First experience of hematopoietic stem cell transplantation treatment of Shwachman–Diamond syndrome using unaffected HLA–matched sibling donor produced through preimplantation HLA typing

Abstract

The only proven cure for Shwachman–Diamond syndrome (SDS) bone marrow failure is allogeneic hematopoietic stem cell transplantation (HSCT). However HSCT with donors other than HLA-identical siblings is associated with high mortality and unfavorable prognosis. This paper presents the first experience of HSCT treatment of SDS using an unaffected HLA-identical sibling produced through preimplantation genetic diagnosis (PGD). The patient was a 6-year-old blood transfusion-dependent SDS baby girl with secondary myelodysplastic syndrome, for whom no HLA-identical donor was available. As a result of PGD, two unaffected HLA matched embryos were identified; one of them was randomly selected for transfer, resulting in a clinical pregnancy and birth of an apparently healthy child. The patient underwent allogeneic transplantation of cord blood hematopoietic stem cells, together with bone marrow from this sibling, resulting in complete hemopoietic recovery. The patient was no longer transfusion-dependent and had normal blood values 160 days after transplantation.

Trends in Outcome of Hematopoietic Stem Cell Transplantation: 5000 Transplantations and 30 Years of Single-Center Experience

“…Subsequently, in 2007, it developed into the specialized RM Gorbacheva Research Institute, focusing on problems of HCT. The team of the RM Gorbacheva Research Institute was the first to introduce several key transplantation technologies in Russia: in 1991-the first allogeneic HCT for a child, the first autologous peripheral blood stem cell transplantation in 1997, the program for unrelated donor HCT in 2000, the first HCT from a haploidentical donor with ex vivo depletion in 2006 [10,11] and the first transplantation with preimplantation donor selection for a patient with hereditary disease in 2017 [12]. Since the first transplantation in 1990, more than 5000 HCTs have been performed.…”

Autosomal dominant Shwachman–Diamond syndrome with a novel heterozygous missense variant in the SRP54 gene causing severe phenotypic features

“…The only curative treatment for patients with SDS who develop BMF or MDS/AML is HSCT; however, these patients experience significant morbidity and mortality. 9 In the largest retrospective cohort (74 SDS patients) published to date the five-year overall survival was 63Á5% with graft failure occurring in approximately 15% of patients. 10 Of the patients who did not survive (n = 28), 25% suffered progressive disease/relapse (graft failure) and 75% died from transplant-related toxicity.…”

Preimplantation Genetic Diagnosis for Human Leukocyte Antigen Matching: The Generation of the Savior Sibling and the “Gift of Life”

“…Today, there is a long list of diseases where an affected child has been cured by the savior sibling providing the "gift of life": cord blood or bone marrow hematopoietic stem cells. The list includes [3] the cure of beta-thalassemia, Fanconi anemia, Diamond-Blackfan anemia, sickle-cell anemia, Wiskott-Aldrich syndrome, X-linked adrenoleukodystrophy, Glanzmann's thrombasthenia, Hurler syndrome, acute mueloid leukemia, acute lympoblastic leukemia and Shwachman-Diamond syndrome [4].…”