LAUSR

Dear Editor, Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder of hematopoietic stem cell characterized by mutations in the PIGA gene leading to complementmediated lysis [1]. Approved in 2009, eculizumab is the first specific treatment for PNH [2]. Nevertheless, this treatment remains only symptomatic and does not lead to the disappearance of the PNH clone. Although spontaneous remissions have been reported to occur in up to 15% of cases [3], the involved mechanisms are not yet fully understood. We describe here a patient in whom PNH remission occurs with the emergence of a new sub-clone in the context of a preexisting myelodysplastic syndrome (MDS). A 71-year-old man was referred because of anemia evolving since 2014. In April 2015, complete blood count results were as follows: white blood cells (WBC) 3.7 × 10/L, hemoglobin 9.6 g/dl with normal mean corpuscular volume, reticulocytes 113 × 10 L, and platelets 140 × 10/L. The martial record was in favor of an iron deficiency (ferritin 17 μg/L, serum iron level 8 μmol/L, transferrin saturation coefficient 11%) together with biological stigmas of hemolysis (LDH 985 UI/L and haptoglobin undetectable). The direct and indirect antiglobulin tests were both negative. A flow cytometric analysis was performed on peripheral blood leucocytes and revealed a PNH neutrophil clone quantified at 33%, which is consistent with the literature [4]. Bone marrow smears analysis was performed and showed an erythroblastic hyperplasia and dysplastic erythroid progenitors without blasts excess (Fig. 1a). Cytogenetic analysis disclosed a clone with a deletion of chromosome 13 (46XY, del(13)(q13q21)) (Fig. 1b). In addition, molecular analysis performed by next-generation sequencing found two somatic hotspot mutations: U2AF1 p.(Ser34Phe) andDNMT3A p.(Arg736Cys). Eculizumab therapy started in May 2015. PNH clone size was monitored regularly and gradually decreased until reaching the size of 0.81% in February 2018 (month 34) leading to eculizumab discontinuation. Hemoglobin level re-increased and the last transfusion was performed in July 2019 (month 51). Concerning MDS evolution, molecular analysis in 2017 (month 31) revealed a novel mutation of the ASXL1 gene (c.1933_1934delGG) in addition to those already known. Because of its localization in a region of guanine nucleotide repetition where sequencing errors can occur, this mutation was confirmed and quantified with a fragment analysis approach. Previous bone marrow aspiration samples were retrospectively analyzed and the ASXL1mutation was not detected