SCCs which develop on chronic skin lesions have a higher incidence of metastasis (9%-36%) as comp... more SCCs which develop on chronic skin lesions have a higher incidence of metastasis (9%-36%) as compared to those arise in the previously normal skin (1%-10%). Bilateral inguinal lymph nodes were enlarged in our case. Fine-needle aspiration or biopsy of inguinal lymph nodes was not done in our case; hence, we cannot comment about metastasis. Pigmentation and mild scaling over the waist are so common in Indian females that they consider it normal and ignore it. This case is presented for its rarity and to bring awareness about saree cancer among Indian women to detect it earlier. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil.
Background Fetal hemoglobin (HbF) levels play significant role in lowering down the morbidity and... more Background Fetal hemoglobin (HbF) levels play significant role in lowering down the morbidity and mortality in sickle cell disease (SCD) patients. Coinheritance of heme oxygenase-1 (HMOX1) rs2071746:A > T polymorphism may contribute to variable HbF levels in Indian SCD patients. Aim and Objective This study was aimed to evaluate the role of HMOX1 polymorphism and its impact on HbF level in Indian SCD patients. Materials and Methods One-hundred twenty confirmed cases of SCD and 50 healthy controls were recruited. Their mean age was 11.5 ± 8.6 years (range: 3–23 years). Quantification of Hb, HbA2, HbF, and HbS was done by capillary zone electrophoresis. Allele-specific polymerase chain reaction was used to genotype HMOX1 (rs2071746:A > T) gene polymorphism. Results Out of the 120 cases of SCD, 65 were hemoglobin sickle-shaped (HbSS) and 55 were sickle-beta thalassemia (Sβ). Out of 65 HbSS patients, 29 (44.6%) were heterozygous (AT), 20 (30.76%) were homozygous (TT), and 16 (24.6...
This retrospective study was aimed to understand the clinical, laboratory, radiological parameter... more This retrospective study was aimed to understand the clinical, laboratory, radiological parameters and the outcome of COVID-19 patients with underlying haematological disease. All patients with known haematological disease admitted with COVID-19-positive status from April to August 2020 in the COVID-19 facility of a tertiary care centre in north India, were included. Their medical records were analyzed for outcome and mortality risk factors. Fifty four patients, 37 males, were included in the study. Of these, 36 patients had haematological malignancy and 18 had benign disorder. Fever (95.5%), cough (59.2%) and dyspnoea (31.4%) were the most common symptoms. Nine patients had severe disease at diagnosis, mostly malignant disorders. Overall mortality rate was 37.0 per cent, with high mortality seen in patients with aplastic anaemia (50.0%), acute myeloid (46.7%) and lymphoblastic leukaemia (40.0%). On univariate analysis, Eastern Cooperative Oncology Group performance status >2 [odd ratio (OR) 11.6], COVID-19 severity (OR 8.2), dyspnoea (OR 5.7) and blood product transfusion (OR 6.4) were the predictors of mortality. However, the presence of moderate or severe COVID-19 (OR 16.6, confidence interval 3.8-72.8) was found significant on multivariate analysis. The results showed that patients with haematological malignancies and aplastic anaemia might be at increased risk of getting severe COVID-19 infection and mortality as compared to the general population.
The Coronavirus disease-19 (COVID-19) pandemic has in multiple ways affected healthcare delivery ... more The Coronavirus disease-19 (COVID-19) pandemic has in multiple ways affected healthcare delivery to non-− COVID patients throughout the world. Adequate transfusion services are fundamental in ongoing therapy of patients with hematological ailments. We present the transfusion services in the hematology daycare under the department of Hematology and supported by the Blood Bank at our institution for the period 12th April 2020− 30th June 2020, which saw the stringent lockdown and unlocking Phase I in India, declared in lieu of the pandemic. A 56 % reduction in total transfusion sessions was observed in 2020 (588 sessions given to 176 patients) compared to 1336 sessions in 516 patients over the same period in 2019. The reductions were seen across the different blood components (packed red blood cells [PRBC]: 585 vs. 1840, platelet rich plasma: 372 vs. 1313, single donor platelet 18 vs. 16), with a significant reduction in the mean PRBC transfused per PRBC transfusion session (1.11 vs 1.99, p<0.001) in 2020, compared to 2019. There were however no major differences in the transfusion practices across the different phases of the lockdown. Our study highlights the detrimental reduction in transfusion services due to the COVID-19 pandemic and related lockdown and showcases the remedial strategies taken to maximize transfusion support to patients during this period. Our observations might help to provide insights to adequately combat possible similar adverse situations in the future.
Mediterranean Journal of Hematology and Infectious Diseases, 2014
Introduction Janus kinase2 (JAK2) V617F mutation in myeloid cells has been reported from the majo... more Introduction Janus kinase2 (JAK2) V617F mutation in myeloid cells has been reported from the majority of patients with Polycythemia vera (PV). Materials & Methods A cross sectional study was conducted to review clinical records of 93 cases of erythrocytosis who were evaluated for JAK2V617F mutation by Amplification Refractory Mutation System polymerase chain reaction at our institution. The significance of this mutation in the context of clinical & hematological features in cases that fulfilled World Health Organisation 2008 diagnostic criteria for PV was investigated. Results 66(71%) patients fulfilled the WHO diagnostic criteria for PV. Erythrocytosis could be attributed to secondary causes in 20(21.5%) cases and in seven (7.5%) cases, erythrocytosis was idiopathic. The JAK2V617F mutant allele was detected in 61 of the 66 patients (92.4%) with 19(31.1%) showing homozygosity. A comparison between JAK2V617F mutation positive and JAK2V617F wild type PV patients at presentation rev...
Acquired aplastic anemia (aAA) is an autoimmune disease, characterized by infiltration of T lymph... more Acquired aplastic anemia (aAA) is an autoimmune disease, characterized by infiltration of T lymphocytes in the bone marrow with destruction of hematopoietic stem cells by the effector cells. Interferon-gamma (IFN-γ) and perforin are important mediators of cell destruction. In this flow cytometry-based study, we have investigated the percentage of intracellular IFN-γ+ and perforin+ CD5+ T cells in peripheral blood of newly diagnosed aAA patients before and after immunosuppressive therapy (IST). Patients were categorized as per standard disease severity and response to IST. The median percentage of IFN-γ+ and perforin+ CD5+ T cells was higher in untreated patients compared to healthy controls. The percentage of these cells was also increased in untreated severe and very severe aplastic anemia when compared with non-severe aplastic anemia patients. In patients before and after IST the median percentage of T cells producing IFN-γ and perforin was elevated in non-responders as compared t...
Introduction: Febrile neutropenia is a common cause in morbidity and mortality during treatment o... more Introduction: Febrile neutropenia is a common cause in morbidity and mortality during treatment of hematological neoplasms. Methods: Subjects included all cases admitted under hematology department with febrile neutropenia from February to June 2018. Each febrile episode was investigated by standard investigations (Blood culture, Chest x ray etc.); Procalcitonin (PCT) and c reactive protein (CRP) was sent at fever onset 0, 24, 48 h, day 7 and day 14. Results: Data was analyzed for 52 febrile episodes in 50 patients. PCT cut off value at 24 h of ≤1.2 ng/ml had a sensitivity and specificity of 62.5% and 87.5% for discriminating Invasive fungal infection (IFI) and Microbiologically documented infection (MDI) (p = 0.033). PCT had a negative predictive value of 70% for the diagnosis of IFI as compared to MDI. CRP cut off > 160 mg/dl at 48 h was suggestive of fever due to fungal infection with a sensitivity of 100%, specificity of 48%, PPV of 33.3% and NPV of 100%. CRP at 24 and 48 h of fever was useful to distinguish non-infectious causes of fever from infectious causes. Conclusion: PCT at 24 h and CRP at 48 h was useful in identifying fungal infection. CRP was a better marker when compared to PCT for identifying disease fever.
Introduction: Allogeneic stem cell transplantation (SCT) is the best form of therapy for a young ... more 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) unde...
The abnormal growth of malignant plasma cells in Multiple Myeloma (MM) require bone marrow (BM) n... more The abnormal growth of malignant plasma cells in Multiple Myeloma (MM) require bone marrow (BM) niche consisting of proteoglycans, cytokines, etc. Versican (VCAN), a chondroitin sulfate proteoglycan promotes progression in solid tumors but there is dearth of literature in MM. Hence, we studied the involvement of VCAN in MM and its regulation by microRNAs as a therapeutic approach. 30 MM patients and 20 controls were recruited and BM stromal cells (BMSCs) were isolated by primary culture. Molecular levels of VCAN, miR-144, miR-199 & miR-203 were determined in study subjects and cell lines. The involvement of VCAN in myeloma pathogenesis was studied using BMSCs-conditioned medium (BMSCs-CM) and VCAN-neutralizing antibody or microRNA mimics. Elevated expression of VCAN was observed in patients especially in BM stroma while microRNA expression was significantly lower and showed negative correlation with VCAN. Moreover, BMSCs-CM showed the presence of VCAN which upon supplementing to MM cells alter parameters in favor of myeloma progression, however, this effect was neutralized by VCAN antibody or miR (miR-144 and miR-199) mimics. The downstream signaling of VCAN was found to activate FAK and STAT3 which subsides by using VCAN antibody or miR mimics. The neutralization of oncogenic effect of BMSCs-CM by VCAN blockage affirms its plausible role in progression of MM. VCAN was observed as a paracrine mediator in the cross-talk of BMSCs and myeloma cells in BM microenvironment. Therefore, these findings suggest exploring VCAN as novel therapeutic target and utilization of microRNAs as therapy to regulate VCAN for better management of MM.
Intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our previous stu... more Intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our previous study showed that the binding of adult hemoglobin (HbA) to glycoprotein (GP) 1bα induced the activation of platelets. The elevated plasma Hb or platelet surface bound Hb positively correlated with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). Furthermore, this study shows that the sickle Hb [HbS, occurs due to single nucleotide polymorphism at A>T of β-globin gene of Hb and causes sickle cell disease (SCD)] also bound to GP1bα and activated platelets in a concentration-dependent manner. The HbS bound to glycocalicin (extramembranous part of GP1bα) with K D~1 0.46 ± 3 μM. HbS induced phosphorylation of signaling adapter proteins, such as Lyn, PI3K, Akt and ERK in platelets, and also increased the surface expression of platelet activation markers such as P-selectin (10.7 fold) and PAC1 binding (10.4 fold) in platelet surface in a concentration-dependent manner. HbS also increased the platelet microparticle-generation (4.7 fold) and thrombus-formation (4.3 fold) in a concentration-dependent manner. An elevated level of extracellular Hb in plasma correlated directly with platelet activation markers such as Pselectin (r = 0.7947), PAC1 binding (r = 0.5914) on platelet surface and plasma levels of platelet-derived microparticles (r = 0.7834) in patients with SCD. Our study therefore suggests that the HbS-induced platelet activation may play a crucial role in intravascular clot formation observed in SCD patients characterized by high propensity to vascular occlusion and hypercoagulable states.
Despite improvements in leukemia therapy, acute myeloid leukemia (AML) remain a difficult disease... more Despite improvements in leukemia therapy, acute myeloid leukemia (AML) remain a difficult disease to treat with a majority of patients having disease relapse without an allogeneic stem cell transplantation within 3 years [1]. Treatment options in AML have improved over the years with the introduction of hypomethylating agents and recently with the FDA approval of Venetoclax, a B cell lymphoma protein 2 (Bcl2) inhibitor [2]. The combination of Venetoclax and Azacitidine (VenAZA) upfront therapy has led to improvement in remission rates and overall survival compared to azacitidine monotherapy in elderly patients ( 75 years) with AML and in those who are unfit for conventional high dose induction chemotherapy [3]. Patients with AML in India are around a decade younger compared to patients in the west, with almost 30% of them presenting with baseline neutropenic infections like fungal pneumonia and multi drug resistance bacteremia, making them high risk candidates for upfront high dose induction chemotherapy [4]. In similar settings the induction mortality in these patients with conventional chemotherapy remains high (around 20–30% across different studies), often due to worsening of the neutropenic infections present at chemotherapy initiation, which are largely refractory to antimicrobials till neutrophil recovery [5]. In our department a majority of young patients with AML (>40%, unpublished data) have severe neutropenic infections at diagnosis (neutropenic sepsis with shock and multiorgan dysfunction; fungal pneumonia based on imaging or broncho-alveolar lavage findings together with respiratory distress; multi drug resistant bacteremia; organ dysfunction like acute kidney injury, type 1 respiratory failure, hepatic dysfunction etc.) making them unfit for upfront conventional chemotherapy. We report here the retrospective analysis of the first 7 relatively young patients with AML (median age of 45 years, range 27–60 years) treated in our department with the VenAZA combination therapy from Jan 2019 to March 2020, 6 of who had conditions preventing the use of upfront high dose induction chemotherapy and 1 with primary induction failure (Table 1). The study was approved by the Institutional ethics committee and informed consent was taken from all the patients for the off label use of Venetoclax and for the use of patient data in scientific reproduction. We collected data about the patient’s demographics, clinical characteristics at presentation (neutropenic infections, organ dysfunction), disease parameters (baseline complete blood count and blast percentage, cytogenetics and mutational profile on the diagnostic bone marrow), treatment parameters and outcomes (time to hematological recovery, bone marrow remission status and survival outcomes). The 2017 European Leukemia Network (ELN) recommendation were used to assess response status [6]. Four patients had intermediate risk AML based on ELN 2017 criteria; one had favorable risk and two patients had adverse risk AML with one having primary induction failure. Azacitidine was administered at 75mg/m/day for 7 days subcutaneously every 28 days and Venetoclax was initiated within the first week of Azacitidine therapy. Venetoclax was started at 50mg (lowest tablet denomination feasible) after withholding concomitant azole antifungals and bridging the venetoclax ramp up period with alternative antifungal prophylaxis or therapy that do not alter in vivo venetoclax drug concentration (micafungin or caspofungin) with increments over a week to reach a maximum dose of 400mg which was continued for 28 days each cycle. Azole antifungals were re-initiated after a steady venetoclax dose was achieved. Dose adjustments were done for concomitant azole therapy; a maximum dose of 100mg per day of venetoclax was administered for concomitant voriconazole and alternate day 50mg/100mg for concomitant posaconazole therapy (given the unavailability of tablet denominations to administer daily 70mg venetoclax with posaconazole). None of the patients in this cohort had a white blood cell (WBC) count > 30 10/L before the initiation of Venetoclax. Adequate tumor lysis syndrome (TLS) prophylaxis like hydration,
Mediterranean Journal of Hematology and Infectious Diseases, 2014
A 45 years old male, known case of T-cell Acute Lymphoblastic Leukemia on maintenance therapy pre... more A 45 years old male, known case of T-cell Acute Lymphoblastic Leukemia on maintenance therapy presented with painless progressive diminution of vision in both eyes. Evaluation revealed Cytomegalovirus Retinitis with low CD4 counts. CMV retinitis is usually seen in HIV disease or in post allogenic stem cell transplant recipient patients. CMV retinitis occurring in ALL maintenance phase is very rare. The patient showed some improvement with intra-vitreal and intra-venous Gancyclovir injections.
Background: The introduction of all-trans-retinoic-acid (ATRA) and arsenic trioxide (ATO) has cha... more Background: The introduction of all-trans-retinoic-acid (ATRA) and arsenic trioxide (ATO) has changed acute promyelocytic leukaemia (APL) from a highly fatal malignancy to a major success in the sphere of haemato-oncology, with long-term survival exceeding 90% in some studies [1]. While literature from the developed world boasts of outstanding outcomes of patients with APL, there is a paucity of data on management strategies, complications and outcomes from the developing world in general and India in particular [2]. With a large population residing in rural areas, high infection rates and limited access to healthcare, we aim to delineate the challenges faced in curing APL in the developing world. Methods: We retrospective collected data from medical records of all patients diagnosed with APL between January 2016 to December 2020 in the department of Hematology. A presumptive diagnosis of APL was made based on the presence of abnormal promyelocytes in peripheral blood or bone marrow...
Background. Coronavirus disease 2019 (Covid-19) has led to a severe medical, social and economic ... more Background. Coronavirus disease 2019 (Covid-19) has led to a severe medical, social and economic crisis globally. Use of antivirals has given inconsistent results; thus systematic summaries of available evidence are required for any recommendations for treatment. We conducted a systematic review and meta-analysis on the use of antivirals for Covid-19. Methods. The databases we searched were—Medline, Embase, Cochrane CENTRAL and Medrxiv. Title/abstract screening, full-text screening and data abstraction were carried out in duplicate by two researchers. Pooled effect sizes and 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method of random effects for meta-analysis. Results. Twenty studies were found eligible for inclusion: 6 randomized controlled trials, 9 cohort studies and 5 case series. Moderate-quality evidence suggests a likely clinical benefit from the use of remdesivir in improving the number of recoveries (RR 1.18; 95% CI 1.07–1.31; I2 = 0%) and time to recovery in days (median –3.02; 95% CI –4.98 to –1.07; I2 = 97%). A possibility of lower mortality is suggested by low-quality evidence with remdesivir (RR 0.74; 95% CI 0.40–1.37, I2 = 58%). Moderate-quality evidence suggests no certain benefit of using lopinavir/ritonavir for Covid-19 compared to arbidol, lopinavir/ritonavir combined with arbidol or other medications used as controls. Conclusion. Further evidence from randomized controlled trials is required for all antivirals to treat Covid-19. At present, remdesivir seems more promising than other antivirals.
SCCs which develop on chronic skin lesions have a higher incidence of metastasis (9%-36%) as comp... more SCCs which develop on chronic skin lesions have a higher incidence of metastasis (9%-36%) as compared to those arise in the previously normal skin (1%-10%). Bilateral inguinal lymph nodes were enlarged in our case. Fine-needle aspiration or biopsy of inguinal lymph nodes was not done in our case; hence, we cannot comment about metastasis. Pigmentation and mild scaling over the waist are so common in Indian females that they consider it normal and ignore it. This case is presented for its rarity and to bring awareness about saree cancer among Indian women to detect it earlier. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil.
Background Fetal hemoglobin (HbF) levels play significant role in lowering down the morbidity and... more Background Fetal hemoglobin (HbF) levels play significant role in lowering down the morbidity and mortality in sickle cell disease (SCD) patients. Coinheritance of heme oxygenase-1 (HMOX1) rs2071746:A > T polymorphism may contribute to variable HbF levels in Indian SCD patients. Aim and Objective This study was aimed to evaluate the role of HMOX1 polymorphism and its impact on HbF level in Indian SCD patients. Materials and Methods One-hundred twenty confirmed cases of SCD and 50 healthy controls were recruited. Their mean age was 11.5 ± 8.6 years (range: 3–23 years). Quantification of Hb, HbA2, HbF, and HbS was done by capillary zone electrophoresis. Allele-specific polymerase chain reaction was used to genotype HMOX1 (rs2071746:A > T) gene polymorphism. Results Out of the 120 cases of SCD, 65 were hemoglobin sickle-shaped (HbSS) and 55 were sickle-beta thalassemia (Sβ). Out of 65 HbSS patients, 29 (44.6%) were heterozygous (AT), 20 (30.76%) were homozygous (TT), and 16 (24.6...
This retrospective study was aimed to understand the clinical, laboratory, radiological parameter... more This retrospective study was aimed to understand the clinical, laboratory, radiological parameters and the outcome of COVID-19 patients with underlying haematological disease. All patients with known haematological disease admitted with COVID-19-positive status from April to August 2020 in the COVID-19 facility of a tertiary care centre in north India, were included. Their medical records were analyzed for outcome and mortality risk factors. Fifty four patients, 37 males, were included in the study. Of these, 36 patients had haematological malignancy and 18 had benign disorder. Fever (95.5%), cough (59.2%) and dyspnoea (31.4%) were the most common symptoms. Nine patients had severe disease at diagnosis, mostly malignant disorders. Overall mortality rate was 37.0 per cent, with high mortality seen in patients with aplastic anaemia (50.0%), acute myeloid (46.7%) and lymphoblastic leukaemia (40.0%). On univariate analysis, Eastern Cooperative Oncology Group performance status &gt;2 [odd ratio (OR) 11.6], COVID-19 severity (OR 8.2), dyspnoea (OR 5.7) and blood product transfusion (OR 6.4) were the predictors of mortality. However, the presence of moderate or severe COVID-19 (OR 16.6, confidence interval 3.8-72.8) was found significant on multivariate analysis. The results showed that patients with haematological malignancies and aplastic anaemia might be at increased risk of getting severe COVID-19 infection and mortality as compared to the general population.
The Coronavirus disease-19 (COVID-19) pandemic has in multiple ways affected healthcare delivery ... more The Coronavirus disease-19 (COVID-19) pandemic has in multiple ways affected healthcare delivery to non-− COVID patients throughout the world. Adequate transfusion services are fundamental in ongoing therapy of patients with hematological ailments. We present the transfusion services in the hematology daycare under the department of Hematology and supported by the Blood Bank at our institution for the period 12th April 2020− 30th June 2020, which saw the stringent lockdown and unlocking Phase I in India, declared in lieu of the pandemic. A 56 % reduction in total transfusion sessions was observed in 2020 (588 sessions given to 176 patients) compared to 1336 sessions in 516 patients over the same period in 2019. The reductions were seen across the different blood components (packed red blood cells [PRBC]: 585 vs. 1840, platelet rich plasma: 372 vs. 1313, single donor platelet 18 vs. 16), with a significant reduction in the mean PRBC transfused per PRBC transfusion session (1.11 vs 1.99, p<0.001) in 2020, compared to 2019. There were however no major differences in the transfusion practices across the different phases of the lockdown. Our study highlights the detrimental reduction in transfusion services due to the COVID-19 pandemic and related lockdown and showcases the remedial strategies taken to maximize transfusion support to patients during this period. Our observations might help to provide insights to adequately combat possible similar adverse situations in the future.
Mediterranean Journal of Hematology and Infectious Diseases, 2014
Introduction Janus kinase2 (JAK2) V617F mutation in myeloid cells has been reported from the majo... more Introduction Janus kinase2 (JAK2) V617F mutation in myeloid cells has been reported from the majority of patients with Polycythemia vera (PV). Materials & Methods A cross sectional study was conducted to review clinical records of 93 cases of erythrocytosis who were evaluated for JAK2V617F mutation by Amplification Refractory Mutation System polymerase chain reaction at our institution. The significance of this mutation in the context of clinical & hematological features in cases that fulfilled World Health Organisation 2008 diagnostic criteria for PV was investigated. Results 66(71%) patients fulfilled the WHO diagnostic criteria for PV. Erythrocytosis could be attributed to secondary causes in 20(21.5%) cases and in seven (7.5%) cases, erythrocytosis was idiopathic. The JAK2V617F mutant allele was detected in 61 of the 66 patients (92.4%) with 19(31.1%) showing homozygosity. A comparison between JAK2V617F mutation positive and JAK2V617F wild type PV patients at presentation rev...
Acquired aplastic anemia (aAA) is an autoimmune disease, characterized by infiltration of T lymph... more Acquired aplastic anemia (aAA) is an autoimmune disease, characterized by infiltration of T lymphocytes in the bone marrow with destruction of hematopoietic stem cells by the effector cells. Interferon-gamma (IFN-γ) and perforin are important mediators of cell destruction. In this flow cytometry-based study, we have investigated the percentage of intracellular IFN-γ+ and perforin+ CD5+ T cells in peripheral blood of newly diagnosed aAA patients before and after immunosuppressive therapy (IST). Patients were categorized as per standard disease severity and response to IST. The median percentage of IFN-γ+ and perforin+ CD5+ T cells was higher in untreated patients compared to healthy controls. The percentage of these cells was also increased in untreated severe and very severe aplastic anemia when compared with non-severe aplastic anemia patients. In patients before and after IST the median percentage of T cells producing IFN-γ and perforin was elevated in non-responders as compared t...
Introduction: Febrile neutropenia is a common cause in morbidity and mortality during treatment o... more Introduction: Febrile neutropenia is a common cause in morbidity and mortality during treatment of hematological neoplasms. Methods: Subjects included all cases admitted under hematology department with febrile neutropenia from February to June 2018. Each febrile episode was investigated by standard investigations (Blood culture, Chest x ray etc.); Procalcitonin (PCT) and c reactive protein (CRP) was sent at fever onset 0, 24, 48 h, day 7 and day 14. Results: Data was analyzed for 52 febrile episodes in 50 patients. PCT cut off value at 24 h of ≤1.2 ng/ml had a sensitivity and specificity of 62.5% and 87.5% for discriminating Invasive fungal infection (IFI) and Microbiologically documented infection (MDI) (p = 0.033). PCT had a negative predictive value of 70% for the diagnosis of IFI as compared to MDI. CRP cut off > 160 mg/dl at 48 h was suggestive of fever due to fungal infection with a sensitivity of 100%, specificity of 48%, PPV of 33.3% and NPV of 100%. CRP at 24 and 48 h of fever was useful to distinguish non-infectious causes of fever from infectious causes. Conclusion: PCT at 24 h and CRP at 48 h was useful in identifying fungal infection. CRP was a better marker when compared to PCT for identifying disease fever.
Introduction: Allogeneic stem cell transplantation (SCT) is the best form of therapy for a young ... more 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) unde...
The abnormal growth of malignant plasma cells in Multiple Myeloma (MM) require bone marrow (BM) n... more The abnormal growth of malignant plasma cells in Multiple Myeloma (MM) require bone marrow (BM) niche consisting of proteoglycans, cytokines, etc. Versican (VCAN), a chondroitin sulfate proteoglycan promotes progression in solid tumors but there is dearth of literature in MM. Hence, we studied the involvement of VCAN in MM and its regulation by microRNAs as a therapeutic approach. 30 MM patients and 20 controls were recruited and BM stromal cells (BMSCs) were isolated by primary culture. Molecular levels of VCAN, miR-144, miR-199 & miR-203 were determined in study subjects and cell lines. The involvement of VCAN in myeloma pathogenesis was studied using BMSCs-conditioned medium (BMSCs-CM) and VCAN-neutralizing antibody or microRNA mimics. Elevated expression of VCAN was observed in patients especially in BM stroma while microRNA expression was significantly lower and showed negative correlation with VCAN. Moreover, BMSCs-CM showed the presence of VCAN which upon supplementing to MM cells alter parameters in favor of myeloma progression, however, this effect was neutralized by VCAN antibody or miR (miR-144 and miR-199) mimics. The downstream signaling of VCAN was found to activate FAK and STAT3 which subsides by using VCAN antibody or miR mimics. The neutralization of oncogenic effect of BMSCs-CM by VCAN blockage affirms its plausible role in progression of MM. VCAN was observed as a paracrine mediator in the cross-talk of BMSCs and myeloma cells in BM microenvironment. Therefore, these findings suggest exploring VCAN as novel therapeutic target and utilization of microRNAs as therapy to regulate VCAN for better management of MM.
Intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our previous stu... more Intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our previous study showed that the binding of adult hemoglobin (HbA) to glycoprotein (GP) 1bα induced the activation of platelets. The elevated plasma Hb or platelet surface bound Hb positively correlated with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). Furthermore, this study shows that the sickle Hb [HbS, occurs due to single nucleotide polymorphism at A>T of β-globin gene of Hb and causes sickle cell disease (SCD)] also bound to GP1bα and activated platelets in a concentration-dependent manner. The HbS bound to glycocalicin (extramembranous part of GP1bα) with K D~1 0.46 ± 3 μM. HbS induced phosphorylation of signaling adapter proteins, such as Lyn, PI3K, Akt and ERK in platelets, and also increased the surface expression of platelet activation markers such as P-selectin (10.7 fold) and PAC1 binding (10.4 fold) in platelet surface in a concentration-dependent manner. HbS also increased the platelet microparticle-generation (4.7 fold) and thrombus-formation (4.3 fold) in a concentration-dependent manner. An elevated level of extracellular Hb in plasma correlated directly with platelet activation markers such as Pselectin (r = 0.7947), PAC1 binding (r = 0.5914) on platelet surface and plasma levels of platelet-derived microparticles (r = 0.7834) in patients with SCD. Our study therefore suggests that the HbS-induced platelet activation may play a crucial role in intravascular clot formation observed in SCD patients characterized by high propensity to vascular occlusion and hypercoagulable states.
Despite improvements in leukemia therapy, acute myeloid leukemia (AML) remain a difficult disease... more Despite improvements in leukemia therapy, acute myeloid leukemia (AML) remain a difficult disease to treat with a majority of patients having disease relapse without an allogeneic stem cell transplantation within 3 years [1]. Treatment options in AML have improved over the years with the introduction of hypomethylating agents and recently with the FDA approval of Venetoclax, a B cell lymphoma protein 2 (Bcl2) inhibitor [2]. The combination of Venetoclax and Azacitidine (VenAZA) upfront therapy has led to improvement in remission rates and overall survival compared to azacitidine monotherapy in elderly patients ( 75 years) with AML and in those who are unfit for conventional high dose induction chemotherapy [3]. Patients with AML in India are around a decade younger compared to patients in the west, with almost 30% of them presenting with baseline neutropenic infections like fungal pneumonia and multi drug resistance bacteremia, making them high risk candidates for upfront high dose induction chemotherapy [4]. In similar settings the induction mortality in these patients with conventional chemotherapy remains high (around 20–30% across different studies), often due to worsening of the neutropenic infections present at chemotherapy initiation, which are largely refractory to antimicrobials till neutrophil recovery [5]. In our department a majority of young patients with AML (>40%, unpublished data) have severe neutropenic infections at diagnosis (neutropenic sepsis with shock and multiorgan dysfunction; fungal pneumonia based on imaging or broncho-alveolar lavage findings together with respiratory distress; multi drug resistant bacteremia; organ dysfunction like acute kidney injury, type 1 respiratory failure, hepatic dysfunction etc.) making them unfit for upfront conventional chemotherapy. We report here the retrospective analysis of the first 7 relatively young patients with AML (median age of 45 years, range 27–60 years) treated in our department with the VenAZA combination therapy from Jan 2019 to March 2020, 6 of who had conditions preventing the use of upfront high dose induction chemotherapy and 1 with primary induction failure (Table 1). The study was approved by the Institutional ethics committee and informed consent was taken from all the patients for the off label use of Venetoclax and for the use of patient data in scientific reproduction. We collected data about the patient’s demographics, clinical characteristics at presentation (neutropenic infections, organ dysfunction), disease parameters (baseline complete blood count and blast percentage, cytogenetics and mutational profile on the diagnostic bone marrow), treatment parameters and outcomes (time to hematological recovery, bone marrow remission status and survival outcomes). The 2017 European Leukemia Network (ELN) recommendation were used to assess response status [6]. Four patients had intermediate risk AML based on ELN 2017 criteria; one had favorable risk and two patients had adverse risk AML with one having primary induction failure. Azacitidine was administered at 75mg/m/day for 7 days subcutaneously every 28 days and Venetoclax was initiated within the first week of Azacitidine therapy. Venetoclax was started at 50mg (lowest tablet denomination feasible) after withholding concomitant azole antifungals and bridging the venetoclax ramp up period with alternative antifungal prophylaxis or therapy that do not alter in vivo venetoclax drug concentration (micafungin or caspofungin) with increments over a week to reach a maximum dose of 400mg which was continued for 28 days each cycle. Azole antifungals were re-initiated after a steady venetoclax dose was achieved. Dose adjustments were done for concomitant azole therapy; a maximum dose of 100mg per day of venetoclax was administered for concomitant voriconazole and alternate day 50mg/100mg for concomitant posaconazole therapy (given the unavailability of tablet denominations to administer daily 70mg venetoclax with posaconazole). None of the patients in this cohort had a white blood cell (WBC) count > 30 10/L before the initiation of Venetoclax. Adequate tumor lysis syndrome (TLS) prophylaxis like hydration,
Mediterranean Journal of Hematology and Infectious Diseases, 2014
A 45 years old male, known case of T-cell Acute Lymphoblastic Leukemia on maintenance therapy pre... more A 45 years old male, known case of T-cell Acute Lymphoblastic Leukemia on maintenance therapy presented with painless progressive diminution of vision in both eyes. Evaluation revealed Cytomegalovirus Retinitis with low CD4 counts. CMV retinitis is usually seen in HIV disease or in post allogenic stem cell transplant recipient patients. CMV retinitis occurring in ALL maintenance phase is very rare. The patient showed some improvement with intra-vitreal and intra-venous Gancyclovir injections.
Background: The introduction of all-trans-retinoic-acid (ATRA) and arsenic trioxide (ATO) has cha... more Background: The introduction of all-trans-retinoic-acid (ATRA) and arsenic trioxide (ATO) has changed acute promyelocytic leukaemia (APL) from a highly fatal malignancy to a major success in the sphere of haemato-oncology, with long-term survival exceeding 90% in some studies [1]. While literature from the developed world boasts of outstanding outcomes of patients with APL, there is a paucity of data on management strategies, complications and outcomes from the developing world in general and India in particular [2]. With a large population residing in rural areas, high infection rates and limited access to healthcare, we aim to delineate the challenges faced in curing APL in the developing world. Methods: We retrospective collected data from medical records of all patients diagnosed with APL between January 2016 to December 2020 in the department of Hematology. A presumptive diagnosis of APL was made based on the presence of abnormal promyelocytes in peripheral blood or bone marrow...
Background. Coronavirus disease 2019 (Covid-19) has led to a severe medical, social and economic ... more Background. Coronavirus disease 2019 (Covid-19) has led to a severe medical, social and economic crisis globally. Use of antivirals has given inconsistent results; thus systematic summaries of available evidence are required for any recommendations for treatment. We conducted a systematic review and meta-analysis on the use of antivirals for Covid-19. Methods. The databases we searched were—Medline, Embase, Cochrane CENTRAL and Medrxiv. Title/abstract screening, full-text screening and data abstraction were carried out in duplicate by two researchers. Pooled effect sizes and 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method of random effects for meta-analysis. Results. Twenty studies were found eligible for inclusion: 6 randomized controlled trials, 9 cohort studies and 5 case series. Moderate-quality evidence suggests a likely clinical benefit from the use of remdesivir in improving the number of recoveries (RR 1.18; 95% CI 1.07–1.31; I2 = 0%) and time to recovery in days (median –3.02; 95% CI –4.98 to –1.07; I2 = 97%). A possibility of lower mortality is suggested by low-quality evidence with remdesivir (RR 0.74; 95% CI 0.40–1.37, I2 = 58%). Moderate-quality evidence suggests no certain benefit of using lopinavir/ritonavir for Covid-19 compared to arbidol, lopinavir/ritonavir combined with arbidol or other medications used as controls. Conclusion. Further evidence from randomized controlled trials is required for all antivirals to treat Covid-19. At present, remdesivir seems more promising than other antivirals.
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Papers by Tulika Seth