Myelodysplastic syndrome (MDS) is a rare, potentially serious bone marrow disease. Currently available treatments for MDS have been only somewhat beneficial. The purpose of this study is to determine the effects of the medication antithymocyte globulin (ATG) in adults with MDS and to determine which individuals with MDS are most likely to benefit from treatment with ATG.

In people with MDS, the bone marrow stops making healthy blood cells and instead produces poorly functioning, malformed, and immature blood cells. This can lead to anemia resulting from too few healthy red blood cells, infection resulting from too few healthy white blood cells, and bleeding resulting from too few healthy platelets. The exact cause of MDS remains unknown, but it may be caused by abnormal autoimmune activity in which activated T cells, a type of white blood cell, prevent normal bone marrow production. ATG, a medication that inhibits immune function, can restore normal blood production in some people with MDS, but it is not known how this happens and why it does not happen in all MDS patients. The purpose of this study is to examine the effects of ATG in adults with MDS and to determine which individuals with MDS are most likely to benefit from treatment with ATG.

Based on disease severity and likely disease progression, participants will be separated into either a high-risk group or a low-risk group. Participants will be hospitalized for a 4-day period during which they will receive daily infusions of ATG. Oral prednisone will be given 2 days before hospitalization, throughout hospitalization, and then for 14 days after hospitalization to limit the side effects of ATG. Antihistamines and acetaminophen will also be given during hospitalization to reduce the chances of an allergic reaction to ATG. After discharge, all participants will attend monthly study visits that will include blood collection, review of disease symptoms, and evaluation of medication response. At Week 16, participants in the high-risk group will undergo additional blood collection, a bone marrow biopsy, and a thorough evaluation of disease progression and the effects of MDS on daily living abilities. Participants in the low-risk group will undergo these same procedures at Week 24. Follow-up for all participants may last up to 2 years.

Inclusion Criteria:

• Diagnosis of MDS that meets International Prognostic Scoring System (IPSS) criteria for low risk, intermediate-1 risk, or intermediate-2 risk. More information about this criterion can be found in the protocol.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• Willing and able to attend study visits
• Willing to use acceptable forms of contraception prior to study entry and for the duration of the study

Exclusion Criteria:

• Any serious medical illness that might limit survival to less than 2 years
• Any other uncontrolled condition or illness. More information about this criterion can be found in the protocol.
• Prior anti-lymphocyte serotherapy (received serum from an immunized animal)
• Proliferative chronic myelomonocytic leukemia
• MDS that is caused by radiotherapy, chemotherapy, and/or immunotherapy for cancerous or autoimmune diseases
• Previous or current cancer. More information about this criterion can be found in the protocol.
• Receiving any other investigational agents
• Certain abnormal lab values. More information about this criterion can be found in the protocol.
• History of a grade 2 National Cancer Institute common toxic criteria allergic reaction to rabbit proteins
• Psychiatric illness that might interfere with study participation
• HIV-1 infection
• Pregnancy or breastfeeding