Results of allogeneic hematopoietic stem cell transplantation in patients with chronic granulomatous disease at the Russian Children’s Clinical Hospital

E B Machneva,V V Konstantinova,O A Filina,E V Skorobogatova,Yu A Nikolaeva,S S Vakhlyarskaya,L V Olkhova,N V Sidorova,A E Burya,A V Mezentseva,E A Pristanskova,O L Blagonravova,I V Kondratenko,K I Kirgizov

doi:10.21682/2311-1267-2020-7-2-23-34

Abstract

Relevance. Chronic granulomatous disease (CGD) belongs to the group of primary immunodeficiencies. Patients with CGD have an impaired quality of life, severe infections and inflammatory organ damage. Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment method for CGD. The authors of the article presented the experience of HSCT in patients with CGD in the Russian Children’s Clinical Hospital.Materials and methods. 20 (19 primary and 1 repeated) HSCT during the period from 2009 to 2020 were performed in nineteen patients with CGD. All patients had a long history of infections, three or more foci of chronic infection, 9 patients had a generalized BCG infection. Bone marrow (ВМ) from a related HLA-identical donor was the source of hematopoietic stem cells (HSC) for 4 (21 %) patients, peripheral blood stem cells (PBSC) for 2 (10.5 %). ВМ from a unrelated fully HLA-identical donor was performed in 9 (47.4 %) patients, PBSC – 2 (10.5 %). ВМ from a unrelated 9/10 HLA-compatible donor was performed in one (5.3 %) patient. In one case (5.3 %) the HSC source became PBSC from a unrelated 9/10 HLA-compatible donor after TcRαβ/CD19+ depletion. In 68.5 % (n = 13) cases the conditioning regimen included threosulfan, fludarabine, melphalan, and antithymocyte globulin. In 2 (10.5 %) patients, melphalan was excluded from the conditioning regimen; in 4 (21 %), it was replaced by thiotepa.Results. The overall survival (OS) was 88.9 ± 10.5 %, the event-free survival (EFS) was 88.1 ± 7.9 %, and there was no transplant mortality. Transplant rejections were observed in two patients who received HSC from a unrelated 9/10 HLA-compatible donor with a previous conditioning regimen that included only one alkylating agent. In 4 patients (21 %) there was a prolonged persistence of mixed chimerism after HSCT without clinical and laboratory signs of CGD. After successful transplantation all patients were cured of the infectious and inflammatory diseases characteristic of CGD.Conclusion. Results of HSCT in patients with CGD can be considered satisfactory, the OS and EFS are high. Failure of HSCT is associated with transplant rejection, which is most likely due to the donor and patient mismatch, as well as the use of conditioning modes with reduced intensity.

Highlights

Results of allogeneic hematopoietic stem cell transplantation in patients with chronic granulomatous disease at the Russian Children’s Clinical Hospital
The authors of the article presented the experience of hematopoietic stem cell transplantation (HSCT) in patients with Chronic granulomatous disease (CGD) in the Russian Children’s Clinical Hospital
Bone marrow (ВМ) from a related HLA-identical donor was the source of hematopoietic stem cells (HSC) for 4 (21 %) patients, peripheral blood stem cells (PBSC) for 2 (10.5 %)

Summary

Introduction

For citation: Machneva E.B., Pristanskova E.A., Olkhova L.V., Mezentseva A.V., Konstantinova V.V., Burya A.E., Blagonravova O.L., Nikolaeva Yu.А., Filina O.A., Sidorova N.V., Kirgizov K.I., Vakhlyarskaya S.S., Kondratenko I.V., Skorobogatova E.V. Results of allogeneic hematopoietic stem cell transplantation in patients with chronic granulomatous disease at the Russian Children’s Clinical Hospital. 1 – patient age at the time of HSCT; 2 – age at the time of diagnosis of CGD; 3Treo – threosulfan, Mel – melphalan, Flu – fludarabine, TT – thiotepa; doses of threosulfan – g/m2, melphalan, fludarabine – mg/m2, thiotepa – mg/kg; 4Rit – rituximab, Thymo – timoglobulin, Tac – tacrolimus, CsA – cyclosporin A, MMF – mycophenolate mofetil, Mtx – methotrexate; 5MSD – matched sibling, MUD – matched unrelated donor, MMUD – mismatched unrelated donor; 6PBSC – peripheral blood stem cells, ВМ – bone marrow; 7 – the content of CD3+ cells in the graft; 8 – in a depleted graft: α/β – 46 × 104/kg, γ/δ – 20 × 106/kg, CD19 – 1.3 × 104/kg; 9 – excluding depleted graft; 10 – the content of CD34+ cells in the graft.

Results

Conclusion