Abstract

Bortezomib has been shown to increase the response rate, time to disease progression, and overall survival in patients with relapsed-refractory multiple myeloma(MM). We currently treated a refractory MM patient and observed extremely elevated lactate dehydrogenase(LDH) and aspartate aminotransferase (AST) levels during bortezomib treatment, but without the abnormal serum electrolyte concentrations and elevated uric acid level. A 67 years old female was admitted to our hospital. She has been suffered with fatigue, lumbar myalgia, dizziness and difficulty in ambulation since Nov 2005. She was found renal inadequacy and intermediate anemia and was diagnosed with stage III MM, IgG type on bone marrow pathology, immunoglobulin analysis and X-ray examination. The disease was not controllable after 3 cycles of VAD regimen (vincristine, adriamycin and dexamethason). She had severe chest and back pain and was on morphine. Bone marrow morphology showed 32 percent plasma cells and her immunoglobulin G (IgG) level was 85g/L, microglobulin β2 level over 10000 ng/ml and creatinine 310.3mmol/L. She was also with hypercalcinemia and elevated serum LDH and AST transaminase level. Bortezomib therapy was considered with her refractory MM in disease progression and deterioration. Bortezomib at 1.3 mg/m2 IV days 1, 4, 8, 11 were planned to be administered in the first three weeks, in combination with dexamethazone at 40 mg on the same days. And a diphosphonate regimen was administered simultaneously. Hydration and alkalinization were initiated one day before the administering of chemotherapy. She was also given allopurinol prophylactically. She was suffered with severe debilitation and mild diarrhea after the second dosage of bortezomib. Gradually elevated LDH and AST were observed, with an extremely high point at 18666 and 9551 respectively on day 9 (table 1). LDH isoenzymes analysis showed that tumor-derived LDH3 and LDH4 were dramatically increased. AST isoenzyme analysis demonstrated elevated serum AST level, with normal level of mitochondria-derived AST level. Although her serum phosphate level was mild elevated and the calcium level was decreased, but the serum potassium, uric acid levels were normal. This could be the effect of diphosphonate regimen. The third and fourth doses of bortezomib were delayed for one week. Her chest and back pain was relieved shortly after the combination therapy. And only 1 percent of plasma cells were found on bone marrow smear prepared on day 20. Her IgG level decreased steadily and it was 19.5g/L on day 28. The microglobulin β2 level was 7200 ng/ml and creatinine was 173 mmol/L. She was still with elevated serum LDH and AST transaminase levels at 1129 and 324 respectively on day 28. We concluded that combination therapy with bortezomib and dexamethazone is very potent and effective in this refractory MM patient. The response is dramatically prompt with rapid tumor lysis demonstrated by extremely elevated LDH and AST level in this case. Carefully prophylactical measurement is recommended for patients under bortezomib treatment to prevent tumor lysis syndrome, a life-threatening metabolic emergency.

Dynamic changes of LDH and AST level during bortezomib treatment

LDH(IU/L)AST(u/L)
day 0 915 529 
day 2 1022 539 
day 5 5032 3120 
day 7 18666 9551 
day 8 14706 6090 
day 9 7354 3575 
day 10 5602 3704 
day 11 4838 3324 
day 13 2847 1220 
day 14 2529 842 
LDH(IU/L)AST(u/L)
day 0 915 529 
day 2 1022 539 
day 5 5032 3120 
day 7 18666 9551 
day 8 14706 6090 
day 9 7354 3575 
day 10 5602 3704 
day 11 4838 3324 
day 13 2847 1220 
day 14 2529 842 

Disclosure: No relevant conflicts of interest to declare.

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