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 - Publisher Copyright:
© 2023 The American Society for Transplantation and Cellular Therapy
PY - 2023/6
Y1 - 2023/6
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
VL - 29
SP - 380.e1-380.e9
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 6
ER -