Hematopoietic stem cell transplantation with alpha/beta T-lymphocyte depletion and short course of eculizumab in adolescents and young adults with paroxysmal nocturnal hemoglobinuria

Autor: O I Illarionova, Larisa Shelikhova, Elena Kurnikova, Michael Maschan, E V Boyakova, Alexey Maschan, U.N. Petrova, G.A. Novichkova, D A Shasheleva
Rok vydání: 2019
Předmět:
young adults
Male
History
medicine.medical_specialty
Myeloid
Transplantation Conditioning
paroxysmal nocturnal hemoglobinuria
Adolescent
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
T-Lymphocytes
Hemoglobinuria
Paroxysmal
lcsh:Medicine
Graft vs Host Disease
Hematopoietic stem cell transplantation
tcr alfa/beta and cd19 depletion
Antibodies
Monoclonal
Humanized
Gastroenterology
Lymphocyte Depletion
Young Adult
hemic and lymphatic diseases
Internal medicine
medicine
Humans
adolescents
Dose-Response Relationship
Drug
business.industry
lcsh:R
Hematopoietic Stem Cell Transplantation
General Medicine
Eculizumab
medicine.disease
Pancytopenia
Fludarabine
Transplantation
medicine.anatomical_structure
Treatment Outcome
Paroxysmal nocturnal hemoglobinuria
Alemtuzumab
eculizumab
Female
Family Practice
business
transplantation
medicine.drug
Zdroj: Терапевтический архив, Vol 90, Iss 7, Pp 57-64 (2018)
ISSN: 0040-3660
Popis: The main goal is to optimize hematopoietic stem cell transplantation (HSCT) approach among adolescents and young adults with paroxysmal nocturnal hemoglobinuria (PNH) by means of Graft-versus-host disease (GVHD) and post-transplant complications risk lowering. Materials and methods. We report our experience of HSCT from HLA-matched unrelated donors using TCR alfa/beta and CD19 depletion in 5 pts (1M/4F) with PNH, developed after successful immunosuppressive therapy (IST) of acquired aplastic anemia (AA). Median age of pts at the moment of transplantation was 17,8 years (range 14,5-22,7), median interval from IST to PNH was 4 years (5mo - 6,5 y). In all patients non-severe pancytopenia was present: granulocytes 0,8х109/l (0,8-1,8 х109/l) platelets 106 х109/l (27-143 х109/l) and Hb -78 g/l, median PNH clone size in granulocytes was 94 (range 75-99)%. One pts previously developed sinus thrombosis. Conditioning consisted of thoraco-abdominal irradiation 4-6 Gy, cyclophosphamide 100 mg/kg, fludarabine 150 mg/m2 and anti-thymocyte globulin (ATG) or alemtuzumab. Eculizumab was given from day (-7) till day (+14) (every 7 days, only 4 times). GVHD prophylaxis was tacrolimus ± methotrexate. Results. Infusedgraft characteristics were: CD34+ - 8,1х106/kg, CD3TCRab·150х103/kg, CD3gd+ - 7,3х106/kg, СD19+ - 221х103/kg, NK -6,4х108/kg. Engraftment was achieved in all 5 pts with a median of 15(12-18) и 13(10-18) days for granulocytes and platelets, respectively. Skin acute GVHD grade I developed in only 1 pt, and subsided with short course of glucocorticoids. CMV reactivation occurred in 1 pt; there were no episodes of Epstein-Barr Virus (EBV) o rAdenovirus (AdV) reactivation. Full donor myeloid chimerism was established in all pts by day +30. Immune reconstitution was delayed until 6 months after transplant but no severe infections occurred. All pts are alive 1,7-5,5 years (med 4 years) after HSCT with normal hematopoiesis and immune function, full donor chimerism and no late sequelae. Conclusions. Transplantation of TCRalfa/beta and CD19 depleted hematopoietic cells from matched unrelated donor after immunoablative conditioning and supported with short course of eculizumab is perfectly safe and efficient technology leading to cure in young patients with PNH.
Databáze: OpenAIRE
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