Matched sibling donor stem cell transplantation for sickle cell disease: Results from the Spanish group for bone marrow transplantation in children

2021 ◽  
Author(s):  
María Isabel Benítez‐Carabante ◽  
Cristina Beléndez ◽  
Marta González‐Vicent ◽  
Laura Alonso ◽  
María Luz Uría‐Oficialdegui ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Marrow Transplantation ◽  
Sickle Cell Disease ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Sickle Cell ◽  
Marrow Transplantation ◽  
Cell Disease ◽  
Matched Sibling

scholarly journals Choice of Donor Source and Conditioning Regimen for Hematopoietic Stem Cell Transplantation in Sickle Cell Disease

2019 ◽  
Vol 8 (11) ◽  
pp. 1997
Author(s):  
Emily Limerick ◽  
Courtney Fitzhugh
Keyword(s):  
Stem Cell ◽  
Sickle Cell Disease ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Sickle Cell ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Matched Sibling

In the United States, one out of every 500 African American children have sickle cell disease (SCD), and SCD affects approximately 100,000 Americans. Significant advances in the treatment of this monogenetic disorder have failed to substantially extend the life expectancy of adults with SCD over the past two decades. Hematopoietic stem cell transplantation (HSCT) remains the only curative option for patients with SCD. While human leukocyte antigen (HLA) matched sibling HSCT has been successful, its availability is extremely limited. This review summarizes various conditioning regimens that are currently available. We explore recent efforts to expand the availability of allogeneic HSCT, including matched unrelated, umbilical cord blood, and haploidentical stem cell sources. We consider the use of nonmyeloablative conditioning and haploidentical donor sources as emerging strategies to expand transplant availability, particularly for SCD patients with complications and comorbidities who can undergo neither matched related transplant nor myeloablative conditioning. Finally, we show that improved conditioning agents have improved success rates not only in the HLA-matched sibling setting but also alternative donor settings.

scholarly journals Transfusion Support in Patients with Sickle Cell Anemia Undergoing Haploidentical Hematopoietic Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3686-3686
Author(s):  
Dilan A Patel ◽  
Deva Sharma ◽  
Jennifer Andrews ◽  
Adetola A. Kassim
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Sickle Cell Disease ◽  
Cell Transplantation ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Marrow Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Marrow Transplant ◽  
Cell Disease

Introduction: Hematopoietic cell transplantation (HCT) is the only curative therapy for sickle cell disease (SCD), though is not widely utilized due to inadequate donor availability. Our center has previously reported improved outcomes with a reduced intensity, haploidentical bone marrow transplant (haplo-BMT) with post-transplant Cytoxan and thiotepa (de la Fuente et al, Biol Blood Marrow Transplant 2019). All patients treated with this protocol require red blood cell (RBC) support for anemia. Alloimmunization to minor RBC antigens can be a barrier to therapies including HCT, especially in those patients with multiple antibodies or those requiring rare RBC units. We report on our experience thus far in seven patients with SCA on this protocol. Materials and Methods: After IRB approval, we report in a cohort of 10 patients who completed haplo-BMT with our ongoing platform (ClinicalTrials.gov Identifier: NCT01850108). Phenotypic matching of RBCs beyond ABO and Rh(D) is necessary since patients with SCD commonly produce antibodies against minor RBC antigens, which can result in transfusion reactions such as delayed hemolysis and hyperhemolysis. Our institutional practice is to obtain minor RBC phenotyping on both the patient and their donor prior to transplant. The blood bank provides RBCs that are phenotypically matched for Rh and Kell antigens regardless of antibody status. If a patient has a history of an antibody or a positive screen, the blood bank provides extended phenotypic matching to include Fya, Fyb, Jka, Jkb, and MNS if possible. Outcomes data were analyzed using the CIBMTR database and EMR. Results: A total of 10 patients underwent haplo-BMT, 7 for sickle cell anemia and 3 for beta thalassemia major. Two patients had alloantibodies prior to haplo-BMT, both of whom had SCA. Three patients were ABO identical with their donor; five patients received minor ABO incompatible transplants, and two received major ABO incompatible transplants. Indications for transplant included transfusion dependence (5 patients), cerebrovascular accidents (4 patients), recurrent pain crises (1 patient), visual impairment (1 patient), and seizures (1 patient). The median recipient age at transplant was 17.8 years for the 8 males and 2 females included. Median donor age was 37.5 years, including 4 males and 6 females, with 7 parental donors and 3 sibling donors. No grade 1 acute graft-versus-host disease (GvHD) was noted, though 30% (3/10) had grades II-IV disease. Limited chronic GvHD occurred in 20% (2/10) patients, without any cases of extensive disease. A median of 3.5 RBC (range 0 - 14) transfusions and a median of 10 (range 1 - 24) platelet transfusions were required from date of transplant until neutrophil engraftment. None of the patients had delayed erythroid engraftment. Conclusion: We report successful haploidentical HCT in 7 patients with sickle cell anemia. Providing appropriate phenotypically matched RBCs is especially important in the era of emerging cures for sickle cell anemia, including gene therapy and haploidentical HCT. Alloimmunization is an understudied barrier to HSCT and must be carefully assessed when planning for HCT or other curative therapies required RBC transfusion support. 1. de la Fuente J, Dhedin N, Koyama T, et al. Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide Plus Thiotepa Improves Donor Engraftment in Patients with Sickle Cell Anemia: Results of an International Learning Collaborative. Biol Blood Marrow Transplant 2019;25:1197-1209. 2. Bolanos-Meade J, Fuchs EJ, Luznik L, et al. HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Blood 2012;120:4285-91. Disclosures No relevant conflicts of interest to declare.

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.

Sign in / Sign up

Export Citation Format

Share Document