Genetic variations in underlying lymphoma influence AIHA types
Study details cases of 2 patients, a man with CAD and a woman with WAIHA
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A man and a woman in China were found to have a type of fast-growing blood cancer called diffuse large B-cell lymphoma (DLBCL) as the underlying cause of their autoimmune hemolytic anemia (AIHA), a group of disorders in which the immune system attacks and destroys red blood cells, according to a study.
B-cell lymphomas are cancers that affect B-cells, the white blood cells responsible for producing antibodies, including those that can drive AIHA.
Different genetic alterations in the two patients’ lymphomas were linked to distinct types of AIHA — cold agglutinin disease (CAD) in the man and warm AIHA (WAIHA) in the woman — and different responses to therapy, suggesting that the cancer’s genetic makeup may influence how the disease develops and how patients respond to treatment.
“[AIHA]-associated diffuse large B cell lymphoma is rare,” researchers wrote. “This report highlights two novel cases demonstrating subtype-specific molecular drivers and treatment outcomes, underscoring the necessity for precision management.”
The study, “Cold versus warm autoimmune hemolytic anemia in diffuse large B cell lymphoma: pathogenic and therapeutic implications: a case series,” was published in the Journal of Medical Case Reports.
Temperature at which antibodies bind to red blood cells defines AIHA type
AIHA occurs when self-reactive antibodies mistakenly attack red blood cells, leading to their destruction (hemolysis) and causing anemia, a condition marked by a shortage of healthy red blood cells. This can lead to symptoms such as fatigue, dizziness, and a rapid heartbeat, or palpitations.
The temperature at which antibodies bind to red blood cells defines the type of AIHA a person has. In CAD, binding occurs at cold temperatures, whereas in WAIHA, it occurs at warmer temperatures. The disease can also be classified as primary, when it develops on its own, or secondary, when it is triggered by an underlying condition, including blood cancers.
DLBCL is an aggressive blood cancer that’s rarely seen with AIHA. Cases of DLBCL-associated CAD or WAIHA appear to differ in their development and response to treatment, but the mechanisms underlying these differences remain unclear.
Man, woman had genetic variations in underlying blood cancer
In this study, researchers at a hospital in China detailed the cases of a man and a woman in whom genetic variations in the underlying DLBCL appeared to drive distinct forms of AIHA.
The first case was that of a 29-year-old man who was admitted to the hospital after two weeks of fatigue and palpitations. Blood tests revealed anemia and ongoing hemolysis, leading to a diagnosis of hemolytic anemia and treatment with oral corticosteroids to suppress the immune system. The therapy brought only temporary relief before his symptoms returned.
Further testing confirmed the diagnosis of CAD. Imaging scans revealed swollen lymph nodes in his abdomen, chest, and pelvis, and a biopsy confirmed DLBCL.
He was first treated with rituximab, a B-cell-depleting therapy often used off-label in CAD to eliminate abnormal B-cells. When DLBCL was confirmed, he began a combination chemotherapy that included polatuzumab vedotin and other anti-cancer drugs.
After three cycles, his blood counts normalized, his fatigue eased, and scans showed partial cancer regression.
Patients carried extra copies of certain genes
The second case was that of a 37-year-old woman who had been living with fatigue and dizziness for more than five years. She was diagnosed with WAIHA and initially responded well to oral corticosteroids, but symptoms eventually returned. Treatment with rituximab, cyclophosphamide, and corticosteroids brought only brief relief.
As her anemia worsened, she received intravenous immunoglobulin — a therapy that delivers specific antibodies to potentially help neutralize self-reactive antibodies and block their production — along with vitamins, blood transfusions to replenish red blood cells, and antibiotics to prevent infections.
She was later readmitted with worsening symptoms. Scans revealed enlarged lymph nodes in her chest and abdomen and multiple spleen nodules. A biopsy confirmed DLBCL.
She began standard chemotherapy for DLBCL, combining rituximab with other anti-cancer drugs. After two cycles, her fatigue eased, and her blood counts stabilized. CT scans showed about a 50% reduction in spleen nodules and lymph node size.
The triad screening model and mechanism-guided treatment approach proposed in this study provide a clinical framework for the early identification and precise intervention of this rare disease.
Further testing revealed that the man’s lymphoma carried extra copies — known as amplifications — of the BCL6 gene, while the woman’s DLBCL showed amplifications of both BCL2 and BCL6.
The researchers noted that such genetic differences may influence the type of self-reactive antibodies the abnormal B-cells produce, IgM in CAD and IgG in WAIHA, which could help explain why the two forms of AIHA develop and respond differently.
Based on these findings, the team proposed a triad screening model, urging doctors to look for anemia that doesn’t improve with treatment (refractory hemolysis), low blood cell counts (cytopenia), and enlarged lymph nodes or spleen to help detect hidden lymphoma earlier in people with AIHA.
“The triad screening model and mechanism-guided treatment approach proposed in this study provide a clinical framework for the early identification and precise intervention of this rare disease,” the researchers wrote. “Further elucidation of the molecular basis of tumor–immune interactions will be crucial for improving patient outcomes in the future.”
