The advancements and challenges in hematology, from the pioneering work in bone marrow transplants to the development of targeted therapeutics, have transformed the treatment of blood diseases but also present new obstacles such as access to care, cost, and survivorship. Over 50 years ago, the first successful, conditioned, allogeneic bone marrow transplant (BMT) in a human offered hope for patients suffering from blood diseases. E. Donnall Thomas received the Nobel Prize in Medicine in 1990 for his pioneering work in BMT. I started my hematology fellowship training shortly after he received this prize. In the 1990s, virtually all BMT conditioning was myeloablative, donors were HLA matched, the patient age limit was roughly 40 years, and the cost was more than $400,000. Less than 20% of patients in need of BMT were eligible, and over 20% of adults experienced transplant-related mortality, with more than 50% of survivors suffering from acute and/or chronic graft-versus-host disease (GVHD).
Underrepresented minorities were often excluded due to inadequate access to care, lack of insurance, and difficulty finding matched unrelated donors in transplant registries. Today, better typing and supportive care, including post-transplant cyclophosphamide, have made BMT safer and more widely available. Virtually everyone can find suitable donors now that outcomes with HLA-haploidentical donors are equal to those with HLA-matched sibling donors. Transplant-related mortality is less than 5%, the risk of grade 3 or higher GVHD is less than 10%, and the cost of BMT is less than $200,000.
Simultaneously, advances in genetics, molecular biology, and immunology have led to targeted therapeutics that have the potential to cure or significantly extend life expectancy for many hematologic diseases. In fact, these new drugs have been so effective that indications for bone marrow transplant (BMT) in hematologic malignancies are decreasing. For instance, tyrosine kinase inhibitors have become tantamount to a cure for most chronic myeloid leukemia patients, making BMT rare. Monoclonal antibodies, bispecific T-cell engagers, Bruton-tyrosine kinase inhibitors, CAR T cells, and immune checkpoint inhibitors have decreased the need for BMT in pediatric and young adult ALL, relapsed aggressive B-cell lymphoma, Hodgkin lymphoma, and even multiple myeloma. In contrast, we have seen an expansion of BMT indications for classical hematologic conditions. The cure rate of BMT for severe aplastic anemia, including with HLA-haploidentical donors, is over 90%, with minimal risk of GVHD and a lower cost than immunosuppressive therapy. Similarly, BMT cure rates for hemoglobinopathies are now 90%, even with haploidentical donors. Potential cures are also being reported with gene therapy and genome editing approaches, although at a higher cost than BMT. Future indications for allogeneic BMT include severe autoimmune diseases (such as lupus and systemic sclerosis) and even solid organ transplantation (such as bone marrow/kidney) to prevent rejection and eliminate the need for long-term immunosuppressive therapy.
Such monumental progress brings new challenges, including how to finance these expensive therapies, train enough hematologists to meet the needs of a rapidly growing population, and shift the focus to survivorship. Additionally, it is crucial to ensure that all patients have equal access to care and that clinical trials enroll patient populations that are representative of our diverse society. The American Society of Hematology (ASH) and its members are working to address these challenges through advocacy, research, and education. ASH continues to lead advocacy efforts with Congress and federal agencies to address issues affecting hematology research and practice, including research and public health funding, access to quality care for patients, physician payment, and coverage for hematologists. ASH’s advocacy efforts have resulted in federal funding through the Centers for Disease Control and Prevention to gather data on the incidence and prevalence of sickle cell disease, which aims to focus resources and programs. To further advance research and improve patient outcomes, the Society has invested over $30 million to establish a research data hub and clinical trials network (through the ASH Research Collaborative), with a focus on sickle cell anemia and multiple myeloma. ASH commits roughly $14 million annually to support career development of trainees, fellows, and junior faculty pursuing clinical, translational, and basic research in hematology and initiated a multi-year, $19 million program to increase the number of hematology fellowship slots, thereby growing the next generation of hematology fellows. To address disparities in access to care and underrepresentation in clinical trials, ASH has a long-standing commitment to diversity, equity, and inclusion, including the establishment of a robust Minority Recruitment Initiative – now in its 20th year. Although challenges remain, the progress made in hematology in recent years is remarkable, and the opportunity to address these challenges is a privilege we must embrace.