Background There is limited data on outcomes in cancer patients with coronavirus disease 2019 (COVID‐19) from lower middle‐income countries (LMICs). Patients and Methods This was an observational study, conducted between 12 April and 10 June 2020 at Tata Memorial centre, Mumbai, in cancer patients undergoing systemic therapy with laboratory confirmed COVID‐19. The objectives were to evaluate cumulative 30‐day all‐cause mortality, COVID‐19 attributable mortality, factors predicting mortality, and time to viral negativity after initial diagnosis. Results Of the 24 660 footfalls and 7043 patients evaluated, 230 patients on active systemic therapy with a median age of 42 (1‐75) years were included. COVID‐19 infection severity, as per WHO criteria, was mild, moderate, and severe in 195 (85%), 11 (5%), and 24 (11%) patients, respectively. Twenty‐three patients (10%) expired during follow‐up, with COVID‐19 attributable mortality seen in 15 patients (6.5%). There were no mortalities in the pediatric cohort of 31 (14%) patients. Advanced stage cancer being treated with palliative intent vs others [30‐day mortality 24%% vs 5%, odds ratio (OR) 5.6, 95% CI 2.28‐13.78, P < .001], uncontrolled cancer status vs controlled cancer (30‐day mortality37.5%% vs 4%%, OR 14, 95% CI 4.46‐44.16, P < .001) and severe COVID‐19 vs mild COVID‐19 (30‐day mortality 71% vs 3%, OR 92.29, 95% CI 26.43‐322.21, P < .001) were significantly associated with mortality. The median time to SARS‐CoV‐2 RT‐PCR negativity was 17 days [interquartile range (IQR)17‐28) in the cohort. Conclusions The mortality rates in cancer patients with COVID‐19 who are receiving systemic anti‐cancer therapy in LMICSs are marginally higher than that reported in unselected COVID‐19 cohorts with prolonged time to viral negativity in a substantial number of patients. The pediatric cancer patients tended to have favorable outcomes.

Central venous catheters (CVCs) represent a significant source of infection in patients undergoing hematopoietic stem cell transplantation and can add to the cost of care, morbidity, and mortality. Organisms forming biofilms on the inner surface of catheters require a much higher local antibiotic concentration to clear the pathogen growth. Antibiotic lock therapy (ALT) represents one such strategy to achieve such high intraluminal concentrations of antibiotics and can facilitate catheter salvage. Patients with catheter colonization (CC) or hemodynamically stable catheter‐related bloodstream infection (CRBSI) received ALT per institutional policy. We analyzed the incidence of CC and CRBSI and salvage rate of tunneled CVCs (Hickman) with ALT in patients undergoing hematopoietic stem cell transplant in this retrospective study. Catheter colonization was noted in 9.8% and CRBSI in 10.7% patients. Gram‐negative bacilli (GNB) accounted for 45% and 83% of isolates in CC and CRBSI, respectively. In patients with CRBSI, the rate of catheter salvage with the use of ALT in addition to systemic antibiotics was 86% compared to 55% in patients with systemic antibiotics use only (P = 0.06). There was no CRBSI related mortality, and no increase in resistant strains was noted at subsequent CRBSI. In conclusion, ALT represents an important strategy for catheter salvage, especially for gram‐negative infections, in a carefully selected patient population.

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PURPOSE Infections remain a major challenge in the treatment of acute myeloid leukemia (AML). Induction-related mortality reported in the literature is approximately < 5% in clinical trials. However, the real-world scenario is different, especially in developing countries, given the high incidence of multidrug-resistant (MDR) organisms, high incidence of fungal pneumonia at baseline, and significant delay before initiation of chemotherapy. We aimed to look at contemporary infections and infection-related mortality and analyze the patterns of infections. MATERIALS AND METHODS This retrospective study was conducted at a large tertiary care oncology center in India. Patients with newly diagnosed AML who were older than age 15 years, considered fit for intensive therapy, and treated in the general wards of the adult hematolymphoid unit from March 1, 2014, until December 31, 2015, were included. RESULTS One hundred twenty-one patients were treated during the study period. The most common presenting complaint was fever (85%). The focus of infection at presentation was found in 63% of patients, with respiratory infection being the most common (47%). MDR organisms were isolated in 55% of patients during induction from various foci. Klebsiella pneumoniae was the most common blood culture isolate (42.9%). Fungal pneumonia was diagnosed in 55% of patients during induction despite antifungal prophylaxis. Treatment-related mortality was 10.7% in all phases, with an induction mortality rate of 7.4%. Complete remission was attained in 69% of patients. Of all patients who received induction chemotherapy, 74% completed all three consolidation cycles. The 121 patients were followed up for a median period of 53 months. Four-year event-free survival was 35.8%, and 4-year overall survival was 41.5%. CONCLUSION Infections and infection-related mortality are major challenges during AML induction. Gram-negative MDR and fungal infections are particularly common in our region.

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Background: Remission induction is the most intensive phase of acute myeloid leukemia (AML) treatment, associated with significant morbidity and mortality. Collaborative research and advances in supportive care have steadily improved outcomes in developed countries with induction mortality less than 5%. Challenges for treatment in resource limited settings are varied including delayed presentation, higher disease burden, baseline infections and poor general condition precluding standard intensive therapy, higher rates of resistant infections, and several social and financial constraints. Consequently, a significant proportion of patients do not receive definitive therapy and for those who are treated there is a considerably high risk of induction mortality. In an attempt to identify the subset of patients with highest risk of death during induction, we have developed a multivariate model of induction mortality score using baseline features relevant to our clinical setting by utilizing Indian acute leukemia research database [INwARD] established in 2018 by Hematology Cancer Consortium (HCC). Method: Retrospective data from January 2018 to May 2019 for adult AML was collected from 11 member institutions in a central online data management system. Selection of potential variables that would predict mortality was based on clinical and statistical significance. Thus, 10 variables defining baseline patient and disease characteristics (age, ECOG performance status, duration of symptoms in days, albumin, creatinine, bilirubin, white cell count, platelet, peripheral blood blast percentage, and presence of infection requiring intravenous antibiotic within one week prior of starting induction), were considered for the predictive model using machine learning algorithms: Logistic regression (LR) and Support Vector Machine (SVM). SVM was chosen as the best algorithm based on the AUCs. In order to get robust threshold, sensitivity, specificity and predictive values bootstrapping was done 10,000 times. The final statistics were based on the mean (SD) of bootstrapped sample. R software was used to bootstrap and analyze the data. Result: Of the 611 adult AML cases available during study period, 392 treated with the intensive '3+7' or its abbreviated regimen were considered for analysis. Median age of this cohort was 36 years (range 18 - 67), male to female ratio 1.34. European Leukemia Net (ELN) risk group distribution is shown in Fig 1a. Complete remission was attained in 52.8%. Induction mortality was 16.9 % ranging from 6.1% to 43% across different centers. Most common cause of death was infection (66.7%). Multi-drug resistant blood stream infection was documented in 25.4% cases. For the SVM model for predicting induction mortality using 10 covariates, the AUC based on the bootstrap validation was 91.3% with the best threshold probability being 0.262 (Fig 1b). Thus, a cut off score of 0.262 in the SVM model predicted induction death with sensitivity of 93.6% and specificity of 87.7%. Performance of each variable in the SVM model is shown in Fig 1c and comparison of the LR and SVM model in Fig 1d. Conclusion: Score predicting induction death with high accuracy will be a valuable tool in guiding clinicians against the use of intensive induction therapy, in tailoring of treatment as per individual patients' risk and proper resource allocation. Despite the limitations of retrospective data, wide disparity in resources, patient profile and treatment costs across centers accounting for variability in mortality rates, this study represents one major attempt to find answer to a locally relevant clinical problem of high induction mortality in a cohort of young adult AML, utilizing contemporary pooled data through multi-center collaboration. Optimal cut off point for the score needs to be validated in independent patient cohorts and have to be re-calibrated periodically. Further, an online calculator is being designed on the HCC online system to work as ready reckoner for clinicians. Figure 1 a) ELN risk group distribution b) descriptive statistics of bootstrapped SVM Model c) performance of each covariate in SVM model d) ROC Curve: Comparison of LR and SVM method Figure 1 Disclosures No relevant conflicts of interest to declare.

Background Transplant related toxicity is a major therapeutic challenge. We have previously reported that the toxicity of chemotherapy is largely not directly because of the drugs themselves; rather it is mainly due to DNA damage, apoptosis and hyper-inflammation triggered by cell-free chromatin particles that are released because of drug-induced host cell death. Cell-free chromatin particles can be inactivated by free-radicals which are generated when the nutraceuticals resveratrol and copper are administered orally. We investigated if a combination of resveratrol and copper would reduce transplant related toxicities in an exploratory, prospective dose-escalation study. Patients and methods Twenty-five patients with multiple myeloma were enrolled between March 2017 to August 2019. Patients were divided into 3 groups: control (Group 1, N = 5) received vehicle alone; group 2 (N = 15) received resveratrol-copper at dose level I (resveratrol = 5.6 mg and copper = 560 ng); group 3 (N = 5) received resveratrol-copper at dose level II (resveratrol = 50 mg and copper = 5 μg). The dose was given twice daily with the first dose administered 48 hours before administering melphalan and continued until day +21 post-transplant. Common Terminology Criteria for Adverse Events version 4.02 was used to assess toxicities which included oral mucositis, nausea, vomiting and diarrhea. Measurement of inflammatory cytokines was done by ELISA. Results All patients (100%) in the control group developed grade 3/4 oral mucositis compared to 8/20 (40%) in both resveratrol-copper group 2 plus group 3 combined (P = 0.039). Reduction in inflammatory cytokines: salivary TNF - α (p = 0.012) and IL—1β (p = 0.009) in dose level I but not in dose level II was observed. Conclusions A combination of resveratrol-copper reduced transplant related toxicities in patients with multiple myeloma receiving high dose melphalan. We conclude that relatively inexpensive nutraceuticals may be useful as adjuncts to chemotherapy to reduce its toxicity. Registration The trial was registered under Clinical Trial Registry of India (no.CTRI/2018/02/011905).

Introduction: One of the mainstays of chemotherapy in acute myeloid leukemia (AML) is induction with a goal to achieve morphological complete remission (CR). However, not all patients by this remission criterion achieve long-term remission and a subset relapse. This relapse is explained by the presence of measurable residual disease (MRD). Methods: We accrued 451 consecutive patients of adult AML (from March 2012 to December 2017) after informed consent. All patients received standard chemotherapy. MRD testing was done at post-induction and, if feasible, post-consolidation using 8- and later 10-color FCM. Analysis of MRD was done using a combination of difference from normal and leukemia-associated immunophenotype approaches. Conventional karyotyping and FISH were done as per standard recommendations, and patients were classified into favorable, intermediate, and poor cytogenetic risk groups. The presence of FLT3 -ITD, NPM1 , and CEBPA mutations was detected by a fragment length analysis-based assay. Results: As compared to Western data, our cohort of patients was younger with a median age of 35 years. There were 62 induction deaths in this cohort (13.7%), and 77 patients (17.1%) were not in morphological remission. The median follow-up was 26.0 months. Poor-risk cytogenetics and the presence of FLT3 -ITD were significantly associated with inferior outcome. The presence of post-induction MRD assessment was significantly associated with adverse outcome with respect to OS ( p = 0.01) as well as RFS ( p = 0.004). Among established genetic subgroups, detection of MRD in intermediate cytogenetic and NPM1 mutated groups was also highly predictive of inferior outcome. On multivariate analysis, immunophenotypic MRD at the end of induction and FLT3 -ITD emerged as independent prognostic factors predictive for outcome. Conclusion: This is the first data from a resource-constrained real-world setting demonstrating the utility of AML MRD as well as long-term outcome of AML. Our data is in agreement with other studies that determination of MRD is extremely important in predicting outcome. AML MRD is a very useful guide for guiding post-remission strategies in AML and should be incorporated into routine treatment algorithms.