We present a 62-year-old gentleman with history of Crohn’s disease, G6PD deficiency, who presented with immune-mediated thrombotic thrombocytopenia purpura (iTTP) one week after the diagnosis of COVID-19 infection. He was admitted with worsening dyspnea, acute renal failure, and profound thrombocytopenia with marked schistocytosis on peripheral smear. ADAMTS13 level was severely deficient. He was treated with oral prednisone, plasma exchange and rituximab with complete clinical resolution. Given the temporal association of this recurrent episode of iTTP with COVID-19 infection and no other discernible cause, COVID-19 infection was the most likely trigger.
Autologous T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19 are approved for the treatment of various CD19+ hematological malignancies. While CAR T cells induce objective responses in a majority of patients, relapse frequently occurs upon loss of CD19 expression by neoplastic cells. Radiation therapy (RT) has been successfully employed to circumvent the loss of CAR targets in preclinical models of pancreatic cancer. At least in part, this reflects the ability of RT to elicit death receptor (DR) expression by malignant cells, enabling at least some degree of CAR-independent tumor killing. In a human model of CD19+ acute lymphoblastic leukemia (ALL), we also observed DR upregulation by RT, both in vitro and in vivo. Moreover, low-dose total body irradiation (LD-TBI) delivered to ALL-bearing mice prior to CAR T cell infusion considerably extended the overall survival benefit afforded by CAR T cells alone. Such an improved therapeutic activity was accompanied by a superior expansion of CAR T cells in vivo. These data encourage the initiation of clinical trials combining LD-TBI with CAR T cells in patients with hematological malignancies.
69‐year‐old man with a history of diffuse large B‐cell lymphoma (DLBCL) presented with severe acute hemolytic anemia 27 months after an autologous hematopoietic stem cell transplantation. Bone marrow aspirate revealed intracellular micro‐organisms (arrows) located within the cytoplasm of red blood cells confirming the diagnosis of severe babesiosis.
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