Asymptomatic COVID-19-Associated Acquired Hemophilia A and Disseminated Intravascular Coagulation From a Bypassing Agent.

Acquired hemophilia A (AHA) is a clotting disorder characterized by the presence of neutralizing antibodies that inhibit factor VIII, resulting in increased bleeding risk. Known etiologies include malignancy, autoimmune conditions, graft-vs-host disease, and more recently coronavirus disease 2019 (COVID-19) infection. In this case report, we describe an 86-year-old female who was found to have AHA incidentally during preoperative workup for meningioma resection. She was subsequently found to have COVID-19 infection which was the likely cause of her development of AHA. She was treated with factor eight inhibitor bypassing agent (FEIBA) and recombinant factor VII (rVII) for a small hematoma on her right arm along with prednisone and cyclophosphamide. She then developed disseminated intravascular coagulation (DIC) initially secondary to FEIBA and subsequently rFVII. DIC resolved after these factor concentrates were withheld. The aim of this case report was to emphasize the importance of monitoring partial thromboplastin time (PTT) in patients with COVID-19 and proceeding with AHA workup if indicated. It is also imperative to know and understand the potentially life-threatening, albeit rare, adverse effects of DIC associated with the administration of factor concentrates, especially in the elderly population and withholding these factor concentrates once DIC is suspected.

Gastrointestinal treatment-related adverse events of combined immune checkpoint inhibitors: a meta-analysis.

Introduction: Combined immune checkpoint inhibitors can cause gastrointestinal adverse events. Methods: We performed a meta-analysis of pooled colonic, hepatic and pancreatic treatment-related adverse events of combined ICI. Results: 53 trials reporting treatment-related adverse events in 6581 patients. All grade diarrhea was the most common adverse event seen in 25.4% patients, followed by all grade hepatitis in nearly 13% patients and pancreatitis in nearly 7.5% patients. Conclusion: Our study provides pooled data of treatment-related adverse events from different combination immune checkpoint inhibitors use in solid tumors and demonstrates a high incidence of all grades and ≥3 grade gastrointestinal adverse events. Further studies are required to characterize these adverse events and assess their overall impact on treatment course and outcomes.

The article talks about a type of medicine called immune checkpoint inhibitors that are used to treat cancer. These medicines can sometimes cause problems in the stomach and liver when used in combination with other cancer treatments, which can lead to hospitalization or, rarely, death. We performed a study on 6581 people who took these medicines in combination with another treatment and determined exactly how often these side effects happened. We also looked at which combinations of medicines were safer. This information can help doctors identify the side effects early and treat them. It can also help scientists design more studies to learn more about these side effects and how to prevent them.

Validation of the Neoadjuvant Rectal Cancer (NAR) Score for Prognostication Following Total Neoadjuvant Therapy (TNT) for Locally Advanced Rectal Cancer.

PURPOSE: The neoadjuvant rectal cancer (NAR) score is a prognostic tool for locally advanced rectal cancer (LARC) treated with total neoadjuvant therapy (TNT). It has been previously validated as an endpoint that predicts survival more accurately than pathologic complete response (pCR) and is the primary endpoint of the ongoing NRG-GI002 Phase II trial. Using the National Cancer Database (NCDB), we aimed to validate the NAR score's ability to predict survival in a large hospital-based dataset. METHODS: We queried the NCDB to identify locally advanced rectal cancer patients from 2004 to 2015 that received TNT followed by surgical resection. Overall survival (OS) was calculated using Kaplan-Meier curves evaluating NAR score and pCR separately. A multivariable Cox proportional hazards model was used to identify factors associated with survival. Multivariate regression was used to evaluate characteristics associated with a favorable (< 14.98) NAR score. RESULTS: From > 264,000 patients diagnosed with rectal adenocarcinoma in the NCDB, our final cohort yielded 209 patients with a median age of 62 years. Factors associated with worse survival included age > 62 years old (p = 0.04), lower income (p = 0.03), and unfavorable (≥ 14.98) NAR score (p = 0.04). On multivariate regression, tumors with perineural invasion and a higher comorbidity score (> 1) were less likely to have a favorable NAR response (p = 0.01 and p = 0.01). pCR was not associated with improved survival (p = 0.09). CONCLUSIONS: Our study validates the NAR score as a prognostic tool in patients receiving TNT for LARC. Tumors with perineural invasion and patients with a higher comorbidity score had worse NAR scores.

Adoptive Cellular Therapy in Acute Myeloid Leukemia: Current Scope and Challenges.

Adoptive cellular therapies have revolutionized the management of hematologic malignancies, particularly lymphoma and multiple myeloma. These therapies targeting disease-specific antigens, such as CD19 in lymphoma and B cell maturation antigen in multiple myeloma, are efficacious and well-tolerated compared with conventional chemotherapies. Unfortunately, their potential remains unrealized in acute myeloid leukemia (AML). This is because most targetable antigens on AML cells are also expressed on healthy myeloid hematopoietic stem cells (HSC). Therefore, targeting them results in severe myeloablative effects and pancytopenia. Several strategies have been devised to overcome this barrier, including identifying AML-specific antigens, limiting CAR-T cell persistence to prevent prolonged myeloablation, and creating AML-specific antigens through manipulating HSCs prior to allogenic transplant. In this review, we discuss these strategies and the ongoing clinical trials on adoptive cellular therapies in AML, limiting our focus to chimeric antigen receptor-T cells (CAR-T) and chimeric antigen receptor-natural killer cells (CAR-NK).

Venetoclax-induced vitiligo in a patient with chronic lymphocytic leukemia.

Venetoclax, a highly selective Bcl-2 inhibitor, is an orally bioavailable drug that has been approved as first-line therapy for chronic lymphocytic leukemia (CLL) in combination with obinutuzumab, as well as monotherapy in the setting of relapsed CLL. Although some of its life-threatening side effects are well known, including tumor lysis syndrome and cytopenias, others less known side effects include skin reactions. Skin rash is commonly reported in literature, which is often mild and not life-threatening. In this case report, the authors describe what is potentially the second case of venetoclax-induced vitiligo reported in literature. A 77-year-old man with CLL Rai stage II with cytogenetics showed 11 q23 deletion in 14% of cells, and 14q32 partial deletion in 9% of cells developed vitiligo in his extremities 2 years into treatment. A decision was made to continue venetoclax with close monitoring as the side effect was mild and not debilitating. The patient continued to do well. Although vitiligo is not associated with increased mortality risk, its development is associated with increased psychological stress. The mechanism by which vitiligo develops remains unclear. There may be an association between drug-induced vitiligo and improved cancer prognosis; however, larger studies need to be carried out to prove this hypothesis.

Testicular Plasmacytoma Masking as Epididymo-orchitis in a Known Multiple Myeloma Patient.

BACKGROUND/AIM: Extramedullary plasmacytoma (EMP) is defined as a localized plasma cell neoplasm that arises in tissues other than the bone. The most common sites of involvement of EMP are the upper airways followed by lymph nodes, gastrointestinal tract, thyroid gland, skin, brain, liver, and lungs. Testicular plasmacytoma has a very rare occurrence with about 70 cases reported in literature to date. CASE REPORT: We describe a 52-year-old-male with a diagnosis of multiple myeloma presenting with lytic lesions of the axial skeleton. He had lambda light chain restricted, R-ISS stage II with high risk cytogenetics as he tested positive for t(4;14). He underwent four cycles of cyclophosphamide, bortezomib and dexamethasone followed by auto-peripheral stem cell transplantation. He was kept on ixazomib, lenalidomide and dexamethasone maintenance therapy, but relapsed soon after and was diagnosed with plasmacytoma of the left lung. Therapy was switched to daratumumab, carfilzomib and dexamethasone and the patient received radiation of his left lung. He then developed left painless testicular mass which was treated with six weeks course of antibiotics. However due to persistence of concerning features on scrotal ultrasound post-treatment, the patient underwent radical orchiectomy with pathology coming back positive for plasma cells. CONCLUSION: The testes serve as a sanctuary site for hematological malignancies due to the presence of the testicular-blood barrier. Hence, it is imperative to keep a high index of suspicion for testicular plasmacytoma in the right clinical context when evaluating a patient with known multiple myeloma.

Intrathecal Chemotherapy as a Potential Treatment for Steroid-refractory Immune Effector Cell-associated Neurotoxicity Syndrome.

BACKGROUND/AIM: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of various B-cell malignancies. However, it can cause serious adverse effects like immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS is attributed to disruption of the blood-brain barrier due to inflammatory cytokines and increased levels of immune effector cells (IECs) in the cerebrospinal fluid (CSF). Corticosteroids and supportive management are the mainstays of ICANS treatment. However, no guidelines exist for the treatment of steroid-refractory ICANS. Some reports have shown favorable outcomes with no long-term complications in patients with steroid-refractory ICANS treated with intrathecal (IT) chemotherapy. CASE REPORT: We describe the outcomes of two patients with steroid-refractory ICANS treated with IT chemotherapy. Both patients had refractory large B-cell lymphoma and were not candidates for autologous transplant. They developed steroid-refractory ICANS after CAR T-cell infusion. IT chemotherapy with 12 mg methotrexate and 50 mg hydrocortisone resulted in prompt neurological improvement in both patients. One of them passed away due to multiple other comorbidities, and the other patient continues to do well without any complications. CONCLUSION: IT chemotherapy could be considered as a potential approach for the management of steroid-refractory ICANS based on our experience. Prospective studies are needed to validate this approach.

Polyserositis as a Unique Presentation of Isolated Myeloid Sarcoma: A Case Report.

BACKGROUND: Myeloid Sarcoma (MS) are tumors containing myeloid blasts occurring in a location other than the bone marrow, including lymph nodes, skin, and soft tissues. MS presenting as polyserositis however is very rare, with only a few cases in the literature. CASE REPORT: A 20-year-old male presented with cough, shortness of breath and was found to have left upper lobe consolidation, left pleural effusion, pericardial effusion, and a large anterior mediastinal mass. A transthoracic echocardiogram showed pericardial effusion with tamponade physiology. He underwent emergent pericardiocentesis and thoracentesis. The fluid studies showed flow cytometry findings consistent with MS/ acute myeloid leukemia (AML) phenotype. A bone marrow aspirate and biopsy were unremarkable and showed no immunophenotypic findings diagnostic of acute leukemia or a lymphoproliferative disorder. Cytogenetics was negative for AML abnormalities per FISH analysis. Videoassisted thoracoscopy surgery (VATS) with biopsy of the mediastinal mass, pericardium, and left upper lobe of the lung was consistent with MS. He was treated with induction cytarabine and idarubicin, and a follow up PET-CT scan showed complete remission. He is currently day 200 + post stem cell transplant with no evidence of disease recurrence. CONCLUSION: To the best of our knowledge, this is the first case of isolated myeloid sarcoma presenting as polyserositis, without prior leukemia/ bone marrow involvement. Hence, fluid studies should involve cytometry analysis and MS should be entertained as a differential for polyserositis, even without a history of prior leukemia. Timely diagnosis can expedite aggressive chemotherapy required for a potentially life-threatening disease.

Management of Non-Small Cell Lung Cancer: Updates from the European Lung Cancer Congress 2022.

The recently concluded European Lung Cancer Congress 2022 (ELCC22) showcased some very exciting data, with more than 200 abstracts presented during the meeting. Through this review, we focus on selected clinically relevant abstracts that in our opinion represent significant updates in the current management of non-small cell lung cancer (NSCLC). Here, we summarize the updates in surgical management, adjuvant therapy and therapy for advanced stage NSCLC and put these advances in the context of the current clinical standard of care.

The prognostic value of KRAS mutation in locally advanced rectal cancer.

BACKGROUND: The prognostic value of the KRAS proto-oncogene mutation in colorectal cancer has been debated. Herein, we analyzed the National Cancer Database (NCDB) to assess the role of KRAS mutation as a prognostic marker in patients with locally advanced rectal cancer (LARC). METHODS: We identified LARC patients treated with neoadjuvant chemoradiation from 2004-2015 excluding those with stage I/IV disease and unknown KRAS status. Multivariable logistic regression identified variables associated with KRAS positivity. Propensity adjusted univariable and multivariable analyses identified predictors of survival. RESULTS: Of the 784 eligible patients, 506 were KRAS-negative (KRAS -) and 278 were KRAS-positive (KRAS +). Median survival was 63.6 months and 76.3 months for KRAS + and KRAS - patients respectively, with propensity adjusted 3 and 5-year survival of 79.9% vs. 83.6% and 56.7% vs. 61.9% respectively (HR 1.56, p 1.074-2.272). Male sex, no insurance, and KRAS + disease were associated with poorer survival on unadjusted and propensity adjusted multivariable analyses. CONCLUSIONS: Our analysis of KRAS + LARC suggest that KRAS + disease is associated with poorer overall survival. Given the inherent limitations of retrospective data, prospective validation is warranted.

Three Cases of Lenalidomide Therapy for Multiple Myeloma and Subsequent Development of Secondary B-ALL.

INTRODUCTION: Multiple myeloma (MM) is the second most common hematological malignancy, accounting for 1% of all cancers, with median age of diagnosis between 66-70 years. MM remains incurable despite advances in treatment over time. Lenalidomide is an important medication used in induction therapy for MM and is also used for maintenance therapy for standard risk patients. With its increasing use, data is emerging about its use being associated with increased risk of secondary primary malignancies (SPM), especially when used as maintenance therapy. CASE SERIES: In this case series, we describe three patients with refractory MM treated with lenalidomide maintenance who later developed sALL. All had a common presentation of pancytopenia. They developed cytopenias while being on lenalidomide which was refractory to lenalidomide cessation, prompting bone marrow biopsy. MANAGEMENT AND OUTCOME: Lenalidomide was subsequently stopped, and patients were treated for secondary B-ALL. However, all passed away either due to relapse of disease or complications arising from treatment. DISCUSSION: The mechanism of lenalidomide associated SPMs is not well understood however its incidence is well documented. At least 13 cases of ALL (predominantly B-cell ALL) following Immunomodulator imide drugs (IMiDs) have been reported in literature. An analysis of a larger cohort of patients is required to determine causality of lenalidomide with sALL. However, benefits of maintenance lenalidomide in patients with MM outweighs the risk of developing SPMs. Albeit persistent pancytopenia on lenalidomide therapy should be evaluated with bone marrow biopsy since it could be caused by secondary B -cell ALL.