Myelodysplastic Syndrome in a Patient With Common Variable Immunodeficiency: A Rare Occurrence.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder caused by impaired B-cell function and antibody production. It commonly presents with chronic sinopulmonary and gastrointestinal manifestations. It is also associated with transformation to acute myeloid leukemia. However, the association of CVID with myelodysplastic syndrome (MDS) is rare. This case report aims to present one such rare association in a 26-year-old patient presenting with severe thrombocytopenia. Bone marrow biopsy revealed hypercellular marrow with 80-90% cellularity along with an increase in CD34 blasts. Cytogenetics revealed loss of the Y chromosome. Diagnosis of MDS with excess blasts-2 was confirmed with a Revised International Prognostic Scoring System score of 4, placing the patient in the intermediate-risk category. The patient was started on azacitidine, a hypomethylating agent. A referral to a bone marrow transplant was also done for the consideration of an allogeneic stem cell transplant.

Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence.

Cancer is associated with higher morbidity and mortality and is the second leading cause of death in the US. Further, in some nations, cancer has overtaken heart disease as the leading cause of mortality. Identification of molecular mechanisms by which cancerous cells evade T cell-mediated cytotoxic damage has led to the modern era of immunotherapy in cancer treatment. Agents that release these immune brakes have shown activity to recover dysfunctional T cells and regress various cancer. Both cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death-1 (PD-1) play their role as physiologic brakes on unrestrained cytotoxic T effector function. CTLA-4 (CD 152) is a B7/CD28 family; it mediates immunosuppression by indirectly diminishing signaling through the co-stimulatory receptor CD28. Ipilimumab is the first and only FDA-approved CTLA-4 inhibitor; PD-1 is an inhibitory transmembrane protein expressed on T cells, B cells, Natural Killer cells (NKs), and Myeloid-Derived Suppressor Cells (MDSCs). Programmed Death-Ligand 1 (PD-L1) is expressed on the surface of multiple tissue types, including many tumor cells and hematopoietic cells. PD-L2 is more restricted to hematopoietic cells. Blockade of the PD-1 /PDL-1 pathway can enhance anti-tumor T cell reactivity and promotes immune control over the cancerous cells. Since the FDA approval of ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody) in 2011, six more immune checkpoint inhibitors (ICIs) have been approved for cancer therapy. PD-1 inhibitors nivolumab, pembrolizumab, cemiplimab and PD-L1 inhibitors atezolizumab, avelumab, and durvalumab are in the current list of the approved agents in addition to ipilimumab. In this review paper, we discuss the role of each immune checkpoint inhibitor (ICI), the landmark trials which led to their FDA approval, and the strength of the evidence per National Comprehensive Cancer Network (NCCN), which is broadly utilized by medical oncologists and hematologists in their daily practice.

A rare case of follicular lymphoma transformed to a high-grade B-cell lymphoma in orbit.

Transformation of lymphoma is an infrequent phenomenon, and involvement of the eye as such is even uncommon. Histological transformation in patients with follicular lymphoma who were previously treated with immune-chemotherapy carry a poor outcome. Here, we illustrate such a case with aggressive histological transformation from a low-grade lymphoma.