Chapter 106. Plasma Cell Disorders (Part 8)

Randomized studies comparing standard-dose therapy to high-dose melphalan therapy (HDT) with hematopoietic stem cell support have shown that HDT can achieve high overall response rates and prolonged progression-free and overall survival; however, few, if any, patients are cured.
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Chapter 106. Plasma Cell Disorders (Part 8) Chapter 106. Plasma Cell Disorders (Part 8) Randomized studies comparing standard-dose therapy to high-dosemelphalan therapy (HDT) with hematopoietic stem cell support have shown thatHDT can achieve high overall response rates and prolonged progression-free andoverall survival; however, few, if any, patients are cured. Although completeresponses are rare ( There is no standard maintenance therapy to prolong time to progression.IFN-α has allowed modest benefit but has significant side effects. Oral prednisonemaintenance therapy was effective in a single trial. Ongoing studies are evaluatingmaintenance thalidomide and lenalidomide to prolong progression-free survivalpost-transplant. Relapsed myeloma can be treated with novel agents including lenalidomideand/or bortezomib. These agents target not only the tumor cell but also the tumorcell–bone marrow interaction and the bone marrow milieu. These agents incombination with dexamethasone can achieve up to 60% partial responses and 10–15% complete responses in patients with relapsed disease. The combination ofbortezomib and liposomal doxorubicin is active in relapsed myeloma.Thalidomide, if not used as initial therapy, can achieve responses in refractorycases. High-dose melphalan and stem cell transplant, if not used earlier, also haveactivity in patients with refractory disease. The median overall survival of patients with myeloma is 5–6 years, withsubsets of patients surviving over 10 years. The major causes of death areprogressive myeloma, renal failure, sepsis, or therapy-related acute leukemia ormyelodysplasia. Nearly a quarter of patients die of myocardial infarction, chroniclung disease, diabetes, or stroke, all intercurrent illnesses related more to the ageof the patient group than to the tumor. Supportive care directed at the anticipated complications of the disease maybe as important as primary antitumor therapy. The hypercalcemia generallyresponds well to bisphosphonates, glucocorticoid therapy, hydration, andnatriuresis. Calcitonin may add to the inhibitory effects of glucocorticoids on boneresorption. Bisphosphonates (e.g., pamidronate 90 mg or zoledronate 4 mg once amonth) reduce osteoclastic bone resorption and preserve performance status andquality of life, decrease bone-related complications, and may also have antitumoreffects. Treatments aimed at strengthening the skeleton, such as fluorides, calcium,and vitamin D, with or without androgens, have been suggested but are not ofproven efficacy. Iatrogenic worsening of renal function may be prevented bymaintaining a high fluid intake to prevent dehydration and to help excrete lightchains and calcium. In the event of acute renal failure, plasmapheresis is ~10 timesmore effective at clearing light chains than peritoneal dialysis; however, its role inreversing renal failure remains controversial. Importantly, reducing the proteinload by effective antitumor therapy with agents such as bortezomib may result infunctional improvement. Urinary tract infections should be watched for andtreated early. Plasmapheresis may be the treatment of choice for hyperviscositysyndromes. Although the pneumococcus is a dreaded pathogen in myelomapatients, pneumococcal polysaccharide vaccines may not elicit an antibodyresponse. Prophylactic administration of IV γglobulin preparations is used in thesetting of recurrent serious infections. Chronic oral antibiotic prophylaxis isprobably not warranted. Patients developing neurologic symptoms in the lowerextremities, severe localized back pain, or problems with bowel and bladdercontrol may need emergency MRI and radiation therapy for palliation. Most bonelesions respond to analgesics and chemotherapy, but certain painful lesions mayrespond most promptly to localized radiation. The anemia associated withmyeloma may respond to erythropoietin along with hematinics (iron, folate,cobalamin). The pathogenesis of the anemia should be established and specifictherapy instituted, where possible. Waldenströms Macroglobulinemia In 1948, Waldenström described a malignancy of lymphoplasmacytoidcells that secreted IgM. In contrast to myeloma, the disease was associated withlymphadenopathy and hepatosplenomegaly, but the major clinical manifestationwas the hyperviscosity syndrome. The disease resembles the related diseaseschronic lymphocytic leukemia, myeloma, and lymphocytic lymphoma. Itoriginates from a post–germinal center B cell that has undergone somaticmutations and antigenic selection in the lymphoid follicle and has thecharacteristics of an IgM-bearing memory B cell. Waldenströmsmacroglobulinemia and IgM myeloma follow a similar clinical course, buttherapeutic options ...