Applicability of and potential barriers preventing allogeneic stem cell transplant in sickle cell patients treated outside a sickle cell program

American Journal of Hematology, EarlyView.
Source: American Journal of Hematology - Category: Hematology Source Type: research

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Background: Sickle cell disease (SCD) is an inherited disorder with an estimate of 300,000 affected newborns per year worldwide. Despite improvements in preventive measures and conventional therapy, substantial morbidity and mortality, resulting in a reduced life expectancy persist. Allogeneic hematopoietic stem cell transplantation (HSCT) with a matched sibling donor (MSD) is currently the curative standard of care. However, matched donor availability is 6 months in T-haplo-HSCT and
Source: Blood - Category: Hematology Authors: Tags: 732. Clinical Allogeneic Transplantation: Results: Poster II Source Type: research
DISCUSSION:In this largest series of gene therapy for the treatment of hemoglobinopathies (to our knowledge), we find it to be clinically effective in terms of reduction in transfusion needs; data to suggest an improved OS and disease free survival is promising, however long term data is awaited. Gene therapy appears to bypass the limitations faced by allo-HCT especially a high early TRM. Randomized trials reporting the efficacy and safety outcomes with longer follow ups are urgently required.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 801. Gene Therapy and Transfer: Poster I Source Type: research
Conclusion: When considering HSCT as treatment for MPS-I, HSCT at a younger age is associated with increased overall survival. This study found that ERT in addition to HSCT had no effect on overall mortality. The lack of difference between transplant and non-transplant ICU admissions indicates that HSCT does not significantly contribute to overall ICU admissions. Likelihood of ICU admission plateaus after one year, regardless of age at transplant. Infection is the most common reason for hospital admission for all patients with MPS-I diagnosis, however severe infection is more common among HSCT patients when compared to non...
Source: Blood - Category: Hematology Authors: Tags: 903. Outcomes Research-Non-Malignant Hematology: Health Outcomes in Sickle Cell Disease and Mucopolysaccharidosis Source Type: research
BackgroundSCD is a chronic debilitating disease secondary to frequent veno-occlusive events resulting in chronic organ damage, including cerebral vasculopathy, acute chest syndrome (ACS), pulmonary hypertension and a significantly shortened life-span (Bunn et al, NEJM, 1997; Lanzkron et al, PHR, 2013; Platt et al, NEJM, 1994). Importantly, SCD survivors also develop significant defects in neurocognition, especially processing speed and have a poor HRQL (Stotesbury et al, Neurology, 2018); Vichinsky et al, JAMA, 2010; Panepinto et al, BJH, 2005). To date the only cure for SCD patients has been HLA matched sibling AlloSCT fo...
Source: Blood - Category: Hematology Authors: Tags: 903. Outcomes Research-Non-Malignant Hematology: Health Outcomes in Sickle Cell Disease and Mucopolysaccharidosis Source Type: research
ConclusionsWe have shown for the first time that TSP-1, PF4,and GAL-1 are associated with engraftment in patients with SCD who undergo haplo HSCT. The study warrants further validation in a larger sample size as well as in vitro and in vivo analyses to evaluate whether our candidate proteins are associated with tolerance induction.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Comorbidity and Novel Strategies to Improve Graft Function Source Type: research
Conclusions: This analysis represents the largest report of outcomes in patients who have received a CD34+ selected stem cell infusion without conditioning for GF. Negative donor/recipient CMV serostatus and sex matching predicted response. In responding patients, GF initially affecting
Source: Blood - Category: Hematology Authors: Tags: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Comorbidity and Novel Strategies to Improve Graft Function Source Type: research
Conclusions: Early results from 2 SCA adults treated with a modified -globin LV modified autologous HSC following RIC transplant showed excellent safety, feasibility, with minimal post-transplant toxicity, rapid count recovery, and sustained stable genetically modified cells in peripheral blood and bone marrow. The first patient shows significant clinical amelioration of the SCA phenotype at 1 year PT, with 20% vector-derived HbF (HbF*) that has caused amelioration of anemia, near elimination of chronic pain and absence of acute sickle events. The second patient, although still early post-transplant shows a similar HbF* tr...
Source: Blood - Category: Hematology Authors: Tags: 801. Gene Therapy and Transfer: Gene Therapy for Blood Cell Disorders Source Type: research
Sickle cell anemia (SCA) is caused by a point mutation in the beta-globin gene. SCA has potentially devastating consequences including chronic hemolytic anemia, episodic vascular occlusion, inflammation and oxidative stress, and cumulative multi-organ damage resulting in early mortality. In fact, with reduction of childhood mortality due to early diagnosis and infection prophylaxis, end-organ damage is the major cause of death in SCA. SCA patients show hyper coagulative state in the absence of vascular occlusion. Recently, our group has shown that reduction of circulating major clotting factor, thrombin, in SCA mice signif...
Source: Blood - Category: Hematology Authors: Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Sickle Cell Disease-Role of Coagulation and Inflammation in Pathophysiology Source Type: research
Conclusions:Our study demonstrates frequent variants in histone modification, splicing, and transcription-associated genes in JMML specimens in addition to known pathogenic RAS pathway mutations. We further report histopathologic CD123+ PDC clustering in JMML specimens analogous to that observed in CMML, which may aid in the workup of this often difficult-to-diagnose disease. Our findings of genetic and immunophenotypic overlap between JMML and CMML suggest similarities in pathogenesis despite typical presentation at extremes of age.DisclosuresTasian: Aleta Biopharmaceuticals: Membership on an entity's Board of Directors o...
Source: Blood - Category: Hematology Authors: Tags: 636. Myelodysplastic Syndromes-Basic and Translational Studies: Poster I Source Type: research
Beta-thalassemia and sickle cell disease are monogenic disorders that are currently treated by allogeneic bone marrow (BM) transplantation although the challenges of finding a suitable matched-donor and the risk of graft vs host disease have limited the adoption of this otherwise curative treatment. A potentially promising approach for hemoglobinopathies aims to reactivate fetal hemoglobin (HbF) as a substitute for defective or absent adult hemoglobin by modifying the patient's own hematopoietic stem and progenitor cells (HSPCs). Here, we evaluated CRISPR/Cas9-induced small deletions in HSPCs that are associated with hered...
Source: Blood - Category: Hematology Authors: Tags: 701. Experimental Transplantation: Basic Biology, Pre-Clinical Models: Hematopoietic Stem Cells and Alternate GVHD Tissues Source Type: research
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