American journal of hematology
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Chimeric antigen receptor modified T (CAR-T) cell therapy against the CD19 antigen has revolutionized the therapeutic landscape for patients with relapsed, refractory B cell non-Hodgkin lymphoma (NHL). Currently, there are two FDA approved products (axicabtagene ciloleucel and tisagenlecleucel) for B cell NHL, with several other constructs under clinical investigation. This review will focus on the clinical outcomes, toxicity profile, and differences among candidate CD19 CAR-T cell products for major subtypes of B cell NHL including diffuse large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Lastly, we will describe novel CAR-T constructs currently under exploration in B cell NHL.
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Ruxolitinib is a promising treatment for steroid refractory graft-vs-host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. ⋯ Ruxolitinib is a promising treatment for acute and chronic GvHD with a high ORR of 77% and 89%, respectively. It produces important changes in immune system, such as increase of CD4 EM cells and decrease in NK and regulatory T cells. Now, we need pharmacokinetic studies to determine ruxolitinib dose in children and close surveillance and antimicrobial prophylaxis.
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Disease Overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms respectively characterized by erythrocytosis and thrombocytosis; other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic or fibrotic transformation. Diagnosis: Bone marrow morphology remains the cornerstone of diagnosis. In addition, the presence of JAK2 mutation is expected in PV while approximately 90% of patients with ET express mutually exclusive JAK2, CALR, or myeloproliferative leukemia mutations. ⋯ Cytoreductive therapy is recommended for high-risk ET and PV but it is not mandatory for intermediate-risk ET. First-line drug of choice for cytoreductive therapy, in both ET and PV, is hydroxyurea and second-line drugs of choice are interferon-α and busulfan. We do not recommend treatment with ruxolutinib in PV, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to the aforementioned drugs.