Email this article An evaluation of the efficacy of allogeneic hematopoietic stem cell transplantation in patients with mucopolysaccharidosis type I (Hurler syndrome): the experience of the R.M. Gorbacheva Research Institute for Pediatric Oncology, Hematology and Transplantation
- Authors: Bykova T.A.1, Ovechkina V.N.1, Osipova A.A.1, Borovkova A.S.1, Dotsenko A.A.1, Markova I.V.1, Semenova E.V.1, Zubarovskaya L.S.1, Afanasyev B.V.1
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Affiliations:
- R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University, Ministry of Healthcare of Russian Federation
- Issue: Vol 19, No 2 (2020)
- Pages: 83-92
- Section: ORIGINAL ARTICLES
- Submitted: 01.07.2020
- Accepted: 01.07.2020
- Published: 01.07.2020
- URL: https://hemoncim.com/jour/article/view/342
- DOI: https://doi.org/10.24287/1726-1708-2020-19-2-83-92
- ID: 342
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Abstract
Mucopolysaccharidosis type I (MPS IH; Hurler syndrome) is a hereditary storage disease caused by a deficiency of the lysosomal enzyme alpha-L-iduronidase. Enzyme replacement therapy may extend the lifespan of affected patients by 6–12 years but the only currently available radical treatment option is allogeneic hematopoietic stem cell transplantation (allo-HSCT). Objectives: We aim to evaluate the influence of conditioning regimens of various intensities and “graft versus host” disease (GvHD) prophylaxis with anti-thymocyte globulin and post-transplant Cyclophosphamide (PTCy) on overall (OS) and event-free (EFS) survival, the incidence of GvHD, the normalization of alpha-L-iduronidase and glycosaminoglycan (GAG) levels over time as well as cardiovascular and cognitive recovery following allo-HSCT. The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University. We included 28 patients with MPS IH who had received allo-HSCT at the clinic at the R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation. The five-year OS was 89%, the EFS – 57%. The use of myeloablative conditioning regimens and allo-HSCT within 12 months of diagnosis improve EFS in affected patients. The cumulative incidence of grade II–IV acute GvHD and grade III–IV acute GvHD was 43% and 18% respectively. The use of PTCy results in a significantly lower incidence of this complication (69% vs 33%, p = 0.013). After allo-HSCT, normal alpha-L-iduronidase levels and urinary GAG excretion were achieved in cases where graft function was normal. Allo-HSCT is an effective treatment for patients with MPS IH. Myeloablative conditioning regimens are the preferred treatment modality for this group of patients but in cases of comorbidities or poor physical status at the time of allo-HSCT, conditioning regimens with reduced intensity may be opted for instead. PTCy may be used for GVHD prevention in patients with MPS IH without increasing the risk of cardiac toxicity.
About the authors
T. A. Bykova
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University, Ministry of Healthcare of Russian Federation
Author for correspondence.
Email: dr.bykova@mail.ru
ORCID iD: 0000-0002-4456-2369
Cand. of Sci. (Med.), Hematologist, Head of the Department of Bone Marrow Transplantation in Children with Orphan Diseases,
Russia, 197022, Saint Petersburg, Lva Tolstogo st., 6–8
Russian FederationV. N. Ovechkina
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University, Ministry of Healthcare of Russian Federation
ORCID iD: 0000-0003-3357-1339
Russian Federation
A. A. Osipova
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University, Ministry of Healthcare of Russian Federation
ORCID iD: 0000-0001-7629-4293
Russian Federation
A. S. Borovkova
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University, Ministry of Healthcare of Russian Federation
ORCID iD: 0000-0002-0205-5529
Russian Federation
A. A. Dotsenko
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University, Ministry of Healthcare of Russian Federation
ORCID iD: 0000-0001-7336-7901
Russian Federation
I. V. Markova
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University, Ministry of Healthcare of Russian Federation
ORCID iD: 0000-0001-5861-7319
Russian Federation
E. V. Semenova
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University, Ministry of Healthcare of Russian Federation
ORCID iD: 0000-0001-5077-9225
Russian Federation
L. S. Zubarovskaya
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University, Ministry of Healthcare of Russian Federation
ORCID iD: 0000-0003-2594-7703
Russian Federation
B. V. Afanasyev
R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation, I.P. Pavlov Saint-Petersburg First State Medical University, Ministry of Healthcare of Russian Federation
ORCID iD: 0000-0002-1235-4530
Russian Federation
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