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BACKGROUND: Treatment with high-dose chemotherapy and stem cell transplantation has prolonged survival in patients of multiple myeloma (MM). A dose-response relationship between number of CD34+ cells infused and leukocyte and platelet recovery, exists. Patients receiving dose of 5 × 10(6)/kg (category 3), the mean (SD) neutrophil engraftment time was 11.3 (0.5) days, 10.6 (0.9) days, and 10.2 (1.3) days respectively. Platelet engraftment time was 12.4 (2.60) days, 10.6 (1.14) days, and 11.2 (1.64) days for category 1, 2, and 3 patients, respectively. Correlation co-efficient between CD 34+cell dose and days for neutrophil and platelet engraftment was found to be −0.24 and −0.20, respectively. Time for neutrophil engraftment was found to be significantly associated with CD34+ cell dose category. CONCLUSION: CD 34+ cell dose appears as the strongest predictor of leukocyte and platelet engraftment. CD 34+ cell dose of >5.0 × 10(6) cells/kg leads to an accelerated neutrophil and platelet engraftment in patients of MM.

PURPOSE The outcomes of patients with myeloma from developing countries are often lacking because of poor record maintenance. Publications from such settings are also limited because of the retrospective nature of the data collection. Information technology can bridge these gaps in developing countries with real-time data maintenance. We present the real-time survival data of the patients with myeloma from a tertiary care center in North India using one such indigenously built software. PATIENTS AND METHODS These are real-time data of all patients with myeloma presenting to a tertiary care center from North India. The patient characteristics (demographics, baseline disease characteristics, risk stratification, and outcomes) were recorded contemporaneously. The survival of the study population was analyzed and grouped based on various disease characteristics at diagnosis. RESULTS The median age of the study population (N = 696) was 65.9 (34.9-94.9) years with male predominance (65%). The median follow-up was 3.7 years (0-18.6 years) with the median overall survival (OS) not achieved. The OS of the study population at 1, 3, and 5 years was 94% (n = 558), 87.5% (n = 394), and 83.1% (n = 267), respectively. Most of the patients presented in advanced stages based on International Staging System (III:70%). On Kaplan-Meier analysis, the presence of weight loss ( P = .01), renal dysfunction ( P = .047), and anemia at diagnosis ( P = .004) had a significant impact on survival. On Cox proportional model univariate analysis, the presence of renal dysfunction, anemia, and weight loss had the significant hazard ratio of 1.68 (1-2.82, P = .049), 3.18 (1.39-7.29, P = .0063), and 2.81 (1.22-6.42, P = .014), respectively, whereas on multivariate analysis of hypercalcemia, renal disease, anemia, and bone disease (CRAB) features, only anemia was found to have a significant hazard ratio of 2.56 (1.01-6.47, P = .046). CONCLUSION The real-world data show OS comparable with the published western literature. Only anemia was found to have significant impact on survival. The use of such software can aid in better data-keeping in resource-constrained settings.

Aims and Objectives In this study the various parameters of acute lymphoblastic leukemia (ALL), including the clinical features, peripheral blood and bone marrow (BM) findings, immunophenotypic and cytogenetic details in ALL cases who had isolated relapse involving the central nervous system (CNS), were studied. Patients/Materials and Methods Duration of the study is from 2015 to 2019 in which 5 ALL cases were presented to this tertiary care center. The presenting symptoms varied from headache, fever, and distension of abdomen. These cases were either on therapy or post completion of chemotherapy. The diagnosis of CNS relapse followed after the examination of cerebrospinal fluid (CSF). Patients also underwent BM examination to rule out systemic relapse. Results Age of patients ranged from 7 months to 42 years. There were three female patients. Two patients had isolated CNS relapse 3.5 years after completing therapy and succumbed to their illness. Two patients had t(9;22) while one patient had t(1;14) cytogenetic abnormality at diagnosis. One patient was diagnosed as T-ALL. Treatment offered was German Multicentre ALL protocol for induction along with 10 cycles of maintenance. Conclusion The most common hematolymphoid malignancy in children namely ALL accounts for 75% of childhood leukemias. Complete remission rates reach up to 70 to 80%. CNS involvement is known to occur in these cases. CNS relapse may occur alone or with systemic relapse. Advances in therapeutic protocols along with CNS prophylaxis have drastically brought down the rates of CNS relapse. It is essential to maintain a high degree of suspicion so that these cases of isolated CNS relapse can be identified at the earliest and definitive therapy can be offered.

Introduction: Acute myeloid leukemia (AML) is the commonest leukemia in adults. Mortality in thew first 30-days ranges from 6% to 43%, while infections account for 30–66% of early deaths. We aim to present our experience of infections in newly-diagnosed AML. Method: This prospective, observational study, was undertaken at a tertiary care hospital in Northern India. Patients with confirmed AML (bone marrow morphology and flow cytometry) and who had developed febrile neutropenia (FN), were included. Result: A total of fifty-five patients were included in the study. The median age of the patients was 47.1 years (12–71) and 28 (50.9%) were males. Fever (33, 60%) was the commonest presentation at the time of diagnosis. One or more comorbid conditions were present in 20 patients (36.36%). Infection at presentation was detected in 17 patients (30.9%). The mean duration to develop febrile neutropenia since the start of therapy was 11.24 days. With each ten-thousand increase in white blood cell (WBC) count, the mean number of days of FN development decreased by 0.35 days ( p = 0.029). Clinical and/or radiological localization was possible in 23 patients (41.81%). Thirty-four blood samples (34/242, 14.04%) from 26 patients (26/55, 47.3%) isolated one or more organisms. Gram negative bacilli (GNB) were isolated in 24 (70.58%) samples. Burkholderia cepacia (8/34, 23.52%) was the commonest organism. The number of days required to develop febrile neutropenia was inversely associated with overall survival (OS). However, when compared, there was no statistically significant difference in OS between patients developing fever on day-10 and day-25 ( p = 0.063). Thirteen patients (23.63%) died during the study period. Discussion: Low percentage of blood culture positivity and high incidence of MDR organisms are a matter of concern. Days to develop febrile neutropenia were inversely associated with overall survival (OS), emphasizing the importance of preventive measures against infections. Conclusion: Infections continues to be a major cause of morbidity and mortality among AML patients.

Background: Waldenstrom macroglobulinemia (WM) is a rare mature B cell Neoplasm, characterized by monoclonal Immunoglobulin M (IgM) in the serum and lymphoplasmacytic infiltration in the bone marrow. It accounts for approx 2% of Non Hodgkin Lymphomas. The disease is slightly more common in elderly males, the median age at diagnosis being 63 years. The disease is very infrequent in India and only a few studies have been published on the disease. Hence, we bring out this study on Clinico-Pathological Profile of WM. Aims and Objectives: To study clinico-pathological profile of WM cases and to distinguish them from other plasma cell neoplasms as both the diseases have different treatment protocols and prognosis. Materials and Methods: A cross sectional observational study was conducted at tertiary care center over a period of two years. Six cases of WM were encountered and enrolled for the study due to their rarity and morphological overlap with plasma cell neoplasms. The WHO criteria were followed and patients fulfilling those criteria were included in the study. The diagnosis of WM was based on the morphologic and immunohistochemistry findings of biopsy specimens, the presence of a monoclonal IgM, and the presence of distinctive clinical characteristics. Results: Median age of patients was 60.5 years with a male preponderance. 33% of cases presented with B symptoms and 100% cases presented with moderate to severe anaemia. 50% of the cases had thrombocytopenia and hepatomegaly. All cases had albumin:globulin ratio reversal. Peripheral smear showed background staining, rouleaux formation, relative lymphocytosis. Plasmacytoid cells were present in two cases. Bone marrow aspirate smears showed features of lymphoplasmacytic infiltration with suppression of other lineages. BM biopsies were hypercellular and showed a diffuse pattern of marrow infiltration by lymphoplasmacytic cells. The immunostaining of the infiltrating lymphocytes were CD 20+ and plasma cells were CD138+. Serum protein electrophoresis and immunofixation electrophoresis confirmed IgM type of monoclonal gammopathy. Conclusion: WM is relatively a rare mature B cell neoplasm which at times can have morphological overlap with other plasma cell neoplasms. We conclude that correlation with clinical laboratory test results while making diagnostic decision is an integral part of recognition of WM due to low grade indolent course of the disease and better outcome.

Background: Chronic myelomonocytic leukemia (CMML) is a clonal hematological neoplasm with features of both myeloproliferation and myelodysplasia with an incidence 0.4 per lakh population. A number of prognostic risks scoring systems have attempted to predict survival and risk of CMML patients, like International Prognostic Scoring System (IPSS), the Spanish Score, the modified Bournemouth Score, the Dusseldorf Score and the MDAP Score. But no prognostic system has been widely accepted. More data from different regions are required to create a widely accepted working prognostic system for CMML. No case series on CMML has been published in literature from India in our knowledge. This article attempts to put to light the various clinicopathological parameters of CMML cases from India and the impact of these parameters on final outcome. Methods: All admitted patients in a tertiary center in western India, with a diagnosis of either a chronic myeloproliferative disease or a myelodysplastic disease over a period of 3 years (2015-2018) were evaluated, out of which nine(n=9) cases fulfilled the diagnostic criteria of CMML. All patients underwent peripheral blood examination, bone marrow aspirate, bone marrow biopsy and cytogenetic studies. Result: All patients (n=9) were between 50 and 80 years and most were males (n=8). Five patients presented with hepatosplenomegaly. Renal and liver function of one patient was deranged who had pleural effusion, ascites. Most patients (n=8) had total leukocyte count above 13000/cumm, while three had low platelet counts. Two out of three patients classified as CMML-II with increased blasts in peripheral blood and bone marrow had fatal outcomes. Patients whose karyotypes were available had normal karyotypes without any additional cytogenetic abnormalities. All were negative for JAK2 and BCR-ABL1. Conclusion: The study concluded that altered biochemical tests (LDH, LFT), blast percentage, CMML II, relative lymphocytosis and transformation to AML were associated with poor outcome.

Multiple myeloma (MM) is a plasma cell-associated cancer and exists as the second most common hematological malignancy worldwide. Although researchers have been working on MM, a comprehensive quantitative Bone Marrow Interstitial Fluid (BMIF) and serum proteomic analysis from the same patients’ samples is not yet reported. The present study involves the investigation of alterations in the BMIF and serum proteome of MM patients compared to controls using multipronged quantitative proteomic approaches viz., 2D-DIGE, iTRAQ, and SWATH-MS. A total of 279 non-redundant statistically significant differentially abundant proteins were identified by the combination of three proteomic approaches in MM BMIF, while in the case of serum 116 such differentially abundant proteins were identified. The biological context of these dysregulated proteins was deciphered using various bioinformatic tools. Verification experiments were performed in a fresh independent cohort of samples using immunoblotting and mass spectrometry based SRM assays. Thorough data evaluation led to the identification of a panel of five proteins viz., haptoglobin, kininogen 1, transferrin, and apolipoprotein A1 along with albumin that was validated using ELISA in a larger cohort of serum samples. This panel of proteins could serve as a useful tool in the diagnosis and understanding of the pathophysiology of MM in the future.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm in which the granulocytes are the major proliferative component and is characterised by the chromosomal translocation t(9;22)(q34.1;q11.2) leading to the formation of Philadelphia chromosome (Ph) containing the BCR-ABL1 fusion gene. This entity is quite rare in paediatric age group and even unusual is a child presenting for the first time in an accelerated or blast crisis. Here we unfold an noteworthy case of a 9 year old school going child presenting with complains of vague abdominal distension who on further evaluation was found to be living through leukaemia.

Plasma cell (PC) neoplasm (PCN) with varied morphology has been described in the literature. The majority of clonal proliferation of PCs is composed of easily recognizable morphology in the bone marrow (BM). However, few cases may cause diagnostic complexity, as they exhibit varied cytological and architectural heterogeneity which may pose problem in morphological diagnosis and require the use of ancillary techniques like immunohistochemistry (IHC). We illustrate here two such cases of PCN with varied morphology in BM aspirate, in the form of clustering/rosetting and multiple clear cytoplasmic vacuoles, respectively, leading to varied differential diagnosis. However, later, the histopathological features on BM biopsy findings were relatively characteristic and IHC confirmed the final diagnosis. The morphological variants documented in both these cases are exceptional and representative of the various forms of atypical PCs.

Multiple myeloma (MM) is a plasma cell‑associated cancer and accounts for 13% of all hematological malignancies, worldwide. MM still remains an incurable plasma cell malignancy with a poor prognosis due to a lack of suitable markers. Therefore, discovering novel markers and targets for diagnosis and therapeutics of MM is essential. The present study aims to identify markers associated with MM malignancy using patient‑derived MM mononuclear cells (MNCs). Label‑free quantitative proteomics analysis revealed a total of 192 differentially regulated proteins, in which 79 proteins were upregulated and 113 proteins were found to be downregulated in MM MNCs as compared to non‑hematological malignant samples. The identified differentially expressed candidate proteins were analyzed using various bioinformatics tools, including Ingenuity Pathway Analysis (IPA), Protein Analysis THrough Evolutionary Relationships (PANTHER), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Database for Annotation, Visualization and Integrated Discovery (DAVID) to determine their biological context. Among the 192 candidate proteins, marginal zone B and B1 cell specific protein (MZB1) was investigated in detail using the RPMI-8226 cell line model of MM. The functional studies revealed that higher expression of MZB1 is associated with promoting the progression of MM pathogenesis and could be established as a potential target for MM in the future.

Among the blood cancers, 13% mortality is caused by Multiple myeloma (MM) type of hematological malignancy. In spite of therapeutic advances in chemotherapy treatment, still MM remains an incurable disease is mainly due to emergence of chemoresistance. At present time, FDA approved bortezomib is the first line drug for MM treatment. However, like other chemotherapy, MM patients are acquiring resistance against bortezomib. The present study aims to identify and validate bortezomib resistant protein targets in MM using iTRAQ and label free quantitative proteomic approaches. 112 differentially expressed proteins were commonly found in both approaches with similar differential expression pattern. Exportin-1 (XPO1) protein was selected for further validation as its significant high expression was observed in both iTRAQ and label free analysis. Bioinformatic analysis of these common differentially expressed proteins showed a clear cluster of proteins such as SMC1A, RCC2, CSE1, NUP88, NUP50, TPR, HSPA14, DYNLL1, RAD21 and RANBP2 being associated with XPO1. Functional studies like cell count assay, flow cytometry assay and soft agar assay proved that XPO1 knock down in RPMI 8226R cell line results in re-sensitization to bortezomib drug. The mass spectrometry data are available via ProteomeXchange with identifier PXD013859. BIOLOGICAL SIGNIFICANCE: Multiple myeloma (MM) is a type of hematological malignancy which constitutes about 13% of all blood cell related malignancies. Chemoresistance is one of the major obstacles for the successful treatment for MM. Bortezomib is a first proteasome inhibitor drug, widely used in MM treatment. The present study aims to identify and validate bortezomib resistant protein targets in MM. Here, we identified 112 candidate proteins to be associated with bortezomib resistance using global quantitative proteomic analysis. Among these candidate proteins, we show that XPO1 plays crucial role in emerging bortezomib resistance using functional studies like cell count assay, flow cytometry assay and soft agar assay. XPO1 could be a potential therapeutic target for MM and development of inhibitors of XPO1 might help to cure MM.

Waldenstrom's macroglobulinemia (WM) is one of the rare hematological malignancies and accounts for 1%–2% of all blood cancers. While fatigue is the most common presentation; hyperviscosity syndrome, symptomatic cryoglobulinemia, and cold agglutinin disease (CAD) are the characteristic symptoms. However, they occur only in 5%–15% of all patients of WM. We discuss a 63-year-old patient who presented with nonhealing ulcers on both lower limbs and severe anemia. His blood clotted in ethylenediaminetetraacetic acid sample tubes, and there was difficulty in getting blood cross matched for transfusing him. During evaluation, he was found to have high erythrocyte sedimentation rate, albumin globulin reversal with serum protein electrophoresis, and immunofixation suggestive of immunoglobulin M monoclonal gammopathy. There was evidence of autoimmune hemolytic anemia and skin biopsy from ulcers revealed hyaline thrombosis and deposition of cryoglobulins. He was diagnosed to have WM with cryoglobulinemia and CAD.

Background: Pancytopenia is characterized by decreased hemoglobin (adult males

Chemoresistance is one of the major hurdles in cancer treatment leading to recurrence of cancer and affects the overall survival of patients. Cancer chemoresistance can be associated with various phenomena including modulation of vital cellular pathways. Unrevealing these alterations could provide a better understanding of chemoresistance and assist in the identification of new targets to overcome it. Recent advances in the field of proteomics and metabolomics have substantially helped in the identification of potential targets for chemoresistance in various cancers. This review highlights the potential of proteomics and metabolomics research to explore the putative targets associated with cancer chemoresistance with a special focus on Multiple Myeloma (MM). MM is a type of hematological malignancy which constitutes about 13% of all blood cell cancers. The therapeutic advancements for MM have increased the median overall survival rate to over 3-fold in the last one and half decade. Although in recent times, significant improvements in the overall survival rate of MM are achieved, MM remains an incurable disease with unpredictable refractory mechanisms. In spite of therapeutic advances, chemoresistance thrives to be a major hurdle in the treatment of multiple myeloma which demands a better understanding of chemoresistance. In this review, we have attempted to highlight the potential applications of proteomics and metabolomics research in the understanding of chemoresistance in MM.

Autologous hematopoietic stem cell transplant (HSCT) for rapidly progressive disease has not been reported in localized scleroderma. Our patient, a 16-year-old girl had an aggressive variant of localized scleroderma, mixed subtype (linear-generalized) with Parry Romberg syndrome, with no internal organ involvement, that was unresponsive to immunosuppressive therapy and was causing rapid disfigurement. She was administered autologous HSCT in June 2011 and has maintained drug-free remission with excellent functional status at almost 3.5 years of follow-up.

Acquired haemophilia or factor VIII (FVIII) deficiency, caused by FVIII inhibitor antibodies, is a very rare condition that commonly results in severe haemorrhagic complications. We report a case of acquired haemophilia presenting with multiple bluish patches affecting face, neck, upper & lower limbs, history of gum bleeding and left knee haemarthrosis. The patient was found to have acquired FVIII inhibitor and lupus anticoagulant (LAC). The simultaneous presence of LAC and FVIII inhibitor is exceedingly rare. The differentiation between these two conditions is crucial, because both result in a prolongation of the activated partial thromboplastin time test, which does not correct when mixed with the plasma of a normal control; however, the clinical manifestations range from thrombosis in the presence of LAC to massive haemorrhage with FVIII inhibitors.

Introduction: The outcomes of Philadelphia positive acute lymphoblastic leukemia(Ph-ALL) have improved significantly after the introduction of tyrosine kinase inhibitors (TKI). The presence of Philadelphia positivity once considered as poor prognosis mandating transplantation, now even can be managed with TKI added to steroids. The data is scarce on Ph-ALL from real-world settings with resource constraints. Objective: To study the characteristics and outcomes of Ph+ve ALL from real world settings. Methodology: It is a retrospective observational study wherein the data of all patients of Ph-ALL managed at a tertiary care center in North India over the last 14 years (2004-2018) were analyzed. All case records of the Ph-ALL were perused, digitalized and their survival statistics derived. Results:Amongst a total of 611 ALL case records, 55 (9%) were Ph-ALL. Ph-ALL cases with complete data (n-51) were analysed for overall survival. The mean age of the patients was 31± 2.41 years (range 3-76) (Fig. 1A). Males constituted 74.5% (n-38) and females, 25.4% (n-13) of our cohort. On risk stratification, 11 (21.5%), 5 (9.8%), and 35 (68.6%) patients were classified as standard, intermediate and high risk. Twenty five percent patients had associated complex karyotype in addition to the Ph positivity. Of these 24 patients (47.05%) received adult ALL (GMALL protocol), 15 patients (29.4%) received paediatric BFM protocol, and12 patients (23.5%) received Hyper-CVAD. Week 4 Bone marrow evaluation was in CR in 87.2% of patients. L-Asparaginase was given in only 60% of the patients. An interruption in the therapy of more than 2 weeks for various reasons was present in 23.4% of the patients, mainly secondary to infections. Prophylactic cranial irradiation was given in 34.7% of the patients and high dose methotrexate was given in 30.4% of the patients. Relapse was seen in 22% of the patients. CNS disease was present in 17.6% of the patients. Only 19.6% of the patients were subjected to transplant. All patients received TKI, of which 44% received high dose imatinib and 56% patients received dasatinib. A total of 19.6% patients succumbed to the illness at various stages of the therapy. The cumulative overall survival at 1y (1y-OS) was 95.68% with 3y and 5y OS being 72.09% and 63.07% (Fig. 1B). The survival was not statistically different between patients with and without complex karyotype (p-0.52),based on type of TKI administered (Dasatinib Vs high dose Imatinib) (p-0.76), males and females (p-0.41), risk category (p-0.41) or by the presence of CNS disease (p-0.21) (Fig. 1C-G). The survivals based on the type of protocol was statistically different with the best survival with GMALL protocol and the least survival with Hyper-CVAD therapy (log rank p Conclusion: We have demonstrated in this study the improved outcomes of Ph-ALL who usually present late in resource constraint settings. There was no additional benefit of dasatinib over high dose imatinib in this cohort. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

There is a growing evidence that rhinosinusitis may be associated with asthma as different manifestations of the same disorder. Several reports suggest the effectiveness of endoscopic sinus surgery (ESS) in asthmatic patients with chronic rhinosinusitis (CRS). Whether ESS has a positive effect on the clinical course of asthma still remains controversial. The aim of this study was to investigate the outcomes of ESS on asthma in patients with coexistent CRS.We performed a study to evaluate the effectiveness of ESS in 70 patients of CRS with associated asthma. The study compares changes in symptoms, medication and objective measures like pulmonary function in patients with persistent bronchial asthma and CRS before and after ESS.Following ESS, there was an improvement in the mean asthma symptoms (wheeze, cough and shortness of breath) and asthma medication use. The number of emergency department visits and hospital admissions also showed a reduction postsurgery. Objective analysis with pulmonary function tests revealed an improvement in the predicted scores. Three patients with extensive polyposis showed poor improvement after surgery and needed revision.This study provides corroborative subjective and objective evidence that ESS is efficacious in the management of patients with CRS and asthma.

Dapsone is a cheap and widely used drug in many diseases. It can rarely cause dose-independent methemoglobinemia. The key to managing such cases is strong clinical suspicion and prompt discontinuation of the drug. Effective antidote is methylene blue which can rapidly reverse effects in seriously ill patients. Here, we present two such cases that we came across who were managed differently and successfully at our center.

Introduction: Endocrine complications are common after hematopoietic stem cell transplant (HSCT). Although HSCT is performed at various centers in India, no study is available for endocrine dysfunctions among them. This study was carried out with the objective to evaluate endocrine dysfunction among patients undergone HSCT in the past. Materials and Methods: We carried out a cross-sectional study in a 50 post-HSCT recipients (39 allogenic, 11 autologous). All relevant data were collected from patient′s records. Samples for hormonal estimation were collected and stimulation tests for cortisol and growth hormone were interpreted based on peak values achieved during insulin tolerance test. Results: The mean age of patients was 26.3 ± 16.9 years (range 4-74). Adrenal insufficiency (AI) was present in 60%, hypergonadotropic hypogonadism (HH) in 60%, growth hormone deficiency (GHD) in 54%, hypothyroidism in 4%, hyperprolactinemia in 4%, new onset diabetes after transplant in 4%, and impaired fasting glucose in 6%. Multiple endocrine complications were common. GHD was present in 77% of children (n = 22) although height standard deviation score was not statistically different compared to those who didn′t have GHD. HH was present in 36% of children. In adults (n = 28), 36% had GHD, all females had HH, and 89% of males had HH. Germ cell dysfunction with compensated Leydig cell dysfunction was the most common pattern of HH in males. Fifteen patients had graft versus host disease (GVHD). GVHD had no bearing on development of endocrine deficiencies. AI was related to duration after and type of transplant, but was unrelated to steroid intake. Conclusions: Endocrine manifestations are common after HSCT; they can occur as early or late complications. All HSCT recipients should have endocrine evaluation as per prevailing guidelines.

Between 2001 and 2009, 121 patients with severe aplastic anemia (SAA) underwent hematopoietic stem cell transplantation (HSCT) using a conditioning protocol of fludarabine and cyclophosphamide at three Indian hospitals. Donors were HLA-identical sibling or family donors. Seventy-six patients were considered "high risk" as per criteria. The graft source included peripheral blood stem cells in 109 and G-CSF-stimulated bone marrow in 12. GVHD prophylaxis consisted of cyclosporine and mini-methotrexate. Engraftment occurred in 117 (96.6%) while two had graft failure and two expired in the first two wk. Neutrophil engraftment was seen at 12.3 d (range: 9-19) while platelet engraftment occurred at 12.4 d (range: 8-32). Grade II-IV acute GVHD was seen in 26.7% and grade IV GVHD in 8.6%. Chronic GVHD occurred in 44% and was extensive in 10%. The five-yr overall survival for the entire cohort is 75.8 ± 3.9% with a survival of 95.6 ± 3.1% in the low-risk group (n = 45) and 64.0 ± 5.6% in the high-risk group (n = 76). Conditioning with fludarabine and cyclophosphamide is associated with very good long-term survival in patients undergoing HSCT for SAA.

Objective To analyse the clinicopathological presentation, outcome and importance of bone marrow haemophagocytosis in patients with infection-associated haemophagocytic lymphohistiocytosis (IA-HLH) in a tertiary care hospital in Northern India. Study design Between January 2007 and December 2009, 26 consecutive patients meeting the diagnostic criteria for IA-HLH, based on the HLH2004 protocol of the Histiocyte Society, were followed up for between 12 and 34 months (median 20 months). Results IA-HLH was diagnosed in three of the five patients who died 5–6 weeks after the onset of the illness, whereas diagnosis in the remaining group was made a median of 2 weeks after the onset of the illness. The predominant presenting features were fever (100%), hepatomegaly (69%), splenomegaly (58%) and anaemia (96%). All patients showed >3% haemophagocytosis on bone marrow studies—in four cases after serial aspiration/biopsies. Twenty-one (80.8%) cases were non-fatal and five (19.2%) patients died. The non-fatal cases included eight (38.1%) cases of viral infection, seven (33.3%) bacterial infections, two (9.6%) fungal and four (19.0%) protozoal infections; whereas four (80%) bacterial infections and one (20%) viral infection were associated with the fatal cases. The mean of the nadir blood counts of white blood cells, absolute neutrophil counts and platelets; the mean of all the peak biochemical parameters of liver function tests, lactate dehydrogenase and ferritin and the lowest fibrinogen values before treatment, differed significantly (p Conclusions IA-HLH is important because it can obscure the typical clinical features of the underlying primary disease, thus delaying the diagnosis and having a negative effect on the outcome. Although bone marrow haemophagocytosis is not a mandatory diagnostic criterion, we found it to be a useful tool together with biochemical parameters for early recognition of HLH, especially in developing countries lacking molecular and flow laboratories. The severity of pancytopenia and derangement in biochemical markers were significantly higher in the patients who died.

Introduction Diamond-Blackfan anemia and Duchenne muscular dystrophy are two rare congenital anomalies. Both anomalies occurring in the same child is extremely rare. Allogeneic hematopoietic stem cell transplantation is a well-established therapy for Diamond-Blackfan anemia. However, in patients with Duchenne muscular dystrophy, stem cell therapy still remains experimental. Case presentation We report the case of a nine-year-old boy of north Indian descent with Diamond-Blackfan anemia and Duchenne muscular dystrophy who underwent successful allogeneic hematopoietic stem cell transplantation. He is transfusion-independent, and his Duchenne muscular dystrophy has shown no clinical deterioration over the past 45 months. His creatine phosphokinase levels have significantly decreased to 300 U/L from 14,000 U/L pre-transplant. The patient is 100% donor chimera in the hematopoietic system, and his muscle tissue has shown 8% to 10.4% cells of donor origin. Conclusion Our patient's Diamond-Blackfan anemia was cured by allogeneic hematopoietic stem cell transplantation. The interesting clinical observation of a possible benefit in Duchenne muscular dystrophy cannot be ruled out. However, further clinical follow-up with serial muscle biopsies and molecular studies are needed to establish this finding.

To determine the survival of children≤18y, treated with immunosuppresive therapy (IST) using equine antithymocyte globulin (e-ATG) and cyclosporine (CsA). Prospective data entry as per a specified format. Tertiary care hospital. From January 1998 to December 2009, 40 children were diagnosed with acquired aplastic anemia; 33 patients, who received IST, were analyzed. 31 children (94%) received one course of e-ATG and CsA. 2 patients (6%) received two courses of ATG. Immunosuppressive therapy using equine ATG and cyclosporine. Overall response and overall survival. The overall response (complete response + partial response) to IST at 6 months was 87.9%. 8 (24.2%) patients achieved CR, 21 (63.6%) patients had PR and 4 (12.1%) patients did not respond to IST. Median follow-up was 24 (6–102) months. Overall survival at 24 months was 90%, with an acturial survival of 85.4% at 5 years. Seventeen patients (51.5%) received G-CSF for a median duration of 32 (23–64) days. The patients who received G-CSF had fewer infectious complications (P=0.002), but G-CSF administration did not influence survival/outcome. No patient developed myelodysplastic syndrome or acute leukemia. The survival of patients who respond to IST is excellent. Also, G-CSF reduces the infectious complications without conferring any survival advantage.

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.

Background: Despite intensive remission induction chemotherapy, up to 5–10% AYAs with acute lymphoblastic leukemia (ALL) are primarily refractory.1,2 Of those that achieve a remission, as much as 70–80% fail consolidation largely due to relapse or sustained aplasia. Allogeneic stem-cell transplantation (allo-SCT) remains the only salvage option with curative potentials available, but the long-term benefits of the procedure and whether all patients should benefit from it remains controversial. There has always been a discussion about best conditioning regimen for ALL transplants especially in resource limited situation where TBI is not available. We analyzed our data on allo-transplants for ALL, wherein we had used non-TBI protocols for conditioning. Study: This study retrospectively analyzes the outcome in 32 patients ( 19 females & 13 males) who underwent Allo-SCT for refractory acute lymphoblastic leukemia at our center between 2000-2013. The median age was 28 years (range, 7–26). 14 patients had relapse, 8 failed re-induction, 5 in partial remission & 7 patients had high risk disease ( Ph+ disease). All patients were in a state of bone marrow remission at the time of transplantation. All received myeloablative conditioning using busulfan( BU) & cyclophosphamide( CY). The stem cell harvesting was done by peripheral G-mobilized stem cell collection from related donors. All patients received graft-versus-host disease (GVHD) prophylaxis with cyclosporin and methotrexate. Infection prophylaxis & supportive care was provided as per standard protocols. The median cell dose was 5.4 MNCx10 7/Kg (3.8-7.6) & CD34 cells 3.7x105/Kg. 31 patients engrafted successfully by median day 12(7-23) for White cells & median day 38 ( 27-48) for platelets. One patient experienced late graft failure. 21 patients developed Gd-II acute-GVHD, 11 of them progressed to severe form( Gd-III). 5 pateints had severe grade IV Ac GVHD. 3 of them died chronic-GVHD appeared in 14 patients,. 19 patients (58%%) remain alive after a median of 60 months (range, 6–174); with 13 deaths, mostly from relapse (n=10) and infections (n=3). Overall survival (OS) and progression-free survival (PFS) at 5 years was 53% and 48%, respectively. OS and PFS were significantly better with blasts 20% and time to transplant 1 year. Conclusions: We conclude that patients with refractory leukemia can benefit from allogeneic BMT, if they are transplanted in a state of remission, by using non-TBI based protocols. Thus in a resource limited situation, the outcome in refractory ALL can still be improved by improvisation of protocols without using TBI in conditioning regimens. Disclosures No relevant conflicts of interest to declare.

Background:Myeloablative chemotherapy using busulfan(BU) & cyclophosphamide(CY) is a standard form of conditioning for thalassemia transplantation. But this is associated with substantial incidence of graft rejection. This is much more common in high risk patients . Methodology:This study retrospectively analyses the outcome of 50 (34 boys & 16 girls) consecutive children, who underwent HLA matched stem cell transplantation from family donors at our centre All patients were classified into 3 risk groups on the basis of inadequate chelation, hepatomegaly and the presence of portal fibrosis in the liver. Pesaro Class 1 patients had none of these, class 2 patients had one or two and class 3 had all three.30 patients received oral BU 1 mg/kg, Q6H for 4 days followed by CY 60 mg/kg/D for two days. & rabbit ATG (2.5 mg/kg/day from Day-5 to Day-1). Patients with advanced disease (class 3) received BU 0.8mg/Kg & CY 50 mg/kg. with same dose of ATG. All patients received stem cells harvested from G-mobilized bone marrow Standard MTX & Cyclosporin based GVHD prophylaxis , infection prophylaxis & supportive care as per standard protocols were given as per standard protocols. Chimerism was routinely monitored at 30, 60, 90, 120 and 365 days post transplant using PCR-based analysis of selected polymorphic STRs loci. Results :OS and thalassemia-free-survival were estimated according to the Kaplan-Meier method. Probabilities of rejection, GVHD and infections were calculated by using the cumulative incidence estimator. The impact of the following parameters on OS and TFS was examined: (1) age of the recipient (above vs below the median value) (2) serum ferritin (above vs, the median value) (3) Pesaro class, (4) total nucleated cells per kg (contained in the graft) (above vs below the median), (5) CD34+ cells contained in the graft (above vs below the median) and (6) BU (oral vs i.v. BU). Both univariate and multivariate analysis of prognostic factors were made according to the log-rank test and to a stepwise Cox proportional hazards regression model, respectively. With a median follow-up of 11 years (range 1—17 years), the overall survival (OS) and thalassemia free survival (TFS) rates were 94% and 90%, respectively. The estimated TRM was 4% while the cumulative incidence of rejection/failure were 2%. One patient ( Class III, & HIV infection) died of severe veno-occlusive disease. ,The patient who rejected the graft after 10 months, received II transplant & is transfusion free with 98% donor chimerism post second transplant. The cumulative incidences of acute GVHD grade II & grade III were 15% & 8 %, respectively. 1 patient developed acute GVHD grade IV. None of the patients developed chronic GVHD. The estimated OS and TFS for patients with Class 1 and 2 disease according to Pesaro criteria were 94% and 92%, whereas for patients with Class 3 disease they were 90% and 85%, respectively. Conclusions: Myeloablative( BU-CY) conditioning with ATG as conditioning from matched sibling donors with innovative modifications can be used to achieve excellent survival , with a low incidence of TRM and graft rejection in low as well as high risk patients. Disclosures No relevant conflicts of interest to declare.

Thirty consecutive cases of Takayasu's arteritis (TA) admitted over a period of four years in a large referral hospital were analysed. The extent of aorta and its branches involvement was assessed by a Duplex Doppler study and aortography. The mean age of patients was 24.7 years with the male to female ratio of 1:1.2. The vascular involvement was, Type I (10%), Type II (40%) and Type III (50%). Renal artery (76.6%), Coeliac and superior mesenteric arteries (46.6%) and right common carotid artery (30%) were the commonly involved branches of aorta. Systemic features were seen in 25 per cent cases. Hypertension (83.3%), unequal pulses (80%) and arterial bruit (66.6%) were common clinical features. Stroke (20%), cardiac failure (10%) and renal failure(10%), were the complications seen. Hypertensive retinopathy was common, but Takayasu's retinopathy was not seen.

Context Acute promyelocytic leukemia (APL), an AML subtype, is characterized morphologically by abnormal promyelocytes. Molecular studies show three possible bcr isoforms of PML-RARα fusion gene. This study undertakes analysis of PML-RARα bcr isoforms and their correlation with haematological parameters and response to treatment in Indian patients. Aims To study different PML-RARα bcr isoforms in Indian patients and to find any correlation with various haematological parameters and response to treatment Settings and Design Patients diagnosed as APL on morphology or flowcytometry and confirmed by RQ PCR were included in the study. Treated APL patients or patients with relapse and on follow-up were excluded from the study. Methods and Material Twenty patients over thirty one months period were included. The clinical, haematological & morphological features were analysed, the latter using routine & special cytochemical stains on blood and bone marrow. Flow cytometric evaluation using 4-color Beckman Coulter FC 500 and molecular studies using RT PCR Fusion Quant® kits for bcr-1, bcr-2 and bcr-3 of PML-RARα bcr isoforms on the instrument Rotor Gene™ 3000 were performed. Statistical analysis used Student t test was applied to correlate different bcr isoforms with various haematological parameters and response to treatment. Results In our study, M:F ratio was 1.5:1 with median age 42 years, Hb - 8.0 g/dl, TLC-7900/μl, and platelet – 35000/μl and varied clinical presentation. Four patients were microgranular variants, and the rest were hypergranular. MPO and CAE positivity were100% and for NSE it was 33.33%. Molecular analysis revealed PML-RARα isoforms of bcr1 in 42.85%, bcr2 in 14.28% and bcr3 in 38.09% patients. No correlation was found between PML-RARα bcr isoforms, different haematological parameters and response to treatment. Conclusions Higher incidence of PML-RARα bcr-1 isoform was found in Indian APL patients with no significant correlation between different haematological parameters and response to treatment.

One case of acute panmyelosis with myelofibrosis (APMF) is being reported. A 45 year old male presented with abrupt onset of rapidly progressing low backache, weakness and pancytopenia. On examination there was no organomegaly. Peripheral blood examination revealed normocytic normochromic red blood cells with 10% circulating blasts. Flowcytometric examination of peripheral blood revealed blasts which were positive for CD 34 ,HLA- DR and myeloid associated antigens (i.e. CD13 and CD33).Blasts were negative for anti MPO. Bone marrow aspirate resulted in a dry tap. Bone marrow biopsy revealed panmyeloid proliferation with scattered blasts which were CD 34 positive on imunohistochemistry and negative for anti MPO. Reticulin stain showed grade III myelofibrosis (WHO). Differential diagnosis considered included AML-M7, MDS-RAEB II and AML with myelodysplasia . He was started on chemotherapy [idarubicin and cytarabine; 3+7 induction regimen followed by three cycles of HIDAC (High dose cytosine arabinoside)] after which patient was in complete morphological remission with markedly reduced bone marrow fibrosis. He is now being worked up for allogeneic stem cell transplantation. Patient is asymptomatic at eight months of diagnosis. In conclusion these patients should be managed aggressively with AML therapy and this case report reaffirms the fact that APMF is subtype of AML.

Abstract 4206 Introduction Multiple myeloma is a plasma cell tumor which accounts for about 10% of hematological malignancies. In recent years some advances in the management of this malignancy have been achieved, especially the newer drugs like thalidomide, lenalidomide and bortezomib. Lenalidomde, a second generation immunomodulatory drug has been shown in various series to be a highly effective agent in management of newly diagnosed as well as relapsed cases of myeloma. The incidence of venous thromboembolism in patients of myeloma taking Lenalidomide – Dexamethasone therapy has been reported as high as 17 %. The risk of thromboembolism is to some extent determined by genetic predisposition of a population. There are no published reports from the Indian subcontinent addressing the incidence of venous thromboembolism in patients with newly diagnosed or relapsed multiple myeloma treated with Lenalidomide – Dexamethasone. Patients and Methods Forty one consecutive patients diagnosed at our centre with multiple myeloma either afresh (n=30) or relapsed on a previously different treatment regime (n=11), were studied between Oct2007 to Jul 2009. Diagnosis was based on serum electrophoresis and immunofixation, bone marrow plasmacytosis, and relevant tissue involvement. Patients were staged as per Durie Salmon system, and all our cases were found to be in stage 3 (3A = 34 cases, 3B = 7 cases). Detailed baseline clinical, haematological, and biochemical parameters were recorded. Colour Doppler flow imaging (CDFI) using a Philips 5000 imager of the lower limbs by an experienced radiologist was performed in all patients for DVT. D dimer using immunoturbidometric semi quantitative slide agglutination assay which measures fibrinogen equivalent units which is usually twice the actual D dimer value ( Results We report an overall response of 95% (nCR + CR : 30%) in newly diagnosed cases of multiple myeloma and 81.8% (nCR + CR : 36%) in patients with thalidomide failure / intolerant group. The primary toxic effect of lenalidomide was haematological and was manageable with dose adjustment of lenalidomide and supportive care. D dimer levels were found to be in the range of 0.5 to 2.4 mcg/ml (mean = 1.46 mcg/ml). On detailed follow up for upto six months there was no episode of venous thromboembolism recorded in any of the patients. All patients were asymptomatic for DVT and CDFI of lower limbs was normal at all points of examination in all patients of myeloma, newly diagnosed or relapsed. Conclusion Lenalidomide – Dexamethasone therapy is a highly effective regime for treatment of newly diagnosed and relapsed myeloma patients. In our cohort of both relapsed and fresh cases (n=41), on thromboprophylaxis with 75 mg asprin, not a single case of DVT was documented, proving its safety profile for venous thromboembolism. Larger trials would however be required to ascertain the exact risk of thromboembolism in patients of myeloma taking this treatment regime. Disclosures: No relevant conflicts of interest to declare.

Abstract 4364 Introduction Most patients with acute myeloid leukemia (AML) who achieve a complete remission after induction chemotherapy will relapse if they do not receive effective consolidation therapy particularly patients of high and intermediate risk. Standard chemotherapy only achieves less than 30% overall survival at 2 years. The most effective consolidation for high risk and intermediate risk patients is allogeneic stem cell transplantation (allo-SCT) which may be related or unrelated. However in the developing world availability of a human leucocyte antigen (HLA) matched donor for those lacking a sibling match is rarely available due to minority of voluntary donors from Indian subcontinent in various registries. Hence autologous stem cell transplant (auto-SCT) is one option that has been studied extensively. The question as to whether auto-SCT after consolidation chemotherapy improves the probability of survival of patients with AML has not been settled. In view of the above considerations, we carried out a retrospective study aimed at analyzing the impact of disease, patient, and transplantation-related factors on relapse, non–leukemia-related death, and LFS of patients with AML. Patients and methods We present here retrospective data of 16 patients of AML who undergone auto SCT in our centre from Jan 2005 to Jan 2009. The median age of patients was 24 yrs with a range from 10 to 40 years. Male: Female ratio was 11:5. The diagnosis was established on both bone marrow morphology and immunophenotyping study. Morphologically there was 1 case each of AML-M1, AML-M4, AML-M5, AML-M6 and rest 13 cases were of AML-M2. Bone marrow karyotyping was done in 11 cases. Out of 11 cases where karyotyping was done, 2 were metaphase failures; 1 was deletion 7; 1 was trisomy 8 and rest had normal cytogenetics. All cases were classified as high risk or intermediate risk either by cytogenetics or by other standard criteria. All patients received standard induction chemotherapy (Idarubicin x 3days, Cytosine CI x 7days) followed by 2 or 3 high dose Cytosine. Fourteen patients were in first remission (CR-1) while 2 patients were in CR-2 (one case of AML-M5 with deletion 7 and one AML-M4 with normal cytogenetics). None of the patients had a related HLA matched donor and all patients underwent auto-SCT, the graft being peripheral blood stem cell. The conditioning regimen for initial 6 cases were Busulfan(16mg/kg over 4 days) and Cyclophosphamide(120mg/kg over 2 days)(BuCy) and the remaining 10 cases were adminstered Idarubicin (60mg/mt2 over 3days) and Busulfan (16mg/kg over 4 days) (IBu). All cases engrafted except one patient who died due to sepsis on 6th day post SCT prior to engraftment. The median engraftment for neutrophil was day10 (9-14) and platelet was on day 16 (13 - 20). Results Nine out of 16 patients are alive and free from leukemia on median follow up of 38 (18 to 56 months). Five patients died due to leukemia relapse; 1 patient had transplant related mortality (Sepsis) and 1 patient died due to unrelated cause (Severe heat exertion with multiorgan failure). The overall (OS) and leukemia free survival (LFS) on a median follow up of 38 months was 56.25% which is better than the chemotherapy group. The treatment related mortality (TRM) was 6.25%. Both patients transplanted in CR-2 relapsed and died. Three out of 6 patients from BuCy and 6 out 10 from IBu conditioning are alive. Out of 9 patients surviving, 5 had normal karyotype while in 4 same was not known. The patients with deletion 7 and trisomy 8 died due to leukemia relapse. Conclusion Auto-SCT is a viable option for AML patients who are in need of a allo-SCT but do not have a donor. However larger studies would be required to establish the exact role of auto-SCT in AML. Disclosures: No relevant conflicts of interest to declare.