ALBERT

Beschreibung: Introduction: Allogeneic stem cell transplantations (allo-SCT) using alternative donors are increasingly used in patients lacking suitable matched sibling or unrelated donor. Recently, the use of post-transplant cyclophosphamide (CY) has allowed to re-consider first-generation relatives (brother, sister, father, mother, son or daughter) as haplo-identical donors for allo-SCT. Indeed, the incidence of severe acute GVHD is lowered by post-transplant administration of CY, due to the early destruction of putative alloreactive T cells. Still, some patients may not have a suitable relative donor for various reasons such as older age of the parents, no siblings nor children, no cord blood available, or because use of a graft from a first-generation haplo-identical relatives is contra-indicated. The probability of having a haplo-identical donor among siblings is 50% while it is almost 100% when considering both biological parents and offspring. When considering as a potential donor the child of a matched or haplo-identical sibling, the probabilities for the donor to be haplo-identical with the recipient remain 50% and 25%, respectively. Thus, second-generation relative donor (i.e. nephew or niece) may be finally considered as a source of stem cell graft. Methods: Here we report the case of a 61-year old man who received a T-replete haplo-identical allo-SCT with high-dose post-transplant CY from his second-generation relative nephew. In 2010, the patient was diagnosed with ALK- CD30+ anaplastic T-cell lymphoma and received 8 cycles of CHOD allowing to obtain morphologic and metabolic partial response. The patient received an allo-SCT from a sibling matched donor (brother) on November 2010 after an FB2A2 reduced-intensity conditioning regimen but secondary graft failure was rapidly documented in spite of donor lymphocyte infusions. Relapse occurred in September 2014 and brentuximab vedotin was administered each 21 days for seven cycles allowing to obtain a complete morphologic and metabolic response. It was decided to perform a second allograft using a different donor. The patient was childless and no unrelated donor or cord blood units were available. It was thus chosen to ask for donor the son of the matched brother, who was haplo-identical and had no antibodies directed against the patient's HLA specificities. This nephew had a O- blood group and negative CMV serology while the recipient was O+ and CMV+. Results: The second allograft was performed on April 2nd 2015 using the Baltimore (Luznik, BBMT 2008) conditioning regimen with 2 days of post-transplant CY. A megadose of peripheral blood stem cell was administered (14.16x106 CD34+ cells/Kg) at day 0. Neutrophils and platelets recovery (〉50 Giga/L) were achieved as early as days +18 and +33, respectively, with full donor whole blood chimerism (99.8%) at day +30, persisting on day +60 and +100 (both whole blood 99.9%, CD3+ T cells: 99.9%).Grade 2 acute cutaneous GVHD occurred at day +21. The evolution was favorable after initiating corticosteroids at 2 mg/kg/day with tapering thereafter. Not surprisingly, CMV reactivation was documented at day+22, controlled by ganciclovir treatment. Immune reconstitution evaluated at days +30, +60 and +100 showed normal monocyte counts while B lymphocytes were undetectable. NK cells increased from 42/mm3 at day+30 to 453/mm3 at day +60 and 665/mm3 at day +100. Interestingly, after profound lymphopenia within the first 100 days post-transplant, CD8+ T large granular lymphocytes expansion was documented at day + 110. At four months post-transplant, the patient is alive in persistent metabolic remission with no active acute or chronic GVHD nor active infection. His outcomes will be updated for the meeting. Conclusion: T-replete haplo-identical allo-SCT with high-dose post-transplant CY using a second-generation relative donor was feasible allowing for full engraftment and moderate acute GVHD in our patient. This result expands the possibility to find a donor for a selected patient, meanwhile paving the way for using unrelated haplo-identical donor, which could be of interest when considering solid transplantation. Indeed, combining solid organ transplantation and allo-SCT from the same haplo-identical donor may open the door to withdraw immunosuppression in this particular setting, because stable tolerance may be induced, as it has been already reported for kidney transplant (Kawai, NEJM 2013). Disclosures Moreau: Celgene: Honoraria, Other: Adboard; Amgen: Other: Adboard; Takeda: Other: Adboard; Janssen: Other: Adboard; Novartis: Other: Adboard.

Beschreibung: Abstract 3889 During the last decade, the role of Interim 2-[18F]fluoro-2-deoxy-D-glucose emission positron tomography (FDG PET-CT) has increased for Hodgkin's lymphoma (HL) evaluation and it is strongly recommended for both staging and post treatment evaluation. Early treatment response assessment is a challenge for risk-adapted therapy and interim PET-CT has emerged as a powerful prognostic tool to predict treatment outcome, a negative exam predicting a favorable disease-free survival while a positive study a worse prognosis. However, FDG PET response criteria are a matter of ongoing debate. So, the aim of our study was to confirm the prognostic value of interim FDG PET-CT performed after 4 courses of chemotherapy (ABVD) but also to compare the respective performances of the different published criteria: International Harmonization Project (IHP), Gallamini criteria, 5-point scale (Gallamini A et al. Haematologica 2006; 91: 475–481; Juweid ME et al. J Clin Oncol 25:571-578, 2007; Barrington SF et al. Eur J Nucl Med Mol Imaging 2009;36(Suppl. 2):S252; Meignan M et al. Leukemia & Lymphoma, August 2009; 50(8): 1257–1260; Gallamini A, et al. Leuk Lymphoma. 2009 Nov;50(11):1761-4.) Design and methods: From 2002 to 2006, newly diagnosed patients with HL who underwent interim PET-CT after 4 courses of ABVD were eligible for the purpose of the present study. Treatment strategy after 4 courses of ABVD was then adapted according to prognostic factors at diagnosis and interim PET-CT result. PET images were interpreted prospectively visually by at least two nuclear medicine physicians with expertise in lymphoma imaging with the criteria used before 2005: negative result was defined as no residual uptake above local background. All other findings were considered as positive. Using these evaluation criteria, interim PET positive patients who were not in CR on CT underwent autologous stem cell transplantation. Interim PET positive patients who reached CR on CT and interim PET negative patients received additional courses of ABVD (patients with advanced HD or bulky disease at diagnosis) or radiotherapy alone (stage I or II without bulky disease). Retrospectively and for the purpose of the present study, interim PET results were interpreted using the more recent criteria (Gallamini criteria, IHP criteria and 5-point scale method) Results: 90 patients were included. Median age at diagnosis was 34.4 (16-71). 49% of the patients presented with B-symptoms and 50% had stage III-IV disease. According to initial criteria, 31 patients had a positive interim PET result. Among these patients, 28 underwent ASCT. Fifty-nine patients had a negative interim PET-CT. Six of 31 patients with positive interim PET-CT and 7 of 59 patients with negative interim result presented treatment failure. Thus, the negative predictive value (NPV) and positive predictive value (PPV) for predicting 2 years progression free survival (PFS) was 95% and 16%, respectively. Retrospectively, interim PET-CT was analyzed according to different recent published criteria using mediastinum and liver background as threshold for positivity. With these criteria, NPV remained very high (from 95% to 96%). However, the PPV increased from 25% to 55% according to the threshold used. Taken together, the statistical analysis revealed that Interim PET-CT was significantly correlated with PFS only for two methods: the Gallamini criteria and the 5-point scale method. Conclusion: The first part of our study using the criteria used before 2005 shows the high NPV of interim PET-CT for predicting treatment outcome in HL. However, better prognostic values are obtained by using higher threshold for positivity such as liver background even after 4 cycles of ABVD. Indeed, our analysis underscores the better results reached by the Gallamini criteria and 5-point scale methods. The better method to predict PFS was obtained by the 5-point scale (scores 1, 2, 3 and 4 were classified as negative while only score 5 was classified as positive) showing a PPV and NPV of 55% and 96%, respectively. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Introduction: Recently, theuse of high-dose post-transplant cyclophosphamide (PTCY) has contributed to reconsider T-replete haplo-identical allo-SCT because of the lower incidence of severe graft-versus-host disease (GVHD) observed in patients. However, the influence of PTCY on early outcomes has been poorly studied so far, especially in comparison to the standard use of anti-thymoglobulin (ATG) as GVHD prophylaxis. Patients and Methods: This retrospective study was conducted at the University Hospital of Nantes with the aim to compare the incidence of early outcomes (engraftment, neutrophils and platelets recovery, viral infections (HHV-6, CMV, EBV, BKv, ADV), acute GVHD, relapse or deaths and day+100 non-relapse mortality (NRM)) between patients receiving either PTCY (n=30) or ATG (n=46) as part of GVHD prophylaxis for a RIC allo-SCT. In the PTCY group, RIC was the Baltimore regimen (Luznic, BBMT 2008) in 17 patients while 9 patients received clofarabine instead of fludarabine because of a myeloid malignancy and 4 patients a sequential approach. In this group, 6 and 24 patients received 1 or 2 days of PTCY, respectively, while donors were matched (sibling n=2, unrelated n=5) in 7 cases and haplo-identical in 23, respectively. All patients received cyclosporine + MMF with PTCY as GVHD prophylaxis. In the ATG group (2 days of ATG for siblings and 10/10, 3 days for 9/10), 13, 11 and 22 patients received respectively a FB2, FB3 or CloB2 RIC regimen (Chevallier, Haematologica, 2014). Donors were siblings in 18, matched unrelated in 23 and mismatched unrelated (9/10) in 5. GVHD prophylaxis was cyclosporine alone in case of sibling donors and cyclosporine +MMF for all other cases. The characteristics of both groups (PTCY vs ATG) were similar in terms of gender (male: 63% vs 54%), type of disease (myeloid: 67% vs 63%) and disease status at transplant (complete remission: 43% vs 67%). PTCY patients were significantly younger (median age: 55.5 vs 63 years, p=0.01) and had been previously allografted in a significantly higher proportion (40% vs 4%, p=0.003). Patients were transplanted between March 2012 and April 2015 and were considered up to day+100 post-transplant. All patients received peripheral blood stem cells as stem cell source except one patient in the PTCY group who received bone marrow. Results: All patients engrafted except one in the ATG group. The median time of neutrophils recovery was similar between both groups (PTCY 18 days vs ATG 19 days, p=0.9). Conversely, median time of platelets recovery was significant higher for the PTCY group (27 vs 13 days, p

Beschreibung: Background: Gemtuzumab Ozogamicin (GO) is a humanized anti-CD33 monoclonal antibody linked to calicheamicin. It was developed to treat relapsed CD33+ AML patients, first at the dose of 9 mg/m² administered twice at day +1 and +14, than combined with chemotherapy but with reduced dose to lower toxicity. In 2008, we reported a 63% (50% of complete remission (CR) + 13% of CR with incomplete platelets recovery (CRp), platelets

Beschreibung: Background: MDS with del 5q are characterized by profound anemia, which until the recent introduction of lenalidomide (N Engl J Med2005; 352: 549–57, J Clin Oncol2005;16S:5), was considered generally unresponsive to available treatments. In order to reevaluate the outcome of those patients in the pre-lenalidomide era, we analyzed response of anemia in MDS with del 5q treated with EPO ± G-CSF and thalidomide in previous GFM trials. Patients: MDS with del 5q included in 419 MDS treated with EPO or Darbepoetin (DAR) ± G-CSF by GFM centers (including 3 successive GFM trials: Blood2004; 104: 321–7; Blood2005;106 suppl 1: 712a; Br J Haematol2006;133: 513–9 and submitted to ASH 2006), and in 134 MDS treated with thalidomide in two successive GFM trials (Br J Haematol2005; 131: 609–18, and submitted to ASH 2006). Patients received at least 30,000 U/w of EPO or 300 mg/w of DAR and doses ranging from 50 to 800 mg/d of Thalidomide during at least 12 weeks. Results: 48 MDS with del 5q received EPO (or DAR) ± G-CSF, including 30 pts with del 5q alone, 9 with one and 9 with 〉1 additional cytogenetic abn; 21/48 had marrow blasts ≥5% (7 had 〉10%). 17 had the “5q- syndrome” according to WHO. Median pre-treatment EPO level was 287 UI/L (range 12–5,665), i.e. significantly more than in non del 5q cases (median 68, p1 additional cytogenetic abn, and marrow blasts ≥5%. Response duration was significantly shorter in MDS with del 5q than in other MDS (mean 12 vs. 24 months, p=0.019) and in pts with 5q- syndrome vs. other MDS with marrow blasts

Beschreibung: We have evaluated the outcome of RIC in 114 adult pts with AML either de novo (74) or secondary to cancer or MDS (40). There were 43 men, median age was 55 yo (22–65). Cytogenetic was available in 104 and was abnormal in 55 (favorable: 13; intermediate: 21; poor: 21). Pts had received a median of 1 line of Tx before RIC (0–3). Twenty had a previous autologous transplant. At time of RIC, 28 patients were refractory or in relapse while 71 were in CR (1st: 48; 2d: 20). The donor was an id sib for 80 and a MUD in 34 (with1allelic mismatch in 6). The cond regimen was of Slavin type in 56, only 11 pts received the Seattle program. Overall 74 had ATG as part of cond reg. GVHD prophylaxis consisted of CSA or CSA-MTX in 95 pts, 14 had CSA-MMF. With a median FU of surviving pts of 21 m (3–73) the 3y survival (OS) and EFS are 40% and 38% respectively. Sixty pts died with the main cause of death being relapse. The probability of TRM at 100 d and 1 y are 7% and 14% respectively. The 2y probability of relapse is 50%. These figures are strictly superimposable for pts with de-novo or secondary AML. The factors affecting significantly (p

Beschreibung: Introduction: Little is known regarding the impact of hematopoietic and immune recoveries after double umbilical cord blood (dUCB) allogeneic stem cell transplantation (allo-SCT), especially after the TCF (low dose 2 Grays total body irradiation + cyclophosphamide 50 mg/Kg 1 day + fludarabine 200 mg/m² 5 days) reduced-intensity conditioning (RIC) regimen, which is considered as a standard RIC regimen for dUCB allo-SCT in adults Patients and Methods: Here we considered a homogeneous cohort of 47 patients (males: n=24; median age: 55.5 years (range: 17.5-69) who engrafted after a dUCB TCF allo-SCT performed between November 2006 and April 2013 in our department. Fifty-three percent of the patients had myeloid disease. The majority of cases were in complete remission at time of transplant (72.3%). GVHD prophylaxis consisted of cyclosporine + mycophenolate mofetyl in all cases. All patients received G-CSF from day 1 until neutrophils recovery. The median nucleated cells dose infused was 4.17 107/kg. The aim of the study was to investigate the impact on outcomes of the recovery of the following cellular subsets: leucocytes, monocytes, lymphocytes, neutrophils at day +30 and day +42, and CD4+, CD8+ T cells, B and NK cells at day+100. Results: Median times for neutrophils and platelets recoveries were 17 days (range: 6-59) and 37 days (range: 0-164), respectively. With a median follow-up of 30.4 months (range: 2.8-77.5), the 3-year overall and relapse-free survivals (OS, RFS), relapse incidence (RI), and non-relapse mortality (NRM) were 65.7%, 57.2%, 27.1% and 19%, respectively. The cumulative incidences of grade II-IV and grade III-IV acute GVHD were 38.3% and 10.6%, respectively, while, 3-year incidence of chronic GVHD was 53.5% (limited 42%, extensive 11.5%). In univariate analysis, 3-year OS was significantly higher in case of lymphoid disease (80.9% vs 51.9%, p=0.05) or when achieving at day+30 or day +42 higher counts of leucocytes (〉 median: 2760/mm3; 79% vs 51%, p=0.05; median 〉 4250/mm3; 78.6% vs 55.4%, p=0.04) or monocytes (〉 median: 615/mm3; 87.5% vs 45.8 %, p=0.02; median 〉 830/mm3, 86.2% vs 54.1%, p=0.03). Older age (〉median: 55 years) and higher monocytes count at day +42 (〉 median: 830/mm3) were significantly associated with higher 3-year RFS (63.6% vs 49.1 %, p=0.046; and 75.7 vs 44.4%, p=0.014). Higher leucocytes count at day +42 (〉median: 4250/mm3) was the only factor associated with significant 3-year lower NRM (7.1% vs 31.7%, p=0.04), while younger age was associated with higher risk of grade 3-4 acute GVHD (16.7% vs 4.4 %, p=0.05). No factor was predictive of chronic GVHD in this series. In multivariate analysis, older age and early higher monocytes count after transplant were the two independent factors associated with a significantly higher OS (〉55 years, HR: 0.21; 95%CI: 0.05-0.85, p=0.028; 〉615/mm3 at day +30, HR: 0.05; 95%CI: 0.01-0.43, p=0.006) while only older age remained independently associated with better RFS (〉55 years, HR: 0.25, 95%CI: 0.08-0.78, p=0.017). No factor was predictive of NRM, grade 2-4 GVHD, grade III-IV acute or chronic GVHD. Conclusion: These results suggest that higher early monocytes recovery is predictive of outcome after dUCB TCF RIC allo-SCT in adults. Immune recovery seems to have no impact on survivals in this series while influence of age has to be confirmed by other studies. Our results pave the way for future studies aiming to closely and prospectively monitor the kinetics of hematopoietic and immune recoveries after this type of graft. As all patients received G-CSF after transplant, other immunostimulatory cytokines should be tested to ensure sufficient hematopoietic recovery in the setting of adult dUCB TCF RIC allo-SCT. Disclosures No relevant conflicts of interest to declare.

Beschreibung: Abstract 3341 Poster Board III-229 Allo-SCT procedures are currently undergoing a profound evolution. The spectra of patients and diseases for which this approach is now considered have increased considerably over the past years. This is mainly due to the introduction in routine practice of the so-called nonmyeloablative or RIC regimens. While it is well established that fludarabine is the backbone drug to secure engraftment, there is a wide variability in the degree of myeloablation between the different RIC protocols, and the toxicity profile might vary significantly from one protocol to another. The combination of fludarabine and Busulfan (usually 8 mg/Kg total dose) with or without ATG, is among the most widely used RIC protocols worldwide. In an attempt to further decrease the toxicity of the transplant procedure, we hypothesized that further reduction (50%) of the Busulfan dose can allow improving transplant outcome. With this background, this pilot study tested the combination of Fludarabine (120 mg/m2), Busulfan (4 mg/Kg total dose administered orally over a single day) and ATG (Thymoglobuline®, 2.5 mg/Kg/d for 2 days) as a RIC regimen prior to allo-SCT in a single centre series of 46 patients. The cohort included 27 males (59%) and 19 females (41%) with a median age at time of allo-SCT of 57 (range, 12-64) y. Diagnoses included 21 cases of AML (46%), 12 NHL (26%), 6 Hodgkin diseases (13%), 3 ALL (6.5%), 2 myeloproliferative syndromes (4%), 1 MDS (2%) and 1 CLL (2%). Before allo-SCT, 23 patients (50%) underwent and failed previous stem cell transplantation (auto or allo). PBSCs were used as stem cell source in 42 patients (91%), while 4 patients (9%) received classical bone marrow. A matched-related donor was used in 18 cases (39%) and an unrelated donor in 28 cases (61%). With a median follow-up of 30.4 (range, 23.7-50.8) months, the median peripheral blood chimerism of donor origin at day 30 after allo-SCT was 99%. 20 patients (43.5%) experienced grade 2-4 acute GVHD, including 13 cases (28.3%) of grade 3-4 acute GVHD. Nine patients (19.6%) experienced some form of chronic GVHD (5 extensive and 4 limited). At time of last follow-up, 26 patients (56.5%) were still alive. Relapse or disease progression occurred in 13 patients at a median of 3.5 (range, 0.6-18) months after allo-SCT. Disease progression accounted for 7 deaths, while transplant-related causes (acute GVHD, n=5; MOF, n=3; infections, n=2; other causes, n=3) were observed in 13 cases, for a TRM rate of 28.3%. The KM estimates of disease-free survival (DFS) and overall survival (OS) at 3 years after allo-SCT were 46.9% and 56.5% respectively. Interestingly, OS was lower in the AML subgroup (n=21) as compared to the remaining 25 patients with other diagnoses (42.9% vs. 68%, p=0.09). We conclude that low dose Busulfan (4 mg/kg total dose) combined with fludarabine and ATG is a feasible RIC regimen that can allow engraftment after allo-SCT in heavily pre-treated patients. The toxicity profile of this regimen is acceptable. However, in the setting of AML, disease control may be a matter of concern, especially in the early period after allo-SCT, suggesting that this type of RIC should be reserved for patients with lymphoid or indolent malignancies. Disclosures No relevant conflicts of interest to declare.

Beschreibung: Background Bortezomib (B) is an effective drug alone or in combination in naive and pretreated WM patients. The interest of high dose of dexamethasone (D) with bortezomib (B) has not been evaluated in WM patients and D is systematically added to bortezomib combination with or without Rituximab (R) (BD, BDR). However, D is responsible for side effects in elderly population. We tested in a phase II trial the efficacy and safety of the addition of D to B after 2 B cycles in patients with a stable or progressive disease (SD, PD). Patients and Methods Bortezomib was used at 1.3mg/m2 IV D1, 4, 8 and 11 every 21 days for 6 cycles. In no responding patients, D (20mg) was added at D1,2, 4, 5, 8, 9, 11 and 12 at Cycles 3 to 6. The main endpoint was the overall response rate (ORR) at two months before D adjunction; secondary outcomes were ORR at 4 and 6 months, response duration, overall survival (OS) and progression-free survival (PFS). Two interim analyses were scheduled and performed after the inclusion of 17 and 27 patients, respectively, using Bayesian estimation of ORR with stopping rules. Results Interim analyses did not allow stopping the trial, with probability of ORR above 35% below 0.9. Thus, a total of 34 patients (pts) were enrolled in the study in two years (2009-2011) in 17 centers. The median age was 70.2 (64.2-79.6).ECOG was ≥1 in 53% of the pts. The median of previous lines, hemoglobin, beta 2 microglobulin, IgM, and albumin was 1, 9.8g/dL, 4.35mg/L, 29g/L, 35 g/L respectively. At 2 cycles, there were 6 partial responses and 10 minor responses(group I), with estimated ORR at 44.1% (95%CI: 27.6-61.9%). D was added in 16/18 pts with stable or progressive disease (group 2). At 4 and 6 cycles, 22/28 and 20/26 pts were in response (12 and 8 in group 1, 10 and 12 in group 2), with resulting 4 and 6 cycles ORR estimated at 75% (95%CI: 47.4-91.7) and 50% (95%CI: 28.0-72.0) in group I and 62.5% (95%CI: 35.9-83.7) and 75% (95%CI: 47.4-91.7) in group 2. A total of 62 adverse events grade 〉 2 (first course: 11, second course: 18, subsequent courses: group 1: 14, group 2: 19) were observed in 38 courses. Of these 62 events (49 grade 3 and 13 grade 4), 52 (84%) consisted in hematological adverse events (18: platelets, 15: hemoglobin, 8: leucocytes, 1 lymphocytes, and 10 neutrophils); 3 neurological toxicities grade 〉2 were observed, 1 after the second course and 2 after the third course in group 1. Otherwise, there were 26 peripheral neurological toxicities grade ≤2, namely 5 for the first 2 courses, 11 in group 1 and 10 in group 2. With a median follow up of 36 months, 23 pts experienced disease progression or died (18 had disease progression and 5 died in response). For patients who achieved at least a minor response, the 18-month progression rates were 31.9% in group 1 and 52.1% in group 2 (p=0.43) and WM unrelated death rates were 6.3% in group I and 16.7% in group 2 (p=0.79). The 2-year survival rate was 79.8% [IC95%: 64.7; 98.3]. The median progression free survival time was 16.8 months [IC95%: 13.0-23.6]. Conclusion We showed that addition of D to B in the elderly population was well tolerated and allowed reaching 6-month response in patients who did not respond to two courses of isolated B. Dexamethasone must be associated to bortezomib-based regimen. Disclosures: Leblond: Mundipharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Roche : Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Off Label Use: Bortezomib in Waldenstrom macroglobulinemi. Dilhuydy:Roche: Honoraria. Leleu:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; LeoPharma: Consultancy, Honoraria; Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Amgen: Honoraria; Novartis: Honoraria. Tournilhac:MUNDIPHARMA: Consultancy, travel funding Other; GSK: Consultancy, travel funding, travel funding Other; Celgene: Consultancy, teaching, teaching Other.

Beschreibung: Introduction: Allogenic stem cell transplantation (Allo-SCT) remains currently the only curative treatment for primary myelofibrosis (PMF) or myelofibrosis secondary (SMF) to essential thrombocythemia (ET)/polycythemia vera (PV). Indication of allo-SCT refers to high-risk patients defined by various scores such as Lille score, IPSS, DIPSS or more recently DIPSS+. However, JAK2, CALR, MPL or triple negative mutation profiles have recently been shown to impact on the outcome of PMF patients and thus may challenge the indication of allo-SCT in the future. CALRmut patients seem to have the best survival conversely to triple-negative patients, while JAK2mut and MPLmut status can be considered as an intermediate molecular signature (Tefferi, Leukemia 2014). The outcome of MF patients with a validated allo-SCT indication who do not proceed to transplant is generally unknown although relatively long survival can be documented, especially since the availability of JAK inhibitors such as ruxolitinib. Also, data regarding impact of mutational status on outcome after allo-SCT remain scarce. Patients and Methods: This single-center retrospective study considered MF patients with a validated indication of allo-SCT between 2000 and 2013. The main objective was to compare the overall survival (OS) between patients who ultimately received allo-SCT or not. Secondary objectives were to analyze the impact of mutational molecular status on OS and the use of ruxolitinib in patients not allografted. Results: An indication of allo-SCT was validated in 67 patients (males: 64%; PMF: 59%; SMF post-ET 25%, SMF post-PV 16%). At the time of indication of ASCT, the median age was 59 years (range: 41-69); DIPSS+ score was: int-2 in 40%, high risk in 60%. Mutational status, available for 86% of patients, was as follows: JAK2V617F (n=37), CALRmut (n=12); MPLmut (n=3), triple-negative (n=6). Thirty-three patients proceeded to allo-SCT (reduced intensity conditioning: 82%) while 34 did not for lack of donor (31%), comorbidity (28%), progressive disease (14%), stable disease on conventional therapy (18%), refusal (9%). The two groups (allo/non-allo SCT) were comparable for gender, year of indication of allo-SCT, type of MF, number of prior lines of treatment before allo-SCT, DIPSS+ categorization, mutational status and median follow-up. Patients who did not proceed to allo-SCT were significantly older (61 vs 57 years, p65%) (median OS: NR vs 18 months, HR: 0.18, 95%CI:0.03 -1.11, p=0.065). Interestingly, the survival of patients who did not proceed to allo-SCT was increased by the use of ruxolitinib (median OS: NR vs 20 months, HR: 2.3, 95%CI: 0.08-0.6, p=0.003). Conclusion: Allo-SCT remains a valid strategy for high-risk MF patients with unfavorable karyotype, high DIPSS+ score and secondary MF while impact of mutational status and JAK2V617F burden have to be confirmed in larger studies. MF patients who cannot proceed to transplant likely benefit from JAK2 inhibitor prescription. Disclosures Milpied: Celgene: Honoraria, Research Funding. Moreau:Celgene, Janssen, Takeda, Novartis, Amgen: Membership on an entity's Board of Directors or advisory committees.