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The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males ; median age at transplantation was 48 years (range: 35–64) and the median number of treatment lines prior to transplantation was 3 (1–10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1–140). Overall, 40 (71%) patients responded to Ibrutinib ; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two- year OS and PFS probabilities were 72% (95% CI: 52–84) and 50% (95% CI: 32– 66), respectively. Patients with late relapse after allo-HSCT (≥24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.

Advances in understanding the pathogenesis and molecular landscape of myelofibrosis have occurred over the last decade. Treating physicians now have access to an ever-evolving armamentarium of novel agents to treat patients, although allogeneic hematopoietic stem cell transplantation remains the only curative approach. Improvements in donor selection, conditioning regimens, disease monitoring and supportive care have led to augmented survival after transplantation. Nowadays, there are comprehensive guidelines concerning allogeneic hematopoietic stem cell transplantation for patients with myelofibrosis. However, it commonly remains difficult for both physicians and patients alike to weigh up the risk-benefit ratio of transplantation given the inherent heterogeneity regarding both clinical course and therapeutic response. In this timely review, we provide an up-to-date synopsis of current transplantation recommendations, discuss usage of JAK inhibitors before and after transplantation, examine donor selection and compare conditioning platforms. Moreover, we discuss emerging data concerning the impact of the myelofibrosis mutational landscape on transplantation outcome, peritransplant management of splenomegaly, poor graft function and prevention/management of relapse.

Introduction: The prognosis of patients diagnosed with blast crisis (BC) chronic myeloid leukemia (CML) is dismal. Allogeneic stem cell transplantation (alloSCT) represents the only curative treatment option. In the current tyrosine kinase inhibitor (TKI) era, however, data on transplant outcomes in patients with BC CML, particularly those with active BC at transplant, are scarce. We hereby report on a multicentre, EBMT-registry based retrospective study of adult patients allografted for BC CML focusing on patients with active disease at transplant and pre-transplant prognostic factors. Patients and methods: Patients with BC CML at transplant (i.e. prior to the start of the conditioning) who underwent alloSCT after the year 2004 within the EBMT database were identified. Next, transplant centers were asked to report the exact disease status at transplant (including blood count, blast count in peripheral blood and bone marrow, achievement and type of remission with corresponding assessment dates, and the reason to proceed with alloSCT in BC CML). A total of 170 patients allografted for BC CML between 2004 and 2016 had complete data for analysis. Overall survival (OS) and leukemia-free survival (LFS) were calculated from date of alloSCT to the appropriate endpoint. For multivariable analysis of predictors of OS and LFS, Cox proportional hazard regression models were performed. Confounding prognostic factors (full models) were: age, disease status prior to alloSCT, Karnofsky performance status (KPS) prior to transplant, interval from diagnosis to transplant, year of transplant, stem cell source, conditioning intensity, donor type, and donor/recipient sex match. All patients provided informed consent for data collection and analysis. Results: Median age at alloSCT was 45 years (range [r], 18-75). Median time from diagnosis to alloSCT was 13.9 months (r, 1.6-367.4). Median follow-up time was 54.7 months (r, 0.1-135.2). Stem cell source was peripheral blood, bone marrow and cord blood in 145 (85%), 18 (11%) and 7 (4%) patients, respectively. Donor types were: unrelated (UD), matched related, and mismatched related in 91 (54%), 64 (38%), and 15 (9%) patients, respectively. Conditioning was myeloablative in 108 (64%) of patients. KPS at alloSCT was ≤80% in 31% of patients. Information on BCR-ABL mutations was available for 41 patients; T315I was present in 28 patients. After thorough analysis of disease parameters, a total of 95 patients had any kind of remission of BC CML (including secondary chronic phase) prior to transplant (termed BC in remission); 75 patients had active BC CML prior to transplant (termed BC active). Main reason for proceeding with alloSCT despite active disease was resistance/refractoriness towards TKI in combination with polychemotherapy. Extramedullary disease was documented in 4 patients. In uni- and multivariable analyses of the entire cohort, besides low KPS, only disease status prior to transplant was significantly associated with shorter OS and LFS (for BC active: HR 2.00, 95%CI 1.35-2.96, p=0.001 and HR 1.80 95%CI 1.27-2.57, p=0.001, respectively). Accordingly, for patients allografted for active BC estimated 3-year OS and LFS was rather short (23.8% 95%CI 13.6-34.0 and 11.6% 95%CI 3.0-20.2, respectively) and significantly lower as compared to patients allografted for BC in remission (3-year OS and LFS: 51.1% 95%CI 40.5-61.7 and 33.8% 95% CI 23.6-44.0, respectively) (Figure 1A and B). Consequently, prognostic factors for survival were analyzed separately according to disease status at alloSCT (slim models, Table 1). For patients with BC in remission at transplant advanced age, lower KPS, shorter interval from diagnosis to transplant, myeloablative conditioning, and UD transplant were risk factors for inferior survival, whereas in patients allografted for active BC, only UD transplant was associated with prolonged LFS and with a trend towards improved OS (Table 1). Conclusion: Survival of BC CML patients after alloSCT in the TKI era remains poor unless disease remission could be achieved. In patients who achieve remission prior to alloSCT, conventional prognostic indicators remain the determinants of transplant outcomes. In patients with active BC CML, UD transplantation appears to be associated with a survival advantage in our study. Disclosures Finke: Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding. Tischer:Jazz Pharmaceuticals: Other: Jazz Advisory Board. Mayer:Eisai: Research Funding; Roche: Research Funding; Affimed: Research Funding; Novartis: Research Funding; Johnson & Johnson: Research Funding. Byrne:Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Ganser:Novartis: Membership on an entity's Board of Directors or advisory committees. Chalandon:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs.

This analysis includes 56 Myelofibrosis (MF) patients transplanted from family mismatched donor between 2009-2015 enrolled in the European Society for Blood and Marrow Transplantation (EBMT) database. The median age was 57 years (range, 38-72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34+ cell dose was 4.8 × 106/kg (1.7-22.9 × 106/kg) (n=43). Conditioning was predominantly myeloablative (MAC) in 70% and reduced intensity (RIC) in the remainder. Regimens were heterogeneous with Thiotepa, Busulphan Fludarabine (TBF) and post-transplant cyclophosphamide (PTCy) used in 59%. The incidence of neutrophil engraftment by 28 days was 82% (range, 70-93%), at a median of 21 days (range,19-23). At 2 yrs. the CI of primary Graft failure was 9% (1-16%) and secondary graft failure was 13% (4-22%).The cumulative incidence (CI) of grades II-IV acute GvHD (aGvHD) and III-IV was 28% (16-40%) and 9% (2-17%) at 100 days. The CI of chronic GvHD (cGvHD) at 1 year was 45% (32-58%) but CI of death without cGVHD by 1 year was 20% (10-31%). With a median follow up of 32 months, the 1- and 2-year OS was 61% (48-74%) and 56% (41-70%) respectively. The 1- and 2- year PFS was 58% (45-71%) and 43% (28-58%) with a 2-year CI of relapse of 19% (7-31%). The 2-year non-relapse mortality (NRM) was 38% (24-51%). This retrospective study of MF allo-SCT utilising family mismatched donors, demonstrates feasibility of the approach, timely neutrophil engraftment in over 80% of cases and acceptable OS and PFS rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimise the risk of graft failure and the relatively high NRM need to be employed, ideally in a multicentre prospective fashion.

INTRODUCTION: Acute graft-versus-host disease (aGvHD) remains a serious complication of allogeneic hematopoietic cell transplantation (HCT) and negatively impacts on patients' outcome. Over recent years improvements in GvHD prophylaxis, HLA typing, donor selection, treatment and supportive care have been achieved. However, it is unknown whether these changes have resulted in improved outcome of patients undergoing allogeneic HCT and particularly in those patients diagnosed with aGvHD and in need of systemic immunosuppressive therapy. METHODS: We examined outcome following diagnosis of grades II-IV and grades III-IV aGvHD according to time period and investigated effects according to maximum overall grade of aGvHD. Between 1990 and 2015, 126 838 patients with a median age of 46.4 (range, 18-83.8) years with malignant disease received a first allogeneic sibling (53.9%) or unrelated donor (46.1%) blood (74.5%) or marrow (25.5%) transplant after myeloablative (58.9%) or reduced-intensity (41.1%) conditioning. Sixty-two percent of patients were in complete remission (CR) at HCT. RESULTS: Incidences of aGvHD grades II-IV by 100 days significantly (p The median (range) follow-up was 217.6 (213.4-221.7) months, 169.9 (167.6-172.9) months, 129 (127.3-130.8) months, 81.3 (80.5-82.1) months and 29.7 (29.2-30.2) months for 1990-1995, 1996-2000, 2001-2005, 2006-2010 and 2010-2015. For the total study population, 3-year overall survival (OS) significantly (p The OS of patients experiencing aGvHD grades II-IV was 66% at 6 months and decreased to 43% at 36 months after HCT. Survival at 36 months after aGvHD grades II-IV increased significantly (p CONCLUSIONS: Incidences of aGvHD grades II-IV and grades III-IV decreased over time and aGvHD-associated survival increased over recent years resulting in improved survival of patients undergoing allogeneic HCT for malignant disease. Disclosures Greinix: Gilead: Speakers Bureau; Roche: Speakers Bureau; Therakos: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Celgene: Consultancy. Chalandon:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs. Mohty:MaaT Pharma: Consultancy, Honoraria.

Background.Infertility is common after HCT predominantly as a result of the chemoradiotherapy used in conditioning. Patients are increasingly encouraged to store gametes, tissue or embryos before transplant for use after their potentially sterilising treatment. Furthermore, some patients do retain or recover fertility and conceive naturally. Methods:We sent questionnaires to 602 EBMT centers requesting retrospective details of number of pregnancies following either allogeneic or autologous HCT, use of artificial reproductive techniques (ART) and pregnancy outcome for all patients treated between 1995-2015. Results:47 centers responded from 17countries detailing 439 patients (216 female, F), who became pregnant/partners conceived. The most frequent underlying diagnoses were Hodgkin Lymphoma (n=80, 18%), AML (n=77, 17.5%) and acquired bone marrow failure (n= 62, 14.1%). Of 181F conceiving where data was available 60 (33%) involved ART. These included hormone stimulation, IVF, cryopreserved embryos, donor eggs or embryos and cryopreserved ovarian tissue. The most frequent method was use of donor eggs (57/87, 65%). Of 223 men (M) whose partners conceived, mode of conception was detailed for 170, 93 of whom conceived with ART (55%). Techniques usually involved use of sperm cryopreserved prior to HCT. In 25 cases, some chemotherapy was given prior to sperm collection. 30/74 (40%) specified intracytoplasmic sperm injections, 13/74 (18%) intrauterine insemination and 24/74 (32%) IVF either with cryopreserved or fresh sperm. In female patients return of menstruation was not invariable prior to conception. Data was available for 146F, 31 of whom were amenorrhoeic prior to conception. 20/31 of the latter conceived by ART (64.5%) compared to 18/116 (15%) whose menstruation returned. Of 53F receiving TBI, 30 (57%) had ART compared to 27/111F (24%) specified as not having TBI. Of 31F receiving reduced intensity conditioning (RIC) where mode of conception was specified, 8 (26%) had ART compared to 43/113 (38%) with myeloablative conditioning (MAC). 69M were specified as having TBI and 111M specified as not. 41/58 (71%) receiving TBI had ART compared to 34/92 (37%) who did not. 24 men had RIC vs 133 MAC. Data on mode of conception was not available for all, but 4/19 (21%) with RIC had ART vs 59/113 (52%) with MAC. 656 pregnancies occurred in 439 patients with 162 patients having more than one child. Multiple births occurred for 50 patients and other patients or their partners had more than one pregnancy. 567/650 where data was available culminated in live birth and the prevalence of miscarriage (42/650, 6%) was low. 2 had still births, 5 had therapeutic abortions, 7 were pregnant at time of data collection. Gestational age (GA) was available for 41% pregnancies following a single HCT; the median GA was 39 weeks (range 22-43 weeks). It was similar in babies born to female patients or partners of male patients (p=0.71). Women who had received TBI had a lower GA at 38 weeks (22-42) compared to non-TBI F at 40 weeks (28-43) (p Birthweight was available for 197/593 (33%) pregnancies (95 to female patients) following single HCT. The median birth weight (BW) to F patients was 2999g(300-4700g) with 26 (27%) weighing 9/300 (3%) pregnancies had congenital abnormalities. The median follow up of offspring was 5 years (range 0-18) but developmental problems and learning difficulties were infrequent at 2/290 and 1/280 respectively. Conclusion:ART frequently underpinned pregnancy in this group of post-transplant patients particularly in male patients vs female, TBI vs non-TBI, amenorrhoeic vs menstruating women, standard conditioning vs RIC. In women receiving TBI and/or conceiving by ART the median GA and median BW were reduced compared to other groups of transplanted patients. However, our data indicates that in patients who conceive after HCT, either naturally or by use of ART, successful pregnancy leading to healthy offspring is the likely outcome. Disclosures Apperley: Incyte: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Bader:Neovii: Research Funding; Riemser: Research Funding; Medac: Patents & Royalties, Research Funding; Novartis: Consultancy, Speakers Bureau; Cellgene: Consultancy.