Sickle cell disease and coronavirus disease-2019 (COVID-19) infection: a single-center experience.

PURPOSE: Sickle cell disease (SCD) has been found to be associated with an increased risk of hospitalization and death from coronavirus disease-2019 (COVID-19). We sought to study clinical outcomes in patients with SCD and a diagnosis of COVID-19 infection. METHODS: We conducted a retrospective analysis of adult patients (>18 years) with SCD who were diagnosed with COVID-19 infection between 1 March 2020 and 31 March 2021. Data on baseline characteristics and overall outcomes were collected and analyzed using SAS 9.4 for Windows. RESULTS: A total of 51 patients with SCD were diagnosed with COVID-19 infection in the study period, out of which 39.3% were diagnosed and managed in the outpatient setting/emergency room (ER) and 60.3% in the inpatient setting. Disease-modifying therapy such as hydroxyurea did not impact inpatient vs outpatient/ER management (P > 0.05). Only 5.71% (n = 2) required intensive care unit admission and were mechanically ventilated and 3.9% (2 patients) died of complications of COVID-19 infection. CONCLUSION: We identified a lower mortality (3.9%) rate among patients in our cohort in comparison to previous studies and a higher burden of inpatient hospitalizations as compared to outpatient/ER management. Further prospective data are needed to validate these findings. Key messages What is already known on this topic COVID-19 has been shown to have a disproportionately unfavorable impact on African Americans, including longer hospital stays, higher rates of ventilator dependence, and a higher overall mortality rate. Limited data also suggest that sickle cell disease (SCD) is associated with an increased risk of hospitalization and death from COVID-19. What this study adds Our analysis did not show a higher mortality due to COVID-19 in patients with SCD. However, we identified a high burden of inpatient hospitalizations in this population. COVID-19-related outcomes did not improve with the use of disease-modifying therapies. How this study might affect research, practice, or policy These results will aid in decision making for triage of patients with COVID-19 and SCD and ensure the most appropriate use of healthcare resources. Our analysis underscores the need for more robust data to identify patients at higher risk of severe disease and/or mortality, necessitating inpatient hospitalization and aggressive management.

Objective Basis for Chronic Pain in Patients with Adult Sickle Cell Disease.

Sickle Cell Disease (SCD) affects approximately 100,000 Americans and due to lack of an organized treatment approach, patients with SCD pose a high economic burden on medical services. The patients with SCD have chronic bone damage from bone marrow infraction and vaso-occulsive events. These bone damages lead to chronic pain in patients with SCD. The inadwquate treatment of chronic pain in adult patients with SCD can lead to pseudo-addictive behavior and also affect their psycho-social life. There are certain barriers to adequate pain management in adult patients with SCD, namely, limited knowledge among the clinicians, inadequate assessment, concerns about addiction, and biases against opioid use. Here by presenting radiographs of patients with adult SCD, we would like to provide objective evidence for the pathologic basis of severe chronic pain in adult patients with SCD.

Real-world Data of Leukopenia Evaluation as Seen in a Community Academic Center.

Leukopenia on routine laboratory testing creates a concerning situation for primary care providers due to its association with hematological malignancies. Although not all leukopenia is due to underlying cancer, it can trigger an expensive and exhausting work-up in the process of ruling it out. There is neither real-world data on the prevalent causes of leukopenia as seen in the community nor definitive guidelines on the utilization of flow-cytometry in this setting. We conducted this retrospective study at our community academic center to demonstrate the distribution of various causes of leukopenia as well as the utility of flow-cytometry. Our study demonstrates that benign reversible causes of leukopenia are most prevalent and flow-cytometry is useful only in some very specific settings. These results provide a real-world estimate for clinicians to make informed decisions while evaluating leukopenia.

Not Your Typical Adenocarcinoma: A Case of Mesonephric Adenocarcinoma of the Cervix With Fibroblast Growth Factor Receptor 2 (FGFR2) Mutation.

Cervical cancer is one of the leading causes of cancer mortality in women. However, there have been great advances in its prevention and treatment. Nevertheless, there are certain rare forms of this cancer that are under-recognized, underreported, and have a paucity of evidence in terms of treatment. Mesonephric adenocarcinoma (AC) is one such rare disease, with less than 50 cases reported in the literature so far. We report a case of mesonephric AC of the cervix in a 73-year-old female who presented with abnormal vaginal bleeding. Our case is unique in that the patient had recurrence with lung metastases as well as fibroblast growth factor receptor 2 (FGFR2) mutation on genetic sequencing. She responded well to platinum-based chemotherapy and is currently on maintenance therapy with lenvatinib and bevacizumab. We aim to bring this patient's disease course and treatment options chosen to the attention of the medical community as this is only the second reported case of mesonephric AC with FGFR2 mutation, and probably the first one to be treated with tyrosine kinase inhibitors and immunotherapy with a favorable response.

A Case of Aplastic Anemia and Colon Cancer With Underlying Spliceosome Mutation: Is It an Incidental Finding or a Novel Association?

Alternative splicing is an epigenetic mechanism that plays a role in the development and function of antigen-specific lymphocytes. One such is the zinc-finger-RNA-binding-motif-and-serine/arginine-rich-2 (ZRSR2), which is clinically implicated in myelodysplastic syndrome and leukemia. Here, we present a case of a young male with myriad autoimmune conditions and adenocarcinoma of the colon in the setting of ZRSR2 mutation. A 28-year-old male with common variable immunodeficiency disease, atopic dermatitis, autoimmune gastroenteropathy, inflammatory polyarthropathy, primary bone marrow failure, colon cancer, and family history of Lynch syndrome was admitted to our hospital for an acute flare of autoimmune enteropathy secondary to subtherapeutic tacrolimus levels. He initially developed pancytopenia at the age of 26 years. Workup for HIV, hepatitis, cytomegalovirus, human-herpesvirus 6, parvovirus was negative. Partial thromboplastin time (PTT), international normalized ratio (INR), d-dimer, ferritin, iron profile, antinuclear antibodies (ANA) screen was unremarkable. Direct, indirect, and super-combs antibodies were undetectable. Chromosomal study for Fanconi-related chromosomal breakage and telomerase gene panel was negative. Flow cytometry did not reveal an abnormal clone. Bone marrow biopsy showed markedly hypocellular marrow with reduced trilineage hematopoiesis and 1% blasts with normal cytogenetics, immunohistochemistry, fluorescence in situ hybridization (FISH), and negative for myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria (PNH). Cincinnati inherited children's bone marrow transplant (BMT) panel was negative. He was diagnosed with aplastic anemia and was treated with antithymocyte globulin, cyclosporine, prednisone, and currently tacrolimus. At the age of 26 years, he was diagnosed with colon cancer. Immunohistochemistry was positive for MLH1, but the confirmatory genetic testing for Lynch syndrome was negative. He underwent total proctocolectomy and ileostomy and is currently in remission. Next-generation sequencing of bone marrow revealed a germline homozygous ZRSR2 mutation.  ZRSR2 spliceosome mutations are more common in males as it's an X-linked gene. They are seen in myelodysplastic syndrome, leukemia, increased autoimmune phenomenon, and 35 cases of colon cancer associated with this mutation are reported. In the setting of aplastic anemia and lynch negative colon cancer, we suspect our patient could have aplastic anemia due to an autoimmune phenomenon, underlying common variable immunodeficiency disease (CVID), or the new ZRSR2 mutation could be playing a role. Further studies and research is warranted to determine its true association with the disease entities. The underlying contributing factor is ZRSR2 mutation.

Myosin Heavy Chain 9 (MYH9)-Related Congenital Macrothrombocytopenia.

Myosin heavy chain 9 (MYH9)-related hereditary macrothrombocytopenia is caused by mutation of the MYH9 gene encoding the heavy chain A of non-muscle myosin of class II. We present a case that emphasizes the importance of awareness of rare disorders which could potentially avoid over-investigation, especially in benign conditions. A 72-year-old Caucasian female presented for preoperative evaluation for cataract extraction. She was noted to have thrombocytopenia of 30 K/uL along with elevated creatinine. She denied any acute symptoms except for a prolonged history of easy bruising. Physical exam revealed bruising over the extremities. Upon further questioning, she was previously investigated for thrombocytopenia and had multiple diagnostic as well as therapeutic interventions including bone marrow biopsies, steroids, intravenous immunoglobulins with no improvement. Her family history is consistent with low platelet counts for at least three generations. Peripheral blood smear showed large platelets, normal red and white blood cells with Döhle bodies. Further genetic testing revealed an inherited MYH9 mutation which is autosomal dominant. MYH9-related disorders are characterized by macrothrombocytopenia, often associated with glomerulonephritis, sensorineural deafness, cataracts, and cytoplasmic inclusion bodies within leukocytes. Management is mainly conservative and directed towards the prevention of iron deficiency anemia in young females. The use of desmopressin, in combination with tranexamic acid, is recommended in a perioperative setting. Our case emphasizes the importance of history-taking skills that could potentially minimize further diagnostic or therapeutic interventions in this benign genetic disorder.

Do the 2013 United States Preventive Services Task Force guidelines for lung cancer screening fail high-risk African American smokers? An institutional retrospective observational cohort study.

BACKGROUND: Lung cancer cause nearly 1.76 million deaths worldwide in 2018. In 2011, the National-Lung-Cancer-Screening-Trial showed 20% relative risk reduction with LDCT and subsequently led to the current USPSTF screening guidelines. However, the predominant focus on elderly, Caucasian questions its generalizability to communities with young, African Americans such as our institution. Hence, the objective of our study is to investigate the need to modify the current screening guidelines at our institution by assessing the applicability of newer individual risk-based prediction models for LDCT screening. METHODS: This is a retrospective observational cohort study of newly diagnosed lung cancer patients at LSU Health Sciences Center Shreveport from 2011 to 2015. One-third of the patients did not meet the current USPSTF screening guidelines. We categorized them into high-risk (groups1 and 2), moderate-risk, and low-risk according to 2018 NCCN Lung Cancer Screening Guidelines Version 1.2020. The high-risk groups were differentiated using the Tammemagi lung cancer risk calculator. RESULTS: Among those who did not meet the screening guidelines, nearly 50% were African American, 95% with known smoking history, and 80% diagnosed at advanced stage at the time of diagnosis. After employing the Tammemagi Risk based calculator, 12.5% were categorized into high-risk group 2, who are also eligible for annual LDCT. CONCLUSION: The current USPSTF guidelines have failed in our population consisting of young African American smokers, questioning the health disparity in medicine. By employing individual risk-based prediction models, we could potentially identify tailored high-risk populations leading to appropriate use of LDCT screening.

Cancer Radiation Therapy May Be Associated With Atrial Fibrillation.

Background: The association of atrial fibrillation (AF) with cancer and cancer types is inconclusive. Similarly, data regarding the association of AF with different cancer therapies are controversial. Objectives: To study the association of AF with cancer subtypes and cancer therapies. Methods: We studied all patients aged 18-89 years who presented to the Feist Weiller Cancer Center, with or without a diagnosis of cancer, between January 2011 and February 2016. Electronic health records were systematically queried for baseline demographics and ICD-9 and ICD-10 codes for specific co-morbidities. Patients with a diagnosis of AF were tabulated based on cross-validation with the ECG database and/or by recorded history. We assessed the prevalence and risk of AF based on cancer diagnosis, specific cancer type, and cancer therapy. Results: A total of 14,600 patients were analyzed. Compared to non-cancer patients (n = 6,801), cancer patients (n = 7,799) had a significantly higher prevalence of AF (4.3 vs. 3.1%; p < 0.001). However, following correction for covariates in a multivariable logistic regression model, malignancy was not found to be an independent risk factor for AF (p = 0.32). While patients with solid tumors had a numerically higher prevalence of AF than those with hematological malignancies (4.3 vs. 4.1%), tumor type was not independently associated with AF (p = 0.13). AF prevalence was higher in patients receiving chemotherapy (4.1%), radiation therapy (5.1%), or both (6.9%) when compared to patients not receiving any therapy (3.6%, p = 0.01). On multivariable logistic regression, radiation therapy remained an independent risk factor for AF for the entire study population (p = 0.03) as well as for the cancer population (p < 0.01). Conclusions: Radiation therapy for cancer is an independent risk factor for AF. The known association between cancer and AF may be mediated, at least in part, by the effects of radiation therapy.

The curious case of hemoglobin DC disease masquerading as sickle cell anemia.

Hemoglobin D is a relatively rare disease first reported in 1951. We present the first reported case of Hemoglobin DC disease. This is a case of a Hemoglobinopathy with DC disease in a woman with a previous diagnosis of Hemoglobin SC disease. A 19-year-old woman presented to the Adult Hematology clinic at a tertiary care hospital in Northwest Louisiana for transition of care from Pediatric Hematology for a diagnosis of Hemoglobin SC disease diagnosed at the age 4. Historical data suggested no avascular necrosis, acute chest syndrome, and very few episodes of pain crisis. She has never taken hydroxyurea. Laboratory work showed persistently normal hemoglobin and white blood cell counts. All sickle cell preparations in the past were negative. Computerized tomography scan of the abdomen was reviewed and showed a spleen grossly normal in size and appearance. Given the incongruent clinical picture for sickle cell disease, repeat hemoglobinopathy evaluation with Capillary electrophoresis and confirmatory acid electrophoresis (to differentiate hemoglobins that co-migrate with Hemoglobin S) showed a probable double heterozygote for Hemoglobin D and C with suspected coexistent alpha thalassemia minor based on red blood cell indices. This case confirms the importance of the required confirmatory method to ensure a correct diagnosis since a misdiagnosis can lead to numerous adverse clinical or psychological effects for patients.

Effect of Stem Cell Transplant on Survival in Adult Patients With Acute Lymphoblastic Leukemia: NCDB Analysis.

BACKGROUND: A retrospective analysis was performed to investigate the survival outcomes in adult acute lymphoblastic leukemia (ALL) based on treatment received. MATERIALS AND METHODS: Data from 17,504 men and women (≥18 years of age) registered in the National Cancer Database who were diagnosed with ALL between 2004 and 2013 and had follow-up to the end of 2014, were analyzed. The primary predictor variable was treatment received, and overall survival was the outcome variable. Additional variables addressed and adjusted included gender, age, race, Charleston Comorbidity Index, level of education, income, insurance, distance traveled, facility type and diagnosing/treating facility. RESULTS: The mean age of patients was 48.8 years with a standard deviation of 19.3 years. In multivariate analysis, after adjusting for secondary predictor variables, treatment modality was a statistically significant predictor of overall survival from ALL. Relative to patients who were treated with chemotherapy only, the patients who got chemotherapy and stem cell transplant had a decreased risk of mortality by 39%. Of the 5,409 patients between the ages of 18 and 39 years i.e. adolescent and young adults (AYA), no statistically significant survival difference was found between patients treated with stem cell transplant and those not. CONCLUSION: Stem cell transplant led to improved survival for all age groups except the AYA.

Use of Eltrombopag in Improving Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation.

Eltrombopag is a thrombopoietin agonist and has been used in aplastic anemia and post-transplantation thrombocytopenia. The c-MPL receptor is present on hematopoietic stem cells. There are no reports of eltrombopag utilization for improving poor graft function in the post-transplant setting. Here were report a case of a young female with post-transplant poor graft function as evident from the low absolute neutrophil count, anemia, and thrombocytopenia on day 60. Eltrombopag was started on day 72 and resulted in improvement in all 3 cell lines. The counts continued to be stable even after eltrombopag was discontinued. The patient tolerated the drug without significant side effects for 1 year.

Automating Quality Oncology Practice Initiative Quality Measure NHL78a.

PURPOSE: Quality measurement and improvement is a focus of ASCO. In the era of electronic health records (EHRs), computerized order entry, and medication administration records, quality monitoring can be an automated process. The EHR data are usually stored within tables in a relational database management system. ASCO Quality Oncology Practice Initiative measure NHL78a (hepatitis B virus antigen test and hepatitis B core antibody test within 3 months before initiation of obinutuzumab, ofatumumab, or rituximab for patients with non-Hodgkin lymphoma) presents an opportunity for automation of a quality measure using existing data in the EHR. METHODS: We used a locally developed Structured Query Language (SQL) language procedure in the Microsoft SQL Query Manager to access the EPIC CLARITY database. Access to the relational database management system of the EHR permits rapid case identification (the denominator set) of the unique ID of all of the patients who have received one of the target medications (ie, obinutuzumab, ofatumumab, or rituximab). Then, we went through a six-step process to find the number of patients who passed or failed the quality measure. RESULTS: When the final SQL procedure executes, it takes < 5 seconds to see the result set for a 12-month period. The procedure can be changed to incorporate a desired date range. Once the SQL procedure is created, there is essentially no labor and low costs to run the procedure at specific time intervals. CONCLUSION: Our method of quality measurement using EHRs is cost effective, fast, and precise, and can be reproduced at other centers.

Effect of Radiation Therapy on Survival in Hodgkin's Lymphoma: A SEER Data Analysis.

BACKGROUND/AIM: Hodgkin's Lymphoma (HL) is curable in up to 80% of patients due, in part, to simultaneous advances in chemotherapy regimens as well as radiation therapy planning and delivery. Concerns regarding the historical use of large-field radiotherapy on overall survival have been published. In this study, we performed a Surveillance, epidemiology, and end results (SEER) data analysis to evaluate the impact of patients and treatments related factors on survival in HL. PATIENTS AND METHODS: Data from 39,700 adult patients registered in the SEER data with diagnosis of HL, between 1983-2011 and follow-up through 2012 were analyzed. Impact of patient demographics (sex, age, race, ethnicity, year of diagnosis, family income, education, unemployment, poverty level and stage of disease) and treatment characteristics (delivery of radiotherapy) on survival were evaluated via multivariate analysis. RESULTS: Median age was 36 years. Most patients were Ann Arbor Stage II (39%) at diagnosis with the remainder distributed evenly between the remaining stages (I, III, IV: 19-21%). In multivariate analysis, after adjusting for secondary predictor variables including stage of disease, Radiation therapy (RT) was a statistically significant predictor of overall survival from HL (HR=0.72, (95% CI=0.68-0.75). At follow up of more than 25 years, Kaplan-Meier analysis showed that RT improved survival for all patients, irrespective of stage. Factors associated with worse survival included older age, male sex, extra nodal disease, advanced stage, African-American race, and non-Hispanic ethnicity. CONCLUSION: Radiation therapy improved survival in patients with all stages of HL. Demographic and disease factors associated with worse survival in this study may be related to particular patterns of care and warrant additional study.

Successful Treatment of Richter Transformation with Ibrutinib in a Patient with Chronic Lymphocytic Leukemia following Allogeneic Hematopoietic Stem Cell Transplant.

Patients with chronic lymphocytic leukemia (CLL) who progress to Richter transformation (RT) have a poor prognosis. Multi-agent chemotherapy regimens do not have good response rates. There are few case reports on the use of ibrutinib in RT. Here, we present a patient who was heavily pretreated for CLL, including allogeneic stem cell transplant, and progressed to RT. She had a mixed response to multi-agent chemotherapy and was started on ibrutinib. She had a complete response for 16 months on single-agent ibrutinib with minimal toxicity.

Excellent response to chemotherapy post immunotherapy.

INTRODUCTION: Immunotherapy in the form of immune checkpoint inhibitors has changed the landscape of cancer treatment. Newer monoclonal antibodies are coming up and are being tested in various cancers during different stages of treatment. With the increasing use of immune checkpoint inhibitors in the management of various types of cancers, the question is raised as to what next can be offered to a patient who has progressed on this newer treatment. Does Sequence matter? There have been reports of improved responses to chemotherapy after immunotherapy in the form of vaccines. Here we present a case series of 6 patients who progressed on immunotherapy with immune checkpoint inhibitors after initial modality of treatment (chemotherapy/radiation), subsequently received chemotherapy with excellent response. METHODS: We have a cohort of six patients who had disease progression on second line Immunotherapy for solid or hematological malignancies and had ECOG < 2. All these patients received third line salvage chemotherapy. Three patients had metastatic head and neck cancer, 2 had non-small cell lung cancer (NSCLC), and one had T -cell rich B- cell lymphoma. Prior review and approval were obtained from our institutional review board. RESULTS: All patients had an excellent response to chemotherapy in third line setting, after immune checkpoint inhibitors and most of them achieved a complete response. CONCLUSION: Targeting cancer with chemotherapy after failure of immunotherapy is a valid option and can lead to better response rates and PFS which may lead to OS. This effect may be secondary to immunotherapy removing the inhibition exerted by tumor cells or other immune cells initially followed by cytotoxic chemotherapy mediated killing of tumor cells.

Predictors of Survival in Acute Myeloid Leukemia by Treatment Modality.

BACKGROUND/AIM: Evaluations of efficacy of treatment modality in analyses on patients with acute myeloid leukemia (AML) often combine chemotherapy and stem cell transplantation (SCT). To account for the effect of SCT and determine the impact of chemotherapy alone, the National Cancer Data Base from 1998-2011 was analyzed. PATIENTS AND METHODS: Patients with AML from 1998-2011 aged 18-64 years were included. Chi-square analysis was used to assess the association between treatment and factors investigated. The Kaplan-Meier method was used to assess overall survival. Log-rank methods were used to determine factors significant for survival. Multivariable Cox regression analysis was used to determine the effect of chemotherapy alone, and both chemotherapy and SCT on survival while adjusting for other variables. RESULTS: A total of 34,816 patients from the National Cancer Database were eligible for this study. Eighty-four percent of patients received chemotherapy alone, 8.3% no chemotherapy or SCT, and 7.5 % received both chemotherapy and SCT. Five-year survival for patients without chemotherapy without SCT was 12%, survival for the group treated with chemotherapy alone was 37.8% and for those receiving both chemotherapy and SCT was 44.1%. Treatment with chemotherapy only and chemotherapy plus SCT had a hazard ratio for death of 0.42 and 0.35 compared to no chemotherapy or SCT. Advanced age, male sex, Black race, diagnosis prior to 2004, multiple comorbidities, Medicare insurance, Medicaid insurance, no insurance, lower income and low education level, distance less than 30 miles from treatment Center, diagnosis and treatment at same facility, were independently associated with worse survival. CONCLUSION: Survival analysis of AML in the National Cancer Database showed multiple factors to be independently associated with survival. Outcomes based on treatment suggest an improved survival when utilizing chemotherapy and SCT as the primary treatment modality.

Cisplatin-gemcitabine therapy in metastatic breast cancer: Improved outcome in triple negative breast cancer patients compared to non-triple negative patients.

UNLABELLED: Triple negative or basal-like breast cancers lack expression of estrogen, progesterone and HER2neu receptors. There are no specific treatment guidelines for this group of patients, however, it has been postulated that their phenotypic and molecular similarity to BRCA-1 related cancers would confer sensitivity to certain cytotoxic agents like cisplatin (CDDP). The aim of the study was to retrospectively examine the clinical outcome at our institution of patients with metastatic breast cancer treated with CDDP and gemcitabine combination chemotherapy who had triple negative breast cancer compared to non-triple negative breast cancer. Thirty-six patients with metastatic breast cancer were treated with CDDP and gemcitabine combination chemotherapy, 17 of whom were triple negative (47%) and 19 were non-triple negative (53%). The median progression free survival for triple negative and non-triple negative metastatic breast cancer patients were 5.3 months and 1.7 months respectively (p = 0.058). By multivariate Cox proportional hazard model after adjusting for age, race and menopausal status the risk of progression was reduced by 47% for triple negative compared to non-triple negative metastatic breast cancer patients (HR = 0.53, p = 0.071). CONCLUSIONS: Our results suggest an improved outcome for metastatic triple negative breast cancer patients compared to non-triple negative breast cancer patients when treated with cisplatin and gemcitabine combination chemotherapy.