Low-Dose Prednisone or Methylprednisolone in Treating Patients With Newly Diagnosed Acute Graft-versus-Host Disease

• >= 33% reduction of cumulative prednisone dose with lower-dose prednisone compared to those given standard-dose prednisone [ Time Frame: At day 42 after initiation of treatment ] [ Designated as safety issue: No ]
  Demonstrated in a prospective fashion.
  
  

• Prednisone-associated toxicity as assessed by hyperglycemia [ Time Frame: Baseline and through 6 weeks after enrollment ] [ Designated as safety issue: Yes ]
  Impact on blood glucose (BG) control will be assessed by comparing average BG and BG-variability between patients given standard-dose and low-dose prednisone. BG levels will be retrieved from the FHCRC clinical database at the conclusion of study.
  
  
• Prednisone-associated toxicity as assessed by invasive bacterial, viral, and fungal tissue or organ infections [ Time Frame: Baseline through 6 weeks ] [ Designated as safety issue: Yes ]
  Assessed in a prospective fashion. Other infection data will be retrieved from FHCRC and Infectious Disease databases at the conclusion of the study.
  
  
• Prednisone-associated toxicity as assessed by myopathy [ Time Frame: Baseline and weekly for 6 weeks ] [ Designated as safety issue: Yes ]
  Assessed using four simple tests of muscle strength: i) 'Manual Muscle Testing" 5-Point Scale of upper and lower extremities; ii) 'Timed Stands Test' (measures lower extremity strength); iii) 'Timed Up and Go' test (measures mobility, balance and overall locomotor performance); and iv) 'Unilateral Forefoot Balance Test" (evaluates gluteus medius weakness).
  
  
• Prednisone-associated toxicity as assessed by hypertension [ Time Frame: Baseline and weekly for 6 weeks ] [ Designated as safety issue: Yes ]
  The number of different anti-hypertensive medications will be abstracted from pharmacy records, the patient chart or the electronic record. Dose increments of individual medications will not be scored as a new medication.
  
  
• Prednisone-associated toxicity as assessed by quality of life [ Time Frame: Baseline and every other week until 6 weeks ] [ Designated as safety issue: Yes ]
  Patients complete the MD Anderson Symptom Inventory (MDASI), which is a quality of life questionnaire validated for oncology/transplant patients.
  
  
• Non-relapse and overall mortality defined as death due to any cause in the absence of documented relapse/progression [ Time Frame: At day 100 and 1 year ] [ Designated as safety issue: No ]
  We will regard a 7.5% excess in overall mortality as the allowable threshold for no-harm.
  
  
• Recurrent or progressive malignancy [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
  Collected as part of long-term follow-up. Documented in a spreadsheet/case report form (CRF) and entered into an electronic database. The completed spreadsheet/CRF will be reviewed and signed by the PI.
  
  
• Progression to grade III-IV acute GVHD [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
  Diagnosed and graded according to established criteria.
  
  
• Secondary therapy for acute GVHD including any intervention intended to control GVHD through an immunosuppressive effect from oral or parenteral administration of any systemic medication not given previously [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
  Secondary systemic treatment is not indicated as long as there is continuing improvement in at least one manifestation of GVHD and no progression of any other manifestations. Initiated within 3-7 days whenever clinical manifestations of GVHD show evidence of progression in a previously involved organ or whenever clinical manifestations appear in an organ that was not previously involved. Secondary systemic treatment should be initiated within 10-14 days whenever manifestations of acute GVHD show no improvement during treatment with the originally prescribed medications.
  
  
• Chronic extensive GVHD [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
  Collected as part of long-term follow-up.
  
  

OBJECTIVES:

I. To determine whether a lower starting dose of prednisone for treatment of newly diagnosed acute GVHD results in decreased prednisone exposure without compromising overall survival.

II. To estimate the magnitude of clinical benefit associated with the reduction in prednisone exposure.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I (Low-dose; prednisone-equivalent dose at initiation of treatment of 0.5 mg/kg/day or 1.0 mg/kg/day; stratified according to initial symptom severity): Patients receive low-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.

ARM II (Standard-dose; prednisone-equivalent dose at initiation of treatment of 1.0 mg/kg/day or 2.0 mg/kg/day; stratified according to initial symptom severity): Patients receive standard-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 year and then annually thereafter.