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Пульмонология, гематология (англ,рус)

In patients without serum M protein, myeloma is indicated by Bence Jones proteinuria > 300 mg/24 h, osteolytic lesions (without evidence of metastatic cancer or granulomatous disease), and sheets or clusters of marrow plasma cells.

Prognosis

The disease is progressive and incurable, but median survival has recently improved to > 5 yr as a result of advances in treatment. Unfavorable prognostic signs at diagnosis are lower serum albumin and higher β2-microglobulin levels. Patients presenting with renal failure also do poorly unless kidney function improves with therapy.

Because multiple myeloma is ultimately fatal, patients are likely to benefit from discussions of end-of-life care that involve their doctors and appropriate family and friends. Points for discussion may include advance directives, the use of feeding tubes, and pain relief.

Treatment

• Chemotherapy for symptomatic patients

• Thalidomide SOME TRADE NAMES  THALOMID , bortezomib SOME TRADE NAMES VELCADE , or lenalidomide with corticosteroids and/or chemotherapy

• Possibly maintenance therapy

• Possibly stem cell transplantation

• Possibly radiation therapy

• Treatment of complications (anemia, hypercalcemia, renal insufficiency, infections, skeletal lesions)

Treatment of myeloma has improved in the past decade, and long-term survival is a reasonable therapeutic target. Therapy involves direct treatment of malignant cells in symptomatic patients and the treatment of the complications. Asymptomatic patients probably do not benefit from treatment, which is usually withheld until symptoms or complications develop. However, patients with evidence of lytic lesions or bone loss (osteopenia or osteoporosis) should be treated with monthly infusions of zoledronic acid SOME TRADE NAMES

ZOMETA or pamidronate SOME TRADE NAMES AREDIA to reduce the risk of skeletal complications.

Treatment of malignant cells: Until recently, conventional chemotherapy consisted only of oral melphalan SOME TRADE NAMES ALKERAN  and prednisone SOME TRADE NAMES DELTASONE given in cycles of 4 to 6 wk with monthly evaluation of response. Recent studies show superior outcome with the addition of either bortezomib SOME TRADE NAMES VELCADE or thalidomide SOME TRADE NAMES THALOMID . Other chemotherapeutic drugs, including other alkylating drugs (eg, cyclophosphamide SOME TRADE NAMES  CYTOXAN, doxorubicin SOME TRADE NAMES ADRIAMYCIN and its newer analog liposomal pegylated doxorubicin SOME TRADE NAMES ADRIAMYCIN ) also are more effective when combined with thalidomide SOME TRADE NAMES THALOMID or bortezomib SOME TRADE NAMES VELCADE . Many other patients are effectively treated with bortezomib SOME TRADE NAMES VELCADE , thalidomide SOME TRADE NAMES THALOMID , or lenalidomide plus glucocorticoids and/or chemotherapy.

Chemotherapy response is indicated by decreases in serum or urine M-protein, increases in RBCs, and improvement in renal function among patients presenting with kidney failure.

Autologous peripheral blood stem cell transplantation may be considered for patients who have adequate cardiac, hepatic, pulmonary, and renal function, particularly those whose disease is stable or responsive after several cycles of initial therapy. Allogeneic stem cell transplantation after non-myeloablative chemotherapy (eg, low-dose cyclophosphamide SOME TRADE NAMES CYTOXAN and fludarabine SOME TRADE NAMES FLUDARA ) or low-dose radiation therapy can produce myeloma-free survival of 5 to 10 yr in some patients. However, allogeneic stem cell transplantation remains experimental because of the high morbidity and mortality from graft vs. host disease.

In relapsed or refractory myeloma, combinations of bortezomib SOME TRADE NAMES VELCADE , thalidomide SOME TRADE NAMES THALOMID, or its newer analog lenalidomide with chemotherapy or corticosteroids may be used. These drugs are usually combined with other effective drugs that the patient has not yet been treated with, although patients with prolonged remissions may respond to retreatment with the same regimen that led to the remission.

Maintenance therapy has been tried with nonchemotherapeutic drugs, including interferon-α, which prolongs remission but does not improve survival and is associated with significant adverse effects. Following a response to corticosteroid-based regimens, corticosteroids alone are effective as a maintenance treatment. Thalidomide SOME TRADE NAMES THALOMID may also be effective as a maintenance treatment, and studies are evaluating maintenance therapy with bortezomib SOME TRADE NAMES VELCADE and lenalidomide among patients who have responded to these drugs alone or in combination therapeutic regimens.

Treatment of complications: In addition to direct treatment of malignant cells, therapy must also be directed at complications, which include anemia, hypercalcemia, renal insufficiency, infections, and skeletal lesions.

Anemia can be treated with recombinant erythropoietin (40,000 units sc q wk) in patients whose anemia is inadequately relieved by chemotherapy. If anemia produces cardiovascular or significant systemic symptoms, packed RBCs are transfused. Plasmapheresis is indicated if hyperviscosity develops (see Plasma Cell Disorders: Symptoms and Signs).

Hypercalcemia is treated with saluresis, IV bisphosphonates, and sometimes with prednisone SOME TRADE NAMES DELTASONE . Most patients do not require allopurinol SOME TRADE NAMES ZYLOPRIM . However, allopurinol SOME TRADE NAMES ZYLOPRIM is indicated for patients with high levels of serum uric acid or high tumor burden and a high risk of tumor lysis syndrome with treatment.

Renal compromise can be ameliorated with adequate hydration. Even patients with prolonged, massive Bence Jones proteinuria (≥ 10 to 30 g/day) may have intact renal function if they maintain urine output > 2000 mL/day. Dehydration combined with high-osmolar IV contrast may precipitate acute oliguric renal failure in patients with Bence Jones proteinuria.

Infection is more likely during chemotherapy-induced neutropenia. In addition, infections with the herpes zoster virus are occurring more frequently in patients treated with newer antimyeloma drugs. Documented bacterial infections should be treated with antibiotics; however, prophylactic use of antibiotics is not routinely recommended. Prophylactic use of antiviral drugs may be indicated for patients receiving specific drugs. Prophylactic IV immune globulin may reduce the risk of infection but is generally reserved for patients with recurring infections. Pneumococcal and influenza vaccines are indicated to prevent infection.

Skeletal lesions require multiple supportive measures. Maintenance of ambulation and supplemental Ca and vitamin D help preserve bone density. Analgesics and palliative doses of radiation therapy (18 to 24 Gy) can relieve bone pain. However, radiation therapy may impair the patient's ability to receive cytotoxic doses of systemic chemotherapy. Most patients, especially those with lytic lesions and generalized osteoporosis or osteopenia, should receive a monthly IV bisphosphonate (either pamidronate SOME TRADE NAMES AREDIA  or zoledronic acid SOME TRADE NAMES ZOMETA). Bisphosphonates reduce skeletal complications and lessen bone pain and may have an antitumor effect.

 

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