Corticosteroids, cyclosporine treat rare CAD, blood cancer case

Researchers withheld turning to Enjaymo due to risk of infection

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A woman with both cold agglutinin disease (CAD) and myelodysplastic syndrome, a rare blood cancer, responded well to treatment with a moderate dose of the corticosteroid prednisolone followed by cyclosporine, an immunosuppressant, a case study reports.

While corticosteroids usually fail to treat CAD, they were used in this case instead of Enjaymo (sutimlimab), the only approved therapy for the condition, due to a risk of serious infection and the woman’s previous history of serious lung infection.

For that reason, the corticosteroids were tapered off rapidly and the corticosteroid-sparing immunosuppressive effects of cyclosporine may explain the woman’s favorable treatment response, the researchers wrote in “Successful treatment of concurrent cold agglutinin disease and myelodysplastic syndrome,” which was published in Transfusion and Apheresis Science by two researchers in Japan.

Bone marrow, the spongy tissue inside bones, is home to stem cells that give rise to blood cells. In myelodysplastic syndrome, or MDS, the bone marrow gets taken over by immature blood cells that aren’t fully developed and not enough healthy blood cells get released into the bloodstream when needed.

Nearly every third patient with MDS has an autoimmune disease, such as autoimmune hemolytic anemia (AIHA). AIHA is a group of rare conditions marked by hemolytic anemia, which happens when red blood cells are destroyed faster than they can be replaced.

MDS rarely co-occurs with CAD, a rare type of AIHA, however. In CAD, self-reactive antibodies called cold agglutinins bind to red blood cells at low temperatures, flagging them for destruction by the immune system. This results in to too few red blood cells, that is, anemia, and poor oxygen transport throughout the body, causing symptoms.

“Hemolytic anemia with cold agglutinin in patients with myelodysplastic syndrome is less common, and the effect of corticosteroids for autoimmune hemolytic anemia caused by cold agglutinin is thought to be limited,” wrote the researchers, who described the case of a 68-year-old woman with MDS and CAD who was successfully treated with a corticosteroid followed by cyclosporine.

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The woman was referred to the hospital for symptoms of anemia, including fatigue and numbness of the hands and feet. Blood tests confirmed low red blood cell numbers and low hemoglobin, the protein that carries oxygen in red blood cells.

The woman also had higher than normal reticulocytes, or immature red blood cells, which can be a sign of the processes underlying both MDS and CAD.

Further testing revealed higher than normal cold agglutinins, confirming a CAD diagnosis. These antibodies were also active at temperatures above the body’s normal 37 C (98.6 F).

Bone marrow aspiration, wherein a small sample of bone marrow is removed for testing, revealed abnormalities in immature blood cells, including red blood cells, that were consistent with a diagnosis of low-risk MDS.

The woman was treated with darbepoetin alfa, a lab-made molecule similar to a hormone called erythropoietin that stimulates red blood cell production, for low-risk MDS.

Her red blood cell counts continued to be low, however, while reticulocytes remained higher than normal and the levels of lactate dehydrogenase (LDH), a marker of red blood cell destruction, were also elevated.

The woman had a history of a serious lung infection and middle lobe syndrome, which occurs when part of the lung collapses, leading to difficulty breathing, cough, and recurrent infection.

Enjaymo would be the first choice to treat her CAD-related hemolytic anemia, but the high risk of a serious infection prompted the doctors to instead start the woman on a moderate dose (35 mg) of prednisolone. However, due to its immunosuppressive effects, a “rapid dose reduction of corticosteroids,” was targeted, the researchers wrote.

Prednisolone led to a gradual decrease in blood LDH levels, but the increase in red blood cells was still insufficient so the woman was also treated with 100 mg of cyclosporine.

A “prominent increase” in red blood cells was observed shortly after, wrote the researchers, who said the “prednisolone was tapered without the relapse of anemia.” The numbers of reticulocytes, as well as LDH levels, returned to normal. Cold agglutinins were still detected, but were now at the upper limit of normal.

“In the present case, in addition to the improvement of [MDS], the corticosteroid-sparing effect on CAD may have played a role in the mechanism underlying the effectiveness of cyclosporine,” the scientists wrote.

Treatment with prednisolone followed by cyclosporine appeared to address both the ineffective blood cell production associated with MDS and the hemolytic anemia caused by CAD.

“Although the elevated levels of reticulocytes and LDH are usually caused by ineffective [blood cell production] in MDS, clinicians should be aware of latent CAD,” wrote the researchers, who noted the effective use of cyclosporine in such cases.