scholarly journals A Prospective, Multicenter Surveillance Study for Adverse Events Associated with Hematopoietic Stem Cell Infusion: Analysis of Pediatric and Low Body-Weight Recipients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2105-2105
Author(s):  
Kazuhiko Ikeda ◽  
Hitoshi Ohto ◽  
Yoshiki Okuyama ◽  
Minami Yamada-Fujiwara ◽  
Heiwa Kanamori ◽  
...  
Keyword(s):  
Body Weight ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Adverse Events ◽  
Research Funding ◽  
Allergic Reactions ◽  
Hematopoietic Stem ◽  
History Of ◽  
Pediatric Recipients ◽  
Transfusion Reactions

Abstract Adverse events (AEs) associated with blood component transfusion have been widely surveyed. In contrast, surveillance of AEs associated with hematopoietic stem cell (HSC) infusion in HSC transplant (HSCT),including bone marrow transplant (BMT), peripheral blood stem cell transplant (PBSCT), and cord blood transplant (CBT),has been less rigorous, even though HSC products contain cells of diverse maturity and viability,plasma with various antigens, cytokines and antibodies, and dimethyl sulfoxide (DMSO) in the case of cryopreserved products. In fact, HSC infusion is associated with several AEs, e.g., allergic reactions, flushing, hypo- or hypertension, and respiratory distress, which have been attributed to toxicity of dead cells and DMSO (Otrock et al, Transfusion, 2017). However, our recent prospective surveillance revealed that HSC infusion-related AEs often occurred in each HSC type and the overall rates of AEs were greater in allo-BMT with no DMSO, compared with auto-PBSCT, allo-PBSCT, and allo-CBT typically cryopreserved with DMSO. Hypertension was the most common AE in each HSC source, with the highest rate in BMT, while allergic reactions were the most frequent in allo-PBSCT. A multivariate analysis identified a history of transfusion reactions as a risk factor of HSC infusion-related AEs (Ikeda et al, Transfus Med Rev, 2018). These findings suggest that some DMSO-independent factor(s), such as plasma components, may contribute to HSC infusion-related AEs. Thus, we asked if HSC volume and component effects were more substantial in small recipients, and if age-related factors alter susceptibility to HSC infusion-related AEs in pediatric patients. So far, data on HSC infusion-related AEs in pediatric and low body-weight recipients are lacking. Here, to address these issues, we investigated AEs due to HSC infusions in 219 recipients of <45 kg body weight, including 90 recipients 15 years old or younger, versus data from 1,125 recipients in general (general recipients)in the prospective study described above. The rates of overall HSC infusion-related AEs were quite similar among HSC sources among low body-weight/pediatric recipients (Table 1) andexclusivepediatric recipients (P= .158 in auto-/allo-HSCT and .867 in allo-HSCT), in contrast to general recipientswhose rate of AEs was highest in BMT. In addition, bradycardia was more often reported in CBT compared with PBSCT and BMT (Table 1), especially in pediatric recipients (30.8% in CBT and 0% in others, P< .001). On the other hand, there were some similar trends between low body-weight/pediatric recipients and general recipients: PBSCT and CBT recipients, but not BMT recipients, complained of malodor, whereas the rate of hypertension was highest in BMT (Table 1). Next, we compared HSC infusion-related AEs between auto- and allo-HSCT using cryopreserved products (Table 2). This comparison showed higher overall rates of AEs in allo-HSCT compared with auto-HSCT, especially in pediatric recipients, suggesting that plasma componentsrather than DMSO contribute to HSC infusion-related AEs in low body-weight/pediatric recipients as well as in general recipients. Of note, pediatric recipients showed a 10-foldhigher incidence of nausea/vomiting in allo-HSCT versus auto-HSCT, instead of allergic reactions, for which the incidence was significantly higher in allo-HSCT than auto-HSCT in general recipients. Subsequently, we sought factors that correlate with HSC infusion-related AEs in allo-HSCT using multivariate analysis with logistic regression, which identified lymphoid neoplasms over myeloid neoplasms as a factor for overall AEs (OR 3.013, P= .026), while history of transfusion reactions did not reach statistical significance (OR 2.368, P= .066). Notably, in a multivariate analysis for any grade ≥2 AEs, there were some factors that did not correlate with general recipients but did with low body-weight/pediatric recipients, including complications before HSCT (OR 5.764, P= .019), without plasma or red blood cell removal for ABO mismatch (OR 3.815, P= .032), and >10 ml/kg infusion volume (OR 5.306, P= .027). In conclusion, our data quantifysome specific symptoms associated with HSC infusionin low body-weight and pediatric recipients. We should be mindful ofinfusion volume and preexisting complications when small recipients receive HSC infusion. Disclosures Fujiwara: Astellas: Consultancy; Kyowa-Hakko: Consultancy; Kirin: Consultancy; Chugai: Consultancy; Pfizer: Consultancy; Shire: Consultancy. Muroi:JCR: Speakers Bureau; Becton: Speakers Bureau; Dickinson and Company: Speakers Bureau; Japanese Red Cross Society: Speakers Bureau. Mori:Astella Pharma: Honoraria; Kyowa Hakko Kirin: Honoraria; Japan Blood Products Organization: Honoraria; MSD: Research Funding; Ono: Honoraria; Novartis Pharma: Honoraria; Eisai: Honoraria; Janssen: Honoraria; Asahi Kasei: Research Funding; Novartis Pharma: Research Funding; Celgene: Honoraria; Taisho Toyama Pharmaceutical Co: Honoraria; Shire Japan: Honoraria; Pfizer: Honoraria; CHUGAI: Honoraria; MSD: Honoraria; SHIONOGI: Honoraria. Nagai:Ono Pharmaceutical Co.Ltd.: Consultancy; Kaneka Corporation: Research Funding; Kawasumi Laboratories Inc.: Research Funding.

Use of First or Second Generation TKI for CML after Allogeneic Stem Cell Transplantation: a Study By the CMWP of the EBMT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4685-4685 ◽  
Author(s):  
Yves Chalandon ◽  
Simona Iacobelli ◽  
Jennifer Hoek ◽  
Linda Koster ◽  
Liisa Volin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Chronic Phase ◽  
Time Interval ◽  
Hematopoietic Stem ◽  
Persistent Disease ◽  
Factors Influencing

Abstract Background: Patients (pts) relapsing with CML after allogeneic hematopoietic stem cell transplantation (alloHSCT) may be treated with tyrosine kinase inhibitors (TKI) and/or donor lymphocyte infusions (DLI). As nowadays the majority of CML patients would have received at least imatinib prior to transplantation, we were interested in analizing a) the type of TKI used after alloHSCT, b) the indication for TKI treatment, c) the outcome of this treatment and d) the temporal relationship with DLI if given. Patients and methods: 435 pts received TKI after first allogeneic HSCT for CML for different reasons. Transplants had been performed in first chronic phase (CP1, n=194), accelerated phase (AP, n= 60) or for more advanced disease (blast crisis (BC)/> CP1, n=177) from HLA identical siblings (n=231) or unrelated donors (n=204) between 2000 and 2013. TKI given prior to transplant was imatinib (n=268), dasatinib (n=162), nilotinib (n=88), bosutinib (n=4) and ponatinib (n=7). Median age at transplant was 44 (18.5-68) years, 274 pts (63%) were male. TKI post alloHSCT were given between 2000 and 2015. 1st TKI given was either imatinib (n=223), dasatinib (n=131), nilotinib (n=67), bosutinib (n=2) or ponatinib (12). The indications for TKI therapy were the same as for transplantation (n=262), for relapse/progression/persistent disease (n=124), for prophylaxis/pre-emptive (n=32), planned (n=5), others (n=8) and missing (n=4). Results: Median follow-up from start of TKI was 55 (1-171) months. The median time interval from transplant to TKI was 6 (0.2-165) months. It was longer for TKI given for relapse/progression with 15 (1-89) months and shorter for TKI given for prophylaxis/pre-emptive with 1.6 (0.2-43) months. It was longer for imatinib with 11 (0.2-121) months vs 3.8 (0.2-165) months for other TKI. Imatinib as 1st TKI was mainly given for relapse/progression/persistent disease (48%) and the other TKI for the same reason as for transplantation (83%). 103/223 (46%) of pts with imatinib, 99/131 (76%) with dasatinib, 55/67 (82%) with nilotinib and 11/14 (79%) with bosutinib/ponatinib post-transplantation had been treated with imatinib prior to transplantation. In total, 196 (45%) patients received DLI after alloHSCT, of which 63/435 (14.5%) had DLI prior to TKI post-alloHSCT, 19/435 (4.4%) had DLI at the same time of TKI and 114/435 (26%) had DLI post-TKI. Best response after TKI was complete molecular remission in 17.7%, cytogenetic remission in 4.4%, hematological remission in 20.2% and no response/progression/relapse in 57.7% of pts. 50% of pts treated with imatinib had a response (molecular/cytogenetic/hematological) vs 34% with nilotinib, 33% with dasatinib and 33% with bosutinib/ponatinib, p=0.014. OS was 60% (55-65%) at 5 years. It was 66% (60-73%) with imatinib vs 51% (42-60%) with other TKI, p=0.0024. 5 years RFS was 47% (42-53%). It was 53% (46-60%) with imatinib vs 40% (32-48%) with other TKI, p=0.0102. 5 years RI was 25% (21-30%). It was 21% (16-27%) with imatinib vs 31% (24-38%) with other TKI, p=0.0454. 5 years NRM was 27% (23-32%). It was 26% (20-31%) with imatinib vs 29% (22-36%) with other TKI, p=0.365. In multivariate analysis for OS, imatinib vs other TKI post-transplant did not show anymore an effect, HR 1.19 (0.85-1.67), p=0.317. Factors influencing OS were time from diagnosis to transplant, HR 1.01 (1.00-1.01), p=0.009, AP vs CP1, HR 1.80 (1.11-2.91), p=0.017 and BC/>CP1 vs CP1, HR 2.3 (1.58-3.33), p<0.0001. In multivariate analysis for RFS as for OS, imatinib vs other TKI did not have an effect, HR 1.11 (0.83-1.48), p=0.496. Other factors having a tendency or influencing RFS were time from diagnosis to transplant, HR 1.00 (1.00-1.01), p=0.054, AP vs CP1, HR 1.52 (1.00-2.31), p=0.050 and BC/>CP1 vs CP1, HR 2.11 (1.55-2.88), p<0.001. Conclusion: These data suggest that TKI after alloHSCT induce a response in about 42% of pts regardless of the type of TKI used and that time from diagnosis to transplantation as well as the phase of disease at transplant remain the main factors influencing the outcome of CML patients relapsing after alloHSCT. Disclosures Kröger: Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding.

scholarly journals Risk Factors and the Therapeutic Efficacy for Thrombotic Microangiopathy in Patients after Allogeneic Hematopoietic Stem Cell Transplantation - Results of the Multicenter Retrospective Cohort Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4554-4554
Author(s):  
Hiroharu Imoto ◽  
Hiroyuki Matsui ◽  
Yasuyuki Arai ◽  
Tadakazu Kondo ◽  
Yasunori Ueda ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Cohort Study ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Therapeutic Interventions ◽  
Post Transplantation ◽  
Hematopoietic Stem

[Introduction] Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, given its relatively low incidence, no large cohort-based study has determined TA-TMA risk factors and its impact on overall survival (OS) or the most effective therapeutic interventions. Recombinant human soluble thrombomodulin (rTM) is a promising therapeutic option; with dual antithrombosis and anti-inflammation activities, a single-center small cohort study in Japan reported rTM to be effective against TA-TMA. This study aimed to clarify risk factors for TA-TMA development and the efficacy of various TA-TMA therapies in a multicenter large cohort. [Methods] This retrospective cohort study conducted by the Kyoto Stem Cell Transplantation Group enrolled adult patients (age ≥ 16 years) with hematological diseases who underwent allogenic HSCT after 2000. Cumulative TA-TMA incidence was calculated using Gray's test; death from any cause was a competing risk. We evaluated OS in patients with or without TA-TMA using the Simon-Makuch method and compared it using the Cox proportional hazard model with TA-TMA development as a time-dependent covariate. Correlations were analyzed between each pre- or post-transplant factor and TA-TMA development using Gray's test. Factors significant in the univariate analysis were subjected to the multivariate analysis using the Fine-Gray proportional hazards model. We evaluated the effect of each therapeutics on response using a logistic regression model. [Results] We enrolled 2,430 patients [median age at HSCT, 50 (range: 16-74) years] from 14 institutes. Overall, 1,234 patients were transplanted for acute myeloid leukemia or myelodysplastic syndrome, followed by acute lymphoblastic leukemia (n = 381) and non-Hodgkin lymphoma (n = 351). Overall, 1,219 patients (50.2%) had advanced disease (non-remission status) at HSCT. The HCT-CI score was higher (≥3) in 213 patients (8.8%), and 360 (14.8%) were transplanted at poorer performance statuses (PS 2-4). In total, 471 patients (19.4%) received related bone marrow transplantation (BMT), 423 (17.4%) received related peripheral blood stem cell transplantation (PBSCT), 871 (35.8%) unrelated-BMT, and 665 (27.4%) unrelated cord blood transplantation. HLA was mismatched in 1,461 (60.1%) patients. After HSCT, TA-TMA was observed in 123 patients; the cumulative incidence of TA-TMA 12 months after HSCT was 5.0%; TA-TMA occurred at a median of 36 days (range: 3-482) (Figure 1). TA-TMA was correlated with a remarkably inferior OS [hazard ratio (HR), 4.93; 95% confidence interval (CI), 4.03-6.02; P < 0.001] when treating TA-TMA as a time-dependent covariate. In the multivariate analysis, poorer PS [HR, 1.64; 95% CI, 1.05-2.58; P = 0.03], higher HCT-CI [HR, 1.70, 95% CI, 1.02-2.83; P = 0.04], and HLA-mismatch [HR, 2.06; 95% CI, 1.34-3.17; P = 0.001] were significant pre-transplantation risk factors for TA-TMA. Post-transplantation factors (acute GVHD (Grade 3-4) [HR, 2.51; 95% CI, 1.64-3.85; P < 0.001] and veno-occlusive disease (VOD/SOS) [HR, 3.70; 95% CI, 2.05-6.70; P < 0.001]) were also significant risk factors for TA-TMA in the multivariate analysis. No infections (bacterial, viral, or fungal) were significantly related to TA-TMA incidence. Regarding therapeutic interventions, 36 (29.3%) patients received rTM-including treatment, 6 (5%) were treated with rTM alone, and 30 (24.4%) were treated with rTM and FFP (14; 11%), PE (5; 4%), or both FFP and PE (11; 9%). No significant differences in response rate [OR, 0.99; 95% CI, 0.39-2.52; P = 0.98] and OS [HR, 0.93; 95% CI, 0.58-1.49; P = 0.77] between the groups treated with or without rTM were identified. The results showed similar trends in other therapeutic interventions. [Conclusion] This study clarified the incidence of TA-TMA, its impact on clinical outcomes, risk factors including post-transplantation factors, and therapy efficacies. Patients with poor PS, high HCT-CI scores, and HLA-mismatched donors were high-risk patients; the development of severe acute GVHD and VOD/SOS also increased the risk of TA-TMA. rTM administration or other treatments did not improve patient outcomes. Therefore, strategies to avoid TA-TMA are essential. Intensification of the GVHD and VOD/SOS prophylaxis or treatment for these high-risk patients may reduce TA-TMA and improve HSCT outcomes. Figure 1 Disclosures Imada: Novartis Pharma K.K.: Honoraria; Takeda Pharmaceutical Co.,LTD.: Honoraria; Celgene K.K.: Honoraria; Bristol-Meyer Squibb K.K.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Ono Pharmaceutical Co., Ltd.: Honoraria; Kyowa Hakko Kirin Co., Ltd.: Honoraria; Astellas Pharma Inc.: Honoraria; Nippon Shinyaku Co.,Ltd.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria. Takaori-Kondo:Kyowa Kirin: Research Funding; Chugai: Research Funding; Takeda: Research Funding; Ono: Research Funding; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Janssen: Honoraria; Pfizer: Honoraria.

scholarly journals Clinical Significance of Mutations and Copy Number Lesions on Prognosis of Patients with MDS after Unrelated Bone Marrow Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1971-1971
Author(s):  
Tetsuichi Yoshizato ◽  
Yoshiko Atsuta ◽  
Yusuke Shiozawa ◽  
Kenichi Yoshida ◽  
Yasuhito Nannya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Bone Marrow Transplantation ◽  
Stem Cell Transplantation ◽  
Copy Number ◽  
Research Funding ◽  
Complex Karyotype ◽  
Clinical Factors ◽  
Hematopoietic Stem

Abstract Background: Myelodysplastic syndromes (MDS) are a group of heterogeneous disorders of hematopoietic stem cells, characterized by defective hematopoiesis and dysplasia of multiple blood lineages. Patients with MDS could achieve complete remission only by allogeneic hematopoietic stem cell transplantation (HSCT). However, because of its high mortality and morbidity, long-term survival is accomplished only in the half of the patients, underscoring the importance of accurate prognostication before the therapeutic choice. For this purpose, several systems, such as the International Prognostic Scoring System, are being successfully applied to predicting patients' clinical outcomes. Advanced molecular diagnostics of recent years might further improve the prediction. Nevertheless, originally established based on the data from patients who are untreated or only supportively treated, existing systems may not always be applied properly to the prediction of outcomes of the patients who are treated by HSCT. Methods: We enrolled 790 patients with MDS who were treated by unrelated bone marrow transplantation between 2006 and 2013 through the Japan Marrow Donor Program. Oncogenic variants and copy number alterations were identified by targeted-capture sequencing of peripheral blood-derived DNA using RNA baits designed for 69 known or putative driver genes in myeloid neoplasms and 1,674 single nucleotide polymorphisms. Results: The median age at HSCT and observation period were 51 years old (16-66) and 1106 days (48-6018), respectively. At the time of transplant, 29%, 34%, 24%, and 5.2% of the cases were diagnosed as low-risk MDS, high-risk MDS, secondary acute myeloid leukemia, and myelodysplastic / myeloproliferative neoplasms, respectively, while the disease subtype was unknown for the remaining 8.2% of the cases. Mutations were observed in 73% of the patients, where U2AF1 was most frequently mutated (13.8%), followed by RUNX1 (12.9%), ASXL1 (12.8%), TP53 (12.4%), and NRAS (7.1%). The mean number of mutations was 2.0 per patient with a mean allelic burden of 43.8%. Sequencing data were successfully used for sensitive detection of CNVs and copy-neutral loss-of-heterozygosity (LOH) (or uniparental disomy; UPD). Among the most frequent lesions were 7q LOH, complex karyotype-like CNVs as defined by 3 or more CNVs excluding UPD in targeted sequencing), 5q LOH, trisomy 8, and 17p LOH, observed in 15.5%, 12.9%, 10.1%, 7.0%, and 6.8% of the patients, respectively. Mutations in TP53, CBL, and EZH2 significantly co-occurred with LOH in 17p, 11q, and 7q, with odds ratios of 190, 75.5, and 11.7, respectively. On the basis of these findings, we combined frequently identified LOH lesions with associated mutations for further analyses of survival. In univariate analysis of overall survival (OS), 9 lesions were significantly associated with shorter OS; TP53 mutation and/or 17p LOH (TP53 / 17p LOH) (HR 2.76, P = 1.6 x 10-14), CSNK1A1 / 5q LOH (HR 2.66, P = 2.13 x 10-12), CBL / 11q LOH (HR 2.42, P = 3.88 x 10-7), EZH2 / 7q LOH (HR 2.29, P = 1.46 x 10-12), NRAS mutations (HR 1.86, P = 2.0 x10-4), ETV6 / 12p LOH (HR 1.83, P = 2.84 x 10-5), 1q gain (HR 1.73, P = 0.0037), 20p LOH (HR 1.57, P = 0.030), and FLT3 mutations (HR 1.53, P = 0.027). The number of these unfavorable lesions significantly correlated with OS (P=8.9 x 10-16). Specifically, those with at least one mutation showed a significantly shorter OS, compared to those with none of these mutations (HR 2.54, P<2.0 x 10-16). TP53 / 17p LOH was the most unfavorable among the 9 lesions by multivariate analysis (HR 1.97, P=1.6 x 10-14). Multivariate analysis with clinical factors revealed that the presence of at least 1 of the 9 lesions was independently associated with poor OS (HR 2.05, P<2.0 x 10-16), together with well-known clinical factors negatively affecting OS, including red blood cell transfusion before HSCT (HR 1.93, P=0.0036), 3 or more grade of the performance status at HSCT (HR 1.92, P=1.6 x 10-4), and older age (HR 1.69, P=2.0 x 10-4). The presence of at least one lesion negatively affected OS irrespective of the presence of complex karyotype-like CNVs. Conclusions: The present study highlights the clinical significance of somatic mutations and CNVs in MDS cases treated by HSCT. Our findings suggest that the novel set of lesions identified in this study could be successfully used for the prediction of outcome in MDS in the setting of stem cell transplantation. Disclosures Kataoka: Yakult: Honoraria; Kyowa Hakko Kirin: Honoraria; Boehringer Ingelheim: Honoraria. Kanda:Otsuka Pharmaceutical: Honoraria, Research Funding. Makishima:The Yasuda Medical Foundation: Research Funding. Ogawa:Takeda Pharmaceuticals: Consultancy, Research Funding; Sumitomo Dainippon Pharma: Research Funding; Kan research institute: Consultancy, Research Funding.

HLA Polymorphisms and Epstein-Barr Virus Infection In The Recipient Of Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3291-3291
Author(s):  
Ren Lin ◽  
Qian Fan ◽  
Sijian Yu ◽  
Zhiping Fan ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Research Funding ◽  
Epstein Barr Virus ◽  
Hematopoietic Stem ◽  
Barr Virus ◽  
Ebv Infection ◽  
Associated Diseases ◽  
Epstein Barr

Abstract Background Epstein-Barr virus (EBV) infection/reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cause fatal post-transplant lymphoproliferative disorders (PTLD) and other EBV-associated diseases. The development of EBV infection/reactivation and EBV-associated diseases are closely related to the immune function. Human leukocyte antigen (HLA) molecules are responsible for antigen processing and presentation to the immune system. Thus, it is supposed that HLA polymorphisms might be associated with EBV infection/reactivation and EBV-associated diseases. In this study, HLA polymorphisms and EBV infection/reactivation or EBV-associated diseases in the recipients of allo-HSCT were analyzed. Methods Three hundred and forty-nine recipients undergoing allo-HSCT were enrolled in this study between July 2008 to June 2013. For recipients and their donors, HLA-A, -B and HLA-DR were analyzed using PCR-sequence specific oligonueleotide probing (PCR-SSOP). The EBV-DNA levels of blood were monitored regularly by quantitative real-time polymerase chain reaction (RQ-PCR). Results With a median follow-up of 389 days post-transplantation (range, 7 to 1828 days), 96 cases developed EBV infection/reactivation and 40 developed EBV-associated diseases including 27 EBV-PTLD and 13 other EBV-associated diseases (i.e. 7 fever, 1 pneumonia, 2 encephalitis, 1 hepatitis, 1 encephalitis accompanying pneumonia and 1 enteritis accompanying hepatitis). The 3-year cumulative incidence of EBV infection/reactivation and EBV-associated diseases were 29.1%±2.6% and 13.1%±2.0%, respectively. 43.8% of the recipients with HLA-A11 developed EBV infection/reactivation, compared with 56.5% of those without HLA-A11 (p=0.039). Multivariate analysis showed that HLA-A11 was a protective factor for EBV infection/reactivation (OR 0.497, 95% confidence interval [CI] 0.284-0.869, p=0.014). The recipients who had the donors with HLA-A31 had a higher incidence of EBV-associated diseases than those whose donors did not have HLA-A31 (10.3% vs. 2.9%, p=0.046); more patients carried HLA-B44 suffered EBV-associated diseases than those not carried HLA-B44 (7.7% vs. 1.3%, p=0.035). In multivariate analysis, recipient HLA-B44 were confirmed to be a risk factor for EBV-associated diseases (OR 17.749, 95% confidence interval [CI] 1.946-161.917, p=0.011). The incidence of PTLD in the recipients with HLA-A74 was 7.4%, compared with 0.6% in those without HLA-A74 (p=0.031); the incidences of PTLD in recipients whose donors had and did not have HLA-DR04 were 37.0% and 20.2%, respectively (p=0.042). Multivariate analysis showed that recipient HLA-A74 (OR 11.350, 95%CI: 1.119-115.178, p=0.040) and donor HLA-DR04 (OR 3.227, 95%CI: 1.323-7.873, p=0.010) were risk factors for development of PTLD. Conclusion Our data suggest that HLA polymorphisms might affect EBV infection/reactivation and EBV-associated diseases. Disclosures: Liu: This work was supported by the National High Technology Research and Development Program of China (863 Program) (No. 2011AA020105), the National Public Health Grand Research Foundation (Grant No. 201202017).: Research Funding; This work was also supported by National Natural Science Foundation of China (Grant No.81000231, No.30971300, No.81270647), the Science and Technology Project of Guangdong Province of China (Grant No.2009A030200007).: Research Funding; This work was also supported by the Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.

scholarly journals Treosulfan Conditioning for Allogeneic Transplantation in Multiple Myeloma Improved Overall Survival in Upfront Hematopoietic Stem Cell Transplantation — a Large Retrospective Study By the Chronic Malignancies Working Party of the EBMT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3464-3464
Author(s):  
Charlotte Gran ◽  
Junfeng Wang ◽  
Hareth Nahi ◽  
Linda Koster ◽  
Goesta Gahrton ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Relapse Rate ◽  
Research Funding ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Significant Difference

Abstract Background Allogeneic hematopoietic stem cell transplantation (AlloSCT) for treatment of multiple myeloma (MM) is controversial mainly due to high non-relapse mortality (NRM) with myeloablative conditioning. However, AlloSCT is probably the only treatment that result in cure of a small fraction of patients. Treosulfan is a prodrug of a bifunctional alkylating agent which has both myelotoxic and immunosuppressive properties. Conditioning regimes with treosulfan have been tried in various hematologic neoplasia such as AML and MDS indicating low NRM and increased progression free survival (PFS). Previous studies on use of treosulfan condition in AlloSCT for MM indicated feasibility, stable engraftment and low NRM. In the present study we have analysed the results of low and high dose treosulfan respectively on OS, RFS, relapse incidence and NRM as well as results of Treosulfan conditioning compared to non-Treosulfan reduced intensity conditioning (RIC) and non-Treosulfan myeloablative conditioning (MAC). Patients and Methods We conducted a retrospective analysis of 4544 patients with MM undergoing AlloSCT 2008-2016 reported to the EBMT data registry. Out of 537 patients receiving Treosulfan based conditioning the impact of dose could be analysed in 441. Three hundred and twenty-seven patients received a total dose of >36g/m2 and 114 <=36g/m2.These patients were compared to 2830 patients receiving RIC, and 1177 receiving MAC. 1103 patients were transplanted upfront and 3441 patients in later lines following relapse/progression. Patient characteristics shown in table 1. Results The 5-year OS in upfront Treosulfan conditioned patients was 62%, which was significantly superior to both non-Treo RIC and MAC patients respectively, apparently due to a tendency for lower NRM (10%) albeit a higher relapse rate (Table 2). Patients in later lines of conditioning had either low NRM (3rd line) or no significant difference (2nd line) (Table 2). Heterogeneity in the material makes it difficult to interpret results in the patients transplanted late in the course of the disease. A higher total treosulfan dose, >36g/m2, showed a tendency for improved OS and RFS compared to the lower dose treosulfan as well as RIC and MAC (table 2) respectively. In multivariate analysis of upfront transplanted patients, with a model adjusted for ISS score at diagnosis, age, Karnofsky score, response at AlloSCT, interval between diagnosis and transplant, donor type and donor - patient sex match, treosulfan and RIC retained significance for OS, HR 0.57 (P=0.006) and RFS, HR 0.65 (P=<0.005). For 2nd line Treosulfan RFS was significantly worse, HR 1.46 (P=<0.005) while there was no significant difference for OS between conditioning regimes in 2nd or for OS and RFS in 3rd line (table 2). The factors associated with most inferior OS in upfront line of conditioning was Karnofsky <90 and ISS score III at diagnosis. ISS score III at diagnosis was also associated with inferior OS also in 2nd and 3rd line (Table 2) A less then partial response at AlloSCT was consistently a factor associated with inferior RFS regardless of line of treatment with HR 1.67 (P=<0.005) in upfront, HR 1,63 (P=<0.005) in 2nd line and HR 1,66 (P=<0.005) for 3rd line or later (Table 2) In multivariate analysis of treosulfan based conditioning regimes, upfront line of conditioning was superior for OS, PFS and relapse as expected (Table 3). Notably was an increased hazard ratio for donor-patient sex match other than female to male in OS, PFS as well as relapse, HR 1.64 (P=0.02), HR 1.66 (P=0.004) and HR 1.83 (P=0.003) respectively (Table 3). Conclusions Conditioning upfront with Treosulfan containing regimens for AlloSCT in multiple myeloma, is associated with a superior overall survival and a low NRM, however with a slightly higher relapse rate compared to other regimens. A higher dose > 36g/m2 tends to further improve OS, RFS and relapse rate without increasing NRM. The better results of Treo conditioning in female to male transplants as compared to other sex combinations and in contrast to MAC transplants may be due to the overall lower NRM with treosulfan, thus utilizing the GVM more effectively as indicated by the trend for lower relapse rate. In conclusion, Treosulfan containing regimens appear to be of value in upfront AlloSCT. Prospective studies on Treosulfan conditioning are warranted to further define the best dosing in MM AlloSCT. Disclosures Niederwieser: Miltenyi: Speakers Bureau; Novartis: Research Funding. Beelen:Medac: Consultancy, Other: Travel Support. Stelljes:Pfizer: Consultancy, Honoraria, Research Funding; MSD: Consultancy; JAZZ: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Finke:Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding. Garderet:Amgen: Consultancy; Celgene: Consultancy; Takeda: Consultancy. Kroeger:Celgene: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; JAZZ: Honoraria; Novartis: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding.

scholarly journals Reduction in Prevalence of Thrombotic Events in Sickle Cell Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-12
Author(s):  
Ameet Patel ◽  
Karina L Wilkerson ◽  
Kathryn A. Culos ◽  
Jennifer Green ◽  
Michael T. Byrne ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Inclusion Criteria ◽  
Cell Disease ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Before And After ◽  
History Of

Background: Venous thromboembolism (VTE) is a recognized complication of sickle cell disease (SCD). SCD confers a life-time risk of development of VTE, with a cumulative incidence of 11.3% by age of 40 years based on Cooperative group studies. Patients with SCD and VTE have a higher mortality rate (HR, 2.32; 95% CI, 1.20-4.46) compared to those without VTE (Naik et al, Am J Med. 2013;126(5):443-449). However, it remains unclear if this thrombotic pre-disposition improves after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: This is a retrospective single institution cohort study of SCD patients with history of VTE and/or cerebrovascular accident (CVA) who underwent allo-HSCT for indications of CVA, recurrent acute chest, or organ dysfunction related to SCD. Inclusion criteria included SCD genotype, VTE of any location, or CVA confirmed on ultrasound, V/Q scan, or CT/MRI angiography/venography. The number and proportion of VTE and CVA events were recorded before and after allo-HSCT. Patients who had VTE events prior to transplant did not have their anticoagulation or aspirin continued post-transplant. Statistical and clinically significant differences were identified using non-parametric analysis using McNemar's method with exact probability and binomial distribution. Multivariate analysis was done to identify potential explanatory variables within results. Results: 26 patients with SCD met inclusion criteria, all had HbSS genotype. 23 patients (88%) underwent HLA-haploidentical bone marrow transplant (haplo-BMT) with reduced intensity conditioning and 3 (12%) patients had myeloablative matched sibling donor transplants (MSD). Graft-versus-Host Disease (GVHD) prophylaxis included posttransplant cyclophosphamide/sirolimus/mycophenolate and cyclosporine/methotrexate in haplo-BMT and MSD, respectively. All patients had standard infection prophylaxis. The median age was 25 years (range: 8-54) at transplant and 17 patients were male (62%). 18 patients were taking hydroxyurea and 9 were on chronic transfusion therapy. Two patients had a second transplant for prior graft failure following haplo-BMT, all achieved 100% donor chimerism on days 30 and 100. Median follow up for the cohort was 74.5 (range:10-212) months total and 28.5 (range: 9-111) post allo-HSCT. Prior to allo-HSCT, 10 patients developed 7 deep vein thrombosis (DVT) and 3 pulmonary emboli. Seven of these (70%) were unprovoked events. 11 patients (40%) had ischemic CVA. Post-transplant, there were two provoked DVTs and one embolic stroke events in three patients, of which two had a history of provoked VTE (Figure). One DVT and the embolic stroke were associated with venous catheter use in a patient with PFO (patent foramen ovale). Only one patient had grade two acute GVHD after development of DVT. All events occurred within 30 days post transplantation and during acute hospitalization. No further VTE occurred after 3 months of anticoagulation in all patients. There was an absolute difference of 25% [95% CI=4.87- 26.9, p=0.015] in the prevalence of VTE events before and after allo-HSCT. In addition, there was an absolute 38.5% [95% CI=10.63-45.96, p=0.006] difference in the number of ischemic CVA before and after allo-HSCT. GVHD status, infection rates, age, history of pulmonary hypertension, and gender did not reach significance in explaining variation in results on logistic multivariate analysis (p &gt; 0.05). Conclusion : In patients with SCD with a history of thrombosis, there is an observed reduction in prevalence of VTE and stroke events post transplantation. Allogeneic stem cell transplantation may attenuate the ongoing activation of the coagulation cascade and hypercoagulable state in SCD. This needs to be validated in a larger prospective cohort study. Disclosures Green: Scripps: Honoraria, Other: travel; North American Thrombosis: Honoraria; CSL: Research Funding; Baxter,: Research Funding; Baxalta: Research Funding; Shire US Inc: Other: clinical trial support. Dholaria:bms: Research Funding; Poseida: Research Funding; Angiocrine: Research Funding; Takeda: Research Funding; J&J: Research Funding.

scholarly journals The Effect of Age and CD34+ Stem Cell Dose on Autologous Hematopoietic Stem Cell Transplantation Outcomes in Multiple Myeloma - Single Institution Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2028-2028
Author(s):  
Madeline Skousen ◽  
Sarah A. Holstein ◽  
Matthew A. Lunning ◽  
Elizabeth R. Lyden ◽  
Gilmore Sheree ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Univariate Analysis ◽  
Single Institution ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Neutrophil Engraftment

Autologous hematopoietic stem cell transplantation (AHSCT) after melphalan (Mel) conditioning has been shown to improve outcomes in patients (pts) with multiple myeloma (MM), including complete response (CR), progression free (PFS) and overall survival (OS). Successful stem cell rescue with adequate number of CD34+ stem cells is thought to be important in achieving these goals post-AHSCT, including reduced platelet (plt) transfusion need, neutrophil engraftment time and previously noted effect on lower cumulative incidence of relapse (CIR). However, there has been some discordance regarding the optimal CD34+ transplantation dose and the effects on outcomes. A retrospective analysis of 508 consecutive MM patients (pts) who underwent AHSCT between 1994-2017 at a single institution was performed to determine the relationship between OS and PFS/CIR at two different CD34+ stem cell infusion dose cutoffs (< 2.5 vs ≥ 2.5 x 106 (mill) CD34+ cells/kg, or < 5.0 vs ≥ 5.0 mill CD34+), an age cutoff (< 65 vs ≥ 65) and a Mel conditioning dose cutoff of 140 mg/m2 vs 200 mg/m2. Multivariate analysis considered high risk MM, defined as either having one of the high risk fluorescent in situ hybridization probes [del17p, t(4;14), t(14;16), t(14;20), gain1q, del1p] or having a complex karyotype (standard risk MM did not contain either), international staging system (ISS) stages I, II and III, and immunomodulatory drug (IMiD)-containing induction (yes/no). Fisher's exact test and the Mann-Whitney test were used to look at the association of CD34+ cutoff groups and patient characteristics. OS was defined as the time from infusion to death from any cause, and was determined by the Kaplan-Meier method; comparisons of survival curves was done using the log-rank test. The CIR was determined using cumulative incidence methods that considered death as a competing event. Gray's test was used to compare CIR curves. Linear regression and Cox regression were used for multivariable analysis. P<0.05 was considered statistically significant. Overall, CD34+ dichotomized at 2.5 or 5.0 mill was not associated with PFS (p=0.25, HR 1.19, CI 0.88-1.62; p=0.99, HR 1.00, CI 0.74-1.35) or OS (p=0.50, HR 1.11, CI 0.82-1.51; p=0.27, HR 0.85, CI 0.63-1.41). When analyzing OS by either age (< 65 vs ≥ 65), Mel conditioning (140 mg/m2 vs 200 mg/m2) or CD34+ infusion cutoffs (< 2.5 vs ≥ 2.5, or < 5.0 vs ≥ 5.0 mill), there was no statistically significant difference. On univariate analysis, the CIR was not statistically different for Mel 140 mg/m2 vs 200 mg/m2 patients at 2.5 mill CD34+ cutoff (p=0.62), but was approaching significance at 5.0 mill cutoff (p=0.054). On univariate analysis, the CIR was not statistically different for patients aged < 65 vs ≥ 65 at 2.5 mill CD34+ cutoff (p=0.92), or 5.0 mill cutoff (p=0.11). On univariate analysis, the CIR was statistically different for CD34+ at 5.0 mill cutoff for patients age ≥ 65 (p=0.01, Figure 1A) and for CD34+ at 5.0 mill cutoff for pts who received Mel140 mg/m2 conditioning (p=0.01, Figure 1B). However, after adjusting for the ISS stage and MM risk in both groups, no difference in CIR was noted (respectively p=0.095, HR: 2.00; 95% CI 0.88, 4.53; p=0.21, HR: 1.77; 95% CI 0.73, 4.29). In a subset analysis for pts ≥ 65 years at the CD34+ 5.0 mill cutoff, mean time in days to neutrophil engraftment on multivariate analysis was shorter for pts who received CD34+ ≥ 5.0 mill compared to < 5.0 mill after adjusting for Mel dose (140 mg/m2 vs 200 mg/m2), ISS stage (I,II vs III), MM risk (standard vs high) and IMiD induction (yes vs no): 11.1 days vs. 12.1 days (p<0.0001). Mean time in days to last platelet infusion on multivariate analysis was also shorter after adjusting for the Mel dose, ISS stage, MM risk and IMiD induction: 7.3 days vs. 10.6 days (p=0.0083). After adjusting for the same variables in multivariate analysis, depth of response at day+100 (CR vs partial response) was not statistically different. Hospitalization duration in days was not significantly affected by either Mel dosing or CD34+ dose. Our single institution experience suggests that there is no significant association between CD34+ stem cell infusion dose at either 2.5 mill or 5.0 mill cutoffs and post-AHSCT outcomes with either Mel dose once controlled for relevant disease specific factors. However, our results do suggest that in pts ≥ 65 years of age, infusing ≥ 5.0 mill CD34+ cells shortens time to neutrophil engraftment and reduces plt transfusion requirements during AHSCT. Disclosures Holstein: Celgene: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Sorrento: Consultancy; GSK: Consultancy; Genentech: Membership on an entity's Board of Directors or advisory committees. Lunning:Curis: Research Funding; Janssen Scientific Affairs, LLC: Consultancy, Research Funding; Juno Therapeutics: Consultancy, Research Funding; MiRagen: Research Funding; TG Therapeutics: Consultancy, Research Funding; AbbVie: Consultancy; Bayer: Consultancy; DAVA: Consultancy; Gilead Sciences, Inc.: Consultancy; Kite: Consultancy; Novartis: Consultancy; OncLive: Consultancy; Portola: Consultancy; Seattle Genetics: Consultancy; Spectrum: Consultancy; VANIUM: Consultancy; Verastem: Consultancy. Armitage:Oncology Analytics: Consultancy; Partner Therapeutics: Consultancy; Samus Therapeutics: Consultancy; Ascentage: Consultancy; Union Pacific: Consultancy; Tesaro bio: Membership on an entity's Board of Directors or advisory committees. Al-Kadhimi:Seattle Genetics: Other: Stocks; Celldex Biotech: Other: Stocks. Vose:Celgene Corporation: Research Funding; Incyte Corporation: Research Funding; Kite Pharma: Honoraria, Other: Grants, Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; AbbVie: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Legend Pharmaceuticals: Honoraria; Acerta Pharma: Honoraria, Other: Grants, Research Funding; Bristol-Meyers Squibb Company: Research Funding. Baljevic:Karyopharm: Other: Internal Review Committee participant; Cardinal Health Specialty Solutions: Consultancy; Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

Dimethyl sulfoxide (DMSO) cryopreserved stem cell infusion-related seizures: A single institution experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19002-e19002
Author(s):  
Shirin Attarian ◽  
Murali Janakiram ◽  
Ali Ezzati ◽  
Rasim A. Gucalp
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Improve Patient Safety ◽  
Primary Cns Lymphoma ◽  
Altered Mental Status ◽  
Severe Neutropenia ◽  
Prior History ◽  
Cns Lymphoma ◽  
Hematopoietic Stem ◽  
History Of

e19002 Background: An essential step in hematopoietic stem cell transplantation (HSCT) is the cryopreservation of stem cells in DMSO. Neurologic complications related to DMSO are well known and include strokes, seizures, encephalopathy and coma, but risk factors have not been identified. We focused on seizures as a DMSO-related neurologic adverse event. Methods: From 1/2006 to 4/2016, 982 cases of HSCT were reviewed. We identified neurologic adverse events within 24h of stem cell infusion (SCI). Results: 16 cases of neurologic adverse events occurred, including transient paresthesias (2), altered mental status (5), syncope (3), stroke (1), and 5 seizures. The mean age of the patients (pt) was 64.2 years (range 52-79), with 2 females and 3 males. All 5 pts developed seizures during SCI. 4 pts had conditioning: 2 Melphalan, 1 BEAM and 1 Bu/Cy. One pt received SCI without conditioning as a last resort to treat severe neutropenia and overwhelming sepsis. Of these 5 cases, one had a prior history of seizures in the setting of primary CNS lymphoma and 1 had a prior history of stroke, and 1 pt had an acute stroke during SCI. These 3 cases had abnormal EEG with a potential focus for seizure. Conclusions: Understanding the predisposing factors for developing seizures with SCI will improve patient safety and outcomes. History of structural brain lesions or seizure may be a risk factor for development of seizures. Applying prophylactic strategies, such as DMSO removal or prophylactic antiepileptic medications prior to SCI may decrease the risk of seizures. [Table: see text]

scholarly journals Daily Chlorhexidine Gluconate Bathing Reduces the Rate of Bloodstream Infections in Adults Undergoing Inpatient Hematopoietic Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2210-2210
Author(s):  
Vinay K. Giri ◽  
Kristin G. Kegerreis ◽  
Yi Ren ◽  
Lauren M. Bohannon ◽  
Erica Lobaugh-Jin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Antibiotic Prophylaxis ◽  
Research Funding ◽  
Bloodstream Infections ◽  
Chlorhexidine Gluconate ◽  
Hematopoietic Stem ◽  
Cell Engraftment ◽  
Clinically Significant

Introduction: While hematopoietic stem cell transplantation (HSCT) has great therapeutic potential, intensive conditioning regimens and variability in time to stem cell engraftment result in a period of pancytopenia and immunosuppression in which patients are vulnerable to infection. Bloodstream infections (BSIs) occur in 20-45% of inpatient autologous and allogeneic transplant patients, leading to prolonged hospitalization and increased mortality. One method of infection prevention is daily application of the antiseptic chlorhexidine gluconate (CHG). Daily CHG bathing, either with a CHG wash or with application of CHG-impregnated cloths, has been shown to reduce the incidence of all-cause hospital-acquired BSIs in critically ill patients, such as those in the ICU, though very few studies include HSCT patients. Methods: We conducted an observational cohort study to assess the impact of daily CHG bathing on the rate of BSIs among adults undergoing inpatient HSCT at the Duke University Medical Center. Patients were included if they were admitted for pre-transplant conditioning and inpatient monitoring for allogeneic or autologous HSCT from January 2016 through December 2018. CHG bathing was instituted in January 2017 for all patients admitted to the inpatient HSCT unit using 2% CHG-impregnated cloths (SAGE™), providing one year of data with no CHG bathing and two years of data with bathing. Patients were tracked from admission until unit discharge, transfer, or first infection. Laboratory-confirmed bloodstream infections (LCBI), central-line associated bloodstream infections (CLABSI), and mucosal barrier injury laboratory-confirmed bloodstream infections (MBI-LCBI) were determined per CDC/NHSN definitions. An additional variable of "clinically-significant infection" was recorded; this included both laboratory-confirmed BSIs and infections deemed significant by the treatment team but that did not meet CDC/NHSN criteria. For example, patients that were febrile, hypotensive, and treated with antibiotics, but with only one positive culture of a common commensal were deemed to have a clinically-significant BSI. Because not all patients adhered to CHG, patients were grouped into four categories by rate of daily CHG usage: High (>75%), Medium (50-75%), Low (1-49%), and None (0%). Baseline characteristics and clinical outcomes between groups were compared via ANOVA, Chi-squared test, or Cochran-Armitage two-sided trend test. Multivariate analysis using the Fine-Grey subdistribution hazard model was conducted to compare time to all infection variables, accounting for the effects of CHG usage, antibiotic prophylaxis regimen, and type of transplant. Results: We evaluated 192 patients hospitalized for HSCT, including 118 (62%) allogeneic transplants and 74 (38%) autologous transplants. Of these, 25 (13%) had high CHG usage, 33 (17%) medium, 45 (23%) low, and 89 (46%) none. Demographics and transplant characteristics were evenly matched between the CHG usage groups with the exception that high usage groups were more likely to receive levofloxacin for antibiotic prophylaxis (p=0.003). Increased CHG usage was significantly associated with decreased incidence of clinically-significant infection (p=0.006), CLABSI (p=0.04), and MBI-LCBI (p=0.002) (Table 1). Multivariate analysis did not demonstrate a significant contribution of antibiotic prophylaxis regimen. No significant difference was found between CHG usage groups in median days to stem cell engraftment, incidence of febrile neutropenia or C. difficile infection, or rashes requiring medical treatment. There were no rashes attributable to CHG usage. Among patients who were VRE rectal swab negative on admission, there was a significant trend toward lower rates of VRE acquisition with increasing CHG usage (High CHG 13.6% vs No CHG 25.3%, p=0.02). Discussion: Increased CHG usage is associated with a significant trend toward lower rates of clinically-significant infection, CLABSI, MBI-LCBI, and VRE colonization in adult inpatients undergoing HSCT. Effects are most strongly seen at >75% daily CHG usage. There were no adverse effects due to CHG application. The significant decrease in MBI-LCBI with topical CHG suggests an interaction between the skin microbial environment and enteric organisms. Therefore, further research exploring the effects of CHG on the skin and gut microbiota is warranted. Disclosures Gasparetto: BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Horwitz:Abbvie Inc: Membership on an entity's Board of Directors or advisory committees. Rizzieri:Celgene, Gilead, Seattle Genetics, Stemline: Other: Speaker; AbbVie, Agios, AROG, Bayer, Celgene, Gilead, Jazz, Novartis, Pfizer, Sanofi, Seattle Genetics, Stemline, Teva: Other: Advisory Board; AROG, Bayer, Celgene, Celltron, Mustang, Pfizer, Seattle Genetics, Stemline: Consultancy; Stemline: Research Funding. Sung:Novartis: Research Funding; Merck: Research Funding; Seres: Research Funding.

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