A Study of Intensive-Dose Melphalan and Topotecan (MT) Followed by Autologous Stem Cell Rescue in Patients With Multiple Myeloma.

Inclusion Criteria:

- Multiple Myeloma Criteria = Newly diagnosed with drug sensitive disease (>50% tumor
response to standard chemotherapy) and poor prognostic indicators, such as
Salmon-Durie stage III, serum b-2-microglobulin >3.0 mg/L, high proliferative
fraction or hypodiploidy. Relapsed patients after a response to standard
chemotherapy. Patients with primary refractory disease. Patients with non-secretory
multiple myeloma are eligible for enrollment on this study. They will be followed
for toxicity, survival and molecular endpoint analyses, but will not be followed for
response. Patients with plasma cell leukemia, either occurring de novo or arising
from existing multiple myeloma, are ineligible for this study.

- Patients greater than or equal to 18 years of age are eligible.

- Patients must have histologically confirmed diagnosis by a pathologic review at the
H. Lee Moffitt Cancer Center and Research Institute.

- Patients must have undergone a complete psychosocial evaluation and been considered
capable of compliance.

- Patients willing and able to receive palifermin (young cohort only)

Exclusion Criteria:

- Patients with a DLCO less than 50% (adjusted) of normal or with symptomatic
obstructive or restrictive disease are ineligible.

- Patients with a serum creatinine of greater than 2.0 mg/dL OR a creatinine clearance
of less than 40 ml/minute. Creatinine clearance can be measured or calculated.
Patients with renal dysfunction secondary to multiple myeloma may be enrolled at the
discretion of the principal investigator. However, patients on hemodialysis or
peritoneal dialysis are ineligible.

- Patients with a total bilirubin greater than 2.0 mg/dL and SGOT or SGPT greater than
two and a half times normal (unless due to primary malignancy), or a history of
severe hepatic dysfunction are ineligible.

- Patients who have evidence of severe cardiac dysfunction are ineligible. A gated
blood pool (MUGA) scan must show an ejection fraction of at least 50%. Patients must
be free of major heart disease. Patients are ineligible if they have received a total
dose of doxorubicin of greater than 450 mg/m2 (or daunorubicin equivalent) unless the
left ventricular ejection fraction by MUGA scan is at least 50%. Patients must not be
taking nitroglycerin preparations for angina pectoris or antiarrhythmic drugs for
major ventricular dysrhythmias. Patients with essential hypertension controlled with
medications are eligible for study. Any patient with congenital or acquired heart
disease or cardiac arrhythmias will have a cardiology consult and evaluation.

- Patients with active infections are ineligible.

- Patients who are HIV antibody positive are ineligible.

- Patients with active leptomeningeal involvement are ineligible. Patients with a
history of previous CSF tumor involvement without symptoms or signs are eligible
provided the CSF is now free of disease on lumbar puncture and MRI of the brain shows
no tumor involvement. Patients with severe symptomatic CNS disease of any etiology
are ineligible.

- Patients with uncontrolled insulin-dependent diabetes mellitus or uncompensated major
thyroid or adrenal dysfunction are ineligible.

- Patients with an ECOG performance status of > or = 2 are ineligible. Patients with
ECOG performance status 2 to 3 secondary to bone pain may be enrolled at the
discretion of the institutional investigator. Patients with ECOG performance status
2 to 3 secondary to a potentially reversible disease-related problem may be enrolled
at the discretion of the institutional investigator.

- Patients who are pregnant or lactating are ineligible.

- Patients with any previous malignancy other than non-melanoma skin cancer are
ineligible, unless the patient is without evidence of disease > or = 5 years after
the treatment for the cancer was completed.

- Patients previously treated with topotecan or any other topoisomerase I inhibitor.