Sickle cell disease (SCD) is an inherited hematologic disease caused by sickle hemoglobin as the predominant RBC hemoglobin or by sickle hemoglobin in combination with other abnormal β-hemoglobin variants like HbC, HbD and others. Sickling of erythrocytes under deoxygenated conditions is the basis of inflammatory and thrombotic cascades which result in multiple serious complications, leading to early morbidity and mortality. While HLA-matched allogeneic bone marrow transplantation is potentially curative, it has considerable limitations due to potential severe toxicities. Despite slow progress towards novel therapeutic strategies for SCD and hydroxyurea being the sole medication that is shown to reduce vaso-occlusive events and mortality for almost 20 years, several pharmacological agents targeting different mechanisms have been examined in clinical trials and recently US- US-FDA-approved, including L-glutamine and crizanlizumab. Voxelotor was previously US-FDA-approved but has been voluntarily withdrawn from the market as the overall benefit did not outweigh the risks. Gene therapies based on CRISPR-Cas9 and lentiviral vectors have been very recently approved. However, excessive costs are a barrier to widespread use. Nonetheless, there is still a large area of unmet needs for patients with SCD, and further research towards better care is warranted.

Anti-CD20 monoclonal antibodies (mAbs) have revolutionized the treatment of lymphomas by improving the survival of patients, particularly in conjunction with chemotherapy. Until recently, the gold standard was based on the utilization of Rituximab (RTX) combined with chemotherapy. With our better understanding of monoclonal antibody (mAb) engineering, anti-CD20 mAb therapy has evolved to enhance clinical outcomes by improving pharmacokinetics, safety, activity and immunogenicity. Efforts to improve the on-targeting CD20 expressed on lymphomas through novel bioengineering techniques have led to the development of newer anti-CD20 mAbs that have accentuated complement-dependent cytotoxicity (CDC), antibody-dependent cell medicated cytotoxicity (ADCC), and/or a direct killing effect. There are several anti-CD20 monoclonal antibodies that have been evaluated for the treatment of lymphomas, some of which are now approved in addition to RTX.

Immune checkpoint inhibitors (ICI) targeting programmed cell death protein-1 (PD-1/PD-L1) pathway as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have demonstrated substantial potential in several malignancies. Pancreatic adenocarcinoma (PC) still carries a high mortality despite tremendous advances in the anti-cancer arsenal. In this review, we discuss completed and ongoing studies on various ICIs in PC. ICIs haven't yielded significant benefits as monotherapy. However, combination with currently utilized therapies as well as with several other newer forms of therapy has delineated encouraging results. Larger trials are currently underway to definitively characterize the utility of ICIs in the treatment algorithm of PC. ICIs are approved for cancers with mismatch repair deficiency (dMMR) or microsatellite instability-high tumors (MSI-H) as a tumor-agnostic treatment strategy usually referred to as hot tumors. Studies evaluating different drugs to transform the tumor microenvironment (TME) from 'cold' to 'hot' have not shown promise in PC. There still needs to be more prospective trials evaluating the efficacy of the combination of ICIs with different therapeutic modalities in PC that can augment the immunogenic potential of those 'cold' tumors. Exploratory biomarker analysis may help us identify those subset of PC patients who may particularly benefit from ICIs.

Kaposi Sarcoma Inflammatory Cytokine Syndrome (KICS) is a serious, uncommon disease that occurs in patients who are positive for HIV and human herpesvirus-8 (HHV-8). It is characterized by a constellation of clinical findings, including fever, weight loss, and fluid retention, as well as a lack of multicentric Castleman disease (MCD) features on histopathology and an elevated serum HHV-8 viral load. Diagnosis is often delayed, and treatment options are limited, culminating in high mortality rates. We hereby present a 32-year-old male patient with HIV who was untreated for a few years and came with fever, night sweats, pancytopenia, and widespread adenopathy. A thorough evaluation of opportunistic infections was unremarkable. Clinically MCD was suspected, but lymph node biopsy only showed Kaposi sarcoma (KS) with no characteristic features of MCD. However, with clinical deterioration, KICS was strongly suspected. Kaposi sarcoma immune reconstitution syndrome (KS-IRIS) was also a possibility as the patient was restarted on antiretroviral therapy. Rituximab was commenced, but the patient suffered a cardiac arrest and could not be revived. Alternative diagnosis must be explored in patients with HIV presenting with constitutional symptoms, cytopenia, and adenopathy after opportunistic infections and malignancies are ruled out. If they have KS with HHV-8 positivity and there is a lack of characteristic features of MCD in lymph node biopsy, prompt suspicion of KICS should be made, and treatment with rituximab and/or chemotherapy should be instituted rapidly. KS-IRIS is also possible if patients have recently received antiretroviral therapy and have a rapid decline in viral load and increase in CD4 counts (immunological recovery). HHV8 viral load levels may help to distinguish between these two inflammatory conditions.

Lung cancer is one of the most common cancers and has the highest risk of mortality in both genders. This devastating cancer is also a significant financial and emotional burden to patients and the healthcare system. Chemotherapy and immunotherapy have become the cornerstone for the treatment of lung cancer. However, treatment may come with severe and sometimes fatal side effects. In this report, we present the case of a 52-year-old Caucasian male who suffered two episodes of prolonged cardiac arrest after the infusion of paclitaxel and pembrolizumab.