TY - JOUR
T1 - Haemopoietic stem-cell transplantation with antibody-based minimal-intensity conditioning
T2 - a phase 1/2 study
AU - Straathof, Karin C.
AU - Rao, Kanchan
AU - Eyrich, Matthias
AU - Hale, Geoff
AU - Bird, Prudence
AU - Berrie, Eleanor
AU - Brown, Lucinda
AU - Adams, Stuart
AU - Schlegel, Paul G.
AU - Goulden, Nicholas
AU - Gaspar, H. Bobby
AU - Gennery, Andrew R.
AU - Landais, Paul
AU - Davies, EG G.
AU - Brenner, Malcolm K.
AU - Veys, Paul A.
AU - Amrolia, Persis Jal
N1 - Funding Information:
IMP (YTH 24.5 and 54.12 monoclonal antibodies) was provided free by the Therapeutic Antibody Centre . Analysis of immune reconstitution (TREC and immunoscope analysis) was supported in part by a programme project grant ( Z-2/7-28.06.04 ) from IZKF Wüzburg to ME and PGS, and by a grant from the Elfrieda Albert Foundation ( 257/147/62012-2006 ) to PGS.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2009
Y1 - 2009
N2 - Background: Stem-cell transplantation can cure primary immunodeficiencies. However, in patients with pre-existing organ toxicity, patients younger than 1 year, and those with DNA or telomere repair disorders, chemotherapy-based conditioning is poorly tolerated and results in major morbidity and mortality. We tested a novel antibody-based minimal-intensity conditioning (MIC) regimen to assess whether this approach allowed curative donor stem-cell engraftment without non-haemopoietic toxicity. Methods: 16 high-risk patients underwent stem-cell transplantation for primary immunodeficiencies with an MIC regimen consisting of two rat anti-CD45 monoclonal antibodies YTH24.5 and YTH 54.12 for myelosuppression, and alemtuzumab (anti-CD52) and fludarabine, and low dose cyclophosphamide for immunosuppression. Donors were matched siblings (n=5), and matched (9) and mismatched (2) unrelated donors. Findings: Antibody-based conditioning was well tolerated, with only two cases of grade 3 and no grade 4 toxicity. Rates of clinically significant acute (n=6, 36%) and chronic graft-versus-host disease (GVHD) (n=5, 31%) were acceptable. 15 of 16 patients (94%) engrafted, of whom 11 (69%) achieved full or high-level mixed chimerism in both lymphoid and myeloid lineages, and three achieved engraftment in the T-lymphoid lineage only. One patient needed retransplantation. At a median of 40 months post-transplant, 13 of 16 patients (81%) in this high-risk cohort were alive and cured from their underlying disease. Interpretation: Monoclonal antibody-based conditioning seems well tolerated and can achieve curative engraftment even in patients with severe organ toxicity or DNA repair defects, or both. This novel approach represents a shift from the paradigm that intensive chemotherapy or radiotherapy, or both, is needed for donor stem-cell engraftment. This antibody-based conditioning regimen may reduce toxicity and late effects and enable SCT in virtually any primary immunodeficiency patient with a matched donor. Funding: None.
AB - Background: Stem-cell transplantation can cure primary immunodeficiencies. However, in patients with pre-existing organ toxicity, patients younger than 1 year, and those with DNA or telomere repair disorders, chemotherapy-based conditioning is poorly tolerated and results in major morbidity and mortality. We tested a novel antibody-based minimal-intensity conditioning (MIC) regimen to assess whether this approach allowed curative donor stem-cell engraftment without non-haemopoietic toxicity. Methods: 16 high-risk patients underwent stem-cell transplantation for primary immunodeficiencies with an MIC regimen consisting of two rat anti-CD45 monoclonal antibodies YTH24.5 and YTH 54.12 for myelosuppression, and alemtuzumab (anti-CD52) and fludarabine, and low dose cyclophosphamide for immunosuppression. Donors were matched siblings (n=5), and matched (9) and mismatched (2) unrelated donors. Findings: Antibody-based conditioning was well tolerated, with only two cases of grade 3 and no grade 4 toxicity. Rates of clinically significant acute (n=6, 36%) and chronic graft-versus-host disease (GVHD) (n=5, 31%) were acceptable. 15 of 16 patients (94%) engrafted, of whom 11 (69%) achieved full or high-level mixed chimerism in both lymphoid and myeloid lineages, and three achieved engraftment in the T-lymphoid lineage only. One patient needed retransplantation. At a median of 40 months post-transplant, 13 of 16 patients (81%) in this high-risk cohort were alive and cured from their underlying disease. Interpretation: Monoclonal antibody-based conditioning seems well tolerated and can achieve curative engraftment even in patients with severe organ toxicity or DNA repair defects, or both. This novel approach represents a shift from the paradigm that intensive chemotherapy or radiotherapy, or both, is needed for donor stem-cell engraftment. This antibody-based conditioning regimen may reduce toxicity and late effects and enable SCT in virtually any primary immunodeficiency patient with a matched donor. Funding: None.
UR - https://www.scopus.com/pages/publications/69949094169
UR - https://www.scopus.com/inward/citedby.url?scp=69949094169&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(09)60945-4
DO - 10.1016/S0140-6736(09)60945-4
M3 - Article
C2 - 19729196
AN - SCOPUS:69949094169
SN - 0140-6736
VL - 374
SP - 912
EP - 920
JO - The Lancet
JF - The Lancet
IS - 9693
ER -