Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy, for which conventional chemotherapy has poor outcomes. CD123, the α-subunit of interleukin (IL)-3 receptor, is constantly overexpressed at the surface of tumoral cells. Tagraxofusp (or SL-401) is a recombinant cytotoxin which consists of human interleukin-3 fused to a truncated diphtheria toxin. It is currently the only novel therapy with a prospective evaluation of efficacy and safety in the treatment of BPDCN and is also the only one to achieve FDA approval. In this short review, the results of tagraxofusp are summarized and perspectives of its use in BPDCN and in other malignancies are discussed. The safety profile is also summarized, since capillary leak syndrome is the main toxic effect of the drug, along with more common toxicities including an increase in transaminases and thrombocytopenia.
ObjectivesComplete responses have been observed in NPM1‐mutated AML patients with dactinomycin, a nucleolar stress‐inducing drug. Here, we report a single‐center experience of compassionate use of dactinomycin in untreated or relapsed/ refractory NPM1‐mutated AML.MethodsFrom September 2015 to February 2019, 26 adult patients with NPM1‐mutated AML received dactinomycin in different situations: front‐line treatment in 4 unfit patients (16%); morphologic (n = 16, 62%), molecular relapses (n = 4, 16%), refractory disease (n = 1, 13%), or postremission therapy in second complete response (n = 1, 13%).ResultsMedian age was 62.5 years. Median number of dactinomycin cycle was 1 (1‐8), and 7 patients (27%) received more than 3 cycles. Three out of 17 patients (18%) in morphologic relapse or refractory to chemotherapy achieved complete remission after the first cycle of dactinomycin. None of the 4 patients unfit for intensive chemotherapy responded to dactinomycin as front‐line therapy. Grade 3‐4 adverse events were thrombocytopenia (n = 11, 42%), neutropenia (n = 11, 42%), GI toxicity (n = 6, 23%), mucositis (n = 5, 19%), lung infection (n = 5, 19%), and skin rash (n = 2, 7.6%).ConclusionsDactinomycin is an inexpensive and easily available drug that may induce significant responses in few AML patients with NPM1 mutations with an acceptable safety profile.
L-asparaginase is a key chemotherapeutic agent in acute lymphoblastic leukemia (ALL). It is also known for multiple and severe specific toxicities, without consensual management. We report the case of a 51-year-old man treated with L-asparaginase for recently diagnosed T-cell ALL. During the treatment, he developed a coma due to multifactorial diffuse cerebral edema, by hepatic encephalopathy, cerebral venous thrombosis, and hyperammonemia, all linked to toxicity of L-asparaginase. Specific and innovative treatments were employed to manage these toxicities: supplementation with L-carnitine, thiamine, and pyridoxine for hepatic toxicity, perfusion of sodium benzoate to decrease ammonemia, and extrahepatic albumin-based dialysis sessions, along with anticoagulation. The patient improved within two weeks and is currently alive 13 months later, in first complete remission, without sequelae, on an alleviated chemotherapy regimen.
Venetoclax with high‐dose methotrexate and rituximab seem effective and safe to treat central nervous system involvement of chronic lymphocytic leukemia.
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