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The treatment landscape of chronic lymphocytic leukemia (CLL) has witnessed immense changes in the past decade. Several newer target therapies and their combinations with anti-CD 20 therapies have got approval for management of CLL in the treatment-naïve and relapsed/refractory setting. Also, the availability of newer diagnostic techniques has helped differentiate the disease into high- and low-risk CLL which acts not just as a prognostic marker but also helps decide the best drug management that can be administered to the patients. Targeted therapy has largely overtaken chemoimmunotherapy in the management of CLL, except for a small subset of the population (young and fit with IGHV mutation). However, with targeted therapy, there is also an issue of previously uncommon treatment-emergent adverse events, the duration of therapy, and financial toxicity. The aim of this review article is to gather results from all landmark CLL trials and discuss the feasibility of incorporating Acalabrutinib in the CLL landscape from an Indian perspective.

Background Eosinophilic myocarditis (EM) is rare but accounts for 12–22% of histologically proven acute myocarditis cases. Acute necrotizing EM is considered an aggressive, life-threatening disease which is usually treated by high-dose corticosteroid therapy. Case summary We report the case of a 27-year-old man with acute severe pericarditic chest pain, moderately reduced left ventricular (LV) ejection fraction, and a small pericardial effusion. Troponin I level was highly elevated in the absence of coronary artery disease, leading to the diagnosis of acute myopericarditis. In the absence of blood eosinophilia and despite a negative cardiac magnetic resonance study, LV endomyocardial biopsy revealed an acute necrotizing EM. With conventional antiphlogistic and heart failure therapy, the patient became symptom-free and inflammatory and cardiac necrosis markers as well as LV ejection fraction normalized within days. Thus, in the absence of a systemic hypereosinophilic disorder, there was no need for steroid therapy. Long-term follow-up over 12 months showed sustained normalization of cardiac structure and function. Discussion Acute necrotizing eosinophilic myopericarditis is not always a dreadful cardiac disease. There are idiopathic cases which may quickly resolve without immunosuppression. There seems to be a publication bias towards critical cases.

Background Creation of an iatrogenic aorto-right atrial fistula is a rare but clinically relevant complication of cardiac surgery. Transfemoral percutaneous closure is an attractive alternative to surgical repair, but there are no reports about transcatheter repair using a complete arm access. Case summary We present the case of a 44-year-old woman with heart failure (NewYork Heart Association Class III) due to a longstanding iatrogenic fistula from the non-coronary aortic cusp to the right atrium (RA) with aorta to RA shunting and severe tricuspid regurgitation (TR) caused by mitral valve replacement 15 years ago. The patient was successfully treated by percutaneous closure with an Amplatzer Vascular Plug II using complete brachial access. Following the procedure right heart chambers and TR decreased and symptoms resolved. Discussion To the best of our knowledge this is the first report of percutaneous repair of an aorto-right atrial fistula using total arm accesses (radial artery and basilic vein). In appropriately selected patients, this approach is an attractive alternative to femoral access.

East Asians, Asian Indians and Amerindians have a five to ten-fold lower age-adjusted incidence rate (AAIR) of chronic lymphocytic leukaemia (CLL) compared with persons of predominately European descent. The data we review suggest a genetic rather than environmental basis for this discordance. All these populations arose from a common African Black ancestor but different clades have different admixture with archaic hominins including Neanderthals, Denisovans and Homo erectus, which may explain different CLL incidences. There are also some differences in clinical laboratory and molecular co-variates of CLL between these populations. Because the true age-adjusted incidence rate in African Blacks is unknown it is not possible to determine whether modern Europeans acquired susceptibility to CLL or the other populations lost susceptibility and/or developed resistance to developing CLL. We also found other B-cell lymphomas and T- and NK-cell cancers had different incidences in the populations we studied. These data provide clues to determining the cause(s) of CLL.

Chronic myeloid leukemia (CML) is characterized by increased and unregulated proliferation of granulocytic lineage in the bone marrow and presence of these immature myeloid cells in the peripheral blood with presence of Philadelphia (Ph) chromosome. Tyrosine kinase inhibitors are the most important drugs in the CML therapy and provide long disease-free survival. Due to the increased survival of CML patients with continual administration of these drugs, the chance of development of secondary malignancies may increase. The most common secondary malignancies are prostate, colorectal and lung cancer, non-Hodgkin lymphoma, malignant melanoma, non-melanoma skin tumors and breast cancer. Herein, we are describing a rare case of Hodgkin lymphoma in a patient of CML after ten year of primary disease presentation. Hodgkin lymphoma in a known case of CML is very rare and further studies are also needed to know the pathogenic relationship between the two entities and to assess the risk of secondary Hodgkin lymphoma in CML patients treated with tyrosine kinase inhibitors. CML itself is a risk factor for development of solid cancers and hematologic malignancies. In addition, patients on chemotherapy are immune-compromised and may be at greater risk of neoplasm driven by infectious agents such as Epstein-Barr virus.

Fifteen apparently healthy male buffalo calves aged between 6 months to one year with body weight range of 70 - 140 Kg divided into 3 groups of 5 buffalo calves each were used in the present investigation. Endotoxic shock was produced by IV infusion of Escherichia coli endotoxin @ 5 μg/kg BW/hr for 3 hours followed by administration of three different treatment regimens comprising of intravenous infusion of hypertonic saline solution(HSS) @ 4 ml/Kg bw, flunixin meglumine @ 1.1 mg/Kg bw and blood @ 20 ml/Kg bw to group-I, HSS, Dextran-40 and Flunixin meglumine to group-II and HSS, Dextran-40, whole blood and Flunixin meglumine to group-III with the objectives to study the major physio-pathological changes during induced endotoxemia in buffalo calves and to compare the effects of different treatment options to find out the best treatment option out of the three combinations. All the animals were further observed up to day 2 or death whichever was earlier. Endotoxin infusion to all the animals caused symptoms of restlessness, respiratory distress, snoring, diarrhoea, profuse salivation along with the significant hypoproteinemia, hypoalbuminemia, hypoglobulinemia, hypokalemia and hypocalcemia. The treatment with HSS, flunixin meglumine and blood infused as one time infusion to these endotoxemic buffalo calves not only alleviated the above mentioned symptoms but also significantly raised the circulating albumin level at 5.5 hrs and day 2 and Fibrinogen level at day 2 of observation. A significant hypocalcaemia was observed at 4.5 hours along with an increase in Alkaline Phosphatase at 3.5, 4.5 and 6.5 hrs. All the endotoxemic buffalo calves which died were subjected to post mortem and histopathological studies. Epicardial and endocardial haemorrhages, haemorrhages on intestinal mucosa, congestion, haemorrhages, emphysema and fibrinous thrombi in microvasculature of lungs were salient histopathological findings. On comparison with observations of the other treatment regimens tried, it was found that the IV infusion of the combination of HSS, Flunixin meglumine, Dextran-40 and blood was found to be the most effective leading to full recovery of 3 out of 5 buffalo calves of group-III where as only 1 out of 5 animals recovered in group-II. None of the group-I animals recovered and all of these succumbed to shock after day-2.

Erdheim–Chester disease (ECD) is a rare multi-system, non-Langerhans cell histiocytic disorder (NLCHD) with only a few hundred cases reported in the literature. Its diverse clinical manifestations require a high level of diagnostic suspicion. BRAFV600E mutation analysis is of critical significance, as it has implications for targeted therapy with BRAF inhibitors such as vemurafenib and dabrafenib. We report a case of symptomatic, central nervous system (CNS)-predominant ECD initially presenting with CNS mass lesions mimicking meningiomas on imaging and prominent periorbital xanthogranulomas. CNS presentation of ECD, although not infrequent, bears particular significance here from a therapeutic point of view, since only partial debulking was possible owing to anatomical complexities. Radiological evaluation following surgery showed no significant change in the size of the lesions. Targeted therapy was commenced following histopathology, immunohistochemistry (IHC), and molecular testing, resulting in marked improvement of clinical symptoms and tumor regression. Thus, diagnostic accuracy was imperative for symptomatic relief in this rare but aggressive neoplasm with a complex clinical presentation and misleading initial radiological impressions, bearing an otherwise grim prognosis.

Ruxolitinib is a Janus kinase (JAK) 2 inhibitor that is an effective therapeutic agent for primary myelofibrosis (PMF), which helps significantly to reduce constitutional symptoms and spleen size. However, this drug has significant immunomodulatory effects that may lead to various opportunistic infections. Reactivation of tuberculosis and certain viral infections have been well documented. Although a few reports of patients with pulmonary cryptosporidiosis on ruxolitinib exist, an extensive literature review shows only one previously reported case of cryptococcal meningoencephalitis in an immunocompetent patient on ruxolitinib, with a history of avian exposure. Here we report another extremely rare incidence of cryptococcal meningitis in a fully immunocompetent male patient on ruxolitinib, with no history of contact with birds. Although this is an approved and effective therapy for PMF, careful evaluation, screening, and prophylaxis in susceptible individuals should be considered before starting therapy.

We report an unusual case of paragonimiasis in a Nepali patient presenting with massive pericardial effusion and pericardial tamponade. The patient reported neither the consumption of crabs or crayfish nor the consumption of wild animal meat, which are the usual sources of infection. It is suspected that the source of infection was instead the ingestion of raw live slugs as part of a traditional medicine treatment.

Background: Hematopoietic progenitor stem cell transplantation (HPSCT) is used as a standard treatment option to improve outcome in hematological and nonhematological disorders. It is important for new HPSCT program to look at its patient outcome data and compare it with the published data to evaluate the efficacy of program. Aims: The aim was to compile and collate the patient outcome data of HPSCT and compare with published reports. Materials and Methods: Patient demographics, indications, stem cell harvest by apheresis, dose collected, infusion, engraftment, and follow-up data were collected from hospital information system from 2010 to 2013 in a tertiary care hospital. HPSCs were mobilized with granulocyte colony-stimulating factor, and harvests were done on the 5th day. Engraftment was decided for neutrophil when counts were 0.5 × 109/L and for platelets when counts were 20 × 109/L on two consecutive days without any transfusion support. Results: There were 133 harvests for 95 patients with various disorders; multiple myeloma was most common in autologous and acute lymphoblastic leukemia in allogeneic group. One hundred harvests were done for autologous and 33 for allogeneic HPSCT. In autologous group, of 66 patients, 60 (90.9%) received stem cell infusion at median dose of 4.63 × 106 CD34+ cells/kg. Similarly, in allogeneic group, of 29 patients, 27 (93.10%) received infusion at median dose of 5.8 × 106 CD34+ cells/kg. 58 (96.9%) patients and 25 (92.6%) engrafted in autologous and allogeneic group, respectively. The median time for neutrophils engraftment was 11 days in autologous group and 12 days in allogeneic group. The median time for platelet engraftment was 11.5 days in autologous group and 13 days in allogeneic group. The 100-day survival rate was 95% n = 57) in autologous group and 77.8% n = 21) in allogeneic group. Conclusion: This data analysis shows reasonably good results of HPSCTs with majority of patients surviving at 100-day follow-up.

Anaplastic large cell neuroblastomas ALCNB are a subset of undifferentiated neuroblastomas with marked pleomorphic and anaplastic cytomorphological features which are characterized by the absence or marked paucity of histological clues for the diagnosis of neuroblastoma that render them diagnostically challenging Here in we are presenting a case of ALCNB in which the clinical radiological and cytological features were misleading to a diagnosis of lymphoma High degree of cytological suspicion especially when an abdominal mass with internal calcification presents in children less than years of age in the absence of classical cytological picture of neuroblastoma like resetting and neuropil but presence of nuclear anaplasia with many bizarre and multinucleated cells mimicking lymphoma might help in delineating these cytological twins Further study of this variant of neuroblastoma is required as it poses a diagnostic dilemma due to the presence of similar types of cells as that of anaplastic large cell lymphoma ALCL It not only elucidates the prognosis but also aids in establishing an appropriate differential diagnosis and determine the optimal therapy

Myelodysplastic syndromes (MDS) are fairly common hematological disorder of elderly. They are a group of clonal malignant hematopoietic stem cell disorders characterized by dysplastic morphology, variable cytopenia and a variable threat of transformation to AML. These dysplastic changes are a result of chromosomal abnormalities and somatic mutations. MDS is the most common myeloid neoplasm of the older adults with median age at diagnosis being 72 years and an average incidence rate of 0.2 per 100,000 people per year. MDS is diagnosed and classified according to the WHO 2008 classification system, which utilizes peripheral blood and bone marrow findings. Other essential investigations include flow cytometry, genetic profile and chromosomal analysis. Various prognostic scoring system have been developed which help guide the treatment. Treatment of complications associated with MDS also forms an essential component of the management of this disease.

Lipomatous tumours are the most commonly encountered benign neoplasms of mesenchymal origin. The lipomas consisting entirely of mature fat are the most common soft tissue tumour of the body occurring predominantly in upper back, shoulder and abdomen; but have been virtually reported arising in every location where fat is normally present. The incidence of lipoma in parotid gland is rare and it commonly presents as gradually progressing painless mass. Hence, it is seldom considered in the differential diagnosis of parotid swelling. Fine Needle Aspiration Cytology (FNAC) has been proved to be unreliable in diagnosing parotid lipomas, but histopathology helps in making the correct diagnosis. Computed Tomography (CT) scan and Magnetic Resonance Imaging (MRI) can lead to an accurate pre-operative diagnosis of parotid lipoma as well as to evaluate the location of the tumour to programme the correct surgical approach. The present case was of parotid lipoma involving the superficial lobe in a 40-year-old male who presented with left parotid swelling. Lipomas are rarely observed in the parotid gland and this case was being presented because of the relative rarity of lipomas in the parotid region.

Title: "A prospective observational study of clinico-pathological features, prognostic factors and treatment response to primary therapy in Multiple Myeloma at a tertiary care centre" Background: Multiple myeloma (MM) is characterised by the neoplastic proliferation of plasma cells leading to excess monoclonal immunoglobulins. The incidence of multiple myeloma in India ranges from 1.2 to 1.8 per 100,000. There is paucity of cytogenetic data from this part of subcontinent. The aim of our study is to report various clinicopathological features, evaluate biological markers of prognostication including cytogenetic variables and assess treatment response after standard primary therapy. Methods and Materials: The study was carried out at a tertiary care center in Northern India. After final diagnosis of multiple myeloma was established, each patient was risk stratified via FISH cytogenetic analysis as per the revised ISS. Definitive management plan was individualised, including assessment for high dose therapy with peripheral blood stem cell support. Treatment response were recorded as per standard IMWG response criteria. Significant toxicities associated with treatment were also recorded. Results: Eighty consecutive patients with newly diagnosed multiple myeloma were enrolled prospectively from April 2017 to November 2018. The median age at diagnosis was 63 years, and number of males & females were equal. The most common presenting symptom was back pain (67.8 % patients) and most frequent clinical sign was pallor (86.4 %). All four CRAB features were documented only in 16.9% patients. M-Band was present in 96.6% patients and on SFLC assay 59.3% and 40.7% were kappa and lambda light chain restricted respectively. Most common heavy chain abnormality detected was IgG. Seventy percent patients had lytic lesions on imaging while only 3% suffered skeletal related events. Cytogenetic evaluation by interphase FISH was carried out in all patients upfront. No chromosomal abnormality was documented in 61.25 % while among those with chromosomal abnormalities, most commonly detected was del13q14.3 (23.75 %). Overall, 66.6% patients were stratified as standard risk, 28.1% as intermediate risk and only 3 (5.3%) patients were categorised as high risk. Most common induction regimen was VRD. Overall response rate was 94.9 % and VGPR or better responses were observed in 77.9% patients. Most common adverse effect of therapy was peripheral neuropathy of all grades. Of the 77 patients who completed primary therapy, 21.4% patients underwent high dose therapy with peripheral blood stem cell support while 67.7% patients were started on maintenance therapy. Four (5.1 %) non-responder was started on 2nd line treatment. On univariate analysis, higher deeper responses (VGPR or better) were observed in patients with IgA & IgG related myeloma and better overall response rates were seen in IgG related myeloma. Those with kappa light chain myeloma had 5.67 times higher likelihood of achieving response as compared to lambda light chain myeloma. Also, patients with kappa light chain myeloma achieved higher VGPRs as compared to lambda light chain myeloma. There was 17 times high risk of non-response in the presence of local bony tenderness. None of the findings were found to be significant on multivariate analysis. Conclusions: Use of interphase FISH to identify various cytogenetic markers help in stratification & staging of the disease which in turn act as a marker for prognostication. They should be a part of standard care in multiple myeloma. In majority we could administer treatment in accordance to standard practice guidelines and response rates were similar to those reported my seminal studies. Our study in a longer follow up will yield some useful information which will help in the better care of the patients. Disclosures No relevant conflicts of interest to declare.

Background: Diffuse Large B cell Lymphoma (DLBCL) accounts for nearly 25% of all Non-Hodgkin's lymphoma (NHL) in the developed world, making it the most common lymphoma. With the diversities in clinical presentation, morphology, molecular and genetic alterations, DLBCL represents a heterogeneous group rather than a single disease entity. Based on the cell-of-origin (COO) concept, gene expression profiling (GEP) has identified two major subtypes of DLBCL with differing prognoses. We aim to study the trends in the clinico-pathological features, prognostic factors and treatment outcomes following standard therapy between the molecular subtypes. Methods: A prospective study with 243 consecutively diagnosed cases of DLBCL between September 2009 and April 2017 were included. The clinico-pathological features, IPI score, extranodal involvement and stage of disease were recorded using a predesigned proforma. All patients received Rituximab based treatment which was modified according to their tolerability. Molecular subtyping to GCB and ABC subtype was performed using immunohistochemistry.Primary objective was to assess the clinico-pathological features, prognostic factors and differences between the molecular subtypes in Indian population. Secondary objective was to study the overall progression free survival (PFS). Results: Out of 243 patients enrolled in the study, 47% (n=129) were > 60 years, the median age being 55 years. Majority were males (63%). Fever (28%), pain abdomen (11%), weight loss (30%) and painless neck swelling (26%) were the most common symptoms. Nodal presentation was more common than extranodal [56.4% (n=137) versus 43.7% (n=106) respectively]; stomach (12.2%) being the most common extranodal site. 22.6%(n=55) high intermediate and 38.3% (n=93) with high IPI score. Bone marrow involvement was detected in 23% population (n=56). 51% (n=124) were diagnosed as stage IV, 24.3% (n=59) stage III, 16% (n=39) stage II and 8.6% (n=21) in stage I. Molecular subtyping was performed in 198 patients (81.4%) with GCB subtype seen in 45.5% (n=90) and ABC in 54.5% (n=108). 62.6% achieved complete metabolic response (CMR) and 18.9% (n=39) had disease progression. ABC subtype had more extranodal presentation [(54.6%, n=59 v/s 35.6%, n=32); p=0.007]. More number of disease progressions [17.8%; n=18 v/s 10.1%, n=9] and deaths [11.9%; n=12 v/s 3.4%, n=3]; p=0.046 were recorded in ABC Subtype. High IPI Score was seen in ABC subtype [45.6%, n=47 v/s 28.1% [n=25], p=0.063. Median survival time of patients was 81 months + SE 1.705 [CI 72.26-78.95]. There was a significant difference in the median PFS among those whose did not progress versus those who did [87.22 months v/s 72.66 months]. ABC subtype, high LDH Levels > 618 and patients with higher stage at presentation had disease progression. In this study, using both univariate and multivariate cox regression model, no risk factor was found to be associated with survival. Conclusions: R-CHOP remains the standard of care for patients with DLBCL. However, literature reports a cure rate of only 60% with standard immuno-chemotherapy with 40% eventually dying of the relapsed disease. DLBCL can no longer be considered and treated as one disease. It is imperative to identify those molecular and prognostic markers that would identify subset of patients who would benefit from a more aggressive course. Disclosures No relevant conflicts of interest to declare.

Coexistence of Diffuse Large B-Cell Lymphoma (DLBCL) with other morphologically and phenotypically distinct lymphoid neoplasm although unusual, has been reported in literature. The most common lymphoid neoplasms associated with DLBCL are Hodgkin’s lymphoma, mantle cell lymphoma and marginal zone lymphoma. However, they have been reported predominantly in the sites other than the bone marrow. Rarely, DLBCL associated with paraproteinemia of IgM type, result of monoclonal plasma cell proliferation, has also been reported in literature. There is either an associated increase in the free light chain levels or disruption in the normal kappa: lambda ratio. However, co-existence of DLBCL with malignant non secretory clonal plasma cells, diagnosed primarily in the bone marrow has not been reported in the literature.

Context: This named patient program evaluated the safety and efficacy of ibrutinib, a selective inhibitor of Bruton's tyrosine kinase in Indian patients with relapsed/refractory chronic lymphocytic leukemia (CLL, with/without chromosome 17 deletion [del17p]) and mantle cell lymphoma (MCL). Subjects and Methods: The eight enrolled patients (relapsed/refractory CLL: n = 6 [4/6 patients with del17p] and relapsed/refractory MCL: n = 2) had median age of 55 years (range, 52–60) and had received a median of 3 (CLL patients) and 4 (MCL patients) prior therapies. Patients received once-daily dose of ibrutinib (420 mg: CLL, 560 mg: MCL). Results: In CLL patients, the median time to response was 3 months (range, 0.5–7) and five of six patients had partial response (PR) whereas one achieved complete response (CR). Median time on treatment was 11.5 months (range, 8–14); five patients continued treatment and one was recommended stem cell transplantation (SCT). Of the two MCL patients, one achieved PR and one showed CR and advanced to SCT. In CLL patients, the median (range) hemoglobin level improved from 9.8 g/dL (7.2–11) at baseline to 12.0 g/dL (9.5–13.2) and median (range) platelet count improved from 150,000 cells/μL (21,000–195,000) at baseline to 190,350 cells/μL (130,000–394,000) at the time of analysis (July 2016). Most adverse events (AEs) reported were infections (n = 2). No Grade 3-4 or serious AEs, dose reductions, or treatment discontinuation due to AEs were reported. Conclusions: In this first real-world experience in Indian patients, ibrutinib demonstrated therapeutic efficacy in relapsed/refractory CLL (with/without del17p) and MCL. Safety results were consistent with the current known profile of ibrutinib.

Introduction Multiple myeloma (MM) is a malignancy involving terminally differentiated plasma cells. It is characterized by a complex pattern of extensive genomic aberrations involving many chromosomes and it constitutes about 1% of all malignancies. Its exact incidence in India is not known. Based on data available from 6 population-based cancer registries in India (covering 0.3% of the population) its incidence varies from 0.3 to 1.9 per 100 000 for men and 0.4 to 1.3 per 100 000 for women. Among various prognostic markers in MM, cytogenetic abnormality detected by conventional cytogenetic and FISH studies are major factors deciding clinical outcome. Interphase FISH studies from various parts of the world have reported variable incidence (40 - 66%) of cytogenetic abberations. However, there is insufficient published data from Indian subcontinent addressing the frequency of chromosomal aberrations using interphase FISH in MM patients. Patients and Methods Sixty eight patients clinically diagnosed with multiple myeloma were studied. The retrospective period of recruitment was from Jan 2015 to June 2016. The diagnosis of MM was based on serum electrophoresis and immunofixation, bone marrow plasmacytosis, and end organ involvement. Interphase FISH analysis was performed on bone marrow samples using specific DNA probes- Del 13q14.3 (LSI D13S25) , t (4;14) ( Kreatech IgH/ FGFR3 DC-DF), t (11;14) (Zytovision directly labeled IgH/CCND1 DC-DF), t (14;16) (Kreatech IgH/ MAF DC-DF), Del 17p13.1( LSI TP53). A total of two hundred nuclei were enumerated for each FISH Panel probe and cut off for detection of deletion/ fusion signal in normal individuals was taken as 3%. An interim analysis of treatment protocols was also done. Results A total of 68 cases with MM were evaluated which included 55 males and 13 females. We report a median age of 58 years (37-86 years). Interphase FISH analysis was done in all patients. Out of sixty eight patients, 23 (33.82%) patients had one genetic abnormality. Results revealed that deletion 13q14.3 was the most frequent aberration. Out of 68 patients, 10 patients have 13q14 (14.7%) abnormality. This includes 70% males and 30% females. In addition absence of p53 at 17p13 was detected in 8/68 (11.8%) patients. Similarly 11q13 abnormality was observed in 3/68 (4.4%). IgH (14q32) aberrations were noted in 2/68 (2.94%) patients. Of which t(4;14) was detected in these patients, whereas none of them showed t(14;16). More than one chromosomal aberrations were present in 4 patients. Data for serum β2-microglobulin at the time of presentation could be evaluated in 52 patients only. Most of the patients 40(76.9%) belonged to ISS stage 3. From the available data, 4 patients with ISS stage 3 had high risk chromosomal abnormality whereas 3 patients with ISS stage 2 and none of the patient of ISS stage I disease had high risk chromosomal abnormality. A total of 40 patients received cyclophosphamide, bortezomib and dexamethasone as the primary treatment whereas 23 patients received Bortezomib, lenalidomide and dexamethasone based therapy. Post 2 cycles of cyclophosphamide based therapy showed an overall response rate (CR + VGPR) of 87.5% whereas in case of lenalidomide based therapy the overall response rate was 91%. Thirteen patients underwent autograft after durable response, out of which one had a clinical relapse within 3 months. Median survival can only be commented on further follow up. Conclusion In comparison to the west, the frequency of chromosomal aberrations are different and much less in India whereas the studies of median survival is comparable. An early age of presentation in Indian subcontinent is another issue to be addressed as we know that secondary mutations accumulate with increasing age, but a younger population presenting with same severity of disease needs exploration of additional abnormalities in India. Being a resource constraint country and non availability of molecular lab at every place, evaluation of each patient is difficult, however increasing awareness of the role of biology in the management of MM is inspiring the clinicians for detailed evaluation and close follow up of these patients. Certainly, larger trials are required to understand the biology of this disease in the country. Disclosures No relevant conflicts of interest to declare.

Introduction: As per the 2008 World Health Organization (WHO) classification, Myeloproliferative neoplasms (MPN) are subclassified into eight clinicopathological groups.1 The discovery of activating JAK2 mutations revolutionized the approach to diagnosis of MPN. Recently there have been studies suggesting an increasing number of mutations distinct from JAK2 associated with MPN. The new mutations being studied are MPL with a mutation frequency of 1-5% commonly seen in Essential Thrombocytosis (ET) and Primary Myelofibrosis (PMF).2 IDH1 has a mutational frequency of 21% for blast phase of MPN and 4% for PMF.3 Other mutations that have been found to be coexistent with MPNs are EZH2, TP53 and TET2.4 Methods: A total of 79 cases with clinical suspicion of MPN were studied over one year. Based on WHO criteria, a total of 20 cases were diagnosed as MPN taking into account complete blood counts, bone marrow and cytogenetic studies with molecular profiling using next generation sequencing (NGS). Out of these, 13 cases were diagnosed as JAK2 positive and 7 as JAK2 negative MPN. All cases were studied for a panel of 50 mutations (Table 1) using NGS (Ion Torrent PGM) and a minimum coverage of 100x was considered to be significant. Table 1. Mutation Panel ABL1 EGFR GNAQ KRAS PTPN11 AKT1 ERBB2 GNAS MET RB11 ALK ERBB4 HNF1A MLH1 RET APC EZH2 HRAS MPL SMAD4 ATM FBXW7 IDH1 NOTCH1 SMARCB1 BRAF FGFR1 IDH2 NPM1 SMO CDH1 FGFR2 JAK2 NRAS SRC CDKN2A FGFR3 JAK3 PDGFRA STK11 CSF1R FLT3 KDR PIK3CA TP53 CTNNB1 GNA11 KIT PTEN VHL Results: Out of 20 MPN cases there were 3 cases of Polycythemia Vera (PV) 8 cases of ET and 9 cases of PMF. From the 14 mutations found in MPN, JAK 2 (65%) was the commonest followed by HRAS (45%), PDGFRA (45%), SMARCB1 (45%), Kit (40%), MET (25%), TP53 (20%), PIK3CA(20%), IDH1 (15%), STK11 (10%), APC (5%), FLT3(5%),PTEN (5%) and PTPN11(5%) (Graph1). Apart from JAK2, statistically significant mutations in the MPN group as compared to the non MPN group were Kit, TP53 and STK11 (Graph 2). Kit showed Single Nucleotide Polymorphism (SNP) with substitution of Adenosine (A) with Cytosine(C) on chr4:55593464 (hg19) and was statistically significant in MPN group as compared to non MPN group (40 % vs16.9 %, p value = 0.016). TP53 mutation showed a C to A SNP on chr17:7577036 (hg19) which was found more often in MPN groups than non MPN (20 % vs. 1.6 %, p value = 0.0018). STK11 mutation showed a C to Guanine (G) SNP on chr19:1223125 and a G insertion at chr19:1221320 and was found to be more associated with MPN than non MPN (10% vs. 1.6%, p value = 0.046) . However all other mutations were statistically insignificant. Graph 1: Total Mutations in MPN versus Non MPN Graph 2: Significant mutations in MPN *p-value: 0.016, **p-value: 0.046, ***p-value: 0.0018 In the MPN group, 13 cases were JAK2 positive and 7 cases were JAK2 negative. There was no statistical significance of presence of mutations between the two groups. In our study there was no significant association of IDH1 in MPN group in comparison to non MPN group ( 15% vs. 11.86%, p value = 0.35), in contrast to earlier studies.3 Conclusion: The mutations in Kit, TP53 and STK11 were found to be significantly more in cases of MPN as compared to non MPN. In future studies, different mutations present in MPN should be identified using NGS which will be crucial to not only diagnose and further characterize MPN cases but also for better understanding of the stepwise pathogenesis leading to cancer development in humans and to develop new targeted therapies. This is the first study of its kind in Indian population, to the best of our knowledge. References: 1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Tumours of Haematopoetic and Lymphoid Tissues. 4th ed. Lyon: International Agency for Research on Cancer (IARC); 2008. 2. Akpinar TS, Hancer VS, Nalcaci M, Diz-Kucukkaya R. MPL W515L/K Mutations in Chronic Myeloproliferative Neoplasms.Turk J Haematol. 2013 March; 30(1): 8-12. 3. Tefferi A, Lasho TL, Abdel-Wahab O, Guglielmelli P, Patel J, Caramazza D, et al. IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia . 2010. July ;24(7):1302-9. 4. Lundberg P, Karow A, Nienhold R, Looser R, Hao-Shen H, Nissen I,et al., Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood. 2014 Apr 3;123(14):2220-8. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.