Donor lymphocyte infusion for prevention of relapse after unmanipulated haploidentical PBSCT for very high-risk hematologic malignancies.

Abstract

Unmanipulated haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) has been an established treatment to cure high-risk leukemia/lymphoma. Relapse is the main cause of treatment failure for patients with relapsed/refractory disease or with very high-risk gene mutations such as TP53, TET2, and DNMT3a. In this study, we aimed to establish the tolerance and efficacy of prophylactic donor lymphocyte infusion (DLI) with G-CSF-primed peripheral blood progenitors for prevention of relapse in these very high-risk patients after haplo-PBSCT. The prophylactic DLI was given at a median of 77 days after transplantation in 31 of 45 consecutive patients with very high-risk leukemia/lymphoma. The median dose of CD3+ cells for infusion was 1.8 × 107/kg. The 100-day incidences of acute graft-versus-host disease (GVHD) grades 2-4 and 3-4 after DLI were 55.3% and 10.2%. The 2-year incidences of chronic GVHD and severe chronic GVHD were 52.0% and 18.2%. The 2-year incidences of non-relapse mortality and relapse were 33.1% and 32.5%. The 2-year probabilities of overall survival and relapse-free survival were 40.1% and 31.9%. Poor-risk gene mutations (p = 0.029), disease in non-remission status prior to transplantation (p = 0.005), and donors older than 40 years of age (p = 0.043) were associated with relapse after DLI. In multivariate analysis, disease in non-remission status prior to transplantation was an independent risk factor of relapse (hazard ratio = 4.079; p = 0.035). These data showed the feasibility of the prophylactic DLI in the haplo-PBSCT setting and the anti-leukemic efficacy in very high-risk leukemia/lymphoma.

• Authors: Xiao-Ning Gao, Ji Lin, Shu-Hong Wang, Wen-Rong Huang, Fei Li, Hong-Hua Li, Jing Chen, Li-Jun Wang, Chun-Ji Gao, Li Yu, Dai-Hong Liu
• Journal: Annals of hematology (Ann Hematol) Vol. 98 Issue 1 Pg. 185-193 (Jan 2019) ISSN: 1432-0584 [Electronic] Germany
• PMID: 30143831 (Publication Type: Clinical Trial, Journal Article, Observational Study)

Chemical References

• Neoplasm Proteins

Topics

• Adolescent
• Adult
• Allografts
• Blood Donors
• Disease-Free Survival
• Female
• Graft vs Host Disease (etiology, genetics, mortality, prevention & control)
• Humans
• Incidence
• Leukemia (genetics, mortality, prevention & control)
• Lymphocyte Transfusion
• Lymphoma (genetics, mortality, prevention & control)
• Male
• Middle Aged
• Mutation
• Neoplasm Proteins (genetics)
• Peripheral Blood Stem Cell Transplantation
• Recurrence
• Retrospective Studies
• Survival Rate