Immunotherapy for Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Blast Phase Chronic Myelogenous Leukemia (BP CML), and Myelodysplastic Syndrome (MDS) Relapse After Allogeneic Transplantation

This is a pilot phase II open label study testing the activity and feasibility of utilizing
a regimen to boost the immune system in order to treat AML, ALL, blast phase CML, and MDS
relapse after allogeneic transplantation. The regimen is a step-wise use of withdrawal of
immunosuppression, cytoreduction if needed, administration of granulocyte-macrophage
colony-stimulating factor (GM-CSF) and pegylated interferon (IFN) α-2b to patients who
relapsed after an allogeneic transplant and will assess efficacy.

Relapse is the major problem following allogeneic hematopoietic progenitor cell transplants.
There is currently no standard way to treat leukemia that relapsed after transplant, and
patients have a poor prognosis.

A retrospective analysis of patients treated at Emory showed that administration of GM-CSF
and interferon-alpha-2b was well-tolerated and affected long-term remissions in a small
number of relapsed patients (after allogeneic transplant). Pre-clinical and clinical data
from ours and other centers showed that relapsed leukemic blasts have down-regulation of
co-stimulatory molecules and a tendency to evade the immune system. Cytokines can
up-regulate co-stimulatory molecules on leukemic blasts and have been shown to increase the
cytotoxicity of T-cells. This effect may be beneficial as a graft vs. leukemia effect for
patients with relapse after allogeneic transplant.

Inclusion Criteria:

1. Age > 1 year.

2. Patients who have received an allogeneic transplant to treat AML, ALL, MDS, or CML
and have relapse or progression of their AML, ALL, MDS, or CML are eligible to
participate in the study. Relapse is defined as: reappearance of leukemic blasts as
determined by morphologic analysis of the blood or marrow, reappearance of a
phenotypic population of leukemia blasts by flow cytometric analysis of the blood or
marrow, reappearance of a chromosome abnormality which is associated with the
original leukemia as determined by chromosomal or FISH testing (ex: a translocation
between chromosomes 9 and 22 for CML), reappearance of the molecular marker which is
associated with the original leukemia as determined by polymerase chain reaction
(PCR) (ex: breakpoint cluster region [BCR]-Abelson murine leukemia [ABL] for CML or
ALL).

*Patients who received allogeneic transplantation to treat AML, ALL, MDS, or CML with
detectable disease, and did not achieve remission of their leukemia after transplant
are eligible.

3. Eastern Cooperative Oncology Group (ECOG) performance status < 2 for adults, and
Lansky status 60% for children.

4. Liver functions tests (AST/alanine aminotransferase [ALT]/bilirubin) < 5x the upper
limit of normal.

5. Creatinine < 3x the upper limit of normal.

6. Lack of active grade 2-4 acute graft-versus-host disease (GVHD) 3 weeks after
discontinuation of immunosuppression.

7. Patients with limited stage and extensive stage chronic GVHD of mild severity
(lichenoid changes), or requiring < prednisone 10 mg/m² daily will be included.

8. Recipients of grafts procured from related and unrelated donors with any level of
human leukocyte antigen (HLA)-matching.

Exclusion Criteria:

1. Pregnant patients are excluded due to unknown risk to the unborn fetus with
cytokines.

2. Allergy to components of interferon-alpha-2b or GM-CSF.

3. Current uncontrolled infection.

4. Current grade 2-4 acute GVHD or chronic extensive GVHD of moderate to severe nature,
requiring treatment with more than 10 mg/m² of prednisone daily.

5. Uncompensated heart failure, New York Heart Association (NYHA) class III-IV:

- Class I: patients with no limitation of activities; they suffer no symptoms from
ordinary activities;

- Class II: patients with slight, mild limitation of activity; they are
comfortable with rest or with mild exertion;

- Class III: patients with marked limitation of activity; they are comfortable
only at rest;

- Class IV: patients who should be at complete rest, confined to bed or chair; any
physical activity brings on discomfort and symptoms occur at rest.

6. Breast feeding, due to unknown risk to the infant.

7. Inability to give informed consent.

8. Children under 1 year of age.