Faculty Collaboration Database

Effect of Autograft CD34⁺ Dose on Outcome in Pediatric Patients Undergoing Autologous Hematopoietic Stem Cell Transplant for Central Nervous System Tumors. Transplant Cell Ther 2023 Jun;29(6):380.e1-380.e9

Date

03/30/2023

Pubmed ID

36990222

Pubmed Central ID

PMC10247464

DOI

10.1016/j.jtct.2023.03.024

Scopus ID

2-s2.0-85153799554 (requires institutional sign-in at Scopus site)

Abstract

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.

Author List

Knight TE, Ahn KW, Hebert KM, Atshan R, Wall DA, Chiengthong K, Rotz SJ, Fraint E, Rangarajan HG, Auletta JJ, Sharma A, Kitko CL, Hashem H, Williams KM, Wirk B, Dvorak CC, Myers KC, Pulsipher MA, Warwick AB, Lalefar NR, Schultz KR, Qayed M, Broglie L, Eapen M, Yanik GA

Authors

Kwang Woo Ahn PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Larisa Broglie MD, MS Assistant Professor in the Pediatrics department at Medical College of Wisconsin
Mary Eapen MBBS, DCh, MRCPI, MS Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antigens, CD34
Autografts
Central Nervous System Neoplasms
Child
Hematopoietic Stem Cell Transplantation
Humans
Neoplasm Recurrence, Local
Retrospective Studies