RATIONALE: High-dose cyclophosphamide may be an effective treatment for acute graft-versus-host disease that did not respond to steroid therapy.

PURPOSE: This phase II trial is studying the side effects, best dose, and how well high-dose cyclophosphamide works in treating patients with acute graft-versus-host disease that did not respond to steroid therapy.

OBJECTIVES:

• Determine the maximum tolerated dose of high-dose cyclophosphamide in patients with steroid refractory acute graft-versus-host disease.
• Determine the efficacy of this regimen at 28 days post-treatment in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive high-dose cyclophosphamide once daily for 1-4 days beginning on day 1 and filgrastim (G-CSF) subcutaneously once daily beginning on day 10 and continuing until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of high-dose cyclophosphamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed weekly for 4 weeks.

• Biological: filgrastim
• Drug: cyclophosphamide

DISEASE CHARACTERISTICS:

• Histologically confirmed acute graft-versus-host disease (GVHD) ≥ clinical grade II, that is steroid refractory

  • Steroid refractory GVHD is defined as GVHD that has progressed (increasing in grading) despite 49 hours of treatment with methylprednisolone of

    • 2.0 mg/kg OR GVHD that has failed to improve (no change in grading stage) despite 4 days of treatment with methylprednisolone of ≥ 2.0 mg/kg
• Prior allogeneic hematopoietic stem cell transplantation using either bone marrow, peripheral blood stem cells, or cord blood OR prior donor lymphocyte infusion required
• Evidence of myeloid engraftment
• No chronic GVHD

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• ANC > 500/mm³
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Must be geographically accessible
• No allergy or intolerance to cyclophosphamide or mesna
• No HIV positivity
• No mechanical ventilation
• No active bleeding (excluding gastrointestinal bleeding) or history of hemorrhagic cystitis

• No other uncontrolled illness including, but not limited to, the following:

  • Ongoing or active infection
  • Medical condition precluding patient from stopping azoles (e.g., fluconazole, itraconazole, or voriconazole) or other adequate antifungal therapy during cyclophosphamide administration
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Psychiatric illness/social situations that would preclude compliance

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics