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Background Mothers of children diagnosed with cancer are found to have coping difficulties in various studies. Most of the studies were done on parents after their child has been newly diagnosed with malignancy, and very few studies were done on coping skills intervention. Hence, this study has been done to assess the impact of cognitive behavioural intervention on caregiver burden in mothers of children diagnosed with cancer. Methods Twenty mothers coming to the outpatient department of paediatric oncology from 01 September 2018 to 30 April 2019 were enrolled for the study. The participants were administered General Health Questionnaire, Brief Coping Operation Preference Enquiry Scale, Zung Self-Rating Anxiety Scale, and Coping Inventory for Stressful Situations-21 (CISS-21) Scale. Sixteen sessions of cognitive behavioural intervention were given over 8 weeks to all the participants. Reassessment was done after 3 months by use of the above mentioned scales. Results Participants’ mean anxiety score was 49.40 (standard deviation [SD] ±8.89). They used adaptive (active coping and positive reframing) more than the maladaptive (denial and self-blame) coping strategies. Task- and emotion-focused coping mean score on CISS-21 revealed 19.25 (SD ±6.20) and 18.90 (SD ±5.76), respectively. Reassessment after cognitive behavioural intervention revealed statistically significant improvement in maladaptive coping styles, mean anxiety index score, avoidance, and emotion-focused coping. Conclusion The study has revealed mild to moderate anxiety and the use of both adaptive and maladaptive coping strategies by participants. There is statistically significant improvement in anxiety, maladaptive coping strategies with cognitive behavioural intervention.

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.

BACKGROUND: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are a spectrum of hematological malignancies with a multistep process of accumulated genetic and epigenetic alterations. DNA methylation is most extensively studied epigenetic alteration in malignancies. Recent research studies in the field have brought out translational implications of promoter methylation of tumor suppressor gene p15 in tumors. Therefore, we studied the role of DNA Methylation of p15 gene in AML and MDS. METHODS: The study was carried out in 41 consecutive AML/MDS cases reporting to hematological OPD of a tertiary care center along with 25 age and sex-matched healthy controls. The methylation status in the promoter region of the p15 gene was assessed by methylation-specific PCR (MSP) from blood samples after ethical approval and informed consent of the patients and controls. The association of methylation status was studied with clinical presentations, AML subtypes, and cytogenetics using Chi-square test/Fisher's exact test tools. RESULTS: A total of 41 cases included in the study comprised 33 cases of AML and 08 cases of MDS with an age range between 06 months and 82 years. Of the 41 cases, 29 revealed promoter methylation of the p15 gene, which compared to healthy controls was found statistically significant (p

Background Antibiotic resistance in bacteria is a cause for concern, especially in hematopoietic stem cell transplant (HSCT) patients. Endogenous bowel microflora in HSCT patients get replaced by hospital multidrug resistant flora and pose risk of serious bacterial infection during the pre-engraftment stage. For decades, many methods to reduce the translocation of gut microbiota in HSCT patients have been attempted. Despite the logic, of using prophylactic antibiotics, there is no consensus on standard regimen. Personalized antibiotic prophylaxis-based on gut microbiota and clinical profile has been suggested by researchers. In this study, gut microbiota in HSCT recipients has been studied with antimicrobial susceptibility testing and detection of various antibiotic resistance phenotypes. Methods Seventy-six HSCT patients (2016–2018) were included. Stool surveillance cultures and antibiotic susceptibility testing were performed. Bacterial isolates were classified into various antibiotic resistance phenotypes. Results This study revealed that 73.75% HSCT recipients had gut colonized with antibiotic resistance microbiota which included extended-spectrum β-lactamase-, multidrug- and extensively drug-resistant phenotypes. Conclusion This study reiterates the importance of individual profiling of gut microbiota in HSCT patients.

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.

In developing countries, anti-D has been used in immune thrombocytopenia (ITP) as a cheaper alternative to human immunoglobulin. We aim to analyze the response and safety profile of anti-D in patients with severe ITP. A retrospective study was conducted at a tertiary care hospital in Northern India. Patients received a single intravenous infusion of 75 μg/kg anti-D. In total, 36 patients (20 females) were included in this study. The median duration from ITP diagnosis to anti-D therapy was 235 days (range 1-1613 days). Four (11.1%) patients received anti-D as an upfront treatment. The patients' platelet counts rose significantly by the end of day three and continued to be significantly high until day 30 of receiving anti-D (p ≤ 0.001). The overall response rate (ORR) by day seven was 88.89%. There was no effect of age, sex, duration of disease, prior therapy, and platelet count on the ORR. Patients were followed up for a median duration of 52 days (longest follow-up: 3080 days). Six (6/36, 16.67%) patients continued to be in remission till the last follow-up. The hemoglobin fall was statistically significant on day three and day seven (p 0.001 and p = 0.001) and got normalized by day 30. We observed equally good ORR in mixed populations and different phases of ITP along with long-term sustained response. The study demonstrates a quick and high response rate along with good safety profile to anti-D in all forms of ITP.

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.

Inhibitors to factor V is a rare phenomenon with varied clinical presentation ranging from asymptomatic states to life-threatening bleeds. They are known to be associated with exposure to bovine thrombin, drugs, autoimmune diseases and malignancies. Establishing the diagnosis of FV inhibitors is challenging and the presence of lupus-like properties of the inhibitor can further complicate the diagnosis. Here we document an unusual case of an asymptomatic elderly female posted for pacemaker implantation and incidentally, the laboratory workup revealed a disproportionately abnormal coagulation screen. The intricacies in the diagnosis and management are discussed along with a brief review of the literature. An awareness of the diverse manifestations of this underrecognized disorder and difficulties in management is essential for medical practitioners, particularly in patients with idiopathic severe bleeding diathesis.

Background: Immune Thrombocytopenia (ITP) is characterized by low platelet counts. Splenectomy has been in practice for the treatment of ITP since the early 20th century. We aimed to analyze the data of ITP patients from our hospital who underwent splenectomy and further present the long-term outcome and safety profile in these patients. Method: This study was a single-center, registry based study conducted at a tertiary care hospital in Northern India. Patients aged 18 years or more, who underwent splenectomy after at least one line of therapy, were included in the study. The primary outcome was the overall response rate (ORR) at one month after splenectomy. Secondary outcomes were sustained response, relapse-free survival, factors affecting the ORR, and adverse events after splenectomy. Results: Forty-five patients of ITP were included in the study. Thirty-six patients underwent splenectomy in the first half (2001-2010), of the study period. The median age of the patients was 38 (19-56) years. The median duration from diagnosis to splenectomy was 1.76 (0.47-2.58) years. The median number of therapy received before splenectomy was 3 (1-6). The overall response rate (ORR) post-splenectomy at day 30 was 89.2% with 61.8% complete response (CR). The ORR was 88.5% at 1-year, with 48.8% CR. The relapse-free survival (RFS) at 5-years was 57.38% (95% Confidence Interval 40.59-71.02%), There was no effect of duration of disease, age, gender, and prior therapy received, on the ORR at one-month. At one year, the platelet response was significantly better in patients who had a CR at one-month than patients who had a partial response at one month. The relapse-free survival was better in patients who achieved CR after 1-month of splenectomy. During the median follow-up of 5.02 (1 month-20 years) years, there were five cases of overwhelming post-splenectomy infection (OPSI). There was no recorded incidence of perioperative mortality, deep vein thrombosis, or mesenteric thrombosis. Discussion: Despite the variation in outcome from different studies, splenectomy gives the best possible long-term treatment-free remission amongst all the available second-line agents. It is also, one of the most financially affordable therapies. Despite advantages, the number of ITP patients undergoing splenectomy has been on the decline and largely attributable to the newer and more effective second-line therapies. There is no pre-surgery variable predicting the ORR after splenectomy. Conclusion: Splenectomy in ITP offers a long-term sustained response at an economical cost.

Background: Immune thrombocytopenia (ITP) is a benign hematological disorder characterized by low platelet counts in peripheral blood and spectrum of various bleeding manifestations. Azathioprine is one of the effective, readily available, and affordable immunosupressants available for ITP management in developing countries. We aimed to study the efficacy and long-term safety profile of our patients with ITP who were treated with azathioprine. Method: This was a retrospective, single-center study conducted at a tertiary care hospital in Northern India. The patients who had received at least one line of therapy before receiving azathioprine were included in this study. All patients received oral azathioprine at a dose of 1 mg/kg/day (50 mg or 100 mg tablet formulations were used), which was increased up to 2 mg/kg/day depending upon the response and adverse effects. Result: Sixty-three patients were analyzed. Their median age was 28 years (range 15-68); 29/63 patients (46.03%) were females. The median duration from diagnosis to azathioprine initiation was 539 days (323 days-980.5 days). The patients included in the study had received a median of 3 (range 1-6) prior lines of therapies; 38/63 patients (60.32%) had received ≥3 prior therapies. Six patients (9.5%) had relapsed after splenectomy, and 16 patients (25.4%) had relapsed after receiving rituximab. The mean baseline platelet count was 10000/μL. The median time to response was 95 days (90 days-not reached) and the cumulative overall response rate (complete and partial response) at day 90 was 38.1%. Only one patient achieved complete response with azathioprine in our study. The cumulative rate of relapse at five years was 21.2%. Twenty-six patients stopped azathioprine after achieving some response (CR/PR) with Azathioprine for a median duration of 1067.5 days (range: 236 days-2465 days). They were followed up for a median of 870 days (range: 392 days-1928 days), and twelve of them relapsed. Twenty-six patients (26/63, 41.27%) reported one or more adverse events while on azathioprine. Leucopenia was the most frequent adverse event, followed by anemia and hepatobiliary laboratory abnormalities. Serious adverse events (grade ≥3 CTCAEv4) were noted in three patients (4.7%). One patient succumbed to severe sepsis multiorgan dysfunction while being on treatment. Conclusion: We conclude that azathioprine has a good response rate in chronic ITP patients. It is well-tolerated with minimal and manageable side effects.

Immune thrombocytopenia (ITP) is characterized by decreased platelet count in the peripheral circulation. The first-line therapy is corticosteroids with 53-80% overall response rate. Eltrombopag has been used as second-line therapy in ITP for over a decade now. The long-term efficacy and safety profile have been widely reported in the western world. However, the data from the resource-constraint settings of the developing world is scarce. We aim to present the real-life experience of efficacy and safety of eltrombopag from the resource-constraint settings. This was a retrospective, single-center study conducted at a tertiary care hospital in Northern India from 2012-2019. On audit of medical records, patients of ITP receiving eltrombopag were screened for inclusion. Patients whose treatment outcomes were not available were excluded. Finally, 53 patients were analyzed using statistical packages of Python v3.7. The patients’ median age was 35 years (range 17-78), with 23 (43.4%) being female. The median time to response was 35 days (range 28-50 days) and the cumulative overall response rates (ORR) at day 30, day 60 and day 90 were 41.5%, 69.8%, and 81.1% respectively. A total of 10 patients on eltrombopag relapsed during follow up. The cumulative rate of relapse at one year, three years, and five years were 6.6%, 25.3%, and 47.7%, respectively. There was no significant difference in outcome (response rate or relapse) in any subgroups depending on age, sex, duration of disease, number of prior lines of treatment, splenectomy, or baseline platelet count. Six patients stopped eltrombopag after having a median sustained response for 796 days (range 658-1185), and after a median follow up of 624 days (range 92-1339), they continued to be in remission. Seventeen patients (17/53, 32%) reported one or more adverse events while on eltrombopag therapy. A total of 49 adverse events (n=4, grade ≥3 CTCAEv4) were noted. Anemia was the most frequent adverse event followed by hepatobiliary dysfunction as reflected by deranged AST/ALT or raised bilirubin. The use of eltrombopag among adult ITP patients in resource-constraint settings was well-tolerated and yielded excellent overall response. The benefit was found to be sustained on long-term follow up. However, events like anemia, hepatobiliary, and thrombotic complications merit closer follow up.

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.

Background Donor factors have a variable correlation with cluster of differentiation (CD)34+ cell dose in allogeneic peripheral blood stem cell (PBSC) harvests. CD34+ cell dose affects the speed of hematopoietic recovery and percentage of donor chimerism in the recipient. Methods A total of 25 allogeneic PBSC transplants performed during a 3-year period were included. All donors underwent mobilization with filgrastim. Leukapheresis, flowcytometric CD34+ cell enumeration, and chimerism analysis were performed and correlated with recipient outcome. Results Besides age, all other donor parameters had a positive correlation with CD34+ cell count. Engraftment kinetics and chimerism had a positive correlation with the CD34+ yield of the PBSC product. Acute graft-vs-host disease (GVHD) was observed in patients with complete chimerism at day 30 after transplantation. Conclusion Adequate CD34+ cell yield happens in healthy donors, independent of donor demographic patterns with G-CSF only. A diverse population of donors can thus be approached for Matched Unrelated Donor (MUD) transplants. An accurate quantitative analysis of early donor chimerism in the recipient (at day 30) is an excellent tool for post-transplant monitoring for acute GvHD.

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.

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

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.

Acute myeloid leukemia and acute lymphoid leukemia differ substantially in response to therapy and course, and accurate differentiation of the two is fundamental to therapeutic decisions. Immunophenotyping is used for this purpose, and various guidelines have been proposed regarding a minimal screening antibody panel. Most of them have been found inefficient.Eighty-two cases of consecutive acute leukemias reporting to this hospital over a period of two years were included in the study. Peripheral blood smear, bone marrow aspirate, and bone marrow biopsy were studied using morphology, cytochemical stains, and relevant immunohistochemical stains on selected biopsy specimens. Flowcytometry analysis was carried out using Indian consensus screening panel and our proposed minimal screening panel (PMSP) for comparison.Immunophenotyping using PMSP resulted in 95.12% accurate diagnosis versus Indian consensus minimal screening panel (ICMSP) with an accuracy of 92.68%. This result was statistically significant as per Chi Square tests.PMSP can be used as a substitute for ICMSP, since it includes lineage-specific cytoplasmic antibodies, as well as lesser number of monoclonal antibodies, and enables us to diagnose mixed lineage leukemia. Fewer markers can be linked to a lower cost as well, which is relevant in a developing economy.

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.