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Objectives: Translocation (8;21) is a RUNX1-RUNX1T1 fusion transcript, a favorable risk cytogenetic abnormality with a variable clinicopathological profile. However, there is a paucity of data on the outcomes of acute myeloid leukemia (AML) with t(8;21) from East India. This report is an analysis of data of AML with t(8;21) at our center. Material and Methods: De novo AML patients with the presence of t(8;21) cytogenetic abnormality from 2015 to 2019 were analyzed for clinical, pathological, and molecular characteristics and were compared with treatment outcomes. Relapse-free survival (RFS) and overall survival (OS) were determined using Kaplan–Meier curves. Results: Twenty-nine patients (10%) with de novo AML had t(8;21) with 18 male patients and a median age of 20 years. Aberrant expression of CD19, CD56, and CD7 expressions was noted in 44.8%, 17.24%, and 10.29% of patients, respectively. Additional cytogenetic abnormality was observed in 31.03%. CD19 had an 80% correlation with the occurrence of C-kit status. High-dose induction therapy had complete remission rates of 100%. The median duration of follow-up was 287.5 days. The presence of myeloid sarcoma (MS) and C-kit positivity had inferior OS and RFS (P < 0.05). The dose of cytosine arabinoside, given in consolidation of 3 g/m2 and 1.5 g/m2, had a median OS of 758 and 479 days (P = 0.661) and median RFS of 348 and 150 days (P = 0.002), respectively. In the group that received intensive therapy, by the end of 3 years, only 15.7% of patients remain in remission. Conclusion: AML with t(8;21) is seen in young patients with a positive correlation between CD 19 with C-kit positivity. The presence of MS and C-kit positivity endowed inferior OS and RFS. Cytosine arabinoside consolidation in a dose of 3 g/m2 offered an advantage in median RFS.

Objectives: Myelodysplastic syndrome (MDS) is a group of myeloid neoplasms. The clinical manifestations and treatments vary depending on the subtype and risk stratification of the disease. There is a paucity of data on Indian patients with MDS. This study was undertaken to understand MDS with regard to their clinical presentation, pathological, cytogenetic profiles and also to assess their therapeutic outcomes and prognosis from our center in Eastern India. Materials and Methods: This is a prospective observational study conducted in the department of hematology at a tertiary care teaching hospital from eastern part of India. The diagnosis of MDS was made from the peripheral blood examination, bone marrow aspirate examination, cytogenetics, and Fluorescence in situ hybridization results, according to the WHO guidelines. Patients were risk stratified using Revised International Prognostic Scoring System (R-IPSS) and subsequent therapeutic planning was done, with either supportive therapy in the form of recombinant human erythropoiesis stimulating agents, colony stimulating factors, packed red blood cell support as needed for low risk MDS patients. High risk patients were treated with hypomethylating agents such as Azacytidine, Decitabine, or Lenalidomide. Results: The mean duration of follow-up of patients with MDS from the point of diagnosis was 1.8 years (range 4 months–6 years). The median OS was 1.33 years. The median OS in the analysis of our patient cohort with low, intermediate, high, and very high R-IPSS was 1.67 years, 1.33 years, 1.67 years, and 1.67 years, respectively. No patients of very low risk group were identified in our study. Conclusion: Our findings reflect that MDS-MLD with low or intermediate R-IPSS risk groups is the most common types of MDS. Although supportive therapy was used to treat patients irrespective of other therapy given (depending on the risk group of the patient), it was used alone even in higher risk groups due to logistic reasons in some cases. Those patients who received supportive care alone also had a good survival duration. However, a longer follow-up duration is required to firmly establish this outcome. The median age of patients (55 years) was also lower than established studies with a median overall survival of 1.67 years.

Objectives: To describe the case series of patients with myeloid sarcoma with their clinicopathological characteristics, cytogenetics, molecular markers, prognosis, and outcome. Material and Methods: Retrospective retrieval of data of myeloid sarcoma cases in acute myeloid leukemia was done from the electronic health records of our hospital and this case series includes the data of three years starting from January 2018 and the follow-up information was assimilated until December 2020. Results: We present twelve patients in this case series with myeloid sarcoma and all these patients had bone marrow involvement at presentation. Most of the cases were less than 20 years of age and orbit (66.7%) was the commonest site of presentation in this series. Aberrant CD 19 expression on immunophenotyping was a common associate (66.9%) and t(8;21) was the commonest cytogenetic abnormality reported in our case series. Despite of high dose intensive therapy with daunorubicin and cytarabine followed by high-dose cytarabine (HiDAC) consolidation, patients had a median relapse-free survival and median overall survival of 160 days and 299.5 days respectively. Local radiotherapy for consolidation in two of our patients had no additional benefit. Conclusion: Myeloid sarcoma is extramedullary collection of myeloid blasts with or without bone marrow involvement. They were commonly seen in young patients and t(8;21) being a common cytogenetic abnormality associated with it. The treatment outcome of patients with myeloid sarcoma seems dismal and systemic therapy remains the modality of choice.

Introduction Acute leukemia (AL) is among the most common treatable cancers in childhood but many children are forced to abandon therapy. Objective We have explored reasons for treatment abandonment through this study. Materials and Methods Retrospective analysis from an ongoing registry data of childhood AL patients, where all newly diagnosed AL patients of ≤18 years of age (June 2014–November 2017) were included. Patients >18 years of age, having any history of treatment of AL outside our institute, and/or patients with relapsed AL were excluded. The primary outcome of the study was treatment abandonment rate. Results A total of 710 AL patients were included in the study, average distance traversed to reach the hospital being 161.66 km. Most children were aged 1 to 10 years (49.4%, n = 351), followed by >10 to 18 years (46.6%, n = 331), and ≤1 year age (3.9%, n = 28). The commonest symptoms were fever (67.4%), pallor (38.6%), bleeding (11.5%), bone pain (13.8%), neck swellings (14.9%), and, rarely, testicular swellings or Superior vena cava (SVC) syndrome (1.1%). A high abandonment rate was noted prior to leukemia subtyping (35.2%, n = 250) mostly among males 62% (n = 155) and the 1- to 10-year group 55.6% (n = 139). A total of 460 (64.8%) patients were subsequently subcategorized by immunophenotyping. Precursor B-cell (Pre-B) Acute Lymphoblastic Leukemia (ALL) in 307 (43.2%) patients was the commonest subtype, followed by early Pre-B ALL (Pro-B ALL) in 10 (1.4%), T-cell ALL (T-ALL) in 51 (7.1%), Acute Myeloid Leukemia (AML) in 45 (6.3%), Acute Promyelocytic Leukemia (APML) in 28 (3.9%), and Mixed Phenotypic Acute Leukemia (MPAL) in 19 (2.6%). Conclusion The most common group of patients was aged 1 to 10 years (median age: 5 years). An abandonment rate of 35.2% was seen prior to complete diagnostic workup. The reason for this high abandonment, despite good disease prognosis, is a relevant social and health issue, and needs further evaluation. The problems discussed in this study are relevant to lower-income families and areas where health care is not easily accessible. The government agencies, nongovernment organizations and society would need to work together to overcome these issues.

Hb E-beta thalassemia is a major public health problem in West Bengal, India and is the predominant symptom producing thalassemia in this part of the country. To search for an easy, reliable and cost effective screening method for HbE that can be used at the community level where more sophisticated methods are not readily available. And the DCIP test was performed for the purpose. Blood samples of 425 asymptomatic family members from 80 diagnosed cases of HbE beta Thalassemia patients were tested for Hb, RBC indices, DCIP test, HPLC, and in discordant cases confirmed by DNA mutation analysis. The present study shows DCIP screening test to have a sensitivity, specificity, positive predictive value and negative predictive value of 96.39%, 97.43%, 96.39% and 97.43% respectively. It also shows a false positive rate and false negative rate in 2.56% and 4.6% cases respectively. The advantage with DCIP over HPLC is that it can be easily performed at the community level by a person with minimum technical skill, few samples (even a single sample) can be tested at time, at a low cost.

Introduction:Sickle cell disorders were originally found in the African regions, Arabian Peninsula and parts of India. However, in today's age of globalization patients with homozygous or compound heterozygous Sickle cell disorders can be found all over the world. The objective of our study was to assess the distribution and clinical presentation of patients with Sickle homozygous or heterozygous diseases in the Eastern part of India. Methods:Patients who attended the Thalassemia Clinic in our tertiary care center, between 1st January 2018 to 31st May 2020 (2 years and 4 months) were retrospectively analysed and the ones with a component of Sickle haemoglobin(HbS), either in the form of Sickle cell anemia/homozygous Sickle cell disorders(SCA) or compound heterozygous diseases, like Sickle cell/β thalassemia(HbS/β), Sickle cell/Delta thalassemia(HbS/D), Sickle cell Haemoglobin/E thalassemia(HbS/E), were included in the study. People having Sickle cell trait (HbS trait), have also been included. Thorough history of painful crises, blood transfusions, family history and treatment history was elicited and every patient was clinically examined. The patients were diagnosed by High Pressure Liquid Chromatography (HPLC) or Thalassemia Mutation analysis by Polymerase Chain reaction (PCR). Results:A total of 95 patients with a component of HbS were considered as our study cohort, with HbS/β thalassemia patients being the majority (53.7%), followed by SCA (30.5%). Age of the study cohort ranged between 2-50 years age. HbS/β thalassemia patients presented at a later age (median 17.5 years) than SCA patients (median 12 years). Their demographic distribution is depicted in Table 1. The most common clinical presentation was painful crisis (32,33.7%), be it abdominal pain (11,11.6%) or bone pain (13,13.7%). Other presenting complaints were pallor (26,27.4%), jaundice (12,12.6%) and fever (4,4.2%). Some rarer presenting manifestations were fatigue (4,4.2%), splenic infarction (1,1%), convulsions (1,1%), Raynaud's phenomenon (1,1%), headache (1,1%) or itchy skin lesions (1,1%). Few patients (4,4.2%) had recurrent pregnancy loss, and one patient was diagnosed incidentally during an antenatal check-up. Most patients had more than one complaint. Very occasionally patients required hospital admission, the reasons being, chest pain, fever, convulsions or abdominal pain. HbS trait was diagnosed incidentally during evaluation for other illnesses, most commonly during evaluation of pallor (3,60%): one patient was later diagnosed with iron deficiency anemia. Most patients who attended our center were from within the state or neighbouring states. The patients were treated with Hydroxyurea, with/without blood transfusions, chelation therapy with Deferasirox as required and Folic acid supplementation. People with HbS Trait continued to receive Folate supplementation. Discussion and Conclusions:This study highlights the varied distribution of HbS among the population attending a tertiary care center, irrespective of a specific area-based population. Till date most studies conducted in India have highlighted the prevalence of Sickle cell disorders among specific focused populations. HbS/β thalassemia was the most common sickle cell disorder in our study. This is in contrast to most findings in published literature from other countries, where SCA is the commonest. Only one other study conducted in eastern India, has depicted a finding similar to ours. The median age of disease presentation was at a later age in our study, in contrast to findings in published literature from other countries. There is a variation in the severity of disease manifestation in our study cohort. The most common painful crisis was bone pain, followed by abdominal pain. Pallor was also one of the commonest presenting symptoms. Stroke, a common manifestation of SCA in other countries, was rare in our study cohort. Disclosures No relevant conflicts of interest to declare.

Hemoglobin (Hb)-F inducers are known to improve Hb level and transfusion dependence in thalassemia. This pilot study was conducted to assess the efficacy and safety of Hb-F inducer thalidomide compared to hydroxyurea (HU) in Hb E-β thalassemia patients.This was a prospective interventional single-centre study with 45 Hb E-beta thalassemia patients equally divided into group-I (thalidomide+folic acid), group-II (HU + folic acid) and group-III (folic acid). Response was assessed at various time intervals with 12-months follow up period. Primary end points were increment in Hb, Hb-F level and improvement in transfusion requirement; secondary end point were tolerability and safety.There was 100% responder (R: Hb-increment ≥1 g/dl) in group-I with 66.67% major responder (MaR: Hb-increment ≥2 g/dl), while there were 40% and 0% responder in group-II and III respectively. Hb-increment was significantly (p-value0.0001) better in thalidomide arm compared to HU. The Hb-increment was attributable to both increase in Hb-F levels and reduction in ineffective erythropoiesis in thalidomide arm. Transfusion reduction was significantly better in group-I compared to group-II (100% vs 34%). No severe adverse effects was reported by patients of any group.Thalidomide showed a persistent significant Hb-increment and transfusion independence in Hb E-β thalassemia patients compared to HU.

Background: Rarity of rare bleeding disorders (RBDs) is attributed to very low incidence based on ethnicity, distribution and complexity of diagnostic tools. There is scarcity of data on RBDs from Eastern India. This study aims to understand the distribution of RBDs in this region for better patient care.Methods: Retrospective study conducted on patients presented with symptoms/signs of bleeding from January 2018 to December 2019 (two years). Patients having bleeding manifestations from causes other than inherited coagulation disorders, IPDs, and vWD were included. Complete haemogram, peripheral blood smear, coagulation tests, vWD assay and platelet function tests were carried out.Results: Out of 2415 patients, 1570 were included after exclusion of other diseases. Immune Thrombocytopenia (ITP) and Hemophilia being excluded, 40/1570 (2.5%) patients were found to have RBDs. Median age was 11.6 years (range, 1.25-40 years). Most common was IPDs (2.9%, n=19); Glanzmann thrombasthenia was commonest (1.5%, n=10). vWD was second (1.7%, n=11) in occurrence; vWD type-III was the commonest subtype (0.9%, n=6). ICDs comprised 1.5% (n=10) of all patients; congenital afibrinogenemia (0.6%, n=4) was most common. Other ICDs prevalent in this cohort included FVII, FV, FX and FXIII deficiencies. Most common presentations were ecchymoses or prolonged bleeding from cut injuries or menorrhagia.Conclusions: RBDs may present in varied ways and are often difficult to diagnose correctly. Distribution of RBDs in this patient cohort differs from published literature from Western studies.

Background Burkholderia cepacia, an aerobic gram-negative bacillus, is a frequent colonizer of fluids used in the hospital ward. It poses little risk of infection to healthy people; however it is a known important opportunistic pathogen causing morbidity and mortality due to its intrinsic resistance to most of the antibiotics in hospitalized patients. Small hospital outbreaks are frequent. B. cepacia may occur as an opportunistic infection in hemato-oncology patients. Here we present an outbreak of Burkholderia cepacia infection in hematology ward of our institute. Methods Febrile episodes as defined by IDSA guideline, 2010 were followed, and blood for culture and sensitivity was sent in all the events. The culture was done by an automated method using Bactalert 3d Biomeriux & sensitivity pattern by Microscan Siemens method and subsequently detected by PCR based method. Results During September 2016 to February 2017 (six months), a total of 498 blood cultures were sent during febrile episodes. Out of which 60 (12%) came out to be positive for different microorganisms. Out of all positive cultures, Burkholderia cepacia was detected in 29 (48%) patients, which reduced drastically following the change in antibiotic administration practice. All isolates showed sensitivity to pipercillin+tazobactum, cefoperazone+sulbactum, fluoroquinolones, cotrimoxazole and carbapenems and resistance to polymyxin B and colistin. With timely intervention by appropriate intravenous antibiotics as per culture sensitivity result and change in antibiotic preparation practice, overall mortality was low 1 (4%) out of 29 culture positive episodes. Conclusion Change of antibiotic preparation practice was the key to control this outbreak, and overall mortality was low.

Introduction: β Haemoglobinopathy, is one of the commonest inherited disorders, with a higher prevalence in the eastern part of India. In view of the lack of facilities for allogeneic stem cell transplantation, including financial constraints, this disease is considered to be incurable in this part of India. So, preventing the birth of a symptomatic Thalassemic child is the best way to prevent the disease, considering the immense medical, social & financial implications in the community. Therefore, prenatal diagnosis is the most important tool for detecting & preventing symptomatic haemoglobinopathies. Objectives: To detect the status of haemoglobinopathies in the foetus of carrier or affected parents, so as to prevent the birth of symptomatic patients with Thalassemia & other haemoglobinopathies. Material & Methods: This is a retrospective analysis of an ongoing registry data of routine prenatal diagnosis of haemoglobinopathy, conducted at NRS Medical College, Kolkata, over a period of approximately 4 ½ years (September,2013-April,2018). The process involves, collection of Ultrasound guided chorionic villous samples (CVS) by an Obstetrician between 12-16 weeks of gestation (maximum up to 19 weeks). Considering the prevalence of specific mutations in this part of India, a total of 25 β mutations are analysed by ARMS-PCR, using specific probes. Some of the common mutations tested are: IVS1-5(G→C), 619bp del, IVS 1-1(G→T), CD 30(G→C), CD 26(G→A) & CD6 (A→T). Results: Total number of CVS were 407(407 mothers were tested), of which 329 samples (80.8%) showed presence of β haemoglobinopathy mutations, & 78(19.2%) did not have any mutations. Among the mutated genotype, heterozygous carrier state was detected in 232(57%), & homozygous/ compound heterozygous state(affected) was detected in 92 foetuses (22.6%). Among the carriers, β Thalassaemia trait was most common(n=185,45.45%), followed by HbE Trait(n=41,10.07%). HbS trait(n=3), HbD trait(n=1) & δβ Thalassemia trait (n=2) were rarely detected. Among the affected foetuses, 44 had compound heterozygous genotype (10.8%), majority being HbEβ thalassemia (n=42,10.3%), followed by δβ-β Thalassemia(n=1) & HbSβ Thalassemia(n=1). The remaining 48 affected cases were homozygous β Thalassemia Major (11.7%). Of the 92 affected pregnancies, 91(22.35%) had been counselled for medical termination of pregnancy (MTP). One case of δβ-β Thalassemia, a milder phenotype, was excluded from MTP counselling. Total number of β mutations detected (both homozygous & heterozygous states) were n=373, and the commonest was IVS1-5(G→C) (n=244,65.4%), followed by CD 26(G→A) (n=85,22.78%), CD 30(G→C) (n=9,2.4%), CD 41/42(-CTTT) (n=8,2.1%), CD 15(G→A) (n=8,2.1%) & CD8/9 (+G) (n=4,1.1%). Rarer β mutations detected were CD15(-T) (n=4,1.1%), CD16(-C) (n=1), CD6 (A→T) (n=4,1.1%), βD-PunjabCD121 (G→C) (n=3) & Asian Indian inversion deletion Gγ (Aγδβ)0(n=2). We know that sometimes maternal cell contamination may occur during villous sampling. So, at the time of childbirth, cord blood was collected & β mutation studies were re-performed. If this could not be done, an HPLC was conducted when the child was >1year old. We have data of 26 children & each time the results have corroborated with the primary CVS sampling data. Among both male and female parents(n=814), the commonest genotype was β Thalassemia Trait (n=621, 76.3%). Among the female parents(n=407), some of the other genotypes were HbE Trait (n=94,23.09%) & HbS trait(n=4,0.98%). Among the male parents(n=407), HbE Trait(n=70,17.19%) was the 2nd most common abnormality, few of the other genotypes being: HbS Trait (5,1.2%), β Thalassemia major (n=3,0.73%) & HbE homozygous disease (n=3, 0.73%). Conclusions: From this cohort, total affected (homozygous/compound heterozygous) foetuses are 92(22.6%). β Thalassemia Major (11.7%) is the most common affliction, followed by HbEβ thalassemia (10.3%) & δβ - β Thalassemia. An attempt at prevention of birth of at least 91(22.35%) future thalassemia patients has been done by means of MTP. Ours is an ongoing registry data and we are following up the children by conducting cord blood mutation studies or HPLC (>1year old child), to study the precision and accuracy of our CVS sampling results. So far there has been 100% concordance. One of the limitations of our study is lesser number of reconfirmation of the born children, in view of social and financial constraints. Disclosures No relevant conflicts of interest to declare.

Introduction Haemoglobin E-beta-thalassaemia (EBT) represent approximately 50 per cent of those affected with severe beta thalassemia.The highest frequencies are observed in India, Bangladesh and throughout Southeast Asia. Endocrinopathies are now amongst the common complications of thalassaemia and it is multifactorial in origin. Iron overload in EBT is also multifactorial. This study was undertaken to evaluate the thyroid dysfunction in patients of EBT and its correlation with serum ferritin levels. Methods EBT patients were evaluated prospectively to assess thyroid dysfunction status and correlate it with serum ferritin levels. High performance liquid chromatography was performed with Bio-rad beta thalassaemia short program variant II. Serum ferritin estimation was done with microplate immunoenzymometric assay and thyroid assay for TSH, free T4 and T3 were done by access 2 Immunoassay System, Beckman Coulter. Results 50 patients with EBT were evaluated. The mean age of patients were 19.7 years (range: 12-47). There were 28 males and 22 females. There were 41(82%) and 9(18%) transfusion dependent and transfusion independent patients respectively and 40(80%) were on chelation therapy. In this cohort 22(44%) patients had thyroid dysfunction. Six (12%) and 16(32%) of patients were having hypothyroidism and subclinical hypothyroidism respectively. Mean ± Standard deviation (S.D) of serum ferritin level with hypothyroidism, subclinical hypothyroidism and euthyroidism was 1077 ± 371.8 ng/ml ,1422 ± 1361.0 ng/ml and 1252 ± 664.4 ng/ml respectively with correlation coefficient =0 [Fig 1 and Fig 2]. Serum ferritin levels do not predict thyroid dysfunction in patients of EBT. Male and female have equal preponderance for thyroid dysfunction. Patients with subclinical hypothyroidism were having few symptoms compared to frank hypothyroidism and majority of symptoms in either scenario were masked by thalassemia itself. Earlier age of onset of EBT is associated more with thyroid dysfunction however the association is not statistically significant (p=0.2). There was no association between spleen size and thyroid dysfunction (p=0.7). Conclusions Thyroid dysfunction was seen in 42% of EBT patients. Prevalence of hypothyroidism was found to be higher in EBT patients compared to general population but a definite correlation with the serum ferritin levels could not be established. Figure 1 Mean serum ferritin level and thyroid status Figure 1. Mean serum ferritin level and thyroid status Figure 2 Correlation of serum TSH and ferritin level (correlation coefficient =0) Figure 2. Correlation of serum TSH and ferritin level (correlation coefficient =0) Disclosures No relevant conflicts of interest to declare.

Context: Polycystic ovarian syndrome (PCOS), the most common endocrinopathy of women in the reproductive age group seems to be adversely affected by associated thyroid dysfunction. Both pose independent risks of ovarian failure and pregnancy related complications. Aims: The present study from Eastern India is, therefore, aimed to investigate the prevalence and etiology of different thyroid disorders in PCOS subjects. Settings and Design: Cross-sectional hospital based survey-single centre observational case-control study. Materials and Methods: This prospective single-center study recruited 106 female patients with hypertrichosis and menstrual abnormality among which 80 patients were defined as having PCOS according to the revised 2003 Rotterdam criteria and comprised the study population. Another 80 age-matched female subjects were studied as the control population. Thyroid function and morphology were evaluated by measurement of serum thyroid stimulating hormone (TSH), free thyroxine levels (free T3 and free T4), anti-thyroperoxidase antibody (anti-TPO Ab), clinical examination and ultrasound (USG) of thyroid gland. Statistical Analysis Used: It was done by Student's t-test and Chi-square test using appropriate software (SPSS version 19). Results: This case-control study revealed statistically significant higher prevalence of autoimmune thyroiditis, detected in 18 patients (22.5% vs. 1.25% of control) as evidenced by raised anti-TPO antibody levels (means 28.037 ± 9.138 and 25.72 ± 8.27 respectively; P = 0.035). PCOS patients were found to have higher mean TSH level than that of the control group (4.547 ± 2.66 and 2.67 ± 3.11 respectively; P value < 0.05). There was high prevalence of goiter among PCOS patients (27.5% vs. 7.5% of control, P value > 0.001). On thyroid USG a significantly higher percentage of PCOS patients (12.5%; controls 2.5%) had hypoechoic USG pattern also compatible with the diagnosis of autoimmune thyroiditis. Conclusions: High prevalence of thyroid disorders in PCOS patients thus points towards the importance of early correction of hypothyroidism in the management of infertility associated with PCOS.