Incidence of pleural effusion with dasatinib and the effect of switching therapy to a different TKI in patients with chronic phase CML.

Dasatinib is one of the second generation tyrosine kinase inhibitors (TKI) which is approved for the treatment of patients with chronic phase CML (CP-CML) both in the front line and in the second line setting. Pleural effusion (PE) is a unique toxicity associated with dasatinib use. Our aim was to study the incidence of pleural effusion in our cohort of patients who were treated with dasatinib for CP-CML and the safety upon TKI switch. A total of 390 patients were treated with dasatinib during their course of treatment for CP-CML. A total of 69 patients (17.6%) developed any grade of PE. About 33 (48%) patients developed CTCAE grade 2 PE, 34 (49%) grade 3 and only 1 patient developed grade 4 PE. Recurrence of PE was observed in 34 (49%) patients. While only 12 patients (17.3%) continued using dasatinib after development of PE, dasatinib was discontinued in the other 57 patients. Therapy was switched to bosutinib in 13 patients out of which 6 (46%) patients re-developed PE. While only 12.5% patients developed re-accumulation of pleural fluid in patients switched to imatinib, none of the patients switched to nilotinib re-developed PE. A change in TKI to bosutinib was associated with a 46% risk of recurrence of PE in patients who develop PE on dasatinib for the treatment of CP-CML. The incidence of recurrent PE was markedly lower in patient switched to imatinib or nilotinib.

Aggressive natural killer cell leukemia: diagnosis, treatment recommendations, and emerging therapies.

INTRODUCTION: Aggressive natural killer cell leukemia (ANKL) is a rare hematologic malignancy characterized by the EBV-driven proliferation of mature natural killer cells. It mostly frequently affects younger adults and has a fulminant course with a median overall survival of 2 months. Challenges in managing this disease include an aggressive clinical course, hematologic complications, limited clinical evidence, and a lack of consensus on therapeutic strategies. AREAS COVERED: Here, authors reviewed the key aspects of the epidemiology and current understandings of the molecular pathogenesis of ANKL. The available clinical evidence and proposed diagnostic and therapeutic algorithms in treating ANKL are discussed. Currently, the only potential cure is induction therapy with L-asparaginase-based combined chemotherapy regimens, followed by allogeneic hematologic stem transplant. However, options are extremely limited in the relapsed/refractory setting. Recently, international efforts have been made to understand the aberrant molecular pathways of ANKL and identify potential drug targets for this disease; PD-1 inhibitors, EBV-specific cytotoxic lymphocyte therapy, BCL-2 inhibitors, and JAK2 inhibitors in combination with other agents have been shown to have promising potential in treating this aggressive disease. EXPERT OPINION: When clinical trials are not available, a personalized approach using next-generation sequencing results should be encouraged in the relapse/refractory setting.

COVID-19 Virus Infection in Three Patients With Hypogammaglobulinemia.

The world is experiencing the COVID-19 outbreak and there are no evidence-based treatment strategies available for immunocompromised patients. COVID-19 is a novel beta coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with cancer are more susceptible to infection than individuals without cancer due to their impaired humoral and cellular immune function caused by the malignancy itself and chemotherapy. We present three cases of cancer patients with hypogammaglobulinemia with varying clinical outcomes associated with infection. These include one mantle cell lymphoma patient with recurrent respiratory infection requiring intravenous immunoglobulin (IVIG) support and two multiple myeloma patients with continued viral shedding.

Long-Term Remission After Matched Sibling Donor Hematopoietic Cell Transplantation in a Patient With Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-Cell Lymphoma.

Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (CD8+ PCAECTL) is an extremely rare neoplasm with a poor prognosis. Chemotherapy typically does not result in a sustained response, and hematopoietic stem cell transplant (HSCT) is the only therapy that has been shown to produce a durable response of any kind. Here, we report a case of a 25-year-old previously healthy male who presented with a painful ulcerative lesion on the bottom of his right great toe and local lymphadenopathy. The biopsy of the lesion was consistent with CD8+ PCAECTL. He received immediate chemotherapy followed by matched related donor HSCT (MRD-HSCT) and remained in complete remission (CR) for eight years post-transplant, longer than any CR reported in the literature. In conclusion, our report provides clinical evidence that early transplant consult and donor search is one of the key factors in the management of CD8+ PCAECTL.

Petechiae, Purpura, and a Pandemic: A Recipe for Scurvy.

This case report presents the case of a 28-year-old man who developed scurvy during the coronavirus disease 2019 (COVID-19) pandemic. Scurvy is a disease resulting from a nutritional deficiency of vitamin C (ascorbic acid). It is a rare condition, whose signs and symptoms can vary from patient to patient. The treatment is vitamin C supplementation, which is often followed by a swift recovery. To our knowledge, this is the first reported case of scurvy during the COVID-19 pandemic. This article highlights a rare acquired bleeding disorder, which may manifest more commonly during a pandemic due to food scarcity or stay-at-home mandates in those already at risk.

Novel therapies in myelodysplastic syndromes.

PURPOSE OF REVIEW: Currently, there is a rapid expansion of novel, efficacious therapies for the treatment of patients with myelodysplastic syndromes (MDS) at a rate never seen to date. In this review, we will outline new treatment strategies in MDS focusing on novel hypomethylating agents (HMA) and combinations in addition to targeted and immune-based therapies. RECENT FINDINGS: Large-scale gene sequencing and immune-based research has given us a great deal of information regarding the complexity and heterogeneity of MDS. This rapid improvement in our knowledge has provided a framework for development of novel therapies with specific gene and immune-based targets. Additionally, expanding and optimizing our current HMA-based strategies has led us to potentially not only ease administration but also improve outcomes. SUMMARY: Novel therapies in MDS are greatly needed is a disease state where few options are currently available, particularly in the HMA failure setting. Fortunately, through comprehensive genetic profiling, characterization of novel underlying pathogenic drivers, and understanding of the immune microenvironment, the treatment paradigm of patients with MDS is encouraging.

Development of flavonoid-based inverse agonists of the key signaling receptor US28 of human cytomegalovirus.

A series of 31 chalcone- and flavonoid-based derivatives were synthesized in good overall yields and screened for their inverse agonist activity on the US28 receptor of human cytomegalovirus (HCMV). With one exception (e.g., 2-(5-bromo-2-methoxyphenyl)-3-hydroxy-4H-chromen-4-one), halogen-substituted flavonoids were typically more potent inverse agonists than their related hydro derivatives. While toxicity could be used to partially explain the inverse agonist activity of some members of the series, 5-(benzyloxy)-2-(5-bromo-2-methoxyphenyl)-4H-chromen-4-one (11b) acted on the US28 receptor as a nontoxic, inverse agonist. The full inverse agonism (efficacy, -89%) and potency (EC50 = 3.5 µM) observed with flavonoid 11b is especially important as it provides both a new tool to study US28 signaling and a potential platform for the future development of HCMV-targeting drugs.