Helical Tomotherapy, Fludarabine Phosphate, and Melphalan Followed By Allo-HSCT in Hematological 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