| Haemopoietic stem-cell transplantation with antibody-based minimal-intensity conditioning: a phase 1/2 study. | |
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MedLine Citation:
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PMID: 19729196 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 YTH 24.5 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. |
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Authors:
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Karin C Straathof; Kanchan Rao; Matthias Eyrich; Geoff Hale; Prudence Bird; Eleanor Berrie; Lucinda Brown; Stuart Adams; Paul G Schlegel; Nicholas Goulden; H Bobby Gaspar; Andrew R Gennery; Paul Landais; E G Davies; Malcolm K Brenner; Paul A Veys; Persis Jal Amrolia |
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Publication Detail:
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Type: Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-02 |
Journal Detail:
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Title: Lancet Volume: 374 ISSN: 1474-547X ISO Abbreviation: Lancet Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-09-14 Completed Date: 2009-09-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985213R Medline TA: Lancet Country: England |
Other Details:
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Languages: eng Pagination: 912-20 Citation Subset: AIM; IM |
Affiliation:
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Great Ormond Street Children's Hospital, London, UK. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / therapeutic use* Antibodies, Neoplasm / therapeutic use Antigens, CD45 / antagonists & inhibitors* Child, Preschool Cyclophosphamide / therapeutic use Disease-Free Survival Female Follow-Up Studies Graft vs Host Disease / epidemiology, etiology, prevention & control Hematopoietic Stem Cell Transplantation / adverse effects, methods* Humans Immunologic Deficiency Syndromes / therapy* Immunologic Factors / therapeutic use* Immunosuppressive Agents / therapeutic use Infant Kaplan-Meiers Estimate Male Rats Transplantation Chimera Transplantation Conditioning / adverse effects, methods*, mortality Treatment Outcome Vidarabine / analogs & derivatives, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Antibodies, Neoplasm; 0/Immunologic Factors; 0/Immunosuppressive Agents; 0/alemtuzumab; 21679-14-1/fludarabine; 50-18-0/Cyclophosphamide; 5536-17-4/Vidarabine; EC 3.1.3.48/Antigens, CD45 |
| Comments/Corrections | |
Comment In:
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Lancet. 2009 Sep 12;374(9693):856-8
[PMID:
19729197
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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