ALBERT

Description: Abstract 483 Background. There is an increasing interest in the development of pharmacological agents able to modulate hepcidin, the peptide hormone that critically regulates iron metabolism. In particular, hepcidin antagonist may have a therapeutic role in the anemia of chronic diseases, where hepcidin levels are often increased by pro-inflammatory cytokines. We previously demonstrated that heparin is a potent inhibitor of hepcidin expression in hepatic cell lines, probably by interfering with BMP/HJV/SMAD signalling, and that it was also effective in reducing hepcidin expression in mice (Poli M, Blood 2011; 117:997–1004). Since the therapeutic use of heparin for hepcidin modulation is hampered by its strong anticoagulant activity, we were interested in evaluating modified heparins without such activity. Methods. Heparins modified to inactivate the antithrombin binding site, with different molecular weight and degree of sulfation, were supplied to hepatic cell lines and mice to evaluate their potential modulation of hepcidin expression. We analysed their interference with the BMP/SMAD signalling, as well as serum hepcidin levels in mice by mass spectrometry. Results. Over 20 modified heparins were initially screened by evaluating their dose-dependent suppression of hepcidin expression before and after BMP induction. All of them showed a certain degree of anti-hepcidin activity, with two glycol-split molecules being as potent as classical unfractionated heparin. These two molecules suppressed BMP/SMAD signalling in HepG2 cells at pharmacological concentrations with maximum inhibition after 6 hours. In mice, treatments with 20 or 60 mg/Kg did not affect coagulation but strongly reduced liver pSMAD, hepcidin mRNA and serum hepcidin. Again, the maximum effect on liver hepcidin expression was observed 6 hours after the injection. This effect was observed also in conditions of high hepcidin caused by experimental inflammation or iron overload. Conclusions. Some non-anticoagulant heparins have strong anti-hepcidin activity both in vitro and in vivo, and may represent promising hepcidin antagonist with potential therapeutic applications. Disclosures: No relevant conflicts of interest to declare.

Description: T-cell depletion of allogeneic hematopoietic stem cell graft (HSCT) represents the most powerful approach to prevent graft-versus-host disease (GvHD), thus allowing to overcome HLA barriers in patients with high risk malignancies, lacking a conventional donor. We hypothesized that early add-back of suicide-gene transduced donor lymphocytes (TK cells) to leukemic patients undergoing haploidentical HSCT (haplo-HSCT) could provide early immune-reconstitution and selective control of GvHD. In a phase II clinical trial (protocol MMTK007), 17 of 29 enrolled pts, (median age 52), received add-backs of 10^7/kg TK cells 42 days after haplo-HSCT. TK cells engraftment, observed in 14 patients, was necessary and sufficient for a rapid and effective immunereconstitution (IR), with a median of 144 (101–336) CD3+, 59 (28–149) CD4+ and 86 (52–279) CD8+ cells/mcl at day 100 after HSCT. Accordingly, engraftment of TK cells was tightly correlated with clinical outcome: while 3/3 pts who failed TK cells engraftment died of infections, only 1/14 TK engrafted patients died from infections (last event at day +166). As shown in Table I, the immune repertoire of treated patients improved significantly at 6 months post transplant and normalized completely in 12 months. High numbers of T cell precursors specific for CMV and EBV were detected at immune reconstitution (median of 86 and 69 gIFN specific spots/10^5 PBMC respectively) and predicted subsequent freedom from viral reactivation (p=0.002). Six pts developed acute (GvHD), (grade I to IV) that was always completely abrogated by the suicide system. Overall survival of TK cells treated patients is 50% at three years. These results indicate that TK-DLI abolish late mortality after CD34+ haplo-SCT in adults. A phase III multicentric study will start in 2007 to validate prospectively the advantage of TK-DLI in haplo-SCT.

Description: Abstract 3707 Poster Board III-643 Introduction response to salvage chemotherapy prior to high–dose therapy (HDT) is of major prognostic concern in relapsed/refractory HL. FDG-PET is able to distinguish between persistent disease and fibrosis/necrosis and has thus become the mainstay to define clinical response in this setting (Cheson et al, JCO 2007). The value of FDG-PET in this subset of patient is less well established. IGEV chemotherapy has shown very encouraging results as induction therapy in refractory/relapsed HL (Santoro et al, Haematologica 2007). Aims to retrospectively evaluate the predictive value of PET in pts with relapsed/refractory HL receiving IGEV and HDT. Methods seventy-two multicentric cases with refractory/relapsed HL who had completed IGEV x 4 courses and HDT between 01/98 and 05/07 were reviewed. FDG-PET evaluation was performed before HDT and, according to revised Cheson criteria, complete remission (CR) was defined as negative FDG-PET, independently from the presence of residual masses at CT scan. Univariate analysis was performed considering FDG-PET as well as other usually evaluated prognostic factors. Results patient characteristics: M/F 30/42, median age 33 (range 16-71), Nodular sclerosis 61 (85%), refractory 28 (39%), relapsed 44 (61%), one previous regimen 60 (83%), B symptoms 18 (25%), bulky disease 7 (10%), extranodal disease 32 (44%), previous radiotherapy 39 (54%). After induction, 36 pts (50%) received single (with BEAM as conditioning regimen ), and 36 (50%) tandem HDT (with melphalan as first and BEAM as second conditioning). After IGEV, on the basis of PET 47 pts (65%) were classified as complete remission (CR), 21 (29%) as partial remission (PR) and 4 (6%) did not respond. Ten of the 47 PET negative pts, and 18 of the 25 PET positive pts relapsed. With a median follow up 48 months, the 3-year PFS was 80% vs 25% for patient with negative vs positive PET respectively (HR 5.7 no CR vs CR - CI 95%: 2.6-12.4). The 3-year overall survival (OS) was 91% vs 56 % for patient with negative vs positive PET respectively (HR 7.8 no CR vs CR CI 95%: 2.6-23.7). In univariate analysis, factors influencing the probability of achieving CR to IGEV were disease status (refractory vs relapse) (p.096) and bulky disease at IGEV (p .088). Factor significantly associated with PFS and OS are reported in table. In multivariate analysis only response to therapy, as defined by pre-transplant PET result, maintained significance as prognostic indicator for both PFS (HR 5.7) and OS (HR 7.8). Conclusions these data in homogeneously treated pts with refractory/relapsed HL underline the crucial prognostic relevance of pre-transplant FDG-PET, even overwhelming the impact of disease status at progression. FDG-PET driven trials are highly recommended in this subset of patients. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: An insufficient production of hepcidin, the master regulator of iron metabolism, is recognized as the key pathogenetic feature of HFE-related hereditary hemochromatosis (HH). There is a growing interest in measuring the hepcidin levels, which may improve diagnosis, prognostic evaluation and clinical management of HH. Nevertheless, few investigative tools are available: an immunodot method for urinary hepcidin developed by a single centre (UCLA), not yet ready for large-scale diffusion, and mass spectrometry (MS) based assays, such as surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF-MS). The latter is well suited to small peptides like hepcidin, and can rapidly analyze crude samples with high throughput. Until now, urinary hepcidin has been measured by SELDI-TOF-MS only in small groups of C282Y homozygous patients, the majority of them under phlebotomy treatment. No data are available on C282Y/H63D compound heterozygotes, that can develop a milder clinical form of HH. This study was aimed to measure urinary hepcidin levels by SELDI-TOF-MS in a large group of HH patients. Methods: We used a protocol based on PBSIIc mass spectromer and Normal Phase chips similar to that recently proven successful for semi-quantitative detection of urinary hepcidin. Urinary samples from 30 control subjects were compared to those obtained from 80 HH patients (57 C282Y homozygotes, 23 C282Y/H63D compound heterozygotes). Eighteen C282Y homozygotes and 11 C282Y/H63D compound heterozygotes were analyzed at diagnosis, the remainder during maintenance phlebotomy (at least 30 days from last phlebotomy). Results: C282Y homozygotes had significantly lower urinary hepcidin levels vs. controls either at diagnosis, or after phlebotomy (P 〈 0.05). C282Y/H63D compound heterozygotes had hepcidin levels at diagnosis similar to controls, while the hepcidin:ferritin ratio was significantly decreased (P 〈 0.001) suggesting a relatively inappropriate hepcidin production. Moreover, also in this group means hepcidin levels after phlebotomy were significantly lower than in controls (P 〈 0.001). Samples from 12 randomly selected control subjects were sent to UCLA for duplicate measurement by the immunodot method, yielding a good correlation (r= 0.77; P

Description: T-cell depletion (TCD) of allogeneic stem cells transplantation (HSCT) is the most powerful approach to overcome HLA barriers in patients with high risk malignancies, lacking a conventional donor. However, the prolonged immune deficiency resulting from TCD significantly impairs the outcome of HSCT from a haploidentical family donor (haplo-HSCT). In a phase I-II clinical trial (protocol MMTK007), we showed that the add-back of suicide-gene transduced donor lymphocytes (TK+ cells) provides early immune-reconstitution (IR), crucial to avoid opportunistic infections and disease relapse. While the achievement of an early and sustained IR significantly reduced the incidence of infectious complications and mortality, the kinetic of abatement of viral reactivations differed in different patients, suggesting variability in the repertoire, function and persistence of viral-specific T cells. To gain insights on the activity of the post-transplant immune system, we focused on immune responses to cytomegalovirus (CMV) and Ebstein Barr virus (EBV) as clinical paradigm of an effective immune system. In our trial 29 patients (median age 52y) were transplanted for high-risk leukemia. Seventeen pts received TK-DLI starting at day +42, 14 pts obtained prompt immune reconstitution with CD3+ 〉100/mcl at day +86 (median) from SCT and day +21 from TK-DLI. Twelve/14 experienced CMV reactivation, 3 reactivation/patient (median), each reactivation required 14 days (median) of pre-emptive treatment with foscarnet to achieve a complete clearance; in 2/38 events, a CMV antigenemia persistent during foscarnet treatment was cleared by ganciclovir administration. In this series, the last CMV reactivation requiring pre-emptive treatment happened at day +84 from SCT and day +19 from TK-DLI. Nine/14 experienced EBV reactivation, 1 reactivation/patient (median), 6 patients required treatment with rituximab (375 mg/mq weekly) for 3 cycles (median). In 3 cases we documented EBV lymphoproliferative disease, that were completely controlled with the treatment. The proportion of lymphocytes committed to produce IFN-γ upon CMV or EBV stimulation normalized within the first 3 months post transplant. The analysis of CMV and EBV T-cell response showed a prevalent host-restriction pattern, suggesting active modulation of the T-cell repertoire by the host environment. The TCR-Vβ repertoire progressively changed from oligoclonal into polyclonal and normalized by 1 year after transplant. The progressive acquirement of a protective, host-restricted, anti-viral response, highly correlated with a decline in the occurrence of any infectious event, that were nearly abrogated by 6th month post transplant. The overall cumulative infectious mortality beyond day +100 post transplant was 12,5% in TK treated patients demonstrating the efficacy of this strategy in building a protective immune system.

Description: Patients with chronic hepatitis C (CHC) often have increased liver iron deposits, a condition associated with reduced sustained response to antiviral therapy, more rapid progression to cirrhosis, and development of hepatocellular carcinoma. The hepatic hormone hepcidin is a major regulator of iron metabolism that inhibits iron absorption and recycling from erythrophagocytosis. Hepcidin decrease is a possible pathophysiological mechanism of iron overload in CHC, but studies in humans have been hampered so far by the lack of reliable quantitative assays for the 25-amino acid bioactive peptide in serum (s-hepcidin). Using a recently validated immunoassay (Ganz T, Blood 2008, epub Aug 8), we measured s-hepcidin levels in 82 CHC naïve patients and 57 sex-matched healthy controls with rigorous definition of normal iron status. All CHC patients underwent liver biopsy with histological iron score (according to Deugnier YM, Gastroenterology 1992). S-hepcidin was much lower in CHC than in controls (geometric means with 95% CIs: 33.7, 21.5–52.9 versus 90.9, 76.1–108.4 ng/ml, respectively; P

Description: INTRODUCTION: The phosphatidylinositol 3-kinase (PI3K) pathway is consistently activated in relapsed/refractory Hodgkin lymphoma (HL). Activation of this pathway is critical for transformation and also for the angiogenic switch in malignant cells. Thus, inhibition of PI3K holds the promise of a multistep strategy for tumor inhibition. Expression of the δ and γ isoforms of PI3K is restricted to cells of the hematopoietic system, suggesting that RP6530, a novel PI3K δ/γ Inhibitor, might represent a promising approach in the treatment of lymphomas. The CD30-directed antibody-drug conjugate, Brentuximab Vedotin (BV), has recently been reported to induce a high overall response rate in relapsed/refractory HL, but is associated with limited response duration. Combination therapies aimed at enhancing the anti-tumor activity of BV and eventually reducing its side effects may have significant clinical impact in the treatment of relapsed/refractory HL. Our study aimed at investigating the activity and mechanism(s) of action of RP6530 in combination with BV in preclinical HL models. METHODS: Three HL cell lines, including L-540, KM-H2 and L-428, were used to investigate the effects of RP6530 and BV on cell growth and survival in vitro. Western blotting (WB) was used to assess the effects of RP6530 on both the PI3K/AKT and MAPK pathways. The efficacy and mechanism of action of RP6530/BV combination was finally analyzed in NOD/SCID mice bearing HL cell line xenografts. To analyze tumor vasculature, we performed in vivo biotinylation of vascular endothelial proteins. RESULTS: Inhibition of the PI3K pathway byRP6530 (1.25 - 20 µM) resulted in reduced Akt phosphorylation, decreased cell proliferation (range, 30% to 40%) and induction of apoptosis (range, 30% to 60%) of HL cells. Interestingly, RP6530 treatment also resulted in an early dose-dependent inhibition of ERK1/2 phosphorylation. BV, at clinically achievable concentrations induced a significant growth inhibition (range, 30% to 40%) in all HL cells. Remarkably, when RP6530 was combined with BV at minimal, or mildly inhibitory concentrations, a highly synergistic inhibition in all HL cells was observed. Following a 48 hour exposure, RP6530 (5 μM) and BV (10 ng/ml) synergistically inhibited the mean (±SEM) growth of HL cells (RP6530: 9 ± 3%; BV: 12 ± 3%; RP6530/BV: 26 ± 3%). While single agents induced only 20% HL cell death, combination of RP6530 and BV caused remarkable induction of apoptosis (90%), with Combination Index (CI) as low as 0.003. Consistent with the lack of vascular CD30 expression, caspase-3 staining of L-540 tumor sections failed to detect apoptotic Tumor Endothelial Cells (TECs) in BV-treated tumors while a marked apoptosis of TECs was detected in mice receiving RP6530 alone or the combination therapy. Additionally, a significant increase of tumor necrosis (2-fold increase, P ≤ 0.0001) was detected in mice receiving RP6530/BV as compared to single agents. Apoptosis of TECs resulted also in a significant reduction of tumor vessel density with a 90% decrease of vessel density over controls being observed in mice receiving RP6530 alone. This finding was paralleled by histological observation of severe disruption of the tumor vasculature, which was deficient in capillaries and lacked most of its branches and sprouts. In keeping with the lack of apoptosis in TECs, treatment with BV alone failed to affect L-540 tumor vessel density and vasculature morphology. Furthermore, the combined RP6530 (100 mg/kg/BID/3 weeks) and BV (0.5 mg/kg/q4x4d) treatment significantly reduced the growth of L-540 and KM-H2 nodules, resulting in a mean tumor growth inhibition of 50% (P ≤.0001), compared to single agents. No mice experienced any apparent treatment-related toxicity. CONCLUSIONS: The novel PI3K δ/γ inhibitor RP6530 synergistically enhances the anti-tumor activity of BV by increasing drug-induced cell death and inhibiting tumor angiogenesis in HL cell line xenografts. These data provide a strong rationale for clinical studies using RP6530/BV in combination in refractory/relapsed HL patients and warrants clinical evaluation. Disclosures Viswanadha: Incozen: Employment. Vakkalanka:Rhizen Pharmaceuticals SA: Employment, Equity Ownership.

Description: Abstract 193 No definitive data exist defining the optimal myeloablative and/or immunosuppressive association of Reduced Intensity Conditioning (RIC) for allo-SCT. In this perspective, we report the first prospective comparison between 2 widely used conditioning regimens based on reduced intensity or non-myeloablative approaches. Pts were randomized between FBA (Study A) (Fludarabine (30mg/m2/5 days)+Oral Busulfan (4 mg/kg/d over 2 days)+Thymoglobuline (2.5 mg/kg/1day)) (Post graft immunosuppression (IS): CSA) and FTBI (Study B) (Fludarabine (25mg/m2/day over 3 days)+2 Gy TBI) (Post Graft IS: CSA+MMF). Primary endpoint was one-year overall survival (OS). Inclusion criteria were: hematological malignancies, pts non eligible for myeloablative allo SCT, age between 18 and 65, suitable HLA identical sibling, written informed consent. 139 pts were randomized and treated between 2003 and 2008 (Group FBA: N=69; group FTBI: N=70) at 4 transplant centers. The 2 groups were comparable in term of pts characteristics; Median age 54 (21–65); Male gender: 65%; Diagnosis: acute leukemia 18%; NHL 23%; MM 39% others 20%; Disease status: only 32% of the 139 pts were in CR while 68% had measurable disease (PR and stable disease=60%; refractory disease: 8%). Graft failure was documented in 4 pts (6%) in FTBI group. Cumulative incidences (CI) of grade 〉= 2 aGVHD and cGVHD were respectively: 37% (Group FBA 51%; Group FTBI 26%; p=.003) and 77% (Group FBA 79%; Group FTBI 76%: p=NS). At 1 year, PFS differed (Group FBA 0.68 [0.56 – 0.78]; Group FTBI 0.51 [0.39 – 0.62]; p=0.048) while OS was similar (Group FBA 0.75 [0.63 – 0.84]; Group FTBI 0.74 [0.62 – 0.83]; p=NS). With a median follow-up of 39 months (3–71), 72 pts were alive (Group FBA: 35; Group FTBI: 37: p=NS) with a 5 year OS probability estimate of 0.45 [0.31– 0.57] and 0.49 [0.35– 0.61] for groups FBA and FTBI respectively (p=NS). 53 pts were progression free with a 5 year PFS probability estimate of 0.35 [0.22– 0.48] for group FBA ,and 0.23 [0.10– 0.38] for Group FTBI (p=NS). Median PFS were 26.3 (IC95%:13.6 – 47.3) and 13.1 (IC95% : 7.4 – 25.6) months (mths) in groups FBA and FTBI respectively. More relapses/progressions occurred in group FTBI (p=.005) with a 5 year relapse/progression cumulative incidence (CI) of 0.28 [0.16– 0.40] for group FBA and 0.50 [0.39– 0.60] for Group FTBI. Three pts died from secondary cancers (Group FBA: 1; Group FTBI: 2) and 38 from transplant related causes with a 5 year TRM CI of 0.37 [0.25– 0.49] for group FBA and 0.24 [0.14– 0.34] for Group FTBI (p=0.199). QOL was assessed over a 1-year period with the EORTC QLQ-C30 questionnaire. FBA regimen had a stronger negative impact on patients' QOL during the treatment administration which resolved 80 days after the SCT. Detailed economic analysis was included in the clinical trial. Preliminary evaluation of medical direct costs (conditioning regimen, transfusions, hospitalisations and anti-infectious drugs consumption) demonstrated a crude advantage for the FTBI group (66,711€ vs 42,080€ for the FBA and FTBI groups respectively, p

Description: INTRODUCTION: High-dose salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for refractory/relapsed (R/R) Hodgkin lymphoma (HL). Achieving complete remission (CR) prior to ASCT represents the strongest prognostic factor for R/R HL patients receiving salvage chemotherapy. Therefore, increasing the CR rate prior to ASCT represents a primary goal in these patients. Since Bendamustine monotherapy induces CR in a substantial proportion (25% to 35%) of R/R HL patients, the present phase II study aimed at investigating efficacy and toxicity of a novel salvage regimen combining Bendamustine, Gemcitabine and Vinorelbine (BeGEV) as second-line salvage chemotherapy in patients with relapsed/refractory HL. PATIENTS AND METHODS: HL patients who were refractory to, or have relapsed after one previous chemotherapy line were eligible. The primary endpoint was CR rate after four cycles of therapy. Secondary endpoints were: overall response rate (ORR), stem cell mobilization activity, and toxicity. Progression free survival (PFS) and overall survival (OS) were also evaluated. BeGEV regimen consisted of: Bendamustine (90 mg/sqm, days 2-3), Gemcitabine (800 mg/sqm, day 1 and 4) and Vinorelbine (25 mg/sqm, day 1) every 3 weeks for a total of 4 courses. RESULTS: Between August 2011 and March 2014, 59 consecutive patients with relapsed (46%) or refractory (54%) HL were enrolled. The median age was 33 years (range 18-68). Out of 59 enrolled patients, 43 (73%) achieved a CR and 6 (10%) a partial response (PR) for an ORR of 83%. One case (2%) showed stable disease (SD), while 8 patients (14%) progressed, and 1 (2%) was not evaluable for response. With a median follow-up of 16 months, the 2-year PFS and OS were 51% and 69%, respectively, without significant difference between relapsed and refractory patients. OS was higher for BeGEV-responding (CR+PR) patients compared with those who failed the induction regimen (2-year OS: 86% vs 0%, p

Description: Background: Incidence of most myeloid malignancies increases with age. Although allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative option for most of myeloid diseases, conventional myeloablative regimens are associated with considerable toxicity in older patients and high rate of non-relapse mortality (NRM). Thus, such standard approach is very rarely performed in the setting of older patients. Recent developments and introduction of reduced intensityoxicity (RIC/RTC) and non-myeloablative (NMAC) regimens have allowed the extension of Allo-HSCT to these older patients. This study aims to report our experience of Allo-HSCT in patients 〉 55 years of age. Patients and Methods: From 2005 to 2014, 171 patients 〉 55 years of age with myeloid malignancies underwent first allogeneic HSCT at our center, with a median age of 63 years (56-72 years). Sixty-five patients (38%) had 65 years or more. Data had been double-checked using individual institutional files along with HSCT database of the IPC. Of all patients 117 had AML, 49 had MDS and 5 had MPN. They were conditioned by RIC (120 patients, 70%), RTC (16 patients, 9%) or NMAC (35 patients, 21%) regimens. One hundred and nineteen patients (70%) were transplanted with HLA-identical donor (sibling donor, n=66; unrelated donor; n=53), while 52 patients (30%) received transplantation from alternative donor (mismatched unrelated donor, n=18; cord blood, n=14; haploidentical donor, n=20). We found that 91 patients (53%) have a hematopoietic cell transplantation comorbidity index (HCT-CI) between 0 and 2, while 80 patients (47%) had a HCT-CI ≥ 3. Disease risk index (DRI) was low, intermediate, high and very high in 4 (2%), 108 (63%), 55 (33%) and 4 (2%) patients, respectively. Results: NRM at day+100 and 3 years were 7% and 23%, respectively. Cumulative incidences of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD were 20% and 28%, respectively. With a median follow-up of 32 months (3.3-99.5), 3-years cumulative incidence of relapse (CIR), overall survival (OS) and progression free-survival (PFS) were 32%, 52% and 45%, respectively. Although we found a trend for higher NRM in patients aged above 65 years (〈 65 vs. 〉= 65 years: 20% vs. 28%, p=0.056), no impact of age was found on PFS (〈 65 vs. 〉= 65 years: 44% vs. 46%, p=0.662) and OS (〈 65 vs. 〉= 65 years: 50% vs. 54%, p=0.750). DRI significantly influenced outcome (low + intermediate vs. high + very high: PFS: 53% vs. 28%, p=0.011; OS: 60% vs. 34%, p=0.020) while patients who received NMAC regimens had significantly lower PFS (NMAC vs. RIC vs. RTC: PFS: 26% vs. 50% vs. 50%, p=0.028) and OS (NMAC vs. RIC vs. RTC: PFS: 30% vs. 57% vs. 63%, p=0.031).There were no significant differences of OS or PFS among patients groups classified according to type of donor, sex mismatch, donors' age, donors' sex, donors' CMV antibodies positivity, patients' sex, HCT-CI, disease classification, graft's source or whether they were transplanted before or after 2010. In multivariate analysis model including conditioning type (NMAC vs. RIC vs. RTC), DRI (low + intermediate vs. high + very high), HCT-CI (0-2 vs. 〉=3), patients' age (continuous) and donors' type (HLA-identical vs. alternative donor), high/very high DRI as well as the use of NMAC regimens were independent poor predictive factor associated with higher CIR and shorter PFS (HR, 95%CI=1.77, 1.16-2.72; p=0.009 for DRI; HR, 95% CI=1.87, 1.11-3.13; p=0.018 for NMAC) and OS (HR, 95% CI=1.75, 1.11-2.75; p=0.016 for DRI; HR, 95% CI=1.98, 1.14-3.45; p=0.016 for NMAC). Patient's age was associated with higher NRM (HR, 95% CI=1.10, 1.01-1.19; p=0.027). Conclusion: Our data shows that though aged patients still generally at a higher risk of NRM, Allo-HSCT using adapted conditioning regimen can provide low NRM and prolonged survival. Beyond the feasibility, disease relapse appears as the major issue after Allo-HSCT. To optimize conditioning regimen for older patients may be a viable option to enhance disease control without raising toxicity. Indeed, the development of RIC/RTC regimens may improve overall outcome of older patients suffering from myeloid diseases. In contrast, truly NMAC regimens may provide insufficient disease control. The optimal conditioning intensity in the setting of older patients with myeloid malignancies remains undefined and should be evaluated in further prospective trials. Disclosures No relevant conflicts of interest to declare.