Haploidentical Stem Cell Transplantation After TCR-αβ+ and CD19+ Cells Depletion In Children With Congenital Non-Malignant Disease
Stefano Giardino, Francesca Bagnasco, Michela Falco, Maurizio Miano, Filomena Pierri, Marco Risso, Paola Terranova, Daniela Di Martino, Erika Massaccesi, Margherita Ricci, Benedetta Chianucci, Gianluca Dell'Orso, Federica Sabatini, Marina Podestà, Edoardo Lanino, Maura Faraci, Stefano Giardino, Francesca Bagnasco, Michela Falco, Maurizio Miano, Filomena Pierri, Marco Risso, Paola Terranova, Daniela Di Martino, Erika Massaccesi, Margherita Ricci, Benedetta Chianucci, Gianluca Dell'Orso, Federica Sabatini, Marina Podestà, Edoardo Lanino, Maura Faraci
Abstract
Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents a valuable alternative for children with nonmalignant disease and ex vivo negative selection of TCR-αβ+ cells is an emerging graft manipulation option that carries several potential advantages in terms of reduced risk of graft-versus-host disease (GvHD) and improved immune reconstitution. We report all consecutive patients with a diagnosis of nonmalignant disease who received a TCR-αβ+ and CD19+depleted haplo-HSCT at "IRCCS Istituto Giannina Gaslini" from 2013 to 2019; the conditioning regimen was myeloablative or non-myeloablative, depending on underlying disease; all patients received antithymocyte globulin and rituximab. No post-transplantation GvHD prophylaxis was given in presence of a TCR-αβ+ cell dose in the graft lower than the threshold of 1 × 105/kg of the recipient's weight. Among 20 HSCTs, engraftment occurred in 17 (85%) after a median of 14 and 12 days from graft infusion for neutrophils and platelets, respectively. Primary graft failure was diagnosed in 3 (15%) patients, and 2 (10%) experienced secondary rejection; all of these patients underwent a second HSCT. The cumulative incidence of a-GvHD and c-GvHD was 15% (2 = grade 1, 1 = grade 4) at 90 days and 5% (1 = grade 1) at 7 months, respectively. Cytomegalovirus reactivation requiring pre-emptive treatment was observed in 9 patients (45%). One patient developed a JC virus-related progressive multifocal leukoencephalopathy, successfully managed with donor-derived virus-specific T-cell infusions. A complete immunological recovery was reached in most patients within 6 months. After a median follow-up of 4 years, 18 patients are alive, with a cumulative survival probability of 90%. Haplo-HSCT after ex vivo TCR-αβ+/CD19+ negative selection may be considered a good option for children with nonmalignant diseases because it ensures a high engraftment rate with an acceptable risk of graft failure, very low incidence of significant GvHD, and good immune reconstitution with low frequency of severe virus-related disease. However, the control of viral infection/reactivation should be kept high to promptly provide pre-emptive treatments and approaches of antiviral adoptive immunotherapy.
Keywords: Congenital bone marrow failure syndromes; Graft manipulation; Haploidentical stem cell transplantation; Nonmalignant disease; Primary immune-regulatory disorders; Primary immunodeficiency; TCR-αβ(+) depletion.
Conflict of interest statement
Conflict of interest statement There are no conflicts of interest to report. Authorship statement: SG contributed to data collection, material preparation, analysis of results, and wrote the manuscript. SG, MF, and EL contributed equally to the study conception and to the patient's management. FB performed all statistical analyses. MR and MF contributed to donor selection and management. MP and FS managed the graft manipulation. MM, FP, GD, BC and MR contributed to data collection and to the clinical management of patients. All authors contributed to the manuscript revision and approved its final version.
Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
Source: PubMed