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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164 net votes
214 up votes
50 down votes
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Goal 2: Reduce Human Disease

Pulmonary Complications of Sickle Cell Disease - Contribution of Airways Disease

What is the contribution of airways disease to acute and chronic pulmonary distress?

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 :

What is known about this topic:

 

1) Pulmonary function testing is abnormal in 80-90% of kids and 90% of adults with SCD.

 

2) SCD kids with asthma have a higher frequency of ACS and those with a history of ACS have a higher prevalence of asthma.

 

3) An elevated TRV in SCD kids and adolescents may not predict mortality but does predict reduced exercise capacity at 22 months which may be irrespective of pulmonary hypertension

 

4) Dyspnea is extremely common in adults with SCD; 50% of HbSS and 40% of HbSC adults report at least mild dyspnea on exertion. The mechanisms responsible for this are unknown.

 

5) Bronchodilators are often used to treat patients with ACS, yet their benefit is unclear.

 

6) Systemic steroids will increase the rate of rebound pain if used during a vasoocclusive crisis.

 

7) Asthma in SCD is frequently under-treated because of fears associated with systemic and even inhaled corticosteroid use.

Feasibility and challenges of addressing this CQ or CC :

Areas of Controversy:

1) Is there an inter-relationship between airway and vascular disease in SCD?

 

2) Are systemic corticosteroids safe in SCD? Are they indicated in treatment of ACS? Are they indicated for treatment of asthma exacerbations?

 

3) Are inhaled corticosteroids useful in treating or preventing ACS?

 

4) What are the mechanisms responsible for the decline in exercise capacity observed as SCD patients go from late adolescence to early adulthood?

 

5) Will more aggressive treatment of asthma prevent this decline?

 

6) What role does nocturnal hypoxemia and OSA play in disease modulation of SCD?

 

7) What are the mechanisms of the restrictive physiology observed by PFTs primarily in adults?

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

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3 net votes
3 up votes
0 down votes
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Goal 4: Develop Workforce and Resources

Sickle cell education for healthcare providers

Although sickle cell was first described more than 100 years ago and more than 100,000 individuals in the US are living with sickle cell disease, healthcare providers still lack basic knowledge of the key components in providing care for individuals with sickle cell. This often leads to poor health outcomes including stigmatization of patients with sickle cell seeking care. Evidenced-based curriculum should be available ...more »

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.

Voting

18 net votes
21 up votes
3 down votes
Active

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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32 net votes
41 up votes
9 down votes
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Goal 3: Advance Translational Research

Dissemination & Implementation of new treatments and therapies in sickle cell disease

Are current advances in gene editing, new drug therapies and less restrictive BMT criteria being explained and rolled out to the sickle cell community in an effective and timely manner? When can people living with sickle cell disease experience a better quality of life on more permanent based on the treatments we already have?

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 :

Bone marrow transplant criteria has become less restrictive yet there has not been a steep increase in procedures. My understanding is that a sibling or child with the trait can be a donor. At some point this treatment needs to become more widely accessible and discussed with all patients by their doctors.

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

Voting

46 net votes
55 up votes
9 down votes
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Goal 3: Advance Translational Research

Implementation Science to Improve Care in Sickle Cell Disease

There are approximately 100,000 individuals living with sickle cell disease in the US, however study after study has shown that many lack access to the few existing evidence based interventions such as hydroxyurea. We need to investigate novel ways to increase acess to hematology care and disease modifying therapies.

Submitted by (@amy.sobota)

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

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12 net votes
14 up votes
2 down votes
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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

Voting

38 net votes
46 up votes
8 down votes
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Goal 2: Reduce Human Disease

Identifying Epistatic Genes in Sickle Cell Disease

What genes are involved in the modulation of phenotype in sickle cell disease?

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 :

The pathophysiology of sickle cell disease results from cellular defects caused directly by the Hb S mutation interacting with the environment and many other gene products—some known, but most yet unidentified–a typical example of epistasis. How normal tissue perfusion is interrupted is complex and why the phenotype of sickle cell disease differs from patient to patient is poorly understood. Answers to this question will provide additional insight into their biological and functional relationships.

Feasibility and challenges of addressing this CQ or CC :

Scientific advances make it feasible to identify additional epistatic genes, which will provide additional insight into their biological and functional relationships.

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

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6 net votes
6 up votes
0 down votes
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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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1 net vote
2 up votes
1 down votes
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Goal 3: Advance Translational Research

Sickle cell disease and fatigue

What factors, other than hemoglobin count, are involved in the extreme fatigue experienced by individuals 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 :

Many in the sickle cell community report continuous fatigue that interrupts their daily activities in spite of normal, or above baseline, hemoglobin levels

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

Voting

17 net votes
29 up votes
12 down votes
Active

Goal 2: Reduce Human Disease

Sickle Cell anemia and Aplastic anemia survivors: Late effects and quality of life issues in Stem Cell Transplant Survivors

Most of the patients suffering from non-malignant hematologic conditions are cured of the original disease with Hematopoitec Stem Cell Transplant (HSCT) but still their survival is less compared to age matched general population, and additionally they suffer from unique complications of HSCT culminating into a variety of late physical, psychologic, financial, and social complications (“late effects”). Considerable improvements ...more »

Submitted by (@hashmi.shahrukh)

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

Details on the impact of addressing this CQ or CC :

One million HSCT mile stone was recently reached and the utilization of HSCTs continues to increase. For many non-malignant hematologic conditions particularly sickle cell anemia and bone marrow failure syndromes, HSCT is the only potentially curative option. Most HSCT survivors are living beyond a year, but can suffer from devastating complications of HSCT which include graft-versus-host-disease, second cancers, diabetes, infertility, congestive heart failure, blindness, and bronchiolitis obliterans, besides many others which lead to increased overall HSCT related disease burden. A lot of efforts are currently being put in cancer survivorship by the ACS, NCI, ASCO and other societies, but very little emphasis is being laid on sickle cell or aplastic anemia survivors. This area of HSCT survivorship becomes more important from health disparities perspective too, since majority of the hemoglobinopathy HSCTs performed in the US are in racial minorities. Comparative effectiveness research (CER) in HSCT survivorship is essential to delineate the overall disease burden this population and understand the risks and outcomes of HSCT late effects. To compare the effectiveness of survivorship programs and research, especially for those survivors who are at risk of health disparities is a top priority of the Institute of Medicine CER 2009 initiative.

Feasibility and challenges of addressing this CQ or CC :

Majority of the HSCT survivors of benign hematologic conditions are now living beyond 2 years post-HSCT. Blood and Marrow Transplant (BMT) Clinical Trials Network (CTN) was established in 2001 to conduct large Multi-Institutional clinical trials and is funded by the NHLBI. Since the infrastructure is in place to conduct studies related to all aspects of HSCT, this would be an area to explore first from feasibility perspective since thousands of patients have already been successfully enrolled through the BMT-CTN studies. From NHLBI strategic perspective, this would place CTN (and Emmes Corporation) in an excellent unique position of addressing CER for survivorship issues and health disparities within one study, since the population understudy would mainly be consistent of racial minorities – with the overall goal of improving the long term health, preventing late effects, improving quality of life, and reduce the overall health burden (DALYs and societal costs) of thousands of HSCT survivors in the US and globally.

Name of idea submitter and other team members who worked on this idea : Shahrukh Hashmi

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71 net votes
89 up votes
18 down votes
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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.

Voting

18 net votes
20 up votes
2 down votes
Active