Multiple myeloma chemotherapy

The primary goal in the treatment of multiple myeloma is to decrease tumor burden and minimize complications associated with the disease. A watch and wait approach is an option for asymptomatic patients who have no lytic lesions in the bone. Once symptoms occur, treatment is required. Chemotherapy can be used to reduce tumor burden in patients with symptomatic disease, but increasingly, immunomodula-tors such as thalidomide and dexamethasone are initial therapy. Almost all patients will become refractory to initial treatment and will require the use of salvage therapies such as bortezomib. Autologous stem cell transplantation prolongs overall survival in patients who can tolerate high-dose chemotherapy and may be the treatment of choice for many patients. 

Carmustine and lomustine can produce remissions that last from 3 to 6 months in 40 to 50% of patients with primary brain tumors. Both drugs also are used as secondary treatment of Hodgkin s disease and in experimental combination chemotherapy for various types of lung cancer. Other tumors in which remission rates of 10 to 30% have been obtained are non-Hodgkin s lymphomas, multiple myeloma, melanoma, renal cell carcinoma, and colorectal cancer. 

Multiple myeloma (bone marrow) Combination chemotherapy... 

Multiple myeloma Melphalan plus prednisone or multiagent combination chemotherapy Cyclophosphamide, vincristine, carmustine, interferon, doxorubicin, epoetin alfa1... 

N., Fiegl, M., Roka, S., Schuster, J., Heinz, R., Ludwig, H., and Huber, H., Presence of ap53 gene deletion in patients with multiple myeloma predicts for short survival after conventional-dose chemotherapy. Blood 92, 802-809 (1998). 

Plasmocytoma Extramedullary plasmocytic lymphoma likewise has its origin in immunoglobulin-secreting B-lymphocytes. It is also termed multiple myeloma. The condition occurs most frequently in 7 decade of life and ends fatally after 1-2 (-3) years. In the liver, there are sometimes sinusoidal and portal infiltrations of B-lym-phocytes and plasmocytic tumour cells nodular formation can also occur. Generally, however, liver involvement is found in 40% of cases. (47, 61) (s. fig. 38.12) Recently, patients with non-response or relapse after high-dose chemotherapy were treated successfully with thalidomide (starting with 200 mg daily, the dose was increased by 200 mg every two weeks until it reached 800 mg per day). (48, 56) Plasma cell leukaemia is a rare complicative variant which tends to have its own individual course. 

Recombinant human erythropoietin (epoetin and darbepoetin) provides effective therapy with a very favorable risk-benefit ratio in hemodialysis patients with end-stage chronic renal insufficiency, and in patients with progressive renal insufficiency who are not yet being dialysed (1). It improves cognitive function and the quality of life of patients with chronic uremia (2-5) and is very effective in children with chronic renal graft rejection and anemia (6). It also offers new opportunities for treating anemia in non-uremic patients. In patients with chemotherapy-induced anemia, epoetin increases hemoglobin concentration, reduces transfusion requirements, and improves quality of life (7,8). The response rate to epoetin in patients with multiple myeloma and anemia, which is 55-85% (9), increases when GM-CSF or G-CSF is... 

The incidence of deep venous thrombosis is increased by the co-administration of doxorubicin, as suggested by a study in 232 patients with multiple myeloma who received a combination of thahdomide and chemotherapy in two protocols that differed only by the inclusion of doxorubicin in one DT-PACE (dexamethasone -I- thahdomide -I-cisplatin -I- doxorubicin + cyclophosphamide -I- etoposide) and DCEP-T (dexamethasone + cyclophosphamide -I-etoposide -I- cisplatin + thalidomide) (25). There was an increased risk of deep venous thrombosis in those who received DT-PACE but not in those who received DCEP-T. Multivariate analysis confirmed that those who received thahdomide + doxorubicin had an increased risk of deep venous thrombosis. In two separate trials in patients taking thahdomide for multiple myeloma, deep venous thrombosis occurred in four of 15 patients who received concomitant treatment with doxorubicin -I- dexamethasone compared with three of 45 who received dexamethasone only (26). 

Zangari M, Anaissie E, Barlogie B, Badros A, Desikan R, Gopal AV, Morris C, Toor A, Siegel E, Fink L, Tricot G. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood 2001 98(5) 1614-15. 

MT is a 49-year-old man admitted for his first cycle of chemotherapy for multiple myeloma. He is scheduled to receive VAD therapy (vincristine, doxorubicin [Adriamycin] and dexamethasone). Past medical history includes asthma and diabetes. Admission laboratory values include WBC count 3400 mm platelets 9500 mm (low), Cr 1.8 mg/dL (high), bilirubin 2.4 mg/dL (high). Which of the following factors may lead you to consider dose modification of doxorubicin ... 

LS is a 57-year-old woman with multiple myeloma being treated with VAD chemotherapy, a regimen consisting of a 4-day continuous infusion of vincristine and doxorubicin (Adriamycin) plus oral dexamethasone. Both vincristine and doxorubicin are vesicants. Which of the following precautions should be taken ... 

Altai M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 1996 335 ... 

Gregory WM, Richards MA, Malpas JS. Combination chemotherapy versus melphalan and prednisolone in the treatment of multiple myeloma an overview of published trials. J Clin Oncol 1992 10 334-42. 

Johnson WJ, Kyle RA, Pineda AA, O Brien PC, Holley KE. Treatment of renal failure associated with multiple myeloma. Plasmapheresis, hemodialysis, and chemotherapy. Arch Intern Med 1990 150 863-9. 

Abildgaard N, Brixen K, Kristensen JE, Eriksen EF, Nielsen JL, Heickendorff L. Comparison of five bio-chemical markers of bone resorption in multiple myeloma elevated pre-treatment levels of S-ICTP and U-Ntx are predictive of early progression of the bone disease during standard chemotherapy. Br J Hematoi 2003 120 235-42. 

Other chronic disorders cause osteomalacia. " " Phosphate depletion from low dietary intake, phosphate-binding antacids, and oncogenic osteomalacia (potentially phosphaturic effect) can cause osteomalacia. Hypophosphatasia is an inborn error of metabolism in which deficient activity of alkaline phosphatase causes impaired mineralization of bone matrix. Acidosis from renal dysfunction, distal renal tubular acidosis, hypergammaglobulinemic states (e.g., multiple myeloma), and drugs (e.g., chemotherapy) compromises bone mineralization. Renal tubular disorders secondary to Fanconi s syndrome, hereditary diseases (e.g., Wilson s disease, a defect in copper metabolism), acquired disease (e.g., myeloma), and toxins (e.g., lead) cause osteomalacia to varying degrees. Chronic wastage of phosphorus and/or calcium limits mineralization, which may be further compromised by acidosis and secondary hyperparathyroidism. 

Impaired humoral immunity Loss of protective barriers Multiple myeloma Chronic lymphocytic leukemia Splenectomy Immunosuppressive therapy (steroids, chemotherapy) Bacteria S. pneumoniae, H. influenzae, N. meningitidis... 

A numher of other groups, including immunocompromised patients (e.g., leukemia, lymphoma, and multiple myeloma), dialysis patients, and acquired immunodeficiency syndrome (AIDS) patients, have reduced antibody production with the vaccine. Asymptomatic HIV-infected patients respond sufficiently to the vaccine. Patients with Hodgkin s disease respond to the vaccine better before splenectomy, chemotherapy, or radiation therapy. 

Stewart AK, Vescio R, Schiller G, et al. Purging of autologous peripheral-blood stem cells using CD34 selection does not improve overall or progression-free survival after high-dose chemotherapy for multiple myeloma results of a multicenter randomized controlled trial. J Clin Oncol 2001 19 3771-3779. 

In a study in 100 patients with newly diagnosed multiple myeloma given induction chemotherapy (dexamethasone, vincristine, doxorubicin, cyclophosphamide, etoposide and cisplatin) with or without thalidomide, deep vein thrombosis developed in 14 of the 50 patients (28%) given thalidomide compared with 2 of 50 patients (4%) not given thalidomide. Deep vein thrombosis has been reported to occur in 10% of patients treated for multiple myeloma but is reported to occur in about 2% in patients with multiple myeloma treated with thalidomide alone. ... 

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