Case Study of Cold AIHA and Rare B-cell Leukemia Suggests Possible ‘Innovative’ Therapies

A case study detailing the treatment of an 84-year-old man who developed B-cell prolymphocytic leukemia and cold type autoimmune hemolytic anemia (AIHA) suggests possible “innovative” therapies for these rare diseases.

The study, a letter to the editor titled “Hot and Cold: A Concurrent Warm and Cold Autoimmune Hemolytic Anemia in B-cell Prolymphocytic Leukemia,” was published in the journal Acta Heamatologica.

B-cell prolymphocytic leukemia (B-PLL) is a rare disease, making up less than 1% of the cancers linked with B-cells, which are the cells in the immune system that produce antibodies — blood proteins that counteract foreign entities, such as viruses and bacteria. In people with B-PLL, an abnormal proliferation of B-cells leads to anemia and enlarged spleen (splenomegaly), among other symptoms.

In this case study, clinicians at the Mount Sinai Hospital in New York, and Harvard Medical School in Boston, described a patient who developed B-PLL and cold AIHA, a medical condition in which the body produces auto-antibodies that attack red blood cells, causing them to stick to each other at low temperatures, and destroying them.

The patient had been diagnosed 16 years earlier with both chronic lymphocytic leukemia, a type of cancer affecting the white blood cells that develops slowly over time, and advanced esophageal cancer.

He had been treated with idelalisib (sold as Zydelig by Gilead), a medicine that promotes the death of malignant leukemia cells. But that treatment had been stopped when he had undergone surgery to remove the esophageal tumor.

At hospital admission, the patient had worsening fatigue. Laboratory tests showed he had anemia (hemoglobin levels of 8.5 g/dL), and abnormally high white blood cell counts, which suggested a worsening of his underlying chronic lymphocytic leukemia.

He was immediately restarted on idelalisib, and also was given rituximab (sold under the brand name Rituxan in the U.S., and MabThera in Europe, among others), an approved therapy for chronic lymphocytic leukemia. He also was given methylprednisolone, a steroid.

Further blood analysis revealed that the abnormally proliferating white cells were primarily B-cells (95%), as shown by their positivity for CD19 and CD20 proteins. Blood smears also confirmed the B-PLL diagnosis.

However, the blood analysis also showed that the patient had warm auto-antibodies as well as cold auto-antibodies, showing positive results for complement C3 and IgG agglutination at room temperature, and pan-agglutination (red blood cells clumping) when the blood was pre-warmed.

These results suggested the patient also was suffering from cold AIHA.

During his hospital admission, and after one month of the three-drug treatment, the hemoglobin levels began to increase when compared with the lowest pick. The idelalisib also appeared to effectively treat his B-PLL, and the therapies also improved the AIHA.

However, the patient died three months later due to problems associated with his esophageal cancer.

This case-report “reflects an innovative and efficacious therapeutic regimen, consisting of prednisone, rituximab, and idelalisib,” in the rare case of co-occurrence of AIHA and aggressive B-PLL, the study concluded.