Placental expanded mesenchymal-like cells (PLX-R18) for poor graft function after hematopoietic cell transplantation: A phase I study Journal Article
| Authors: | McGuirk, J. P.; Metheny, L.; Pineiro, L.; Litzow, M.; Rowley, S. D.; Avni, B.; Tamari, R.; Lazarus, H. M.; Rowe, J. M.; Sheleg, M.; Rothenstein, D.; Halevy, N.; Zuckerman, T. |
| Article Title: | Placental expanded mesenchymal-like cells (PLX-R18) for poor graft function after hematopoietic cell transplantation: A phase I study |
| Abstract: | Persistent cytopenia in the post-hematopoietic cell transplantation (HCT) setting can occur despite adequate engraftment of donor cells. PLX-R18, a placental-derived mesenchymal-like cell product, is expanded ex vivo in a 3-dimensional environment. PLX-R18 cells secrete a large array of hematopoietic factors, which promote regeneration, maturation, and differentiation of hematopoietic cells and stimulate their migration to peripheral blood. This phase 1, first-in-human study (NCT03002519), included 21 patients with incomplete hematopoietic recovery post-HCT. Patients were treated with escalating doses of PLX-R18: 3 patients received 1 million cells/kg, 6 received 2 million cells/kg, and 12 received 4 million cells/kg via multiple intramuscular injections. While patients received only two administrations of cells during the first week, peripheral blood counts continued to increase for months, peaking at 6 months for hemoglobin (Hb, p = 0.002), lymphocytes (p = 0.008), and neutrophils (ANC, p = 0.063), and at 9 months for platelets (p < 0.001) and was maintained until 12 months for all but ANC. The need for platelet transfusions was reduced from 5.09 units/month at baseline to 0.55 at month 12 (p = 0.05). Likewise, red blood cell transfusions decreased from 2.91 units/month at baseline to 0 at month 12 (p = 0.0005). PLX-R18 was safe and well tolerated and shows promise in improving incomplete hematopoietic recovery post-HCT. © 2023, The Author(s). |
| Keywords: | adult; clinical article; controlled study; clinical trial; constipation; drug tolerability; diarrhea; drug safety; quality of life; thrombocyte; cell maturation; nausea; vomiting; granulocyte macrophage colony stimulating factor; cohort analysis; hemoglobin; hematopoietic stem cell transplantation; cell differentiation; coughing; drug dose escalation; febrile neutropenia; fever; pneumonia; questionnaire; blood; engraftment; neutrophil; interleukin 6; peripheral edema; cell migration; pregnancy; injection site pain; headache; cell regeneration; blood cell count; phase 1 clinical trial; graft rejection; erythrocyte transfusion; ex vivo study; lymphocyte; granulocyte colony stimulating factor; cytopenia; placenta; thrombocyte transfusion; blood platelets; graft dysfunction; procedures; interleukin 11; platelet transfusion; humans; human; male; female; article; avoplacel; placental expanded mesenchymal like cell |
| Journal Title: | Bone Marrow Transplantation |
| Volume: | 58 |
| Issue: | 11 |
| ISSN: | 0268-3369 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-11-01 |
| Start Page: | 1189 |
| End Page: | 1196 |
| Language: | English |
| DOI: | 10.1038/s41409-023-02068-3 |
| PUBMED: | 37553467 |
| PROVIDER: | scopus |
| PMCID: | PMC10622312 |
| DOI/URL: | |
| Notes: | Published erratum at DOI: 10.1038/s41409-024-02469-y -- Source: Scopus |
