Health Outcomes After Curative Therapies

For many clinical studies the goal is to understand what immediate effects a treatment has on the disease or condition being studied. In this study we want understand the late effects of a treatment on various health outcomes. As described in different sections of this website, sickle cell disease has negative effects on multiple organ systems. Understanding long term effects of curtaive therapy in persons with different levels of sickle cell disease severtiy will be critical to helping individuals make informed decisions for their healthcare.

Heart health after curative therapy for sickle cell disease

There is little data on whether curative therapy for sickle cell disease leads to improvement of heart disease. We do know that specifically an elevated tricuspid regurgitant jet velocity (TRJV) can be a predictor of higher risk of death in adults, and an elevated TRJV is one of the indications to consider curative therapy for a person with sickle cell disease. There is some information to support that adults who had an elevated TRJV prior to a HSCT did have improvement in their TRJV one year after their transplant. A small group of people also had improvement in their TRJV three years after transplant (1). This suggests that the benefits of a transplant on heart function may be sustained. There is even less information about heart disease in children with sickle cell disease that undergo transplant. There is some information to suggest that children who receive HSCT do not go on to get pulmonary hypertension (2). Some children may have improvement in their blood pressure, but others may have worsening of blood pressure (3). Furthermore, medicines used for HSCT and medicines used to prevent complications after curative therapy can also lead to higher blood pressure.

By collecting information on participants’ heart function before and after curative therapy, we will be able to gain a better understanding about how various curative treatment methods affect heart disease in patients with sickle cell disease. We will also be able to follow these participants over time to see how their heart function changes with time.

Lung health after curative therapy for sickle cell disease

There is little information about how lung function is affected after curative therapy for sickle cell disease. We do know that lung disease can start at a young age, and specifically a low forced expiratory volume (FEV1) can be associated with increased risk of death. There are some data to support that the FEV1 does not change much after a myeloablative haploidentical HSCT (4). Some children may have stable to improved lung function after HSCT (5). However, medicines used for curative therapy can themselves also lead to lung complications not necessarily related to sickle cell disease.

Through the COALESCE study, we will be able to assess the incidence of kidney function in adults and children who have received curative treatment for sickle cell disease. We will hopefully be able to understand more about how these treatments affect kidney function over time.

Kidney health after curative therapy for sickle cell disease

There is not much information about how kidney function changes after curative therapy, particularly in adults. We do know that chronic kidney disease is common among people with sickle cell disease, and this is a risk factor for early death. Some children may have improvement in their kidney function after HSCT that may even approach normal levels (6). The hyperfiltration that is seen as early signs of kidney disease in children may also be improved after treatment (7). On the other hand, some people may have worsening kidney disease after curative therapy. Some of the medicines used during a transplant may also affect kidney function long turn, unrelated to underlying sickle cell disease.

Through the COALESCE study, we will be able to assess the incidence of kidney function in adults and children who have received curative treatment for sickle cell disease. We will hopefully be able to understand more about how these treatments affect kidney function over time.

Reproductive health after curative therapy for sickle cell disease

Sickle cell disease can affect many aspects of the reproductive system including: fertility, erectile dysfunction, gonadal failure, and menstrual issues. We however, do not have a lot of information on how curative therapies affect the reproductive system in people with sickle cell disease. Furthermore, certain curative treatments, such as hematopoietic stem cell transplant, can lead to risk of long-term infertility endocrine dysfunction.

Pain after curative therapy for sickle cell disease

The burden of pain varies for patients with sickle cell disease, and this holds true after curative therapy as well. While acute episodes of pain secondary to sickling cells may improve after curative therapy, and many people are able to be weaned off opioids, chronic pain may persist. Certain risk factors such as older age, higher pain burden pre treatment, and more symptoms of anxiety may be associated with more persistent pain after transplant (8). The complexity of the biology of pain in people with sickle cell disease definitely plays a role in the continued pain that some people experience after transplant.

Through participant surveys that we will gather in the COALESCE study, we will hopefully be able to understand how people experience pain before and after curative therapy.

References

  1. Sachdev V, Hsieh M, Jeffries N, et al. Reversal of a rheologic cardiomyopathy following hematopoietic stem cell transplantation for sickle cell disease. Blood Adv. Oct 8 2019;3(19):2816-2824. https://doi.org/10.1182/bloodadvances.2019000387

  2. Bhatia M, Jin Z, Baker C, et al. Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease. Bone Marrow Transplant. Jul 2014;49(7):913-20. https://doi.org/10.1038/bmt.2014.84

  3. Stenger E KK, Ross D, et al. Increased Proportion of Sickle Cell Disease Patients Develop Cardiovascular Disease Risk Factors Following Successful Hematopoietic Cell Transplantation. Blood 12/07/2017 2017:130. https://ashpublications.org/blood/article/130/Supplement%201/1999/71260/Increased-Proportion-of-Sickle-Cell-Disease

  4. Walters MC, Hardy K, Edwards S, et al. Pulmonary, gonadal, and central nervous system status after bone marrow transplantation for sickle cell disease. Biol Blood Marrow Transplant. Feb 2010;16(2):263-72. https://doi.org/10.1016/j.bbmt.2009.10.005

  5. Friedman D, Dozor AJ, Milner J, et al. Stable to improved cardiac and pulmonary function in children with high-risk sickle cell disease following haploidentical stem cell transplantation. Bone Marrow Transplant. Sep 2021;56(9):2221-2230. https://doi.org/10.1038/s41409-021-01298-7

  6. Matthes-Martin S, Lawitschka A, Fritsch G, et al. Stem cell transplantation after reduced-intensity conditioning for sickle cell disease. Eur J Haematol. Apr 2013;90(4):308-12. https://doi.org/10.1111/ejh.12082

  7. Pedersen SJV, Monagel DA, Mammen C, Lewis VA, Guilcher GMT, Bruce AA. Stable renal function in children and adolescents with sickle cell disease after nonmyeloablative hematopoietic stem cell transplantation. Pediatr Blood Cancer. Sep 2020;67(9):e28568. https://doi.org/10.1002/pbc.28568

  8. Darbari DS, Liljencrantz J, Ikechi A, et al. Pain and opioid use after reversal of sickle cell disease following HLA-matched sibling haematopoietic stem cell transplant. Br J Haematol. Feb 2019;184(4):690-693. https://doi.org/10.1111/bjh.15169