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  • Association of fludarabin, ...
    Penel‐Page, Mathilde; Plesa, Adriana; Girard, Sandrine; Marceau‐Renaut, Alice; Renard, Cécile; Bertrand, Yves

    Pediatric blood & cancer, June 2020, Letnik: 67, Številka: 6
    Journal Article

    Context Acute myeloid leukemia (AML) is a rare disease in children, with only 50% to 60% event‐free survival. Among patients with AML, 10% do not respond to first‐line chemotherapy. There is no recommendation concerning second‐line treatments. Gemtuzumab ozogamicin (GO) is a monoclonal antibody targeting CD33, linked to calicheamicin. We report the efficacy and tolerance of a salvage regimen of fludarabin, cytarabine, and GO (FLA‐GO) in patients refractory to first‐line treatment. Methods Eight patients (median age 14.5 years), who had more than 2% minimal residual disease (MRD) by flow cytometry (MRD flow), received gemtuzumab 3 mg/m² on days 1, 4, 7, associated with cytarabine 2000 mg/m² and fludarabin 30 mg/m² on days 1 to 5. Results Six patients achieved complete remission (CR) (blast count morphology ≤5 × 10−2, CR‐MRD flow <1 × 10−3 for four patients). Five patients received a second course. We observed 11 episodes of febrile neutropenia, including 6 septicemias without complication. There was no fungal infection or toxic death. Two patients received granulocyte colony stimulating factor. One patient had partial platelet recovery; one, prolonged pancytopenia. All patients received hematopoietic stem cell transplantation (HSCT). We observed five mild‐to‐severe sinusoidal obstruction syndromes during HSCT procedures, particularly in patients who did not receive defibrotide prophylaxis. At the date of last contact (median follow‐up: 58 months; range: 22‐78), six patients were in continuous CR with negative MRD. Two patients died of post‐HSCT relapse. Conclusion FLA‐GO is a good salvage regimen for pediatric refractory AML, with significant but acceptable toxicity. HSCT is mandatory to achieve sustained CR in these patients.