Treatment with erythropoietin (EPO), a hormone that stimulates the production of red blood cells, lowers hemoglobin levels in adults with cold agglutinin disease (CAD) and other autoimmune hemolytic anemias (AIHA), according to a single-center study in Italy. was found to be able to be safely raised.
Data show that this treatment is effective in patients with abnormally low levels of immature red blood cells.
the study, “Recombinant erythropoietin in autoimmune hemolytic anemia with inadequate bone marrow response: a prospective analysis” was published in a magazine Blood Advances.
AIHA is a group of rare diseases characterized by immune-mediated destruction of red blood cells. CAD is a subtype of AIHA in which cells are destroyed at low temperatures. AIHA can also occur under warm conditions (wAIHA) and can be of mixed or atypical subtypes.
Autoimmune hemolytic anemia reduces hemoglobin levels and causes anemia
AIHA also reduces levels of hemoglobin, a protein in red blood cells that carries oxygen throughout the body, causing anemia. In response, the kidneys secrete the hormone EPO to stimulate the production of new red blood cells in the bone marrow and restore oxygen transport.
Such rapid blood cell production, as seen in AIHA, leads to an increased number of immature red blood cells called reticulocytes in the bloodstream.
Still, about one-third of patients with AIHA have a poor bone marrow response, characterized by abnormally low reticulocyte levels, leading to more severe anemia and requiring blood transfusions.
A recent multicenter study showed that laboratory-made or recombinant EPO (rEPO) can increase hemoglobin in AIHA patients with low reticulocyte levels. Such rEPO treatments are used as supportive care for CAD in North America, but are less common in Europe.
In this study, Italian researchers set out to determine the safety and effectiveness of rEPO treatment in 47 AIHA patients aged 19 to 94 with anemia and insufficient reticulocyte levels. Of the 25 men and 22 women, more than half were over 60 years old, and 19 (40%) were diagnosed with CAD. 22 people (47%) cooperated with Waiha. and 6 (13%) had mixed or atypical disease.
“The relatively high prevalence of CAD in our study population (40%) may indicate that inadequate bone marrow response is a prevalent feature in patients with CAD,” the researchers wrote. It pointed out.
Severe anemia was identified in 27 (57%) patients with AIHA and is defined as a hemoglobin level of less than 8 grams per deciliter of blood (g/dL). Nearly all patients (91%) had previously received AIHA medications, including steroids, immunosuppressants, and rituximab (sold as Rituxan in the United States and MabThera in Europe). One patient underwent surgery to remove the spleen.
All patients received weekly subcutaneous injections of epoetin alfa, an rEPO formulation sold as Epogen, Procrit, Retacrit, etc., in parallel with standard clinical therapy.
91% of patients experienced a partial or complete rEPO response after 1 year
As a result, 55% of patients had a partial or complete rEPO response after 15 days, increasing to 74% after 3 months, 80% after 6 months, and 91% after 1 year.
At the same time, hemoglobin levels increased over the same period, from a median increase of 1.4 g/dL after 3 months to 4.4 g/dL after 1 year. The need for blood transfusions also decreased from 9% after 15 days to 0% after 1 year.
Overall response rate was higher in wAIHA than in CAD patients (73% vs. 26%), as was hemoglobin increase (11.3 vs. 9.7 g/dL). Levels of lactate dehydrogenase, a sign of red blood cell destruction, gradually decreased after 15 days, while reticulocyte levels increased. Recurrence was reported in 12 of her patients (26%).
Seven patients with CAD received rituximab four times weekly during the study period, but there was no association between additional drug use and rEPO response. “Responses were observed in patients with CAD, regardless of rituximab treatment,” the research team noted.
Median treatment duration was 4 months, with a range of 1 week to 4 years. After 1 year, 35 (74%) patients discontinued rEPO primarily due to sustained response (64%), whereas older patients with AIHA had no response (4%), adverse events (1%), There were also deaths (4%).
5 adverse events reported in the study
Five adverse events were reported, including two waiha patients with blood clots, one patient with acute renal failure, and two infections in a CAD patient and a wAIHA patient.
The researchers then compared these findings to those of 43 AIHA patients with similar clinical characteristics who did not receive rEPO treatment. All AIHA drugs used were similar between rEPO and non-rEPO patients.
Partial or complete response rates were significantly higher in patients treated with rEPO than in patients not treated with rEPO at day 15 (55% vs. 32%). Consistently, hemoglobin levels were significantly higher in rEPO-treated patients at her 15th day (9.4 vs. 8.6 g/dL) and at his 1st year (12.2 vs. 11.2 g/dL). Additionally, fewer blood transfusions were required with rEPO treatment than without treatment (9% vs. 15%). The frequency of adverse events was similar between the two groups.
This study “supports the use of rEPO in addition to immunosuppressive therapy to promote early recovery.” [red blood cell] “It can reduce the need for blood transfusions in AIHA with inadequate bone marrow compensation,” the researchers concluded.