ALBERT

Description: Introduction Deep molecular response (DMR) are now highly desirable goals in the treatment of CP-CML, especially in the front-line setting, because it can lead to a definitive treatment-free remission (TFR). However, such a goal is difficult to attain and does not concern the majority of patients (pts), but currently the precise number of pts able to access to TFR is unknown. Aims We aim to determine the number or newly diagnosed CP-CML pts reaching DMR, stable DMR, and access to TFR, on Imatinib (IM, Glivec®) first-line. Methods We retrospectively analyzed in an observational study, a cohort of newly diagnosed CP-CML pts treated with IM first-line 400 mg daily alone in our 3 reference centers between 2000→2018. All pts were followed according to the ELN recommendations 2006, 2010 and 2013. Clinical data were extracted from medical files, and responses (hematologic, cytogenetic, molecular) were analysed according to standard methods. Molecular results were standardised according to the ELN/Eutos programs since 2003, and were all expressed as BCR-ABLIS in %. DMR have been defined according to the ELN (NCP. Cross et al., Leukemia 2015). Stability of DMR has been defined as a stable if ≥2 years at least on 4 datapoints. TFR has been proposed to pts presenting the only current recommended criteria: MR4.5 ≥2 years at least on 4 datapoints [(Rea et al., Cancer 2018)], in the 3 centers involved, within clinical trials, pioneered in our country, or now as a clinical routine recommendation. Loss of MMR was the trigger for TKI resumption after IM cessation for TFR. Overall survival (OS), progression-free survival (PFS), failure-free survival (FFS, defined as progression to advanced phases death, loss of CHR, CCyR, or MMR, discontinuation of IM for toxicity, primary cytogenetic resistance) were analysed since IM initiation in intention-to-treat. Results Four hundred and eighteen pts have been included in this study, with a median age of 60.7 (48-70) years at diagnosis, with 57% males and 43% females. Sokal score (n=401) was low in 32%, intermediate in 51% and high in 17%. ACA were present at diagnosis in 5.5% of the pts (NA in 1.44%). Major BCR transcripts were found in 98% of pts, and atypical transcripts in 1.9%. CHR was reached in a median of 1 (0.85 to 1.64) month of IM,

Description: Acquired molecular abnormalities (mutations or chromosomal translocations) of the RUNX1 transcription factor gene are frequent in acute myeloblastic leukemias (AMLs) and in therapy-related myelodysplastic syndromes, but rarely in acute lymphoblastic leukemias (ALLs) and chronic myelogenous leukemias (CMLs). Among 18 BCR-ABL+ leukemias presenting acquired trisomy of chromosome 21, we report a high frequency (33%) of recurrent point mutations (4 in myeloid blast crisis [BC] CML and one in chronic phase CML) within the DNA-binding region of RUNX1. We did not found any mutation in de novo BCR-ABL+ ALLs or lymphoid BC CML. Emergence of the RUNX1 mutations was detected at diagnosis or before the acquisition of trisomy 21 during disease progression. In addition, we also report a high frequency of cryptic chromosomal RUNX1 translocation to a novel recently described gene partner, PRDM16 on chromosome 1p36, for 3 (21.4%) of 14 investigated patients: 2 myeloid BC CMLs and, for the first time, 1 therapy-related BCR-ABL+ ALL. Two patients presented both RUNX1 mutations and RUNX1-PRDM16 fusion. These events are associated with a short survival and support the concept of a cooperative effect of BCR-ABL with molecular RUNX1 abnormalities on the differentiation arrest phenotype observed during progression of CML and in BCR-ABL+ ALL.

Description: Abstract 1115 Poster Board I-137 Introduction Nilotinib, a potent and highly selective BCR-ABL kinase inhibitor, is approved for the treatment of patients (pts) with Philadelphia chromosome-positive chronic myelogeneous leukemia (Ph+ CML) in chronic phase (CML-CP) or accelerated phase (CML-AP) who are resistant or intolerant to prior therapy, including imatinib. The ENACT study is a Phase IIIb, open-label, multicenter study that evaluated the efficacy and safety of nilotinib in adult pts with imatinib-resistant or intolerant CML in a clinical practice setting outside of a registration program. It is the largest single source of efficacy and safety information of any available tyrosine kinase inhibitor (TKI) in CML. Data from ENACT are used to characterize the patterns and management of adverse events (AEs) in nilotinib pts with imatinib-resistant or -intolerant CML-CP or -AP. Methods Pts received nilotinib 400 mg twice daily. Safety assessments included monitoring for all AEs and cardiac procedures. The first occurrence of the following AEs were selected on the basis of the following criteria: 1) the most frequently reported hematologic or biochemical laboratory abnormalities; or 2) identified by participating investigators as AEs of interest that may lead to study drug discontinuation: thrombocytopenia, neutropenia, hyperglycaemia, elevated lipase, elevated amylase, hyperbilirubinaemia, elevated alanine transaminase (ALT), and elevated aspartate transaminase (AST). There were no differences observed between the pattern of management between AEs suspected and regardless of study drug relationship as well as all grades vs. grade 3/4. For this reason this analysis covers management of grade 3/4 AEs suspected of study-drug relationship including duration and subsequent management. The following actions taken were reported by the treating physicians: study drug dose adjusted or temporarily interrupted, non-drug therapy given, no action taken, study drug permanently discontinued, concomitant medication taken or hospitalization/ prolonged hospitalization. More than one action was allowed to be selected. Results The AEs experienced by 1,603 pts (1,422 CP and 181 AP) were generally identified during nilotinib treatment and lasted for short durations. The number of the grade 3 and 4 AEs in CP and AP, median time from start of treatment and median duration are reported in Table. For all included AEs, the overall most common action taken for the first occurrence was dose adjustment or temporary interruption with the exception of hyperglycaemia which was most often managed by treatment with concomitant medications (8/11 of hyperglycaemia AEs in CP and 1/2 in AP). In the majority of the biochemical abnormalities other than hyperglycaemia there was no additional action taken. 49/308 (16%) events of thrombocytopenia in CP pts (9 in AP) were managed by non-drug therapy. 31/204 (15%) events of neutropenia in CP pts were managed by concomitant medication (6/33 events in AP). Permanent discontinuation of study drug was infrequently observed (number of pts in CP; AP): thrombocytopenia (25; 7), neutropenia (15; 2), hyperglycaemia (1; 0), elevated lipase (3; 0), elevated amylase (0; no pts), hyperbilirubinaemia (2; 0), elevated ALT (3; 0), and elevated AST (1; 0). Conclusions Based on a large cohort of 1,603 nilotinib pts with CML-CP and CML-AP, nilotinib is well-tolerated. Most study drug-related grade 3/4 AEs could be managed by temporary treatment interruption or dose adjustment, such that permanent discontinuation of study drug due to AEs was infrequent. The only events requiring concomitant medication administration or non-drug therapy were thrombocytopenia, neutropenia, hyperglycaemia and hyperbilirubinaemia. The AE profile observed was predictable and similar to that seen in registration trial. Disclosures le Coutre: Novartis: Honoraria, Research Funding; BMS: Honoraria. Ceglarek:Novartis Pharmaceuticals: Honoraria. Turkina:Novartis Pharmaceuticals: Honoraria. Kim:Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Wyeth: Research Funding. Shen:Novartis Pharmaceuticals: Honoraria. Smith:Novartis Pharmaceuticals: Honoraria. Rizzieri:Novartis Pharma: Honoraria, Research Funding, Speakers Bureau. Szczudlo:Novartis: Employment. Berton:Novartis Pharmaceuticals: Employment. Wang:Novartis Pharmaceuticals: Employment. Dial:Novartis Pharmaceuticals: Research Funding. Nicolini:Novartis Pharma: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Chemgenex: Honoraria, Speakers Bureau.

Description: Abstract 2201 Poster Board II-178 Introduction: Nilotinib, a potent and highly selective BCR-ABL tyrosine kinase inhibitor (TKI), is approved for the treatment of patients (pts) with Philadelphia chromosome-positive chronic myelogeneous leukemia (Ph+ CML) in chronic phase (CP) and accelerated phase (AP) who are resistant or intolerant to prior therapy, including imatinib. The ENACT study is a Phase IIIb, open-label, multicenter study that evaluated the efficacy and safety of nilotinib 400 mg twice daily in 1,422 pts with CP who were resistant and/or intolerant to imatinib. It is the largest single source of efficacy and safety information of any available TKI in CML. Study results are presented for all CP pts as well as 2 subpopulations: (1) 2nd-line pts who received imatinib as the only prior CML therapy with no prior exposure to other therapy including interferon (IFN), busulfan and ara-c; and (2) pts with 6- and 12-month suboptimal cytogenetic response (SoR) to prior imatinib therapy. Methods: In addition to all CP pts, ENACT study results are presented for 2 subpopulations, defined as follows. (1) Pts who received nilotinib as 2nd-line therapy received only imatinib (hydroxycarbamide was allowed) prior to nilotinib. Pts with any other therapy, including interferon, busulfan and ara-c were excluded. (2) Pts with 6- or 12-month cytogenetic SoR to imatinib were identified as: a) received imatinib as 1st-line therapy within 12 months of CML diagnosis; b) did not have imatinib resistance; and c) met ELN criteria for cytogenetic SoR (

Description: Background: Prior clinical trials demonstrated that 33-61% of patients with CML maintain disease control following TKI discontinuation in the 1st line and beyond (Thielen, Eur J Cancer. 2013; Mahon, Lancet Oncol. 2010; Hochhaus, ASCO 2016; Hughes, ASCO 2016; Imagawa, Lancet Haematol. 2015). Patients who relapsed after discontinuation regained major molecular response (MMR) upon retreatment. Dasatinib, a 2nd generation TKI, induces fast and deep molecular responses, making it an effective option for patients in view of a possible TFR. Here, we report interim results from the phase 2 DASFREE study, investigating TFR with dasatinib in the 1st and 2nd line settings. Methods: DASFREE (CA180-406/NCT01850004) is a phase 2 open-label, single-arm study in adults with CML-CP who were on dasatinib for ≥2 yr as 1st line or subsequent therapy, had confirmed dasatinib-induced DMR (defined as MR4.5, BCR-ABL1 ≤0.0032% [IS]) for ≥1 yr prior to enrollment, and achieved a 1-log reduction in BCR-ABL1 from baseline within 3-6.5 mo of starting dasatinib. Prescreening for MR4.5 was done at a local lab, with confirmation at a central lab twice over a 3-mo interval prior to dasatinib discontinuation (screening phase). BCR-ABL1 was monitored centrally after treatment discontinuation every mo in the 1st yr, then every 3 mo. If loss of MMR occurred, patients resumed dasatinib at the previous dose. The primary endpoint is MMR rate at 1 yr after dasatinib discontinuation. Secondary endpoints include kinetics of loss of response, event-free survival (EFS; no loss of MMR), relapse-free survival (RFS; no loss of MMR, complete cytogenetic response, or complete hematologic response, or progression to accelerated/blast phase CML), progression-free survival, and overall survival. Exploratory analyses include frequency of adverse events (AEs) after discontinuation and during dasatinib treatment, and molecular response rates after reinitiating dasatinib. All patients will be followed for up to 5 yr. This analysis reflects a planned interim assessment of patients followed for TFR for ≥1 yr. Results: Currently, 71 patients are enrolled out of 79 planned. Thirty patients (14 male; median age 51 yr [range: 29-76]; Sokal scores: 60% low, 27% intermediate, 3% high, 10% unknown) followed for ≥1 yr after dasatinib discontinuation were included in this interim analysis. MMR rate at 1 yr following discontinuation was 63% (95% CI: 46-81). EFS rate at 1 yr following discontinuation was 63% (95% CI: 44-78; Figure). RFS rate at 1 yr following discontinuation will be presented. Eleven of 30 patients lost MMR, with a median time to loss of MMR of 4 mo (range: 1-8). Median time on dasatinib prior to discontinuation was 40 mo (range: 26-114) for patients who lost MMR and 55 mo (range: 31-87) for patients who retained MMR. Eleven patients who lost MMR restarted dasatinib therapy: 10 regained MMR, and 1 patient chose to restart therapy at a nonstudy site, discontinued study, and was lost to follow-up. The kinetics of molecular relapse, the number of patients that regained DMR, and the time to regain MMR or DMR will be presented. No transformation events or deaths were observed at the time of this analysis. After discontinuation, 5 patients had musculoskeletal AEs; in 2 patients (with 3 events) these AEs were attributed to withdrawal from dasatinib by investigators. Additional AEs following discontinuation included hypertension (17%) and skin disorders (13%). For patients who restarted dasatinib, AEs were consistent with the known safety profile, and none of the on-treatment AEs resulted in discontinuation. Conclusions: This interim analysis of the first 30 patients enrolled in DASFREE demonstrated patients with dasatinib-induced DMR treated in the 1st and 2nd line had high rates of success at maintaining remission after treatment was discontinued (63% MMR and EFS at 1 yr), and there was rescue of molecular response in all patients once dasatinib was reinitiated. There is a suggested correlation between time on dasatinib prior to discontinuation and maintaining MMR. Dasatinib withdrawal appears to be tolerable, as there was a low incidence of withdrawal symptoms. These data build upon the growing body of evidence supporting the feasibility of TFR in patients with CML-CP and demonstrate that with frequent monitoring of BCR-ABL1, patients treated with dasatinib in the 1st and 2nd line can successfully discontinue treatment. Longer-term follow-up is ongoing. Figure Figure. Disclosures Shah: Bristol-Myers Squibb, ARIAD, Pfizer, Daiichi-Sankyo, Plexxikon: Research Funding. Paquette:Bristol-Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Ariad: Research Funding, Speakers Bureau. Müller:Ariad, BMS, Novartis, Pfizer: Honoraria; Ariad, BMS, Novartis, Pfizer: Consultancy; Institute for Hematology and Oncology, IHO GmbH: Employment, Equity Ownership. Saussele:Novartis, BMS, Ariad, Pfizer: Honoraria; Novartis, BMS: Research Funding. Garcìa-Gutiérrez:Novartis, BMS, Ariad and Pfizer: Consultancy; Novartis, BMS, Ariad and Pfizer: Research Funding. Nicolini:Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria. Mauro:ARIAD: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria. Mahon:Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria, Research Funding; Ariad: Honoraria. Rea:Novartis: Honoraria; Ariad: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Martin-Regueira:Bristol-Myers Squibb: Employment. Subar:Bristol Myers-Squibb: Employment. Li:Bristol-Myers Squibb: Employment. Lipton:BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.

Description: Background: ENESTop (NCT01698905) is an ongoing, single-arm, phase 2 study evaluating treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) who achieved sustained molecular response 4.5 (MR4.5; BCR-ABL1 ≤ 0.0032% on the International Scale [BCR-ABL1IS]) on second-line nilotinib (NIL). In the primary analysis, 57.9% (95% CI, 48.8%-66.7%) of pts who stopped NIL maintained TFR (no loss of major molecular response [MMR; ie, BCR-ABL1IS 〉 0.1%], confirmed loss of MR4 [ie, consecutive BCR-ABL1IS 〉 0.01%], or treatment reinitiation) at 48 weeks. Adverse events (AEs) were reported in 73.8% of pts during the first 48 weeks of TFR vs 77.0% during the year prior to stopping treatment. The incidence of musculoskeletal pain-related AEs was higher during TFR (42.1% vs 14.3%). To assess the potential effect of stopping NIL on quality of life (QOL), pt-reported outcomes were assessed before and during TFR. Methods: ENESTop enrolled adult pts with CML-CP with ≥ 3 years of prior tyrosine kinase inhibitor (TKI) therapy (〉 4 weeks of imatinib [IM], then ≥ 2 years of NIL). Pts must have achieved sustained MR4.5 on NIL after switching from IM. Enrolled pts entered a 1-year NIL treatment consolidation phase; those without confirmed loss of MR4.5 (ie, consecutive BCR-ABL1IS 〉 0.0032%) entered the TFR phase and stopped NIL. Pts with loss of MMR or confirmed loss of MR4 during the TFR phase reinitiated NIL. QOL was assessed via questionnaires completed by pts at specified time points. The MD Anderson Symptom Inventory for CML (MDASI-CML) questionnaire assessed, for a defined set of symptoms, the levels of severity and interference with daily life on a scale of 0 to 10, with 0 being the lowest level. The EQ-5D-5L questionnaire assessed problems experienced by pts (no, slight, moderate, severe, or extreme [ie, interfering with functioning] problems) in 5 dimensions: mobility, self-care, usual activities, anxiety/depression, and pain/discomfort; additionally, overall level of health was assessed on a scale of 0 to 100 using the EQ VAS, with 0 being the lowest level. Results: Of 163 enrolled pts, 126 met the criteria for stopping NIL in the TFR phase; of these 126, 53 had loss of MMR or confirmed loss of MR4, of whom 51 reinitiated NIL. Among pts who completed each questionnaire at week 48 of the consolidation phase, week 12 of the TFR phase, or week 48 of the TFR phase, mean MDASI-CML severity scores were 1.7, 1.5, and 1.2, respectively; mean MDASI-CML interference scores were 1.7, 1.6, and 1.4, respectively; and mean EQ VAS scores were 82.2, 78.8, and 82.3, respectively (Table). Among pts with sustained TFR and scores at both week 48 of the consolidation phase and week 12 or 48 of the TFR phase, minimal changes were observed in MDASI-CML and EQ VAS scores during TFR vs week 48 of the consolidation phase. Among pts who reinitiated NIL, mean MDASI-CML severity and interference scores and mean EQ VAS scores at 24 weeks after the start of retreatment were 1.6, 1.5, and 78.8, respectively; changes in scores between week 24 after treatment reinitiation and week 48 of the consolidation phase were minimal among pts with scores at both time points. Among pts who completed the EQ-5D-5L questionnaire, the proportions who reported problems (any level of severity) in the 5 dimensions were generally similar across time points, although problems with mobility and pain/discomfort were more common during TFR vs week 48 of the consolidation phase, particularly at week 12 of the TFR phase (Table). Conclusion: Changes in QOL after stopping NIL, as assessed using these questionnaires, were minimal. This may be related to pts having a relatively high QOL prior to stopping treatment given that they had tolerated ≥ 3 years of TKI therapy, including ≥ 2 years of NIL, prior to enrollment. Despite the higher incidence of musculoskeletal pain-related AEs observed during TFR (42.1% vs 14.3%), the overall QOL was generally similar between the TFR and consolidation phases. This suggests that these AEs did not have a significant negative impact on QOL. Longer follow-up in ENESTop will be needed to further evaluate trends in QOL after stopping second-line NIL. Disclosures Mahon: NOVARTIS PHARMA: Honoraria, Research Funding; BMS: Honoraria; ARIAD: Honoraria; PFIZER: Honoraria. Boquimpani:BMS: Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Takahashi:Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; BMS: Honoraria. Shuvaev:Novartis pharma: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Ailawadhi:Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy. Lipton:Novartis: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Turkina:Novartis Pharma: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Moiraghi:NOVARTIS: Speakers Bureau; BMS: Speakers Bureau. Nicolini:Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria. Sacha:Pfizer: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Adamed: Consultancy, Honoraria. Kim:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ILYANG: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Fellague-Chebra:Novartis: Employment. Acharya:Novartis Healthcare Pvt. Ltd.: Employment. Brandt:Novartis: Employment. Gnanasakthy:Novartis: Consultancy, Equity Ownership, Research Funding. Jin:Novartis: Employment, Equity Ownership. Hughes:Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: Background: In the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT), donor and/or recipient cytomegalovirus (CMV) seropositivity is still associated with a lower overall survival (OS) despite current strategies to decrease CMV disease incidence. However, recent studies have suggested that early CMV reactivation decreases the risk of disease relapse after allo-HSCT. Other reactivations like Epstein-Barr virus (EBV) and BK virus (BKV) with an adverse impact on OS have not been evaluated in the same context. The aim of our study was to evaluate the impact of early CMV, EBV and BK-V reactivation after allo-HSCT on the relapse incidence. Patients and methods: We evaluated 292 allo-HSCT in adults recipients with acute myeloid leukemia (n=114), acute lymphoid leukemia (n=60), multiple myeloma (n=41), non-Hodgkin lymphoma (n=27), myelodysplastic syndrome (n=18), Hodgkin's disease (n=14), myeloproliferative neoplasms (n=13), and chronic lymphoid leukemia (n=7) treated at the University Hospital Centre of Lyon between years 2008 and 2013. At transplantation, 77% of patients were in complete response (CR) or chronic phase and 23% in less than CR. One hundred and thirty-two (45%) patients received bone marrow, 119 peripheral blood stem cells, 41 cord blood, conditioning regimen was myeloablative (MAC) in 163 (56%) cases. Antithymocyte globulin was used in conditioning regimen for GVHD prophylaxis in 70% of patients. After allo-HSCT, patients underwent twice weekly screening for CMV and EBV reactivation using a RQ-PCR until day 90 whereas BKV was screened in case of urinary symptoms and/or hematuria. CMV and EBV reactivation was defined as any level of DNAemia ≥ 1000 copies/mL, the diagnosis of BKV reactivation was relied on the presence of hemorrhagic cystitis with positive BKV viruria and/or viremia. Results: In the global population, the cumulative incidence of CMV, EBV, BKV reactivations by day 90 was 29.1% (95%CI: 24-34), 33.9% (95%CI: 29-39), and 16.8% (95% CI: 13-21) with a median occurrence time after allo-HSCT of 40 days, 41 days, and 36 days respectively. The cumulative incidence of relapse at 2 and 4 years was 26% (21-31%) and 29% (24-34%) respectively with a cumulative incidence of NRM of 16% (12-21) and 24% (19-29) respectively. Among the 99 patients with EBV reactivation, 32 (32.3%) needed treatment with rituximab. In univariate analysis, disease status at transplantation and type of conditioning were significantly impacting relapse incidence. In multivariate analysis, when adjusting on type of conditioning regimen and disease status at transplantation, patients with CMV reactivation had significantly lower rate of relapse, HR=0.81, 95% CI: 0.67-0.98, p=0.03, this was the same for those with EBV reactivation, HR=0.86, 95%CI: 0.72-1), p=0.05, as well as for BKV, HR=0.79, 95%CI: 0.66-0.95, p=0.012. In addition, we found that patients who had a simultaneous reactivation of CMV and EBV were at higher risk of relapse, HR=4.2, 95%CI: 1.9-8.1, p=0.002. Conclusion: We confirmed the positive impact viral reactivation after allo-HSCT on relapse incidence, which could be explained as a stimulation of both function and amplification of NK compartment. Our finding about viral co-reactivation that includes EBV with a higher risk of relapse should be further explored and carefully interpreted as this might come from EBV treatment by rituximab that impairs the immunological system by impacting the GVL effect and therefore leads to more relapse. Disclosures Michallet: Octapharma: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy; Novartis: Research Funding.