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Promising Therapy for Bone Marrow Failure from Myelodysplastic Syndromes FREE

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The summary below is from the full report titled “Antithymocyte Globulin for Treatment of the Bone Marrow Failure Associated with Myelodysplastic Syndromes.” It is in the 6 August 2002 issue of Annals of Internal Medicine (volume 137, pages 156-163). The authors are JJ Molldrem, E Leifer, E Bahceci, Y Saunthararajah, M Rivera, C Dunbar, J Liu, R Nakamura, NS Young, and AJ Barrett.


Ann Intern Med. 2002;137(3):I-27. doi:10.7326/0003-4819-137-3-200208060-00003
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What is the problem and what is known about it so far?

Bone marrow makes blood cells, including red blood cells, white blood cells, and platelets. In some older persons, there is a problem with the bone marrow in which the marrow cannot make new blood cells effectively (myelodysplastic syndromes). These persons get low numbers of red blood cells (anemia), white blood cells (neutropenia), or platelets (thrombocytopenia). Low numbers of red blood cells and platelets require frequent transfusions to prevent tiredness, shortness of breath, and bleeding. Low numbers of white blood cells lead to infections and a frequent need for antibiotics.

Therapies for myelodysplastic syndromes often fail. Most people die because they reach a point at which they cannot make any blood cells. Others start making abnormal blood cells and die of cancer of the blood (leukemia). Doctors want better ways to treat the syndromes. They are beginning to test whether powerful drugs that reduce activity of the body's immune system (immunotherapy) will work.

Why did the researchers do this particular study?

To see whether immunotherapy with antithymocyte globulin (ATG) improves outcomes in patients with myelodysplastic syndromes.

Who was studied?

61 adults with myelodysplastic syndromes. All had low numbers of red blood cells and required blood transfusions at least monthly. Most (two thirds) also had low numbers of platelets and white blood cells.

How was the study done?

The researchers gave patients ATG through a vein over 4 to 8 hours each day for 4 days. They also gave patients steroid pills (prednisone) for about 2 weeks to help prevent severe side effects from ATG. The researchers then checked patients every few months to see how their blood cell counts were doing and to see whether they needed continued transfusions.

What did the researchers find?

All patients developed transient side effects from ATG, such as fever, rash, and joint pains. Within 8 months of ATG treatment, 21 patients (one third) began to make more of their own red blood cells and no longer needed red blood cell transfusions. Of these, 17 did not need transfusions for several months to years (average transfusion-free period was 3 years). Numbers of white blood cells and platelets improved in half of the patients who had very low numbers of these cells before treatment. Twenty-three patients died during an average follow-up period of 3 to 4 years. Only one of these patients had “responded” to ATG. Twelve patients died of infection related to very low numbers of white blood cells or bleeding related to very low numbers of platelets. Eleven died of blood cancer.

What were the limitations of the study?

The study did not directly compare ATG with any other therapy or with usual care.

What are the implications of the study?

Antithymocyte globulin is a promising therapy for some patients with myelodysplastic syndromes who need frequent blood cell transfusions. However, before we routinely recommend ATG, we need results from controlled studies that compare it with other therapies.

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