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Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology 2006-Dec

[Salvage therapy with proteasome inhibitor bortezomib for relapsed and refractory multiple myeloma].

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Wen-Rong Huang
Rong Li
Yu Jing
Yi-Zhuo Zhang
Xiao-Xiong Wu
Chun-Ji Gao
Jian Bo
Li Yu
Quang-Shun Wang
Wan-Ming Da

Sleutelwoorden

Abstract

Multiple myeloma is a malignant disease with high incidence in middle-aged and old-aged population. Bortezomib is a proteasome inhibitor which target mainly is NF-kappaB. This observation is to study the clinical treatment effect of bortezomib in one relapsed multiple myeloma (MM) patient and one primary refractory MM patient. The first patient diagnosed as IgA IIIA stage, whose state of disease became worse after 8 months of autologous peripheral blood stem cell transplantation. And the disease became further aggressive with 4 courses of chemical therapy regimen including methylprednisolone, Arsenic trioxide, dexamethasone, cyclophosphamide, mitoxantrone, VM-26. Myeloma cells in bone marrow and abnormal monoclonal immunoglobulin in blood plasma both increased. Bone destruction became severe, and there was a plasmacytoma about 5 x 6 cm on the patient's right upper chest wall. Therefore, the patient received therapy of bortezomib combined with doxrubicin, dexamethasone and thalidomide (VADT). After one course of therapy with this VADT regimen, IgA in blood plasma decreased from 54 g/L to 6.6 g/L, and abnormal plasma cells in bone marrow decreased from 40% to 0.6%, and plasmacytoma on the patient's right upper chest wall almost absorbed. But there was no obvious clinical effect after the second course of therapy of VADT, and the disease status became progressive again. The second patient was MM patient with a light chain kappa type, III B stage. There was no any effect after two courses of VAD therapy and one course of MOFP therapy. The patient acquired near complete remission after one course of treatment with VADT. Quantity of kappa protein in urine reduced from 24 - 30 g/24 hours to 1.12 g/24 hours. Blood creatinine reduced from 475.3 micromol/L to 124.2 micromol/L. Beta2-MG reduced from 161g/L to 64 g/L. And this patient got complete remission after three consecutive VADT therapy. The mainly side effects of the bortezomib regimen in the first patient include markedly lassitude, diarrhea, numbness of the end of extremities, marked increase of LDH. All the side effects could be tolerated and became disappeared after contraposing treatment and stopping the bortezomib regimen therapy. The second patient complicated with severe subacute left hemiplegia after the bortezomib dose had been increased to 1.45 mg/m2 at the third time of the first VADT course and the complication became worst at the following day. The upper limb muscle strength was only 1 grade and the lower limb muscle strength was 2 grade. Then the condition improved with the support therapy and gradually recovered after two weeks. Therefore, bortezomib is an effective target drug for therapy in refractory multiple myeloma, and more attentions to the side effects should be paid in order to deal with those side effects in time.

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