Review of real-world experience with lurbinectedin in relapsed/refractory small cell lung cancer.

Lurbinectedin, a novel antineoplastic agent, was granted the orphan drug designation by the United States Food and Drug Administration (US FDA) and approved for use in relapsed/refractory small cell lung cancer in June 2020. The approval was granted after its efficacy was demonstrated in a multicenter open-label, multi-cohort study enrolling 105 participants. Since then, real-world studies have examined the efficacy and safety profiles of lurbinectedin in clinical practice. By examining these outcomes, this review aims to provide clinicians with the tools necessary to make informed clinical decisions.

Recurrent Left Renal Fossa Clear Cell Renal Cell Carcinoma With Pancreatic Tail Invasion Presenting as Intestinal Obstruction.

Distant renal cell carcinoma (RCC) metastatic disease is mostly seen in the lungs, bones, and lymph nodes. The incidence of local recurrences within the ipsilateral retroperitoneum (RFR) is very low. We report a case of a 79-year-old male with recurrent left renal fossa RCC with pancreatic tail invasion who presented with large bowel obstruction. To the best of our knowledge, no cases have been reported of recurrent left renal fossa RCC initially presenting as extrinsic large bowel obstruction.

Acral lentiginous melanoma with multiple bone metastasis: case report.

Acral lentiginous melanoma (ALM) is a type of melanoma that is traditionally seen on the soles of the feet, palms of the hand, and under the fingernails or toenails. It is the least frequently diagnosed melanoma among the four histologic subtypes of cutaneous melanoma, accounting for less than 5% of all cases. ALM is frequently diagnosed at late stages and has higher incidences in non-white populations in relation to the other forms of cutaneous malignant melanoma. The most common sites of metastases in melanoma are the skin and subcutaneous tissue followed by lung, liver, brain, and bone. Bone metastases from malignant melanoma usually occur in patients who already have widespread metastases. We present this paper as a unique case study of ALM lesion in an 84-year-old African American male presenting originally in the base of right fifth toe plantar aspect then found multiple bone metastases without any other organ involved.

Role of Next Generation Immune Checkpoint Inhibitor (ICI) Therapy in Philadelphia Negative Classic Myeloproliferative Neoplasm (MPN): Review of the Literature.

The Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs), which include essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are enduring and well-known conditions. These disorders are characterized by the abnormal growth of one or more hematopoietic cell lineages in the body's stem cells, leading to the enlargement of organs and the manifestation of constitutional symptoms. Numerous studies have provided evidence indicating that the pathogenesis of these diseases involves the dysregulation of the immune system and the presence of chronic inflammation, both of which are significant factors. Lately, the treatment of cancer including hematological malignancy has progressed on the agents aiming for the immune system, cytokine environment, immunotherapy agents, and targeted immune therapy. Immune checkpoints are the molecules that regulate T cell function in the tumor microenvironment (TME). The first line of primary immune checkpoints are programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4). Immune checkpoint inhibitor therapy (ICIT) exerts its anti-tumor actions by blocking the inhibitory pathways in T cells and has reformed cancer treatment. Despite the impressive clinical success of ICIT, tumor internal resistance poses a challenge for oncologists leading to a low response rate in solid tumors and hematological malignancies. A Phase II trial on nivolumab for patients with post-essential thrombocythemia myelofibrosis, primary myelofibrosis, or post-polycythemia myelofibrosis was performed (Identifier: NCT02421354). This trial tested the efficacy of a PD-1 blockade agent, namely nivolumab, but was terminated prematurely due to adverse events and lack of efficacy. A multicenter, Phase II, single-arm open-label study was conducted including pembrolizumab in patients with primary thrombocythemia, post-essential thrombocythemia or post-polycythemia vera myelofibrosis that were ineligible for or were previously treated with ruxolitinib. This study showed that pembrolizumab treatment did not have many adverse events, but there were no pertinent clinical responses hence it was terminated after the first stage was completed. To avail the benefits from immunotherapy, the paradigm has shifted to new immune checkpoints in the TME such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin domain 3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT), V-domain immunoglobulin-containing suppressor of T cell activation (VISTA), and human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) forming the basis of next-generation ICIT. The primary aim of this article is to underscore and elucidate the significance of next-generation ICIT in the context of MPN. Specifically, we aim to explore the potential of monoclonal antibodies as targeted immunotherapy and the development of vaccines targeting specific MPN epitopes, with the intent of augmenting tumor-related immune responses. It is anticipated that these therapeutic modalities rooted in immunotherapy will not only expand but also enhance the existing treatment regimens for patients afflicted with MPN. Preliminary studies from our laboratory showed over-expressed MDSC and over-expressed VISTA in MDSC, and in progenitor and immune cells directing the need for more clinical trials using next-generation ICI in the treatment of MPN.

Demographics and outcomes of hemoglobin genotype in hospitalized patients with COVID-19 and sickle cell disease in the United States.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with poor outcomes in sickle cell disease (SCD) patients. However, there is a paucity of data comparing hemoglobin (Hb) genotypes in SCD and infection outcomes. METHODS: The National Inpatient Sample was used to identify the record of hospitalizations with COVID-19 and SCD in 2020 using the International Classification of Disease, Tenth Revision codes. Study outcomes (invasive mechanical ventilation, extracorporeal membrane oxygenation, shock, vasopressor use, measures of resource utilization, and in-hospital mortality) were compared between hemoglobin SS, SC, and S-beta thalassemia (Sß). RESULTS: Of the 102 975 COVID-19 hospitalizations with SCD, 87.26% had HbSS, 7.16% had HbSC, and 5.58% had HbSß. Younger patients were more likely to have HbSS, while older patients were likely to have HbSC and HbSß. HbSS was more frequent with Blacks, while HbSß was more prevalent with Whites and Hispanics. Though measures of resource utilization were higher in HbSS, there was no significant difference in in-hospital outcomes between the three genotypes. CONCLUSION: There is no difference in COVID-19 outcomes among Hb genotypes in SCD. Further studies are needed to explore the reasons for this observation.

Amyloidoma and Plasmacytoma Presented as a Solitary Lung Nodule in a Patient of Multiple Myeloma With AL-Amyloidosis: A Case Report and Review of Literature.

Nodular amyloidoma in the lungs is a rare entity, also the occurrence of extramedullary plasmacytoma (EMP) in the lungs is rare. To have concomitant EMP and amyloidoma presented as a single lung mass is even rarer. There was only one similar case reported in the abstract form previously. Our case did not respond to many novel chemotherapy agents, suggesting that this combination of amyloidoma and plasmacytoma belonged to a poor prognosis entity, requiring different treatment modalities, such as early bone marrow transplantation or CART (chimeric antigen receptors T) therapy.

Review of Merkel cell carcinoma with solitary pancreatic metastases mimicking primary neuroendocrine tumor of the pancreas.

OBJECTIVE/BACKGROUND: Merkel cell carcinoma (MCC) but metastases to the pancreas are very rare. There are only a few cases of isolated metastases of MCC to the pancreas. Because of this rarity, it can be wrongly diagnosed as a neuroendocrine tumor of the pancreas(pNET), especially the poorly differentiated neuroendocrine carcinoma (PNEC) subtype, in which the treatment is vastly different than that of MCC with isolated metastases of the pancreas. METHODS: An electronic search of the PubMed and google scholar databases was performed to obtain the literature on MCC with pancreatic metastases, using the following search terms: Merkel cell carcinoma, pancreas, and metastases. Results are limited to the following available article types: case reports and case series. We identified 45 cases of MCC with pancreatic metastases from the PubMed and Google Scholar database search and examined their potential relevance. Only 22 cases with isolated pancreatic metastases were taken for review including one case that we encountered. RESULTS: The results from our review of cases of isolated pancreatic metastases of MCC were compared to the characteristics of the poorly differentiated pancreatic neuroendocrine tumor (PNEC). We found the following: (a) MCC with isolated pancreatic metastases occurred at an older age than PNEC and with male gender predominance (b) Most of the metastases occurred within 2 years of initial diagnosis of MCC (c) Resection of pancreatic mass was the first line treatment in case of resectable PNECs whereas resection of metastases was infrequently performed in MCC with pancreatic metastases.

Outcomes of COVID-19 hospitalizations in patients with sickle cell disease: A nationwide analysis.

INTRODUCTION: There is a paucity of data on the outcomes of coronavirus disease 2019 (COVID-19) in patients with sickle cell disease (SCD) in the United States. We examined the outcomes of patients with COVID-19 and SCD. METHODS: We utilized the National Inpatient Sample (NIS) to identify the data of patients diagnosed with COVID-19 and SCD in 2020 using the International Classification of Disease, Tenth Revision codes. In-hospital outcomes (invasive mechanical ventilation and mortality) were compared between SCD and non-SCD groups. RESULTS: Of the 1 057 550 COVID-19 hospitalizations, 2870 (0.3%) had SCD. The median age of the SCD group was 42 (IQR: 31) vs. 66 (IQR: 23) in the non-SCD group (p < .0001). Patients with SCD were likely to be females (62.02% vs. 37.98%, p < .0001), Blacks (87.81% vs. 12.19%, p < .0001), and in the lowest income quartile (50.62% vs. 11.15%, p < .0001). There was no difference in the outcomes between the two groups. There were increased odds of invasive mechanical ventilation and in-hospital mortality in COVID-19 in Asians, Hispanics, Native Americans, and Blacks (except for in-hospital mortality) compared to Whites. CONCLUSION: In-hospital mortality and invasive mechanical ventilation outcomes in SCD are comparable to that in non-SCD patients hospitalized with COVID-19.

Prevalence and outcomes of pulmonary embolism with sickle cell disease: Analysis of the Nationwide Inpatient Sample, 2016-2020.

INTRODUCTION: The outcomes of pulmonary embolism (PE) in sickle cell disease (SCD) are poorly established in the literature. This study examined the prevalence and outcomes of patients with PE and SCD. METHODS: The National Inpatient Sample was used to identify patients' data with a diagnosis of PE and SCD in the United States from 2016 to 2020 using the International Classification of Disease, 10th Revision codes. Logistic regression was used to compare outcomes between those with and without SCD. RESULTS: Of the 405 020 patients with PE, 1504 (0.4%) had SCD, and 403 516 (99.6%) did not have SCD. The prevalence of PE with SCD was stable. Patients in the SCD group were more likely to be female (59.5% vs. 50.6%; p < .0001), Black (91.7% vs. 54.4%; p < .0001), with a lower rate of comorbidities. The SCD group had higher in-hospital mortality (odds ratio [OR] = 1.41, 95% confidence interval [CI]:1.08-1.84; p = .012) but lower catheter-directed thrombolysis (OR = 0.23, 95% CI: 0.08-0.64; p = .005), mechanical thrombectomy (OR = 0.59, 95% CI: 0.41-0.64; p < .0029), and inferior vena cava filter placement (OR = 0.47, 95% CI: 0.33-0.66; p < .001). CONCLUSION: In-hospital mortality remains high in PE with SCD. A proactive approach, including maintaining a high index of suspicion for PE, is needed to reduce in-hospital mortality.

Racial and ethnic differences in sickle cell disease within the United States: From demographics to outcomes.

INTRODUCTION: Sickle cell disease mainly affects African Americans, and studies on racial differences in sickle cell disease outcomes are scanty. This study examined racial and ethnic differences in sickle cell disease prevalence, comorbidities, and outcomes. METHODS: Using the National Inpatient Sample database from 2016 to 2018, we identified patients' records with a diagnosis of sickle cell disease using the International Classification of Diseases, Tenth Revision codes. The overall study population was further stratified by race into Blacks, Whites, and Hispanics. Using logistic regression, comorbidities and outcomes among sickle cell disease patients were compared between the three races/ethnicities. RESULTS: Of the 74 817 hospitalized for sickle cell disease, 69 889 (93.4%) were Blacks, 3603 (4.8%) were Hispanics, and 1325 (1.8%) were Whites. Compared to Whites, Blacks were more likely to have significantly higher odds of sickle cell crisis (odds ratio [OR]: 3.32; 95% confidence interval [CI]: 2.66-4.14) and blood transfusion (OR: 1.66; 95% CI: 1.37-2.02). There was no difference in mortality between Blacks and Whites. Compared to Hispanics, Blacks had significantly higher odds of sickle cell crisis (OR: 1.35; 95% CI: 1.19-1.53) and blindness (OR: 2.94; 95% CI: 1.22-7.11), lower odds of asplenia (OR: 0.57; 95% CI: 0.45-0.71) and gallstones (OR: 0.75; 95% CI: 0.58-0.95). However, Blacks had statistically significantly lower odds of mortality of 0.60 (95% CI: 0.38-0.93) than Hispanics. CONCLUSION: Prevalent sickle cell type, severity, complications, and comorbidities vary in different races. Physicians need to be aware of these differences to manage sickle cell patients efficiently. This study hopes to inform further research regarding the reasons for varying disease characteristics among racial groups and bridge a gap in tailored management protocols.

PD-1/PD-L1, MDSC Pathways, and Checkpoint Inhibitor Therapy in Ph(-) Myeloproliferative Neoplasm: A Review.

There has been significant progress in immune checkpoint inhibitor (CPI) therapy in many solid tumor types. However, only a single failed study has been published in treating Ph(-) myeloproliferative neoplasm (MPN). To make progress in CPI studies on this disease, herein, we review and summarize the mechanisms of activation of the PD-L1 promoter, which are as follows: (a) the extrinsic mechanism, which is activated by interferon gamma (IFN γ) by tumor infiltration lymphocytes (TIL) and NK cells; (b) the intrinsic mechanism of EGFR or PTEN loss resulting in the activation of the MAPK and AKT pathways and then stat 1 and 3 activation; and (c) 9p24 amplicon amplification, resulting in PD-L1 and Jak2 activation. We also review the literature and postulate that many of the failures of CPI therapy in MPN are likely due to excessive MDSC activities. We list all of the anti-MDSC agents, especially those with ruxolitinib, IMID compounds, and BTK inhibitors, which may be combined with CPI therapy in the future as part of clinical trials applying CPI therapy to Ph(-) MPN.

Eltrombopag-Induced Thrombocytosis and Thrombosis in Patients With Antiphospholipid Syndrome and Immune Thrombocytopenic Purpura.

Antiphospholipid syndrome (APS) may be either as a primary or in association with an underlying systemic autoimmune etiology (36.2%), particularly systemic lupus erythematosus (SLE). Thrombocytopenia is infrequently observed in APS patients, with an occurrence of 22% to 42% with the frequency of thrombocytopenia, higher in APS and SLE combination than in primary APS. There have been some controversial reports regarding the treatment of APS syndrome with thrombocytopenia with TPO agonists. We like to report a case with APS syndrome with severe thrombocytopenia treated with TPO-RA and developed severe thrombocytosis and thrombosis. Our case represented the first case of TPO-RA in treating APS syndrome developed severe thrombocytosis and our case also concurred that use of TPO-RA agents should be strongly discouraged in APS until larger studies clarify the safety of TPO-RA agents in APS.

Cardiac Tamponade in Patients With Breast Cancer: A Systematic Review.

Cardiac tamponade is a rare presentation in breast cancer and may be associated with poor prognosis. In this article, we reviewed the characteristics and survival outcomes of patients with breast cancer who developed cardiac tamponade. Three databases (PubMed, EMBASE and SCOPUS) were searched for relevant articles published from 1978 to 2022 and 16 articles were identified comprising 64 cases. The median age of the cases was 52 years. Cardiac tamponade was diagnosed with echocardiogram or computerized tomography of the chest or both in 91.9%, 1.6% and 6.5% of the cases, respectively. Cytology of the pericardial fluid was done in 90.5% of the cases while biopsy in addition to cytology was done in 9.5% of cases. Tamponade was proven to be malignant in 97.4% of the cases. The initial treatment for tamponade was pericardiocentesis. Adjunct therapies ranged from the insertion of a pericardial window, pericardiectomy, radiotherapy and chemotherapy. The median time from the first treatment of breast cancer to the onset of tamponade was 24 months while the median survival following diagnosis of tamponade was 13 months. There was no significant correlation (spearman rank-sum correlation coefficient= 0.35, p = 0.165) between time to tamponade (interval time from the first diagnosis of breast cancer and the onset of cardiac tamponade) and survival. Cardiac tamponade may adversely affect survival in patients with breast cancer. Early diagnosis with echocardiogram and cytology may guide management and expectations. Further observational studies are needed to determine the predictors of cardiac tamponade and optimal treatment in patients with breast cancer.

HTLV-1-Associated Lymphoma Presented as Massive Lymphadenopathy.

Adult T-cell leukemia/lymphoma is an aggressive T-cell malignancy caused by the long-term infection of human T-cell lymphotropic virus type 1 (HTLV-1). Our understanding of clinical features still largely relies on the Shimoyama classification developed 30 years ago, which described the 4 clinical subtypes (the smoldering, chronic, lymphoma, and acute types) based on the manifestations of lymphocytosis, elevated lactate dehydrogenase, hypercalcemia, lymphadenopathy, and involvement of the skin, lung, liver, spleen, central nervous system, bone, ascites, pleural effusion, and gastrointestinal tract. HTLV-1-associated lymphoma has a variety of presentations but the presentation of massive lymphadenopathy and compression symptoms is rare and has not been emphasized in the literature. In this article, we describe 2 cases of adult T-cell leukemia/lymphomas that presented with massive cervical nodes or mediastinal nodes with compressing symptoms as the major presenting clinical features. Clinicians should remain aware of this type of presentation by HTLV-1-associated lymphoma, especially in patients who came from endemic areas, even if not all clinical features are present and particularly with hypercalcemia and lytic bone lesions.

Aggressive Diffuse Intermediate Size B-Cell Lymphoma With P53 Mutation Presented as Primary Bone Marrow Lymphoma.

Primary bone marrow lymphoma (PBML) is a disease entity in which lymphoma primarily originates in the bone marrow without signs of involvement of lymph nodes, spleen, liver, or any other organs, and excludes leukemia/lymphoma. PBML has been a rare presentation of malignant lymphoma, and most of the cases have a poor prognosis and require rapid diagnoses and treatments. Among all PBMLs, diffuse large B-cell lymphoma (DLBCL) is the most common pathological subtype. Over 25 years and from 7 institutions, the International Extranodal Lymphoma Study Group retrospectively collected PBML cases and, in 2012, published these 21 cases, including 19 cases of B-cell lymphoma and 2 cases of peripheral T-cell lymphoma. Among the B-cell types, DLBCL accounted for 79% and follicular lymphoma (FL) for 21%. DLBCLs were characterized by the existence of large cells. In this article, we present a rare case of high-grade aggressive type with P53 mutation, intermediate-sized B-cell lymphoma, excluded FL by the absence of FL lymphoma markers, presented as PBML. Our patient had rapid progression and succumbed to the disease shortly after diagnosis. Upon literature review, 62 B-cell lymphoma cases were identified that presented as PBML (51 high-grade and 11 low-grade)-mostly case reports. Among these, only one case was reported as intermediate-sized DLBCL-like lymphoma but not with aggressive features. Our case represents the first case of aggressive intermediate-sized lymphoma, not a FL, with P53 mutation, highly elevated lactate dehydrogenase, and Ki-67 presented as PBML. Such a profile would need to be quickly recognized and aggressive treatment applied, such as CART (chimeric antigen receptor T-cells) therapy or DA-EPOCH-R (dose-adjusted EPOCH [etoposide-prednisone-oncovin-cyclophosphamide-hydroxydaunorubicin] and rituximab) with or without venetoclax.

Pancytopenia and TTP-like picture secondary to pernicious anaemia.

A 21-year-old man presented to the emergency department with generalised weakness, weight loss and decreased appetite for few weeks. He had evidence of severe pancytopenia and haemolysis. His peripheral smear with many schistocytes was suspicious for thrombotic thrombocytopenic purpura (TTP). He was supported with blood transfusions and daily plasmapheresis. His platelet counts worsened despite 4 days of therapy. Bone marrow biopsy was significant for hypercellular bone marrow with megaloblastic changes. Further workup revealed normal ADAMTS13 level, low vitamin B12, positive intrinsic factor antibodies and high methylmalonic acid. Diagnosis of pernicious anaemia was established and he was started on daily treatment with intramuscular vitamin B12 which subsequently improved his symptoms and haematological parameters. This report highlights the importance of checking vitamin B12 level in patients presenting with pancytopenia and TTP-like picture before making a diagnosis of TTP.

TTP-like syndrome associated with hemoglobin SC disease treated successfully with plasma and red cell exchange.

BACKGROUND: Sickle cell hemoglobinopathies are associated with end organ damage but very rarely present with a clinical and laboratory picture of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia, characteristic of thrombotic microangiopathy (TMA). CASE PRESENTATION: We present a patient with HbSC disease who developed thrombotic microangiopathy, needing both RBC exchange transfusion and therapeutic plasma exchange (TPE) for complete clinical recovery. CONCLUSION: Although literature showed therapeutic plasma exchange alone can abrogate a similar clinical scenario, we did an in-depth review which concluded that in most of the TMA cases secondary to sickle cell disease, treatment with both with plasma exchange and red cell exchange transfusion are necessary.

Fever of Unknown Origin due to Primary Hepatic Diffuse Large B-cell Lymphoma: A Case Report.

We present a rare case of primary hepatic lymphoma. An 82-year-old female patient presented with altered mental status, and fever. Her labs were significant for abnormal liver functions with markedly elevated lactate dehydrogenase. All infectious and auto-immune workup was negative. Imaging studies were only significant for hepatosplenomegaly, and no liver masses were detected. A liver biopsy was diagnostic of CD5+ CD20+ diffuse large b-cell lymphoma of the liver. Chemotherapy was planned with rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Unfortunately, the patient died before initiation of therapy. This case would highlight the importance of early liver biopsy in patients with abnormal liver functions and with no clear explanation, even if there were no discrete masses on computed tomography (CT) or magnetic resonance imaging (MRI). Lymphomas and other infiltrative processes should be considered in the differential diagnosis in such cases.

Chronic myelomonocytic leukemia as a transformation from polycythemia vera.

The hallmark of Polycythemia vera (PV) is the presence of JAK2V617F mutation and increased RBC mass. Chronic myelomonocytic leukemia (CMML) is defined as persistent blood absolute monocyte count (AMC) >/= 1 × 109/L for at least 3 months with myeloid cell dysplasia. Few cases of evolved CMML from PV have been described. We present a case of PV that progressed to CMML. We demonstrated the CMML clone was most likely derived from PV- JAK2V617F clone. This clone carried a complex genetic mutations of ASXL1, RUNX1, SRSF2 and TET2, NRAS, KRAS, plus CMML cells were of the classical phenotype CD14+ CD16-by flow cytometry.