + 3.3% vs 62.8 + 2.5%; p = 0.006), better for Flu/Cy compared to Cy based conditioning (69.8 + 2.2% vs 57.8 + 5.6%; p = 0.002) and better for PBSC compared to BM (68.9 + 2.2% vs 56.1 + 4.8%; p = 0.020). There has been significant improvement in outcomes over the past 15 years [3 yr OS of 41.9 + 1.3% for 1984-1995, 40.9 + 1.2% for 1996-2000, 70.6 + 5.0% for 2001 -2005, 70.3 + 3.1% for 2006-2010 and 68.8 + 3.0% from 2011 onwards]. Conclusion: Outcomes of patients with aplastic anaemia are improving and patients have a 70% chance of getting cured with a HLA identical sibling donor transplant. The use of PBSC as graft source is not associated with inferior outcomes. Disclosures No relevant conflicts of interest to declare.

Mast cell disease (MCD) is a clonal disorder of the mast cell and its precursor cells. Cardiac surgery in MCD is rarely described. We report an unusual case of a 14-year-old girl who was admitted for atrial septal defect closure and incidentally found to have hepatosplenomegaly with lymphadenopathy who underwent a successful open-heart surgery, after a diagnosis of MCD.

Data on 90 patients (55 adults and 35 children) with chronic idiopathic thrombocytopenic purpura (ITP) and a platelet count of

Major ABO incompatibility in stem cell transplant recipients has been associated with pure red cell aplasia (PRCA). Reduction of incompatible isohaemagglutinin titres pre-transplant by various methods has been thought to reduce the incidence of PRCA. Our data suggest that pre-transplant reduction of incompatible isohaemagglutinin titres by donor group plasma infusion does not reduce the incidence of PRCA. We also failed to find any relationship between pre-transplant ABO isohaemagglutinin titre and the risk of developing PRCA.

Iron deficiency anemia is the commonest cause of anemia in the developing countries. Iron status is the result of the balance between the rate of erythropoiesis and the amount of iron stored in the body. Various biochemical parameters have been used to assess iron status such as iron levels, transferrin, transferrin saturation and ferritin, and all of them may be influenced by acute phase response and are also expensive tests 1–4. In our situation where patients cannot afford exhaustive tests to document iron deficiency we utilized the LHD values as a predictor of iron status based on the formula provided by Urrechaga 5.

Introduction: The thalassemias are the most common of the inherited abnormalities of hemoglobin, typically characterized by a quantitative defect in the synthesis of either the alpha or beta globin chain, resulting in reduced or absent synthesis of either of the globin chains followed by ineffective erythropoiesis with hemolysis. Beta thalassemia is prevalent in the populations of the Mediterranean region, the Middle East, India, Pakistan, and Southeast Asia. Patients are treated with red blood cell transfusions and iron chelation to prevent organ iron overload. Currently, the only cure for thalassemia is allogeneic bone marrow transplantation which corrects the genetic defect in the hematopoietic system by the use of allogeneic stem cells. Methods: We retrospectively and prospectively analyzed the outcomes in transfusion dependant beta Thalassemia patients, who underwent allogeneic HSCT between June 2004 and June 2014. The patients were classified into Class 1, 2 and 3 as per the Pesaro criteria. Results: Sixty seven patients (Males n=40; females n=27) with a median age of 7 years (range 2 to 22 years) underwent HSCT during this time. Fifty seven patients were classified as Class 2, 8 as Class 3 and 2 as Class 1. The conditioning regimens used consisted of Bu-Cy-ATG (n=30), Bu-Cy (n=2), Flu-Bu-Cy-ATG (n=23), Treo-Flu-Thio (n=8), Treo-Flu-Thio-ATG(n=3) and Flu-Bu-Cy-Thio-ATG(n=1) with cyclosporine and methotrexate as GVHD prophylaxis. Stem cell source was marrow, peripheral stem cells and cord in 50, 17 and 1 patients respectively. Sixty four patients had matched sibling transplant and three non-sibling donors (one unrelated cord, one matched unrelated and one haplo-identical ). One patient received both both marrow as well as peripheral stem cells. The median TC cell dose was 6.4x108/kg (range 3 to 16.3 x108/kg) and median CD34 cell dose of 2.4 x106/kg (range 0.6 to 19.6 x106/kg). Hematological recovery was seen in all patients except three patients, who died before engraftment. Neutrophil and platelet engraftment occurred at a median of 14 days (range, 10-22 days) and 22 days (range, 10-35 days), respectively. Twenty four patients developed veno-occlusive disease, 20 patients developed Gr II-IV acute graft-versus-host disease (GVHD), and 3 patients had chronic GVHD. At day +28, thirty five patients showed more than 90% donor chimersim and rest had mixed chimerism. Four patients experienced graft rejection. Treatment-related mortality (TRM) for the whole cohort was 10.4% at 100 days and 14.9% at 6 months post transplant. TRM was 12.28% and 37.5% for Class 2 and class 3 patients respectively. At a median follow up of 416 days, overall survival and thalassemia free survival are 82.1%, and 74.6% respectively. Conclusion: Similar outcomes have been reported from developed countries. Outcome of Class 3 patients still continues to be poor and VOD rates are high in this patient group. Disclosures No relevant conflicts of interest to declare.

To better plan recruitment of volunteer adult unrelated donors for a registry and umbilical cord blood donations for cord banks to supply grafts for hematopoietic cell transplantation to serve Indian transplant candidate patients, we analyzed existing HLA typing data to estimate Indian national and regional populations’ HLA haplotype frequencies. Indian BMT centers, renal transplant centers, adult donor registries and cord blood banks collaborated to collect HLA typing and demographic data. We have produced a catalogue of the frequency, and regional diversity, of HLA haplotypes in the Indian population. Haplotype frequency analysis was performed on the registry datasets (N=26,239) using a maximum-likelihood method capable of providing high-resolution estimates from typing data with ambiguities. These frequencies were generated for 20 regional subgroups into cohorts defined by either geographic state or by native language; and the 14 largest groups were used to develop a computational model of match rates. Patient family typing data was used to set phase for a group of N=485 patients that was used to run searches against the NMDP registry. The match rates for Indian patients searching the NMDP USA database (over 11 million donors including DKMS) were 39.7% at the 8/8 allele level (A, B, C, DRB1 high-resolution) and 92.2% at the 7/8 level. Matching models for patients (averaged across the 14 regional subgroups) showed a match rate within India at the current registry sizes of 13.7% at the 8/8 level and 38.2% at the 7/8 level. Increasing the registry to 1,000,000 would raise this to 55.0% for 8/8 and 84.1% for 7/8. A cord blood inventory of 50,000 units would provide a match rate of 22.2% at the 6/6 level and 78.9% at the 5/6 level. Increasing to a cord blood inventory of 250,000 units would increase these match rates to 42.5% at the 6/6 level and 90.3% at the 5/6 level. These data will define the needs and serve as critical planning data to define and direct donor recruitment goals to establish an effective Donor Registry and cord blood banking facilities able to serve the needs of Indian patients who could benefit from the curative potential of transplantation. Developed data will be shared with the broader scientific community to facilitate future studies of HLA in areas such as disease association, anthropology and transplantation. Disclosures: Joshi: Manipal Hospital, Bangalore: Employment. Damodar:NARAYAN HRUDAYALAYA: Employment. Cereb:Histogenetics: Employment. Young Yang:Histogenetics: Employment. Dedhia:Marrow Donor Registry (India): Employment.