Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients.

Autor: Bethge WA; Department of Hematology, Oncology, Clinical Immunology and Rheumatology, Center for Internal Medicine, University Hospital Tuebingen, Tuebingen, Germany. wolfgang.bethge@med.uni-tuebingen.de., Eyrich M; University Children's Hospital Wuerzburg, Wuerzburg, Germany., Mielke S; Karolinska Institutet and University Hospital, Department of Laboratory Medicine and Department of Medicine Huddinge, CAST, Karolinska Comprehensive Cancer Center, Stockholm, Sweden.; Department of Internal Medicine II, Wuerzburg University Medical Center, Wuerzburg, Germany., Meisel R; Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany., Niederwieser D; University Leipzig, Leipzig, Germany., Schlegel PG; University Children's Hospital Wuerzburg, Wuerzburg, Germany., Schulz A; Department of Pediatrics, University Medical Center Ulm, Ulm, Germany., Greil J; University Children's Hospital Heidelberg, Heidelberg, Germany., Bunjes D; Department of Internal Medicine III, University of Ulm, Ulm, Germany., Brecht A; KMT-Abteilung, Helios Dr. Horst Schmidt Kliniken, Wiesbaden, Germany., Kuball J; Department of Haematology and Center for Translational Immunology, University Medical Centre, Utrecht, The Netherlands., Schumm M; CureVac RE GmbH, Tuebingen, Germany.; Department of Hematology/Oncology, University Children's Hospital Tuebingen, Tuebingen, Germany., Vucinic V; University Leipzig, Leipzig, Germany., Wiesneth M; Institute of Transfusion Medicine, University of Ulm, Ulm, Germany., Bonig H; Institute for Transfusion Medicine and Immunohematology, and German Red Cross Blood Service BaWüHe, Goethe University, Frankfurt, Germany., Westinga K; Cell Therapy Facility, University Medical Center Utrecht, Utrecht, The Netherlands., Biedermann S; Miltenyi Biotec, Bergisch Gladbach, Germany., Holtkamp S; Miltenyi Biomedicine, Bergisch Gladbach, Germany., Karitzky S; Miltenyi Biomedicine, Bergisch Gladbach, Germany., Malchow M; Miltenyi Biomedicine, Bergisch Gladbach, Germany., Siewert C; Miltenyi Biotec, Bergisch Gladbach, Germany., Handgretinger R; Department of Hematology/Oncology, University Children's Hospital Tuebingen, Tuebingen, Germany., Lang P; Department of Hematology/Oncology, University Children's Hospital Tuebingen, Tuebingen, Germany. peter.lang@med.uni-tuebingen.de.
Jazyk: angličtina
Zdroj: Bone marrow transplantation [Bone Marrow Transplant] 2022 Mar; Vol. 57 (3), pp. 423-430. Date of Electronic Publication: 2021 Dec 24.
DOI: 10.1038/s41409-021-01551-z
Abstrakt: Hematopoietic stem cell transplantation (HSCT) from haploidentical donors is a viable option for patients lacking HLA-matched donors. Here we report the results of a prospective multicenter phase I/II trial of transplantation of TCRαβ and CD19-depleted peripheral blood stem cells from haploidentical family donors after a reduced-intensity conditioning with fludarabine, thiotepa, and melphalan. Thirty pediatric and 30 adult patients with acute leukemia (n = 43), myelodysplastic or myeloproliferative syndrome (n = 6), multiple myeloma (n = 1), solid tumors (n = 6), and non-malignant disorders (n = 4) were enrolled. TCR αβ/CD19-depleted grafts prepared decentrally at six manufacturing sites contained a median of 12.1 × 10 6 CD34 + cells/kg and 14.2 × 10 3 TCRαβ + T-cells/kg. None of the patients developed grade lll/IV acute graft-versus-host disease (GVHD) and only six patients (10%) had grade II acute GVHD. With a median follow-up of 733 days 36/60 patients are alive. The cumulative incidence of non-relapse mortality at day 100, 1 and 2 years after HSCT was 5%, 15%, and 17% for all patients, respectively. Estimated probabilities of overall and disease-free survival at 2 years were 63% and 50%, respectively. Based on these promising results in a high-risk patient cohort, haploidentical HSCT using TCRαβ/CD19-depleted grafts represents a viable treatment option.
(© 2021. The Author(s).)
Databáze: MEDLINE
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