Bone marrow transplant: A two-decade single centre hematology experience.

Background: Bone Marrow Transplant (BMT) is a curative form of therapy for many hematological disorders in both the adult and pediatric patients. The availability of BMT in the AFMS at AHRR for the last 02 decades has been a game changer for the patients. Methods: We reviewed our BMT data since the inception of the program till Feb 2023. Results: Over 700 patients with more than 23 different types of hematological disorders have undergone this procedure 58%% patients underwent an Autologous BMT and 42% an allogenic BMT. Autologous BMT for Multiple Myeloma and Allogenic BMT for Aplastic Anemia and Acute Leukemias have been the most common indications. 73% patients were adults, and 27% patients were of the pediatric age group. The male: female ratio was 2:1. The spectrum of allogenic Hematopoietic Stem Cell Transplant (HSCT) has expanded from Matched Sibling Donor (MSD) transplants to Matched Unrelated Donor (MUD) Transplants and Haploidentical Donor Transplants. 93% of our Allogenic BMT patients underwent a MSD BMT, 1% MUD BMT and 06% Haploidentical BMT. Today no patient with a malignant hematological disorder requiring a BMT is denied the procedure due to the lack of an HLA donor due to the availability of haploidentical BMT. Conclusion: The evolution of a BMT program has a long learning curve and the expanded pool of eligible donors has led to a situation of "transplant for all". Haploidentical HSCT for nonmalignant hematological disorders is an unmet need. CART cell therapy and Cellular therapies need to be prioritized for future inclusion.

Impact of cognitive behavioural intervention on caregiver burden in mothers of children diagnosed with cancer.

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.

Supplemental Pioglitazone to Patients of CML with Suboptimal TKI Response: A Pragmatic Pilot Study.

Tyrosine kinase inhibitors (TKIs) have improved outcomes of chronic myeloid leukemia (CML). However, 20-30% of patients require second-line TKIs following suboptimal response. The cost and adverse events limit their use in resource-constraint settings. We conducted a pilot study to ascertain the benefit of adding pioglitazone to TKIs with suboptimal response in real-world resource-constraint settings. In this pragmatic pilot study from 01 Jan 2017 to 31 July 2021, CML patients from a tertiary care center in North India with sub-optimal response to TKIs were additionally given pioglitazone after ruling out imatinib resistance mutation (n - 31). Pioglitazone was stopped if there was disease progression on follow-up, and second-line TKI was started. The data were analyzed with the intention-to-treat principle using JMP Ver.15.1.1. The median age of the study population was 54y (27-82), who were followed up for a median duration of 1023.5d (59-1117). Pioglitazone showed the benefit of one-log reduction in BCR-ABL in 89.7% of the study participants. 1y, 2y and 3y-PFS were 92.57%, 76.5%, and 68.3% respectively. During follow-up period, the disease progressed in 38.7%, of which two succumbed. No adverse events to Pioglitazone were documented. This study proved that adding Pioglitazone to the existing TKI regime in CML with sub-optimal response can benefit. The addition of Pioglitazone was well tolerated. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01561-x.

A retrospective study to assess the impact of ABO incompatibility on outcomes of allogeneic peripheral blood stem cell transplants at a tertiary care hospital in Western Maharashtra.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) has emerged as a curative measure for life-threatening hematological disorders. It can be autologous or allogeneic depending on the disease characteristics. Providing transfusion support to the transplant patients can be challenging, especially in AB-mismatched allogeneic HSCT. In this study, we investigated the impact of ABO incompatibility in patients undergoing allogeneic HSCT. MATERIALS AND METHODS: A retrospective review was conducted in 76 patients with hematological diseases who underwent allogeneic HSCT. Transfusion requirements, engraftment profile, incidence of graft versus host disease (GvHD), and mortality for a period of 1 year were analyzed. RESULTS: ABO incompatibility between donor and the patient did not significantly affect the neutrophil and platelet (PLT) engraftment time (P = 0.389, 0.349, respectively), packed red blood cells transfusion requirement, and duration of initial hospital stay. However, patients of ABO-incompatible HSCT received more PLT transfusions posttransplant which was statistically significant. 29.1% of ABO compatible and 16.7% incompatible HSCT patients developed GVHD. Mortality rates in the two groups were 16.7% and 8.3%, respectively. However, differences in both the parameters were not statistically significant. CONCLUSION: Our study showed that ABO incompatibility does not significantly affect the outcome and should not be a limiting factor for selection of donor. Donor availability and human leukocyte antigen (HLA) matching remain the critical selection criteria.

Association of CD 34 positive cell dose with engraftment kinetics in autologous peripheral blood stem cell transplant patients of multiple myeloma.

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 <2.0 × 106 CD34+ cells/kg have delayed engraftment. The level of optimal cutoff for accelerated engraftment is yet to be validated. Hence, this study was undertaken to study the association of CD 34+ cell dose with engraftment kinetics in patients of MM who underwent autolgous peripheral blood stem cell transplant (PBSCT). Methods: We retrospectively analyzed 19 patients of MM who underwent PBSCT at our center between December 2016 to December 2018. Complete blood counts were carried out daily after transplantation to record neutrophil and platelet engraftment. Results: Based on the CD34+ cell dose given : <5 × 106/kg (category 1), 5-10 × 106/kg (category 2), >5 × 106/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 × 106 cells/kg leads to an accelerated neutrophil and platelet engraftment in patients of MM.

Real-world experience of anti-D immunoglobulin in immune thrombocytopenia.

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.

Isolated CNS Relapse in Acute Lymphoblastic Leukemia (ALL): An Experience from a Tertiary Care Center.

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.

Safety and efficacy of splenectomy in immune thrombocytopenia.

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.

The clinical profile, management, and outcome of febrile neutropenia in acute myeloid leukemia from resource constraint settings.

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.

A study on DNA methylation status in promoter region of p15 gene in patients of acute myeloid leukemia and myelodysplastic syndrome.

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 < 0.001). The methylation status did not significantly correlate with AML subtypes or the cytogenetic abnormalities detected in cases. CONCLUSION: The outcome of the study indicates p15 promoter DNA methylation in cases of AML and MDS may identify those individuals who might benefit from the targeted therapeutic approaches.

Real-world Experience of Rituximab in Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is a relapsing-remitting disease often requiring more than one line of therapy. Rituximab is a recommended second-line therapy, but the real-world data on its efficacy and safety from resource constraint settings is limited. We aimed to analyze the safety and efficacy of rituximab in ITP. This is a single-center, retrospective study. This study was conducted at a tertiary care hospital in Northern India from 2005 to 2019. On audit of medical records, all patients of ITP (n-513) who had received rituximab (n-81) were screened for inclusion. Patients whose response assessment was not possible were excluded. Finally, 66 patients were analyzed using statistical packages of Python v3.7. The cumulative incidence of overall response on day 20 was 30.61%, and day 30 was 51.72%. The median time to response was 28 day (range 21-51 day). Cumulative incidence of complete response was 16.67%, and partial response 37.88%. After a median follow-up of 789 day (range 181-5260 day), the cumulative incidence of relapse was 30.32%, 36.12%, and 56.57% at 1, 2, and 5 years respectively. There was no effect of age, sex, duration of disease, lines of therapy received, and platelet count on either cumulative incidence of overall response or relapse. ANA positivity was significantly related to the better cumulative incidence of overall response (p = 0.012), but not with relapse. Infusion-related reactions were the commonest adverse event noted (n-4, grade ≥ 3 CTCAEv4). Rituximab and its generic version are safe and effective second line agent in ITP with a good overall response and sustained response.

Safety and efficacy of azathioprine in immune thrombocytopenia.

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.

Survival Outcomes of Newly Diagnosed Multiple Myeloma at a Tertiary Care Center in North India (IMAGe: 001A Study).

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.

Isolated CNS relapse in FLT 3 mutation positive CMML post allogeneic stem cell transplant: Report of a rare case.

Chronic myelomonocytic leukemia is a clonal chronic hematopoietic disorder that has been classified under the category of Myelodysplastic syndrome/Myeloproliferative neoplasms (MDS/MPN). CMML has high chances of transforming to acute leukemia, however isolated CNS relapse in CMML has never been reported in literature. We report an extremely rare case of a 47 yearold female diagnosed to have CMML- 2 in remission, who developed an isolated central nervous system relapse after matched related allogeneic hematopoietic stem cell transplantation. To our knowledge this is the first report of isolated CNS relapse in CMML post allogeneic stem cell transplant.

Gut microbiota profiling in hematopoietic stem cell transplant recipients: Towards personalized medicine.

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 ß-lactamase-, multidrug- and extensively drug-resistant phenotypes. CONCLUSION: This study reiterates the importance of individual profiling of gut microbiota in HSCT patients.

Real-world experience of eltrombopag in immune thrombocytopenia.

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.

Proteomics and functional study reveal marginal zone B and B1 cell specific protein as a candidate marker of multiple myeloma.

Multiple myeloma (MM) is a plasma cell­associated 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 patient­derived MM mononuclear cells (MNCs). Label­free 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 non­hematological 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.

A Prospective Observational Multi-institutional Study on Invasive Fungal Infections Following Chemotherapy for Acute Myeloid Leukemia (MISFIC Study): A Real World Scenario from India.

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.

Proteomic Alterations in Multiple Myeloma: A Comprehensive Study Using Bone Marrow Interstitial Fluid and Serum Samples.

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.