TY - JOUR
T1 - Effect of Autograft CD34+ Dose on Outcome in Pediatric Patients Undergoing Autologous Hematopoietic Stem Cell Transplant for Central Nervous System Tumors
AU - Knight, Tristan E.
AU - Ahn, Kwang Woo
AU - Hebert, Kyle M.
AU - Atshan, Rasha
AU - Wall, Donna A.
AU - Chiengthong, Kanhatai
AU - Rotz, Seth J.
AU - Fraint, Ellen
AU - Rangarajan, Hemalatha G.
AU - Auletta, Jeffery J.
AU - Sharma, Akshay
AU - Kitko, Carrie L.
AU - Hashem, Hasan
AU - Williams, Kirsten M.
AU - Wirk, Baldeep
AU - Dvorak, Christopher C.
AU - Myers, Kasiani C.
AU - Pulsipher, Michael A.
AU - Warwick, Anne B.
AU - Lalefar, Nahal Rose
AU - Schultz, Kirk R.
AU - Qayed, Muna
AU - Broglie, Larisa
AU - Eapen, Mary
AU - Yanik, Gregory A.
N1 - Funding Information:
Conflict of interest statement: T.E.K. reports partial salary support from Hold'Em for Life Oncology Fellowship, Garron Family Cancer Center Research Fellowship, and BMO Financial Group Oncology Fellowship. D.A.W. reports steering committee participation for CRISPR/Vertex Pharmaceuticals and Editas Medicine; acting as a study advisor for CRISPR/Vertex Pharmaceuticals and Editas Medicine; acting as a clinical trial site-PI for CRISPR Therapeutics, Vertex Pharmaceuticals, and Novartis; and research funding from CRISPR Therapeutics, Vertex Pharmaceuticals, and Novartis. S.J.R. reports acting as a resource for Clinical Investigation in Blood and Marrow Transplantation (RCI BMT) (employment). H.G.R. reports serving as the BMT Medical Monitor for NMDP (no financial reimbursements); and having served as honorary consultant for Medexus. J.J.A. reports employment with National Marrow Donor Program (NMDP); and advisory council participation for Ascella Health. A.S. reports consulting for Spotlight Therapeutics, Medexus Inc., Vertex Pharmaceuticals, and Sangamo Therapeutics; research funding from CRISPR Therapeutics. Clinical Trial site-PI: CRISPR Therapeutics, Vertex Pharmaceuticals, Novartis Pharmaceuticals, Magenta Therapeutics, Beam Therapeutics, Honoraria: Vindico Medical Education. C.L.K. reports advisory board participation for Horizon Therapeutics. K.M.W. reports research funding from NHBLI, Leukemia Lymphoma Society, and PeachBowl Legacy Foundation. C.C.D. reports consulting for Jazz Pharma, and Alexion Inc. K.C.M. reports research funding for an investigator initiated clinical trial from Incyte and sponsored research from Elixirgen Therapeutics. M.A.P. reports advisory board participation with Novartis, Gentibio, Bluebird, Vertex, Medexus, Equillium, and Mesoblast; and honoraria from Novartis, Miltenyi, and Adaptive; and study support from Miltenyi, and Adaptive. M.Q. reports honoraria from Vertex and Novartis.
Publisher Copyright:
© 2023 The American Society for Transplantation and Cellular Therapy
PY - 2023
Y1 - 2023
N2 - Consolidation with autologous hematopoietic stem cell transplantation (HSCT) has improved survival for patients with central nervous system tumors (CNSTs). The impact of the autologous graft CD34+ dose on patient outcomes is unknown. We wanted to analyze the relationship between CD34+ dose, total nucleated cell (TNC) dose, and clinical outcomes, including overall survival (OS), progression-free survival (PFS), relapse, non-relapse mortality (NRM), endothelial-injury complications (EIC), and time to neutrophil engraftment in children undergoing autologous HSCT for CNSTs. A retrospective analysis of the CIBMTR database was performed. Children aged <10 years who underwent autologous HSCT between 2008 to 2018 for an indication of CNST were included. An optimal cut point was identified for patient age, CD34+ cell dose, and TNC, using the maximum likelihood method and PFS as an endpoint. Univariable analysis for PFS, OS, and relapse was described using the Kaplan-Meier estimator. Cox models were fitted for PFS and OS outcomes. Cause-specific hazards models were fitted for relapse and NRM. One hundred fifteen patients met the inclusion criteria. A statistically significant association was identified between autograft CD34+ content and clinical outcomes. Children receiving >3.6×106/kg CD34+ cells experienced superior PFS (p = .04) and OS (p = .04) compared to children receiving ≤3.6 × 106/kg. Relapse rates were lower in patients receiving >3.6 × 106/kg CD34+ cells (p = .05). Higher CD34+ doses were not associated with increased NRM (p = .59). Stratification of CD34+ dose by quartile did not reveal any statistically significant differences between quartiles for 3-year PFS (p = .66), OS (p = .29), risk of relapse (p = .57), or EIC (p = .87). There were no significant differences in patient outcomes based on TNC, and those receiving a TNC >4.4 × 108/kg did not experience superior PFS (p = .26), superior OS (p = .14), reduced risk of relapse (p = .37), or reduced NRM (p = .25). Children with medulloblastoma had superior PFS (p < .001), OS (p = .01), and relapse rates (p = .001) compared to those with other CNS tumor types. Median time to neutrophil engraftment was 10 days versus 12 days in the highest and lowest infused CD34+ quartiles, respectively. For children undergoing autologous HSCT for CNSTs, increasing CD34+ cell dose was associated with significantly improved OS and PFS, and lower relapse rates, without increased NRM or EICs.
AB - Consolidation with autologous hematopoietic stem cell transplantation (HSCT) has improved survival for patients with central nervous system tumors (CNSTs). The impact of the autologous graft CD34+ dose on patient outcomes is unknown. We wanted to analyze the relationship between CD34+ dose, total nucleated cell (TNC) dose, and clinical outcomes, including overall survival (OS), progression-free survival (PFS), relapse, non-relapse mortality (NRM), endothelial-injury complications (EIC), and time to neutrophil engraftment in children undergoing autologous HSCT for CNSTs. A retrospective analysis of the CIBMTR database was performed. Children aged <10 years who underwent autologous HSCT between 2008 to 2018 for an indication of CNST were included. An optimal cut point was identified for patient age, CD34+ cell dose, and TNC, using the maximum likelihood method and PFS as an endpoint. Univariable analysis for PFS, OS, and relapse was described using the Kaplan-Meier estimator. Cox models were fitted for PFS and OS outcomes. Cause-specific hazards models were fitted for relapse and NRM. One hundred fifteen patients met the inclusion criteria. A statistically significant association was identified between autograft CD34+ content and clinical outcomes. Children receiving >3.6×106/kg CD34+ cells experienced superior PFS (p = .04) and OS (p = .04) compared to children receiving ≤3.6 × 106/kg. Relapse rates were lower in patients receiving >3.6 × 106/kg CD34+ cells (p = .05). Higher CD34+ doses were not associated with increased NRM (p = .59). Stratification of CD34+ dose by quartile did not reveal any statistically significant differences between quartiles for 3-year PFS (p = .66), OS (p = .29), risk of relapse (p = .57), or EIC (p = .87). There were no significant differences in patient outcomes based on TNC, and those receiving a TNC >4.4 × 108/kg did not experience superior PFS (p = .26), superior OS (p = .14), reduced risk of relapse (p = .37), or reduced NRM (p = .25). Children with medulloblastoma had superior PFS (p < .001), OS (p = .01), and relapse rates (p = .001) compared to those with other CNS tumor types. Median time to neutrophil engraftment was 10 days versus 12 days in the highest and lowest infused CD34+ quartiles, respectively. For children undergoing autologous HSCT for CNSTs, increasing CD34+ cell dose was associated with significantly improved OS and PFS, and lower relapse rates, without increased NRM or EICs.
KW - Autograft
KW - Autologous hematopoietic stem cell transplant
KW - CD34+
KW - Central nervous system
KW - Medulloblastoma
KW - TNC
UR - http://www.scopus.com/inward/record.url?scp=85153799554&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85153799554&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2023.03.024
DO - 10.1016/j.jtct.2023.03.024
M3 - Article
C2 - 36990222
AN - SCOPUS:85153799554
SN - 2666-6375
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
ER -