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IPSS-R is a well established prognostic factor for transplant outcome in patients with MDS, irrespective whether it is assessed at diagnosis or at transplant. However it is unclear how a change in IPSS-R, e.g. by reducing bone marrow blasts through therapy, would potentially affect transplant results. In particular the decision to treat patients before transplant or perform an upfront allogeneic transplantation can so far not be based on evidence. We did a registry search based in the MDS quality initiative conducted by EBMT to identify transplanted patients with MDS and sufficient data to calculate IPSS-R at diagnosis and before transplant. The search was limited to patients reveiving a first allogeneic stem cell transplantation in the period 2005 -2018. 1482 patients were identified. Median age at alloHCT was 59 (interquartile range 51-64) years, 60% were male. Donors were related in 36%, graft source was PBSC in 85% of cases. Conditioning was standard dose in 33% and reduced intensity in 67%. IPSS-R both at diagnosis and at transplant had a significant impact on OS and RFS after alloHCT. To investigate the effect of a change in IPSS-R between diagnosis and transplant we constructed 3 subgroups: stable IPSS-R, improved IPSS-R, worsened IPSS-R. A change in IPSS-R was noted in 77.5% of patients with prior chemotherapy, 72% with prior HMA and 59.8% of untreated patients. Univariate analysis showed no significant difference in OS or RFS in patients with stable IPSS-R compared to improved or worsened IPSS-R. In patients treated with chemotherapy before transplant OS and RFS was significantly worse with worsened IPSS-R, while this effect was not found in patient treated with hypomethylating agents (HMA) or untreated patients. The same analysis was performed regarding the difference in bone marrow blasts and the cytogenetics score: OS and RFS after transplant were significantly worse with increased blasts (p=0.04 and p=0.001) and a worsened cytogenetic score before transplant (both p In this retrospective analysis from a large cohort of patients with MDS we found that worsening of IPSS-R, blast count or cytogenetic score had a negative prognostic impact in chemotherapy-treated patients, while only worsened blast count and cytogenetics were significant negative factors in HMA-treated or untreated patients. Conversely we did not find a positive effect of improved IPSS-R, decreased blasts or improved cytogenetics in any of the subgroups of treated or untreated patients. Thus for MDS patients receiving an allogeneic transplantation our results provide no clear signal that prior therapy is able to improve transplant outcome. Disclosures Scheid: Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria; Takeda: Honoraria, Research Funding. Blaise:Jazz Pharmaceuticals: Honoraria. Chevallier:Incyte Corporation: Honoraria. Yakoub-Agha:Celgene: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria.

Aim: Dynamic assessment of trends over time in patient- and transplant-specific characteristics and outcomes for patients undergoing 1st allogeneic haematopoietic cell transplant (allo-HCT) for Myelofibrosis (MF). Methods and Results: A total of 4142 MF patients were analysed who underwent allo-HCT between 1995-2018 (24-year period) across 278 centres based on data reported to the European Society for Blood and Marrow Transplantation. For analysis, 4 cohorts were considered based on year of allo-HCT: 60 years accounted for 8.7% of adults undergoing allo-HCT whereas for 2015-2018 this was 47%. Over time, increasing number of patients with a Karnofsky performance status (KPS) Conclusions: Despite a marked increase over this 24-year period in recipient age, RIC regimen utilisation and use of both URD and MMRD, this comprehensive analysis demonstrates stable OS and EFS rates. However, rates of GVHD have decreased over time, in particular extensive cGVHD. Further work is required to improve both the considerable NRM and relapse rates which remain significant. Disclosures McLornan: JAZZ PHARMA: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau; NOVARTIS: Honoraria, Speakers Bureau. Platzbecker:Amgen: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Geron: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Chevallier:Incyte Corporation: Honoraria. Martínez-Lopez:Altum, Hosea: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Vivia Biotech: Honoraria; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Roche: Speakers Bureau; Janssen: Speakers Bureau; Incyte: Research Funding, Speakers Bureau; Bristol Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding. Yakoub-Agha:Celgene: Honoraria; Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Janssen: Honoraria.

Thanks to the recent developments in transplant procedures, an increasing number of patients with acute myeloid leukemia (AML) with a poor Karnofsky Performance Status (KPS) score are currently offered an allogeneic hematopoietic stem cell transplantation (allo-HCT). Nevertheless, little data is available about outcome of this fragile population. We report here the results of a retrospective study designed to evaluate outcome of patients with AML undergoing allo-HCT with KPS score ≤80%. The analysis included patients with AML aged ≥18 years, undergoing allo-HCT in first remission between 2000 and 2018, with a KPS score at the time of transplant between 50% and 80%. Patients who received manipulated grafts or had incomplete data about cytogenetics were excluded. Conditioning intensity was defined according to EBMT definitions. A total of 2,963 patients were identified. Median age at transplant was 55 years (18-77 years). Median year of transplant was 2014. The KPS score was =80% in 85% of the patients and Cumulative incidence of grade II-IV and III-IV acute GVHD (aGvHD) was 26% and 8%, respectively. The 2-year cumulative incidence of chronic GVHD (cGvHD) and severe cGVHD was 38% and 18%. Non-relapse mortality (NRM) and relapse incidence (RI) at 2 years were 19% and 27%, respectively. Notably, in the subgroup of patients with KPS On multivariate analysis, transplant from a MSD was associated with a reduced risk of aGvHD (10/10 UD HR 1.8, 9/10 UD HR 2.4, haplo HR 1.9, CB HR 3.4, p In order to compare outcome following MAC and RIC conditioning the analysis was restricted to patients receiving transplant from MSD or UD. Patients with a KPS score =80% or In conclusion, allo-HCT is feasible in patients with acute myeloid leukemia in first remission and KPS score Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Kröger:Sanofi-Aventis: Research Funding; Celgene: Honoraria, Research Funding; DKMS: Research Funding; JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding. Socie:Alexion: Consultancy. Blaise:Pierre Fabre medicaments: Honoraria; Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Molmed: Consultancy, Honoraria. Byrne:Ariad/Incyte: Honoraria, Speakers Bureau. Esteve:Astellas: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

Recently, an increasing number of patients with acute lymphoblastic leukemia with a poor Karnofsky Performance Status (KPS) score are considered for allogeneic hematopoietic stem cell transplantation (allo-HCT). Nevertheless, there is paucity of available data about outcome of this fragile population. We report here the results of a retrospective study designed to evaluate outcome of ALL patients undergoing allo-HCT with KPS score ≤80%. The analysis included ALL patients aged ≥18 years, undergoing allo-HCT in first remission between 2000 and 2018, with a KPS score of 50% to 80% at the time of transplant. Patients who received manipulated grafts or had incomplete data about cytogenetics were excluded. Conditioning intensity was defined according to EBMT definitions (Aoudjhane M. et al, Leukemia 2005; 19: pp. 2304-2312). A total of 1,010 patients were identified. Median age at transplant was 43 years (18-76 years). Median year of transplant was 2011. The KPS score was =80% in 83% of the patients and On multivariate analysis, transplant from 10/10 UD was associated with higher incidence of aGVHD (HR 1.8, p In conclusion, allo-HCT is feasible in patients with acute lymphoblastic leukemia in first remission and KPS score ≤80%, with acceptable NRM and survival rates. Transplant from a sibling donor was associated with reduced risk of NRM and aGVHD as compared to matched unrelated donor. Interestingly, despite the poor KPS score of the patients included in the analysis, a MAC protocol was associated with similar NRM, lower relapse and better LFS and GRFS as compared to RIC in the selected population. Finally, administration of ATG was associated with reduced acute and chronic GVHD rates. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Socie:Alexion: Consultancy. Kröger:JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding; Sanofi-Aventis: Research Funding; Celgene: Honoraria, Research Funding; DKMS: Research Funding. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

Background: In a previously published single-center study (Blood 2000) we randomized 108 consecutive adult patients with a malignant hematological disorder undergoing allogeneic bone marrow transplantation from an HLA-identical sibling donor to receive (n=53) or not to receive (n=55) methylprednisolone (MP+ or MP-, respectively) as a part of graft-versus-host disease (GVHD) prophylaxis. All patients received cyclosporine A and methotrexate. MP administration was initiated on day 14 post-transplantation with 0.5 mg/kg, the dose was increased to 1 mg/kg on day 21 and thereafter tapered and discontinued on day 110. The cumulative incidence of acute GVHD was 19 % among the patients given and 56 % among those not given MP prophylaxis (p=0.0001), and that of grade II-IV acute GVHD 13 and 36 %, respectively (p=0.005). There was a non-significant trend toward a lower cumulative incidence of chronic GVHD (cGVHD) and better survival in the MP+ group. There were fewer infections and the stay at hospital was shorter among the patients given MP prophylaxis. No difference was seen in the relapse rate. We have now carried out a long-term follow-up to find out possible late effects of the intensified GVHD prophylaxis. Results: The median follow-up time of living patients was 24.5 (range 22.7-26.9) years; two patients were lost for follow-up at 37 and 80 months. In the MP+ group the overall survival (OS, p=0.021) (Figure 1) and relapse-free survival (RFS, p=0.024) were significantly higher and the non-relapse mortality (NRM) lower (p=0.003) than in the MP- group. There was a trend toward lower cumulative incidence of cGVHD in the MP+ group (36 vs. 48 %, p=0.17). The prevalence of cGVHD, analyzed with data available from ten years of scheduled follow-up, was significantly (p=0.031) lower in the MP+ group and the difference became more marked with time. Among the patients alive at ten years, none in the MP+ group but 28 % of the patients in the MP- group had active cGVHD. There was no difference in the relapse rate between the MP+ and MP- groups, the cumulative incidences were 36 and 38 %, respectively. Seven patients in each group developed a secondary malignancy, one patient in both groups had two secondary tumors. At 15 years, the survival was 55 % in the MP+ group and 47 % in the MP- group, and the NRM 21 and 30 %, respectively. Thereafter there was marked non-relapse mortality in the MP- group, eleven patients died after this time point, whereas there were no deaths during this period in the MP+ arm. At the end of the follow-up, the OS in the MP+ and MP- groups were 55 and 20 % and the RFS 54 and 18 %, respectively. The causes of the late deaths in the MP- group were: bacterial infection 3, obstructive bronchiolitis 1, acute myocardial infarction 1, intracerebral bleeding 1, sudden death of unknown cause 1, lung cancer 2, colon cancer 1, and esophagus cancer 1. Conclusion: The addition of corticosteroid to cyclosporine and methotrexate in GVHD prophylaxis, resulting in a marked decrease in the incidence of acute GVHD, did not cause adverse late effects. Long-term survival was higher among the patients given MP prophylaxis. Unexpectedly, there was marked late non-relapse mortality in the group not given MP prophylaxis, possibly contributed to by the higher prevalence of cGVHD. Disclosures No relevant conflicts of interest to declare.

Introduction: The reported incidences of sinusoidal obstruction syndrome/veno-occlusive disease of the liver (VOD) have varied widely. In recent reviews the present incidence has been stated to be up to 10-15 %. The differences in the incidences may be due to different patient materials and transplantation methods or differences in the application and interpretation of diagnostic criteria. Modified Seattle criteria (McDonald et al 1993) or Baltimore criteria (Jones et al 1986) are used to establish the diagnosis. The diagnosis is based on a combination of clinical criteria. However, the diagnosis of VOD should only be made if there are no other conditions that could explain the clinical findings. More than one condition causing liver problems may be present at the same time, leaving space for subjective interpretation that could essentially affect the incidence of this disorder. Along with the improving opportunities for prophylaxis and treatment of VOD, it is important to have a correctpicture of its incidence. We evaluated the differential diagnostic component of VOD diagnosis in our single-center material. Patients: The hospital notes of 300 consecutive adult patients treated with allogeneic stem cell transplantation between March 2011 and February 2015 at the Helsinki University Hospital were retrospectively reviewed. All but one had a malignant hematological disease. The most common diagnoses were AML 106, ALL 48, MM 46, NHL 34, and MDS 24. The total of 135 patients (45%) received conventional myeloabative conditioning, CyTBI (n=79) or BuCy (n=56), 151 were given treosulfan in myeloablative (n=77) or reduced (n=74) dose with fludarabine, 5 received BuFlu and 9 other regimen. Of the donors 75 % were unrelated, and 77 % of the grafts were from peripheral blood. All patients received ursodeoxycholic acid (UDCA) prophylaxis. GvHD prophylaxis consisted of CsA and a short course of MTX. ATG was given in transplantations from unrelated donor. Methods: We identified all patients who had a total serum bilirubin concentration exceeding 34 µmol/l during the first three weeks after the transplantation. Among them we evaluated whether they had a weight increase of more than 2 % or 5 % compared to the admission weight. We also registered the clinical notes of liver enlargement, upper right abdomen pain and ascites as well as ultrasound examinations. Results: Of the 300 patients, 54 had a serum bilirubin concentration exceeding 34 µmol/l within three weeks post-transplantation. The peak bilirubin concentration was 35-193 (median 47) µmol/l. Of these patients, 43 showed a weight gain exceeding 2 % and 29 patients exceeding 5 % of the admission weight. Thus, forty-three patients fulfilled the minimum modified Seattle criteria with the 2 % weight gain criterion and 29 with the 5 % criterion (modification, Corbacioglu et al 2012). Two patients had enlarged liver and right upper quadrant pain. No case of abnormal venous blood flow was seen. According to institutional policy, preemptive treatment with defibrotide according to bilirubin levels was started in 10 patients but in most cases discontinued within a few days based on the clinical course. Twenty-eight (65 %) of the 43 patients fulfilling the minimal VOD criteria had other clinical conditions that were regarded by the treating team as a plausible cause for the findings: infection 22, non-conditioning drug effect 4, cholecystitis or cholestasis 2, engraftment syndrome 2, GvHD 1, and hemolysis 1. In the remaining 15 patients there was no obvious alternative cause. Thirteen of these cases were mild, showing no hepatomegaly, and they had not been labelled as VOD. Conclusion: According to the modified Seattle criteria, 15 patients (2% weight criterion) or 10 patients (5 % weight criterion), without an alternative cause to the clinical findings, had VOD. Two patients fulfilled the Baltimore criteria, but as one of them had a simultaneous septic infection, the diagnosis of VOD could not be confirmed. Therefore, depending on the criteria used and the differential diagnostic interpretations, the incidence of VOD in this material was between 5 % and 0.3 %. All cases were mild. UDCA prophylaxis and preemptive defibrotide treatment probably affected the incidence. Differences in differential diagnostic interpretations may contribute significantly to the variable incidences of VOD reported. Disclosures No relevant conflicts of interest to declare.

Abstract 3133 The treatment of multiple myeloma (MM) has been rapidly evolving with the introduction of new drugs, but this disease is still regarded as incurable, with few exceptions. The role of allogeneic stem cell transplantation in the treatment of MM is unclear at present. It offers the possibility to harness the curative potential of the graft-versus-myeloma effect, but high transplant-related mortality, as previously reported, has limited its use. We report our single-center experience of 120 patients treated with allogeneic transplantation at the Helsinki University Central Hospital since the year 2000 showing low transplant-related mortality and a significant proportion of patients achieving prolonged progression-free survival. The median age of the patients was 50 (range 28–65) years. Sixty-three patients were male, 57 female. The immunoglobulin classes were IgG 75, IgA 16, IgD 3, and light chain 26. Forty-nine patients received a myeloablative (MA) conditioning, 71 patients a reduced intensity conditioning (RIC). The MA regimens were cyclophosphamide 120 mg/kg + fractionated TBI 12 Gy, lungs 10 Gy (n= 30) and treosulfan 42 g/m2 + fludarabine 150 mg/m2 (n= 19), the RIC regimens TBI 2 GY (n= 52) or treosulfan 36 g/m2 (n= 19) with fludarabine. In 43 cases allotransplantation, conditioned with low-dose TBI-based regimen, was performed in a preplanned combination with autologous transplantation which preceded the allotransplantation with the median of 5 (range 2–8) months. Overall, 79 patients had an autologous transplantation in their previous history. The number of chemotherapy lines preceding allogeneic transplantation was 1 in 49, 2 in 30, and 3–7 in 41 cases. The median time from the diagnosis of MM to allotransplantation was 10 (range 5–82 ) months in transplantations with MA conditioning and 16 (7–170) months in those with RIC. Of the donors 74 were HLA-matched siblings and 46 unrelated. The graft was from peripheral blood in 99 and from bone marrow in 21 cases. In transplantations with low-dose TBI based conditioning the GVHD prophylaxis consisted of CsA and MMF. The other patients received CsA + MTX, in sibling transplantations with TBI-based MA conditioning added with methylprednisolone. ATG was given in transplantations from an unrelated donor except to patients conditioned with low-dose TBI. The state of the disease preceding the allotransplantation was the following: CR 18 (15 %), VGPR 7 (6 %) PR 82 (68 %), MR 3 (3 %), and progression 10 (8 %). At 100 days post-transplantation 30 patients (25 %) were in CR, 6 (5 %) in VGPR, 63 (53 %) in PR, 2 (2 %) in MR; 2 (2 %) had no change, and 13 (11 %) progressed. Five patients had died. The best response, achieved at the median of 3 (range 0 – 80) months post-transplantation, was CR 53 (44 %), VGPR 6 (5 %), PR 48 (40 %), MR 1 (1 %), NC 2 (2 %), and progression 10 (8 %). The median follow-up of living patients was 62 (range 1–140) months. The cumulative incidence of grade II-IV acute GVHD was 29 %; that of chronic GVHD 65 % (extensive 25 %) in MA transplantations and 80 % (extensive 51 %) in RIC transplantations. Seventy-three patients had disease progression; the cumulative incidence of progression until 10 years was 70%. There was no significant difference in the incidence of progression between MA and RIC transplantations. Thirty-six patients received DLI for the treatment of progression. Fifty-three patients have died, 38 of them in disease progression, and 15 of non-relapse causes. The cumulative incidences of non-relapse mortality (NRM) in MA and RIC transplantations were 0 vs. 3 % at 100 days, 2 vs. 9 % at 1 year and 8 vs. 26 % at 5 years. The survivals of MA and RIC patients were 92 vs. 87% at 1 year, 87 vs. 72% at 2 years, 64 vs. 56% at 5 years, and 49 vs. 35% at 10 years, respectively. The proportion of the whole patient population surviving without disease progression was 26% from 7 years on until the end of follow-up. There was no significant difference in the survival between transplantations from sibling and unrelated donor. In conclusion, the low NRM, particularly in transplantations with myeloablative conditioning, and the significant proportion of patients with long-term progression-free survival suggest a role for allogeneic transplantation in the treatment of myeloma. The optimal combination of modern drug treatment with allogeneic transplantation providing graft-versus myeloma effect should be assessed in clinical trials. Disclosures: No relevant conflicts of interest to declare.

40 pregnancies of 16 women with ET were analyzed retrospectively. In 6 patients ET was diagnosed before the first pregnancy. In 10 patients thrombocytosis was detected for the first time during a pregnancy, and the diagnosis of ET was confirmed in the median of 17 months from the delivery. Of the pregnancies 45% (18/40) were complicated, 55% (22/40) uncomplicated, and 63% (25/40) resulted in live birth. 9/16 women had at least one complicated pregnancy. The most common complication was spontaneous abortion during the first trimester, seen in 33% of all pregnancies and comprising 72% of all complications. 2 intrauterine fetal deaths occurred at weeks 22 and 28. 3 pregnancies were complicated by eclampsia or pre-eclampsia. The non-pregnancy-related symptoms of ET or platelet counts before conception or during pregnancy did not correlate with the risk of complications. The median of maximum platelet counts during the first trimester in 16 pregnancies resulting in live birth was 757 x 109/l (255 – 1561 x 109/l) and in 13 pregnancies ending in pregnancy loss 835 x 109/l (697 – 1525 x 109/l) (p=0.25). The intrauterine fetal deaths occurred with platelet counts 553 and 574 x 109/l. In patients with eclampsia or pre-eclampsia the platelet counts were normal at the onset of the symptoms. Only 2 patients had other ET-related symptoms during pregnancy. 9 patients had ET-related symptoms before or between the pregnancies. In 4 of them the pregnancies were uncomplicated. Treatment for ET was or had been given to 11/16 (67%) women in 13 pregnancies either during the pregnancy or before conception or both. Acetylsalicylic acid (ASA) was given in 10 pregnancies of 9 patients. 2 continued with ASA throughout the pregnancy. In 7 patients ASA was started at 4–27 weeks of gestation, in 4 of them during the first trimester. 7 patients had received platelet lowering drugs before conception. 5 were on interferon (IFN) before conception; 3 of them switched over to ASA after conception, one continued with IFN after a 4-week break from week 15 onwards, one continued with IFN throughout the pregnancy. Both patients on IFN during the pregnancy received also ASA. 2 women had been treated with busulphan before conception; one because of previous recurrent miscarriages successfully before two pregnancies, and the other with no pregnancy planning 26 months before the conception. Pregnancy complications occurred in 18/27 (67%) pregnancies in women without any treatment and in 0/13 pregnancies in those with treatment before or during the pregnancy (p