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 (GVHD).
• 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.

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 (Eastern Cooperative Oncology Group) performance status (PS) 0-2 OR Karnofsky PS 60-100%

• ANC (absolute neutrophil count) > 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

Study site prefers to describe the study population as one set due to very small sample sizes for each arm.

every week through Day 30

The following events only were collected per the protocol's definition of an adverse event: unexpected adverse events that were attributed to the study drug by the investigator.