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- Title
Donor lymphocyte infusions in adult haploidentical transplant:a dose .nding study.
- Authors
Lewalle, P.; Triffet, A.; Delforge, A.; Crombez, P.; Selleslag, D.; De Muynck, H.; Bron, D.; Martiat, P.
- Abstract
Haploidentical transplantation has become a clinical option for patients lacking a compatible donor. However, patients are still referred at advanced stages and are usually heavily pretreated. This results in a high risk of toxicity, relapses and infections. We therefore started a donor lymphocyte infusion (DLI) dose-finding protocol, to try to improve both relapse rate and immunity reconstitution. In all, 12 consecutive patients were investigated. Ail had a refractory, some progressive, disease. Conditioning consisted of TBI, melphalan, ATG, fludarabine and CSA pretransplant. In four rapidly progressive patients, Ara-C had to be given 1 week preconditioning. The graft was T- and B-cell depleted with a fixed reinfused CD3 dose of 5 x 104/kg. All patients engrafted before day 20. G-CSF was given from day 5 post-transplant and replaced with GM-CSF in the last three patients. Nonrelapse related mortality was 0/12 at I year. DLI were started at day 28 (3 X 104 CD3/kg) in the two first patients. This resulted in acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) in both, but they did not relapse. The next dose was 1 x 104/kg monthly for 3 months. This was well tolerated with only one grade I GVHD. Given the high relapse rate, we escalated doses (1, 3 and 10 x 104/kg). This produced GVHD in all. We next moved, to GM-CSF and 1 x 104 CD3/kg monthly. Overall, 6/12 patients relapsed and received therapeutic DLI, starting at 1 x 105 CD3/kg with escalation every 2 weeks. We conclude that prophylactic DLI are feasible in adult haploidentical transplantation, without GVHD at a monthly dose of 1 x 104 CD3/kg. They result in faster CD4 recovery and a low rate of infections. The impact of GM-CSF remains to be further investigated. This scheme seems ideal for patients...
- Subjects
TRANSPLANTATION of organs, tissues, etc.; LYMPHOCYTES
- Publication
Bone Marrow Transplantation, 2003, Vol 31, Issue 1, p39
- ISSN
0268-3369
- Publication type
Article
- DOI
10.1038/sj.bmt.1703779