Helical Tomotherapy, Fludarabine Phosphate, and Melphalan Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

PRIMARY OBJECTIVES: I. To assess the feasibility in terms of toxicity and safety of HT in
combination with Fludarabine (fludarabine phosphate) and Melphalan as a preparative regimen
for allogeneic stem cell transplantation in patients with Hematological Malignancies: acute
lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndromes
(MDS).

SECONDARY OBJECTIVES: I. To evaluate within the confines of this pilot study, incidence of
neutrophil and platelet engraftment, survival on day +180, the overall survival, and disease
free survival in patients with Hematological Malignancies: ALL, AML, and MDS.

II. To evaluate incidence of primary and secondary engraftment failure, incidence of relapse,
incidence of acute and chronic transplant related complications, including veno-occlusive
disease of the liver (VOD), organ toxicity, secondary malignancies, including
treatment-related myelodysplastic syndrome, and acute and chronic graft-versus-host disease
(GVHD), as well as post-transplant chimerism.

OUTLINE: PREPARATIVE REGIMEN*: Patients receive fludarabine phosphate intravenously (IV) on
days -7 to -3 and melphalan IV on day -2. Patients also undergo HT twice daily on days -7 to
-4.

TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day
0. NOTE: *Treatment begins 2 days earlier in patients receive tacrolimus and/or sirolimus for
GVHD prophylaxis.

After completion of study treatment, patients are followed up periodically for 2 years.

Inclusion Criteria:

- Recipient, or recipient's parents, or recipient's legal guardians must have signed a
voluntary, informed consent in accordance with institutional and federal guidelines

- Must have histopathologically confirmed diagnosis in one of the followed categories:

- AML

- MDS with intermediate or high-risk disease

- ALL

- Children and adults at any age with significant morbidity, as determined by the
primary bone marrow transplant (BMT) doctor (MD), and approved by the principal
investigator (PI)

- Able to lie supine in a full body cast for approximately 30 minutes, the anticipated
duration of each treatment session; for younger patients deep conscious sedation may
be required

- Performance status evaluated by Zubrod or Karnofsky (KPS) Performance Scales in
patients > 16 years or Lanksy Performance Scale in children =< 16 years must have a
score >= 70%

- Adequate cardiac function: cardiac ejection fraction > 50% by multi gated acquisition
scan (MUGA) scan and/or by echocardiogram

- Adequate pulmonary function: adults (older than 16 years): diffusing capacity of
carbon monoxide (DLCO) > 50%; for young children in whom pulmonary function tests
(PFT) are not applicable: assessment by a pediatrician or pulmonary consult

- Adequate renal function as demonstrated by: creatinine clearance or glomerular
filtration rate (GFR) > 60 cc/min (24 hour urine collection)

- Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase
(SGPT) =< 5.0 times the institutional upper limits of normal

- Patients must have less than 15% peripheral blasts

- Pre-treatment tests must have been preformed within 30 days prior to initiation of
high-dose chemotherapy

- No other medical and/or psychosocial problems, which in the opinion of the primary
physician or principle investigator would place the patient at unacceptable risk from
this regimen

Exclusion Criteria:

- Patients with Acute Undifferentiated Leukemia (AUL), i.e. no lymphoid or myeloid
markers

- Previous radiation therapy to more than 20% of bone marrow containing areas, or to any
area exceeding 2000 cGy

- Patients with Fanconi Anemia

- Major medical or psychiatric disorders that would seriously compromise patient
tolerance of this regimen

- Human immunodeficiency virus (HIV) infection

- Evidence of Hepatitis B or C infection or evidence of cirrhosis

- Uncontrolled viral, bacterial or fungal infection

- Patients with recent (within 4 weeks) serious viral, fungal, or bacterial infection
are excluded

- Patients with radiographic changes indicating pulmonary disease, including but not
limited to: pulmonary nodules, infiltrates, pleural effusion are excluded unless
cleared by pulmonary biopsy showing no evidence for active pulmonary disease