Treatments
*The treatments 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 patient’s primary hematologist.
Red Blood Cell Transfusions
Diamond Blackfan anemia syndrome (DBAS) is a rare disorder characterized by the failure of the bone marrow to make red blood cells. DBAS 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 9.5 to 10.5 g/dL, and can vary from patient to patient based on the patients’ symptoms. The guidelines for transfusing patients have been revised to allow patients to have adequate growth and development and to improve quality of life.
Corticosteroids and red blood cell transfusions are the mainstays of therapy. The DBAR and other investigators throughout the world generally recommend that patients under the age of 1 year 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 9-10 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 35-40% of patients are currently receiving chronic (usually monthly) red cell transfusions. Of these,
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some patients were never steroid responsive (i.e. always have required transfusions because they never responded to steroids)
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some patients became steroid refractory (i.e. had responded to steroids but lost the response to steroids over time)
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some patients 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)
Iron Chelation
Iron accumulates with each blood transfusion, and as the patients do 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. If not appropriately managed, iron overload may occur as a result of transfusion therapy. 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 iron overload can be managed.
Corticosteroids
Usually at around one year of age the patient can be tried on a trial of corticosteroids. Corticosteroid treatment usually is done with Prednisone or Prednisolone. In the DBAR, the patient response to the first course of steroids is as follows:
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82% were initially responsive to steroids
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16% were non-responsive to initial steroids and required transfusion therapy
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2% of patients were never treated with steroids
In a cross-sectional analysis of the DBAR, approximately 40% of patients are currently on corticosteroids.
Steroid-related side effects were observed in many of the patients. Of these,
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40% of patients had Cushingoid features (puffy face, swelling)
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12% had pathologic fractures (bone fractures occurring with no or minimal trauma)
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7% had cataracts
With decreased doses these side effects can be reduced and even prevented.
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 treatment for the ANEMIA of DBAS. In the DBAR, a significant survival of 94% was observed in patients less than 9 years of age who were transplanted from matched sibling donors. Also improvements have been seen in survival from alternative donor SCT performed after the year 2000. Many transplants occurred during childhood. Radiation is not generally used during transplantation for DBAS. Newer preparative regimens for SCT include chemotherapy and immunosuppressive medications for related and alternative donor (mismatched family or unrelated donor) transplants.