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Alemtuzumab and CXCL9 levels predict likelihood of sustained engraftment after reduced-intensity conditioning HCT.
Geerlinks, Ashley V; Scull, Brooks; Krupski, Christa; Fleischmann, Ryan; Pulsipher, Michael A; Eapen, Mary; Connelly, James A; Bollard, Catherine M; Pai, Sung-Yun; Duncan, Christine N; Kean, Leslie S; Baker, K Scott; Burroughs, Lauri M; Andolina, Jeffrey R; Shenoy, Shalini; Roehrs, Philip; Hanna, Rabi; Talano, Julie-An; Schultz, Kirk R; Stenger, Elizabeth O; Lin, Howard; Zoref-Lorenz, Adi; McClain, Kenneth L; Jordan, Michael B; Man, Tsz-Kwong; Allen, Carl E; Marsh, Rebecca A.
Afiliación
  • Geerlinks AV; Division Hematology and Oncology, Children's Hospital at London Health Sciences Centre, Western University, London, ON, Canada.
  • Scull B; Division of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
  • Krupski C; Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
  • Fleischmann R; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
  • Pulsipher MA; Division of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
  • Eapen M; Division of Hematology and Oncology, Primary Children's Hospital, Huntsman Cancer Institute, Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, UT.
  • Connelly JA; Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.
  • Bollard CM; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
  • Pai SY; Center for Cancer and Immunology Research, Children's National Hospital and The George Washington University, Washington, DC.
  • Duncan CN; National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD.
  • Kean LS; Dana-Farber Cancer Institute, Boston Children's Hospital, Boston, MA.
  • Baker KS; Dana-Farber Cancer Institute, Boston Children's Hospital, Boston, MA.
  • Burroughs LM; Clinical Research Division, Fred Hutchinson Cancer Center and Department of Pediatrics, University of Washington School of Medicine, Seattle, WA.
  • Andolina JR; Clinical Research Division, Fred Hutchinson Cancer Center and Department of Pediatrics, University of Washington School of Medicine, Seattle, WA.
  • Shenoy S; Department of Pediatrics, Golisano Children's Hospital, University of Rochester Medical Center, Rochester, NY.
  • Roehrs P; Division of Pediatric Hematology-Oncology, Washington University School of Medicine, St. Louis, MO.
  • Hanna R; Pediatric Hematology/Oncology, Department of Pediatrics, University of Virginia, Charlottesville, VA.
  • Talano JA; Department of Pediatric Hematology and Oncology and BMT, Cleveland Clinic, Cleveland, OH.
  • Schultz KR; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI.
  • Stenger EO; Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
  • Lin H; Aflac Center and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, GA.
  • Zoref-Lorenz A; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Houston, TX.
  • McClain KL; Hematology Institute, Meir Medical Center, Kfar Saba, Israel.
  • Jordan MB; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Man TK; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
  • Allen CE; Division of Pediatric Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
  • Marsh RA; Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Houston, TX.
Blood Adv ; 7(14): 3725-3734, 2023 07 25.
Article en En | MEDLINE | ID: mdl-37042921
Overall survival after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using alemtuzumab, fludarabine, and melphalan is associated with high rates of mixed chimerism (MC) and secondary graft failure (GF). We hypothesized that peritransplantation alemtuzumab levels or specific patterns of inflammation would predict these risks. We assessed samples from the Bone Marrow Transplant Clinical Trials Network 1204 (NCT01998633) to study the impact of alemtuzumab levels and cytokine patterns on MC and impending or established secondary GF (defined as donor chimerism <5% after initial engraftment and/or requirement of cellular intervention). Thirty-three patients with hemophagocytic lymphohistiocytosis (n = 25) and other IEIs (n = 8) who underwent HCTs with T-cell-replete grafts were included. Patients with day 0 alemtuzumab levels ≤0.32 µg/mL had a markedly lower incidence of MC, 14.3%, vs 90.9% in patients with levels >0.32 µg/mL (P = .008). Impending or established secondary GF was only observed in patients with day 0 alemtuzumab levels >0.32 µg/mL (P = .08). Unexpectedly, patients with impending or established secondary GF had lower CXCL9 levels. The cumulative incidence of impending or established secondary GF in patients with a day 14+ CXCL9 level ≤2394 pg/mL (day 14+ median) was 73.6% vs 0% in patients with a level >2394 pg/mL (P = .002). CXCL9 levels inversely correlated with alemtuzumab levels. These data suggest a model in which higher levels of alemtuzumab at day 0 deplete donor T cells, inhibit the graft-versus-marrow reaction (thereby suppressing CXCL9 levels), and adversely affect sustained engraftment in the nonmyeloablative HCT setting. This trial was registered at www.clinicaltrials.gov as #NCT01998633.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Células Madre Hematopoyéticas / Anticuerpos Monoclonales Humanizados Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Blood Adv Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Células Madre Hematopoyéticas / Anticuerpos Monoclonales Humanizados Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Blood Adv Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos