Damlaj, Moussab

Abstract Background The impact of cytomegalovirus (CMV) infection on the risk of relapse after Hematopoietic Cell Transplantation (HCT) remains controversial, with some studies demonstrating lower risk (Green et al, Blood 2013), while others demonstrating no impact (Schmidt-Hieber et al, Blood 2013), or lower relapse risk only in myeloablative (MA) (Manjappa et al, BBMT, 2014) or in reduced intensity conditioning (RIC) (Cichocki et al, ASH 2014) HCT. Furthermore, the majority of studies have used antigenemia for CMV monitoring, while there is limited data with the use of Quantitative Nucleic Acid Testing (QNAT). Aim To determine the impact of CMV infection, as detected by QNAT, on transplant-related outcomes for patients with acute myeloid leukemia (AML), stratified by MA or RIC HCT. Methods After IRB approval, consecutive adults with AML who underwent allogenic HCT from HLA-matched peripheral blood (PB) grafts at our institution between 2006 and 2014 were retrospectively reviewed. All grafts were T-cell replete. Early CMV infection was defined as any positive CMV result by PCR assay during the first 100 days post HCT. Relapse incidence (RI), non-relapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) were compared between patients with and without CMV infection, and stratified according to MA or RIC. DFS and OS were estimated using the Kaplan-Meier method, and compared with log-rank test. Cumulative incidence of relapse and NRM were analyzed as competing events, using Gray's test. Multivariable analyses adjusting for patient's age, disease status at transplant, cytogenetic risk, and ABO incompatibility were performed using Cox's proportional hazards regression, and the Fine and Gray approach. Results A total of 190 consecutive patients, including 94 (49%) MA and 96 (51%) RIC HCT were analyzed. Patients, disease, and transplant characteristics are shown in table 1. Of the 94 MA HCT (median age 45 y, 50% male), 66 (70%) received total body irradiation. After a median follow up of 18 m, 36 (38%) CMV infection, 16 (17%) relapses, 22 (23%) NRM and 35 (37%) deaths occurred in the MA group. Median time to CMV infection and to relapse in this group was 38 (range 8-241) and 140 (29-1690) days, respectively. Among the recipients of MA HCT, patients with early CMV infection showed no difference in the RI (figure 1), but had a significant trend towards higher NRM and significantly lower DFS and OS in both univariate and multivariable analysis (figure 2) (P values shown in table 2). Among 96 RIC HCT (median age 59 y, 56% male), fludarabine plus melphalan was used in 62 (65%) and fludarabine plus busulfan in 34 (35%) patients. In this group, early CMV infection occurred in 33 (34%), relapse in 25 (26%), NRM in 25 (26%), and deaths in 46 (48%) patients after a median follow up of 21 m (1-91 m). Among the recipients of RIC HCT, median time to CMV infection and to relapse was 40 (17-175) and 291 (19-1971) days, respectively. In the RIC group, early CMV infection was associated with a significant trend towards lower RI (figure 1) and higher NRM in both univariable and multivariable analysis, but no difference in DFS and OS (figure 2). Conclusion Our study of a large homogenous group of AML patients who underwent a uniform HLA-matched PB HCT demonstrates a significantly lower risk of relapse associated with early CMV infection detected by QNAT following RIC, but not MA HCT. Early CMV infection in MA HCT is associated with higher NRM and therefore inferior survival, whereas in the RIC HCT, there is no impact on survival as the benefit of lower relapse is offset by the higher NRM. Table 1. Patients, disease and transplant characteristics according to CMV infection All Patients Patients with CMV Viremia Patients without CMV Viremia P value Patients, no (%) 190 (100) 69 (36) 121 (64) - Median age, y (range) 54 (18-72) 54 (26-70) 54 (18-72) 0.75 Male Patients, no (%) 104 (55) 30 (43) 74 (61) 0.02 D/R CMV Serostatus, no (%) <0.0001 -/- 29 (15) 1 (1) 28 (23) +/+ 64 (34) 35 (51) 29 (24) +/- 13 (7) 1 (1) 12 (10) -/+ 84 (44) 32 (47) 52 (43) Conditioning 0.65 MA 96 (51) 33 (48) 63 (52) RIC 94 (49) 36 (52) 58 (48) Disease status at Transplant 0.96 CR1 129 (68) 46 (67) 83 (69) CR2 34 (18) 13 (19) 21 (17) Other 27 (14) 10 (14) 17 (14) Cytogenetic 0.65 Favorable 8 (4) 2 (3) 6 (5) Intermediate 130 (68) 46 (67) 84 (69) Unfavorable 52 (28) 21 (30) 31 (26) Disclosures Al-Kali: Novartis: Research Funding.

Abstract Background: Acute graft versus host disease (aGVHD) is the leading cause of morbidity and mortality following allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first line treatment although <50% of patients with severe aGVHD (grades III-IV) achieve durable remissions. Monoclonal antibodies (mAb) are often used as second line agents for steroid refractory aGVHD (SR-aGVHD) (Patriarca et. al.; 2004). However, data regarding their tolerability and efficacy is retrospective and limited. We carried out this study to assess the clinical outcomes related to mAb therapy (Infliximab and Tocilizumab) for SR-aGVHD. Methods: Patients with SR-aGVHD that received therapy with either Infliximab or Tocilizumab between January 2003 and May 2016 were retrospectively identified. Clinical grading of aGVHD was per the Glucksberg criteria (Glucksberg et. al.; 1974). SR-aGVHD was defined as any grade progression within 3 days or failure to achieve at least one grade improvement within 7 days of initiation of systemic steroids. Infliximab and Tocilizumab were administered intravenously at 10mg/kg and 8mg/kg weekly for a total of 4 doses, respectively. Clinical response was evaluated at 4 weeks and 12 weeks post mAb treatment. Complete response (CR) was defined as sustained resolution of all clinical signs of aGVHD; partial response (PR) was defined as overall improvement of 1 or more grades; no response (NR) was defined as neither improvement nor worsening of the overall aGVHD grade. Overall response (OR) was defined as either CR or PR. Overall survival (OS) was calculated from the first day of mAb treatment until death or last available follow up. Results: Forty-three patients (median age 54, range 29-74 years; male 67%) with severe SR- aGVHD were included in the study. Of these, 35 (81%) received Infliximab for a median of 4 (range 1-6) cycles and 8 (19%) received Tocilizumab for a median of 3 (range 1-4) cycles. Both groups were comparable with regards to age, gender, conditioning regimen, graft source, degree of HLA match, ABO blood group, CMV incompatibility, and GVHD prophylaxis regimens. Only differences seen were a higher proportion of unrelated donor (p = 0.004) and cord blood HCT (p = 0.031) in the Tocilizumab group. Twenty (57%) of 35 patients treated with Infliximab and 6 (75%) of 8 patients treated with Tocilizumab had an overall aGVHD grade of IV prior to initiation of mAb therapy (p = 0.44). Organ specific distribution and severity of aGVHD are described in table 1. At 4 weeks post mAb therapy, 17 (40%) patients had an OR, 7 (16%) had no response, and 19 (44%) had died. Twenty-six (60%) patients died at 12 weeks, with OR and no response observed in 9 (21%) and 8 (19%) patients, respectively (table 2). Overall response for Tocilizumab versus Infliximab was comparable at 4 weeks (38% vs. 40%; p = 1.0) and at 12 weeks (38% vs. 17%; p = 0.33). Outcomes per aGVHD grade and gastrointestinal-specific stage at 4 weeks and 12 weeks are shown in figures 1-A and 1-B, with organ specific responses shown in figures 1-C and 1-D, respectively. The estimated median OS was 41 (range 4-3837) days for patients treated with Infliximab and 60 (range 10-756) days for those treated with Tocilizumab (p = 0.48). Disease relapse occurred in 5 (11%) patients treated with Infliximab and in none (0%) treated with Tocilizumab (p = 0.56). Thirty-four (79%) patients had infectious complications during and up to one month after mAb therapy. These included 31 (72%) patients with bacterial blood stream infection and 10 (23%) with invasive fungal infections. Overall, infectious complications were comparable (Infliximab - 83% vs. Tocilizumab - 63%; p = 0.33). CMV reactivation occurred in 11 (31%) and in 2 (25%) patients who were treated with Infliximab and Tocilizumab, respectively (p = 1.0). Given the retrospective nature of the study and the concomitant presence of aGVHD, it was difficult to attribute and grade gastrointestinal and hepatobiliary side effects. Conclusions: The use of anti-inflammatory monoclonal antibody therapy in patients with steroid refractory acute GVHD is associated with significant infectious complications (~80%) and poor response rates (~20% at 12 weeks). Current data, limited by a small sample size, does not show any advantages of using Tocilizumab over Infliximab or vice versa. Prospective clinical trials addressing this question are needed. Disclosures No relevant conflicts of interest to declare.

Abstract Background: Adult T-cell acute lymphoblastic leukemia / lymphoma (T-ALL) is a rare and aggressive hematological malignancy. Unlike B-cell ALL, apart from age and presenting WBC, additional prognostic factors remain largely unknown. Additionally, the prognostic impact of a monosomal karyotype, which has a negative impact on survival in myeloid neoplasms, remains to be determined in T-ALL (Kenderian et al, BCJ 2013) Aim: To study predictors of survival including the role of a monosomal karyotype in T-ALL. Methods: After due IRB approval, adults diagnosed with T-ALL from 1990-2014 at Mayo Clinic Rochester were identified. All clinical and pathologic data including FISH studies and cytogenetics were retrospectively reviewed. Chi-square test was used to compare variables. Survival was estimated and compared using the Kaplan-Meier Method and log-rank test. Univariate and multivariate analysis was performed using the Cox regression model. Results: Between 1990 and 2014, a total of 92 consecutive patients (pts) with T-ALL were identified, 41 had acute lymphoblastic lymphoma (LBL), and 51 (55%) acute lymphoblastic leukemia (ALL). Median age at diagnosis was 33 years (range; 18-88 years) with 72%males. Median follow up of our cohort was 25 months (range; 0.9-260 months) during which time 42 deaths (45%) were documented. A. Baseline characteristics: Fifty six (67%) had constitutional symptoms, and 63 (77%) had lymphadenopathy at diagnosis. Mediastinal mass was identified in 49 (55%) pts with palpable splenomegaly in 16 (20%) pts. Fifty one (58%) pts had extranodal disease, and 17 (19%) pts had CNS involvement. Pleural and pericardial effusion were evident in 16 (19%), and 6 (7%) pts, respectively. Median laboratory values included; LDH 288 U/L (115-6590), hemoglobin (Hb) 12.8 g/dl (4.5-18.2), WBC 8.65 x109 (1.4-406), platelets 169 x109 (8-485), bone marrow blasts 29% (0-99). B. Treatments: Induction therapies were variable and included; 11 (12%) CHOP like regimens, 7 (8%) modified NHL regimens (Asparginase+CHOP), 54 (58%) ALL like regimens (CALGB 9111, E2993, or HyperCVAD), 13 (14%) Pediatric regimens (ALL 10403, CCG 1961, BFM, Augmented BFM, GRAALL 2003, or Hoelzer regimen), with 7 (8%) patients' receiving palliative care only. Seventy-one (77%) pts achieved complete remission (CR1) during induction therapy while eight pts had refractory disease (8%). Thirty-three (35%) pts underwent stem cell transplant; 7 (21%) autologous and 26 (79%) allogeneic. Forty one (44%) pts had disease relapse and median time to relapse was 10.8 months (range; 8.2-16 months) C. Predictors of survival: In univariate analysis, that included age > 60 years, leukocyte count Hb, Plt, Blast percentage, mediastinal mass, LDH and CNS involvement, only age >60 and CNS involvement were predictors of inferior survival and both retained significance in the multivariable analysis with HR 3.9 (CI 1.5 - 9; p=0.0055) and 2.8 (1.3 - 5.7; p =0.0085), respectively (Figure 1 and 2). In this cohort age >60 was a better stratification that the conventionally used age above 40 (p = 0.1). Among 56 pts with evaluable cytogenetics data, 7 (13%) pts had MK which did not have an impact on survival with HR 1.9 (CI 0.4-5.6; p=0.33). Conclusion: In this large cohort of adult T-ALL patients, we observed that age >60 years and CNS involvement were independent predictors of inferior survival. MK was infrequent, but unlike in myeloid neoplasms, does not seem to impact overall survival. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Al-Kali: Celgene: Research Funding. Thompson:Kite Pharma: Research Funding. Witzig:Novartis: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Spectrum: Research Funding; Valeant Pharma: Equity Ownership.

Abstract Background: Myelodysplastic syndrome (MDS) is a heterogeneous disease characterized by cytopenias and a propensity to progress into acute myeloid leukemia in a subset of patients. Clinical trials which led to FDA approval of hypomethylating agents (HMAs) stratified patient's risk status per the IPSS. In 2008, WHO further categorized patients into different groups and the IPSS was revised into the IPSS-R. Therefore, there is a paucity of data regarding the response rates and clinical outcomes of HMA therapy when stratified per WHO subtype and IPSS-R. Goal: We carried this review to assess whether WHO subtypes or IPSS-R had a differential response with corresponding impact on survival. Methods: After IRB approval, all MDS pts who received hypomethylating agents (HMA) (azacitidine or decitabine) with available response data (2000-2014) were included. Clinical characteristics were obtained retrospectively. IPSS-R (Greenberg 2012) was used for risk stratification. Response assessment was based on IWGR 2006 criteria. Statistical comparisons were performed with the χ2 test for categorical variables and the Wilcoxon test for continuous variables. Survival analysis was based on the Kaplan-Meier method and log rank test. For all analyses, P ≤ 0.05 was considered statistically significant. Results: We identified 823 pt in our MDS database; among those that received HMA therapy 70 patients (pts) had evaluable response data. The median age at diagnosis was 67 years (31-85) and 49 (70%) were males. MDS subtypes per WHO 2008 classification were 31(44%) RAEB1/2, 26(37%) RCMD, 10(14%) MDS-U, 2(3%) RARS, and 1(1%) MDS 5q. Fifteen (33%) patients had secondary MDS. 23(32%) developed AML, and median time to leukemic transformation was 14 months (7.8-21). Median time to start HMA was 2.7 months (0-77). Median follow up from initial diagnosis was 20 months (3-118) at which time 22(31%) deaths were documented. A. Patient characteristics: Prior to HMA therapy median laboratory values included; Hemoglobin 9.6 g/dL (6.6-14.8), ANC 1.1 x1010 (0.01-16), Platelet 66 x1010 (4-937), peripheral blast % 0 (0-18), and bone marrow blast % 5 (0-17). IPSS-R for our cohort was as the following, 15(27%) Very high, 14(25%) high, 10(18%) intermediate 12(21%) low, and 5(9%) very low risk. B. HMA Response rates based on WHO subtype: We observed no significant difference in response (p = 0.6) when comparing response rate among different groups. Response rates per WHO subtype were as follows: i. RAEB: 7 (22%) pts achieved CR/Marrow CR, 1(3%) had HI/PR, 17(55%), and 6(20%) had stable disease (SD) and progressive disease (PD), respectively. ii. RCMD: 2 (8%) pts achieved CR/Marrow CR, 4(16%) had HI/PR, 12(46%), and 8(30%) had SD and PD, respectively. iii. MDS-U: 1 (10%) pt achieved CR/Marrow CR, 1(10%) had HI/PR, 6(60%), and 2(20%) had SD and PD, respectively. iv. MDS 5q/RARS: 1(33%) had SD, and the remaining three pts had PD. C. HMA Response rates based on IPSS-R: i. Very low: 1(20%) had HI/PR, 3(60%), and 1(20%) had SD. ii. Low: 2(17%) pts achieved CR/Marrow CR, 3(25%) had HI/PR, 4(33%), and 3(25%) had SD and PD, respectively. iii. Intermediate: 2 (20%) pts achieved CR/Marrow CR, 5(50%), and 3(30%) had SD and PD, respectively. iv. High: 2(14%) pts achieved CR/Marrow CR, 2(14%) had HI/PR, 7(50%), and 3(21%) had SD and PD, respectively. v. Very high: 1(7%) pts achieved CR/Marrow CR, 9(60%), and 5(33%) had SD and PD, respectively. Comparing responses among IPSS-R risk stratification groups, was not statistically significant (p = 0.49). We did not observe a difference in response rate when we further classified pts into low risk (very low, low & intermediate), and high risk (high, very high) (p = 0.27). D. Response effect on Survival: Overall survival was not statistically different among responders (CR/Marrow CR/HI &PR) and non-responder (SD & PD); 22.3 vs 14.7 months respectively (p = 0.21) (Figure1). Conclusion: Using contemporary MDS risk stratification and WHO classification was not predictive of response to hypomethylating agents. Responders did not seem to benefit from prolongation of survival. Given the small sample size in this cohort, this should be further explored in larger groups to identify if there are any potential subgroups that would benefit more from such therapy. Figure 1. Figure 1. Disclosures Al-Kali: Celgene: Research Funding.

Abstract Background: Acute erythroleukemia (AML-M6) is an aggressive myeloid leukemia, with poor outcomes (median survival < 12months). In 2008, the WHO further sub-classified this disease into two subgroups- erythroid leukemia and pure erythroid leukemia, based on the number of erythroblasts and myeloblasts. We carried out this study to evaluate differences in presenting features and outcomes between erythroid leukemia and pure erythroid leukemia. Methods: After due IRB approval, out of 923 AML, 43(4.6%) pts who met the 2008 WHO criteria for acute erythroleukemia (2000-2014) were identified, and clinical characteristics retrospectively reviewed. A diagnosis of erythroid leukemia (M6a) was considered if > 50% of the total nucleate BM cells were of erythroid lineage and > 20% of non-erythroid cells were myeloblasts. Pure erythroid leukemia (M6b) was diagnosed in pts who presented with > 80% of BM nucleate cells consisting of immature erythroid precursors. Cytogenetic risk stratification was based on NCCN AML guidelines. Statistical comparisons were performed with the χ2 test for categorical variables and the Wilcoxon test for continuous variables. Univariate and multivariate analyses were performed with the Cox logistical regression. Survival analysis was based on the Kaplan-Meier method and log rank test. For all analyses, P ≤ 0.05 was considered statistically significant. Results: The median age at diagnosis was 65 years (27-90) and 34(79%) were male. 30 (69%) had M6a and 13 (30%) had M6b. 27 (62%) had de novo AML M6, whereas 16 (37%) had secondary AML (9 underlying MDS and 7 therapy related).The median time to leukemic transformation for pts with underlying MDS was 8 months (2-83). Median follow up in our cohort was 7.2 months (2-157) at which time 13 (30%) deaths were documented. A. Patient characteristics: At time of diagnosis median laboratory values included; Hemoglobin 8.5 g/dL (4.6-11), WBC 2x109 (0.7-11.1), ANC 0.47x109 (0.01-4.07), Platelet 33x 109 (7-177), peripheral blast % 2 (0-35), and bone marrow blast % 11 (0-84). Cytogenetic information was available in 38 pts; of which 6(16%) were diploid, 21(55%) were complex/monosmal and 1(3%) was complex/non monosomal. Intermediate risk cytogenetic was observed in 15 pts (39%), and poor risk cytogenetic was identified in 23(61%). Comparing M6a and M6b, we observed that pts with M6a tend to have more leukopenia and neutropenia and higher marrow blast percentage compared to M6b (Table 1). None of the patients experienced extramedullary disease or CNS involvement. B. Outcome and prognostics: We did observe a trend towards worse survival in pts with M6b, 7 months vs 12.9 months with M6a (p= 0.08) (Figure 1). There was no difference in survival in acute erythroleukemia compared to other acute myeloid leukemias, 10.1 vs 14 months (p= 0.28), respectively (Figure 2). In univariate analysis, WBC, ANC, and cytogenetic risk impacted survival (Table 2), however only cytogenetic risks retained significance in the multivariate model; Intermediate risk HR 0.18 (0.05-0.51; p = 0.0009) and poor risk HR 5.4 (1.9-17.6; p = 0.0009). Conclusion: Acute Erythroid Leukemia is a rare leukemia with ~5% incidence in our cohort. We observed that regardless of the percentage of bone marrow erythroblasts and myeloblasts, survival in patients with Acute Erythroleukemia are predominantly impacted by cytogenetic risk stratification. This raises a question on the clinical relevance of the sub-categorization of acute erythroleukemia into erythroid leukemia and pure erythroid leukemia. Larger studies are needed to validate our results. Figure 1. Figure 1. Disclosures Al-Kali: Celgene: Research Funding.

Abstract Background:Morphologic complete remission (CR) is the gold standard for assessing response in acute myelogenous leukemia (AML). CR with incomplete count recovery (CRi) and CR with incomplete platelet recovery (CRp) are associated with inferior overall survival post induction therapy (Walter et al, JCO 2010 and Chen et al, JCO 2015). Furthermore, residual cytogenetic disease is associated with a higher relapse compared with patients with cytogenetic CR (CCR; Chen et al, JCO 2011). There is a paucity of literature regarding the impact of CRi, CRp and CCR prior to allogeneic transplantation. Aim:To study the impact of CRi, CRp and CCR and their impact on relapse incidence (RI), non-relapse mortality (NRM) and overall survival (OS) in reduced intensity allogeneic stem cell transplantation (RIC-SCT). Methods:After due IRB approval, patients (pts) with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) who received RIC-SCT at our institution between 2008-2014 were identified. All clinical and pathologic data were retrospectively extracted. CR, CRi, CRp and CCR were defined in accordance to the international working group definition. Categorical and continuous variables were analyzed using Pearson's chi-squared and Wilcoxon/Kruskal-Wallis, respectively. Survival estimates were calculated using the kaplan-meier and log-rank test. RI was estimated on a competing event analysis using Grey's model. Cox proportional regression was used to compute hazard ratios (HR). Results: A. Baseline characteristics: A total of 134 patients were identified. A total of 70 (52%) were in CR, 40 (30%) in CRi and 24 (18%) in CRp. 129 patients had evaluable cytogenetic data pre-SCT; 81 (63%) were in CCR and 48 (37%) had persistent cytogenetic disease. Baseline patient, disease and transplant characteristics stratified by peripheral count recovery pre-SCT are shown (Table 1). Significantly more patients in CR had higher KPS, higher proportion AML diagnosis, more likely to be in first complete remission (CR1), higher rate of cytogenetic CR and a higher proportion of minor ABO mismatched donor. No other significant variables were identified between the three cohorts. B. Transplant outcomes: Median follow up of the entire cohort was 41.9 months and the 2-yr OS, RI and NRM were 61.7%, 25.7% and 21.9%. Patients in CR, CRi and CRp had a similar 2-year rates of RI (26.3%, 18.4% and 28.9%, respectively; p = 0.66), 2-year NRM (20.5%, 38.8% and 22.1%, respectively; p = 0.18) and 2-year OS (61.8%, 55.1% and 58.6%, respectively; p = 0.82). RI was significantly lower for patients in CCR pre-SCT with HR 0.25 (95% CI 0.11-0.51 p = 0.0001) without a difference in overall survival HR 0.68 (0.41-1.15; p = 0.14). However, we observed a similar RI in CR, CRi and CRp patients who had persistent cytogenetic disease pre-SCT (p = 0.55). The outcome remained similar between strata after excluding MDS patients (data not shown). Conclusion: We observed equivalent post-transplant outcomes between CR, CRi and CRp despite the presence of persistent cytogenetic disease. This suggests that RIC SCT had a role in mitigating the negative prognosis associated incomplete hematologic recovery. These findings have implications as physicians may not need to postpone SCT to await count recovery. This important question should be further validated in a larger cohort of patients. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Al-Kali: Novartis: Research Funding.

AbstractBackgroundScreening for vancomycin‐resistant Enterococcus (VRE) is performed at many transplant centers, but data on the impact of VRE colonization and bloodstream infection (BSI) on hematopoietic cell transplantation (HCT) outcomes remain conflicting.MethodsConsecutive adults with acute myeloid leukemia who underwent allogeneic HCT between 2004 and 2014 were retrospectively reviewed. Patients were screened by perirectal PCR swabs targeting vanA and vanB twice weekly while inpatient.ResultsOf a total of 203 patients (median age 54 years), 73 (36%) were VRE colonized prior to HCT, 23 (11%) became colonized within the first 100 days, and 107 (53%) remained non‐colonized through day 100 post HCT. A landmark analysis on HCT day 0 revealed no significant difference in overall survival according to pre‐transplant colonization status (P=.20). However, patients with subsequent VRE colonization within the first 100 days of HCT had a significantly worse survival on both univariable (P=.04) and multivariable (P=.03) analyses. During the first 30 days post HCT, 11 (5% of total and 11% of the VRE colonized) patients developed VRE BSI. Ten (91%) of these had screened positive for VRE colonization before the bacteremia. Age ≥60 years, HCT‐comorbidity index ≥3, and VRE colonization were independent risk factors for VRE BSI on multivariable analysis (P=.04, .03, .003, respectively). Only 1 (9%) patient with VRE BSI died within the first 100 days post HCT.ConclusionVRE colonization is a surrogate marker and not an independent predictor of worse outcomes post HCT. VRE BSI is associated with increased morbidity, but does not impact post‐HCT survival.

AbstractBackgroundRespiratory syncytial virus (RSV) infection causes significant morbidity and mortality in allogeneic stem cell transplant (allo‐SCT) recipients. Although ribavirin and immunoglobulins are common components of therapy, the role of adjunct corticosteroids is not established.ObjectivesWe sought to evaluate corticosteroid utilization in the setting of post‐allo‐SCT RSV infection in our center and assess post‐transplant outcomes including pulmonary function decline.MethodsPatients with a history of RSV infection from 2008 to 2014 seen at our institution were identified. Treatment and outcome data were retrospectively collected. Forced expiratory volume at 1 s (FEV1) and carbon monoxide diffusion capacity (DLCO) were collected pre‐ and post‐RSV infection.ResultsDuring the observation period, RSV was isolated in 53 of 552 patients undergoing allo‐SCT (10%) and 45 had evaluable therapy data. RSV‐related mortality in this cohort was 4/45 (9%). Twenty‐one (47%) were on corticosteroids prior to RSV diagnosis, of whom 11 (24%) had a dose increase post symptom onset. Eight (18%) patients were started on corticosteroids at the time of RSV infection. Corticosteroid therapy at symptom onset was associated with a higher rate of upper respiratory infection (URTI) to lower respiratory infection (LRTI) progression risk ratio (RR) 2.49 (1.21–5.13; P = 0.016), hospital admission RR 2.05 (1.24–3.37; P = 0.005), or intensive care unit admission RR 2.91 (1.89–5.01; P = 0.002). No significant difference was seen with FEV1 and DLCO decline (P = 0.3 and 0.24, respectively) or mortality (P = 0.26).ConclusionAdjunct corticosteroid use in the setting of RSV infection did not improve RSV‐related outcomes including long‐term pulmonary function. Our results do not support the routine use of corticosteroids; however, this finding does need to be verified in a larger cohort of patients.

BACKGROUNDABO incompatibility is not a contraindication to hematopoietic cell transplantation (HCT), but it has been associated with additional risks including delayed engraftment, pure red cell aplasia (PRCA), and higher transfusion needs. Data on these events and on patient survival after reduced‐intensity conditioning (RIC) HCT are limited.STUDY DESIGN AND METHODSA total of 127 consecutive patients, 86 with acute myeloid leukemia and 41 with myelodysplastic syndromes, who underwent HLA‐matched peripheral blood RIC allogenic HCT between 2005 and 2014 were retrospectively analyzed.RESULTSEighty ABO‐compatible, 26 major/bidirectional, and 21 minor‐ABO‐mismatch HCT were identified. Compared to the ABO‐compatible group, major/bidirectional mismatches had increased red blood cell (RBC) transfusion requirement during the first 100 days (p = 0.009), delayed RBC and PLT engraftment (p = 0.0011 and p = 0.005, respectively), and higher incidence of grade II to IV acute graft‐versus‐host disease (aGVHD; p = 0.037). In multivariable analysis, major/bidirectional mismatches had significantly higher non‐relapse mortality (NRM) and inferior disease‐free survival (DFS) and overall survival (OS) compared with ABO‐compatible patients (p = 0.01, p = 0.04, and p = 0.035, respectively). Minor ABO mismatch had no impact on survival (p = 0.99). Four (15%) of 26 major/bidirectional mismatches developed PRCA. There was a significant association between fludarabine plus busulfan conditioning and PRCA (p = 0.0046).CONCLUSIONMajor/bidirectional ABO mismatch is associated with higher NRM and shortened DFS and OS in the setting of RIC HCT. Increased transfusion need, delayed RBC and platelet engraftment, PRCA, and increased severity of aGVHD are additional complications contributing to the morbidity.