Second haploidentical stem cell transplantation (HAPLO-SCT2) after relapse from a first HAPLO-SCT in acute leukaemia — a study on behalf of the Acute Leukaemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

For patients with acute myeloid and lymphoblastic leukaemia (AML/ALL) lacking a matched sibling or unrelated donor, haploidentical stem cell transplantation (HAPLO-SCT) is increasingly used. However, available data on the treatment of relapse after HAPLO-SCT, including feasibility and efficacy of a second HAPLO-SCT (HAPLO-SCT2), is scarce. Hence, adults with AML/ALL, that had undergone HAPLO-SCT2 without ex-vivo manipulation after haematologic relapse from HAPLO-SCT1 were selected for a retrospective registry analysis. Eighty-two patients (AML, n = 63, ALL, n = 19, median follow-up: 33 months) were identified. Engraftment rate was 87%. At day +180, cumulative incidences of acute GvHD II-IV°/chronic GvHD were 23.9%/22.6%, respectively. Two-year overall survival/leukaemia-free survival (OS/LFS) were 34.3%/25.4%; 2-year non-relapse mortality (NRM) and relapse incidence (RI) were 17.6% and 57%. Leukaemia was the most frequent cause of death. Separated by disease, 2-year OS/LFS/NRM/RI were 28.7%/22.3%/16.2%/61.6% in AML, and 55.3%/38.4%/23.5%/38.2% in ALL patients. In a risk-factor analysis among patients with AML, stage at HAPLO-SCT1 and HAPLO-SCT2, and interval from HAPLO-SCT1 to relapse significantly influenced outcome. Our data demonstrate that HAPLO-SCT2 is a viable option in acute leukaemia relapse after HAPLO-SCT1. Engraftment, toxicity, risk factors and long-term outcome are comparable to data reported after allo-SCT2 in a matched donor setting

Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors

Background Graft-versus-host disease (GVHD) remains a major contributor to mortality and morbidity after allogeneic stem-cell transplantation (allo-HSCT). The updated recommendations suggest that rabbit antithymocyte globulin or anti-T-lymphocyte globulin (ATG) should be used for GVHD prophylaxis in patients undergoing matched-unrelated donor (MUD) allo-HSCT. More recently, using post-transplant cyclophosphamide (PTCY) in the haploidentical setting has resulted in low incidences of both acute (aGVHD) and chronic GVHD (cGVHD). Therefore, the aim of our study was to compare GVHD prophylaxis using either PTCY or ATG in patients with acute myeloid leukemia (AML) who underwent allo-HSCT in first remission (CR1) from a 10/10 HLA-MUD. Methods Overall, 174 and 1452 patients from the EBMT registry receiving PTCY and ATG were included. Cumulative incidence of aGVHD and cGVHD, leukemia-free survival, overall survival, non-relapse mortality, cumulative incidence of relapse, and refined GVHD-free, relapse-free survival were compared between the 2 groups. Propensity score matching was also performed in order to confirm the results of the main analysis Results No statistical difference between the PTCY and ATG groups was observed for the incidence of grade II-IV aGVHD. The same held true for the incidence of cGVHD and for extensive cGVHD. In univariate and multivariate analyses, no statistical differences were observed for all other transplant outcomes. These results were also confirmed using matched-pair analysis. Conclusion These results highlight that, in the10/10 HLA-MUD setting, the use of PTCY for GVHD prophylaxis may provide similar outcomes to those obtained with ATG in patients with AML in CR1.Peer reviewe

Prognostic impact of number of induction courses to attain complete remission in patients with acute myeloid leukemia transplanted with either a matched sibling or human leucocyte antigen 10/10 or 9/10 unrelated donor:An Acute Leukemia Working Party European Society for Blood and Marrow Transplantation study

Introduction: For the majority of patients with acute myeloid leukemia (AML) an allogeneic stem cell transplant (SCT) in first complete remission (CR) is preferred. However, whether the number of courses required to achieve CR has a prognostic impact is unclear. It is unknown which factors remain important in patients requiring more than one course of induction to attain remission. Methods: This Acute Leukaemia Working Party study from the European Society for Blood and Marrow Transplantation identified adults who received an allograft in first CR from either a fully matched sibling or 10/10 or 9/10 human leucocyte antigen (HLA)‐matched unrelated donor (HLA‐A, HLA‐B, HLA‐C, HLA‐DR, or HLA‐DQ). Univariate and multivariate analyses were undertaken to identify the prognostic impact of one or two courses of induction to attain CR. Results: A total of 4995 patients were included with 3839 (77%) patients attaining a CR following one course of induction chemotherapy (IND1), and 1116 patients requiring two courses (IND2) to attain CR. IND2 as compared to IND1 was a poor prognostic factor in a univariate analysis and remained so in a multivariate Cox model, resulting in an increased hazard ratio of relapse (1.38; 95% confidence interval [CI], 1.16–1.64; p = .0003) and of death (1.27; 95% CI, 1.09–1.47; p = .002). Adverse prognostic factors in a multivariate analysis of the outcomes of patients requiring IND2 included age, FLT3‐ITD, adverse cytogenetics, and performance status. Pretransplant measurable residual disease retained a prognostic impact regardless of IND1 or IND2. Conclusion: Initial response to chemotherapy as determined by number of courses to attain CR, retained prognostic relevance even following SCT in CR

Integrating biological HLA-DPB1 mismatch models to predict survival after unrelated hematopoietic cell transplantation

Non peer reviewe

Late relapse after hematopoietic stem cell transplantation for acute leukemia: a retrospective study by SFGM-TC.

peer reviewedLate relapse (LR) after allogeneic hematopoietic stem cell transplantation (AHSCT) for acute leukemia is a rare event (nearly 4.5%) and raises the questions of prognosis and outcome after salvage therapy. We performed a retrospective multicentric study between January 1, 2010, and December 31, 2016, using data from the French national retrospective register ProMISe provided by the SFGM-TC (French Society for Bone Marrow Transplantation and Cellular Therapy). We included patients presenting with LR, defined as a relapse occurring at least 2 years after AHSCT. We used the Cox model to identify prognosis factors associated with LR. During the study period, a total of 7582 AHSCTs were performed in 29 centers, and 33.8% of patients relapsed. Among them, 319 (12.4%) were considered to have LR, representing an incidence of 4.2% for the entire cohort. The full dataset was available for 290 patients, including 250 (86.2%) with acute myeloid leukemia and 40 (13.8%) with acute lymphoid leukemia. The median interval from AHSCT to LR was 38.2 months (interquartile range [IQR], 29.2 to 49.7 months), and 27.2% of the patients had extramedullary involvement at LR (17.2% exclusively and 10% associated with medullary involvement). One-third of the patients had persistent full donor chimerism at LR. Median overall survival (OS) after LR was 19.9 months (IQR, 5.6 to 46.4 months). The most common salvage therapy was induction regimen (55.5%), with complete remission (CR) obtained in 50.7% of cases. Ninety-four patients (38.5%) underwent a second AHSCT, with a median OS of 20.4 months (IQR, 7.1 to 49.1 months). Nonrelapse mortality after second AHSCT was 18.2%. The Cox model identified the following factors as associated with delay of LR: disease status not in first CR at first HSCT (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.04 to 1.64; P = .02) and the use of post-transplantation cyclophosphamide (OR, 2.23; 95% CI, 1.21 to 4.14; P = .01). Chronic GVHD appeared to be a protective factor (OR, .64; 95% CI, .42 to .96; P = .04). The prognosis of LR is better than in early relapse, with a median OS after LR of 19.9 months. Salvage therapy associated with a second AHSCT improves outcome and is feasible, without creating excess toxicity

Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy

Mise en place d un système d éducation thérapeutique à l intention des patients ayant bénéficié d une allogreffe de cellules souches hématopoïétiques (application aux Unité Fonctionnelles Greffe de Moelle Osseuse et Thérapie Cellulaire et Hôpital de Jour de Cancérologie et Hématologie au CHU de Grenoble)

Introduction: les patients ayant bénéficié d une allogreffe de cellules souches hématopoïétiques ont une prise en charge très lourde et ne bénéficient d aucune structure éducative. Ce travail a pour objet de créer un programme d éducation thérapeutique au sein du CHU de Grenoble qui leur soit spécifiquement adressé. Méthodologie : les recommandations nationales et internationales ont été suivies pour imaginer cette structure éducative qui s appuiera notamment sur un document destiné aux patients. Résultats : ce travail a permis de réaliser, d évaluer et de valider un document d information destiné aux patients et des documents destinés aux professionnels de santé intervenant dans leur éducation thérapeutique. De plus, il a pu être posé les fondements d une structure éducative multidisciplinaire capable de prendre en charge plus de 50% des patients allogreffés au CHU de Grenoble. Conclusion : cette structure éducative doit maintenant être mise en place et son impact doit être évalué.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Use of Real-Time PCR To Process the First Galactomannan-Positive Serum Sample in Diagnosing Invasive Aspergillosis

Positive galactomannan (GM) antigenemias are included as a microbiological item in the diagnosis of probable or possible invasive aspergillosis (IA). Because false-positive GM results frequently occur, at least two positive results on two different samples are required. Waiting for clinical specimens can delay the initiation of treatment. As an alternative, we wondered whether detection of circulating Aspergillus DNA on the first positive GM serum sample could aid in diagnosing IA. Therefore, we retrospectively screened the first GM-positive serum samples from 29 patients from our hematology unit for Aspergillus DNA using real-time PCR. We compared the real-time PCR results with the final classification of proven, probable, and possible IA according to consensual criteria. No clear correlation between PCR results and the classification with the medical files could be shown. However, a positive PCR result was associated with a poor prognosis (Fisher's test; P = 0.01). Our preliminary data suggest that a positive PCR result could indicate a more advanced stage of the disease. Therefore, concomitant positive PCR and GM results may justify the initiation of antifungal therapy in neutropenic patients. In contrast, a negative PCR on the first positive GM sample may argue for postponing costly antifungal administration until additional arguments for the diagnosis of IA are presented

In vitro functional defects of bone marrow-derived CD34+ progenitors from newly diagnosed mature B-cell malignancies with bone marrow tumor involvement.

International audienceOBJECTIVE: We hypothesized that the presence of tumor cells in bone marrow (BM) could alter hematopoietic progenitor cell functions. Therefore, we evaluated phenotypic and in vitro functional properties of BM-derived CD34+ progenitors issued from untreated and newly diagnosed patients presenting a mature B-lymphoproliferative disorder (LPD) involving the BM (Inv+). PATIENTS AND METHODS: In vitro proliferation and differentiation capacities of primitive and committed progenitors were evaluated by cobblestone area-forming cell (CAFC) and colony-forming cell (CFC) assays, and ex vivo cell expansion. Migratory capacities of CD34+ cells were explored by chemotaxis assays using a CXCL12alpha gradient. RESULTS: Our results showed that CD34+ cells from Inv+ patients overexpressed CD117 and had a significant decrease of week-3 and -6 CAFC, and CFC frequencies, compared to cells obtained from healthy volunteers and LPD patients without BM involvement (Inv-). In addition, progenitors from Inv+ patients maintained a significantly decreased CFC capacity after ex vivo cell expansion, compared to healthy volunteers. However, the former cells held their migratory capacity in response to CXCL12alpha. CONCLUSION: Functional defects of primitive and committed CD34+ progenitors detected among LPD patients with BM tumor involvement suggest either that tumor cells may induced bystander effects on progenitors or that "unusual" CD34+ cells may exist in the BM that could belong to the proliferating tumor tissue