Browsing by Subject "Transplantation Conditioning"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Outcomes of Pediatric Patients with Therapy-Related Myeloid Neoplasms
    (Springer Nature, 2021) Sharma, Akshay; Huang, Sujuan; Li, Ying; Brooke, Russell J.; Ahmed, Ibrahim; Allewelt, Heather B.; Amrolia, Persis; Bertaina, Alice; Bhatt, Neel S.; Bierings, Marc B.; Bies, Joshua; Brisset, Claire; Brondon, Jennifer E.; Dahlberg, Ann; Dalle, Jean-Hugues; Eissa, Hesham; Fahd, Mony; Gassas, Adam; Gloude, Nicholas J.; Goebel, W. Scott; Goeckerman, Erika S.; Harris, Katherine; Ho, Richard; Hudspeth, Michelle P.; Huo, Jeffrey S.; Jacobsohn, David; Kasow, Kimberly A.; Katsanis, Emmanuel; Kaviany, Saara; Keating, Amy K.; Kernan, Nancy A.; Ktena, Yiouli P.; Lauhan, Colette R.; López-Hernandez, Gerardo; Martin, Paul L.; Myers, Kasiani C.; Naik, Swati; Olaya-Vargas, Alberto; Onishi, Toshihiro; Radhi, Mohamed; Ramachandran, Shanti; Ramos, Kristie; Rangarajan, Hemalatha G.; Roehrs, Philip A.; Sampson, Megan E.; Shaw, Peter J.; Skiles, Jodi L.; Somers, Katherine; Symons, Heather J.; de Tersant, Marie; Uber, Allison N.; Versluys, Birgitta; Cheng, Cheng; Triplett, Brandon M.; Pediatrics, School of Medicine
    Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs.
  • Thumbnail Image
    Item
    Prognostic biomarkers for acute graft-versus-host disease risk after cyclophosphamide-fludarabine nonmyeloablative allotransplantation
    (Elsevier, 2014-11) Nelson, Robert P.; Khawaja, Muhammad Rizwan; Perkins, Susan M.; Elmore, Lindsey; Mumaw, Christen L.; Orschell, Christie M.; Paczesny, Sophie; Department of Pediatrics, IU School of Medicine
    Five candidate plasma biomarkers (suppression of tumorogenesis 2 [ST2], regenerating islet-derived-3α [REG3α], elafin, tumor necrosis factor receptor 1 [TNFR1], and soluble IL-2 receptor-alpha [sIL2Rα]) were measured at specific time points after cyclophosphamide/fludarabine-based nonmyeloablative allotransplantation (NMAT) in patients who did or did not develop acute graft-versus-host disease (aGVHD). Plasma samples from 34 patients were analyzed at days +7, +14, +21, and +30. At a median follow-up of 358 days, 17 patients had experienced aGVHD with a median time to onset at day +36. Risk of aGVHD was associated with elevated plasma ST2 concentrations at day +7 (c-statistic = .72, P = .03), day +14 (c-statistic = .74, P = .02), and day +21 (c-statistic = .75, P = .02); elevated plasma REG3α concentrations at day +14 (c-statistic = .73, P = .03), day +21 (c-statistic = .76, P = .01), and day +30 (c-statistic = .73, P = .03); and elevated elafin at day +14 (c-statistic = .71, P = .04). Plasma concentrations of TNFR1 and sIL2Rα were not associated with aGVHD risk at any of the time points studied. This study identified ST2, REG3α, and elafin as prognostic biomarkers to evaluate risk of aGVHD after cyclophosphamide/fludarabine-based NMAT. These results need to be confirmed in an independent validation cohort.