• Toxicity [ Designated as safety issue: Yes ]
  
• Facilitation of long-term engraftment [ Designated as safety issue: No ]
  
• Incidence and severity of acute and chronic graft-versus-host disease (GVHD) [ Designated as safety issue: No ]
  

• Progression-free survival [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  
• Response (partial and complete) as measured at 1, 3, 6, and 12 months post allografting and within 1 week after the onset of documented GVHD if > 1 month separates any of the response evaluation timepoints [ Designated as safety issue: No ]
  
• Frequency and durability of the induction of full donor chimerism of lymphocytes as measured at 1, 3, 6, and 12 months post allografting [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the toxicity and tolerability of allogeneic peripheral blood stem cell transplantation after a nonmyeloablative preparative regimen comprising anti-thymocyte globulin, high-dose melphalan, and fludarabine in women with chemotherapy-refractory or poor-prognosis metastatic adenocarcinoma of the breast.
• Determine the ability of this preparative regimen to facilitate long-term engraftment of allogeneic stem cells and lymphocytes in these patients.
• Determine the response in measurable/evaluable disease and its temporal relationship to the preparative chemotherapy used and to the onset of clinical graft-versus-host disease (GVHD) in patients treated with this regimen.

Secondary

• Determine the progression-free and overall survival of patients treated with this regimen.
• Determine the tumor response and its temporal relationship to administration of high-dose chemotherapy and to the onset of GVHD in patients treated with this regimen.
• Determine the frequency and durability of the induction of full donor chimerism of lymphocytes in patients treated with this regimen.

OUTLINE: This is a nonrandomized, pilot study.

• Nonmyeloablative preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4, anti-thymocyte globulin IV over 4 hours on days -7 to -4, and high-dose melphalan IV over 30 minutes on days -3 and -2.
• Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV (and then orally when tolerated) every 12 hours beginning on day -4 and tapered after day 42 (if no GVHD occurs) or after day 90 (if grade I acute GVHD occurs). Patients also receive methotrexate IV on days 1, 3, and 6.
• Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 0 and continuing until blood counts recover.
• Donor lymphocyte infusion (DLI): Patients who show disease progression or fail to achieve full donor type T-cell chimerism (at least 90% donor derived T-cells) by the 90-day assessment posttransplantation, and have no evidence of active GVHD may receive DLI. Patients who have unresponsive disease with no active GVHD receive subsequent DLIs every 6-8 weeks.

Patients are followed at 1, 3, 6, 12, 18, 24, 30, and 36 months.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast

  • Metastatic disease

• Meets 1 of the following criteria:

  • Chemotherapy-unresponsive disease defined as 1 of the following:

    • Less than a partial response to 2 consecutive chemotherapy regimens that included an anthracycline and a taxane in combination or succession
    • Progression of disease during or within 3 months of completion of a taxane, anthracycline, or platinol-based regimen
  • Histologically confirmed tumor involvement on bone marrow biopsy

• Measurable or evaluable disease* defined as the following:

  • Bidimensionally reproducible measurable mass by physical examination, ultrasonography, radiography, CT scan, or MRI

  • Evaluable lesions apparent on clinical exam, x-ray, CT scan, or MRI which do not fit the criteria for measurability (e.g., ill-defined post-surgical masses or masses assessable in 1 dimension only)

    • Elevation of biological markers (e.g., CA 27.29) is considered evaluable disease NOTE: *Bone lesions or pleural or peritoneal effusion alone are not considered measurable or evaluable disease
• Appropriate candidate for allogeneic stem cell transplantation
• No active CNS metastases

• Available HLA-identical sibling donor

  • 6/6 antigen match
  • Donor CD34 cells at least 2 times 10^6/kg recipient weight

• Hormone receptor status:

  • Estrogen receptor negative or positive

    • Estrogen receptor positive tumors must demonstrate progression on at least 1 hormonal manipulation

PATIENT CHARACTERISTICS:

Age

• 18 to 60

Sex

• Female

Menopausal status

• Not specified

Performance status

• Karnofsky 70-100% OR
• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 1,500/mm^3
• Platelet count at least 30,000/mm^3

Hepatic

• Bilirubin less than 3 times normal*
• AST and ALT less than 3 times normal* NOTE: *Unless abnormality due to malignancy

Renal

• Creatinine no greater than 1.6 mg/dL

Cardiovascular

• LVEF greater than 40% by echocardiography or MUGA
• No myocardial infarction within the past 6 months

Pulmonary

• DLCO greater than 40% of predicted

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No serious localized or systemic infection
• No hypersensitivity to E. coli-derived products
• No history of non-breast malignant disease within the past 5 years except completely excised nonmelanoma skin cancer or carcinoma in situ of the cervix
• No chronic inflammatory disorder requiring concurrent glucocorticosteroids or other immunosuppressive medication
• No psychological condition or social situation that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• No concurrent glucocorticoids

Radiotherapy

• No prior radiotherapy to an indicator lesion unless the lesion shows evidence of progression after discontinuation of the therapy

Surgery

• Not specified

Other

• No concurrent immunosuppressive medication