Medication, Transplants Key in Treating Immune Aplastic Anemia

Immunosuppressive therapy and transplant strategies are critical in the management of immune aplastic anemia (AA), a hematologist told colleagues during a recent Association of VA Hematology/Oncology (AVAHO) webinar on rare and ultrarare blood disorders. But the first major challenge is diagnosis, said Emma M. Groarke, MD, of the National Heart, Lung, and Blood Institute at the National Institutes of Health.

According to Groarke, patients with bone marrow failure—a large category that includes AA—typically present with bone marrow hypocellularity (abnormally few cells) and reticulocytopenia (abnormally few immature blood cells). But these conditions also may be the result of other disorders, such as malignant cancer, medication-induced cytopenias, vitamin deficiencies, infection, or advanced liver disease.

After diagnosing a patient with bone marrow hypocellularity, clinicians need to consider whether the underlying etiology is immune or inherited, she said. Radiation can also cause AA, but that is not common outside chemotherapy.

“In younger patients, you have a higher threshold of suspicion for an inherited or germline disorder,” she said. “Whereas in older patients, it's more likely to be acquired or immune-mediated. It’s really important to differentiate these because the treatments are very different depending on whether this is immune-mediated versus genetic.”

Treatment Options: Transplant

Everyone diagnosed with severe AA should be seen by a transplant specialist and have human leukocyte antigens typing and donors identified “because things can change very quickly,” Groarke said. However, hematopoietic stem cell transplant isn’t for everyone. While it is often offered to patients aged < 40 years with a matched sibling donor, older adults typically take medication instead because of the higher transplant-related mortality risk.

“It’s really individualized for patients,” Groarke explained. Patients aged ≥ 40 years with profound neutropenia may be good candidates for transplantation despite their age. Younger patients with less severe disease may not require immediate transplant, she said.

Treatment Options: Medication

Groarke, who coauthored a 2023 American Society of Hematology report on inherited bone marrow failure in adults, said that horse antithymocyte globulin (ATG) and cyclosporin have been “the mainstay” of treatment for older adults with immune AA based on a 1995 Blood study. Response rates were 67% by 3 months and 70% to 80% by 1 year.

Researchers tried for years to boost responses but failed until the rise of a combination therapy that includes ATG, cyclosporin, and eltrombopag. This combination therapy has become the standard of care.

There have been questions about using ATG in patients aged > 60 years. Groarke said research supports the medication in this population. “They seem to respond equally well as younger patients,” she said.

While older patients do have more cardiac complications, Groarke said her clinic still administers ATG to them. However, “the one history that gives us some pause is a significant cardiac history.”

Disclosures for Groarke were not provided.