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Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) predominantly occurs in adults ≥60 years old; 10–20% of cases are pediatric or adolescent/young adult (AYA) patients. Tagraxofusp (TAG, Elzonris®) is the only approved treatment for BPDCN; in the United States it is approved for patients aged ≥2 years. Data on treating pediatric and AYA BPDCN patients are limited. We present a case series of pediatric and AYA patients with BPDCN treated with TAG. Eight patients (five newly diagnosed; three relapsed/refractory [R/R]), aged 2–21 years, received 12 mcg/kg TAG. Seven patients were female; most had skin (n = 6) and/or bone marrow (n = 4) involvement. No new safety signals were identified. Grade 3 adverse events were headache (n = 1) and transaminitis (n = 2). Three patients with newly diagnosed BPDCN achieved complete response, one achieved partial response, and one had stable disease (SD). One patient with R/R BPDCN achieved a minor response; one had SD. Seven patients (88%) were bridged to stem cell transplant: 80% of newly diagnosed patients and 100% of R/R patients. Five patients remained alive at last follow‐up. These cases highlight the efficacy and safety of TAG in pediatric and AYA patients for whom there is no other approved BPDCN therapy.

IntroductionB-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy in children. The current conventional chemotherapy regimens have high overall survival but with significant short- and long-term toxicities, sometimes requiring delay and termination of chemotherapy. Bispecific T-cell engager antibody blinatumomab has been successful in achieving bone marrow remission and acting as bridging therapy in minimal residual disease (MRD)-positive relapsed adult and pediatric B-ALL patients. Its role as upfront therapy is being explored. Here, we report the first case to our knowledge showing the feasibility, tolerability, and sustained remission using blinatumomab upfront as consolidation and maintenance therapy for 2 years in a pediatric patient with high-risk B-ALL who had significant toxicities with conventional chemotherapy.'Case presentationAn 11-year-old Hispanic girl presented with complaints of fever, abdominal pain, and fatigue. On further evaluation, she had tachycardia, pallor, cervical lymphadenopathy, and pancytopenia. Bone marrow studies confirmed high-risk B-ALL. The patient was started on induction chemotherapy per AALL1131. Her induction course was complicated by syncope, febrile neutropenia, and invasive cryptococcal fungal infection. End-of-induction bone marrow results were MRD negative. Further chemotherapy was withheld due to cardiopulmonary and renal failure, along with ventricular arrhythmias requiring intensive care. The patient received two cycles of blinatumomab as consolidation therapy and then transitioned back to conventional consolidation therapy; however, it was terminated mid-consolidation due to Pseudomonas and Aspergillus sepsis. She was then given blinatumomab maintenance therapy for 2 years and tolerated it well without any irreversible toxicity. She had an episode of Staphylococcus epidermidis sepsis and pneumonia treated by antibiotics and a single episode of a seizure while on blinatumomab therapy. At the time of publication, she is 25 months off treatment and in sustained remission without any further transplant or chemotherapy. She received monthly intravenous immunoglobulin G during the blinatumomab maintenance.ConclusionBlinatumomab given upfront as consolidation and maintenance therapy for 2 years in a pediatric high-risk B-ALL patient with significant toxicities to conventional chemotherapy was feasible and very well tolerated without any irreversible toxicity and led to sustained remission without any bridging transplant or further chemotherapy.

Abstract  PDGF isoforms are a family of polypeptides that bind to cell surface receptors and induce fibroblast proliferation and chemotaxis. PDGF-A and -B chain isoforms have previously been shown to be involved in murine lung development. A new PDGF polypeptide, PDGF-C, was recently recognized and differs from the PDGF-A and -B isoforms in that it requires proteolytic cleavage before it can bind and activate the PDGF alpha receptor. In these studies PDGF-C was over-expressed during embryogenesis using the lung specific surfactant protein C promoter. PDGF-C transgenic pups died from respiratory insufficiency within minutes following birth. At E18.5, nontransgenic lungs exhibited lung morphology consistent with the saccular stage of lung development. In contrast, E18.5 transgenic lungs retained many features of the canalicular stage of lung development and had abundant numbers of large poorly differentiated mesenchymal cells. These results suggest that PDGF-C is activated during lung development and is a potent growth factor for mesenchymal cells in vivo. [ABSTRACT FROM AUTHOR]