Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in children with sickle cell disease

2015 ◽  
Vol 169 (5) ◽  
pp. 726-736 ◽  
Author(s):  
Luisa Strocchio ◽  
Marco Zecca ◽  
Patrizia Comoli ◽  
Tommaso Mina ◽  
Giovanna Giorgiani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Sickle Cell Disease ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Sickle Cell ◽  
Haematopoietic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Haematopoietic Stem Cell ◽  
Cell Disease

scholarly journals In utero Therapy for the Treatment of Sickle Cell Disease: Taking Advantage of the Fetal Immune System

2021 ◽  
Vol 8 ◽  
Author(s):  
Alba Saenz de Villaverde Cortabarria ◽  
Laura Makhoul ◽  
John Strouboulis ◽  
Giovanna Lombardi ◽  
Eugene Oteng-Ntim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Immune System ◽  
Sickle Cell Disease ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Sickle Cell ◽  
In Utero ◽  
Haematopoietic Stem Cell ◽  
Cell Disease ◽  
Fetal Immune System

Sickle Cell Disease (SCD) is an autosomal recessive disorder resulting from a β-globin gene missense mutation and is among the most prevalent severe monogenic disorders worldwide. Haematopoietic stem cell transplantation remains the only curative option for the disease, as most management options focus solely on symptom control. Progress in prenatal diagnosis and fetal therapeutic intervention raises the possibility of in utero treatment. SCD can be diagnosed prenatally in high-risk patients using chorionic villus sampling. Among the possible prenatal treatments, in utero stem cell transplantation (IUSCT) shows the most promise. IUSCT is a non-myeloablative, non-immunosuppressive alternative conferring various unique advantages and may also offer safer postnatal management. Fetal immunologic immaturity could allow engraftment of allogeneic cells before fetal immune system maturation, donor-specific tolerance and lifelong chimerism. In this review, we will discuss SCD, screening and current treatments. We will present the therapeutic rationale for IUSCT, examine the early experimental work and initial human experience, as well as consider primary barriers of clinically implementing IUSCT and the promising approaches to address them.

Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2749-2756 ◽  
Author(s):  
Françoise Bernaudin ◽  
Gérard Socie ◽  
Mathieu Kuentz ◽  
Sylvie Chevret ◽  
Michel Duval ◽  
...  
Keyword(s):  
Stem Cell ◽  
Sickle Cell Disease ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Sickle Cell ◽  
Conditioning Regimen ◽  
Long Term Results ◽  
Cell Disease ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem

Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for sickle cell disease (SCD); nevertheless, its use has been limited by the risk of transplantation-related mortality (TRM). Between November 1988 and December 2004, 87 consecutive patients with severe SCD ranging from 2 to 22 years of age received transplants in France. Cerebral vasculopathy was the principal indication for transplantation (55 patients). All the patients received grafts from a sibling donor after a myeloablative conditioning regimen (CR). The only change in the CR during the study period was the introduction of antithymocyte globulin (ATG) in March 1992. The rejection rate was 22.6% before the use of ATG but 3% thereafter. With a median follow-up of 6 years (range, 2.0 to 17.9 years), the overall and event-free survival (EFS) rates were 93.1% and 86.1%, respectively. Graft versus host disease (GVHD) was the main cause of TRM. Importantly, cord blood transplant recipients did not develop GVHD. No new ischemic lesions were detected after engraftment, and cerebral velocities were significantly reduced. The outcome improved significantly with time: the EFS rate among the 44 patients receiving transplants after January 2000 was 95.3%. These results indicate that HLA-identical sibling HSCT after myeloablative conditioning with ATG should be considered as a standard of care for SCD children who are at high risk for stroke.

scholarly journals RH genotyping in a sickle cell disease patient contributing to hematopoietic stem cell transplantation donor selection and management

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2836-2838 ◽  
Author(s):  
Ross M. Fasano ◽  
Alessandro Monaco ◽  
Emily Riehm Meier ◽  
Philippe Pary ◽  
A. Hallie Lee-Stroka ◽  
...  
Keyword(s):  
Stem Cell ◽  
Sickle Cell Disease ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Blood Group ◽  
Sickle Cell ◽  
Disease Patient ◽  
Nucleotide Sequencing ◽  
Cell Disease ◽  
Hematopoietic Stem

Abstract African individuals harbor molecular RH variants, which permit alloantibody formation to high-prevalence Rh antigens after transfusions. Genotyping identifies such RH variants, which are often missed by serologic blood group typing. Comprehensive molecular blood group analysis using 3 genotyping platforms, nucleotide sequencing, and serologic evaluation was performed on a 7-year-old African male with sickle cell disease who developed an “e-like” antibody shortly after initiating monthly red blood cell (RBC) transfusions for silent stroke. Genotyping of the RH variant predicted a severe shortage of compatible RBCs for long-term transfusion support, which contributed to the decision for hematopoetic stem cell transplantation. RH genotyping confirmed the RH variant in the human leukocyte antigen–matched sibling donor. The patient's (C)ces type 1 haplotype occurs in up to 11% of African American sickle cell disease patients; however, haplotype-matched RBCs were serologically incompatible. This case documents that blood unit selection should be based on genotype rather than one matching haplotype.

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