Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma

OBJECTIVES:

- Determine the incidence of early mortality in patients with multiple myeloma treated
with melphalan and autologous peripheral blood stem cell (PBSC) transplantation followed
by fludarabine, cyclophosphamide, and allogeneic PBSC transplantation.

- Determine the incidence of early allogeneic graft failure (before day 100 after
allogeneic PBSC transplantation) and the incidence of severe acute graft-versus-host
disease (GVHD) in patients treated with this regimen.

- Determine the toxicity of this regimen in these patients.

- Determine the overall and disease-free survival of patients treated with this regimen.

- Correlate changes in the T-cell population with clinical outcome, such as survival, in
patients treated with this regimen.

- Correlate changes in the T-cell population with the incidence of GVHD, use of
immunosuppressive agents, and effects of fludarabine in patients treated with this
regimen.

- Determine the degree of chimerism after allogeneic PBSC transplantation and the time
course over which it is established in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive melphalan IV over 15 minutes on day -1. Autologous peripheral blood stem
cells (PBSCs) are reinfused on day 0. Patients also receive sargramostim (GM-CSF)
subcutaneously (SC) or IV over at least 30 minutes daily beginning on day 1 and continuing
until blood counts recover. Beginning 100-182 days after autologous PBSC transplantation,
patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over
1-2 hours on days -3 and -2. Allogeneic PBSCs are infused on day 0. Patients may receive a
second allogeneic PBSC infusion on day 1. Patients also receive GM-CSF SC or IV over at least
30 minutes daily beginning on day 1 and continuing until blood counts recover. Cyclosporine
is administered IV or orally twice daily as graft-versus-host disease (GVHD) prophylaxis,
beginning on day -1 and continuing until day 60, followed by a taper in the absence of GVHD.

Patients are followed for 5 years.

PROJECTED ACCRUAL: A total 19-46 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

- Diagnosis of multiple myeloma meeting 1 of the following criteria:

- Bone marrow plasmacytosis with at least 10% plasma cells

- Sheets of plasma cells

- Biopsy-proven plasmacytoma

- Meets at least 1 of the following criteria:

- Presence of myeloma (M)-protein in the serum

- Presence of M-protein in the urine

- Radiographic evidence of osteolytic lesions

- Generalized osteoporosis allowed if at least 20% plasma cells in bone marrow

- No non-secretory myeloma

- Prior M-protein in serum or urine allowed provided patient is now in complete
remission

- Must be receiving conventional-dose chemotherapy as initial therapy or as salvage
therapy

- Must have HLA-A, -B, and -DR genotypically identical sibling donor

PATIENT CHARACTERISTICS:

Age:

- 18 to 70

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

- See Disease Characteristics

Hepatic:

- AST no greater than 3 times upper limit of normal

- Bilirubin less than 2.0 mg/dL

Renal:

- Not specified

Cardiovascular:

- LVEF greater than 40% at rest if symptomatic cardiac disease is present

Pulmonary:

- DLCO greater than 50% of predicted (corrected for hemoglobin) if symptomatic pulmonary
disease is present

Other:

- Not pregnant or nursing

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No prior autologous or allogeneic peripheral blood stem cell or bone marrow
transplantation

Chemotherapy:

- See Disease Characteristics

- More than 28 days since prior chemotherapy (including primary chemotherapy for
hematopoietic stem cell collection)

- No other concurrent cytotoxic chemotherapy between autologous and allogeneic
transplantation

Endocrine therapy:

- Prior dexamethasone or other corticosteroids allowed

- Concurrent corticosteroids between autologous and allogeneic transplantation allowed

Radiotherapy:

- Concurrent radiotherapy between autologous and allogeneic transplantation allowed

Surgery:

- Not specified