Thalassemias are a group of inherited disorders that result in an imbalance in the usual ratio between alpha and beta globin chain synthesis. As a result, hemoglobin cannot be produced in normal amounts, resulting in anemia and smaller than normal red blood cells (microcytosis). Alpha thalassemias result when alpha globin genes are affected and may manifest in the intrauterine period, immediately postnatal, in childhood with moderate anemia, or at any time with mild anemia. Beta thalassemias result when beta globin genes are affected, and manifest with severe anemia in infancy requiring regular transfusions for survival (thalassemia major), moderate anemia later in life which may not be transfusion-dependent (thalassemia intermedia), or a mild microcytic anemia without significant clinical manifestation (thalassemia minor or thalassemia trait). On occasion co-inheritance of alpha gene deletions, mutations or triplications occur in combination with beta thalassemia and can result in modifying the degree of anemia. In general, thalassemias where other genes are affected (such as delta or gamma), are not usually severe.
Transfusion-dependent individuals require red cell transfusions every two to four weeks, and may develop complications related to these transfusions including allergic or hemolytic reactions, alloimmunization (antibody development), and iron overload. Iron deposition in the heart and endocrine organs may contribute greatly to heart failure, arrhythmias, growth retardation or failure, delayed puberty, bone disease and diabetes. The majority of deaths result from heart failure or cardiac arrhythmias, but iron overload can be prevented or treated using chelation therapy. Therefore, the management of thalassemia major and intermedia is complex and lifelong, requiring intensive treatment and close monitoring. Thalassemia major and intermedia are rare disorders, with an estimated 2,000 individuals affected in the U.S. The care of most of these individuals occurs in the setting of a thalassemia center, with experienced hematologists and a team of other specialists, practitioners, geneticists, social workers and coordinators.
With the advent of an effective iron chelation program, and the addition of oral chelators to our treatment regimens, we have been able to treat iron overload and prevent its complications to a large extent. Non-invasive tissue iron measurements have vastly improved our ability to monitor iron burden closely and accurately, and individually tailor chelation regimens based on the results. Stem cell transplantation is one of our primary curative therapies, and has been fine-tuned to achieve excellent results when the donor is a matched sibling. Gene therapy is another promising option, with curative intent and a much wider application; however, it remains in the investigational phase.
Patients who are not able to avail of curative treatment must continue to receive specialty care, regular transfusions and chelation, including regular screening for and monitoring of complications. Given the frequency of transfusions (between two and four weeks for most patients), we see patients regularly and are able to reinforce compliance, and perform the necessary screening, testing and referral to specialists for management of complications. This model of comprehensive care has vastly improved patient quality of life, as well as reduced mortality and morbidity.
Continued improvement in outcomes depends on the provision of this care by a multidisciplinary team comprised of physicians who:
- understand the nature of the underlying condition
- are able to closely follow patients
- screen and monitor for complications
- prevent complications as far as possible
- address other concerns including transition to adult providers and psychosocial counseling