Observational study of asymptomatic Waldenström’s Macroglobulinemia and Phase II study of tandem autologous transplant and maintenance treatment for patients with symptomatic disease

Observation: Pts must have WM with measurable disease within 28 days prior to reg. Pts must have Zubrod Performance Status 0-2. Prior chemo/radiotherapy is allowed, must be at least 28 days from last treatment and recovered to < Grade 1 tox. Pts must not have hypersensitivity to boron or mannitol and must not have previous bortezomib treatment. Pts must not be planning on receiving concomitant glucocorticoids (unless needed to control autoimmune disease associated with WM). Pts. Must be offered participation in repository. Pts must have serum creatinine < 3 mg/dl and creatinine clearance > 30 ml/min. Pts Must have SGOT/SGPT < 2 x IULN and bilirubine < 2.0 mg/dl. Pts. Must not have myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrollable hypertension, or difficult to control cardiac arrhythmia within past 6 months. Pts. Must have ejection fraction (ECHO or MUGA) > 50%; pts. with amyloidosis must have ECHO. Pts. Must not be Hep B, Hep C or HIV positive. Pts. Must not have history or multi-infarced dementia or multiple strokes. No prior malignancy is allowed except adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer, or other cancer for which the pt has been disease free for five years. Pts must be informed of investigational nature of the study and give written consent.

Treatment: Pts must register within 28 days of experiencing disease related symptoms (hemoglobin < 11 mg/dl, platelets < 100 x 109/l, marked tumor mass defined as lymphadenopathy > 2 cm, palpable hepatomegaly, splenomegaly or significant marrow involvement (> 50%), serum albumin < 2.5 gm/dl, persistently elevated beta-2-microglobulin > 3.0 mg/l in absence of renal impairment or active infection, presence of B symptoms [fever, night sweats, weight loss > 10% baseline], appearance of new or worsening neuropathy manifested by numbness and tingling or pain, sympromatic cryoglobulinemia [Raynaud phenomenon, skin ulcers, cold uticaria, skin necrosis], symptoms of hyperviscosity if measured viscosity > 4 cp [new headaches, vertigo, ataxia, dizziness with or without eveident causes of changes in fundoscopic exam including retinal vein engorgement, hemorrhages, exerdates]). Compete reassessment of disease status must be done if pt has been under observation (first reg) for at least 28 days. Pts must have serum creatinine < 3 mg/dl and creatinine clearance > 30 ml/min. Pts must not be pregnant or nursing. Women of reproductive potenential msut have negative pregnancy test within 24 hours of reg. Women/men must agree to contraception. WM pts must be aware of teratogenic potential of thalidomide and agree to comply with guidelines. Pts must not have > Grade 2 peripheral neuropathy, must have SGOT/SGPT < 2 x ULN and bilirubin < 2 mg/dl, must have ANC > 1,500/mcl (unless more marked cytopenias are due to marrow involvement or autoimmune myelosuppression), must not have had myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrollable hypertension or difficult to control cardiac arrhythmia within past 6 months, and must have ejection fraction by ECHO/MUGA > 50%.