Effects of Antithymocyte Globulin in Adults With Myelodysplastic Syndrome

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