Stem Cell Transplant, Chemotherapy, and Biological Therapy in Treating Patients With High-Risk or Refractory Multiple Myeloma

DISEASE CHARACTERISTICS:

* Diagnosis of myeloma meeting 1 of the following criteria:

  * Myeloma has relapsed, progressed, or failed to respond after at least one prior course of therapy (consisting of at least 2 treatment cycles or months of therapy)

    * Failure to respond would correspond to a reduction of less than or equal to 25% of the original, diagnostic serum or urine paraprotein measurement
  * Myeloma has responded partially to initial therapy but a complete response (immunofixation negative) has NOT developed after a minimum of 3 cycles or months of initial therapy
  * Myeloma has high-risk features as defined by the presence of one or more cytogenetic abnormalities known to confer a poor outcome even after standard autotransplants (e.g., complex karyotype \[≥ 3 abnormalities\], t(4;14), t(14;16), del (17) (p13.1), and/or chromosome 13 abnormalities)

    * May be enrolled even while in complete or near-complete remission
    * Extended disease-free survival after autotransplantation would be unexpected for these patients and therefore especially meaningful
* Must have measurable disease

  * Measurable disease may include quantifiable or detectable levels of serum or urine paraprotein

    * For patients with minimally secretory disease or non-secretory myeloma on study entry, serum free λ or κ light chain levels may be measured and used for disease monitoring if abnormal
    * Patients who are in complete remission at the time of proposed study entry (serum and urine immunofixation consistently negative) are not eligible unless their disease meets the criteria for high-risk disease
* No known history of myelodysplasia

PATIENT CHARACTERISTICS:

Inclusion criteria:

* ECOG performance status 0-2 (unless due solely to bone pain)
* Creatinine ≤ 3.0 mg/dL and not on dialysis
* WBC ≥ 3,000/mm³
* Platelet count ≥ 100,000/mm³
* AST ≤ 2 times upper limit of normal
* Bilirubin ≤ 2.0 mg/dL (unless due to Gilbert's syndrome)
* LVEF ≥ 45%

  * A lower LVEF is permissible if a formal cardiologic evaluation reveals no evidence for clinically significant functional impairment
* FEV1, FVC, TLC, and DLCO ≥ 40% predicted

  * Patients who are unable to complete pulmonary function tests due to bone pain or fracture must have a high-resolution CT scan of the chest and must have acceptable arterial blood gases (room air PO\_2 \> 70 mmHg)
* Women of child-bearing potential and their spouses or partners must be willing to use adequate contraception for the duration of the active treatment phase of the study

  * Contraceptive measures must be continued as long as the patient remains on maintenance thalidomide in accordance with the STEPS program

Exclusion criteria

* Pregnant or nursing
* HIV, HTLV-1/2 seropositivity
* Known history of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy)
* Active hepatitis B (as defined by positive hepatitis B surface antigen)

  * Positive hepatitis C virus (HCV) antibody is NOT an exclusion
* History of severe autoimmune disease requiring steroids or other immunosuppressive treatments
* Active immune-mediated diseases including:

  * Connective tissue diseases
  * Uveitis
  * Sarcoidosis
  * Inflammatory bowel disease
  * Multiple sclerosis
* Evidence or history of other significant cardiac, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease that might increase the risks of participating in the study
* Active bacterial, viral or fungal infections.

PRIOR CONCURRENT THERAPY:

Inclusion criteria

* Recovered from any toxicities related to prior therapy or at least returned to their baseline level of organ function
* Patients should be off of glucocorticoids for at least 2 weeks and/or thalidomide therapy for at least 1 week prior to enrollment
* At least 2 weeks since prior steroid therapy or chemotherapy

Exclusion criteria

* Prior autotransplant or allogeneic transplant
* More than 4 distinct, prior courses of therapy for myeloma
* Also see Disease Characteristics