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Wingard, John R.

https://orcid.org/0000-0001-7478-5398

Mayo Clinic

University of Florida

Citations 21

Impact of Cryopreservation of Donor Grafts on Outcomes of Allogeneic Hematopoietic Cell Transplant (HCT)
Hsu, Jack W., Farhadfar, Nosha , Logan, Brent R. , Bo‐Subait, Stephanie, Goldstein, Steven C., Horowitz, Mary M. , Schwanke, Joshua, Shaw, Bronwen E. , Murthy, Hemant S. , Frey, Noelle V. , Lazarus, Hillard M. , Shah, Nirali N , Spellman, Stephen R. , Switzer, Galen E. , Devine, Steven M. , Wingard, John R.

Blood | November 4, 2020 | Volume: 136 | Issue: Supplement 1 | Pages: 33-34

10.1182/blood-2020-136778 Get It

Introduction: Cryopreservation of peripheral blood stem cell (PBSC) or bone marrow (BM) grafts is rarely performed, thus information about the effect of cryopreservation on graft characteristics and HCT outcomes is limited. Given the global pandemic leading to changing practices for donor graft collection and increasing utilization of cryopreservation, we evaluated the outcomes of HCT recipients who received either fresh or cryopreserved allogeneic BM or PBSC grafts. The primary endpoint was engraftment. Secondary endpoints were incidence of acute graft-vs.-host disease (aGVHD), relapse, transplant related mortality (TRM), disease free survival (DFS), and overall survival (OS). Methods: We included 7397 patients transplanted between 2013 and 2018. 1883 cryopreserved graft recipients were divided into three cohorts based on graft source and donor type: matched related (MRD) PBSC (n=1,051), matched unrelated (MUD) PBSC (n=678), and matched related or unrelated bone marrow donors (n=154). All patients received conventional calcineurin-based GVHD prophylaxis strategies. Patients who received cryopreserved grafts were matched with 5514 patients who received fresh adjusting for graft type (BM vs. PB), donor source (MRD vs. 8/8 MUD), Disease Risk Index (DRI, low risk vs. intermediate risk vs. high risk), recipient age (within 5-years) and propensity score (within 1 standard deviation from pooled sample). The propensity score was based on age, Karnofsky score, diagnosis, disease risk index, HCT-comorbidity index, and conditioning intensity. The level of statistical significance for the main analyses was p<0.01 due to multiple comparisons. The reason for cryopreservation was available on a subset of URD product recipients. Results: Baseline characteristics for all cohorts are shown in Table 1. CD34+ doses reflect enumeration at infusion. In univariate analyses, rates of graft failure and neutrophil recovery at day 28 were similar for cryopreserved and fresh grafts for BM or related PBSC recipients but differed in cryopreserved vs. fresh MUD PBSC (5% vs 2%, p<0.001 and 87 vs 94%, p<0.001, respectively). Rates of platelet recovery within 28 days were similar in marrow cohorts, but lower with cryopreserved related (92% vs 96%, p<0.001) and MUD PBSC (87 vs 94%, p<0.001) grafts. In matched pair multivariable analyses, there were no significant differences in any outcomes with cryopreserved vs fresh BM grafts, irrespective of donor type. With related donor PBSC, cryopreservation was associated with decreased platelet recovery (HR=0.73, CI=0.68-0.78, p<0.001) and an increased risk of both grade II-IV (HR=1.27, CI=1.09-1.48, p=0.002) and grade III-IV (HR=1.48, CI=1.19-1.84, p<0.001) aGVHD, but had no impact on other outcomes. In contrast, with MUD PBSC grafts, cryopreservation was associated with delayed engraftment of neutrophils (HR=0.77, CI=0.71-0.84, p<0.001) and platelets (HR=0.61, CI=0.56-0.66, p<0.001), an increased risk of TRM (HR=1.4, CI=1.18-1.66, p<0.001) and relapse (HR=1.32, CI=1.11-1.58, p=0.002), and decreased DFS (HR=1.36, CI=1.20-1.55, p<0.001) and OS (HR=1.38, CI=1.22-1.58, p<0.001) but did not affect the incidence of aGVHD. In a subset analysis of 299 URD recipients, the most common reason for cryopreservation was delays due to patient-related events, eg., additional chemotherapy, infection. These recipients had decreased OS compared to products cryopreserved for non-patient reasons (HR=0.65, CI=0.44-0.96, p=0.029). Conclusions: The retrospective nature of this analysis, and the fact that cryopreservation is likely to have been performed in recipients with a different (higher) risk profile compared to those receiving fresh products limits our ability to draw firm confusions. Despite these limitations, we conclude that cryopreservation in some patient populations may have a negative impact on engraftment and transplant outcomes. The decision to cryopreserve donor grafts, particularly PBSC grafts, should be carefully considered and highlights the need for further investigation of the effect of cryopreservation of allogeneic grafts where patient factors can be controlled for. Disclosures Farhadfar: CSL Behring: Research Funding; Incyte pharmaceutical: Other: Member of GVHD advisory forum. Frey:Kite Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Syntax: Consultancy, Honoraria. Devine:Magenta Therapeutics: Consultancy. Shaw:Orca Bio: Consultancy. Wingard:Shire: Other: Personal Fees - serve on data monitoring committee for clinical trial; Ansun: Other: Personal Fees - serve on data monitoring committee for clinical trial; Merck: Other: Personal Fees - serve on data monitoring committee for clinical trial; Cidara: Other: Personal Fees - serve on data monitoring committee for clinical trial; ReViral: Other: Personal Fees - serve on data monitoring committee for clinical trial.
Impact of Renal Dysfunction Measured By Estimated Glomerular Filtration Rate (eGFR) on Outcomes after Allogeneic Hematopoietic Cell Transplantation (HCT)
Farhadfar, Nosha , Dias, Ajoy , Wang, Tao , Fretham, Caitrin, Logan, Brent R. , Mineishi, Shin , Stadtmauer, Edward A. , Wingard, John R. , Ganguly, Siddhartha , Pasquini, Marcelo C. , Murthy, Hemant S. , Savani, Bipin N. , Chhabra, Saurabh

Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 3256-3256

10.1182/blood-2019-125761 Get It

Introduction Renal dysfunction is a recognized risk factor for mortality after HCT, as it is included in the comorbidity index (HCT CI). Yet, further understanding on outcomes in patients with different level of renal dysfunction or undergoing hemodialysis (HD) at time of transplant remains scant. This study explores the impact of different levels renal dysfunction on major HCT outcomes in a large population using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Methods The study population included 8,102 patients age 40 years and older who received HCT for treatment of malignancies from 2008 to 2016, with available pre-transplant creatinine measurement. eGFR, calculated using CKD-EPI (CKD-epidemiology collaboration) method, was used to assigned patients in four categories: eGFR ≥ 90ml/min (eGFR≥ 90, N=4,237, reference), eGFR 60-90ml/min (eGFR 60-90, N=3,158), eGFR 45-59ml/min (eGFR 45-59, N=538) and eGFR <45ml/min(eGFR<45, N=169). A separate cohort of patients on HD at time of HCT (N=46) was analyzed independently. Multivariate analysis models were built for assessment of overall mortality, transplant-related mortality (TRM), disease relapse or progression, graft-versus-host disease (GVHD), hepatic sinusoidal obstructive syndrome (SOS), thrombotic microangiopathy (TMA), idiopathic pneumonia syndrome (IPS) and need of HD post-transplant. Common patient-, disease- and transplant-related covariates were tested on all models and HCT CI was computed without reported renal dysfunction comorbidity to avoid collinearity. Results Patient characteristics are shown in table 1. The groups were comparable on disease risk index, graft and donor source, but patients with eGFR>90 were younger and received myeloablative conditioning more frequently. The cohort of eGFR <45 had a higher proportion of patients with HCT CI ≥3. TRM and overall survival according to eGFR groups are shown in Figure. In the multivariate analysis models eGFR as the main effect was associated with TRM (p<0.0001), overall mortality (p<0.0001), and requirement of HD post HCT (p<0.0001), but not for relapse/progression (p=0.98), GVHD (grades II-IV, p=0.34; III-IV, p=0.70; and chronic, p=0.20), TMA (p=0.46), SOS (p=0.02) or IPS (p=0.06). Compared to eGFR ≥90, the hazard ratio (HR) for TRM for eGFR 60-89 was 1.12 (p=0.07), for eGFR 45-59 was 1.46 (p<0.001) and for eGFR<45 was 1.74 (p=0.004). Corresponding HRs for overall mortality were 1.0 (p=0.9), 1.17 (p=0.03) and 1.63 (p<0.0001), respectively. Similarly, for the need of HD post HCT, HR for eGFR60-89 was 1.29 (p=0.03), eGFR45-59 was 2.45 (p<0.001) and for eGFR<45 was 3.09 (p<0.0001). Only eGFR<45 was associated with higher risk of SOS (HR2.66, p=0.03). Among 46 patients on HD prior to HCT, one-year probability of overall survival was 20% (95% Confidence Interval [CI] 10-32%) and cumulative incidence of TRM at one year was 67% (95% CI, 50-81%). Conclusion These findings indicate that degree of renal dysfunction is an independent predictor of OS, TRM, probability of receiving HD and SOS when adjusted for other risk factors. The impact of eGFR on the need of HD, a complication that increases morbidity post HCT is an important finding. Additionally, the outcomes of a subset of patients on HD at time of transplants are dismal. These results can further assist the prognostic assessment of candidates for an allogeneic HCT. Disclosures Stadtmauer: Celgene: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Novartis: Consultancy, Research Funding; Tmunity: Research Funding; Abbvie: Research Funding. Wingard:Ansun: Consultancy; Pluristem: Consultancy; Celgene: Consultancy; Merck: Consultancy; Shire: Consultancy. Ganguly:Seattle Genetics: Speakers Bureau; Daiichi Sankyo: Research Funding; Kite Pharma: Honoraria, Other: Advisory Board; Janssen: Honoraria, Other: Advisory Board. Pasquini:Pfizer: Other: Advisory Board; Amgen: Consultancy; Medigene: Consultancy; BMS: Research Funding; Novartis: Research Funding; Kit Pharma: Research Funding.
Diet Quality of Long-Term Allogeneic and Autologous Stem Cell Transplant (HCT) Survivors
Farhadfar, Nosha , Mead, Lacey, Nair, Shalini R., Brown, Randy A., Hiemenz, John W., Hsu, Jack W., Wingard, John R. , Kelly, Debra Lynch , Nair, Shalini, Murthy, Hemant S. , May, William Stratford , Dahl, Wendy J.

Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 4565-4565

10.1182/blood-2019-127648 Get It

Introduction Long-term hematopoietic stem cell transplant (HCT) survivors are burdened by a high prevalence and early onset of chronic diseases. Healthy dietary patterns have been associated with lower risks of chronic health conditions in the general population, yet no study to date has comprehensively documented the adherence of HCT survivors to the Dietary Guidelines for Americans (DGA), specifically designed to provide guidance for making healthy food choices. The aims of this study were to evaluate the extent to which HCT survivors adhere to the DGA and to determine nutrient intake adequacy. A secondary aim was to assess their willingness to take part in a future nutritional program or dietary intervention. Methods The study population included adults (≥18 y), who had undergone autologous or allogeneic HCT for a hematologic disease and were at least 1-year post-transplantation. Dietary intake was assessed using the Block 2014 food frequency questionnaire and diet quality (adherence to the DGA) was estimated using the Healthy Eating Index-2015 (HEI-2015). A HEI score of ≤50 indicates "poor diet quality", 51-80 suggests a "diet that needs improvement", and >81 indicates "good diet quality" out of maximum of 100. HEI-2015 scores by patient and transplant characteristics were analyzed by ANCOVA. Nutrient intake adequacies of the group were estimated by determining the percentage of the group falling below the Estimated Average Requirement (EAR) of the Dietary Reference Intakes. Receptivity to participate in a dietary intervention to stay healthy was measured by the question, "How willing would you be to take part in a healthy nutrition program or diet intervention?" Response categories included, "not at all," "somewhat," and "definitely". Results Between December 2017 and September 2018, 124 survivors were invited to participate, of whom 90 (51 autologous and 39 allogeneic HCT survivors) completed the dietary intake assessment and were included in the analysis. Majority were male (56%), White (72%), married (81%) and completed some college education (57%). Most participants were overweight (34%) or obese (37%). The median time from the HCT was 5.2 years. Mean ±SE HEI-2015 scores were 61.6 ± 1.3 and 60.7 ± 2.2 for the 18-64 y and ≥65 y age groups, respectively, slightly higher than the US general population. Adherence to a good quality diet was reported by only 10% of survivors. The majority of the survivors reported a diet in need of improvement (82%) or a poor-quality diet (8%). Intakes of vitamin A (720 ± 447 mcg/d), vitamin C (82 ± 73 mg/d), vitamin D (4.4 ± 3.4 mcg/d), magnesium (253 ± 133 mg/d), and calcium (781 ± 430 mg/d) suggested inadequacy, as more than 50% of the group fell below the specific EARs. Sodium intake at 2834 ± 1345 mg/d exceeded the DGA recommendation of 2300 mg/d. Fiber intake at 8.9 g per 1000 kcal/d was significantly below the Adequate Intake of 14 g per 1000 kcal/d. "Change in taste" was the only variable associated with lower quality of diet (p=0.02). Interestingly, 29% of HCT survivors reported persistent altered taste sensation. No significant relationships were seen for participant's demographics and diet quality which may be due to a sample population skewed toward older, causations and socioeconomically advantaged individuals. More than two thirds of participants (73%) indicated an interest in participating in dietary intervention. HCT survivors within 2 years of transplant were more likely to be receptive to participation in a diet intervention study compared to survivors beyond 2 years (52% vs 28%, p=0.0013). Conclusion Adult HCT survivors report poor adherence to the 2015 Dietary Guidelines for Americans and have numerous short-fall nutrient intakes. However, the willingness to participate in a nutritional program or dietary intervention in this survivorship population was relatively high. These findings reinforce the need to incorporate nutrition into HCT survivor care. Disclosures Wingard: Celgene: Consultancy; Merck: Consultancy; Shire: Consultancy; Ansun: Consultancy; Pluristem: Consultancy.
Vitamin D Effect On Umbilical Cord Blood Characteristics: A Comparison Between African Americans and Caucasians
Eldjerou, Lamis, Rosenau, Emma, Lu, Xiaomin , Bennett, Clayton , Hoyne, Jonathan , Lambert, Amy J. , Hertel, Lindsay, Sazama, Kathleen, Wingard, John R. , Sugrue, Michele W. , Zubair, Abba C.

Blood | October 13, 2019 | Volume: 122 | Issue: 21 | Pages: 693-693

10.1182/blood.v122.21.693.693 Get It

Abstract Background Umbilical cord blood (UCB) is an important alternative source of stem cells for patients who lack matched adult donors, particularly in ethnic minorities. The infused total nucleated cell (TNC) and CD34+ cell dose are important prognostic factors on transplant outcomes. UCB units collected from African Americans (AA) have lower TNC and CD34+ cell counts and more likely to be disqualified for banking compared to other racial and ethnic groups. Furthermore, AA, including pregnant women, have increased prevalence of vitamin D deficiency. Vitamin D has an established role in hematopoiesis; therefore, we investigated the racial differences in UCB vitamin D content and its correlation with UCB cell composition and hematopoietic potential. Methods 119 UCB units that did not meet the TNC count banking criteria were analyzed. 51 UCB units were collected from AA mothers and 68 from Caucasian mothers. We analyzed UCB variables including volume, hematocrit (HCT), TNCs, mononucleated cells (MNC), CD34+ cells, plasma 25-Hydroxy vitamin D [25(OH)D] and in vitro progenitor cell hematopoietic potential measured by Colony-Forming Cell (CFC) assay. Results The median values of 25(OH)D in UCB units were significantly lower in AA compare to Caucasians (p= <.0001). Severe vitamin D deficiency < 10 ng/mL was exclusively detected in UCB units from AA (19/51; 37%) and plasma 25(OH)D concentration < 20 ng/mL was more prevalent in AA (43/51 units; 84%), compare to Caucasians (15/68 units; 22%). UCB units from AA had lower absolute numbers of TNC (p= .0016), MNC (p= .0261), and CD34+ cells (p= .0257) compare to Caucasians. No difference in median CFC/10,000 MNC was detected between AA and Caucasians (p= 0.661) (Table 1). Univariate analysis of 25(OH)D effect on UCB variables revealed a correlation between 25(OH)D level and TNC (r= 0.193, 95% CI 0.013-0.36; p= .0353) and UCB HCT (r= 0.196, 95% CI 0.016-0.363; p= .0327). A significantly higher MNC count was noted when 25(OH)D concentration was ≥ 20ng/mL (4.5x 108, range (1.7-9.5) vs. 3.9x 108, range (0.8-9); p= .0329). This correlation between 25(OH)D level and TNC and MNC was not detected after adjustment for race (Figure 1). However, 25(OH)D concentration ≥ 20 ng/mL significantly correlated with CBU HCT in AA race (median 31.9% (24-42) vs. 27.8%, range (21.4 - 40); p= .0124). Conclusion 25(OH)D level, TNC and HCT are all significantly lower in UCB units from AA compare to Caucasians. Independent of race, 25(OH)D directly correlated with TNC and MNC. These data suggest vitamin D and other yet to be determined factors play an important role in the mechanism of low UCB cell and progenitor counts. Disclosures: No relevant conflicts of interest to declare.
Do Hematopoietic Cell Transplant Patients Treated on a Clinical Trial Do Better? Comparison of Characteristics and Outcomes of Patients Enrolled Versus Not Enrolled on Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) 0201 Trial
Khera, Nandita , Brazauskas, Ruta , Aljurf, Mahmoud , Akpek, Görgün, Beattie, Sara , Bredeson, Christopher , Burns, Linda J. , Dehn, Jason , Freytes, César O. , Hale, Gregory A., Inamoto, Yoshihiro , LeMaistre, Charles F. , Palmer, Jeanne , Paulson, Kristjan, Schears, Raquel M. , Steinberg, Amir , Szwajcer, David , Wirk, Baldeep , Hahn, Theresa , Loberiza, Fausto R., Majhail, Navneet S. , Wang, Zhiwei Peter , Atsuta, Yoshiko , Chen, Allen R. , Gupta, Vikas , Lazarus, Hillard M. , Wingard, John R. , Wood, William A. , Joffe, Steven , Lee, Stephanie J.

Blood | October 10, 2019 | Volume: 124 | Issue: 21 | Pages: 209-209

10.1182/blood.v124.21.209.209 Get It

Abstract Background: The association of clinical trial participation with outcomes in cancer patients is controversial, with some studies reporting better outcomes for trial participants while others do not. It is possible that the difference in outcomes is due to differences in baseline characteristics of participants and non-participants. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 trial was a large randomized, multi-center study comparing peripheral blood (PB) with bone marrow (BM) for hematopoietic cell transplantation (HCT) from HLA-matched or 1 allele mismatched unrelated donors (URD) in patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndromes. The trial reported no significant survival differences between PB and BM; there was decreased risk of graft failure but increased risk of chronic graft-versus-host disease (GVHD) with PB grafts (Anasetti et al NEJM 2012). Methods: We compared characteristics of BMT CTN 0201 study participants (n=494) with HCT recipients who did not participate on the trial (n=1384) but were potentially eligible by virtue of known characteristics. These patients received similar conditioning and GVHD prophylaxis as trial participants at 38 United States trial centers during the study time-period. Centers that had no eligible non-trial participants were excluded. Outcomes between patients on and off trial were compared using Cox proportional hazards regression models. Data were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) that collects patient data on all trial and non-trial allogeneic HCT recipients through its registry function. Results: Approximately 29% [494/1878] of apparently eligible patients were randomized and analyzed as part of the trial. There were no significant differences between study participants and non-participants in age or sex distribution, disease types, HLA or sex matching, comorbidities, or interval from diagnosis to HCT. Higher proportions of non-participants were Hispanic, had a lower performance status and lower disease risk, and received myeloablative conditioning and antithymocyte globulin (ATG) or Campath than the study participants. PB was used more commonly as the graft source in the non-participants as compared to the study participants (65% vs. 50%, p<0.001). In multivariate models, overall mortality (HR 1.09, 95% CI 0.95-1.25, p=0.22), transplant-related mortality (HR 1.08, 95% CI 0.89-1.32, p=0.42) and risks of acute grade II-IV (HR 0.96, 95% CI 0.82-1.12, p=0.57) and chronic GVHD (HR 1.06, 95% CI 0.92-1.23, p=0.41) were comparable between study non-participants and participants. Non-participants were at higher risk for relapse than participants (HR 1.24, 95%CI 1.04-1.49, p=0.02) in the multivariate analysis adjusted for disease risk and other clinical variables. Center effect was examined and was not found to be significant (p=0.10). There was no significant interaction between graft source and trial participation (P=0.22) and the risk of mortality was comparable for BM (HR 0.99, 95% CI 0.80-1.22, p=0.90) and PB recipients (HR 1.17, 95% CI 0.97-1.41, p=0.09) whether on trial or off trial. (Figure) Conclusion: Approximately 29% of patients who appeared eligible and were treated with conditioning and GVHD prophylaxis regimens allowed on the trial were enrolled. Despite some differences in clinical characteristics, most of the outcomes of non-trial participants were comparable to trial participants, suggesting that there is no definitive evidence that the outcomes of patients in a clinical trial are superior to those of the non-participants treated in a similar fashion. The comparable outcomes also indicate that the results of this trial were not seriously affected by selection bias and are therefore representative of the larger population. Figure 1: Adjusted overall survival in BMT CTN 0201 trial participants and non-participants Figure 1:. Adjusted overall survival in BMT CTN 0201 trial participants and non-participants Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
Tacrolimus/Sirolimus Vs. Tacrolimus/Methotrexate for Graft-Vs.-Host Disease Prophylaxis After HLA-Matched, Related Donor Hematopoietic Stem Cell Transplantation: Results of Blood and Marrow Transplant Clinical Trials Network Trial 0402
Logan, Brent R. , Nakamura, Ryotaro , Johnston, Laura, Choi, Sung Won , Porter, David L. , Pasquini, Marcelo C. , Wingard, John R. , Waller, Edmund K. , Wu, Juan , Hu, Zhen‐Huan , Carter, Shelly L., Horowitz, Mary M. , Antin, Joseph H. , Waller, Edmund K , Cutler, Corey S. , Hogan, William J. , MacMillan, Margaret L. , Grupp, Stephan A. , McCarthy, Philip L. , Choi, Sung Won

Blood | October 9, 2019 | Volume: 120 | Issue: 21 | Pages: 739-739

10.1182/blood.v120.21.739.739 Get It

Abstract Abstract 739 The combination of a calcineurin inhibitor and methotrexate has been the standard of care in graft-vs.-host disease (GVHD) prophylaxis for over 25 years, with resultant rates of grade II-IV acute GVHD between 30–50%. The mTOR inhibitor, sirolimus, has demonstrated promise in a number of Phase II trials as an immunosuppressant used for GVHD prophylaxis. The BMT CTN, sponsored by the NHLBI and NCI, conducted a multicenter, randomized controlled trial comparing the combination of tacrolimus and sirolimus (Tac/Sir) with tacrolimus and methotrexate (Tac/Mtx) as GVHD prophylaxis after matched, related donor (MRD) hematopoietic stem cell transplantation (HSCT). Methods: Eligible patients were between ages 2 – 60 years, and had acute leukemia in remission, myelodysplasia or chronic myeloid leukemia in chronic or accelerated phase. All had adequate organ function, and a 6/6 HLA-A, B, DRB1 matched sibling donor. 304 patients were randomly assigned to either Tac/Sir (n = 151) or Tac/Mtx (n = 153) as GVHD prophylaxis after TBI-based conditioning and MRD HSCT. An intent-to-treat analysis was performed on the primary endpoint of Grade II-IV GVHD-free survival 114 days from randomization. Ten subjects who received busulfan-based conditioning and were previously reported were excluded from analysis. Three subjects who did not undergo HSCT are included in the primary analysis, but not secondary analyses. Results: Treatment groups were well balanced. The median age of participants was 44 years (range 13 – 59) and 83% had acute leukemia. Neutrophil and platelet engraftment were both faster in the Tac/Sir group (14 vs. 16 days, p < 0.001; 16 vs. 19 days, p = 0.03, respectively), but this did not affect the time to first hospital discharge (20 vs. 21 days, p = 0.37). The incidence of grade II-IV and grade III-IV acute GVHD at 100 days were lower in the Tac/Sir group (26 vs. 34%, p = 0.17; 8 vs. 15%, p = 0.05). Day 100 treatment-related mortality was no different between groups (7 vs. 7%, p = 0.43). The primary endpoint of 114-day acute GVHD-free survival was not statistically different between groups (67 vs. 62%, p = 0.38, Figure). The cumulative incidence of relapse at 2 years from transplantation was not different between groups (27 vs. 30%, p = 0.81). The competing-risk cumulative incidence of chronic GVHD was higher in the Tac/Sir arm (54 vs. 43%, p =0.044). Overall toxicities were not different between groups, with two notable exceptions. The peak and average OMAS oral mucositis scores were lower in the Tac/Sir arm (peak 0.70 vs. 0.96, p < 0.001; average 0.31 vs. 0.47, p < 0.001), however, there was an increased rate of the endothelial injury syndromes, veno-occlusive disease (11 vs. 4%, p = 0.03), and thrombotic microangiopathy (5 vs. 1%, p = 0.05) in the Tac/Sir arm. Causes of death were not different between groups. At 2 years from transplantation, disease-free (DFS) and overall survival (OS) were not different between study arms (DFS 53 vs. 53%, p = 0.76; OS 60 vs. 61%, p = 0.44). Conclusions: No difference in 114-day acute GVHD-free survival was noted between treatment arms. Compared with Tac/Mtx in MRD HSCT, Tac/Sir is associated with more rapid engraftment, less severe acute GVHD and oral mucositis, excess chronic GVHD and endothelial injury syndromes, and similar long-term outcomes. Understanding the trade-offs between regimens, Tac/Sir can be used as an alternative to Tac/Mtx in MRD HSCT. Disclosures: Cutler: Pfizer, inc: Research Funding; Astellas, Inc: Consultancy, Research Funding. Off Label Use: Sirolimus - Prevention of GVHD Tacrolimus - Prevention of GVHD. Waller:Outsuka: Research Funding.
Increased overall and bacterial infections following myeloablative allogeneic HCT for patients with AML in CR1
Üstün, Celalettin , Kim, Soyoung , Chen, Min , Beitinjaneh, Amer , Brown, Valerie I. , Daly, Andrew , Freytes, César O. , Ganguly, Siddhartha , Hashmi, Shahrukh K. , Hildebrandt, Gerhard , Olsson, Richard F. , Page, Kristin , Saad, Ayman , Seo, Sachiko , William, Basem M. , Wirk, Baldeep , Auletta, Jeffery J. , Lindemans, Caroline A. , Riches, Marcie , Freytes, Cesar O , Hashmi, Shahrukh K , Hildebrandt, Gerhard C , Lazarus, Hillard M , Nishihori, Taiga , Olsson, Richard F , Saad, Ayman , Yared, Jean A , Komanduri, Krishna V , Riches, Marcie L , William, Basem , Dahi, Parastoo B , Díaz, Miguel Ángel , Lazarus, Hillard M. , Nishihori, Taiga , Papanicolaou, Genovefa A. , Wingard, John R. , Yared, Jean A. , Perales, Miguel‐Angel , Komanduri, Krishna V. , Auletta, Jeffery J , Kim, Soyoung

Blood Advances | August 30, 2019 | Volume: 3 | Issue: 17 | Pages: 2525-2536

10.1182/bloodadvances.2019000226 Get It

Abstract Presumably, reduced-intensity/nonmyeloablative conditioning (RIC/NMA) for allogeneic hematopoietic cell transplantation (alloHCT) results in reduced infections compared with myeloablative conditioning (MAC) regimens; however, published evidence is limited. In this Center for International Blood and Marrow Transplant Research study, 1755 patients (aged ≥40 years) with acute myeloid leukemia in first complete remission were evaluated for infections occurring within 100 days after T-cell replete alloHCT. Patients receiving RIC/NMA (n = 777) compared with those receiving MAC (n = 978) were older and underwent transplantation more recently; however, the groups were similar regarding Karnofsky performance score, HCT–comorbidity index, and cytogenetic risk. One or more infections occurred in 1045 (59.5%) patients (MAC, 595 [61%]; RIC/NMA, 450 [58%]; P = .21) by day 100. The median time to initial infection after MAC conditioning occurred earlier (MAC, 15 days [range, &lt;1-99 days]; RIC/NMA, 21 days [range, &lt;1-100 days]; P &lt; .001). Patients receiving MAC were more likely to experience at least 1 bacterial infection by day 100 (MAC, 46% [95% confidence interval (CI), 43-49]; RIC/NMA, 37% [95% CI, 34-41]; P = .0004), whereas at least a single viral infection was more prevalent in the RIC/NMA cohort (MAC, 34% [95% CI, 31-37]; RIC/NMA, 39% [95% CI, 36-42]; P = .046). MAC remained a risk factor for bacterial infections in multivariable analysis (relative risk, 1.44; 95% CI, 1.23-1.67; P &lt; .0001). Moreover, the rate of any infection per patient-days at risk in the first 100 days (infection density) after alloHCT was greater for the MAC cohort (1.21; 95% CI, 1.11-1.32; P &lt; .0001). RIC/NMA was associated with reduced infections, especially bacterial infections, in the first 100 days after alloHCT.
Phaeohyphomycosis in transplant recipients: Results from the Transplant Associated Infection Surveillance Network (TRANSNET)
McCarty, Todd P , Walsh, Thomas J. , Alexander, Barbara D. , Perl, Trish M. , Walker, Randall C., Schuster, Mindy G. , Lyon, G. Marshall, Wingard, John R. , Andes, David R. , Park, Benjamin J., Brandt, Mary E., Pappas, Peter G. , Investigators, TRANSNET, McCarty, T P , Walker, Randall, Baddley, John W. , Kontoyiannis, Dimitrios P. , Patterson, Thomas F. , Investigators, TRANSNET

Medical Mycology | April 24, 2015 | Volume: 53 | Issue: 5 | Pages: 440-446

10.1093/mmy/myv018 Get It

Vitamin D effect on umbilical cord blood characteristics: a comparison between African Americans and Caucasians
Eldjerou, Lamis, Rosenau, Emma, Lu, Xiaomin , Bennett, Clay A., Sugrue, Michele W. , Hoyne, Jonathan , Lambert, Amy J. , Ashley, Lindsay, Sazama, Kathleen, Fields, Gary, Wingard, John R. , Cogle, Christopher Ramin , Zubair, Abba C.

Transfusion | April 22, 2015 | Volume: 55 | Issue: 7 | Pages: 1766-1771

10.1111/trf.13124 Get It

BACKGROUNDUmbilical cord blood (UCB) units collected from African Americans (AAs) have lower total nucleated cell (TNC) and CD34+ cell counts and are more likely to disqualify for banking compared to other ethnic groups. Furthermore, AAs have higher prevalence of 25‐hydroxyvitamin D (25(OH)D) deficiency. Given the importance of 25(OH)D in hematopoiesis, we examined the racial differences in UCB unit 25(OH)D content and its correlation with UCB cellular characteristics.STUDY DESIGN AND METHODSA total of 119 UCB units that did not meet the TNC count banking criteria were analyzed. Fifty‐one UCB units were collected from AA mothers and 68 from Caucasian mothers. We analyzed UCB volume, hematocrit (Hct), TNCs, mononuclear cells (MNCs), CD34+ cells, plasma 25(OH)D concentration, and progenitor clonogenic capacity measured by colony‐forming cell (CFC) assay.RESULTSCompared to Caucasians, AAs had significantly lower UCB 25(OH)D levels (p < 0.0001), TNCs (p = 0.002), MNCs (p = 0.026), and CD34+ cells (p = 0.026). Severe deficiency (25(OH)D < 10 ng/mL) was only detected in AAs. No difference in median CFC count/10,000 MNCs was detected between AAs and Caucasians. Independent of race, a significant association was detected between 25(OH)D level and TNCs (r = 0.193 p = 0.035) and Hct (r = 0.196 p = 0.033).CONCLUSIONThese results indicate the importance of 25(OH)D level as a racially independent predictor of UCB cellular characteristics and support further investigation of bioactive vitamin D and other predictors of hematopoiesis on cord blood quality.
Reduction in False-Positive Aspergillus Serum Galactomannan Enzyme Immunoassay Results Associated with Use of Piperacillin-Tazobactam in the United States
Vergidis, Paschalis , Wheat, L. Joseph , Estes, Lynn L., Caliendo, Angela M. , Baden, Lindsey R. , Wingard, John R. , Assi, Maha, Chandrasekar, Pranatharthi , Shields, Ryan K. , Freifeld, Alison G. , Köhler, Richard, Kleiman, Martin B., Walsh, Thomas J. , Hage, Chadi A. , Estes, Lynn, Razonable, Raymund R. , Baddley, John W. , Norris, Steven J. , Nguyễn, Hồng Quân , Vergidis, Paschalis

Journal of Clinical Microbiology | April 9, 2014 | Volume: 52 | Issue: 6 | Pages: 2199-2201

10.1128/jcm.00285-14 Get It

ABSTRACT Piperacillin-tazobactam (PTZ) is known to cause false-positive results in the Platelia Aspergillus enzyme-linked immunoassay (EIA), due to contamination with galactomannan (GM). We tested 32 lots of PTZ and 27 serum specimens from patients receiving PTZ. GM was not detected in the lots of PTZ; one serum specimen (3.7%) was positive. PTZ formulations commonly used in the United States today appear to be a rare cause for false-positive GM results.