Cyclophosphamide in Treating Young Patients With Severe Autoimmune Enteropathy

OBJECTIVES:

Primary

• Determine the rate of treatment-free remission in young patients with severe autoimmune enteropathy treated with high-dose cyclophosphamide.

Secondary

• Determine the toxic effects of this drug in these patients.

OUTLINE: Patients receive cyclophosphamide IV over 1 hour on days 1-4. Patients then receive filgrastim (G-CSF) IV or subcutaneously once daily beginning on day 10 and continuing for 3 days or until blood counts recover.

After completion of study treatment, patients are followed periodically for up to 1½ years.

PROJECTED ACCRUAL: A total of 7-11 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Diagnosis of severe autoimmune enteropathy

• Condition is resistant to conventional therapy
• Histologic evidence of severe villous atrophy with intense lymphocytic infiltrate of the lamina propria by small intestinal biopsy within the past 3 months
• Disease failed to respond after ≥ 2 months of corticosteroid therapy at a dose of ≥ 0.5 mg/kg/day or ≥ 40 mg/day for patients > 20 kg AND 1 of the following therapies:

• Cyclosporine resulting in ≥ 1 whole blood level of > 200 ng/mL
• Tacrolimus resulting in ≥ 1 whole blood level of 5 ng/mL
• At least 50% estimated caloric needs provided by parenteral nutrition
• History of intractable diarrhea, defined as frequent watery stools for > 3 months that does not respond to dietary restriction
• No celiac disease, defined by a history of positive antiendomysial antibody or tissue transglutaminase antibody
• No primary immunodeficiency or x-linked autoimmunity-allergy dysregulation

PATIENT CHARACTERISTICS:

Performance status

• Lansky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• Ejection fraction ≥ 40% OR shortening fraction ≥ 20%

Pulmonary

• FVC or FEV_1 ≥ 50% of predicted (for patients > 8 years of age)
• No clinically abnormal pulmonary function or abnormal pulse oximetry (for patients ≤ 8 years of age)

Other

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 9 months after completion of study treatment
• No known chromosomal abnormality

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No immunizations for at least 6 months after completion of study treatment

Endocrine therapy

• See Disease Characteristics
• At least 5 days since prior corticosteroids
• No concurrent dexamethasone as an anti-emetic

Other

• At least 5 days since other prior immunosuppressive medications (e.g., tacrolimus or cyclosporine)