Search

Background Chronic graft-versus-host disease (cGvHD) is one of the most common life-threatening complications following allogeneic haematopoietic stem cell transplantation (alloHSCT). Understanding outcome after alloHSCT requires a full evaluation of the patient’s health status, including cGvHD and patient reported outcomes (PROs). In an effort to better understand practice patterns across European countries, a survey was initiated by the Integrated European Network on cGvHD (an EU-funded COST Action CA17138 EUROGRAFT, www.gvhd.eu) and the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation (EBMT). This report shares results of the survey, offering a snapshot view of current practice patterns in the context of long-term care of cGvHD patients. Methods Our self-designed 38-item online survey (Supplementary Material) was intended to collect data regarding transplant center characteristics, data registration practices, the use of NIH criteria in clinical routine, biopsies/biomarkers for clinical assessment, cGvHD cell-based therapies, and PROs. The survey used computer adapted testing methods and took ~10 min to complete. All centers participating in the COST Action EUROGRAFT and all EBMT centers performing alloHSCT were invited by email for participation in the survey. Data were collected between July 2019 and July 2020. Appropriate descriptive statistics were used. In case of multiple entries for a single center (n = 4), only the entry from the most senior staff member was included for the analysis. Missing data was reported as such. Findings Center characteristics Survey results are summarized in Table 1. A total of 72 centers out of 424 invited centers from 24 countries responded to the survey, representing ~17% of all alloHSCT centers and 19.6% of all transplanted patients within the EBMT network [1]. The majority of participating alloHSCT centers were from Europe with exception of three centers based in Asia and one in Latin America. Survey responses were mainly submitted by physicians and data managers. Of note, the size of the transplant programs differed between responding (mean ± SD, n = 47 ± 40 transplants/year) vs. non-responding (mean ± SD, n = 39 ± 31 transplants/year) centers (Supplementary Material).

No epidemiological data exist so far on invasive mucormycosis (IM) in Polish hematopoietic cell transplantation (HCT) and pediatric hemato-oncology (PHO) centers. The objective of this study was to analyze the incidence, clinical course, therapy, and outcome of IM in pediatric and adult patients undergoing HCT and children with hemato-oncological diseases in Poland. A total number of 12425 at-risk patients were retrospectively analyzed, and the period between 2010 and 2019 was included. Patients were analyzed in three groups: nontransplant children with malignancies, children undergoing HCT, and adults after HCT. Twenty-one patients were diagnosed with IM, including 15 children (10 non-HCT, 5 HCT) and 6 HCT adults. Proven IM was confirmed in 18 patients, probable in 2 patients, and possible in 1 patient. Proven IM was diagnosed in 7.1% of all patients with invasive fungal diseases (IFDs), including 8.1% among PHO patients, 5.4% among pediatric HCT patients, and 7.0% among adult HCT patients. Clinically, pneumonia was diagnosed in 10 (47.6%) patients, involvement of the paranasal sinuses was found in 3 (14.3%) patients, gastrointestinal disease was noted in 2 (9.5%) patients, and disseminated mucormycosis was found in 6 (28.6%) patients. The probability of overall survival in IM patients was 0.50 ± 0.11. Infection-related mortality (IRM) was 10% for pediatric nontransplant IM patients and 82% for transplant IM (pediatric + adult) patients (p = 0.004). Among the transplant patients, all adults died within 120 days. IRM for pediatric HCT patients was 60% (p = 0.038). The only prognostic factor was HCT, which adversely influenced survival in IM patients.

Background Multiple myeloma (MM) has become a chronic disease in majority of patients, and remission consolidation with autologous hematopoietic stem cell transplant (ASCT) remains the backbone of treatment in transplant-eligible patients. Objective The aim of this multicenter cross-sectional nationwide retrospective study was to evaluate the epidemiology, etiology, and outcome of infections in patients with MM undergoing ASCT in 13 Polish transplant centers, carried out on behalf of the Infectious Complications Study Group of the Polish Adult Leukemia Group. Methods A total number of consecutive 1374 patients with MM treated in Polish adult transplant centers from 2012 to 2014 were followed for infectious complications up to day +100 after ASCT in nationwide study. Results Altogether 490 infection episodes in 336 patients (49% male, aged 21-72 years) were reported, including 145 episodes of neutropenic fever (103 patients) and 34 episodes of clinically documented infections (CDIs) (27 patients). Among microbiologically confirmed infections there were 251 episodes of bacterial infections (180 patients), 42 episodes of fungal infections (38 patients), and 18 episodes of viral infections (17 patients). The overall incidence of infections reached 13.1% for bacterial, 3.6% for fungal, and 1.3% for viral infections. There were 16 cases of infection-related deaths after ASCT (1.2%). The mortality risk factors included multidrug-resistant bacteria etiology (odds ratio [OR], 3.5; P = .033), coexistence of bacterial and fungal infection (OR, 6.3; P = .002), and CDI (OR, 5.5; P = .007). Conclusion ASCT in patients with MM was connected with low risk of life-threatening infections. However, multidrug-resistant bacteria bacterial etiology, mixed etiology, and CDI increased the risk of fatal outcome.

W artykule przedstawiono symptomatologię, diagnostykę i leczenie inwazyjnej choroby grzybiczej (IFD) o etiologii pleśniowej. Autorzy skupili się na nowym leku dostępnym w leczeniu IFD – izawukonazolu, porównując go z innymi lekami, głównie z nowymi formułami amfoterycyny B. Przedstawiono charakterystykę farmakologiczną oraz wyniki najważniejszych badań klinicznych, dzięki którym izawukonazol uzyskał rejestrację w leczeniu inwazyjnej aspergilozy i mukormykozy. Autorzy podjęli także próbę zidentyfikowania konkretnych sytuacji klinicznych, w których należy rozważyć zastosowanie izawukonazolu.

Incidence and outcome of microbiologically documented bacterial/viral infections and invasive fungal disease (IFD) in children and adults after hematopoietic cell transplantation (HCT) were compared in 650 children and 3200 adults in multicenter cross-sectional nationwide study. Infections were diagnosed in 60.8% children and 35.0% adults, including respectively 69.1% and 63.5% allo-HCT, and 33.1% and 20.8% auto-HCT patients. The incidence of bacterial infections was higher in children (36.0% vs 27.6%; p 21 days were risk factors for death from infection. In conclusion, pediatric patients have 2.9-fold higher incidence and 2.5-fold better outcome of infections than adults after HCT.

Background:Myeloid neoplasms are a diverse group of malignant diseases with different entities and numerous patho-clinical features. They arise from mutated clones of hematopoietic stem- and progenitor cells which expand by outperforming their normal counterparts. The intracellular signaling profile of cancer cells is the sum of genetic, epigenetic and microenvironmental influences, and the multiple interconnections between different signaling pathways make pharmacological targeting complicated.Objective:To present an overview of known somatic mutations in myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) and the inflammatory signaling pathways affected by them, as well as current efforts to therapeutically modulate this aberrant inflammatory signaling.Methods:In this review, we extensively reviewed and compiled salient information with ClinicalTrials.gov as our source on ongoing studies, and PubMed as our authentic bibliographic source, using a focused review question.Results:Mutations affecting immune signal transduction are present to varying extents in clonal myeloid diseases. While MPN are dominated by a few common mutations, a multitude of different genes can be mutated in MDS and AML. Mutations can also occur in asymptomatic persons, a finding called clonal hematopoiesis of indeterminate potential (CHIP). Mutations in FLT3, JAK, STAT, CBL and RAS can lead to aberrant immune signaling. Protein kinase inhibitors are entering the clinic and are extensively investigated in clinical trials in MPN, MDS and AML.Conclusion:In summary, this article summarizes recent research on aberrant inflammatory signaling in clonal myeloid diseases and the clinical therapeutic potential of modulation of signal transduction and effector proteins in the affected pathways.

Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a standard of care for patients with high risk acute myeloid leukemia (AML). However, the procedure using conventional myeloablative conditioning regimens based on either busulphan (Bu) or total body irradiation (TBI) in combination with cyclophosphamide is associated with significant risk of non-relapse mortality (NRM). The use of reduced-intensity conditioning regimens results in improved tolerance but increased incidence of disease recurrence. In order to reduce toxicity while maintaining the anti-leukemic efficacy alternative conditioning regimens have been proposed including the use of Bu or TBI in combination with fludarabine (Flu). The goal of this retrospective, multicenter study was thus to compare Bu4Flu and TBI12Gy/Flu. Patients and methods: Adult patients with AML treated with alloHSCT from either HLA-matched sibling (MSD) or unrelated donor (URD) between year 2012 and 2017 were included in the analysis. The following conditioning regimens have been selected for the comparison: intravenous Bu at the total dose 12.8 mg/kg (4 days) + Flu (Bu4Flu, N=60) or TBI at the total dose of 12 Gy given in three fractions + Flu (TBI12Flu, N=40). Results: 100 patients (Bu4Flu, n=60; TBI4Flu, n=40) were included in the analysis. Median age was 42 (19-62) years in Bu4Flu group and 36 (19-64) for TBI12Flu group (p=0.01). Proportion of patients given transplant from URD was 72% and 70%, respectively (p=NS). The rates of patients treated with HSCT CR1, CR>1 and active disease were 75%, 25%, 0% in the Bu4Flu group while 82.5%, 10% and 7% in the TBI12Flu group (p=NS). All patients engrafted except for one patient in the TBI12Flu group who died of infection before engraftment. Time to neutrophil recovery was significantly faster after TBI12Flu (median 15 days, range 11-24) compared to Bu4Flu (18, 12-36 days) (p=0.000007). With the median follow up of 18 months, the cumulative incidence of relapse at 2 years was 11% (+/-6) and 30% (+/-7), respectively (p=0.14) while NRM was 19% (+/-8) and 10 (+/-5%), respectively (p=0.34). The probability of OS was 76% (+/-8) after TBI12Flu and 71% (+/-7%) after Bu4Flu (p=0.69). The LFS rates were 70% (+/-8%) and 60% (+/-7%), respectively (p=0.53). No signficant differences regarding survival could be detected in analysis restricted to patients transplanted in CR. Conclusion: Both Bu4Flu or TBI12Flu as conditioning regimens pre-alloHSCT for patients with AML are highly effective, which together with acceptable tolerance leads to survival rates of more than 70% at two years. TBI12Flu is associated with faster engraftment and a tendency to reduced risk of relapse. Prospective studies comparing both regiemens are needed. Disclosures No relevant conflicts of interest to declare.

BACKGROUND: Recent EBMT analysis showed that infections are responsible for 21% of deaths after allo-HCT and 11% after auto-HCT. However, the risk, types and outcome of infections vary between age groups. The aim of the study is the direct comparison of risk factors of incidence and outcome of infections in children and adults. PATIENTS AND METHODS: We analyzed risk factors for the incidence and outcome of bacterial, fungal, and viral infections in 650 children and 3200 adults who received HCT between 2012-2015. The risk factors were determined by multivariable logistic regression analysis. RESULTS: A total number of 395/650 (60.8%) children and 1122/3200 (35.0%) adults were diagnosed for microbiologically confirmed infection, including 345/499 (69.1%) and 679/1070 (63.5%), respectively after allo-HCT, and 50/151 (33.1%) and 443/2130 (20.8%) respectively, after auto-HCT. At 2 years after HCT, the incidences of microbiologically documented bacterial infection were 36.0% and 27.6%, (p21d) hematological recovery (HR=3.3; p21 days (HR=1.4; p=0.038) were associated with increased risk of death from infection. Among patients with bacterial infections, the risk was higher in G- infections (HR=1.6; p=0.031). Among auto-HCT patients, no child died of infection. In adults, the risk of death was higher if duration of treatment of infection was >21 days (HR=1.7; p CONCLUSIONS: The profile of infections and related deaths varies between children and adults. MMUD transplants, diagnosis of acute leukemia, chronic GVHD, CMV reactivation and prolonged infection are relative risk factors for death from infection after HCT. Disclosures Kalwak: Sanofi: Other: travel grants; medac: Other: travel grants.

Cytogenetic analysis of leukemic blasts has become a part of the standard diagnosis approach of acute myeloid leukemia patients. Chromosomal aberrations findings separate AML patients into three broad prognostic categories: favorable, intermediate and high risk. We analyzed retrospectively 179 adults with de novo acute myeloid leukemia (AML), younger than 60 years admitted to our Department between January 1999 and April 2009 to evaluate the prognostic impact of cytogenetic abnormalities on complete remission (CR) rate, disease free survival (DFS), and overall survival (OS). All patients received similar induction therapy. Median follow-up of 3.8 years for favorable cytogenetic group CR rate was 85%, 3-year DFS was 70% and 3-year OS was 65%, for intermediate group CR rate, 3-year DFS and 3-year OS were respectively: 64%, 43%, and 38%. Among high risk patient CR rate was 40%, 3-year DFS was 24%, 3-year OS was 17%. We conclude that cytogenetics is among the most useful factors in predicting attainment of CR, DFS, and long-term overall survival in adult de novo AML patients younger than 60 years.

Multiple myeloma (MM) is one of the hematologic malignancies in which the impact of dose intensity has been demonstrated. In 2005 it was the most common disease for which autologous stem cell transplantation (ASCT) was performed. However, ASCT is not curative, and most patients relapse within a median of 3 years, the introduction of high-dose therapy resulted in prolonged survival. Novel agents such as thalidomide, bortezomib, or lenalidomide have been introduced to improve high-dose therapy outcome. From April 1998 to December 2008, 65 patients with MM underwent in our Department high-dose chemotherapy supported by autologous transplantation of peripheral blood stem cells (APBSCT). Transplantation of progenitor cells was conducted as consolidation of first line treatment in the majority of patients. Double transplantation was performed in 20 patients (31%). Conditioning regimen consisted of high-dose melphalan (200 mg/m2), in the second procedure the dose of melphalan was reduced to 140 mg/m2. Transplant related mortality was not observed. The duration of hematological recovery after first and second transplantation did not differ significantly. At the time of the analysis (June 2009) 51/65 (78.5%) patients are alive, 14/65 (21.5%) died due to disease progression. Median overall survival (OS) and progression free survival ( PFS) obtained were 86 (range 24-128) and 33 (range 4-110) months respectively. This retrospective analysis confirms the efficacy and safety of APBST in multiple myeloma patients.

The 3 case reports presented here constitute a pilot study assessing the profile of changes in concentrations of selected inflammatory markers, including C-reactive protein, serum amyloid A, neopterin, and interleukin 18, in an early period after allogeneic stem cell transplantation.

Assessment of frequency and clinical course of EBV infection in patients that underwent non-manipulated allo-HCT from matched-related donors.Active EBV infection was confirmed based on the presence of anti-EA antibodies (ELISA) and/or viral DNA (nPCR) isolated from peripheral leukocytes. For positive DNA-isolations semi-quantitative analysis were done. Patients were examined repeatedly, the time of monitoring was approximately 6 +/- 5 months.Active EBV infection was confirmed in 27 among 56 examined allo-HCT recipients. Primary infection was detected in 5 patients, in the remaining patients it was probably the result of virus reactivation. In most cases EBV-load was approximately 200 copies per 1 million of leukocytes, 1 patient with lymphoproliferative disorder (PTLD) had 2 million copies. EBV infection was asymptomatic in most cases (17), in 7 cases aminotransferase levels were insignificantly increased, in 2--diarrhea was observed and in 4 patients GvHD was intensified.In recipients without risk of PTLD, permanent monitoring of the EBV-load has no clinical justification.

Abstract 4516 Since June 2010 to July 2012 since in Department of Hematology of the University Hospital in Krakow five patients with advanced hematological malignancies have been subjected to allogeneic transplantation from matched related donors with clofarabine as a part of conditioning regimen. Indications for transplantation were relapsed/refractory acute myeloid leukemia in four patients and CML lymphoblastic crisis in relapse after RIC alloPBSCT in one patient. In a case of three patients conditioning regimen consisted of two phases. First phase: cytoreduction with clofarabine 20mg/m2/day + ARA-C 2000 mg/day for 4 days in 2 patients with refractory AML and Clofarabine 20mg/m2/day + Cyclophosphamide 400mg/day for 4 days in one (CML lymphoblastic crisis). Second phase: Busilvex + Fludarabine (Bu4Flu). Two later patients were treated without cytoreduction. One patient with extramedullary AML in second CR was treated with Clofarabine 30mg/m2 for 4 days + TBI. Last patient with early AML relapse was conditioned with Clofarabine30mg/m2 for 5 days+ Busilvex (BuClo). G-CSF mobilized peripheral blood was used as a source of stem cells in all the patients. Results: One patient died during conditioning regimen after cytoreduction (Clofarabine + Cyclophosphamide). It was the patient with CML lymphoblastic crisis relapse after RIC allogeneic transplantation. The other patients treatment toxicity was moderate (mucositis garde I-III). Aplastic period was complicated in one patient with septic infection. One patient relapsed 5 months after transplantation. He was diagnosed with AML secondary to MDN/MPD with very high cytogenetics (t(3;3) with 7 monosomy) Three of patient series remain in complete remission. All of them were diagnosed with relapse/refractory AML with CR duration 6 months to 26 months. Conclusions: Use of clofarabine as a part of conditioning regimen is valuable therapeutic option especially in the group of patients with relapsed/refractory AML. Disclosures: No relevant conflicts of interest to declare.

Abstract 3109 The outcome of patients (pts) relapsing after stem cell transplantation (SCT) is poor with limited therapeutic approaches in this group. A second or subsequent SCT is an option, however both high treatment related mortality (TRM) and high rate of disease relapse have been reported after such procedure so far. The objective of the study was to determine efficacy and safety of allogeneic SCT in patients relapsing with lymphoproliferative diseases after prior alloSCT or autoSCT. Material and methods. Fifty pediatric and adult patients with Hodgkin lymphoma (HL-24), non-Hodgkin lymphoma (NHL-10), acute lymphoblastic leukemia (ALL-9) and multiple myeloma (MM-7) in median age 33.5 (range: 3–56) years were included into the study. Nine pts relapsed after previous alloSCT and 41 after autologous transplant. The median time interval between previous transplant and relapse and median time interval between transplants were 8 (range :1–45) and 19 (range: 3–89) months, respectively. Complete remission (CR) was achieved in 23 pts before current transplant, while remaining 27 pts undergone alloSCT with active disease. For conditioning, reduced intensity protocols based on fludarabine were used in 46 pts, 4 were treated with myeloblative therapy based on total body irradiation (TBI). Stem cells from sibling (27) or unrelated (23) donors were grafted in median dose 4.1 (1.5–12.4)x10e6 of CD34+ cells/kg. Results: Engraftment was observed in 44 (88%) pts, 6 pts died before +21 day after transplant. Severe toxic complication (CTCAE grade 3–4) developed in 13 (26%) pts with multiorgan failure (MOF) in 7 of them. Infectious complications were observed in 41 (82%) pts (febrile of unknown origin 25, bacterial 10, fungal 3, bacterial+fungal 3). Acute graft versus host disease (GVHD) 2–4 grade occurred in 19 (38%) pts, while chronic extensive GVHD in 10 (20%) pts. Fifteen (30%) patients relapsed after treatment. Over a median follow–up duration of 7 (range: 0–83) months, 19 (38%) pts were alive with median survival 25 (95%CI=14.5–35) months. Probability of 3-years overall survival (pOS) was 0.117±0.091. Among 31 (62%) pts who died, 11 early deaths (before +100 day post transplant) occurred: 4 due to infection and 7 because of MOF. Late deaths were caused by relapse (9), GVHD (7), toxicity (2) and infections (2). TRM was 44%. The only factor contributing to 3-year pOS was remission vs active disease before transplant (0.458±0.140 vs 0.085±0.073; p=0.006). CR before second transplant reduced 2.9-fold (95%CI=1.3–6.2, p=0.008) the risk of death after procedure. Other estimated factors for OS (age, type of first transplant, pts and donor gender, conditioning method, stem cell source, toxic and infectious complications, GVHD occurrence, interval time between relapse and second transplant and between transplants) by Kaplan-Meier method were not statistically significant. Patients with late relapse (>6 months) after previous transplant reached survival plateau at 2 years (pOS=0.364±0.095 vs 0.0; ns). Conclusions: allogeneic SCT as a second procedure may be an option in relapsing patients with lymphoproliferative diseases after previous SCT. Remission status at time of salvage transplant is the most important determinant for the outcome. High rate of TRM remains a concern. Disclosures: No relevant conflicts of interest to declare.

Palifermin (Keratinocyte Growth Factor, KGF) is indicated to decrease the incidence, persistence and severity of mucositis in patients with hematologic malignancies receiving myeloablative chemotherapy with consecutive hematopoietic stem cell support. Hereby we present a clinical case of acute lymphoblastic leukemia (ALL) patient with a high risk of gastrointestinal complications who received intensive reinduction and consolidation chemotherapy together with KGF. 21-years old male with common ALL (BCR/ABL negative) with primary central nervous system (CSN) infiltration diagnosed in 2003, received two doses of standard induction therapy (vincristine + epirubicin) and four doses of intrathecal methotrexate (4 x 20mg) and arabinoside cytosine (4 x 50mg) with consecutive development of severe intestinal mucositis resulted in ileus perforation. After repeated procedure of laparotomy surgery the extended right hemicolectomy must had been performed. The patient remained in complete remission (CR) and was disqualified for following chemotherapy. After 23 months the patient relapsed with 90% of bone marrow infiltration and right testis involvement. Local irradiation was performed. Because of a high risk of severe life-threatening intestinal mucositis KGF was administered together with the second induction therapy according to PALG4-2002 protocol (Polish Adult Leukemia Group www.palg.pl). Patient’s informed consent and local Ethics Committee approval were obtained. KGF was administered 60μg/kg during three consecutive days before each cytostatics infusion with retaining of 24–48 hrs period between KGF and chemotherapy dose. No gastrointestinal side effects were observed, thus consolidation chemotherapy with non-reduced doses was performed. The only side effects that occurred during the treatment were taste alteration and subjective sensation of gustatory buds hypertrophy. A generalized intense bone pain during concomitant administration of KGF and granulocyte-colony stimulating factor (G-CSF) was observed. This seems to be significant because the symptom did not appear when the two drugs were administered separately. Currently the patient remains in CR and is qualified as eligible for allogeneic stem cell transplantation (SCT). A cytoprotective activity of KGF on distal parts of gastrointestinal tract has been concluded based on the case of intensive chemotherapy administered together with KGF in patient with high risk of severe chemotherapy-related intestinal mucositis. That may allow significantly reduce incidence and severity of gastrointestinal mucositis not only in patients receiving myeloablative chemotherapy but also in those who developed chemotherapy-related severe mucositis after non-myeloablative treatment. The excellent chemotherapy tolerability without any serious complication and no gastrointestinal side effects allows taking into consideration KGF administration in patients with hematological malignancies and high risk of severe mucositis.

Introduction Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome of extreme hyperinflammation. It does not self-limit and needs to be stopped by effective treatment. This reaction can be triggered by numerous factors, including infection, malignancy and autoimmune disease. HLH used to be diagnosed in children, but in last few years more and more adults with this syndrome are treated. This raising awareness enabled creating retrospective registry of adult HLH patients in Poland. Methods A multicenter retrospective analysis of adult (≥18 years) patients was performed. Inclusion criteria were based on the HLH-2004 protocol. Results Forty four adult (median age 34, range 18-80) patients from 13 clinical centers were reported. The gender ratio was balanced (M/F: 23/21). Patients fulfilled on the average 5.2 of HLH-2004 criteria. Due to the lack of possibility of sCD25 and NK activity testing in majority of centers only 6 criteria were actually evaluated. Also 6 patients with strong clinical suspicion (e.g. recurrent HLH) fulfilling 4 out of 6 available criteria were included. The most frequent triggering factor was malignancy (14/44) with lymphoma (T-cell 6/14, B-cell 4/14) being the most common. Infection-associated HLH was present in 13 patients, most of which was attributed to EBV (11/13; additionally CMV and B19 occurred). One patient suffered from both T-lymphoma and EBV infection. The most frequent autoimmune diseases identified were Still's disease (n=3) and systemic lupus erythematosus (n=2). In 11 patients clear triggering factor could not be identified. Three patients underwent liver transplantation. Baseline characteristics of all patients are shown in Table 1. Briefly, almost all patients presented with extreme hyperferritinemia, fever, splenomegaly. Other Important features are liver involvement and coagulopathy. Majority of patients were treated according to HLH-2004 protocol, except of patients with malignancy treated with disease-specific chemotherapy regimens (with emphasis on inclusion of etoposide if appropriate). None of the patients underwent stem cell transplantation (SCT) as HLH therapy; one patient had HLH triggered by EBV reactivation after alloSCT. Median survival was 66 days (Fig.1), 39% of patients survived with median observation of 21 months (3-98). Conclusions Heterogeneity of HLH syndrome was confirmed in Polish population, with malignancy and EBV infection being the most frequent triggering factors. Awareness of HLH in adults is raising, but it should be fostered as HLH is still underdiagnosed. Further studies are needed to deepen our knowledge about HLH in adults. Analysis of additional, newly diagnosed cases is ongoing and will be presented at the meeting. Table 1. Baseline patient characteristics Characteristic [unit] (n) % Median Range Fever (n=44) 97.7 Splenomegaly (n=44) 90.9 Hemophagocytosis (n=41) 70.7 Hyperferitinemia [µg/l] (n=44) 100 14280 846-126680 Hemoglobin [g/dl] (n=44) 8.3 6.1-13.9 Neutrophil count [G/l] (n=41) 1.1 0-173 Platelet count [G/l] (n=44) 43 4-349 Triglycerides [mg/dl] (n=38) 316 74-1559 Fibrinogen [mg/dl] (n=43) 166 30-901 PT [s] (n=30) 15.9 9-46.6 APTT [s] (n=39) 36 22-86.8 CRP [mg/l] (n=40) 40.1 0.4-373 LDH [U/l] (n=39) 970 195-13160 AST [U/l] (n=39) 150 16-16280 ALT [U/l] (n=40) 100 18-12390 Total Bilirubin [mg/dl] (n=37) 3.7 0.34-25.6 PT indicates Prothrombin Time; APTT, Activated Partial Thromboplastin Time; CRP, C-Reactive Protein; LDH, lactate dehydrogenase; AST, aspartate aminotransferase; ALT, alanine aminotransferase Disclosures Knopinska-Posluszny: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; Teva: Other: travel, accommodation, Speakers Bureau. Wiktor-Jedrzejczak:Amgen, Inc.: Research Funding; Onconova: Other: Advisory Board; Novartis: Research Funding; Pfizer: Other: Advisory Board; Roche: Other: Advisory Board, Research Funding; Jansen: Other: Advisory Board; Celgene: Other: Advisory Board.

Background: Allogeneic stem cell transplantation (alloSCT) is a potential curative treatment for patients (pts) with myelodysplastic syndrome (MDS), with reported long-term survival of 27% to 54% depending on risk group. Myeloablative conditioning (MAC) considered as standard therapy is associated with substantial treatment related mortality (TRM), especially in older pts or those with therapy related disease (tMDS); on the other hand, high rate of relapse have been reported after reduced intensity conditioning (RIC). Therefore, Polish Adult Leukemia Group (PALG) in cooperation with Polish Pediatric Group for Hematopoietic Stem Cell Transplantation analyzed the outcome of MDS pts transplanted between 2000 and 2013 with respect to conditioning intensity. Material and methods. Three hundred and four pediatric and adult patients with median age of 38 years (range: 1-69) were retrospectively analyzed. The study cohort included pts with intermediate-2/high risk according to IPSS (136), unfavorable cytogenetics (86), secondary AML (43) and tMDS (35). Among adult pts (216), 74 (34%) were older than 50. The median time between diagnosis and transplant was 8 months (range:1-117). Before transplantation 202 pts had 10%. For conditioning, RIC protocols based on fludarabine were used in 180 pts and 102 pts were treated with myeloablative therapy based on busulphan. Stem cells from related (144) or unrelated (160) donors were grafted in median dose 4.75 (1.3-27.4)x106 of CD34+ cells/kg. Peripheral blood (PB) stem cells were transplanted in 222 pts. Thirty nine pts received allograft from HLA mismatched donors. Results: Engraftment occurred in 285 (94%) pts and 8 pts died before +21 day after transplantation. Infectious complications were observed in 252 (82%) pts during neutropenia (febrile of unknown origin 163, bacterial 53, fungal 24, bacterial and fungal 12). Late infections, assessed in those who survived 100 days, occurred in 130 (50%) pts, and were related mainly to CMV infection. Severe toxic complications (CTCAE grade 3-4) developed in 67 (22%) pts. Acute graft versus host disease (GVHD) grade 2-4 occurred in 77 (27%) pts, while chronic extensive GVHD in 37 (14.5%) pts. Forty seven pts experienced disease relapse after treatment. Over a median follow-up of 43 months (range: 15-70) 156 (51%) pts were alive. In 44 cases deaths were related to relapse, 36 pts died due to GVHD, 43 due to infection and 25 because of organ toxicity. Probability of 3-years overall survival (OS), disease free survival (DFS), relapse incidence (RI) and TRM were 0.51±0.03, 0.50±0.03, 0.18±0.03 and 0.47±0.03, respectively. OS (0.56±0.04 vs 0.44±0.04, p=0.036) and TRM (0.31±0.04 vs 0.43±0.04, p=0.040) were statistically better for pts transplanted after 2007 (Figure 1). In multivariate analysis the only factors associated with lower OS were bone marrow blasts before alloSCT >10% (p=0.05, HR 1.5), mismatched donor (p=0.015, HR 1.8), PB as source of stem cells (p=0.048, HR 1.5) and alloSCT performed after 2007 (p=0.029, HR 1.6). There were no statistically significant differences in OS, DFS, RI and TRM between pts conditioned with RIC or MAC when analyzed in whole study cohort or with respect to age group, IPSS risk group, cytogenetics, interval from diagnosis to alloSCT. Conclusions: Allogeneic SCT is an option for MDS patients in different age groups. Disease status at time of transplant, mismatched donor and PB source of stem cells, but not conditioning intensity are the most important determinant for the outcome. High rate of TRM remains a concern, despite improvement over time. Fig 1. Results of alloSCT in MDS Fig 1. Results of alloSCT in MDS Disclosures Jedrzejczak: Amgen, Novartis : Consultancy, Research Funding.