LETTER TO THE EDITOR Spontaneous molecular response of IDH2 acute myeloid leukemia Sabine Khalife-Hachem 1 & Jean Pegliasco 1 & Véronique Saada 2 & Eric Hernandez 3 & Valerie Camara-Clayette 4 & Sophie Cotteret 2 & Raouf Benabdelali 5 & Stephane de Botton 1,6 & Christophe Marzac 2,6 & Jean-Baptiste Micol 1,6 Received: 2 July 2019 /Accepted: 26 November 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Dear editor, We report a fast-morphologic leukemia-free state (MLFS) associated with spontaneous molecular response in a patient with an IDH2 mutant acute myeloid leukemia (AML). A 52-year-old female patient was transferred to Gustave Roussy Cancer Center (GRCC) after being hospitalized in another institution for the hypoxemic left lower lobe pneumo- nia, with cytopenia (white blood cell (WBC) count 2.6 G/L with no circulating blasts cells, hemoglobin 11.2 g/dl, platelets 14 G/L). She was diagnosed with acute myelomonocytic leu- kemia with 61% of bone marrow (BM) blasts. Cytogenetic revealed a complex karyotype (45–46, XX, der(7;?)(p11;?), - 9, + mar1). DNA analysis by next-generation sequencing (NGS) showed IDH2 R140Q (variant allele frequency (VAF) 28%) and KRAS K117N (VAF 22%) mutations. On admission at GRCC, we repeated the BM aspirate. Intriguingly, we found, in a rich bone marrow, a decrease in the blast count from 61 to 17%, with presence of many histiocytes and erythrocytophagia. We were also able to perform cytogenetic studies and NGS, showing disappearance of the complex karyotype but presence of a del(1)(q25q32) and decrease in the IDH2 R140Q mutation (5%) with persistence of BRAF mutation (31%), suggesting a clonal evolution. Patient was transferred to the intensive care unit because of acute respira- tory distress. Considering patient’ s poor performance status, and the discordance in the BM results, we decided to withhold the initiation of chemotherapy and performed a 3rd BM aspi- rate; cytogenetic and NGS were not performed at this time point. Surprisingly, this 3rd evaluation, 9 days after the diag- nosis of AML, showed < 5% blasts in a normocellular bone marrow with many images of cytophagia. In order to confirm this response, we quantified the IDH2 R140Q mutation by crystal digital PCR (cdPCR) with the Naica System (Stilla technologies, France) at the 3 time points. Figure 1 shows the longitudinal VAF profiling of the IDH2 R140Q mutation in parallel to the percentage of BM blasts. Interestingly, we found, without any specific treatment, a dramatic decrease in the IDH2 mutation from 28.15% (standard deviation (SD), 0.05) to 2.32% (SD, 0.35). Unfortunately, the patient died Fig. 1 Evolution of allele frequency of IDH2 R140Q by crystal digital PCR at 3 time points performed in triplicates Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00277-019-03876-8) contains supplementary material, which is available to authorized users. * Jean-Baptiste Micol Jeanbaptiste.MICOL@gustaveroussy.fr 1 Département d’Hématologie, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France 2 Département de Biologie et Pathologie médicales, Gustave Roussy, Université Paris-Saclay, F-94805 Villejuif, France 3 CHIV, 94190 Villeneuve-Saint-Georges, France 4 Laboratoire de Recherche Translationnelle, AMMICa INSERMUS23/CNRS UMS3655, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France 5 Laboratoire CERBA, 95310 Saint-Ouen-l’Aumône, France 6 Inserm U1170, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France Annals of Hematology https://doi.org/10.1007/s00277-019-03876-8