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- Title
Blinatumomab Redirects Donor Lymphocytes against CD19 + Acute Lymphoblastic Leukemia without Relevant Bystander Alloreactivity after Haploidentical Hematopoietic Stem Cell Transplantation.
- Authors
Mancusi, Antonella; Zorutti, Francesco; Ruggeri, Loredana; Bonato, Samanta; Tricarico, Sara; Zei, Tiziana; Iacucci Ostini, Roberta; Viglione, Valerio; Sembenico, Rebecca; Sciabolacci, Sofia; Cardinali, Valeria; Martelli, Massimo Fabrizio; Mecucci, Cristina; Carotti, Alessandra; Martelli, Maria Paola; Velardi, Andrea; Pierini, Antonio
- Abstract
Blinatumomab alone or with donor leukocyte infusions (DLI) has been used after allogeneic hematopoietic stem cell transplantation (HSCT) as a salvage therapy in relapsing patients with CD19+ hematological malignancies. It was effective in a fraction of them, with low incidence of Graft-versus-Host Disease (GvHD). Immunosuppressive drugs used as GvHD prophylaxis hinder T cell function and reduce the efficacy of the treatment. Because T cell-depleted haploidentical HSCT with donor regulatory and conventional T cells (Treg/Tcon haploidentical HSCT) does not require post-transplant immunosuppression, it is an ideal platform for the concomitant use of blinatumomab and DLI. However, the risk of GvHD is high because the donor is haploidentical. We treated two patients with CD19+ acute lymphoblastic leukemia (ALL) who had relapsed after Treg/Tcon haploidentical HSCT with blinatumomab and DLI. Despite the mismatch for one HLA haplotype, they did not develop GvHD and achieved complete remission with negative minimal residual disease. Consistently, we found that blinatumomab did not enhance T cell alloreactivity in vitro. Eventually, the two patients relapsed again because of their high disease risk. This study suggests that treatment with blinatumomab and DLI can be feasible to treat relapse after haploidentical transplantation, and its pre-emptive use should be considered to improve efficacy.
- Subjects
HEMATOPOIETIC stem cell transplantation; LYMPHOBLASTIC leukemia; ACUTE leukemia; T cells; REGULATORY T cells; TUMOR lysis syndrome; CD19 antigen; ALLELES; BRAIN death
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 22, p16105
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms242216105