Ruxolitinib as a promising treatment for corticosteroid-refractory graft-versus-host disease

International audienc

The lenalidomide/bortezomib/dexamethasone regimen for the treatment of blastic plasmacytoid dendritic cell neoplasm

International audienceWe describe the use and value of a lenalidomide/bortezomib/dexamethasone regimen for the treatment of three patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN, a disease that lacks a consensus treatment). After five cycles of chemotherapy, we observed two complete responses and one clinical remission. Together with the encouraging literature data on the effects of lenalidomide and bortezomib on BPDCN cells, our results might prompt further investigations of this regimen's value in BPDCN

Sequential conditioning in unfavorable AML: a single center experience

44th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Lisbon, PORTUGAL, MAR 18-21, 2018International audienc

Sequential conditioning in unfavorable AML: a single center experience

44th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Lisbon, PORTUGAL, MAR 18-21, 2018International audienc

Immunomodulation with azacytidine and donor lymphocyte infusion following sequential conditioning allogenic stem cell transplantation improves outcome of unfavorable AML

61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Orlando, FL, DEC 07-10, 2019International audienceBackground:Patients with acute myeloid leukemia in relapse or refractory to induction therapy have dismal prognosis. Response rates to common salvage regimens are low and allogenic hematopoietic stem cell transplantation is the only curative option. Several studies have demonstrated that salvage chemotherapy with sequential conditioning could reduce leukemia relapse risk with an acceptable toxicity profile for unfavorable acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). [1] Therefore, we decided to assess this procedure in our center at Amiens University Hospital.MethodsWe conducted a monocentric retrospective study, including 53 patients aged over 18 years undergoing a hematopoietic stem cell transplant (HSCT) with sequential conditioning between January 2012 and December 2018, for relapse/refractory AML or high risk MDS. 44 (83%) patients received sequential conditioning containing clofarabine (SET-RIC) or Amsacrine (FLAMSA) and 9 (17%) thiotepa based (TEC-RIC) with post-transplant cyclophosphamide for mismatched donors. Patients who were GVHD free after immunosuppressors withdrawal received immunomodulation as relapse prevention with azacytidine 37.5mg/m²/day 5 days every 4 weeks for 12 cycles with 3 donor lymphocyte infusions (DLI) alterned between azacytidine cycles.ResultsThe median age was 52 years (range 18-70). Before conditioning, 48 patients had unfavorable AML with ELN intermediate score refractory to at least one course of induction therapy or in relapse, or unfavorable ELN score; 5 patients had high risk MDS with complex karyotype. 32 patients (60,5%) had active disease and 21 (39,5%) were in complete remission (CR) including 12 with positive MRD. 13 (24,5%) patients had HLA-identical sibling donors, 27 (51%) match unrelated donors (MUD), 4 (7,5%) mismatch unrelated donors (MMD) and 9 (17%) haploidentical donors. Majority of patients (90,5%) received peripheral blood stem cell (PBSC) PBSC with median CD34+ count of 7,94.106/kg (1,84-8,44). Acute GvHD prophylaxis with Ciclosporin A, in combination with Mycophenolate mofetil for MUD/MMR/Haplo, was withdrawal with a median time of 90 days.With a median follow-up of 40 months, overall survival (OS) at 1 and 2 years was 68% and 52%. Median OS was 18,7 months (0-72,4 months) and median disease free survival (DFS) was 14,9 months (0-72,4 months). 17 patients (32%) experienced relapse after HSCT with a median time from HSCT to relapse of 6 months (1-35 months). 22 (41,5%) of patients presented with grade I-II acute graft versus host disease (GVHD) and 6 (11,3%) with grade III IV aGVHD . GVHD free relapse free survival (GRFS) at 1 and 2 years was 53% and 34,2%. One-year cumulative incidence of disease related death and non-relapse mortality was 12,6% and 17% respectively. 19 patients received immunomodulation with 5 Azacitidine and DLI if no GVHD occurred within day 120. OS was 79 % in the 19 patients receiving DLI. In univariate analysis immunomodulation post HSCT (Figure 1) was significantly associated with overall survival and leukemia free survival (p=0,0164 and p=0,0359 respectively) but not the disease status before HSCT (p=0,7). Immunomodulation administration with azacytidine and DLI was not significantly associated with cGVHD occurrence (p=0.31). Benefit of immunomodulation OS persisted in multivariate analysis (p=0.0284).Conclusion:Sequential conditioning regimen on refractory AML with secondary immunomodulation with azacytidine and DLI shows very good results with an acceptable toxicity profile in unfavorable AML. We achieve very good OS and DFS whatever disease status before HSCT. GRFS is also encouraging comparing to previously report datas [1]

Fast CMV and EBV Reactivations after Ruxolitinib for Graft-Versus-Host Disease Treatment

61st Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Orlando, FL, DEC 07-10, 2019International audienc

Impact of Residence in an Agricultural Zone on AML Characteristics

International audienceBackground: Acute Myeloid Leukemia (AML) is associated with several well-established risk factors. These include cigarette smoking, exposure to benzene, to ionizing radiation, and previous exposure to chemotherapy. Interestingly, studies have observed higher incidence rates of AML in farming regions, suggesting that farming activities and related exposures, such as pesticides, may increase the risk. However, data regarding the potential variations in clinical, cytogenetic, and molecular profiles between individuals living in rural and urban areas are lacking. Therefore, we aim to specifically examine the characteristics and the outcomes of AML patients living in agricultural areas. Patients and methods: We performed a retrospective analysis including 315 patients newly diagnosed with AML from two French institutions, namely Amiens University Hospital and Lille University Hospital, from 2008 to 2013. We collected patient demographics, along with comprehensive data encompassing clinical and biological information, including cytogenetics and molecular data. The data was obtained from the Observatoire des Hauts-de-France, enabling a comprehensive and exhaustive review of the AML cases in this specific region. We geocoded the patients' residential addresses. This process involved linking the patient's location to the corresponding agricultural areas per municipality, by using geographical information from the French Ministry of Agriculture's statistics department (AGRESTE, https://www.agreste.agriculture.gouv.fr). This enabled us to establish a connection between the patients' locations and the specific agricultural regions they resided in. We categorized the population into terciles based on the proportion of local companies engaged in farming activities. Results: Approximately one-third (n=108) of patients were living in areas with less than 1.3% of farm companies, one-third (n=102) lived in regions with a percentage ranging from 1.3% to 6.9%, while the remaining third (n=105) lived in areas where the proportion of farm companies exceeded 6.9%. Sex ratio (p=0.7) and median age at diagnosis (60 vs 60.5 vs 58 years, p=0.5) were similar between the 3 groups. There was no difference in body mass index (BMI), smoking activity, alcohol consumption and performance status score between the three groups. At baseline, there was no difference in blood counts (hemoglobin, platelets, leukocytes, and circulating blasts levels), bone marrow blasts percentage, AML type (de novo vs. post MDS or MPN), or WHO classification between the 3 groups. Regarding cytogenetic abnormalities, people living on agricultural lands had fewer normal karyotypes (27% vs 33% and 43%, p=0.045) and more MLL rearrangement (20% vs 8% and 5%, p=0.013). However, there was no difference in the SWOG and ELN 2017 classifications. Regarding molecular characteristics, NPM1 mutations were found less frequently in people living in agricultural regions (13% vs 30% and 29%, p=0.021). There was no difference for FLT3-ITD positivity and CEBPA mutation. There was no difference in complete remission rate and hematopoietic stem cell transplantation treatment though we could underline an especially low rate of HSCT in the < 1.3% group. OS was also similar between the three groups (Table 1.). Conclusions: Our study showed a correlation between living in agricultural areas and a higher prevalence of unfavorable cytogenetic and molecular features in AML patients, although clinical outcomes remain unchanged. These findings suggest that the proximity to agricultural activities could have an impact on leukemogenesis, by increasing the rate of MLL rearrangements and chromosomic abnormalities

Chemotherapy Treatment Doesn't Beneficiate to a Group of Elderly AML Patients with Absence of Complex Karyotype and Circulating Blasts

60th Annual Meeting of the American-Society-of-Hematology (ASH), San Diego, CA, DEC 01-04, 2018International audienceIntroductionAlthough the median age at diagnosis of acute myeloid leukemia (AML) is 67 years, with approximately one third of patients aged 75 years or older, limited treatment options are available for the elderly. There is no standard of care for older patients with AML unfit for intensive chemotherapy. In this case, despite specific treatment such as low-dose cytarabine (LDA) and 5 azacytidine (5AZA), outcome remains extremely poor, without cure (Thomas X, Current Treat Options Oncol 2017, 18(1):2). The goal of our study is to establish a prognostic model of survival in order to identify whether the absence of specific treatment may not be harmful in a subset of patients.Patients and MethodsThe French Hauts-de-France AML observatory is a population-based database reporting AML cases diagnosed and supported in 9 Hospital Centers from the French region Haut-de-France. From January 2008 to December 2016, 572 patients older than 75 years were included in the observatory. Among them 324 patients received best supportive care (BSC) alone, 142 hypomethylating agents, 82 low doses aracytine, and 24 other treatments. As a general consensus accepted in all participating centers, BSC was proposed in unfit patients, after performance status and comprehensive geriatric assessment according to results of a preliminary fast geriatric assessment oncodage G8 (Bellera CA, Ann Oncol 2012, 23(8):2166-72). Clinical data were collected in each center. The study was conducted according to the Declaration of Helsinki and was approved by the Human Research Committee of Lille and the internal review board of the Lille University Hospital Tumor Bank (certification NF 96900-2014/65453-1).ResultsIn the BSC group, median age at diagnosis was 82 years (interquartile range [IQR] 78-86). Median WBC count was 7.3 x10^3/mL (IQR 2.18-42.5) with a median peripheral blood blasts percentage of 21% (IQR 6-59.5). Median bone marrow blasts was 51% (IQR 30-75). Karyotype was available for 181 patients. Two patients were in the favorable, 111 patients (61%) were in the intermediate, 68 patients (38%) were in the unfavorable cytogenetics group and 58 patients (32%) had a complex karyotype.For the BSC group, median survival was 3.2 months (IC 2.3- 4) with a 18% 12-months survival estimate.In univariate Cox models, WBC count (p 75 years), 18% are alive at 12 months without any chemotherapy. Our results indicate that the absence of chemotherapy may not be detrimental in a small subset of unfit patients identified by the absence of both complex karyotype and circulating blasts. However further studies are mandatory for characterizing most of patients alive at 12 months with BSC