Browsing by Author "Wagner, John E"
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Item Open Access Analysis of risk factors influencing outcomes after cord blood transplantation in children with juvenile myelomonocytic leukemia: a EUROCORD, EBMT, EWOG-MDS, CIBMTR study.(Blood, 2013-09) Locatelli, Franco; Crotta, Alessandro; Ruggeri, Annalisa; Eapen, Mary; Wagner, John E; Macmillan, Margaret L; Zecca, Marco; Kurtzberg, Joanne; Bonfim, Carmem; Vora, Ajay; Díaz de Heredia, Cristina; Teague, Lochie; Stein, Jerry; O'Brien, Tracey A; Bittencourt, Henrique; Madureira, Adrienne; Strahm, Brigitte; Peters, Christina; Niemeyer, Charlotte; Gluckman, Eliane; Rocha, VandersonWe retrospectively analyzed 110 patients with juvenile myelomonocytic leukemia, given single-unit, unrelated donor umbilical cord blood transplantation. Median age at diagnosis and at transplantation was 1.4 years (age range, 0.1-6.4 years) and 2.2 years (age range, 0.5-7.4 years), respectively. Before transplantation, 88 patients received chemotherapy; splenectomy was performed in 24 patients. Monosomy of chromosome 7 was the most frequent cytogenetic abnormality, found in 24% of patients. All but 8 patients received myeloablative conditioning; cyclosporine plus steroids was the most common graft-versus-host disease prophylaxis. Sixteen percent of units were HLA-matched with the recipient, whereas 43% and 35% had either 1 or 2 to 3 HLA disparities, respectively. The median number of nucleated cells infused was 7.1 × 10(7)/kg (range, 1.7-27.6 × 10(7)/kg). With a median follow-up of 64 months (range, 14-174 months), the 5-year cumulative incidences of transplantation-related mortality and relapse were 22% and 33%, respectively. The 5-year disease-free survival rate was 44%. In multivariate analysis, factors predicting better disease-free survival were age younger than 1.4 years at diagnosis (hazard ratio [HR], 0.42; P = .005), 0 to 1 HLA disparities in the donor/recipient pair (HR, 0.4; P = .009), and karyotype other than monosomy 7 (HR, 0.5; P = .02). Umbilical cord blood transplantation may cure a relevant proportion of children with juvenile myelomonocytic leukemia. Because disease recurrence remains the major cause of treatment failure, strategies to reduce incidence of relapse are warranted.Item Open Access Consensus opinion on immune-mediated cytopenias after hematopoietic cell transplant for inherited metabolic disorders.(Bone marrow transplantation, 2021-06) Gupta, Ashish O; Jan Boelens, Jaap; Ebens, Christen L; Kurtzberg, Joanne; Lund, Troy C; Smith, Angela R; Wagner, John E; Wynn, Robert; Blazar, Bruce R; Orchard, Paul JHematopoietic stem cell transplantation (HCT) has been increasingly used for patients with inherited metabolic disorders (IMD). Immune mediated cytopenias (IMCs) after HCT, manifesting as hemolytic anemia, thrombocytopenia, and/or neutropenia, are recognized as a significant complication in this patient population, yet our understanding of the incidence, risk factors, and pathophysiology is currently limited. Review of the published literature demonstrates a higher incidence in younger patients who undergo HCT for a nonmalignant disease indication. However, a few reports suggest that the incidence is even higher among those with IMD (incidence ranging from 10 to 56%). This review summarizes the literature, provides an approach to better understanding of the possible etiology of IMCs, and proposes a diagnostic and management plan for patients with IMD who develop single or multi-lineage cytopenias after HCT.Item Open Access One-unit versus two-unit cord-blood transplantation for hematologic cancers.(The New England journal of medicine, 2014-10) Wagner, John E; Eapen, Mary; Carter, Shelly; Wang, Yanli; Schultz, Kirk R; Wall, Donna A; Bunin, Nancy; Delaney, Colleen; Haut, Paul; Margolis, David; Peres, Edward; Verneris, Michael R; Walters, Mark; Horowitz, Mary M; Kurtzberg, Joanne; Blood and Marrow Transplant Clinical Trials NetworkBackground
Umbilical-cord blood has been used as the source of hematopoietic stem cells in an estimated 30,000 transplants. The limited number of hematopoietic cells in a single cord-blood unit prevents its use in recipients with larger body mass and results in delayed hematopoietic recovery and higher mortality. Therefore, we hypothesized that the greater numbers of hematopoietic cells in two units of cord blood would be associated with improved outcomes after transplantation.Methods
Between December 1, 2006, and February 24, 2012, a total of 224 patients 1 to 21 years of age with hematologic cancer were randomly assigned to undergo double-unit (111 patients) or single-unit (113 patients) cord-blood transplantation after a uniform myeloablative conditioning regimen and immunoprophylaxis for graft-versus-host disease (GVHD). The primary end point was 1-year overall survival.Results
Treatment groups were matched for age, sex, self-reported race (white vs. nonwhite), performance status, degree of donor-recipient HLA matching, and disease type and status at transplantation. The 1-year overall survival rate was 65% (95% confidence interval [CI], 56 to 74) and 73% (95% CI, 63 to 80) among recipients of double and single cord-blood units, respectively (P=0.17). Similar outcomes in the two groups were also observed with respect to the rates of disease-free survival, neutrophil recovery, transplantation-related death, relapse, infections, immunologic reconstitution, and grade II-IV acute GVHD. However, improved platelet recovery and lower incidences of grade III and IV acute and extensive chronic GVHD were observed among recipients of a single cord-blood unit.Conclusions
We found that among children and adolescents with hematologic cancer, survival rates were similar after single-unit and double-unit cord-blood transplantation; however, a single-unit cord-blood transplant was associated with better platelet recovery and a lower risk of GVHD. (Funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; ClinicalTrials.gov number, NCT00412360.).Item Open Access One-unit versus two-unit cord-blood transplantation.(The New England journal of medicine, 2015-01) Wagner, John E; Eapen, Mary; Kurtzberg, JoanneItem Open Access Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies.(Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2017-06) Barker, Juliet N; Kurtzberg, Joanne; Ballen, Karen; Boo, Michael; Brunstein, Claudio; Cutler, Corey; Horwitz, Mitchell; Milano, Filippo; Olson, Amanda; Spellman, Stephen; Wagner, John E; Delaney, Colleen; Shpall, ElizabethUnrelated donor cord blood transplantation (CBT) results in disease-free survival comparable to that of unrelated adult donor transplantation in patients with hematologic malignancies. Extension of allograft access to racial and ethnic minorities, rapid graft availability, flexibility of transplantation date, and low risks of disabling chronic graft-versus-host disease (GVHD) and relapse are significant advantages of CBT, and multiple series have reported a low risk of late transplantation-related mortality (TRM) post-transplantation. Nonetheless, early post-transplantation morbidity and TRM and the requirement for intensive early post-transplantation management have slowed the adoption of CBT. Targeted care strategies in CBT recipients can mitigate early transplantation complications and reduce transplantation costs. Herein we provide a practical "how to" guide to CBT for hematologic malignancies on behalf of the National Marrow Donor Program and the American Society of Blood and Marrow Transplantation's Cord Blood Special Interest Group. It shares the best practices of 6 experienced US transplantation centers with a special interest in the use of cord blood as a hematopoietic stem cell source. We address donor search and unit selection, unit thaw and infusion, conditioning regimens, immune suppression, management of GVHD, opportunistic infections, and other factors in supportive care appropriate for CBT. Meticulous attention to such details has improved CBT outcomes and will facilitate the success of CBT as a platform for future graft manipulations.Item Open Access Phase I/II Study of Stem-Cell Transplantation Using a Single Cord Blood Unit Expanded Ex Vivo With Nicotinamide.(Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2019-02) Horwitz, Mitchell E; Wease, Stephen; Blackwell, Beth; Valcarcel, David; Frassoni, Francesco; Boelens, Jaap Jan; Nierkens, Stefan; Jagasia, Madan; Wagner, John E; Kuball, Jurgen; Koh, Liang Piu; Majhail, Navneet S; Stiff, Patrick J; Hanna, Rabi; Hwang, William YK; Kurtzberg, Joanne; Cilloni, Daniela; Freedman, Laurence S; Montesinos, Pau; Sanz, GuillermoPurpose
Increasing the number of hematopoietic stem and progenitor cells within an umbilical cord blood (UCB) graft shortens the time to hematopoietic recovery after UCB transplantation. In this study, we assessed the safety and efficacy of a UCB graft that was expanded ex vivo in the presence of nicotinamide and transplanted after myeloablative conditioning as a stand-alone hematopoietic stem-cell graft.Methods
Thirty-six patients with hematologic malignancies underwent transplantation at 11 sites.Results
The cumulative incidence of neutrophil engraftment at day 42 was 94%. Two patients experienced secondary graft failure attributable to viral infections. Hematopoietic recovery was compared with that observed in recipients of standard UCB transplantation as reported to the Center for International Blood and Marrow Transplant Research (n = 146). The median time to neutrophil recovery was 11.5 days (95% CI, 9 to 14 days) for recipients of nicotinamide-expanded UCB and 21 days (95% CI, 20 to 23 days) for the comparator ( P < .001). The median time to platelet recovery was 34 days (95% CI, 32 to 42 days) and 46 days (95% CI, 42 to 50 days) for the expanded and the comparator cohorts, respectively ( P < .001). The cumulative incidence of grade 2 to 4 acute graft-versus-host disease (GVHD) at day 100 was 44%, and grade 3 and 4 acute GVHD at day 100 was 11%. The cumulative incidence at 2 years of all chronic GVHD was 40%, and moderate/severe chronic GVHD was 10%. The 2-year cumulative incidences of nonrelapse mortality and relapse were 24% and 33%, respectively. The 2-year probabilities of overall and disease-free survival were 51% and 43%, respectively.Conclusion
UCB expanded ex vivo with nicotinamide shortens median neutrophil recovery by 9.5 days (95% CI, 7 to 12 days) and median platelet recovery by 12 days (95% CI, 3 to 16.5 days). This trial establishes feasibility, safety, and efficacy of an ex vivo expanded UCB unit as a stand-alone graft.Item Open Access Standardizing Definitions of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, and Donor Chimerism in Allogeneic Hematopoietic Cell Transplantation: A Report on Behalf of the American Society for Transplantation and Cellular Therapy.(Transplantation and cellular therapy, 2021-08) Kharfan-Dabaja, Mohamed A; Kumar, Ambuj; Ayala, Ernesto; Aljurf, Mahmoud; Nishihori, Taiga; Marsh, Rebecca; Burroughs, Lauri M; Majhail, Navneet; Al-Homsi, A Samer; Al-Kadhimi, Zaid S; Bar, Merav; Bertaina, Alice; Boelens, Jaap J; Champlin, Richard; Chaudhury, Sonali; DeFilipp, Zachariah; Dholaria, Bhagirathbhai; El-Jawahri, Areej; Fanning, Suzanne; Fraint, Ellen; Gergis, Usama; Giralt, Sergio; Hamilton, Betty K; Hashmi, Shahrukh K; Horn, Biljana; Inamoto, Yoshihiro; Jacobsohn, David A; Jain, Tania; Johnston, Laura; Kanate, Abraham S; Kansagra, Ankit; Kassim, Adetola; Kean, Leslie S; Kitko, Carrie L; Knight-Perry, Jessica; Kurtzberg, Joanne; Liu, Hien; MacMillan, Margaret L; Mahmoudjafari, Zahra; Mielcarek, Marco; Mohty, Mohamad; Nagler, Arnon; Nemecek, Eneida; Olson, Timothy S; Oran, Betul; Perales, Miguel-Angel; Prockop, Susan E; Pulsipher, Michael A; Pusic, Iskra; Riches, Marcie L; Rodriguez, Cesar; Romee, Rizwan; Rondon, Gabriela; Saad, Ayman; Shah, Nina; Shaw, Peter J; Shenoy, Shalini; Sierra, Jorge; Talano, Julie; Verneris, Michael R; Veys, Paul; Wagner, John E; Savani, Bipin N; Hamadani, Mehdi; Carpenter, Paul AAllogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized.Item Open Access The influence of stem cell source on transplant outcomes for pediatric patients with acute myeloid leukemia.(Blood advances, 2019-04) Keating, Amy K; Langenhorst, Jurgen; Wagner, John E; Page, Kristin M; Veys, Paul; Wynn, Robert F; Stefanski, Heather; Elfeky, Reem; Giller, Roger; Mitchell, Richard; Milano, Filippo; O'Brien, Tracey A; Dahlberg, Ann; Delaney, Colleen; Kurtzberg, Joanne; Verneris, Michael R; Boelens, Jaap JanWhen hematopoietic stem cell transplant (HSCT) is necessary for children with acute myeloid leukemia (AML), there remains debate about the best stem cell source. Post-HSCT relapse is a common cause of mortality, and complications such as chronic graft versus host disease (cGVHD) are debilitating and life-threatening. To compare post-HSCT outcomes of different donor sources, we retrospectively analyzed consecutive transplants performed in several international centers from 2005 to 2015. A total of 317 patients were studied: 19% matched sibling donor (MSD), 23% matched unrelated donor (MUD), 39% umbilical cord blood (UCB), and 19% double UCB (dUCB) recipients. The median age at transplant was 10 years (range, 0.42-21 years), and median follow-up was 4.74 years (range, 4.02-5.39 years). Comparisons were made while controlling for patient, transplant, and disease characteristics. There were no differences in relapse, leukemia-free survival, or nonrelapse mortality. dUCB recipients had inferior survival compared with matched sibling recipients, but all other comparisons showed similar overall survival. Despite the majority of UCB transplants being HLA mismatched, the rates of cGVHD were low, especially compared with the well-matched MUD recipients (hazard ratio, 0.3; 95% confidence interval, 0.14-0.67; P = .02). The composite measure of cGVHD and leukemia-free survival (cGVHD-LFS), which represents both the quality of life and risk for mortality, was significantly better in the UCB compared with the MUD recipients (HR, 0.56; 95% confidence interval, 0.34-1; P = .03). In summary, the use of UCB is an excellent donor choice for pediatric patients with AML when a matched sibling cannot be identified.Item Open Access Umbilical Cord Blood Transplantation in Children with Acute Leukemia: Impact of Conditioning on Transplantation Outcomes.(Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2017-10) Eapen, Mary; Kurtzberg, Joanne; Zhang, Mei-Jie; Hattersely, Gareth; Fei, Mingwei; Mendizabal, Adam; Chan, Ka Wah; De Oliveira, Satiro; Schultz, Kirk R; Wall, Donna; Horowitz, Mary M; Wagner, John EThe Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0501) randomized children with hematologic malignancies to transplantation with 1 or 2 cord blood units (UCB) between 2006 and 2012. While the trial concluded that survival was similar regardless of number of units infused, survival was better than previously reported. This prompted a comparison of survival of trial versus nontrial patients to determine the generalizability of trial results and whether survival was better because of the trial treatment regimen. During the trial period, 396 recipients of a single UCB unit met trial eligibility but were not enrolled. Trial patients (n = 100) received total body irradiation (TBI) 1320 cGy, cyclophosphamide 120 mg/kg, and fludarabine 75 mg/m2 (TCF). Nontrial patients either received the same regimen (n = 62; nontrial TCF) or alternative regimens (n = 334; nontrial regimens). Five-year survival between trial and nontrial patients conditioned with TCF was similar (70% versus 62%). However, 5-year survival was significantly lower with nontrial TBI-containing (47%; hazard ratio [HR], 1.97; P = .001) and chemotherapy-only regimens (49%; HR, 1.87; P = .007). The results of BMT CTN 0501 appear generalizable to the population of trial-eligible patients. The survival difference between the trial-specified regimen and other regimens indicate the importance of conditioning regimen for UCB transplantation.