The initial molecular response predicts the deep molecular response but not treatment-free remission maintenance in a real-world chronic myeloid leukemia cohort

In chronic myeloid leukemia, the identification of early molecular predictors of stable treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) discontinuation is challenging. The predictive values of residual disease (BCR::ABL1 quantification) at months 3 and 6 and more recently, BCR::ABL1 transcript halving time (HT) have been described, but no study compared the predictive value of different early parameters. Using a real-world cohort of 408 patients, we compared the performance of the ELTS score, BCR::ABL1 HT, and residual disease at month 3 and 6 to predict the molecular response, achievement of the TKI discontinuation criteria, and TFR maintenance. The performances of BCR::ABL1 HT and residual disease at month 3 were similar. Residual disease at month 6 displayed the best performance for predicting the optimal response (area under the ROC curve between 0.81 and 0.92; cut-off values: 0.11% for MR4 at month 24 and 0.12% for MR4.5 at month 48). Conversely, no early parameter predicted reaching the TKI discontinuation criteria and TFR maintenance. We obtained similar results when patients were divided in subgroups by first-line treatment (imatinib vs second generation TKI, 2G-TKI). We identified a relationship between ELTS score, earlier milestones and TFR maintenance only in the 2G-TKI group. In conclusion, this first comparative study of early therapeutic response parameters showed that they are excellent indicators of TKI efficacy (BCR::ABL1 transcript reduction) and best responders. Conversely, they did not predict the achievement of the TKI discontinuation criteria and TFR maintenance, suggesting that other parameters are involved in TFR maintenance

PENGARUH ATOPI TERHADAP TIMBULNYA DERMATITIS KONTAK PADA MAHASISWIRNPENDIDIKAN DOKTER FAKULTAS KEDOKTERAN UNIVERSITAS SYIAH KUALA RNBANDA ACEH

Dermatitis kontak adalah inflamasi non infeksi pada kulit yang disebabkan karena pemaparan dengan suatu zat tertentu yang dapat mengiritasi kulit atau menyebabkan reaksi alergi. Perempuan lebih sering mengalami dermatitis kontak dibandingkan laki-laki. Atopi merupakan salah satu faktor predisposisi timbulnya dermatitis kontak. Penelitian ini bertujuan untuk mengetahui pengaruh atopi terhadap timbulnya dermatitis kontak pada mahasiswi Pendidikan Dokter Fakultas Kedokteran Universitas Syiah Kuala Banda Aceh. Penelitian ini bersifat analitik dengan pendekatan cross sectional. Data yang digunakan adalah data primer yang diperoleh dengan wawancara langsung pada responden. Uji statistik dengan menggunakan Chi Square diperoleh nilai p yang signifikan sebesar 0,00, ini berarti p < 0,05 maka secara statistik didapatkan hubungan antara atopi dengan dermatitis kontak dengan rasio prevalensi 2,17, artinya seseorang yang menderita atopi memiliki peluang sebesar 2,17 kali untuk mengalami dermatitis kontak dibandingkan dengan orang yang tidak menderita atopi. Bahan yang paling sering menyebabkan dermatitis kontak pada mahasiswi adalah deterjen dan kosmetik. Hasil penelitian yang diperoleh ada pengaruh atopi terhadap timbulnya dermatitis kontak pada mahasiswi Pendidikan Dokter FK Unsyiah Banda Aceh, dimana mahasiswi yang menderita atopi cenderung mengalami dermatitis kontak.Kata kunci: Atopi, Dermatitis kontak Alergi, Dermatitis kontak iritanBanda Ace

Serum albumin or body mass index: Which prognostic factor for survival in patients with acute myeloblastic leukaemia?

International audienc

Management of car-t cell-related encephalopathy syndrome in adult and pediatric patients: recommendations of the french society of bone marrow transplantation and cellular therapy (sfgm-tc)

International audienceCAR-T cell-related encephalopathy syndrome (CRES) reflects the potential neurotoxicity of this therapeutic approach and must be considered in the presence of any neurological symptom after the infusion of the CAR-T. This is the second most common adverse event under this therapy and its incidence varies between 12 and 55%. The median time of the onset of the first neurologic symptoms is 4days after CAR-T infusion. The duration of CRES symptoms is generally between 2 and 4days, but late CRES may occur. Monitoring and diagnosis of CERS includes clinical exam, magnetic resonance imaging and electroencephalography. In addition to symptomatic treatments, corticosteroids represent the cornerstone of the high-grade CERS treatment. Drugs targeting IL-6 should be restricted to severe forms, especially those associated with cytokine release syndrome. The purpose of this workshop is to provide practical help in dealing with this complication.L’encéphalopathie liée à l’utilisation des lymphocytes dotés de récepteur à l’antigène chimérique (CAR-T) (CAR-T cell-related encephalopathy syndrome, CRES) traduit la neurotoxicité potentielle de cette approche thérapeutique et doit être envisagée devant la survenue de tout symptôme neurologique après l’infusion des cellules CAR-T. Il s’agit du second effet indésirable le plus fréquent sous cette thérapie et son incidence varie entre 12 et 55 % selon les études. Le délai médian de survenue des premiers symptômes neurologiques est de quatre jours suivant l’infusion de cellules CAR-T. La durée des symptômes du CRES est comprise généralement entre deux et quatre jours mais des CRES tardifs peuvent survenir. La surveillance fait appel notamment au suivi clinique, à l’imagerie par résonance magnétique et à l’électroencéphalographie. La prise en charge, en dehors des mesures symptomatiques, consiste, en premier lieu, en une corticothérapie, les thérapies ciblant IL-6 étant plutôt réservées aux formes sévères. Le but de cet atelier est d’apporter une aide pratique à la prise en charge de cette complication

Allogeneic Hematopoietic Stem Cell Transplantation Improves Outcome of Elderly Patients with Acute Myeloid Leukemia in First Complete Remission: A Time-Dependent and Multistate Analysis from the French Innovative Leukemia Organization

60th Annual Meeting of the American-Society-of-Hematology (ASH), San Diego, CA, DEC 01-04, 201

Impact of Arsenic Trioxide in the Treatment of Higher Risk Acute Promyelocytic Leukemia

International audienceINTRODUCTION: Acute promyelocytic leukemia (APL) accounts for 5-8% of all cases of acute myeloid leukemia (AML). The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) without chemotherapy is currently the reference treatment of standard APL (ie with baseline white blood count (WBC)&lt;10 G/L), curing about 90% of the patients. However, the prognosis of high-risk APL (ie with WBC&gt;10 G/L) remains more challenging, with higher rates of early death and relapse. Here we compared the French practices for the treatment of high-risk APL patients whether patients were treated with ATRA-Chemo or ATRA-ATO according to physician decision, and evaluate the response rates, overall survival (OS) and leukemia-free survival (LFS) in the real-life settings. PATIENTS AND METHODS: ATO (in combination with ATRA) became accessible in France for the first line treatment of standard risk APL in 2012, but some patients with high-risk APL also received the same combination (generally with some form of cytoreductive chemotherapy) from that date. We retrospectively analyzed cases of high-risk APL diagnosed between 2010 and 2021 in 12 French centers, constituting a cohort of 135 patients with diagnostic of APL confirmed by cytogenetic, FISH and molecular biology assays. RESULTS: Among the 135 patients with WBC&gt;10 G/L, 88 (65%) were classified as APL variant according to FAB classification. Median age was 46 years (range 18-89) and 62 % were male. Median diagnostic WBC was 39.1 G/L (range 10-270) and median platelet count was 27 G/L (range 5-344). At diagnosis, 112 patients (83%) had hemorrhagic manifestations and disseminated intravascular coagulation (DIC) was observed in 124 patients (92%). Pulmonary and cerebral leucostasis were reported in 10 (7%) and 14 (10%) patients, respectively. Eighty-five patients received corticosteroid prophylaxis (81 (95%) with Dexamethasone and 5 (5%) with Prednisolone). Induction therapy consisted in ATRA-ATO for 50 patients (38%) while 85 patients (62%) were treated with ATRA combined with chemotherapy (anthracycline and cytarabin) but without ATO. All patients treated with ATO were cytoreduced: 7 with Hydroxyurea (14%), 17 with Idarubicin (34%) and 26 with both (52%). 29 patients treated without ATO during induction were cytoreduced with Hydroxurea (34%). Most patients experienced one or more adverse events during induction, including sepsis (49 in the ATO group versus 71 in the non ATO group, 98% versus 83.5%, p=0.01), differentiation syndrome (20 in the ATO group versus 27 in the non ATO group, 40% versus 31.7%, p=0.33), transaminase increased (14 in ATO group versus 11 in the non ATO group, 28% versus 12.9%, p=0.03), and bleeding (7 in the ATO group versus 13 in the non ATO group, 14% versus 15.3%, p=0.8). Following induction, 110 patients (81%) achieved complete remission (CR): 45 in the ATO group and 65 in the non ATO group (90% versus 76.4%, p=0.052). One patient (receiving ATRA with chemotherapy) was refractory, and 24 patients experienced early death (5 in the ATO group and 19 in the non ATO group, 10% versus 22.3%, p=0.069) mostly due to hemorrhage or sepsis. Median time between diagnosis and early death was 4.5 days (0-42). Relapse was observed in 6 (5.5 %) patients (5 patients treated without ATO and 1 patient with ATO during induction). After a median follow-up of 34.6 months (0-121.1), OS at 3 years was significantly higher for the ATO group (89.9% (81.8-98.7) versus 75.1% (66.3-84.9) for the non ATO group, p= 0.035, Figure). LFS at 3 years was significantly higher for the ATO group (87.6% (78.7-97.4) versus 71.2% (62-81.7) for the non ATO group, p=0.028). CONCLUSIONS: The survival outcomes were significantly poorer in high-risk APL patients treated without ATO during induction, regardless of the cytoreduction strategy. The toxicity profile of ATO was acceptable. Combining ATO and ATRA limits the use of cytotoxic chemotherapy, which could reduce myelosuppression and long-term complications such as cardiotoxicity and secondary myeloid neoplasms. Early disease-related mortality, due to haemorrhagic or infectious complications, remains the major issue for these patients but tend to be reduced in those receiving ATRA-ATO based regiment. This retrospective study shows that ATO-ATRA and limited chemotherapy could be a better approach than ATRA and standard intensive chemotherapy in terms of early deaths, LFS and OS

CPX-351 Induces Deep Response and Suppress the Impact of Poor Prognosis Mutations (TP53, ASXL1, RUNX1 and EVI1) Defined By ELN-2017 in t-AML and MRC AML: A Report from a Multicentric French Cohort

61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Orlando, FL, DEC 07-10, 2019International audienceIntroductionCPX-351 is a liposomal formulation of cytarabine and daunorubicin packaged at a 5:1 molar ratio. This drug has recently been approved by FDA and EMEA for patients with therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML).The primary objective of this study was to analyze the efficacy of CPX-351 in a real-life setting, evaluating the impact of mutations on response and minimal residual disease (MRD) in responding patients.MethodsWe retrospectively collected data from patients treated by CPX-351 in eleven centers in France. Clinical, biological and treatment information were available for all patients. NGS (19 genes or more) was performed in 67 patients (84%) at diagnosis.Overall response rate (ORR) was defined by complete remission (CR) and CR with incomplete haematological recovery (CRi). Among the patients in CR or CRi, 25 (56%) had MRD evaluation assessed by NGS or flow cytometry. Overall survival (OS) was calculated from the date of AML diagnosis to the date of death or last follow-up. All statistical analyses were performed using SPSS v.22 software (IBM SPSS Statistics).ResultsBetween April 2018 and July 2019, 80 patients treated with CPX-351 were included in this study. Sex ratio M/F was 43/37 and median age was 66 years old (range 20-83). AML subtypes were MRC-AML (61%) including AML with prior myelodysplastic syndrome (MDS-AML) (33%), prior chronic myelomonocytic leukemia (CMML-AML) (7%), or t-AML (29%). Sixteen patients (20%) had received prior treatment by hypomethylating agents (HMA), at the time of MDS diagnosis, before AML evolution. According to ELN 2017 classification, genetic risk was favorable, intermediate and adverse in 1 (1%), 31 (38%) and 47 (58%), respectively. 36% and 28% patients had complex and monosomal karyotypes, respectively. Assessed by NGS the most frequent mutated gene were : RUNX1 (n=17, 25%), TP53 (n=15, 22%), ASXL1 (n=14, 21%), TET2 (n=13, 19%), DNMT3A (n=11, 16%), srsf2 (n=9, 13%), FLT3-ITD (n=8, 12%), CBL (n=7, 10%), WT1 (n=7, 10%), and EZH2 (n=7, 10%). According to a genetic ontogeny-based classifier (Lindsley et al., Blood 2015), 23 patients (34%), 29 (43%), 15 (22%) had de novo/pan-AML, secondary type mutations AML, and TP53 mutated AML, respectively.Only 4 patients discontinuing treatment due to prolonged haematological toxicity. Early death rate was 5% and 8.75% through day 30 and day 60, respectively.Median time to neutrophil recovery (>0,5 G/L) and platelet recovery (>20G/L) after induction was 29 days (range 19-78) and 28 days (range 12-77), respectively. Seventy-five patients (95%) had at least one grade 3 or more AEs, including 69 (86%) febrile neutropenia. We observed gastrointestinal toxicity 32 patients (40%) (nausea/vomiting (30%/11%), mucositis (15%)) including 4% with grade 3 or more and alopecia in only 12%.ORR was 45/80 (56%) after induction 1 including 53% CR and 3% CRi. ORR increased to 58% after induction 2. Among the 45 CR/CRi patients, 25 were evaluable for MRD at the time of the 1st consolidation. 72% had MRD below 10-3 (64% below 10-4). Prior treatment by HMA and presence of monosomal karyotype were identified as factors predicting a lower rate of CR/CRi (P=0.001 and P=0.002, respectively). Lindsley's classifier predicted significantly a better chemosensitivity in de novo/pan-AML mutations (P= 0.037). Poor molecular prognosis subgroups defined by 2017 ELN risk stratification (n = 53) as TP53, ASXL1, RUNX1 and EVI1 mutations were not associated with a lower response rate with CPX-351 (Table 1).Twenty-one (26%) patients underwent an allogeneic haematopoietic stem cell transplant (HSCT) with an improved median OS compared to non-transplanted patients (non reached vs 8 months, P= 0.004). With a median follow up of 8.5 months, median OS was not reached. Survival analysis in subgroups will be available for the ASH meeting.ConclusionThese data confirmed the efficacy and safety of CPX-351 in poor risk AML (t-AML and MRC-AML). The high rate of CR with low MRD compares favorably with previous report using 7+3 in elderly unfavorable AML (Sylvie D. Freeman et al., JCO 2013) and may explain the favorable outcome observed in patients after HSCT. Moreover, CPX-351 erases the poor prognosis associated with unfavorable mutations defined in 2017 ELN risk stratification. Lindsley's classifier was the best prognostic scoring system in patients treated by CPX-351

Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: a multicentric French cohort

International audienceCPX-351 is a liposomal formulation of cytarabine and daunorubicin approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). We retrospectively analyzed the efficacy and safety of CPX-351 in a real-world setting in 103 patients from 12 French centers, including the evaluation of molecular abnormalities at baseline and minimal residual disease (MRD) in responding patients, compared with a historical data set from Bordeaux-Toulouse DATAML registry. A favorable safety profile was observed, with a low frequency of alopecia (11%) and gastrointestinal toxicity (50%). The overall response rate after induction was 59%, and MRD,1023 was achieved in 57% of complete response (CR)/CR with incomplete hematological recovery (CRi) patients. Only the presence of mutated TP53 (P = .02) or PTPN11 (P = .004) predicted lower response in multivariate analysis. Interestingly, high-risk molecular prognosis subgroups defined by 2017 European LeukemiaNet risk stratification, including ASXL1 and RUNX1 mutations, were not associated with a significantly lower response rate using CPX-351. With amedian follow-up of 8.6 months, median overall survival (OS) was 16.1 months. Thirty-six patients underwent allogeneic stem cell transplantation with a significantly longer median OS compared with nontransplanted patients (P60 years