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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.

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.

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.

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.

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.

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 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.

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.