*The treatment schema reviewed here are the treatment management opinions of the DBAR Investigators. Each patient is unique and all treatment decisions should be made in consultation with the DBA patient’s primary physician and hematologist.
Red Blood Cell Transfusions
Diamond Blackfan anemia (DBA) is a rare disorder characterized by the failure of the bone marrow to make red blood cells. DBA is treated with corticosteroid therapy. However, for those patients who are unresponsive to corticosteroid therapy, chronic transfusion therapy is required. Transfusion therapy consists of receiving red blood cell transfusions every 3 to 4 weeks to maintain an adequate hemoglobin. This adequate hemoglobin can range from 7.5 to 10 g/dL, and can vary from patient to patient based on the patients’ symptoms. Some patients become symptomatic with headaches, difficulty concentrating, weakness, and tiredness with hemoglobin levels less than 8-8.5 g/dL.
Corticosteroids and red blood cell transfusions are the mainstays of therapy. The DBAR and other investigators throughout the world now generally recommend that patients under the age of 2 years old who present with severe anemia are transfused. Chronic transfusions are given every 3-5 weeks as needed to ensure adequate growth of the infant. Usually the hemoglobin is maintained at 8-9 gm/dL at the lowest time before the next transfusion. Transfusions are continued until 6-12 months of age.
In a cross-sectional analysis of the DBAR, approximately 35% of patients are currently receiving chronic (usually monthly) red cell transfusions. Of these,
about 30% were never steroid responsive (i.e. always have required transfusions because they were non-responsive to steroids)
about 15% became steroid refractory (i.e. had been on steroids but lost the response to steroids over time)
about 50% could not be weaned to an acceptable dose of steroids (i.e. only had a response to high doses of steroids with too many side effects)
1% never received steroid therapy
1% are being transfused for reasons unknown
If not appropriately treated, iron overload may occur as a result of transfusion therapy. Iron accumulates with each transfusion and as the patient does not use the iron to make new blood cells, the iron stored in the body increases. After normal storage sites are filled, accumulation will occur in the endocrine organs, namely the pancreas, thyroid gland, hypothalamus, pituitary gland, ovaries and testes, as well as the heart and liver. In order to remove the excess iron from the body, an iron chelator (a drug that can bind to the excess iron) must be used. This drug can eliminate the iron in the urine or stool, and accumulation can be kept to a minimum.
Usually at around one year of age the patient can be tried on a trial of corticosteroids. Corticosteroids may include Prednisone, Methylprednisolone or Dexamethasone. In the DBAR, the patient response to the first course of steroids is as follows:
82% were initially responsive to steroids
16% were non-responsive to initial steroids and required transfusion therapy
2% of patients were never treated with steroids
In a cross-sectional analysis of the DBAR, approximately 45% of patients are currently on corticosteroids.
Steroid-related side effects were observed in many of the patients. Of these,
40% of patients had Cushingoid features (puffy face, swelling)
12% had pathologic fractures (bone fractures occurring with no or minimal trauma)
7% had cataracts
Stem Cell Transplant
Stem cell transplantation (SCT), also known as bone marrow or cord blood transplantation (depending on the donor source), is the only curative approach for the anemia of DBA. A significant survival improvement was observed in patients less than 9 years of age transplanted from matched sibling donors (93.8% vs. 54.8% for patients greater than 9 years of age at the time of SCT). Also improvements have been seen in survival from alternative donor SCT performed after the year 2000 (85.7% vs. 32.1% for SCT done from 1994-1999). The median age at transplant for all patients was 6 years 10 months. Most of the sibling transplants used chemotherapy alone as a conditioning regimen. Most of the alternative donor (mismatched family or unrelated donor) transplants used a combination of chemotherapy with or without radiation therapy for pre-transplant conditioning.