title: Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRαβ and CD19 Depletion in Children with Primary Immunodeficiency Syndromes.
abstract: The transplantation of stem cells from a matched unrelated donor (MUD) or a haploidentical mismatched related donor (MMRD) is a widely used variant of curative treatment for patients with primary immunodeficiency (PID). Currently, different strategies are used to reduce the risk of post-transplant complications and enhance immune reconstitution. We report the preliminary results of MUD and MMRD transplantation with TCRαβ/CD19 depletion in patients with PID (trial registered at www.clinicaltrials.gov as NCT02327351). Thirty-seven PID patients (median age, 2.6 years; range, .2 to 17) were transplanted from MUDs (n = 27) or haploidentical MMRDs (n = 10) after TCRαβ(+)/CD19(+) graft depletion. The median numbers of CD34(+) and TCRαβ(+) cells in the graft were 11.7 × 10(6)/kg and 10.6 × 10(3)/kg, respectively. Acute graft-versus-host disease (GVHD) was observed in 8 patients (22%), without a statistically significant difference between MUDs and MMRDs; 7 of these patients had grade II acute GVHD and responded to first-line therapy, whereas 1 patient had grade IV acute GVHD with transformation to extensive chronic GVHD. Primary and secondary graft failure (nonengraftment or rejection) was observed in 10 patients (27%), 9 of whom were treated with 1 alkylating agent in the conditioning regimen. All these patients were successfully retransplanted with different rescue protocols. Preliminary data on immune reconstitution were very encouraging. Most patients had significant numbers of T lymphocytes detected on the first assessment (day +30) and more than 500 T cells/μL, on day +120. Based on our preliminary data, no significant difference was seen between MMRD and MUD hematopoietic stem cell transplantation (HSCT). With a median follow-up period of 15 months, the cumulative probabilities of overall patient survival and transplant-related mortality were 96.7% and 3.3%, respectively. Based on the results, the ability to control the main post-transplant complications and the immune reconstitution rates are the main factors leading to successful outcome in patients with PID after TCRαβ(+)-depleted HSCT.
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Electronic address: bala8@yandex.ru.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Balashov
authors.affiliation: Department of Clinical Immunology, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Shcherbina
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Michael
authors.initials: M
authors.lastname: Maschan
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Trakhtman
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Skvortsova
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Larisa
authors.initials: L
authors.lastname: Shelikhova
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Laberko
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Livshits
authors.affiliation: Department of pediatric hematology and oncology, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Galina
authors.initials: G
authors.lastname: Novichkova
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Alexei
authors.initials: A
authors.lastname: Maschan
mesh_terms: D000293:Adolescent; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D007223:Infant; D008212:Lymphocyte Depletion; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use; D011446:Prospective Studies; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014185:Transplantation, Isogeneic; D061349:Unrelated Donors
chemical_list: D018941:Antigens, CD19; D019653:Myeloablative Agonists; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: Primary immunodeficiency syndromes; Stem cell transplantation; TCRαβ depletion