Treatment challenges and outcomes of older patients with acute myeloid leukemia from India.

Globally, overall survival (OS) of older patients with AML continues to be suboptimal with very little data from India. In a multicenter registry analysis, we evaluated 712 patients with AML older than 55 years. Only 323 (45.3%) underwent further treatment, of which 239 (74%) received HMAs, and 60 (18%) received intensive chemotherapy (IC). CR was documented in 39% of those receiving IC and 42% after HMAs. Overall, 100 (31%) patients died within 60 days of diagnosis, most commonly due to progressive disease (47%) or infections (30%). After a median follow-up of 176 days, 228 (76%) of patients had discontinued treatment. At one year from diagnosis, 211 (65%) patients had died, and the median OS was 186 days (IQR, 137-234). Only 12 (3.7%) patients underwent stem cell transplantation. Survival was significantly lower for those older than 60 years (p < 0.001). Patients who died had a higher median age (p = .027) and baseline WBC counts (p = .006). Our data highlights suboptimal outcomes in older AML patients, which are evident from 55 years of age onwards, making it necessary to evaluate HMA and targeted agent combinations along with novel consolidation strategies to improve survival in this high-risk population.

Clinical Outcomes and Determinants of Survival in Patients with Hematologic Malignancies Admitted to Intensive Care Units with Critical Illness.

Outcomes of patients with hematologic malignancies requiring ICU care for critical illness are suboptimal and represent a major unmet need in this population. We present data from a dedicated haematology oncology setting including 63 patients with a median age of 60 years admitted to the ICU for critical illness with organ dysfunction. The most common underlying diagnosis was multiple myeloma (30%) followed by acute myeloid leukemia (25%). Chemotherapy had been initiated for 90.7% patients before ICU admission. The most common indication for ICU care was respiratory failure (36.5%) and shock (17.5%) patients. Evidence of sepsis was present in 44 (69%) patients. After shifting to ICU, 32 (50%) patients required inotropic support and 18 (28%) required invasive mechanical ventilation. After a median of 5 days of ICU stay, 43.1% patients had died, most commonly due to multiorgan dysfunction. Risk of mortality was higher with involvement of more than two major organs (p = .001), underlying AML (p = .001), need for mechanical ventilation (p = .001) and high inotrope usage (p = .004). Neutropenia was not associated with mortality. Our study indicates high rates of short term mortality and defines prognostic factors which can be used to prognosticate patients and establish goals of care. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-024-01757-3.

Autologous stem cell transplantation for multiple myeloma in the novel agent era: Systematic review of Indian data and implications for resource constrained settings.

Treatment of multiple myeloma has undergone significant advances in the last two decades, leading to meaningful improvement in overall and progression free survival. The incurable nature of disease necessitates serial sequencing of treatment options and continuous therapy once disease remission is achieved. Autologous stem cell transplantation (ASCT) has continued to offer a meaningful survival advantage with a consistent reduction in toxicity and costs. Despite the advent of newer drugs leading to deeper and sustained responses, ASCT continues to be the standard of care for all eligible patients and is ostensibly more cost effective than continued treatment with newer agents. However, ASCT continues to be underutilized in India, due to concerns about cost, safety, and sporadic expertize. We present a systematic review of available data on ASCT for multiple myeloma from India to evaluate safety and efficacy of the procedure, and provide evidence re-affirming its utility in resource constrained settings.

Distinctive Attributes of Indian Patients With Classical BCR::ABL1 Negative Myeloproliferative Neoplasms: Unified Clinical and Laboratory Data.

INTRODUCTION: We report one of the largest single center data from a mixed referral setting in India describing baseline characteristics and outcomes of patients with classical BCR::ABL1 negative myeloproliferative neoplasms (MPNs). MATERIALS AND METHODS: Patients diagnosed from June 2019 to 2022 were included. Workup and treatment was as per current guidelines. RESULTS: Diagnosis comprised polycythemia vera (PV) in 51(49%), ET in 33(31.7%) and prefibrotic primary myelofibrosis (MF) pre fibrotic myelofibrosis (prePMF) and myelofibrosis in 10(9.6%) patients each. Median age at diagnosis was 52 years for PV and ET, 65.5 for MF and 79 years for prePMF. Diagnosis was incidental in 63(56.7%) and after thrombosis in 8(7.2%) patients. Baseline next generation sequencing (NGS) was available for 63(60.5%) patients. Driver mutations in PV: JAK2 in 80.3%; in ET: JAK2 in 41%, CALR in 26%, MPL in 2.9%; in prePMF JAK2 in 70%, CALR in 20%, MPL in 10%, and in MF: JAK2 in 10%, MPL in 30% and CALR in 40%. Seven novel mutations were detected of which 5 were potentially pathogenic on computational analysis. After median follow up of 30 months, 2 patients had disease transformation and none had new episodes of thrombosis. Ten patients died, most commonly with cardiovascular events(n = 5,50%). Median overall survival was not reached. Mean OS time was 10.19 years(95%CI, 8.6 to 11.74) and mean time to transformation was 12.2 years(95% CI,11.8 to 12.6). CONCLUSION: Our data indicates comparatively indolent presentation of MPNs in India with younger age and lower risk of thrombosis. Further follow up will enable correlation with molecular data and guide modification of age based risk stratification models.

Clinical profile of patients with cardiac amyloidosis in India.

Limited data exists on patients with cardiac amyloidosis (CA) in India, due to underdiagnosis and late presentation. We present single centre data from 13 patients over a 4 year period with a median age of 65 years. A majority presented with symptomatic heart failure (69%) and eight patients had confirmed AL amyloidosis. At the end of the follow up period, 46% patients died, with 30% of the overall cohort dead within six months. Among the survivors, 71% continue to have NYHA grade III/IV symptoms. A suggested algorithm for earlier diagnosis in resource constrained settings is also presented.

Considerations for Peripheral Blood Stem Cell Apheresis in a Low Body Weight Infant.

INTRODUCTION: Peripheral blood stem cell (PBSC) apheresis in infants (<10 kg body weight) requires specific precautions to prevent periprocedural complications. CASE REPORT: A 9 month old child was diagnosed with high-risk neuroblastoma and planned for autologous stem cell transplantation after induction chemotherapy. We illustrate the precautions and technical details observed while performing PBSC collection in this patient. DISCUSSION: Use of continuous flow devices, priming of apheresis circuits, appropriate flow rates and continuous monitoring can help to mitigate several procedure related complications. CONCLUSIONS: PBSC apheresis in infants (<10 Kg) is safe and feasible with appropriate precautions detailed above.

Thrombocytopenia in COVID-19: Focused Summary of Current Understanding of Mechanisms and Clinical Implications.

Thrombocytopenia is noted in corona virus disease-2019 (COVID-19) with a prevalence of 5% to 41%, and has been observed to be associated with inferior outcomes. The pathogenesis of thrombocytopenia in COVID-19 is unique and differs from other viral syndromes in terms of clinical presentation and causative mechanisms. Platelets act as both targets and the initial defense against severe acute respiratory syndrome-coronavirus 2 and work in concert with the underlying thrombophilic mechanisms to modulate the final disease phenotype. Understanding these mechanisms may possibly allow targeting of a key component of COVID-19 pathogenesis. We provide a focused review of the current mechanisms implicated in development of thrombocytopenia in COVID-19 and therapeutic implications of the same.

Mitigation of in-hospital risk of coronavirus disease 2019: Experience from a haematology-oncology and stem cell transplant setting.

Background: . Coronavirus disease 2019 (Covid-19) was first described in December 2019 and has evolved into an ongoing global pandemic. Cancer patients on chemotherapy are immunocompromised and are at the highest risk of Covid-19-related complications. We describe our experience with the management of haematology-oncology and stem cell transplant (SCT) patients receiving curative chemotherapy in a hospital with a high influx of Covid-19 patients. Methods: . We did a prospective observational study at a 99-bedded cancer centre of a tertiary care teaching hospital from April 2020 to September 2020. Preventive measures taken were categorized as follows: (i) staff: screening, mandatory use of personal protective equipment (PPE), risk stratification of potential exposure and testing and isolation as needed; (ii) patients: mandatory viral polymerase chain reaction testing, segregation of positive and untested patients and testing of family members; and (iii) environment: mandatory regular cleaning, visitor restriction, telemedicine services and reassignment of priority to clinic visits. Treatment of the underlying conditions was continued with added precautions. Results: . A total of 54 patients were included in the analysis, including 48 with haematological malignancies and 6 for stem cell therapy. Preventive measures were universally applied, and chemotherapy with a curative intent was initiated as per protocol. Three patients were detected to have Covid-19 infection before admission and one after the institution of chemotherapy. Nine patients died after the first cycle of chemotherapy, 2 due to severe Covid-19-related illness and 7 due to complications of chemotherapy or disease progression. Conclusions: . In the wake of the Covid-19 pandemic, treatment for haematological malignancies must continue while balancing the risk of Covid-19 infections. Our report emphasizes the effectiveness of measures such as hand hygiene, social isolation, patient segregation, use of masks and PPE and universal pre-treatment testing for Covid-19 in reducing the risk of infection in a high-risk clinical setting.

Cross-sectional Survey of Anticoagulant Use among Specialist Physicians with a Focus on Direct Anticoagulants.

INTRODUCTION: Direct oral anticoagulants (DOACs) have been available for clinical use since 2010 and offer the advantages of a lower bleeding risk with similar efficacy compared to Vitamin K antagonists (VKAs). However, no data is available on practice patterns anticoagulation usage and determinants of the same among physicians in India. METHODS: A cross-sectional survey was conducted using Google Forms comprising of 24 questions in 4 categories on baseline information, practice details, knowledge, and outlook. RESULTS: A total of 412 physicians were contacted, of which complete responses were received from 50 (12%). Majority had a subspecialist (58%) or a specialist (32%) qualification, with 54% working in a medical college. VKAs were the preferred first-line agent for 46%, with the most common perceived disadvantage being need of regular monitoring. The absence of regular blood testing was the most prominent advantage attributed to novel oral anticoagulants (NOACs) by 76% participants. Equivalent number of participants perceived efficacy to be similar in both groups, and 86% indicated NOACs to have better safety. Most participants responded to knowledge-based questions correctly and cited high costs of DOACs as the most common barrier to clinical use (78%). CONCLUSIONS: Our survey indicates VKAs as the preferred first-line agents despite perceived disadvantages. Among specialist physicians, high drug costs and not lack of knowledge or familiarity appear to be predominant factors precluding more frequent use of NOACs.

Real world data on clinical profile, management and outcomes of venous thromboembolism from a tertiary care centre in India.

OBJECTIVES: Venous thromboembolism (VTE) is a major cause of mortality and morbidity worldwide. This study describes a real-world scenario of VTE presenting to a tertiary care hospital in India. METHODS: All patients presenting with acute VTE or associated complications from January 2017 to January 2020 were included in the study. RESULTS: A total of 330 patient admissions related to VTE were included over 3 years, of which 303 had an acute episode of VTE. The median age was 50 years (IQR 38-64); 30% of patients were younger than 40 years of age. Only 24% of patients had provoked VTE with recent surgery (56%) and malignancy (16%) being the commonest risk factors. VTE manifested as isolated DVT (56%), isolated pulmonary embolism (PE; 19.1%), combined DVT/PE (22.4%), and upper limb DVT (2.3%). Patients with PE (n = 126) were classified as low-risk (15%), intermediate-risk (55%) and high-risk (29%). Reperfusion therapy was performed for 15.7% of patients with intermediate-risk and 75.6% with high-risk PE. In-hospital mortality for the entire cohort was 8.9%; 35% for high-risk PE and 11% for intermediate-risk PE. On multivariate analysis, the presence of active malignancy (OR = 5.8; 95% CI: 1.1-30.8, p = 0.038) and high-risk PE (OR = 4.8; 95% CI: 1.6-14.9, p = 0.006) were found to be independent predictors of mortality. CONCLUSION: Our data provides real-world perspectives on the demographic sand management of patients presenting with acute VTE in a referral hospital setting. We observed relatively high mortality for intermediate-risk PE, necessitating better subclassification of this group to identify candidates for more aggressive approaches.

Clinical and Molecular Attributes of Patients With BCR/ABL1-negative Myeloproliferative Neoplasms in India: Real-world Data and Challenges.

INTRODUCTION: Classic BCR/ABL1-negative myeloproliferative neoplasms (MPNs) are characterized by clinical and genetic heterogeneity and include 4 distinct constituents. Very little data on clinical presentation and epidemiology of the same is available from the Indian setting. PATIENTS AND METHODS: Patients referred to Hematology-Oncology from January 2018 to August 2020 with suspected MPNs were included in the analysis and prospectively followed-up. All patients were initially screened, and only those meeting the updated World Health Organization 2016 criteria were included in the analysis. Epidemiologic, clinical, and molecular characteristics were documented, and patients were followed-up prospectively. RESULTS: A total of 233 patients were referred for evaluation of MPN, of which 63 were included in the analysis, including 39 males and 24 females. The median age at diagnosis was 57 years (range, 28-82 years), and 38% patients were younger than 50 years of age. The most common presentations were incidental detection in 35 (55.5%), abdominal symptoms in 13 (20%), fatiguability in 7 (11%), and recent vascular events in 6 (9.5%) patients. Final diagnosis was polycythemia vera in 27, essential thrombocytosis (ET) in 21, prefibrotic myelofibrosis in 9, and myelofibrosis in 6 patients. The frequency of driver mutations in polycythemia vera included JAK2 in 75%; in ET, JAK2 in 33%, CALR in 33%, and MPL in 4%; and in prefibrotic myelofibrosis, JAK2 in 66% and CALR in 33%. Aspirin was used for all patients along with risk-adapted cytoreduction with hydroxyurea. Ruxolitinib was reserved for symptoms refractory to hydroxyurea. After a median follow-up of 15 months (interquartile range, 10-28 months) from diagnosis, disease progression was noted in 4 patients. Two patients died at the end of the follow-up period, including 1 with secondary acute myeloid leukemia post myelofibrosis and one with ET and coexistent oral malignancy. The remaining 61 patients are alive and on regular treatment. RESULTS: This is one of the first systematic descriptions and prospective follow-up of patients with BCR/ABL-negative MPNs from India. Our study indicates a younger median age of presentation and higher proportion of JAK2-unmutated disease across all subtypes. The primary role of bone marrow morphology and supportive role of somatic mutations in differentiating MPN subtypes is indicated. CONCLUSIONS: This study sets the stage for a collaborative registry for defining epidemiologic data and long-term outcomes with MPN in India.

Treatment of Acute Leukemia During COVID-19: Focused Review of Evidence.

The Coronavirus disease-2019 (COVID-19) pandemic is an unprecedented health care crisis and has led to over 1.5 million deaths worldwide. The risk of severe COVID-19 and mortality is markedly raised in patients with cancer, prompting several collaborative groups to issue guidelines to mitigate the risk of infection by delaying or de-escalating immunosuppressive therapy. However, delayed therapy is often not feasible for patients requiring treatment for acute leukemia or stem cell transplantation. We provide a focused review of the recommendations and evidence for managing this high-risk group of patients while minimizing the risk of COVID-19 infection, and provide a small snapshot of treatment data from our center.