TY - JOUR
T1 - Association of busulfan exposure and outcomes after HCT for patients with an inborn error of immunity
AU - Bognàr, Tim
AU - Garcia-Rosa, Moises
AU - Lalmohamed, Arief
AU - Güngör, Tayfun
AU - Hauri-Hohl, Mathias
AU - Prockop, Susan
AU - Oram, Layne
AU - Pai, Sung Yun
AU - Brooks, Jordan
AU - Savic, Rada M.
AU - Dvorak, Christopher C.
AU - Long-Boyle, Janel R.
AU - Krajinovic, Maja
AU - Bittencourt, Henrique
AU - Teyssier, Anne Charlotte
AU - Théoret, Yves
AU - Martinez, Cary
AU - Egberts, Toine C.G.
AU - Morales, Erin
AU - Slatter, Mary
AU - Cuvelier, Geoffrey D.E.
AU - Chiesa, Robert
AU - Wynn, Robert F.
AU - Coussons, Mary
AU - Cicalese, Maria P.
AU - Ansari, Marc
AU - Long, Susan E.
AU - Ebens, Christen L.
AU - Lust, Hannah
AU - Chaudhury, Sonali
AU - Nath, Christa E.
AU - Shaw, Peter J.
AU - Keogh, Steven J.
AU - van der Stoep, M. Y.C.Eileen
AU - Bredius, Robbert
AU - Lindemans, Caroline A.
AU - Boelens, Jaap Jan
AU - Bartelink, Imke H.
N1 - Publisher Copyright:
© 2024 American Society of Hematology. All rights reserved.
PY - 2024/10/8
Y1 - 2024/10/8
N2 - Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment strategy for patients with inborn errors of immunities (IEIs). The objective of this study was to assess the optimal busulfan exposure before allogeneic HCT for patients with an IEI who received an IV busulfan–based conditioning regimen. Patients from 17 international centers were included. The main outcome of interest was event-free survival (EFS). Patients were categorized into 4 IEI subgroups: combined immunodeficiency (CID), severe combined immunodeficiency (SCID), neutrophil disorders, and hemophagocytic lymphohistiocytosis (HLH)–related disorders. Busulfan exposure was calculated by individual centers (area under the curve [AUC]CENTER) and re-estimated using a nonlinear mixed–effects model (NONMEM; exposure defined as AUCNONMEM). Overall, 562 patients were included: 173 (30.8%) with CID, 154 (27.4%) with SCID, 101 (18.0%) with HLH-related disorders, and 134 (23.8%) with neutrophil disorders. The median busulfan AUCNONMEM was 69.0 mg × h/L and correlated poorly with the AUCCENTER (r2 = 0.54). In patients with SCID, HLH-related, and neutrophil disorders with a busulfan AUCNONMEM of 70 to 90 mg × h/L, 2-year EFS was superior to <70 mg × h/L, and >90 mg ×h/L. Full donor chimerism increased with higher busulfan AUCNONMEM, plateauing at 90 mg × h/L. For patients with CID, the optimal AUCNONMEM for donor chimerism was found to be >70 mg × h/L. Improved EFS and higher donor chimerism may be achieved by targeting a cumulative busulfan AUCNONMEM of 80 mg × h/ L (range, 70-90).
AB - Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment strategy for patients with inborn errors of immunities (IEIs). The objective of this study was to assess the optimal busulfan exposure before allogeneic HCT for patients with an IEI who received an IV busulfan–based conditioning regimen. Patients from 17 international centers were included. The main outcome of interest was event-free survival (EFS). Patients were categorized into 4 IEI subgroups: combined immunodeficiency (CID), severe combined immunodeficiency (SCID), neutrophil disorders, and hemophagocytic lymphohistiocytosis (HLH)–related disorders. Busulfan exposure was calculated by individual centers (area under the curve [AUC]CENTER) and re-estimated using a nonlinear mixed–effects model (NONMEM; exposure defined as AUCNONMEM). Overall, 562 patients were included: 173 (30.8%) with CID, 154 (27.4%) with SCID, 101 (18.0%) with HLH-related disorders, and 134 (23.8%) with neutrophil disorders. The median busulfan AUCNONMEM was 69.0 mg × h/L and correlated poorly with the AUCCENTER (r2 = 0.54). In patients with SCID, HLH-related, and neutrophil disorders with a busulfan AUCNONMEM of 70 to 90 mg × h/L, 2-year EFS was superior to <70 mg × h/L, and >90 mg ×h/L. Full donor chimerism increased with higher busulfan AUCNONMEM, plateauing at 90 mg × h/L. For patients with CID, the optimal AUCNONMEM for donor chimerism was found to be >70 mg × h/L. Improved EFS and higher donor chimerism may be achieved by targeting a cumulative busulfan AUCNONMEM of 80 mg × h/ L (range, 70-90).
UR - http://www.scopus.com/inward/record.url?scp=85207362278&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2024013275
DO - 10.1182/bloodadvances.2024013275
M3 - Article
C2 - 39074263
AN - SCOPUS:85207362278
SN - 2473-9529
VL - 8
SP - 5137
EP - 5145
JO - Blood Advances
JF - Blood Advances
IS - 19
ER -