Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRαβ and CD19 Depletion in Children with Primary Immunodeficiency Syndromes.
| Title: | Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRαβ and CD19 Depletion in Children with Primary Immunodeficiency Syndromes. |
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| Authors: | Balashov D; 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.; Shcherbina A; Department of Clinical Immunology, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.; Maschan M; Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.; Trakhtman P; Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.; Skvortsova Y; Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.; Shelikhova L; Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.; Laberko A; Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.; Livshits A; Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.; Novichkova G; Department of pediatric hematology and oncology, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.; Maschan A; Department of Hematopoietic Stem Cell Transplantation, Dmitry Rogachev Federal Research and Clinical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. |
| Source: | Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [Biol Blood Marrow Transplant] 2015 Nov; Vol. 21 (11), pp. 1955-62. Date of Electronic Publication: 2015 Jul 15. |
| Publication Type: | Clinical Trial; Journal Article |
| Language: | English |
| Journal Info: | Publisher: Carden Jennings Publishing Country of Publication: United States NLM ID: 9600628 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-6536 (Electronic) Linking ISSN: 10838791 NLM ISO Abbreviation: Biol Blood Marrow Transplant Subsets: MEDLINE |
| Imprint Name(s): | Publication: Charlottesville, VA : Carden Jennings Publishing; Original Publication: Charlottesville, VA : Kluge Carden Jennings Publishing, Co., Ltd., [1995- |
| MeSH Terms: | Hematopoietic Stem Cell Transplantation*; Antigens, CD19/*immunology ; Immunologic Deficiency Syndromes/*therapy ; Receptors, Antigen, T-Cell, alpha-beta/*immunology ; T-Lymphocytes/*immunology ; Transplantation Conditioning/*methods; Antigens, CD19/genetics ; Graft vs Host Disease/immunology ; Graft vs Host Disease/mortality ; Graft vs Host Disease/pathology ; Immunologic Deficiency Syndromes/immunology ; Immunologic Deficiency Syndromes/mortality ; Immunologic Deficiency Syndromes/pathology ; Myeloablative Agonists/therapeutic use ; Receptors, Antigen, T-Cell, alpha-beta/deficiency ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; T-Lymphocytes/cytology ; Adolescent ; Child ; Child, Preschool ; Female ; Haplotypes ; Histocompatibility Testing ; Humans ; Infant ; Lymphocyte Depletion ; Male ; Prospective Studies ; Survival Analysis ; Transplantation Chimera ; Transplantation, Isogeneic ; Unrelated Donors |
| 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.; (Copyright © 2015. Published by Elsevier Inc.) |
| Contributed Indexing: | Keywords: Primary immunodeficiency syndromes; Stem cell transplantation; TCRαβ depletion |
| Molecular Sequence: | ClinicalTrials.gov NCT02327351 |
| Substance Nomenclature: | 0 (Antigens, CD19); 0 (Myeloablative Agonists); 0 (Receptors, Antigen, T-Cell, alpha-beta) |
| Entry Date(s): | Date Created: 20150719 Date Completed: 20160720 Latest Revision: 20151012 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.bbmt.2015.07.008 |
| PMID: | 26187864 |
| Database: | MEDLINE |
Clinical Trial; Journal Article