Relapsed Waldenstrom's Macroglobulinemia and Therapy-Related Myelodysplastic Syndrome with Complex Cytogenetics: A Treatment Dilemma.

Waldenstrom's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by the infiltration of the bone marrow by clonal lymphoplasmacytic cells that produce monoclonal immunoglobulin M as defined by the World Health Organization Classification of hematological malignancies. Historically, the treatment options for WM were limited to alkylating agents and purine analogs. The introduction of immune therapy, including CD20 targeted therapy, proteasome inhibitors, and immune modulators, has provided benefit to those patients and has now become the standard of care. As WM patients become long-term survivors, treatment's late toxicities have become more apparent. Here, we report a case of a 74-year-old female who presented to the hospital with fatigue and was diagnosed with WM. She was treated with bortezomib, doxorubicin, and bendamustine, followed by rituximab. After a remission period of 15 years, the patient had a relapse of WM, and bone marrow biopsy findings were consistent with intermediate-risk t-MDS with complex cytogenetics, presenting us with a treatment dilemma. We decided to treat WM, and the patient went into VGPR with residual lymphoma cells. Despite having dysplasia and complex cytogenetics, she did not have any cytopenia. Currently, she is under observation anticipating the progression of her MDS, given her intermediate I risk status. This case features the occurrence of t-MDS after therapy with bendamustine, cladribine, and doxorubicin. This highlights the need for closer monitoring and consideration of long-term adverse effects when treating patients with indolent lymphomas, especially WM. Late complications need to be considered, and risk versus benefit analysis needs to be carefully evaluated, especially in younger patients with WM.

Aortic Thrombosis and Acute Limb Ischemia Secondary to COVID Hypercoagulability.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), first identified in December 2019 in Wuhan, China, has rapidly spread worldwide, is now a public health emergency, and has been declared a pandemic. While SARS-CoV-2 is known to cause significant pulmonary disease, ranging from pneumonia to acute respiratory distress syndrome (ARDS), various extrapulmonary manifestations of COVID-19 have also been reported. Growing evidence suggests that COVID-19 leads to a hypercoagulable state leading to micro and macro-vascular angiopathies. We present a case of an 80-year-old male without a previous history of prothrombotic disorders who developed descending aortic thrombosis, approximately 40% stenosis, at the level of the diaphragmatic hiatus and acute limb ischemia secondary to COVID-19 requiring emergent surgical intervention. After 12 days of persistent ischemic left lower extremity imaging despite thrombectomy, bypass, and therapeutic heparin, the patient's limb was deemed non-salvageable and underwent left above-knee amputation. Transthoracic echocardiogram revealed normal left ventricular function, moderate pulmonary hypertension, and no evidence of atrial septal defect, aortic root abnormalities, or intraventricular thrombi. Evaluation of autoimmune and inflammatory vasculitis was negative. While further study into the prothrombotic nature of this condition still needs to be pursued, the thromboembolic risk of COVID-19 represents an urgent need for appropriate anticoagulation for venous thrombosis. Arterial thrombosis requires other kinds of management to avoid the severe adverse effects of emboli and related ischemia. This current case highlights the need for randomized control trials testing different prophylactic strategies. Further evidence is also required for the role of amputation surgery when initial interventions for revascularization fail to restore blood flow.

Autoimmune Hemolytic Anemia as Presenting Symptom of Hodgkin Lymphoma.

Autoimmune hemolytic anemia (AIHA) is related to an underlying condition in an estimated 50 to 60%, while the remaining is idiopathic, as a result of a combination of immune activation, deficiency, or dysregulation. AIHA is associated with viral infections, autoimmune disorders, immunodeficiencies, lymphoproliferative disorders, and pregnancy. AIHA has predictive properties and may be a harbinger of future lymphoproliferative disorders in up to 20% of AIHA cases. Autoimmune hemolytic anemia (AIHA) has been associated with lymphoproliferative disorders particularly chronic lymphocytic leukemia and non-Hodgkin lymphoma. Rarely is it seen in Hodgkin disease. In the following report, we describe the presentation of AIHA, ultimately resulting in the diagnosis of nodular sclerosis Hodgkin lymphoma (stage III). From the limited reports and reviews available, it is understood that advanced Hodgkin (stage III or IV) of nodular sclerosis (NS) or mixed cellularity (MC) types portend a stronger affiliation to AIHA. The majority of AIHA-associated Hodgkin lymphoma presents as stage III or IV disease with the hemolysis being the presenting symptom, as in this case. The mainstay of AIHA therapy has been corticosteroids; however, this first-line regimen appears to be less effective when treating AIHA in the setting of HL. The exact mechanism of AIHA related to HL is unclear, and it may be thought to be that tumor cell produced autoantibodies. Other hypotheses include paraneoplastic phenomena or more, perhaps immunity to tumor cells may cross-react with antigens on the red cells. Although these mechanisms require further investigation, the relationship of the AIHA and HL represents a piece to a larger puzzle between autoimmune disorders and lymphoproliferative conditions.