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Working Parties WORKING PARTIES Acute Leukemia While the positive impact of RIC allo-SCT in terms of NRM reduction has been well established, the putative higher incidence of disease relapse after RIC allo-SCT has been a major mater of concern. Therefore, many investigators were not keen to WP001 propose RIC allo-SCT strategies for those patients who could Genotypes and their impact on upfront and postremission tolerate a standard or conventional myeloablative conditioning treatment strategies (MAC). However, the advent of novel conditioning regimens R. F. Schlenk1,* including purine analogs combined with myeloablative doses of 1Internal Medicine III, University of Ulm, Ulm, Germany drugs such as IV busulfan, thiotepa, and ATG proved to be safe (lower NRM) and effective in high risk patients with acute Genetic heterogeneity is one hallmark of acute myeloid leukemia towards optimizing outcome. With this background, the leukemia (AML). Disease classification, prognostication and field is currently moving progressively from the so-called non- prediction are based on the cytogenetic but even more and myeloablative RIC regimens to a more comprehensive approach more important on the molecular profile of the disease. As focusing on Reduced Toxicity Conditioning (RTC) regimens. This promising molecularly targeted therapeutics and early allo- review will aim to address some of the practical issues related to geneic transplant strategies in selected risk-constellations the use of RTC allo-SCT in acute leukemia patients, including becoming available fast pre-therapeutic molecular screening some perspectives in the haplo-mismatch setting. at diagnoses including fusion genes such as PML-RARA, RUNX1- Disclosure of Interest: None declared. RUNX1T1 and CBFB-MYH11 as well as gene mutations such as NPM1, FLT3, CEBPA and TP53 are increasingly performed in WP003 routine care. The identification of the genetic determinants of AutoSCT for acute leukemia-revisited:reducing TRM response to standard but also to experimental treatment is by IV Bu based conditioning used for patient counseling, to guide clinical decisions A. Nagler1,* on behalf of ALWP making at diagnosis, during consolidation treatment and 1Hematology Division and Bone Marrow Transplantation, Chaim follow-up as well as after relapse. In addition, the pre-treatment Sheba Medical Centre, Ramat Gan, Israel risk-defining parameters have been supplemented by markers evaluated at distinct time points during treatment and follow Autologous stem cell transplantation (AutoSCT) is an effective up. In this context, residual disease assessment is increasingly therapeutic modality for adults with acute leukemia. Many used to dynamically fine tune treatment recommendations. randomized studies have demonstrated lower relapse inci- Once a complete remission of the disease is achieved after dence following AutoSCT compared to chemotherapy and induction therapy, the gold standard to counterbalance a lower transplant related mortality (TRM) and better quality of higher risk of relapse by treatment strategies based on life (QoL) compared to allogeneic SCT. However, due to the hematopoietic stem cell transplantation (HSCT) with grafts development of reduced intensity and reduced toxicity from matched related or unrelated donors is still valuable, preparative regimens for allogeneic transplants over the last whereas autologous hematopoietic stem cell transplantation 15 years, the number of AutoSCTs in Europe has drastically showed promising results especially in patients categorized as declined. Recent developments including the use of targeted low-risk. Nonetheless, more targeted approaches in combina- therapy like tyrosine kinase inhibitors (TKI) pre or post- tion with or sequentially before or after intensive chemother- AutoSCT for ALL, better techniques for detection and apy and/or allogeneic HSCT are currently in clinical evaluation monitoring of minimal residual disease (MRD) pre and post- and may lead to more targeted- instead of purely risk-adapted transplant and the use of new compounds and new drug treatment strategies. formulations (like intravenous busulfan) may improve AutoSCT Disclosure of Interest: None declared. outcome. These developments make AutoSCT an attractive option for elderly patients with AML and in particular those WP002 with good risk and some of those with intermediate risk From Reduced Intensity to Reduced Toxicity leukemia. We have recently analyzed, within the ALWP of the Conditioning EBMT the outcomes of 952 AML patients who underwent M. Mohty1,* on behalf of Acute Leukemia Working Party AutoSCT with intravenous busulfan-based conditioning, rather 1Hematology Dpt., Hopital Saint-Antoine, Paris, France than with oral busulfan, the historical backbone of pre transplant conditioning. 531 (56%) were male and the median In the last decade, the so-called reduced intensity conditioning age at transplantation was 50.5 years. Two-year overall (RIC) regimens prior to allogeneic stem cell transplantation survival, leukemia-free survival, and relapse incidence were (allo-SCT) have emerged as an attractive modality to decrease 67±2%, 53±2%, and 40±2%, respectively. The non-relapse allo-SCT-related toxicities and non-relapse mortality (NRM). mortality rate at 2 years was 7±1%. Five patients died of Indeed, RIC allo-SCT represents an attempt to harness the veno-occlusive disease of the liver. Overall leukemia-free immune graft-versus-tumor (GVT) effect while attempting to survival and relapse incidence at 2 years did not differ control or overcome toxicity. The work of different pioneering significantly between the 815 patients transplanted in the first groups rapidly proved that this approach is feasible in several complete remission (52±2% and 40±2%, respectively) and disease settings or patients’ categories, and had the added the 137 patients transplanted in the second complete benefit of expanding the transplant option to patients who are remission (58±5% and 35±5%, respectively). Cytogenetic ineligible for standard myeloablative allo-SCT. Currently, an risk classification and age were significant prognostic factors increasing number of studies are addressing the specific role for transplant outcomes. The 2-year leukemia-free survival was and potential benefits of RIC allo-SCT versus other treatment 63±4% in patients with good risk cytogenetics, 52±3% in strategies. However, the RIC approach proved to be much those with intermediate risk cytogenetics, and 37±10% more complex than originally thought. in those with poor risk cytogenetics (P ¼ 0.01). Patients S97 r50 years old had better overall survival (77±2% versus reduce the risk of disease recurrence broadly consist of 56±3%; Po0.001), leukemia-free survival (61±3% versus intensification of the conditioning regimen, without a 45±3%; Po0.001), relapse incidence (35±2% versus 45±3%; concurrent increase in toxicity, and optimisation of a graft- Po0.005), and non-relapse mortality (4±1% versus 10±2%; versus-leukaemia (GVL) effect. The great majority of patients Po0.001) than older patients. The combination of intravenous who are destined to relapse post-transplant do so within the busulfan and high-dose melphalan was associated with the first 12 months post-transplant and consequently strategies best overall survival (75±4%). These results suggest that the aimed at augment a GVL effect must be implemented early if use of intravenous busulfan simplifies the autograft procedure they are to be of clinical relevance. Epigenetic therapies, such and confirm the usefulness of AutoSCT in AML. As in as DNA methyltransferase inhibitors have been shown to up- allogeneic transplantation, veno-occlusive disease is an regulate the expression of epigenetically silenced putative uncommon complication after an autograft using intravenous tumour antigens and also hasten T regulatory cell reconstitu- busulfan. Based on these and other recently published data, tion post allograft. In a recent EBMT ALWP study the DNMTi the role of AutoSCT in acute leukemia should be revisited. azacitidine (AZA) was shown to possess significant clinical Disclosure of Interest: None declared. activity in a cohort of 272 patients with AML and myelodys- plasia who had relapsed post alloSCT. Predictors of response to AZA included time to relapse post-transplant and presenta- WP004 tion karyotype. A scoring system including time to relapse, Strategies to prevent relapse following alloSCT for acute presentation karyoytpe and marrow blast percentage at the leukemia—the 2015 perspective time of relapse predicts CR rate and 2 year overall survival (OS) C. Schmid1,*, M. Labopin2,3, A. Mailhol2,4, E. Polge2,3, A. Nagler5 after AZA salvage. A number of small studies have demon- 1Department of Haematology and Oncology, Klinikum Augsburg, strated adjunctive AZA can be administered early after alloSCT University of Munich, Augsburg, Germany, 2Service d’He´matolo- and we therefore prospectively studied the impact of post- gie et The´rapie Cellulaire, Hopital Saint Antoine, 3Acute Leukemia transplant AZA on the incidence of disease relapse and GVHD Working Party of EBMT, 4Leukemia Working Party of EBMT, Paris, in 37 adults with high risk AML undergoing allogeneic SCT France, 5Hematology Division, Tel-Aviv University, Sheba Medical using an alemtuzumab based reduced intensity conditioning Center, Tel-Hashomer, Israel regimen. AZA was administered at a dose of 36 mg/m2 for five consecutive days at four weekly intervals until 12 months post- Introduction: Relapse after allogeneic stem cell transplanta- transplant. AZA was
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