Strategic Goal: Goal 2: Reduce Human Disease

Disease Severity Biomarkers for Sickle Cell Disease

Can we identify biomarkers that can predict sickle cell disease severity?

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Identifying reliable biomarkers that can predict severity of sickle cell disease could help doctors and patients make better decisions about a wide range of clinical decisions, including weighing the risks vs. benefits of bone marrow transplantation, chemotherapeutic manipulation of Hb F level, and gene therapy, all of which have potentially life-threatening complications.

Feasibility and challenges of addressing this CQ or CC :

Scientific advances make it feasible to identify biomarkers of disease severity. However, identifying biomarkers with good sensitivity and specificity is likely to be a challenge.

Name of idea submitter and other team members who worked on this idea : The Sickle Cell Association of New Jersey

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Strategic Goal: Goal 3: Advance Translational Research

psychosocial care in sickle cell disease

What are the most effective trans-disciplinary and multi-level strategies for accelerating psychosocial care with sickle cell disease and how psychosocial factors impact families?

Submitted by (@sicklecellwarrior)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Since sickle cell has multiple layers in medical treatment strategies, how can the same thought process happen when it comes to psychosocial matters? How can the NHLBI develop effective patient engagement trans-disciplinary and multi-level strategies that work with medical strategies to deal with psychosocial matters for individuals and families?

Name of idea submitter and other team members who worked on this idea : Sickle Cell Warriors, Inc community members

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Strategic Goal: Goal 2: Reduce Human Disease

Single nucleotide polymorphisms, microarray and sickle cell disease

Do SNPs account for any of the variability seen in the phenotypic expression of sickle cell disease? Can microarray analysis be used to map these SNPs, promoting refined care plans for those living with sickle cell disease?

Submitted by (@sicklecellwarrior)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Multiple Single Nucleotide Polymorphisms (SNPs) have previously been identified in the mu opioid receptor and it is estimated that millions might exist throughout the genome. Drastic phenotypic variability exists among patients in the sickle cell community. Do SNPs account for any of this variability and can this information be used to more effectively treat sickle cell disease.

Name of idea submitter and other team members who worked on this idea : Sickle Cell Warriors, Inc. community members

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Strategic Goal: Goal 2: Reduce Human Disease

Family centered interventions in sickle cell

Sickle cell is a genetic disease with lifelong health consequences for affected individuals and their families. Interventions for individuals with sickle cell must be patient and family-centered.

Submitted by (@coretta.jenerette)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Name of idea submitter and other team members who worked on this idea : International Association of Sickle Cell Nurses and Physician Assistants, Inc.

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Strategic Goal: Goal 3: Advance Translational Research

Financial and psycosocial impact of transition in sickle cell disease

What are the financial and social implications for individuals living with SCD from adolescence transitioning into adult care? What impact does this transition have on the caregiver and family as a whole?

Submitted by (@sicklecellwarrior)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

It is very difficult for many living with SCD to maintain employment (many people have to rely on disability benefits to survive) finish school, even maintain relationships. Greater understanding of the financial and social impact would enable advocacy and direct patient service organizations to better prepare the transitioning population, reducing the financial strain on the individual and the growing medical debt incurred by hospitals and government social service programs.

Name of idea submitter and other team members who worked on this idea : Sickle Cell Warriors, Inc. community members

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Strategic Goal: Goal 2: Reduce Human Disease

Hypoxia, acute chest syndrome and sickle cell disease

What markers in sickle cell disease can predict hypoxia after acute chest syndrome or pneumonia?

Submitted by (@sicklecellwarrior)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Understanding that sickle cell disease has a character of depriving oxygen, is there any predicators that can tell if a child will have hypoxia after experiencing acute chest syndrome or pneumonia.

Name of idea submitter and other team members who worked on this idea : Sickle Cell Warriors, Inc. community members

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Strategic Goal: Goal 2: Reduce Human Disease

Optimization of Existing Therapies for Sickle Cell Disease

How can the safety, dosing and benefits of existing therapies for sickle cell disease such as hydroxyurea, be optimized in order to increase its efficacy and improve patient adherence?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Hydroxyurea is a widely available disease-modifying therapy for sickle cell disease (SCD), but its effectiveness is currently limited by inadequate utilization, and less than optimal response. Research is needed to improve adherence to this evidence-based therapy and emphasis needs to be placed on determining whether therapy with hydroxyurea can prevent or even reverse organ dysfunction. In addition, research identifying new adjunct therapies to blood transfusion and hydroxyurea, as well as disease-specific therapies for co-morbidities such as kidney disease, hypertension, obstructive lung disease, and pulmonary hypertension will be valuable in the management and treatment of SCD.

Name of idea submitter and other team members who worked on this idea : Alice Kuaban on behalf of the American Society of Hematology (ASH)

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Strategic Goal: Goal 2: Reduce Human Disease

Symptom management in sickle cell

Symptom management is a significant challenge for individuals living with sickle cell. In most cases, sickle cell research in symptom management focuses on pain. Although important, many other symptoms such a fatigue, anxiety, and depression need to be identified and intervened on to improve the quality of life for individuals living with sickle cell disease.

Submitted by (@coretta.jenerette)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Name of idea submitter and other team members who worked on this idea : International Association of Sickle Cell Nurses and Physician Assistants, Inc.

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Strategic Goal: Goal 2: Reduce Human Disease

Pulmonary Complications of Sickle Cell Disease

What is the effectiveness and safety of treatment of the co-morbid condition of asthma with medications known to improve asthma outcomes in individuals without SCD?

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

We and others have demonstrated that a doctor diagnosis of asthma is associated with increased morbidity and mortality in those with SCD. While doctor diagnosis of asthma is the issue for children, wheezing symptoms even without a diagnosis is the risk factor for adults.

 

This suggests either that asthma is under diagnosed in adults or that the disease patterns shifts from childhood to adulthood.

 

Making a diagnosis of asthma in individuals with SCD is difficult, as SCD by itself causes respiratory symptoms that can be similar to asthma in general populations, but diagnostic criteria are being proposed. There is concern about the value of treatment of the co-morbid of asthma in prevention of symptoms and even more so in reducing morbidity of pain and ACS episodes. There is also concern with regard to the potential side effects of inhaled corticosteroids by themselves increasing pain episodes and also having adverse effects on bone density, which can be affected by SCD itself.

Name of idea submitter and other team members who worked on this idea : ATS Member

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Strategic Goal: Goal 2: Reduce Human Disease

Apheresis Medicine in the Management of Sickle Cell Disease

Despite advances in care, patients with sickle cell disease have significant morbidity and mortality. One challenge is the optimal use of simple vs exchange transfusion vs no transfusion when managing these patients. Simple transfusions lead to iron overload while exchange transfusions may expose patients to increase numbers of red blood cell units. The mechanism of benefit from transfusion (oxygen delivery vs marrow ...more »

Submitted by (@bsachais)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

SCD is the most common genetic disease in the United States affecting 100,000 individuals or 1 in 400 African American births. Pain, stroke, acute chest syndrome and priapism are common morbidities affecting patients with sickle cell disease, which often result in emergency room visits and/or hospitalizations. Despite advances in treatment, sickle cell disease is associated with significant mortality and shortened life expectancy. Defining the optimal role of red blood cell exchange and plasma exchange (which may be used to remove plasma molecules such as inflammatory factors and free hemoglobin) in the management and prevention of the complications of sickle cell disease and may not only prolong the life of these patients but is expected to improve the quality of their lives. In addition, clearly defining the indications for simple verses exchange transfusion therapy has the potential to minimize both alloimmunization to red blood cells (reported to occur in up to 75% of patients with sickle cell disease) and iron overload associated with transfusion.

 

Transfusion therapy may be efficacious to sickle cell patients by providing increased oxygen delivery to tissues and/or decreasing the amount of sickle hemoglobin present by suppression of erythropoiesis. Understanding the relative contributions of these mechanisms will assist with optimal use of transfusion therapy as well as inform the development of novel alternative therapies

Feasibility and challenges of addressing this CQ or CC :

Multi-center trials should be feasible, given the number of patients with sickle cell disease in the US. Participation by larger academic centers which care for sickle cell patients should facilitate trials. Methods for automated red cell exchange and plasma exchange are available and in common use at many centers. Great interest exists among physicians caring for sickle cell patients (as exemplified by the recent NIH consensus document and ASFA sickle cell consensus conference) which is a strength of this proposal. Challenges include agreement on standard treatment protocols across centers and long term follow up of patients. Maintaining vascular access in sickle cell patients is another challenge when performing apheresis procedures on sickle cell patients

Name of idea submitter and other team members who worked on this idea : Bruce Sachais on behalf of ASFA

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Strategic Goal: Goal 3: Advance Translational Research

Allogeneic transplantation as a safe and universally available therapeutic strategy for treating non-malignant blood diseases

Can new advances in allogeneic blood or marrow transplantation (BMT) make the procedure a safe and universally available therapeutic strategy for treating non-malignant blood and immune disorders such as sickle cell anemia, thalassemia, aplastic anemia, and severe combined immune deficiency?

Submitted by (@rjjones)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

The ability of allogeneic blood or marrow transplantation (BMT) to cure diverse non-malignant diseases is well-documented. However, widespread use in diseases such as sickle cell anemia that cause substantial morbidity and shorten life but are not immediately life-threatening, has been limited by transplant-related toxicity and mortality especially in the majority of these patients who lack HLA-matched donors. Several new therapeutic approaches now exist that are promising strategies, separately or in combination, for addressing issues of donor availability, graft rejection, organ toxicity and acute and chronic graft-versus-host disease more effectively. Evaluation and refinement of these therapeutic strategies in both preclinical and Phase I-III clinical trials now offers a real possibility that allogeneic BMT could be applied early in the course of these diseases, allowing normal growth, development, quality of life and lifespan. If successful, allogeneic BMT offers a major advantage over gene therapy approaches even if such approaches become possible in the future; i.e., allogeneic BMT can be done with low-dose, non-toxic conditioning while gene therapy requires high-dose myeloablative therapy which not only can be toxic/fatal to these patients who often have end-organ dysfunction but also universally induces infertility, a major concern of patient groups who usually survive beyond child-bearing years.

Feasibility and challenges of addressing this CQ or CC :

There are now single institution and registry (CIBMTR) data showing that related haploidentical allogeneic BMT using post-transplantation cyclophosphamide (PTCy) produces results similar to those seen with HLA-matched sibling donors. Accordingly, every patient in need of allogeneic BMT now can safely undergo the procedure, including those ethnic groups (such as African-Americans and Hispanics) who are unlikely to find a donor in unrelated registries. Combining PTCy with other approaches for preventing graft-versus-host disease (GVHD) can even eliminate GVHD and transplant-related mortality. Although recurrence of malignant diseases remains an issue, especially as GVHD is eliminated, relapse is not a concern for non-malignant diseases after successful allogeneic engraftment. Moreover, the average cost of allogeneic BMT, about $150K, is a cost-savings over the long-term management of many of these diseases. The NHLBI-funded BMT Clinical Trials Network (CTN) has developed the infrastructure to rapidly and efficiently carry out large multi-institutional BMT trials. Over the last 15 year, thousands of patients have been entered on BMT CTN trials. Of note, African-Americans and Hispanics remarkably represent 30% of the accruals on one such trial, CTN1101, studying unrelated umbilical cord and related haploidentical allogeneic BMT. However, funding for the infrastructure for continuing this work remains problematic, since BMT trials generally lack corporate funding.

Name of idea submitter and other team members who worked on this idea : Rick Jones

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Strategic Goal: Goal 2: Reduce Human Disease

Pulmonary Complications of Sickle Cell Disease

What are the risk factors and components of clinical course associated with progression to restrictive lung disease, and what approaches to treatment can limit this progression?

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

RLD is a major risk factor for death in adults, but there is minimal knowledge of the sequelae of contributing factors. There is no longitudinal study to demonstrate the risk factors, determinants, biological. A cross sectional study of adults could determine prevalence of lung function abnormalities, obstructive and restrictive, using standardized testing and understand the factors associated with the presence of these abnormalities. This study could be associated with a clinical trial of treatment of RLD with outcomes of symptom reduction as well as improvement of the restriction.

Name of idea submitter and other team members who worked on this idea : ATS Member

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