40 Years of Advances in Hematology by Karyn Brundige
Many of us are aware that the outcomes for children with cancer have improved significantly in the past 40 years, not just in overall survival but in decreased toxicity due to the evolution of targeted and tailored therapies. But what about children with hematology disorders, whether acute or chronic, “benign” or even life-threatening conditions? I’m amazed at the treatment options available for my hematology patients today that didn’t exist 25 years ago when I started as a new graduate nurse. Take a quick journey with me to celebrate some of the advances!
Did you know that in the 1970s the average lifespan for children with sickle cell disease was only 14 years? The goal of the first sickle cell trial was simple: prevent children from dying of infection. The Prophylactic Penicillin Study (PROPS) conducted in the mid-1980s randomized assignment between penicillin twice daily and a placebo, vitamin C. The study closed early due to an 84% reduction in S. pneumoniae infections and no fatalities in the group taking penicillin prophylaxis! I remember this study – and the children I’ve cared for who have died from sepsis – when I remind families with young children who have sickle cell disease about why adherence to daily penicillin is so crucial. Other amazing milestones of the 1990s included the use of transcranial screening (TCD) to identify patients at risk for stroke who would benefit from prophylactic blood transfusion, approval of hydroxyurea to decrease complications of sickle cell disease by stimulating the body to produce fetal hemoglobin (HgbF), and a multi-center study of bone marrow transplantation that demonstrated children with sickle cell disease could be cured if they received a transplant from an unaffected matched sibling. Very recently we heard the news of gene therapy being used to cure a French teenager with sickle cell disease!
In the early 1970s, deferoxamine (Desferal) began to be used more widely in children with thalassemia to decrease the iron toxicity caused by frequent blood transfusion. Amazing as this treatment was, the daily subcutaneous infusions proved challenging for many patients. I will never forget caring for a teenage girl who developed debilitating cardiomyopathy secondary to iron overload and eventually died from multi-organ failure. The emergence of a new generation of oral chelation therapy, including deferasirox (Exjade/Jadenu) and deferiprone (Ferriprox), has resulted in both better control of iron overload as well as improved adherence by simplifying the home chelation regimen for patients requiring chronic transfusion. The wider availability of magnetic resonance imaging to measure cardiac and hepatic iron overload provides a more precise and less invasive method of evaluation and has led to earlier initiation of chelation therapy prior to patients’ developing iron-related organ damage.
When I consent patients for blood transfusion, I remember my patients with hemophilia. First, there were those who died from HIV, and then there were those who died because of chronic hepatitis infections contracted from contaminated blood products. Advances in transfusion medicine have improved the lives of all children with hematological disorders, from better screening methods to reduce the risk of infection, to computerized provider order entry to increase patient safety.
Hemophilia care has undergone many other substantial improvements in the past 40 years. Families first started “self-administering” clotting factor concentrates at home in the 1970s. In the past two decades the development of recombinant concentrates has greatly improved the safety and availability of therapy. Treatment now focuses on prophylaxis and prevention of long term side effects of the disease, allowing children with hemophilia to lead healthy, active lives. Other recent advances in hemophilia care include better methods to measure and eliminate inhibitor antibodies as well as curative gene therapy trials.
Recombinant technologies have also benefitted my patients with inherited and chronic cytopenias. In the early 1990s I was a primary nurse for an engaging and energetic teenage boy with severe chronic neutropenia who had his leg amputated as toddler due to a severe infection. Today my patients with congenital neutropenia can receive subcutaneous injections of recombinant human granulocyte colony stimulating factor (G-CSF) to maintain their neutrophil count in a safe range. In a similar success story, epoetin alfa (Epogen) has become one of the most widely used drugs created through recombinant DNA technology, minimizing the need for blood transfusion to treat anemia in children with chronic kidney disease, AIDS and myelodysplastic syndrome. And for the 20% of children with Idiopathic thrombocytopenic purpura (ITP) who develop chronic disease, eltrombopag (Promacta) is now available. This oral thrombopoietin receptor agonist was FDA-approved in 2016 for children one year and older with chronic ITP, decreasing the need for corticosteroids or splenectomy to manage their disease.
Did you know that aplastic anemia was often fatal prior to the 1990s when immunosuppressive therapy with anti-thymocyte globulin (ATG) and cyclosporine became the standard of care? An astounding array of genetic panels is now available to diagnose patients with inherited bone marrow failure syndromes, as well as screen sibling donors if transplantation is required. We’ve also learned that bone marrow – not peripheral blood – is the preferred stem cell source for these patients to decrease chronic graft versus host disease and that nonmyeloablative, reduced intensity conditioning regimens improve survival and decrease late treatment-related toxicity. And due to the improved outcome of unrelated donor transplantation, studies are now comparing immunosuppressive therapy to unrelated donor transplant in patients with newly diagnosed aplastic anemia.
Finally, there have also been significant advances in anticoagulation therapy for venous thrombosis. Low molecular weight heparin is now used to both prevent and treatment thromboembolic disorders in children and teenagers. The majority of patients no longer need to be hospitalized and can receive therapy entirely as outpatients! New oral anticoagulants, recently approved for adults, are also being tested in children; they can be administered at fixed daily doses and do not require routine laboratory monitoring.
The care of children with hematologic disorders has changed significantly in the past 40 years. I’m excited to watch for the next new therapy or technology that simplifies treatment, improves outcomes and increases quality of life for our patients and their families.#Blog #Advances #Hematology