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Since the Sickle Cell Anemia Act, steady progress has been made in the screening and treatment of sickle cell disease. Despite the development of new medical therapies, sickle cell disease remains an incurable condition for most affected individuals. Hematopoietic stem cell transplantation represents the only currently available curative option for individuals living with sickle cell disease. Hematopoietic stem cell transplantation may be autologous, requiring genetic modification of the patient's stem cells to correct the genetic mutation characteristic of sickle cell disease, or allogeneic, involving replacement of the defective stem cells with healthy stem cells from a suitable donor. Although HSCT is curative for most patients, the procedure is associated with significant toxicities and occasionally fatal complications. Care must be exercised when selecting patients for HSCT. This activity reviews the therapeutic role of HSCT in sickle cell disease and highlights the role of the interprofessional team in caring for patients who undergo the procedure. Objectives: Identify patients with sickle cell disease who may be candidates for hematopoietic stem cell transplantation based on their clinical history. Assess and manage the complications of hematopoietic stem cell transplantation in sickle cell disease. Effectively counsel patients with sickle cell disease and their caregivers about the risks and benefits of hematopoietic stem cell transplantation. Develop and implement interprofessional team strategies to improve outcomes for patients with sickle cell disease undergoing hematopoietic stem cell transplantation. Access free multiple choice questions on this topic.

Sickle cell disease (SCD) is the most common hemoglobinopathy in the United States. SCD affects about 100,000 Americans, mostly of African descent.[1] Approximately 20 million individuals worldwide are affected by SCD. The molecular basis of SCD was poorly understood when the disease was first described in the early 1900s. It was not until 1949 when Dr. Linus Pauling carried out a landmark study, that it was determined that this condition is caused by abnormal hemoglobin that sickles when exposed to a low-oxygen environment. The abnormal form of hemoglobin in SCD arises from a single amino acid mutation in the beta-globin gene called hemoglobin S.[2] Because SCD is an autosomal recessive disorder, both beta-globin genes must be mutated for an individual to develop overt disease. When only a single copy of the gene is mutated, the resulting phenotype is termed sickle cell trait. Sickle cell trait is usually benign, but affected persons may develop sickled cells when exposed to exceptionally low pressures of oxygen. Since 1949, scientists have made steady progress in understanding the complex molecular pathology of SCD. However, until about two decades ago, no known cure for this genetic disorder existed. According to Dr. Mary T. Basset, a physician during the American civil rights movement, SCD research, screening, and treatment received little to no funding and was neglected because patients were primarily of African descent.[3] One of the significant achievements of the civil rights movement in the 1970s was the establishment of the Sickle Cell Disease Association of America and the creation of the Sickle Cell Anemia Act of 1972. Since then, there has been greater public awareness of SCD and incrementally more funding towards finding a cure, culminating in the first bone marrow stem cell transplant for SCD.

Since 1949, scientists have made steady progress in understanding the complex molecular pathology of SCD. However, until about two decades ago, no known cure for this genetic disorder existed. According to Dr. Mary T. Basset, a physician during the American civil rights movement, SCD research, screening, and treatment received little to no funding and was neglected because patients were primarily of African descent.[3] One of the significant achievements of the civil rights movement in the 1970s was the establishment of the Sickle Cell Disease Association of America and the creation of the Sickle Cell Anemia Act of 1972. Since then, there has been greater public awareness of SCD and incrementally more funding towards finding a cure, culminating in the first bone marrow stem cell transplant for SCD. The Sickle Cell Anemia Act also improved screening processes for SCD. Today, in most parts of the United States, sickle cell screening is performed before discharging neonates from the hospital. This screening allows for early medical intervention and reduces morbidity and mortality from SCD. Treatment of SCD has improved, incorporating penicillin prophylaxis for children younger than 5, hydroxyurea to boost fetal hemoglobin levels, prophylactic blood transfusions, and pain medications, including opioids. Unfortunately, most of these treatments are palliative, and patients continue to experience poor quality of life because of recurrent pain episodes, end-organ damage, and a reduced life expectancy, underscoring the importance of seeking a cure for this condition. In September 2018, the National Heart, Lung, and Blood Institute (NHLBI) launched the Cure Sickle Cell Initiative. Under this initiative, efforts are being made to develop new genetic approaches to cure SCD.[4][5] Advancement in gene therapy techniques has shown promising results in preclinical and clinical trials, but formal approval by the United States Food and Drug Administration (FDA) is still awaited.[2][3][6][7]

Since the first HSCT was performed in 1984, over 1200 cases have been described. Complications arising from transplantation can be grouped into medical complications from the conditioning regimen, the transplantation itself, the immunosuppressive therapy used after transplantation, or financial toxicity. Conditioning regimens are highly toxic and can be associated with short-term organ injury and long-term effects such as infertility and secondary malignancies.[24][25] Transplantation itself is associated with a high risk of morbidity and mortality, especially if there is a mismatch. HSCT is safest when a matched donor is available, but unfortunately, only a few transplant candidates have such donors. Even with a suitable donor, there is still a 9% risk of graft rejection and a 15% risk of chronic GVHD.[15] The immunosuppressive therapy needed to suppress GVHD predisposes patients to opportunistic infections, which can occasionally be fatal. Nonhealing leg wounds in some patients compound the risk of infection, although this is not necessarily a barrier to HSCT.[26] Finally, significant financial costs associated with HSCT can be burdensome, especially for patients from socioeconomically disadvantaged backgrounds.[27] The potential for one or more of these complications should be carefully considered when evaluating an individual with SCD for HSCT. The patient and their caregivers should be educated about these complications to make an informed decision. Moreover, with appropriate counseling, the patient and their caregivers are better prepared to deal with complications, ultimately improving outcomes. Mitigation strategies for these complications vary depending on the circumstances. Complications in the immediate period during and after transplantation, such as infections, organ injury from the conditioning regimen, and acute GVHD, are usually managed by the transplant team with protocols similar to those used in patients receiving HSCT for other indications. However, more long-term complications, such as late secondary malignancies, are often managed with close screening, the burden of which is shared between the transplant team and other health professionals. Infertility should be managed preemptively with counseling regarding fertility preservation options before the transplantation procedure.

Sickle cell disease is a complex disorder affecting multiple organ systems that requires care coordination among various teams of healthcare professionals to ensure optimal outcomes. HSCT is a highly specialized field requiring a team of trained physicians, nurses, pharmacists, stem cell technicians, and other services such as infectious disease and intensive care teams. Close coordination among these teams is critical for successful outcomes; HSCT procedures are only performed at tertiary care centers with adequate experience and infrastructure. However, optimizing these outcomes requires extending this effort beyond the transplant center to pediatric and adult hematologists working in the community so that affected individuals are referred at the appropriate time for evaluation for HSCT. Creating awareness of this therapeutic option among hematologists caring for individuals living with SCD is critical. Expanding access to HSCT and continuing research into improving the safety and efficacy of HSCT in patients with SCD represent the measures most likely to improve patient safety and outcomes.