Patient-Specific Risk Factors Independently Influence Survival in Myelodysplastic Syndromes in an Unbiased Review of EHR Records

Background: Myelodysplastic syndromes (MDS) are clonal hematologic neoplasms stratified by risk by the international prognostic scoring system (IPSS) and IPSS-revised (IPSS-R) which measure risk by morphologic dysplasia, clinical cytopenias, blast count, and cytogenetic abnormalities. (PMID: 9058730, 22740453) The IPSS/IPSS-R do not consider clinical comorbid conditions, though MDS patients with higher burden of comorbid disease have higher rates of non-leukemic death, particularly those with cardiovascular and pulmonary disease. (19324411) Despite this, there has been limited investigation into how specific comorbid conditions may help define subgroups of patients with MDS. Methods: We identified 2676 cases of MDS as defined by ICD-9 code (238.72 - 238.75) in Vanderbilt's Synthetic Derivative (SD). The SD is a de-identified electronic health record (EHR) of over 2.2 million patients with a companion biorepository of DNA (BioVU) for a subset of these patients, including all of the patients with MDS. The 2676 cases were matched by age, gender, race, burden of comorbidities in EHR, and age at last appointment in EHR with 5287 controls. ICD-9 codes for other myeloid disease (e.g., myeloproliferative neoplasms, acute myeloid leukemia) or history of hematopoietic stem cell transplant were excluded among the controls. Characterization of comorbidities, via phecode analysis, was conducted on all cases and controls. Phecodes are groups of related ICD-9 codes describing a clinical syndrome or medical problem, previously demonstrated to be useful in phenome-wide associated studies in EHRs. (28686612) A case was defined as having a phecode only if a representative ICD-9 code was present on two distinct days in the EHR. Next, a cluster analysis of the study population and their associated comorbidities, via a bipartite stochastic block model, was completed, and the study population was organized into hierarchical structure based upon the similarities in comorbidity patterns among patients. Results: ICD-9 codes from the study population made up 181 phecodes, which were found in hierarchical cluster analysis to further cluster into 54 sub-groups and 16 larger groups. MDS patients clustered throughout all groups, the majority of which contained control patients; yet some MDS cases sub-clustered into groups that included a majority of MDS cases and these were further analyzed. Notably, two groups had equivalent size and MDS status were found to have significant differences in phecode profiles. Group 1 had 795 total patients with 783 MDS cases (98.5%) and Group 2 had 769 total patients with 684 MDS cases (88.9%), as per Fig 1a. There were no significant difference in sex between the two groups. Group 1 patients were significantly younger than Group 2 patients (58.3y vs 62.9y; p = 1.36 x 10-7), yet tended have increased risk of renal, cardiovascular and thromboembolic disease than Group 2, as per Fig 1b. Additionally, a higher proportion of Group 2 patients (695/769 or 90.4%) were alive at time of data extraction than Group 1 patients (451/795 or 56.7%) (OR 4.51, p = <2.2 x 10-16). Conclusions: By performing a phenome-wide analysis of patients with MDS in a large electronic health record (EHR), we reveal specific subgroups of MDS patients with distinct comorbidities and different survival, not affected by age or sex. This study demonstrates the ability to study comorbid conditions of MDS patients in an unbiased fashion, independent of disease specific risk factors that inform IPSS-R and which have historically been most important in stratifying risk in MDS. The role of comorbidity is instinctually clear to the adroit clinician, and this technique could provide distinct comorbid disease patterns which impute risk, or perhaps etiology in MDS. Disclosures Savona: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm Therapeutics: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Selvita: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Patents & Royalties; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees.

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Exploration of Survival Stratification of Patients with Multiple Myeloma after First Relapse Using Real World Data

Blood ◽

10.1182/blood.v128.22.2417.2417 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2417-2417 ◽

Cited By ~ 1

Author(s):

Roman Hájek ◽

Jiri Jarkovsky ◽

Walter Bouwmeester ◽

Maarten Treur ◽

Lucy DeCosta ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Treatment Decision ◽

Advisory Committees ◽

Patient Risk ◽

First Relapse ◽

Survival Expectations ◽

Group 2 ◽

Group 1

Abstract Risk stratification tools in multiple myeloma (MM), such as the International Staging System (ISS) and the revised-ISS (R-ISS), have improved understanding of survival expectations using the strongest known predictors at time of diagnosis. Given their value at diagnosis, these have been used to define risk after first relapse in clinical trials and standard practice. Although these tools have not been validated in this setting, their use arises because of the need to better characterize patients in order to define survival expectations and treatment decisions. Once the patient has relapsed, there are additional variables that may need to be considered in order to systematically assess patient risk, understand drivers of disease progression and ensure that treatment strategies are aligned with patient risk. Using data from the Czech Registry of Monoclonal Gammopathies (RMG), this study assessed predictors of overall survival (OS) and developed a new Risk Stratification Tool (RST) to predict OS at time of treatment decision after first relapse (TTD1). The RST was developed by estimating the strongest predictors of OS at both diagnosis and TTD1 to define the final parameters for inclusion. The cut-offs for each parameter reflect conventional cut-offs used in clinical practice and some were supported by evidence using a K-adaptive Partitioning for Survival (KAPS) approach, which stratified data based on distinct survival expectations. The hazard ratio (HR) of the selected predictors was used to assign a score per parameter at a patient level where missing data were entered with a contribution equal to 1. Using the full RMG data set at TTD1 (N=1418) the (KAPS) method was run to define 4 distinct group of patients based on survival expectations. The RST consists of 4 dimensions and 12 item questions based on the strongest predictors of survival at TTD1, "Patient Factors" (age and Eastern Cooperative Oncology Group (ECOG) performance status), "Existing Stratification Factors (R-ISS at diagnosis and ISS at TTD1), "Disease Factors" (calcium level, number of bone lesions, extramedullary disease, thrombocyte count, clonal cells in bone marrow aspiration cytology, lactate dehydrogenase [LDH]) and "Treatment history" (refractory to prior therapy, time-to-next-treatment [from initiation of treatment of first anti-myeloma drug to initiation of treatment at first relapse]) (Table 1). Subsequently, we explored each group based on distribution of frailty-driven measures (age and ECOG) and aggressiveness of the disease (rest of parameters) to understand what is driving stratification. Figure 1 shows the KM curve of survival after TTD1 for each of the 4 groups estimated by KAPS. The new analysis shows strong differentiation in survival expectations between the 4 groups (Table 2), showing significantly different OS for all groups compared with reference. The median OS and Confidence Intervals per group did not overlap, supported by the positive association of HR across groups. The distribution of the Total Score (Figure 2) is between 1 and 2, which shows sufficient sensitivity to differentiate these groups by survival expectations. The RST can then be split into Frailty Score and Aggressiveness Score (Figure 3a & b) to understand what is driving disease severity. The distribution of these two scores shows that group 1 consists of low patient frailty and low disease aggressiveness, whereas group 4 shows high on both elements. Group 2 has an increased score for frailty and marginal increase in aggressiveness compared with group 1, and group 3 stratification is driven by an increase in aggressiveness over group 2. The analysis showed that predictors, patient's experience of prior treatment and level of disease impact at the point of treatment decision after first relapse provided an initial framework to demonstrate strong differentiation between groups based on patient severity and what is driving patient risk (patient frailty vs aggressiveness of disease). The RST has shown promising results when applied to the RMG, however further validation of this work is required using other real-world and clinical trials data. Nevertheless, this analysis is a first step in systematically assessing patient risk to improve the selection of treatments based on improved understanding of patient profiles. Disclosures Hájek: Amgen: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; BMS: Honoraria; Takeda: Consultancy; Celgene: Consultancy, Research Funding. Bouwmeester:Amgen: Consultancy. Treur:Amgen: Consultancy. DeCosta:Amgen: Employment, Other: Holds Amgen Stock. Campioni:Amgen: Employment, Other: Holds Amgen Stock. Delforge:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Raab:BMS: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Schoen:Amgen: Employment, Other: Holds Amgen Stock. Szabo:Amgen: Employment, Other: Holds Amgen Stock. Lucie:Amgen: Consultancy. Gonzalez-McQuire:Amgen: Employment, Other: Holds Amgen Stock.

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RAEB-1 with Erythroid Hyperplasia and Erythroleukemia Share Clinico-Biological Features and Outcome: A Same Disease with Different Labels?

Blood ◽

10.1182/blood.v126.23.2866.2866 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2866-2866

Author(s):

Xavier Calvo ◽

Leonor Arenillas ◽

Mar Tormo ◽

David Valcárcel ◽

Elisa Luño ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

De Novo ◽

Erythroid Cell ◽

Advisory Committees ◽

Biological Features ◽

Erythroid Hyperplasia ◽

Group 2 ◽

Group 1 ◽

Who 2008

Abstract Introduction: Based on the 2008 World Health Organization classification (WHO 2008), erythroleukemia is defined by the presence of ≥50% erythroid precursors in bone marrow (BM) and ≥20% myeloblasts in the non-erythroid cell population. Multilineage dysplasia is almost always present with high rates of MDS-like cytogenetic abnormalities, specially complex karyotypes. Therefore an extensive comparison with myelodysplastic syndromes (MDS) with ≥50% erythropoesis seems crucial to elucidate whether erythroleukemia and MDS with erythroid hyperplasia should be considered as different biological entities. Aim: To elucidate this issue, the outcome and cytogenetic alterations of erythroleukemia patients were studied and compared to MDS patients with ≥50% erythropoesis with <5% BM blasts (RA, RARS, CRDM, MDS-U) or those with ≥5%-<10% (RAEB-1). In this subset of patients, the diagnosis of RAEB-2 is not possible because those with ≥50% erythropoesis and ≥10% BM blasts were formally diagnosed with erythroleukemia when the blast percentage was assessed in the non-erythroid cell population. Methods: We retrospectively analyzed 448 de novo MDS with ≥50% erythropoesis and 59 de novo erythroleukemias from the MDS Spanish registry (RESMD). Diagnosis was done according to WHO 2008 and patients with ≥80% erythropoiesis with less than 20% of myeloblasts in the non-erythroid cell compartment were excluded assuming a diagnosis of pure erythroid leukemia. Results: Median age of presentation was 74 years (25-94 years), median follow-up was 29.4 months, 63% were males. Median overall survival (OS) of MDS patients with ≥50% erythropoiesis and <5% of BM blasts (n=389; group-1) was significantly longer than MDS with ≥50% erythropoiesis and ≥5%-<10% (n=59; group-2/RAEB-1) (69 months vs. 18 months, p <0.001). Although erythroleukemia patients (n=59) presented a shorter median OS than group-1 patients (69 months vs. 14.5 months, p <0.001), there was no significant differences compared to group-2 patients (RAEB-1) (18 months vs. 14.5 months, p =0.679). Figure 1. Percentage of abnormal karyotypes was significantly higher in the group-2 and EL vs. group-1 but there was no significant differences between group-2 and erythroleukemia (56.9% vs. 44.1%, p =0.165). Moreover no significant differences were observed in the percentage of high-risk karyotypes defined by the IPSS (complex karyotype, chromosome 7 abnormalities) between RAEB-1 and erythroleukemia (30.5% vs. 23.7%, p =0.408). Finally, the presence of a high-risk IPSS karyotype was capable to discriminate two risk groups in the subset of patients with ≥5% BM blasts (RAEB-1 and erythroleukemia). Figure 2. Conclusion: Erythroleukemia and RAEB-1 with ≥50% erythropoiesis share clinico-biological features and outcome. Our findings suggest that erythroleukemia is a continuum of MDS with erythroid hyperplasia and karyotype rather than an arbitrary blast cut-off is the main prognostic marker in this subset of patients. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Valcárcel: Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Díez-Campelo:Celgene: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Janssen: Research Funding. Ramos:GlaxoSmithKline: Honoraria; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria.

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Acute Myeloid Leukemia with Myelodisplasia-Related Changes (AML-MRC) Defined Only By Morphological Findings May Not Represent a Poor Prognosis AML

Blood ◽

10.1182/blood-2019-129153 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2612-2612

Author(s):

Ana Pérez ◽

Olga Salamero ◽

Helena Pomares ◽

Maria Julia Montoro ◽

Montserrat Arnan Sangerman ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Myeloid Leukemia ◽

Research Funding ◽

Poor Prognosis ◽

Advisory Committees ◽

Group 3 ◽

Group 2 ◽

Acute Myeloid ◽

Group 1

According to the 2016 WHO classification, AML-MRC encompasses an heterogeneous group of acute myeloid leukemias (AML) comprising: AML emerged from a previous myelodysplastic syndrome (MDS) or myeloproliferative /myelodysplastic disease (group 1), AML with MDS-defining cytogenetic abnormalities (group 2), or acute myeloid leukemia (AML) with dysplasia in at least 2 cell lineages without the above mentioned (group 3). In spite that AML-MRC has been considered a high-risk entity with poor prognosis, little is known on the relationship of clinical and biological characteristics with outcomes in these three groups. The aim of this study was to describe the clinical and biological characteristics of patients with AML-MRC and analyze their prognostic variables and outcomes. We retrospectively analyzed AML-MRC cases diagnosed between January-2009 and December- 2018 in two institutions. Descriptive variables were studied to compare the three AML-MRC groups. AML cytogenetic risk and response were defined according to the European Leukemia Net recommendations. Overall survival (OS) was considered as the time from the diagnosis to the last visit. Survival analysis were performed with Kaplan Meier method and comparisons with the log-rank test. Among 575 cases of AML identified, 186 (32.3%) met AML-MRC criteria and were included in the study. The main patient characteristics are shown in Table1. Median age was 72 (range, 22-88) years and 32% were female. Adverse karyotype was present in 29% of patients, being more prevalent in the AML-MRC group 2. Sixty one patients (33%) received an intensive chemotherapy approach and 36 (19%) an allogeneic stem cell transplantation. Patients in group 3 exhibit a higher probability of achieving a complete response than groups 1 and 2 (Table 2). After a median follow-up for survivors of 28.5 months (range, 5-130), 149 (80%) died in this period. Three years Overall Survival (OS) for patients in groups 1, 2 and 3 was 3 (0-117), 5 (0-93) and 10 (0-130) months, respectively (p=0.012) (Figure 1). Type of treatment (intensive, non intensive or best supportive care) and cytogenetic risk also showed impact on OS. Multivariant analysis adjusting these factors showed that patients in group 3 also presented better OS than patients in group 1 (HR=0,42 [IC95% 0,18-0,84], p=0,02), both with around a 30% of patients with adverse cytogenetics. To conclude the present study suggests that group 3 of AML-MRC, for which the diagnosis is based solely on morphologic findings, showed better prognosis than the other groups. A more detailed molecular characterization might contribute to improve prognostic stratification of this heterogeneous AML entity, particularly in patients with non-high risk cytogenetics. Disclosures Salamero: Pfizer: Honoraria; Daichii Sankyo: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Valcárcel:Jazz Pharmaceuticals: Honoraria; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: spouse is an employee in the company, Speakers Bureau; Pfizer: Honoraria. Bosch:AstraZeneca: Honoraria, Research Funding; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Improved Treatment Outcomes for Patients with Hodgkin Lymphoma Relapsing after Autologous Hematopoietic Stem Cell Transplantation in the Brentuximab Vedotin Era - the Real-Life Report from the Polish Lymphoma Research Group

Blood ◽

10.1182/blood-2019-130484 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5276-5276

Author(s):

Anna Czyz ◽

Anna Lojko-Dankowska ◽

Agnieszka Giza ◽

Monika Dlugosz-Danecka ◽

Wojciech Jurczak ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Salvage Chemotherapy ◽

Brentuximab Vedotin ◽

Salvage Treatment ◽

Study Group ◽

Advisory Committees ◽

Historical Group ◽

Group 2 ◽

Group 1

Background Brentuximab vedotin (BV) is an effective salvage treatment in patients with relapsing/progressive Hodgkin lymphoma (HL). However, it is unclear how much BV improved the outcome of BV naïve patients who relapsed after autologous hematopoietic stem cell transplantation (autoHCT) in real life. To address this question, we compared the outcome of patients who received conventional salvage treatment before the BV era to those who were treated with BV in haematological centres allied within the Polish Research Study Group. The goals of the study were to compare: the response rates to the conventional salvage chemotherapy and to the BV-based treatment, the proportion of patients proceeding to subsequent allogeneic (allo) or second autologous HCT and finally the overall survival (OS), and progression-free survival (PFS) of relapsing patients after autoHCT treated with and without BV. Methods and study group The study group consisted of adult patients with classical HL relapsing after first autoHCT who were treated either with conventional salvage chemotherapy (between 2001 and 2013; Group 1, n=121) or BV based treatment (between 2012 and 2018; Group 2, n=44). The groups did not differ in terms of age or gender. The patients in Group 2 received more chemotherapy lines before post-transplant salvage treatment (median 3, range 1-6) compared to those in historical Group 1 (median 2, range 1-6) (p=0.013). No patient was treated with immune check points inhibitors. The response to salvage treatment in the majority of patients in historical Group 1 was assessed with conventional computer tomography (CT), while in all patients in Group 2 with CT combined with positron emission tomography. Results The rate of the objective response rate defined as the complete or partial response was higher in Group 2 (84% vs 60%, p<0.001). Of a total of 121 patients in Group 1, 34 (28%) proceeded to the second autoHCT, and 27 (22%) to alloHCT, compared to 4 (9%) and 20 (45%) of 44 patients in Group 2, respectively (p=0.004). The median follow-up time of survivors is longer in the historical Group 1 compared to Group 2 (40 months vs 19 months, p <0.001). However, at 2 years after the start of post-transplant salvage treatment, the estimated OS for patients in Group 1 was 55.2 % (95 % CI 45.8-64.3 %) compared to 81.9 % (95 % CI 66.5-91.2 %) for patients treated with BV (p=0.009) (figure). The respective estimated 2-year PFS was 41.2% (95 % CI 32.3-50.8 %) for Group 1 and 56.2% (95 % CI 38.5-72.4 %) for Group 2 (p=0.038). Importantly, the OS of patients who proceeded to alloHCT after BV-based salvage treatment was statistically significantly better compared to patients treated with alloHCT in the historical pre-BV group (2-year OS 81% vs 55%, p< 0.001). Conclusions In the era of brentuximab vedotin, significantly more patients with HL relapsing after autoHCT achieve objective response and proceed to allogeneic HCT. This most likely translates to the better PFS exceeding 24 months and most importantly to the significantly better OS of patients treated with BV compared to those treated with conventional salvage chemotherapy in the pre-BV era. Figure Disclosures Czyz: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dlugosz-Danecka:Roche: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Macrogenomics: Research Funding; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jurczak:Gilead: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Roche: Research Funding; Servier: Research Funding; MorphoSys: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding; Novo Nordisk: Research Funding; Bayer: Research Funding; Celtrion: Research Funding. Walewski:Gilead: Other: Travel Expenses; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wrobel:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zaucha:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Significance of Degree of HLA Disparity When Using Haploidentical Donors with T-Replete PBSC and Post-Transplantation Cyclophosphamide (PTCy) in Acute Myeloid Leukemia (AML) in First Complete Hematologic Remission (CR1)

Blood ◽

10.1182/blood-2021-149651 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3910-3910

Author(s):

Mohamed A. Kharfan-Dabaja ◽

Myriam Labopin ◽

Ernesto Ayala ◽

Ali Bazarbachi ◽

Didier Blaise ◽

...

Keyword(s):

Board Of Directors ◽

Cumulative Incidence ◽

Research Funding ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Hazard Ratio ◽

Advisory Committees ◽

Group 2 ◽

Hla Mismatches ◽

Group 1

Abstract Background: Haploidentical allogeneic hematopoietic cell transplantation (haplo) has expanded applicability of the procedure to patients for whom a suitable HLA compatible donor was not available in the past. A small multicenter retrospective study of 185 patients with hematologic malignancies who received a nonmyeloablative preparative regimen followed by infusion of bone marrow (BM) hematopoietic cells from haploidentical donors showed no significant association between the number of HLA mismatches (HLA-A, -B, -C, and -DRB1 combined) and risk of acute grade 2-4 graft-versus-host disease (GVHD) (hazard ratio [HR]=0.89; P=0.68 for 3-4 mismatches vs fewer antigen mismatches). This haploidentical transplant platform has certainly evolved. Nowadays, G-CSF mobilized peripheral blood stem cells (PBSC) are commonly used owing to its increased convenience vis-à-vis performing a BM harvest. Study population: Here, we evaluate post transplant outcomes when using haploidentical donors with T-replete PBSC and PTCy in AML in CR1. A total of 494 patients (4/8 HLA mismatch (group 1)=360, 2-3/8 HLA mismatch (group 2)=134) underwent the procedure at an EBMT participating center. The primary endpoints were cumulative incidences of grade 2-4 acute GVHD and chronic (all grades) GVHD. Secondary endpoints included cumulative incidence of relapse (RI), non-relapse mortality (NRM), leukemia-free (LFS) and overall survival (OS) and GVHD-free relapse-free survival (GRFS). Results: Group 1 and group 2 were not statistically different in regards to median age at allografting (54.1 vs. 56.1 years, p=0.51), median year of haplo transplantation (2018 vs. 2018, p=0.36), incidence of de novo AML (86.4% vs. 88.1%, p=0.63), Karnofsky equal or more than 90 (77.5% vs. 79.1%, p=0.70), and use of myeloablative conditioning (MAC) (44.7% vs. 48.5%, p=0.45). Patients in group 1 had a longer time from diagnosis to haplo-transplantation (5.3 vs. 4.9 months, p=0.03). In multivariate analysis, group 1 and group 2 did not differ in cumulative incidence of grade 2-4 acute GVHD (Hazard ratio (HR)=0.89 (95%CI=0.62-1.26), p=0.51) but group 1 had a significantly higher incidence of chronic (all grades) GVHD (HR=1.49 (95%CI=1.02-2.16), p=0.04). There was no difference in RI (HR=0.73 (95%CI=0.47-1.14), p=0.17), NRM (HR=1.25 (95%CI=0.78-2.02), p=0.36), LFS (HR=0.95 (95%CI=0.69-1.31), p=0.76), OS (HR=1.09 (95%CI=0.76-1.55), p=0.64) and GRFS (HR=1.07 (95%CI=0.81-1.42), p=0.64) between the groups. Presence of adverse cytogenetics was independently associated with higher RI (HR=1.90 (95%CI=1.20-2.99), p=0.006), inferior LFS (HR=1.59 (95%CI=1.15-2.19), p=0.005), inferior OS (HR=1.48 (95%CI=1.05-2.08), p=0.03), and worse GRFS (HR=1.54 (95%CI=1.17-2.04), p=0.002). Conclusion: Results show that patients undergoing haplo-transplantation with 4/8 (vs. 2-3/8) HLA mismatches have a higher incidence of chronic GVHD (all grades) without adversely affecting acute grade 2-4 GVHD, RI, LFS, OS and GRFS. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Bazarbachi: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hikma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees. Blaise: Jazz Pharmaceuticals: Honoraria. McDonald: BioCryst Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Forcade: Novartis: Other: travel grant. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Mohty: Takeda: Honoraria; Astellas: Honoraria; Adaptive Biotechnologies: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Jazz: Honoraria, Research Funding; Pfizer: Honoraria; Amgen: Honoraria.

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Risk Factors Associated with the Development of Infusion-Related Reactions in Patients with Chronic Lymphocytic Leukaemia Treated with Anti-CD20 Monoclonal Antibodies: Analysis of the CLL11 Study Dataset

Blood ◽

10.1182/blood.v124.21.3339.3339 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3339-3339 ◽

Cited By ~ 4

Author(s):

Ciara Louise Freeman ◽

Mark Dixon ◽

Richard Houghton ◽

Kathryn Humphrey ◽

Gunter Fingerle-Rowson ◽

...

Keyword(s):

Risk Factors ◽

Monoclonal Antibodies ◽

Board Of Directors ◽

Research Funding ◽

Lymphocytic Leukaemia ◽

Signs And Symptoms ◽

Leukemic Cells ◽

Tumour Burden ◽

Advisory Committees ◽

Anti Cd20

Abstract Background: The administration of anti-CD20 monoclonal antibodies (mAb) in patients with B-cell lympho-proliferative disorders is frequently accompanied by a constellation of signs and symptoms that have been labelled as infusion-related reactions (IRR). The pathophysiology of IRR remains poorly understood as do predictors of risk, which may relate to the mechanism of action of the anti-CD20, disease-related factors such as tumour burden or host factors such as polymorphisms of Fc gamma receptor 3A (FcγRIIIA). In the CLL11 trial (NCT01010061), patients with previously untreated chronic lymphocytic leukaemia and comorbidities were randomised to receive either rituximab (type I anti-CD20 mAb) or obinutuzumab (type II and glycoengineered anti-CD20 mAb) in combination with chlorambucil for six cycles. Obinutuzumab led to faster depletion of B cells and achieved an improvement in outcome parameters such as response and progression-free survival compared with the rituximab arm, but was also associated with a higher rate and increased severity of IRR. To better understand the profile of risk for IRR in patients with CLL, we performed an exploratory analysis on data obtained from patients treated with either one of the two antibodies given in combination with chlorambucil. Methods: Patients from the prospective, randomized Phase III CLL11 study who received a first infusion of obinutuzumab (N=331) or rituximab (N=326) were included. Baseline pre-treatment risk factors thought to play a possible role in the development of IRR were identified a priori and included patient demographics, concurrent conditions and premedications, parameters of disease burden, prognostic factors, laboratory variables and FcγR genotype. Baseline values for mean fluorescence intensity (MFI) of CD20, gated on the circulating CLL clone, and MFI of CD16, gated on the natural killer (NK) cell population (CD56+16+) in peripheral blood were also available for N=510 patients. The primary outcome, development of an IRR with the first infusion, was defined as the occurrence of related signs and symptoms during or within 24 hours of administration of antibody. Due to the short-term nature of the initial IRR a multivariate logistical regression analysis was performed rather than a time to event analysis. Internal validation of this model, derived from a single dataset, was conducted using the established resampling technique of bootstrapping. This assessed the proportion of times each variable retained significance at α=0.10 when the model was fitted to bootstrapped samples of the dataset. Results: Patients that appeared to be at greater risk of developing any grade of IRR with the first infusion of rituximab or obinutuzumab were those treated with obinutuzumab, those with higher surface expression CD20 on CLL cells (MFI CD20) and greater FcγRIIIA (MFI CD16) on NK cells in peripheral blood, those with higher affinity FcγRIIIA genotype (VV), more pronounced neutropenia and splenomegaly at baseline (Table 1). Higher baseline absolute lymphocyte count and the presence of respiratory comorbidity also appeared to increase risk. All variables significant for inclusion in the model are shown in Table 1. Looking at those patients treated with obinutuzumab only, the most important determinant of risk was MFI CD20 (OR 3.6 95% CI 1.6-7.9). The impact of glucocorticoid premedication in reducing risk in obinutuzumab treated patients was not sufficient to reach significance, however, patients were not randomised to this intervention. Conclusion: This work identifies novel disease- and patient-specific biological variables that appear to play a role in the development of IRR in patients with CLL treated with anti-CD20 mAb, although the treatment received (obinutuzumab >rituximab) confers greatest risk. In addition to parameters of tumour burden, target antigen expression and gene polymorphisms of FcγR also appear to contribute to the risk of developing an IRR. Our results support the hypothesis that higher rates of IRR seen with the administration of obinutuzumab may result from stronger activation upon binding to CD20 on leukemic cells and subsequent enhanced cross-linking between CD20 expressing leukemic cells and FcγRIIIA bearing effector cells. Further studies involving obinutuzumab in this patient population will be needed to externally validate the results of this exploratory analysis. Disclosures Freeman: Roche Pharmaceuticals: clinical research fellowship supported by Roche Pharmaceuticals (secondment from Bart's) Other. Dixon:Roche Pharmaceuticals: Employment. Houghton:Roche Pharmaceuticals: Employment. Humphrey:Roche: Employment. Fingerle-Rowson:Roche Pharmaceuticals: Employment. Kreuzer:Roche Pharmaceuticals: Research Funding. Engelke:Roche: Travel grants Other. Hallek:Roche Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau. Goede:Bristol Myers Squibb: Honoraria; Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel grants Other.

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Clinical and Biomarker Predictors for Avascular Necrosis in Sickle Cell Disease

Blood ◽

10.1182/blood-2021-147829 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3091-3091

Author(s):

Michael Rabaza ◽

Maria Armila Ruiz ◽

Liana Posch ◽

Faiz Ahmed Hussain ◽

Franklin Njoku ◽

...

Keyword(s):

Risk Factors ◽

Sickle Cell Disease ◽

Board Of Directors ◽

Avascular Necrosis ◽

Sickle Cell ◽

Research Funding ◽

Medical Attention ◽

Cell Disease ◽

Advisory Committees ◽

Early Management

Abstract Introduction Sickle cell disease (SCD) affects 1 in 365 African Americans and approximately 25 million people world-wide. A common skeletal system complication is avascular necrosis (AVN), which can cause substantial pain and a reduced quality of life. While early management of AVN is focused on increasing range of motion with physical therapy and pain relief, there are no clear predictors for who is more likely to develop AVN and earlier institution of these preventive measure could help decrease disease progression. Vascular endothelial growth factor (VEGF) is a biomarker of endothelial injury and may indicate reduced vascular supply to the femoral or humeral head. Here we describe potential risk factors and biologic pathways for AVN in SCD, as understanding these may lead to improvements in future monitoring, early detection, and early intervention practices. Methods We investigated clinical and laboratory risk factors associated with AVN in a cohort of 435 SCD patients from our center. Blood samples, clinical, and laboratory data were collected at the time of enrollment during a clinic visit. Genotyping for alpha thalassemia was performed by PCR and the serum concentration of VEGF was measured by ELISA. AVN status was confirmed by review of the medical record and available imaging. We conducted a cross-sectional analysis comparing categorical and linear variables by AVN status using the chi-square and Kruskal-Wallis test, respectively. The independent association of the clinical and laboratory variables with AVN status was determined by logistic regression analysis. The initial model included variables with a P-value < 0.1 on univariate analysis and the final model was ascertained by stepwise forward and backward selection. Median values and interquartile range (IQR) are provided. Results The median age of the cohort was 32 (IQR, 24 - 43) years, 57% (250/435) were female, and 46% (198/435) were on hydroxyurea. AVN was observed in 34% (149/435) of SCD patients. SCD patients with AVN were older, had more frequent vaso-occlusive crises requiring medical attention, and had a higher body mass index (Table I) (P ≤ 0.002). We measured VEGF in 241 of the SCD patients with serum samples available at the time of enrolment. Serum VEGF concentrations trended higher in SCD patients with versus without AVN (420 vs. 359 pg/mL, respectively; P = 0.078). In the multivariate analysis model, AVN was independently associated with increased number of vaso-occlusive crises (OR 1.1, 95% CI: 1.0 - 1.14; P = 0.02), AST concentration (natural log OR 0.5, 95% CI: 0.2 - 0.9; P = 0.03), VEGF concentration (natural log OR 1.4, 95% CI: 1.0 - 1.9; P = 0.047), and tobacco use (OR 1.9, 95% CI: 0.9 - 3.7; P = 0.078). Discussion In conclusion, we demonstrate a high prevalence of AVN in an adult cohort of SCD patients. The presence of AVN was independently associated with a greater frequency of vaso-occlusive pain episodes, which may demonstrate a shared pathophysiology between AVN and vaso-occlusion that merits further investigation. We demonstrate that serum VEGF concentrations are higher in SCD patients with AVN and may be a clinical tool to identify those at high-risk and for earlier intervention for this complication. Figure 1 Figure 1. Disclosures Gordeuk: Modus Therapeutics: Consultancy; Novartis: Research Funding; Incyte: Research Funding; Emmaus: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; CSL Behring: Consultancy. Saraf: Pfizer: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Hypercholesterolemia In Imatinib Intolerant/Resistant CML-CP Patients Treated With Nilotinib: A Retrospective Analysis

Blood ◽

10.1182/blood.v122.21.1503.1503 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1503-1503 ◽

Cited By ~ 9

Author(s):

Devendra K. Hiwase ◽

David T Yeung ◽

Lisa Carne ◽

David Ross ◽

Andrew Grigg ◽

...

Keyword(s):

Risk Factors ◽

Lipid Profile ◽

Retrospective Analysis ◽

Board Of Directors ◽

Research Funding ◽

Lipid Profiles ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Advisory Committees ◽

Before And After

Abstract Background CML patients (pts) enjoy prolonged leukaemia-free survival with tyrosine kinase inhibitor (TKI) treatment. Addressing common non-CML causes of morbidity and mortality such as cardiovascular disease (CVD) and its associated risk factors is therefore increasingly important. Anecdotal evidence suggests a possible association between nilotinib (NIL) therapy and vascular events though there is little good quality evidence in this regard. The incidence of hyperlipidaemia and hyperglycaemia is higher in NIL-treated pts compared to imatinib- (IM) treated pts; conversely IM treatment may retard development of dyslipidaemia and hyperglycaemia. This retrospective analysis assessed the lipid profile of CML-CP pts before and after changing from IM to NIL therapy. Method Plasma lipid profile (total cholesterol, LDL, HDL and triglycerides), TKI exposure, and CVD risk factors before and after switchover to NIL of chronic phase CML pts were analysed. Baseline measurements were done during IM treatment or within 2 weeks of changing from IM to NIL. Follow-up results were obtained at least 1 month after starting NIL. Results Thirty-one CML pts were switched to NIL (median dose 400mg bd) after a median of 27 (1-96) months of IM therapy, predominantly for intolerance (16/31, 52%) or for failure to achieve deep molecular responses (13/31, 42%). Median age at NIL start was 51 (17-80) years (Table I). After switching to NIL, three pts had new onset PVD/IHD and one patient had multiple recurrences of PVD. Antihypertensive and hypoglycaemic medications were started in one additional patient each after switching over to NIL. Three pts were excluded from further analysis because of lack of data (n=2) or pre-existing dyslipidemia (n=1). The remaining pts had 90 TC assays, 72 of which were full lipid profiles whilst on NIL. Observations were censored at the time of statin commencement. Median time to 1st lipid measurement on NIL was 108 days (28-633) after switching. Median TC on IM was 4.7mM (2.1-6.4), compared to 6.1mM on NIL (3.1-8.5). Median peak TC on NIL was 6.8mM. Full fasting lipid profiles available for 11 pts before and after switching showed significantly increased LDL to be the major contributor to the increase in TC (Fig. 2). Thirteen pts had a fasting TC >5.5 mM (210 mg/dL) whilst on NIL, peaking at 312 days (medians). Eight of 13 pts started statins treatment for dyslipidemia whilst on NIL; (all retrospectively confirmed to be appropriate according to Australian National Heart Foundation guidelines, using a composite measure of CVD risk); whilst the other 5 were offered lifestyle modifications only. Of note, 2 pts had dyslipidaemia prior to starting IM treatment, discontinued statins whilst on IM, and had recurrence of dyslipidaemia after switching to NIL necessitating resumption of statin treatment. In addition, the 2 pts with PVD were also offered statins (total starting statin n=10) Discussion This retrospective analysis showed a high incidence of dyslipidemia in a cohort of CML pts treated with second-line NIL after IM therapy; 10/31 pts required lipid lowering agent. While the epidemiological association between nilotinib and CVD remains controversial, the increase in TC may have a contributing effect. Monitoring lipid levels in NIL-treated pts is prudent, along with screening for and minimisation of concomitant CVD risk factors, especially in pts previous treated with IM which may mask underlying metabolic syndromes. # DKH DTY and LC contributed equally to this work. Disclosures: Hiwase: Novartis Pharmaceuticals: Research Funding. Yeung:Novartis: Honoraria, Research Funding; BMS: Honoraria. Hughes:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

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Incidence Of Hypotension In Patients With Multiple Myeloma During High Dose Chemotherapy and Autologous Stem Cell Rescue

Blood ◽

10.1182/blood.v122.21.3324.3324 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3324-3324 ◽

Cited By ~ 1

Author(s):

Priya Sehgal ◽

Noa Biran ◽

Gagan Sahni ◽

Ajai Chari

Keyword(s):

Board Of Directors ◽

Discharge Summary ◽

Infectious Complications ◽

High Dose ◽

Inclusion Criteria ◽

Advisory Committees ◽

Gastrointestinal Complications ◽

Group 2 ◽

Al Amyloid ◽

Group 1

Abstract Background The median age of patients diagnosed with multiple myeloma (MM) is 69. Up to 60-80% of patients in this age group have hypertension (HTN) (Burt VL et al. Hypertension 1999), and are on anti-hypertensive medications. A standard treatment for MM is high dose melphalan (HDM) chemotherapy with autologous stem cell transplant (ASCT), which often results in gastrointestinal complications that can result in hypovolemia. The combined effect of anti-HTN agents and ASCT-related complications may result in blood pressure (BP) ranges that are precariously low. To date, the incidence of hypotension in the setting of ASCT for MM is unknown. In this case series of 102 patients who received ASCT for MM, we compare the characteristics of those who became hypotensive with those who did not. Methods We reviewed the charts of 102 consecutive MM/AL amyloid patients admitted for HDM chemotherapy with ASCT at Mount Sinai Hospital between May 2011 and June 2013. May 2011 was chosen as the date of inclusion because at this time, electronic medical records were implemented, allowing for detailed review of vital signs and other clinical data. Patients were classified into two groups. Patients included in group 1 demonstrated a drop in BP which was defined as meeting at least 1 of the following criteria: A) One or more anti-HTN medications were discontinued during ASCT B) Although normotensive on admission for ASCT, the median systolic or diastolic blood pressure (SBP or DBP) on date of discharge was ≤ 100 or 60 mm Hg respectively C) A decrease in SBP of ≥ 20 mm Hg was observed between admission and discharge Patients who did not meet any of the above criteria were classified into group 2. Baseline and peri- SCT characteristics of the two groups were compared using the chi square test. Results Of the 102 patients analyzed, 6 had AL amyloid and the remaining 96 had MM. 43 met at least one inclusion criteria for group 1 and the remaining 59 were classified as group 2. Specifically, of the patients in group 1, 18 met inclusion criteria A, 21 met inclusion criteria B, and 23 met inclusion criteria C. Among the patients in group 1 who met 2 criteria: 4 patients met criteria A and B, 4 patients met criteria A and C, and 9 patients met criteria B and C. Baseline characteristics including median age (64 and 63), gender distribution (55.8% and 47.5% females respectively), and a history of HTN (41.9% vs. 37.3%) were comparable in both groups (p>0.05). The median length of stay was 17 days in both groups. The incidence of gastrointestinal complications was comparable in both groups including diarrhea 72.1% vs. 62.7%, mucositis 14.0 % vs 8. 5%, and Clostridium difficile infection 9.3% vs. 6.8%. The ensuing weight loss in the 2 groups was also comparable 2.4 kg and 1.9 kg respectively. The incidence of infectious complications was similarly comparable in the 2 groups with fever 51.1 % vs 61% and bacteremia occurring in 7.0% vs 11.9%. Of the 43 patients in group 1, one patient had shock requiring ICU transfer for vasopressors in the setting of adrenal insufficiency and sepsis/bacteremia. Interestingly, of the 102 included patients, only 15 were reported to have clinically significant hypotension on the discharge summary. Of these 15 patients, 3 experienced transient hypotension, (i.e. for 1 -2 days,) with rapid normalization of pressure, and therefore, did not meet our inclusion criteria of persistent hypotension. Conclusions Although the incidence of hypotension in this series of MM patients undergoing ASCT was 42%, only 15% had documentation of this occurrence in the discharge summary. Interestingly, there were no statistically significant differences in the risk factors for ASCT associated hypotension in the 2 groups, including gastrointestinal and infectious complications. Given the unexpectedly high incidence of hypotension during ASCT, consideration should be given to the following: 1) Prior to SCT, anti-HTN medications should not be added (as is sometimes done for perioperative clearance) or titrated up; 2) During ASCT, anti-HTN medications may need to be discontinued; 3) Prior to discharge from ASCT, physical therapy/orthostatic evaluation and risk of falls from new relative hypotension needs to be assessed, especially in the setting of recovering thrombocytopenia. Although further studies are required, we hypothesize that fatigue, presyncopal events, and falls post SCT could be minimized with increased attention to HTN management peri ASCT. Disclosures: Chari: Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Millenium : Membership on an entity’s Board of Directors or advisory committees; Onyx: Membership on an entity’s Board of Directors or advisory committees.

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Prophylactic Use of a Combination of an Anticoagulant and Ursodeoxycholic Acid for Sinusoidal Obstruction Syndrome after Allogeneic Myeloablative Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v128.22.5755.5755 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5755-5755

Author(s):

Hiroshi Okamura ◽

Mitsutaka Nishimoto ◽

Takahiko Nakane ◽

Hideo Koh ◽

Yasuhiro Nakashima ◽

...

Keyword(s):

Risk Factors ◽

Research Funding ◽

Gemtuzumab Ozogamicin ◽

Adult Patients ◽

Allogeneic Hsct ◽

History Of ◽

Group 3 ◽

Group 2 ◽

Prophylactic Use ◽

Group 1

Abstract Introduction: Sinusoidal obstruction syndrome (SOS) is one of the potentially fatal complications of hematopoietic stem cell transplantation (HSCT). In particular, severe SOS frequently leads to multiple organ failure, and a worse prognosis. Thus, prophylaxis against development of SOS could contribute improved survival after HSCT. Previous reports demonstrated the effectiveness of the prophylactic use of ursodeoxycholic acid (UDCA) or certain anticoagulants, including unfractionated and low-molecular-weight heparin, for SOS. In two randomized controlled trials and two meta-analyses it was reported that UDCA, a hydrophilic bile acid, was an effective and safe drug for prophylaxis against SOS. The usefulness and feasibility of prophylactic use of anticoagulants after allogeneic HSCT are however still controversial. In addition, to our knowledge no study has evaluated the feasibility of usage of UDCA combined with an anticoagulant for SOS prevention after allogeneic HSCT in adult patients. To assess the efficacy and safety of use of UDCA combined with an anticoagulant as SOS prophylaxis, we performed a retrospective cohort study to examine the occurrences of SOS and hemorrhagic events in patients who underwent myeloablative allogeneic HSCT at our institution. We examined use of any anticoagulant together with simultaneous administration of UDCA, in comparison with UDCA alone for the prevention of SOS. Patients and methods: We reviewed the charts of consecutive adult patients in whom myeloablative allogeneic HSCT was performed at our hospital from November 1994 to May 2014, and who received either unfractionated heparin or dalteparin (low-molecular-weight heparin) with UDCA (group 1), danaparoid with UDCA (group 2), or UDCA only (group 3), used for prophylaxis against SOS. Results: A total of 280 patients (group 1: n=52; group 2: n=33; and group 3: n=195) were investigated. The proportions of patients with risk factors for SOS-including non-remission at the time of HSCT, a second or subsequent HSCT, high aspartate aminotransferase (AST) levels before HSCT, high ferritin levels before HSCT, a history of receiving gemtuzumab ozogamicin, and HLA disparity-were similar across the three groups. In group 1, a conditioning regimen containing busulfan was used less frequently (P = 0.002). SOS occurred in seven patients (13.7%) in group 1, five patients (15.2%) in group 2, and 28 patients (14.4%) in group 3, all meeting the Seattle criteria. None of the patients in group 1, two (6.1%) in group 2, and nine (4.6%) in group 3 had SOS diagnosed according to the Baltimore criteria. There was no significant difference in the incidence of SOS among the three groups. In addition, with regard to the cumulative incidence of severe SOS, no statistically significant difference was present among the three groups. The incidence of hemorrhagic events within 30 and 100 days following allogeneic HSCT was not significantly different across the three groups (30 days; 5.8%, 3.0%, 5.1%, P = 0.843, 100 days; 17.6%, 15.2%, 14.4%, P=0.843, respectively). Furthermore, the probabilities of OS and NRM until day 100 after allogeneic HSCT were similar among the three groups (P = 0.733 and P = 0.637, respectively). In a univariate model, a history of gemtuzumab ozogamicin treatment, high serum ferritin levels before HSCT, an HLA mismatched donor, and non-complete remission of disease at the time of allogeneic HSCT were found to be significant risk factors for SOS. Multivariate analysis revealed that a history of gemtuzumab ozogamicin therapy, a mismatched HLA donor, and non-complete remission of disease at the time of allogeneic HSCT were significant and independent risk factors for SOS. In the multivariate as well as univariate analyses, combined administration of UDCA and any anticoagulant for SOS prophylaxis did not have a significant effect on the incidence SOS, when compared to prophylaxis with UDCA alone. Conclusion: Our study results suggest that the combined use of UDCA and an anticoagulant for SOS prophylaxis after myeloablative allogeneic HSCT in adult patients was not beneficial. Establishment of an optimal strategy for prophylaxis against SOS after HSCT is still needed. Disclosures Nakane: Mundipharma KK: Research Funding. Koh:Pfizer: Consultancy, Honoraria. Hino:Pfizer: Honoraria, Research Funding; Nippon Shinyaku: Honoraria, Speakers Bureau; Alexion: Honoraria, Research Funding. Nakamae:Mochida Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis Pharma KK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel/accommodation/meeting expenses, Research Funding.

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