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


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Abstract

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.

About the authors

D A SHASHELEVA

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Department of optimization treatment and prevention of complications of hematopoietic stem cell transplantation

Email: shasheleva@mail.ru
врач-гематолог отд-ния ТГСК №1, ORCID 0000-0002-5641-8567; тел.: +7(926)576-89-12 Moscow, Russia

A A MASCHAN

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Department of optimization treatment and prevention of complications of hematopoietic stem cell transplantation

зам. генерального директора по научной работе, ORCID 0000-0002-0016-6698 Moscow, Russia

L N SHELIKHOVA

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Department of optimization treatment and prevention of complications of hematopoietic stem cell transplantation

зав. отд-нием ТГСК №1, ORCID 0000-0003-0520-5630 Moscow, Russia

U N PETROVA

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Department of optimization treatment and prevention of complications of hematopoietic stem cell transplantation

врач-гематолог отд-ния детской гематологии и онкологии, ORCID0000-0002-1258-8281 Moscow, Russia

E E KURNIKOVA

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Department of optimization treatment and prevention of complications of hematopoietic stem cell transplantation

врач-трансфузиолог отд-ния трансфузиологии, заготовки и процессинга ГСК, ORCID 0000-0003-4767-5382 Moscow, Russia

O I ILLARIONOVA

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Department of optimization treatment and prevention of complications of hematopoietic stem cell transplantation

врач-лаборант лаб. клеточной иммунологии и иммуногенеза, 0000-0003-2685-674X Moscow, Russia

E V BOYAKOVA

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Department of optimization treatment and prevention of complications of hematopoietic stem cell transplantation

зав. лаб. трансплантационной иммунологии и иммунотерапии гемобластозов Moscow, Russia

G A NOVICHKOVA

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Department of optimization treatment and prevention of complications of hematopoietic stem cell transplantation

медицинский директор, зам. генерального директора по научно-клинической работе, ORCID 0000-0003-4911-0553 Moscow, Russia

M A MASCHAN

Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Department of optimization treatment and prevention of complications of hematopoietic stem cell transplantation

ам. генерального директора, директор Высшей школы молекулярной и экспериментальной медицины, ORCID 0000-0003-1735-0093 Moscow, Russia

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