Supportive Care Measures Research Articles

Current Status of CAR T Cell Therapy for Leukemias.

Chimeric antigen receptor (CAR) T-cell therapy has become the standard of care for children and young adults with relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL), and it is a highly promising therapy under investigation for adults with relapsed disease. Despite having potentially life-threatening toxicities, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, the benefits of CAR T-cell therapy far outweigh these risks, particularly as increased experience and improved supportive care measures are mitigating these toxicities. CAR T cells can result in complete remission for significant proportion of patients with relapsed and refractory B-ALL and permit them to proceed to potentially curative allogeneic hematopoietic stem cell transplantation (allo-HSCT). CAR T cells may also be curative by themselves. Herein lie the greatest challenges and questions for clinical investigators, specifically, how are CAR T cells best employed and how do we overcome mechanisms of resistance to them? The primary clinical question is the timing and even the necessity of allo-HSCT. Relative to resistance, we know that target antigen loss, specifically CD19, is a major contributor to resistance. However, current investigations of alternative targets, such CD22, and CAR T cells expressing dual targeting antigen receptors have demonstrated encouraging initial results and provide a high degree of optimism that the efficacy and the broader application of CAR T-cell therapy will gradually increase in B-ALL. That optimism is not as high and the challenges are increased for the application of CAR T cells in T-cell leukemias and acute myeloid leukemia due to the relative lack of suitable leukemia surface targets that are not also expressed on normal hematopoietic progenitors. Despite these significant challenges, considerable research is being conducted into the development of CAR T cells for these diseases utilizing unique technologies, which may be applicable to other diseases.

POEMS syndrome: 2021 Update on diagnosis, risk-stratification, and management.

POEMS syndrome is a paraneoplastic syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyradiculoneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis. The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. Risk factors include low serum albumin, age, pleural effusion, pulmonary hypertension, and reduced eGFR. For those patients with a dominant plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement and for those who have progression of their disease 3-6months after completing radiation therapy should receive systemic therapy. Corticosteroids are temporizing, but alkylators are the mainstay of treatment, either in the form of low dose conventional therapy or high dose with stem cell transplantation. Lenalidomide shows promise with manageable toxicity. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.

Interprofessional care team practices and perspectives on immuno-oncology (IO) therapies for metastatic non-small cell lung cancer (mNSCLC): Insights from a nationwide survey.

e21147 Background: Appropriate molecular testing, biomarker-directed treatment selection, and management of immune-related adverse events (irAEs) are essential best practices for managing patients with mNSCLC who are eligible for IO therapies. Identifying real-world challenges among mNSCLC care teams is necessary to inform educational interventions that support optimal care. Methods: From 10/2020 to 01/2021, 75 health care professionals (HCPs) who treat mNSCLC completed surveys assessing practice patterns, challenges, and confidence related to the use of IO therapies. To reflect current real-world practice across treatment settings, surveys were administered at 10 clinics nationwide and through a large oncology practice network. Results: Participants represented the interprofessional mNSCLC care team: oncologists (50%), primary care physicians (23%), advanced practice professionals (13%), and nurses (13%). Nearly one-third reported that PD-L1+ mNSCLC presented greater management challenges than other mNSCLC sub-types. Regarding patients who are eligible for IO therapies, the most commonly reported challenges were applying pathology results to treatment decisions (29%), differentiating IO therapies (19%), and managing irAEs (19%). Case-based questions revealed gaps in care relative to guidelines: 65% incorrectly identified which patients should be tested for PD-L1; 49% failed to identify the most appropriate IO regimen based on case details; and 65% failed to identify an inappropriate strategy for managing mild irAEs (Table). Further, HCPs reported inappropriate reasons to exclude patients from IO therapy and suboptimal use of supportive care measures. Confidence gaps echoed these challenges; most HCPs reported less-than-high confidence in their ability to apply molecular test results to treatment decisions (80%), differentiate IO therapies based on PD-L1 expression (65%), or coordinate irAE care (85%). Conclusions: In current real-world practice, mNSCLC care teams report challenges in biomarker testing and interpretation; differentiation of IO therapies based on patient, disease, and treatment factors; and irAE management. These identified gaps represent key opportunities for future interventions to improve mNSCLC care. [Table: see text]

Characterizing unplanned resource utilization associated with cancer-related diarrhea.

e18625 Background: In clinical oncology practice, diarrhea is a very common and severe side effect of cancer treatments including from radiotherapy, chemotherapy, and targeted therapies. Cancer-related diarrhea (CRD) leads to increased healthcare resource consumption due to unscheduled outpatient visits, and , increased hospital stays requiring intensive supportive care measures. We evaluated CRD patients receiving chemotherapy, targeted therapy, or both, requiring emergency department (ED), physician office visits, hospitalizations, and length of stay (LOS) compared to a matched cohort of non-CRD patients. Methods: We performed a longitudinal study among adult patients ( > 18 yrs) with CRD identified by diagnosis codes or pharmacy claims compared to matched non-CRD patients using claims data derived from the IQVIA PharMetrics Plus database. Index date was the first cancer claim date and patients were re-indexed based on their CRD claim. Each patient had a 6-month pre-index period, a minimum 3-month post-index period and had ≥12 months of continuous enrollment following the CRD index date. To adjust for selection bias and baseline differences, we matched CRD patients to non-CRD patients (1:1) by age, gender, geography and payer type. Patients were stratified by cancer therapy type (chemotherapy, targeted therapy or both treatments). We reported proportion of patients with hospitalizations, average length of stay (LOS), and ED visits. A generalized estimating equation model with log link and binomial distribution adjusted for type of cancer, therapy, and Charlson Comorbidity Index (CCI) was built to estimate the difference in occurrence of hospitalization between CRD and non-CRD cohorts. Results: We evaluated a total of 104,135 matched pairs of CRD and non-CRD adult patients with solid or hematologic cancer with 12-month continuous enrollment. The proportion of patients with ED visits (36.2% vs 18.9%, p < 0.0001) and hospitalizations (29.6% vs 12.8%, p < 0.0001) were significantly higher among CRD versus non-CRD cohort. When compared to non-CRD patients, CRD patients were more likely to be hospitalized (adjusted OR 2.28. 95% CI of 2.23-2.33). Mean CRD-specific office/hospital visits were significantly higher in the CRD cohort compared to the non-CRD cohort over the 12-month post-index period and patients had more CRD-specific visits to ED (7.5% vs 1.8%); physician’s offices (14.7% vs 3.8%); laboratory testing (11.6% vs 3.2%) and outpatient ancillary services (10.9% vs 2.6%) (all p < 0.0001). Mean hospital LOS among patients with CRD was higher than non-CRD patients (6.6±8.9 vs 5.8±10.5 days, p < 0.0001). Conclusions: Patients with CRD used significantly more resources, including outpatient services, ED visits, and hospitalizations. Effective prevention of CRD remains an unmet strategy to reduce the overall cost of cancer care.

Health disparities experienced by Black Americans with multiple myeloma in the United States: A population-based study.

e18512 Background: Multiple Myeloma (MM) is the most common hematologic malignancy in Black Americans. Incidence and death rates for MM in Black Americans are more than double those in Whites. Our study aimed to evaluate trends of all cause in-hospital mortality among Black Americans with MM and to investigate characteristics of MM-related hospitalizations. Methods: We conducted a retrospective cross-sectional study of hospitalizations in adult patients with MM during 2008-2017 using the National Inpatient Sample (NIS), the largest all-payer inpatient care database in the US. We used joinpoint regression to assess temporal trends in the national incidence of in-hospital death. We conducted adjusted survey logistic regression to generate adjusted odds ratios to measure the likelihood of in-hospital death among MM related hospitalizations. Results: Admissions related to MM constituted 0.32% of all hospitalizations in the study period (913,967 out of 285,876,821). The prevalence of MM related hospitalizations was higher in Black Americans when compared with Whites (476.0 vs 305.6 per 100,000 hospitalizations, p <0.01). In-hospital mortality with MM was higher in older patients, males, those belonging to lowest zip code quartile, and who self-paid for their treatment. Average Annual Percent Change (AAPC) showed a statistically significant decline of in-hospital mortality among all MM patients except Black Americans who had the highest inpatient mortality in 2016 and 2017. Black Americans received less autologous stem cell transplantation (ASCT) (2.8% vs. 3.8%, p <0.01), more blood product transfusions (23.0% vs. 21.1%, p <0.01), less palliative care consultation (4.0% vs. 4.6%, p <0.01), less chemotherapy (10.8% vs. 11.2%, p <0.01), and more intensive care utilization (5.3% vs. 4.3%, p <0.01), when compared with Whites. Adjusted association between race/ethnicity and various outcomes confirmed observed differences [Table]. Conclusions: Black Americans with MM had the slowest improvement and highest inpatient mortality in recent years. Data suggests higher disease burden, more frequent hospitalizations, delay in accessing care and lower utilization of supportive care measures compared with White MM patients. Data highlight disparities in MM care for Black Americans necessitating a clarion call for urgent changes in health care systems.[Table: see text]

Daily step counts to predict hospitalizations during chemoradiotherapy for head and neck cancer.

1571 Background: Wearable activity trackers could provide useful data for managing cancer patients with respect to treatment selection, toxicity monitoring, and implementation of supportive care measures. Here, we seek to evaluate the association between daily step counts and hospitalizations in a cohort of patients with head and neck cancer (HNC). Methods: This analysis consists of patients enrolled in one of three prospective trials involving activity monitoring (NCT02649569, NCT03115398, NCT03102229) during chemoradiation. Study subjects were asked to wear a commercial fitness tracker continuously during the therapy. ECOG performance status (PS) was assessed at baseline, and quality of life (QoL) EORTC QLQ-C30 questionnaires were completed weekly. Multivariable Cox regression models with time-dependent covariates (average step count over the past 3 days, most recent QoL score) and time-fixed covariates (age, sex, baseline PS, study number, baseline tumor volume, and treatment setting [definitive versus postoperative]) were used to identify predictors of first hospital admission during the chemoradiotherapy course. In addition to the Cox regression models, linear mixed models were fitted with daily step count as the dependent variable to examine its relationship with certain independent variables including age, sex, weekend status, days after treatment initiation, and study number. Results: Sixty-six HNC patients who received chemoradiotherapy between 2015 and 2019 were included in the analysis. Median age was 60 (range: 27-88). 47% of patients had ECOG PS score 0, 47% ECOG score 1, and 6% ECOG score 2. 29% of patients had HPV-positive oropharyngeal tumors, and the most common other tumor subsites were larynx (27%), and nasopharynx (12%). The Cox regression survival model demonstrated a 26% reduction in the short-term hospitalization risk for every 1000 daily steps (averaged over the past 3 days, hazard ratio 0.74; 95% confidence interval (CI) 0.55-0.98, p = 0.0367). Hospitalizations were not significantly associated with most recent QoL or baseline ECOG PS. Additionally, according to the linear mixed model results, daily step count was not associated with age (p = 0.8048). Study subjects moved less on weekends (on average 245 fewer steps on weekends than weekdays, 95% CI 134-357, p < 0.0001). Also, an increase in most recently measured ECOG PS was associated with a decrease in daily step count (167 fewer steps for every increase in ECOG PS, 95% CI -289 to -45, p < 0.0072). Conclusions: Daily step counts are a dynamic predictor of hospitalizations in patients undergoing chemoradiotherapy for head and neck cancer. Interventional studies are needed to demonstrate feasibility of leveraging physical activity data to optimize supportive care during cancer therapy and enhance cancer care quality. Clinical trial information: NCT02649569, NCT03115398, NCT03102229.

Palliative care for patients undergoing stem cell transplant: intervention components and supportive care measures.

An inpatient palliative care intervention during HCT led to improvement in patient QOL and mood. We sought to describe components of the intervention, investigate differences in supportive care practices by treatment arm, and explore whether these differences mediated the impact of the intervention on patient QOL and mood. We conducted a secondary analysis of a randomized trial investigating inpatient palliative care integrated with transplant care versus standard transplant care for HCT recipients. Palliative care clinicians completed weekly surveys to describe topics addressed during visits. We extracted use of supportive care medications from the medical record. Participants completed QOL and mood assessments at baseline and two weeks post-HCT. Causal mediation assessed whether differences in supportive care practices mediated the impact of the intervention on patient-reported outcomes. A total of 160 HCT recipients participated. Palliative care visits most frequently focused on managing symptoms and coping with HCT. Patients randomized to the intervention were more likely to use Patient-Controlled Analgesia (PCA) (32.1% vs. 15.2%, p = 0.02) and atypical antipsychotics (35.8% vs. 17.7%, p = 0.01). Neither PCA nor atypical antipsychotics mediated the effect of the intervention on patient-reported outcomes. Future work to explore mechanisms by which the palliative care intervention improves QOL and mood is needed.

Risk factors for high-dose methotrexate-induced nephrotoxicity.

High-dose methotrexate (MTX) is widely used for the treatment of hematological malignancies. Despite the application of routine supportive care measures, such as intensive fluid hydration and urine alkalinization, nephrotoxicity is still a problem. The present study aimed to evaluate the risk factors for MTX-induced nephrotoxicity. We retrospectively reviewed 88 patients who received a regimen consisting of high-dose MTX (1000mg/m2) and cytosine arabinoside between 2006 and 2018. Nephrotoxicity (≥ grade 2) was observed in 11 patients. Nephrotoxicity was observed only in patients with a high MTX concentration. Other than the MTX concentration, the serum uric acid level and urine pH at day 1 were associated with nephrotoxicity. A multivariate analysis revealed that urine pH was an independent risk factor for MTX-induced nephrotoxicity. Urine pH < 7.0 at day 1 was a significant risk factor for nephrotoxicity (odds ratio, 8.05; 95% confidence interval 1.95-33.3) and was also a predictor of delayed MTX elimination at 72h after injection. Among pre-treatment factors, a low serum calcium level predicted urine pH < 7.0 at day 1. In conclusion, the present study suggests that low urine pH at day 1 is an independent risk factor for MTX-induced nephrotoxicity.

ABCDEF Bundle and Supportive ICU Practices for Patients With Coronavirus Disease 2019 Infection: An International Point Prevalence Study.

To investigate implementation of evidence-based and supportive cares in ICUs, such as the ABCDEF, nutrition therapy, and ICU diary, for patients with coronavirus disease 2019 infection in ICUs and their association with ICU clinical practice and setting. A worldwide, 2-day point prevalence study. The study was carried out on June 3, 2020, and July 1, 2020. A total of 212 ICUs in 38 countries participated. Clinicians in each participating ICU completed web-based online surveys. The ICU patients with coronavirus disease 2019. None. The implementation rate for the elements of the ABCDEF bundle, other supportive ICU care measures, and implementation-associated structures were investigated. Data were collected for 262 patients, of whom 47.3% underwent mechanical ventilation and 4.6% were treated with extracorporeal membrane oxygenation. Each element was implemented for the following percentages of patients: elements A (regular pain assessment), 45%; B (both spontaneous awakening and breathing trials), 28%; C (regular sedation assessment), 52%; D (regular delirium assessment), 35%; E (early mobility and exercise), 47%; and F (family engagement and empowerment), 16%. The implementation of element E was 4% for patients on mechanical ventilation and 8% for patients on extracorporeal membrane oxygenation. Supportive care, such as protein provision throughout the ICU stay (under 1.2 g/kg for more than 50% of the patients) and introduction of ICU diary (25%), was infrequent. Implementation rates of elements A and D were higher in ICUs with specific protocols and fewer ICU beds exclusively for patients with coronavirus disease 2019 infection. Element E was implemented at a higher rate in ICUs that had more ICU beds assigned for them. This point prevalence study showed low implementation of the ABCDEF bundle. Specific protocols and the number of ICU beds reserved for patients with coronavirus disease 2019 infection might be key factors for delivering appropriate supportive care.

Patent ductus arteriosus management and the drift towards therapeutic nihilism – What is the evidence?

The published literature on patent ductus arteriosus (PDA) management is challenging to interpret due to poorly designed trials with high rates of open label treatments, homogenisation of patients with varying physiological subtypes, poor treatment efficacy, and spontaneous closure in more mature infants. The perceived lack of clinical benefit has led to a drift away from medical and surgical treatment of all infants with a PDA. This therapeutic nihilism as a default response to PDA management fails to recognise the physiological relevance of a left-to-right shunt with early haemodynamic instability after birth and subsequent pulmonary volume overload with prolonged exposure. Clinicians need to know if therapeutic nihilism is safe. This review will provide an overview of the available data on the efficacy of known PDA treatments, conservative management and supportive care measures that are currently applied.

The impact of the COVID-19 outbreak on supportive care for oral mucositis: current concepts and practice.

The outbreak of coronavirus disease 2019 (COVID-19) markedly affected the way healthcare professionals approach patients with cancer worldwide, not only in terms of therapeutic decision-making but also in terms of supportive care. With the rapid appearance of signs and symptoms and the need of close re-assessment, standard management of oral mucositis has been challenged by physical distancing and limited resources due to the global crisis. Building on the clinical experience developed during the acute phase by members of the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO), the implications of COVID-19 on the prevention, assessment, and treatment of mucositis are critically reported. Inspired by the restructuring of supportive care measures in response to the pandemic, suggestions for new models of approaching acute side effects are also discussed.

Outcome of Infants with Hypoxic-Ischemic Encephalopathy Treated by Whole Body Cooling and Magnesium Sulfate

AbstractTherapeutic hypothermia (TH) either by selective head cooling or whole-body cooling decreases brain damage and provide neuroprotection and reduced mortality rate in cases of moderate-to-severe hypoxia-ischemia encephalopathy (HIE) of newborns, especially if started at first 6 hours after birth. Also, management with adjuvant therapies like magnesium sulfate (MS) provides more neuroprotection. The interventional randomized controlled research aimed to assess short-term actions of TH as sole therapy and in combination with MS as a neuroprotective agent for the treatment of HIE newborn infants. A total of 36 full-terms and near-term infants delivered at Assiut University Children's Hospital and fulfilled HIE criteria were enrolled. They were divided equally into three groups; Group 1 (n = 12) received whole body cooling during first 6 hours of life as a sole therapy; Group 2 (n = 12) received whole body cooling in addition to MS as adjuvant therapy; Group 3 (n = 12) received supportive intensive care measures as a control. TH plus MS group (group 2) had a significantly good short-term outcomes as short period of respiratory support and mechanical ventilation (p-value =0.001), less in incidence of convulsion (p-value = 0.001) and early in feeding initiation (p-value = 0.009), compared with other groups managed by TH (group 1) or by supportive treatment (group 3). In conclusion, whole body cooling in addition to MS as adjunctive therapy for the treatment of HIE neonates is safe therapy that improves short-term outcome both clinically and radiologically.

Genomics and precision medicine in pediatric acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most frequent malignant disease in the pediatric population, accounting for about 25% of childhood cancers. Drastic therapeutic improvements have been made for pediatric ALL since the early 1960s, marking the most successful treatment paradigm in pediatric oncology. The clinical success derived from refined risk-adapted therapy based on presenting features, cytogenetics and minimal residual disease, prevention of central nervous system relapse, and improvement of supportive care measures. With contemporary therapies, survival of children with ALL now exceeds 90%. However, ALL represents one of leading causes of cancer-related death, as 15%-20% of patients continue to relapse and outcomes post-relapse remain poor. Since the early 2000s, large-scale genomic studies of ALL, greatly facilitated by the advent of next generation sequencing (NGS), have enabled the development of a novel taxonomy for ALL in the molecular era. The access to NGS technologies identifies novel ALL subsets characterized by “driver” oncogenic alterations, previously cryptic on conventional karyotyping methods. With genomic characterization, the group of formerly unclassified B-lineage ALL reduces from 25% to a marginal 5% of ALL. The revised molecular classification of ALL confers prognostic significance and describes the predilection of unfavorable ALL subtypes with increasing age, partially elucidating the worst outcome of adolescents and young adults with ALL. Large-scale genomic analysis also reveals inherited alterations predisposing to ALL occurrence or to different drugs’ sensitivities. Most importantly, the genomic portrait of ALL uncovers novel therapeutic vulnerabilities, paving the way towards precision medicine opportunities in ALL.

Rapid-onset and fatal pneumonitis from trametinib treatment of non-small cell lung cancer: A case report

Introduction: Lung cancer remains the leading cause of death in both men and women worldwide. Oral targeted therapy remains the recommended first-line approach for those with actionable mutations. The combination of trametinib and dabrafenib has shown durable responses as both a first line and second line treatment in patients with non-small cell lung cancer (NSCLC) with a BRAFV600E mutation. Respiratory complications with trametinib have rarely been documented, with an incidence of less than 2%. Case Report: A 58-year-old former female smoker who presented with dyspnea on exertion and was found to have a right hilar mass. The mass was biopsied and found to be a poorly differentiated carcinoma consistent with NSCLC. Tumor proportion score (TPS) was 100% for programmed death-ligand 1 (PD-L1) expression, and molecular analysis confirmed a BRAFV600E mutation. She was started on treatment with dabrafenib 150 mg twice daily with trametinib 2 mg once daily. After ten days, she developed fever followed by leukocytosis and hypoxia. Chest imaging was suggestive of pneumonitis, and she was initiated on high-dose steroids and antibiotics. Her cultures remained negative, though she was unable to be weaned from high-flow oxygen. She transitioned to hospice care several days later and subsequently passed in another 12 days. Conclusion: Trametinib-induced interstitial pneumonitis, while a relatively rare occurrence, can become rapidly life-threatening and should prompt immediate cessation of the medication followed by urgent supportive care measures.

Odronextamab (REGN1979), a Human CD20 x CD3 Bispecific Antibody, Induces Durable, Complete Responses in Patients with Highly Refractory B-Cell Non-Hodgkin Lymphoma, Including Patients Refractory to CAR T Therapy

Odronextamab (REGN1979), a Human CD20 x CD3 Bispecific Antibody, Induces Durable, Complete Responses in Patients with Highly Refractory B-Cell Non-Hodgkin Lymphoma, Including Patients Refractory to CAR T Therapy

Chronic Lymphocytic Leukemia Treatment in México: Up to Half Patients May Not Requiere Treatment

Introduction Chronic lymphocytic leukemia (CLL) is a lymphoid neoplasm which represents the most frequent hematologic malignancy in Caucasians. Every year, there are15,000 new diagnoses and 5000 CLL deaths in the United States. Its prevalence in México and other non-Caucasian populations is substantially lower and the clinical course of CLL patients has been described to be less aggressive Methods All consecutive patients seeking medical care after 1983 in our institution as a result of CLL and followed for at least 3 months were entered in the study. The study was approved by the institutional review board. The treatment of patients was withheld in: (a) Persons with CLL Rai stage 0 or 1, until progression; (b) Persons with CLL Rai stage 2-4, with a negative expression of ZAP-70 until progression. Progression was defined by: Anemia, thrombocytopenia, massive symptomatic or progressive splenomegaly and or adenopathy, progressive lymphocytosis (&amp;gt;50% increase in two months or lymphocyte doubling timeless than 6 months), autoimmune hemolytic anemia not responding to standard therapies, or constitutional symptoms: Weight loss greater than 10% in 6 months, unexplained night sweats or unexplained fever for 2 or more weeks. Refractoriness of the disease was defined as progression despite treatment for a minimum of 3 months. Results Among 98 patients with CLL who were accrued in the study between 1983 and 2019, 49 (50%) were followed for three or more months and accordingly, entered in the study. Median follow up time of the patients is 61 months (95% CI 46.1-75.8). There were 15 females and 34 males, the median age was 65 years (range 23-86). According to the Rai staging system, there were 24 stage 0, 7 stage I, 8 stageII, 0 stage III and 10 stage IV; 80% of patients were identified in stages 0-II. In 28 patients a complete immune phenotype of the malignant cells was analyzed: 89% of patients were ZAP-70 negative (ZAP expression in less than 20% of malignant cells), 79% expressed CD5, 100% CD19 and 86% CD23. Three patients were born in European countries, whereas 6 had an immediate European ancestor, indicating that a Caucasian background was identified in 9/49patients (18%). There were no instances of T-cell CLL. Median OS for all the patients has not been reached, being above 247 months (20 years). The OS of patients given or not any treatment was not statistically different (p= 0.09). It is clear that patients who needed treatment did worse than those not needing treatment but the differences were not significant. Patients with advanced stages (III and IV) had a worse outcome than those in early stages. Median OS for patients given no treatment at all has not been reached and is above 247 months; median OS for patients given CP was 115 months, median OS for those given FC has not been reached and is above 132 months, whereas median OS for persons given FCR has not been reached, being above 136 months; all these differences are not statistically significant. Eight of 49 patients were found to be refractory to treatment; they were receiving CP (5 cases); FC (2 cases) and FCR (one case); these refractory patients were given, FCR (7 cases) and rituximab/ifosfamide/carboplatin/etoposide (one case). No patient had to be given cladribine, pentostatin, alemtuzumab (anti-CD52), bendamustine, ofatumumab (anti-CD20), obinutuzumab (anti-CD20), lenalidomide, ibrutinib nor idelalisib. Conclusion In the era of novel anti-CLL drugs, we have found that the clinical course of these patients in México seems to be less aggressive than in Caucasian populations and that, in consequence, circa 50% of them do not need any treatment at all. In those needing treatment, the use of a simplified approach and taking advantage of improved supportive care measures, acceptable results are obtained even if all of the new CLL drugs are not employed. These observations may be critical in developing countries, where the cost of the drugs will continue to be a major factor in choosing therapies. Disclosures No relevant conflicts of interest to declare.

Incidence of Invasive Fungal Infection (IFI) in ACUTE Myeloid Leukemia (AML) on Primary Prophylaxis with Voriconazole in Tertiriary Care Center in Pakistan

OBJECTIVE: The aim of this study was to establish the incidence of IFI in AML patients receiving voriconazole prophylaxis in developing country. METHOD: This prospective study was conducted at The Children's Hospital, Lahore from July 2019 to December 2019 under Prospective AML registry approved by Institutional Review Board. All, consecutive patients of AML, either newly diagnosed or previously diagnosed cases with persistent fever and prolonged neutropenia, were included. Moreover, all patients of AML receiving chemotherapy also received voriconazole prophylaxis. Data of 64 patients was computed in accordance with age, gender, FAB classification, chemotherapy regimen and anti-fungal therapy. EORTC/MSG criteria was used to determine and classify IFI as proven, probable, or possible after performing CT chest and PNS, x-ray PNS, and abdominal ultrasound. CT scan was independently reviewed by a trained radiologist. Data was analyzed by SPSS version 22. RESULTS: Total 64 patients of AML were included in the study. The mean age of presentation was 6 years, range 1.5years to 16 years with 45 % males. Out of 64 patients, fungal infection was suspected in 50 patients (78%) due to persistent fever and prolonged neutropenia. In suspected 50 patients, probable and possible fungal infections were found in 22(34.37%) Patients. Eighteen 18/22 (81.81 %) were probable and 4/22 (18.18 %) were possible fungal infection. Majority of the cases 13/22 (59%) patients developed fungal infection during or after course of first induction therapy. CONCLUSION: Patients with high-risk hematologic malignancies especially AML are more at risk to develop IFI. In our study despite primary prophylaxis with voriconazole, incidence was higher than that reported in the literature from developed countries. Our data suggests that there is need to further improve supportive care measures and implement IFI preventive measures to decrease the incidence of IFI and improve survival. Disclosures No relevant conflicts of interest to declare.

Incidence and Risk Factors for Bleeding in Patients with Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy

Background : Bleeding is a major complication of intensive AML induction therapy that has been linked to increased early mortality. Identifying patients with increased bleeding risk could improve outcomes by allowing development of preventative strategies. Prior studies have focused on clinical trial or registry cohorts to identify factors associated with bleeding outcomes, and may not reflect typical clinical practice or have adequately detailed clinical or genetic data. Therefore, we sought to define the incidence and distribution of bleeding in a real-world cohort of AML patients and determine which pretreatment clinical, laboratory and genetic factors were associated with bleeding. Patients and methods: We identified 341 consecutive adult patients with newly diagnosed AML who received anthracycline-based induction chemotherapy. The median age was 61 years (range 19-79). Diagnostic samples from all patients were sequenced for recurrently mutated myeloid genes. We collected pretreatment clinical and laboratory data, and annotated bleeding events during the first 60 days of treatment according to the WHO bleeding assessment scale. Bleeding was classified as clinically significant if WHO grade ≥2, or grade 1 if it prompted a change in platelet transfusion threshold. Disseminated intravascular coagulation (DIC) was assessed using a modified ISTH DIC-score including platelet count, PT-INR, and fibrinogen, where a score ≥3 points indicates high risk of DIC. D-dimer was excluded due to missing data. Results: A total of 87 patients (26%) had clinically significant bleeding events, most commonly involving gastrointestinal (n=35), genitourinary (n=31), and central nervous system [CNS (n=12)] sites. Patients with clinically significant bleeding events had worse survival within the first 60 days of induction treatment compared to patients without clinically significant bleeding (HR 5.24; 95% CI: 2.50-10.96, P &amp;lt; 0.001). The incidence of clinically significant bleeding was higher among patients with a high pretreatment modified DIC score compared to those with a low modified DIC score (44% vs. 24%, P = 0.002, Figure A-B). This difference was most prominent among patients with WHO grade 4 bleeds (22% vs. 3%, P &amp;lt; 0.001, Figure A). Most clinically significant bleeding events (n=57) occurred within the first two weeks of induction treatment (Figure B). Using multivariable logistic regression analysis, we found that pretreatment platelet count &amp;lt;50 x 109/L, PT-INR &amp;gt;1.3, and the presence of a DNMT3A mutation were independently associated with bleeding within the first 60 days of AML induction treatment (Table). Other factors previously linked with bleeding risk, including age, sex, hepatic and renal function, and leukocyte count, were not associated with an increased risk of bleeding in this cohort. Early mortality was particularly high (58%) in patients who experienced a CNS bleed, which events included intraparenchymal and/or subdural hemorrhage (n=9), and hemorrhagic transformation of ischemic stroke (n=3). Two thirds (n=8) of patients with CNS bleeds had high pretreatment modified DIC scores. Using univariate regression analysis, we found that the presence of DNMT3A or TET2 mutations had significantly increased odds ratios for CNS bleeds (3.84; 95% CI: 1.20-12.2 and 4.18; 95% CI: 1.27-13.71, respectively). The frequency of CNS bleeds was significantly higher amongst patients with DNMT3A and/or TET2 mutations compared to patients without these mutations (8% vs. 1%, P = 0.004). Conclusions: The incidence of bleeding in this real-world cohort of AML patients receiving intensive induction chemotherapy was higher than previously reported in selected clinical trial cohorts. Clinically significant bleeding during initial induction was associated with poor short-term survival. Low platelet count, elevated PT-INR and DNMT3A mutations were independently associated with clinically significant bleeding. The incidence of CNS bleeds was highest in patients with DNMT3A or TET2 mutations, and rare in patients without these mutations, raising the possibility that genetic events driving early leukemogenesis may exert pleiotropic effects that impact hemostasis. Together, these results identify a subset of AML patients who may benefit from additional supportive care measures to prevent early bleeding associated with morbidity and mortality of intensive induction treatment. Disclosures Wolach: Amgen: Other: Fees for lectures and Consultancy; Janssen: Other: Fees for lectures and Consultancy; Astellas: Consultancy, Honoraria, Other: Fees for lectures and Consultancy; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures and Consultancy, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Fees for lectures and Consultancy. Neuberg:Celgene: Research Funding; Madrigak Pharmaceuticals: Current equity holder in publicly-traded company; Pharmacyclics: Research Funding. Lindsley:MedImmune: Research Funding; Takeda Pharmaceuticals: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding; Bluebird Bio: Consultancy.

Emerging treatment strategies for COVID-19 infection.

The new type of coronavirus (COVID-19), SARS-CoV-2 originated from Wuhan, China and has led to a worldwide pandemic. COVID-19 is a novel emerging infectious disease caused by SARS-CoV-2 characterized as atypical pneumonia. As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. The typical manifestations of COVID-19 include fever, sore throat, fatigue, cough, and dyspnoea combined with recent exposure. Most of the patients with COVID-19 have mild or moderate disease, however up to 5–10% present with severe and even life-threatening disease course. The mortality rates are approximately 2%. Therefore, there is an urgent need for effective and specific antiviral treatment. Currently, supportive care measures such as ventilation oxygenation and fluid management remain the standard of care. Several clinical trials are currently trying to identify the most potent drug or combination against the disease, and it is strongly recommended to enroll patients into ongoing trials. Antivirals can be proven as safe and effective only in the context of randomized clinical trials. Currently several agents such as chloroquine, hydroxychloroquine, favipiravir, monoclonal antibodies, antisense RNA, corticosteroids, convalescent plasma and vaccines are being evaluated. The large numbers of therapeutic interventions aim to define the most efficacious regimen. The aim of this article is to describe the treatment strategies that have been used for COVID-19 patients and review all the available literature.

Evaluation of Clinical Trials Addressing Supportive Care Measures for Acute and Chronic Radiation Toxicities

Despite advances in treatment delivery techniques, a variety of acute and late side effects secondary to radiation therapy occur. Significant research efforts have focused on preventing occurrence of toxicity; however, there is continued demand for evidence-based supportive care measures to treat radiation side effects. The purpose of this analysis is to characterize the state of supportive care trials in radiation oncology and to identify areas needing further study. Clinicaltrials.gov was queried using the search term “radiation toxicity” to identify past and current registered trials with a primary endpoint of toxicity management. To evaluate the proportion of supportive care trials, studies were classified as toxicity prevention or as supportive care interventions. Information regarding country of origin, trial era, study phase, disease site, toxicity evaluated, intervention, industry sponsorship, single- vs. multi-institutional status, sample size, and the use of patient-reported outcomes were evaluated for all supportive care trials. A total of 223 trials were identified. After exclusion of terminated trials or trials focused on radiation techniques (e.g., 3D-CRT vs. IMRT, protons), 71 studies met the criteria of either radiation toxicity prevention (n = 50) or supportive care (n = 21). Fourteen of these trials were active (8 prevention, 6 supportive care), with the remainder inactive, unknown, or complete. Within the group of 21 supportive care trials, the design included randomized phase III interventions in 6 studies (29%) with the remainder phase II (n = 4, 19%), phase I/II (n = 1, 5%), phase I (n = 1, 5%), or observational/uncategorized (n = 9, 43%). The most common disease site studied was head and neck (n = 6, 29%), followed by CNS (n = 3, 14%). Xerostomia, mucositis, and neurocognitive function (n = 3, 14% each) were the most commonly evaluated toxicities. The majority of studied interventions (n = 11, 52%) were medications with hyperbaric oxygen and diet as the next most common (n = 3, 14% each). Twelve trials were single institution (57%) and the median sample size was 91 (range: 11 to 320). Twelve studies included patient-reported outcomes (PROs), of which 7 trials (33%) had PROs as a primary endpoint. While numerous studies evaluating toxicity reduction exist, effective management of radiation-related toxicities remains important to promote quality of life during and after radiation therapy. There are few supportive care trials in radiation oncology and only a small portion of these are currently designed to generate level I evidence to evaluate interventions. There is a significant need for well-designed supportive care trials with patient-reported endpoints to guide management of radiation toxicity.