scholarly journals Optimal disease management and health monitoring in adults with sickle cell disease

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 505-512 ◽  
Author(s):  
Jo Howard ◽  
Swee Lay Thein
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Multidisciplinary Care ◽  
Organ Damage ◽  
Cell Transplant ◽  
Cell Disease ◽  
Adult Care ◽  
Pharmacological Agents ◽  
Hematopoietic Stem ◽  
Age Related

Abstract In countries with access to organized health care, survival of children with sickle cell disease (SCD) has greatly improved, resulting in a growing population of adults with SCD. Transition from pediatric to adult care presents many challenges for the patient, who now faces the reality of emerging complications in many organs that are cumulative, adding to other age-related nonsickle conditions that interact and add to the disease morbidity. We recommend regular comprehensive annual assessments, monitoring for early signs of organ damage and joint clinics with relevant specialists, if applicable. While maintaining a low threshold for intervention with disease-modifying therapies, we should always keep in mind that there is no single complication that is pathognomonic of SCD, and nonsickle comorbidities should always be excluded and treated if present. We need to reevaluate our approach to managing adults with SCD by putting a greater emphasis on multidisciplinary care while proactively considering curative options (hematopoietic stem cell transplant and gene therapy) and experimental pharmacological agents for adults with SCD of all ages before complications render the patients ineligible for these treatments.

scholarly journals The Role of Hematopoietic Stem Cell Transplantation in the treatment of Sickle Cell Disease

2020 ◽  
Vol 7 (09) ◽  
pp. 5024-5032
Author(s):  
Carolina Wishner ◽  
Colleen Taylor ◽  
Monica Williams ◽  
Derian Kuneman
Keyword(s):  
Stem Cell ◽  
Sickle Cell Disease ◽  
Hematopoietic Stem Cell ◽  
Sickle Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Organ Damage ◽  
Cell Transplant ◽  
Cell Disease ◽  
Hematopoietic Stem

Abstract   Sickle cell disease (SCD) affects millions of people around the world and is associated with significant morbidity and premature mortality. It is a chronic, life-long illness that affects virtually every tissue in the body, worsens over time, with varying degrees of morbidity in everyone with the disease.  Before hematopoietic stem cell transplant (HCST), the mainstay of the management of SCD included early identification of the disease through newborn screening, infection prophylaxis with vaccinations and antibiotics, management of pain crises, blood transfusions, and hydroxyurea.   These treatments although beneficial, do not cure SCD, stop the progressive end-organ damage associated with this disease, and are lifelong.   Hematopoietic stem cell transplant is one of two treatment options that offer a cure for SCD and stops the progressive end-organ damage. The purpose of this article is to examine traditional treatments (best medical practice) and HCST for SCD and their associated complications.  The role of HCST in the treatment of sickle cell disease, as well as recent research on HSCT as a cure for SCD, risk factors, patient selection, limitations, and future use of this treatment option, are also reviewed.  Major issues surrounding the use of HCST for treating SCD include the optimal age for transplantation, disease severity, donor source, and the conditioning regimen before transplantation. The future of HCST including gene therapy is also discussed.

scholarly journals Potential role of LSD1 inhibitors in the treatment of sickle cell disease: a review of preclinical animal model data

2018 ◽  
Vol 315 (4) ◽  
pp. R840-R847 ◽  
Author(s):  
Angela Rivers ◽  
Ramasamy Jagadeeswaran ◽  
Donald Lavelle
Keyword(s):  
Reactive Oxygen Species ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Globin Gene ◽  
Reactive Oxygen ◽  
Organ Damage ◽  
The United States ◽  
Oxygen Species ◽  
Cell Disease ◽  
Hematopoietic Stem

Sickle cell disease (SCD) is caused by a mutation of the β-globin gene (Ingram VM. Nature 180: 326–328, 1957), which triggers the polymerization of deoxygenated sickle hemoglobin (HbS). Approximately 100,000 SCD patients in the United States and millions worldwide (Piel FB, et al. PLoS Med 10: e1001484, 2013) suffer from chronic hemolytic anemia, painful crises, multisystem organ damage, and reduced life expectancy (Rees DC, et al. Lancet 376: 2018–2031, 2010; Serjeant GR. Cold Spring Harb Perspect Med 3: a011783, 2013). Hematopoietic stem cell transplantation can be curative, but the majority of patients do not have a suitable donor (Talano JA, Cairo MS. Eur J Haematol 94: 391–399, 2015). Advanced gene-editing technologies also offer the possibility of a cure (Goodman MA, Malik P. Ther Adv Hematol 7: 302–315, 2016; Lettre G, Bauer DE. Lancet 387: 2554–2564, 2016), but the likelihood that these strategies can be mobilized to treat the large numbers of patients residing in developing countries is remote. A pharmacological treatment to increase fetal hemoglobin (HbF) as a therapy for SCD has been a long-sought goal, because increased levels of HbF (α2γ2) inhibit the polymerization of HbS (Poillin WN, et al. Proc Natl Acad Sci USA 90: 5039–5043, 1993; Sunshine HR, et al. J Mol Biol 133: 435–467, 1979) and are associated with reduced symptoms and increased lifespan of SCD patients (Platt OS, et al. N Engl J Med 330: 1639–1644, 1994; Platt OS, et al. N Engl J Med 325: 11–16, 1991). Only two drugs, hydroxyurea and l-glutamine, are approved by the US Food and Drug Administration for treatment of SCD. Hydroxyurea is ineffective at HbF induction in ~50% of patients (Charache S, et al. N Engl J Med 332: 1317–1322, 1995). While polymerization of HbS has been traditionally considered the driving force in the hemolysis of SCD, the excessive reactive oxygen species generated from red blood cells, with further amplification by intravascular hemolysis, also are a major contributor to SCD pathology. This review highlights a new class of drugs, lysine-specific demethylase (LSD1) inhibitors, that induce HbF and reduce reactive oxygen species.

scholarly journals 2019 sickle cell disease guidelines by the American Society of Hematology: methodology, challenges, and innovations

2019 ◽  
Vol 3 (23) ◽  
pp. 3945-3950 ◽  
Author(s):  
M. Hassan Murad ◽  
Robert I. Liem ◽  
Eddy S. Lang ◽  
Elie A. Akl ◽  
Joerg J. Meerpohl ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Guideline Development ◽  
A Priori ◽  
Cell Transplant ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Assessment Development ◽  
Cerebrovascular Complications ◽  
American Society

Abstract The American Society of Hematology (ASH) convened 5 guideline panels to develop clinical practice recommendations addressing 5 management areas of highest importance to individuals living with sickle cell disease: pain, cerebrovascular complications, pulmonary and kidney complications, transfusion, and hematopoietic stem cell transplant. Panels were multidisciplinary and consisted of patient representatives, content experts, and methodologists. The Mayo Clinic Evidence-Based Practice Center conducted systematic reviews based on a priori selected questions. In this exposition, we describe the process used by ASH, including the GRADE approach (Grades of Recommendations, Assessment, Development and Evaluation) for rating certainty of the evidence and the GRADE Evidence to Decision Framework. We also describe several unique challenges faced by the guideline panels and the specific innovations and solutions used to address them, including a curriculum to train patients to engage in guideline development, dealing with the opioid crisis, and working with indirect and noncomparative evidence.

Allogeneic hematopoietic stem cell transplant for sickle cell disease: The why, who, and what

Blood Reviews ◽  
2021 ◽  
pp. 100868
Author(s):  
Emanuela Cimpeanu ◽  
Maria Poplawska ◽  
Brian Campbell Jimenez ◽  
Dibyendu Dutta ◽  
Seah H. Lim
Keyword(s):  
Stem Cell ◽  
Sickle Cell Disease ◽  
Hematopoietic Stem Cell ◽  
Sickle Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Cell Disease ◽  
Hematopoietic Stem

scholarly journals Evidence-Based Minireview: In young children with severe sickle cell disease, do the benefits of HLA-identical sibling donor HCT outweigh the risks?

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 190-195
Author(s):  
Niketa Shah ◽  
Lakshmanan Krishnamurti
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Medical Condition ◽  
Human Leukocyte ◽  
Female Child ◽  
Cell Transplant ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Febrile Episodes ◽  
First Year Of Life

Abstract In case 1, a 14-month-old male child with sickle cell disease (SCD) was referred for evaluation for an allogeneic hematopoietic stem cell transplant (HCT). The patient had a history of dactylitis 3 times in his first year of life and febrile episodes twice at the consult. His 4-year-old sister was found to be human leukocyte antigen (HLA) identical. The patient was started on hydroxyurea (HU) at 2.5 years of age. His parents again sought consultation when he was 5 years old because of concerns about his medical condition. At the time, the patient had experienced 2 vaso-occlusive pain episodes (VOEs) requiring hospitalization during the previous 2 years. He had also experienced intermittent pain crises requiring rest at home for 2 to 3 days. The child has not attended school in person due to the COVID-19 pandemic. The family is considering HCT but is ambivalent about it because of potential toxicity. In case 2, an 8-year-old female child is 3 years out from HCT for SCD from her HLA-identical sibling. Before HCT, despite receiving HU, she had experienced >5 VOEs requiring hospitalization and 2 episodes of acute chest syndromes in the previous 3 years. She had also been missing almost 50 days of school days each year. After HCT, she is now attending school regularly and participating in all normal age-appropriate activities. The parents believe that HCT has been transformative in their child's life.

scholarly journals How I treat the older adult with sickle cell disease

Blood ◽  
2018 ◽  
Vol 132 (17) ◽  
pp. 1750-1760 ◽  
Author(s):  
Swee Lay Thein ◽  
Jo Howard
Keyword(s):  
Sickle Cell Disease ◽  
Older Adult ◽  
Sickle Cell ◽  
Organ Damage ◽  
Cell Disease ◽  
Older Patient ◽  
Preventative Measures ◽  
Age Related ◽  
Low Threshold ◽  
Delays In Diagnosis

Abstract With increasing survival, cumulative complications of sickle cell disease (SCD), which develop insidiously over time, are becoming more apparent and common in older patients, particularly those in their fifth decade and beyond. The older patient is also more likely to develop other age-related nonsickle conditions that interact and add to the disease morbidity. A common misconception is that any symptom in a SCD patient is attributable to their SCD and this may lead to delays in diagnosis and appropriate intervention. We recommend regular comprehensive reviews and monitoring for early signs of organ damage and a low threshold for the use of hydroxyurea and blood transfusions as preventative measures for end-organ disease. Treatable comorbidities and acute deterioration should be managed aggressively. Although the primary goal in management of the older adult with SCD is improving anemia and minimizing organ damage, the time has come for us to be more proactive in considering curative therapies previously offered to the younger patient. Curative or experimental interventions should be discussed early, before complications render the patients ineligible for these treatments.

The ethics of a proposed study of hematopoietic stem cell transplant for children with “less severe” sickle cell disease

Blood ◽  
2014 ◽  
Vol 124 (6) ◽  
pp. 861-866 ◽  
Author(s):  
Robert S. Nickel ◽  
Jeanne E. Hendrickson ◽  
Ann E. Haight
Keyword(s):  
Stem Cell ◽  
Sickle Cell Disease ◽  
Hematopoietic Stem Cell ◽  
Sickle Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Individual Autonomy ◽  
Cell Transplant ◽  
Cell Disease ◽  
Hematopoietic Stem

Abstract Hematopoietic stem cell transplant (HSCT) is the only cure for sickle cell disease (SCD). HSCT using an HLA-identical sibling donor is currently an acceptable treatment option for children with severe SCD, with expected HSCT survival >95% and event-free survival >85%. HSCT for children with less severe SCD (children who have not yet suffered overt disease complications or only had mild problems) is controversial. It is important to consider the ethical issues of a proposed study comparing HLA-identical sibling HSCT to best supportive care for children with less severe SCD. In evaluating the principles of nonmaleficence, respect for individual autonomy, and justice, we conclude that a study of HLA-identical sibling HSCT for all children with SCD, particularly hemoglobin SS and Sβ0-thalassemia disease, is ethically sound. Future work should explore the implementation of a large trial to help determine whether HSCT is a beneficial treatment of children with less severe SCD.

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