Browsing by Author "Logan, Brent R"

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    ItemOpen Access
    Effect of cord blood processing on transplantation outcomes after single myeloablative umbilical cord blood transplantation.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2015-04) Ballen, Karen K; Logan, Brent R; Laughlin, Mary J; He, Wensheng; Ambruso, Daniel R; Armitage, Susan E; Beddard, Rachel L; Bhatla, Deepika; Hwang, William YK; Kiss, Joseph E; Koegler, Gesine; Kurtzberg, Joanne; Nagler, Arnon; Oh, David; Petz, Lawrence D; Price, Thomas H; Quinones, Ralph R; Ratanatharathorn, Voravit; Rizzo, J Douglas; Sazama, Kathleen; Scaradavou, Andromachi; Schuster, Michael W; Sender, Leonard S; Shpall, Elizabeth J; Spellman, Stephen R; Sutton, Millicent; Weitekamp, Lee Ann; Wingard, John R; Eapen, Mary
    Variations in cord blood manufacturing and administration are common, and the optimal practice is not known. We compared processing and banking practices at 16 public cord blood banks (CBB) in the United States and assessed transplantation outcomes on 530 single umbilical cord blood (UCB) myeloablative transplantations for hematologic malignancies facilitated by these banks. UCB banking practices were separated into 3 mutually exclusive groups based on whether processing was automated or manual, units were plasma and red blood cell reduced, or buffy coat production method or plasma reduced. Compared with the automated processing system for units, the day 28 neutrophil recovery was significantly lower after transplantation of units that were manually processed and plasma reduced (red cell replete) (odds ratio, .19; P = .001) or plasma and red cell reduced (odds ratio, .54; P = .05). Day 100 survival did not differ by CBB. However, day 100 survival was better with units that were thawed with the dextran-albumin wash method compared with the "no wash" or "dilution only" techniques (odds ratio, 1.82; P = .04). In conclusion, CBB processing has no significant effect on early (day 100) survival despite differences in kinetics of neutrophil recovery.
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    Immune Reconstitution and Survival of 100 SCID Patients Post Hematopoietic Cell Transplant: A PIDTC Natural History Study.
    (Blood, 2017-10-11) Heimall, Jennifer; Logan, Brent R; Cowan, Morton J; Notarangelo, Luigi D; Griffith, Linda M; Puck, Jennifer M; Kohn, Donald B; Pulsipher, Michael A; Parikh, Suhag; Martinez, Caridad; Kapoor, Neena; O'Reilly, Richard; Boyer, Michael; Pai, Sung-Yun; Goldman, Frederick; Burroughs, Lauri; Chandra, Sharat; Kletzel, Morris; Thakar, Monica; Connelly, James; Cuvelier, Geoff; Davila Saldana, Blachy J; Shereck, Evan; Knutsen, Alan; Sullivan, Kathleen E; DeSantes, Kenneth; Gillio, Alfred; Haddad, Elie; Petrovic, Aleksandra; Quigg, Troy; Smith, Angela R; Stenger, Elizabeth; Yin, Ziyan; Shearer, William T; Fleisher, Thomas; Buckley, Rebecca H; Dvorak, Christopher C
    The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010-2014, including 68 with typical SCID and 32 with leaky SCID, Omenn Syndrome or Reticular Dysgenesis. Most (59%) were diagnosed by newborn screening or family history. The 2-year overall survival (OS) was 90%but was 95% for those infection-free at HCT vs. 81% for those with active infection (p=0.009). Other factors, including the diagnosis of typical vs. leaky SCID/Omenn Syndrome, diagnosis via family history or newborn screening (FH/NBS), use of preparative chemotherapy, or the type of donor utilized did not impact survival. While 1-year post-HCT median CD4 counts and freedom from IVIG were improved after use of preparative chemotherapy, other immunologic reconstitution parameters were not affected and the potential for late sequelae in extremely young infants requires further evaluation. Following a T-cell-replete graft, landmark analysis at Day +100 post-HCT revealed that CD3 <300 cells/uL, CD8 <50 cells/uL, CD45RA <10%, or a restricted Vβ T cell receptor repertoire (<13 of 24 families) was associated with need for second HCT or death. In the modern era, active infection continues to pose the greatest threat to survival for SCID patients. Although NBS has been effective in diagnosing SCID patients early in life, there is an urgent need to identify validated approaches through prospective trials to ensure that patients proceed to HCT infection free. The trial is registered at www.clinicaltrials.gov as NCT01186913.
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    Impact of Changes of the 2020 Consensus Definitions of Invasive Aspergillosis on Clinical Trial Design: Unintended Consequences for Prevention Trials?
    (Open forum infectious diseases, 2021-10) Wingard, John R; Alexander, Barbara D; Baden, Lindsey R; Chen, Min; Sugrue, Michele W; Leather, Helen L; Caliendo, Angela M; Clancy, Cornelius J; Denning, David W; Marty, Francisco M; Nguyen, M Hong; Wheat, L Joseph; Logan, Brent R; Horowitz, Mary M; Marr, Kieren A

    Background

    Consensus definitions for the diagnosis of invasive fungal diseases (IFDs) were updated in 2020 to increase the certainty of IFD for inclusion in clinical trials, for instance by increasing biomarker cutoff limits to define positivity. To date, there is a paucity of data as to the impact of the revised definitions on clinical trials.

    Methods

    In this study, we sought to determine the impact of the new definitions on classifying invasive aspergillosis (IA), the most common invasive mold disease in immunocompromised patients. We reclassified 226 proven and probable IA cases plus 139 possible IFD cases in the Aspergillus Technology Consortium (AsTeC) and in an antifungal prophylaxis trial (BMT CTN 0101) using the new criteria.

    Results

    Fewer cases met the more stringent diagnostic 2020 criteria after applying the reclassification criteria to define probable IA. Of 188 evaluable probable cases, 41 (22%) were reclassified to 40 possible IA and 1 probable IFD. Reclassification to possible IFD occurred in 22% of hematologic malignancy (HM) patients, 29% of hematopoietic cell transplant (HCT) patients, and in no lung transplant (LT) patients. Date of diagnosis was established a median (range) of 3 (1-105) days later in 15% of probable IA cases using the new criteria. Applying the new definitions to the BMT CTN 0101 trial, the power to detect the same odds ratio decreased substantially.

    Conclusions

    The updated IA consensus definitions may impact future trial designs, especially for antifungal prophylaxis studies.
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    ItemOpen Access
    Unlicensed Umbilical Cord Blood Units Provide a Safe and Effective Graft Source for a Diverse Population: A Study of 2456 Umbilical Cord Blood Recipients.
    (Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2020-04) Ballen, Karen; Logan, Brent R; Chitphakdithai, Pintip; Kuxhausen, Michelle; Spellman, Stephen R; Adams, Alexia; Drexler, Rebecca J; Duffy, Merry; Kemp, Ann; King, Roberta; Babic, Aleksandar; Delaney, Colleen; Karanes, Chatchada; Kurtzberg, Joanne; Petz, Lawrence; Scaradavou, Andromachi; Shpall, Elizabeth J; Smith, Clayton; Confer, Dennis L; Miller, John P
    Umbilical cord blood (UCB) transplantation (UCBT) is a curative procedure for patients with hematologic malignancies and genetic disorders and expands access to transplantation for non-Caucasian patients unable to find a fully matched unrelated donor. In 2011, the US Food and Drug Administration required that unrelated UCBT be performed using either licensed UCB or unlicensed UCB under the Investigational New Drug (IND) program. The National Marrow Donor Program manages an IND under which 2456 patients (1499 adults and 957 children, 564 with malignant diseases and 393 with nonmalignant diseases) underwent single or double UCBT between October 2011 and December 2016. The median patient age was 31 years (range, <1 to 81 years), and 50% of children and 36% of adults were non-Caucasian. The median time to neutrophil engraftment (ie, absolute neutrophil count ≥500/mm3) was 22 days for adults, 20 days for pediatric patients with malignant diseases, and 19 days for pediatric patients with nonmalignant diseases, with corresponding rates of engraftment at 42 days of 89%, 88%, and 90%. In these 3 groups of patients, the incidence of acute graft-versus-host disease (GVHD) grade II-IV was 35%, 32%, and 24%; the incidence of chronic GVHD was 24%, 26%, and 24%; and 1-year overall survival (OS) was 57%, 71%, and 79%, respectively. In multivariate analysis, younger age, lower Hematopoietic Cell Transplantation-Specific Comorbidity Index, early-stage chemotherapy-sensitive disease, and higher performance score were predictive of improved OS for adults. In a subset analysis of children with malignancies undergoing single UCBT, the use of either licensed UCB (n = 48) or unlicensed UCB (n = 382) was associated with similar engraftment and survival. The use of unlicensed UCB units is safe and effective and provides an important graft source for a diverse population.