Rinsho Ketsueki

In recent years, novel drugs for multiple myeloma such as bortezomib and thalidomide have been shown to be effective. However, in Japan, these drugs are indicated only for patients with relapsed or refractory multiple myeloma. There are no established criteria for the definition of refractory cases, and it is often difficult to determine when treatment methods should be changed for those cases. Therefore, we performed a retrospective study to investigate whether treatment responses can be predicted in the early stage of VAD therapy. After the first and third cycles of VAD, the M-protein reduction rate was evaluated. As a result, it was estimated with a 50% probability that an M-protein reduction rate of 87.6% (lower limit of the 95% CI, 73.9%) after the first cycle of VAD can predict a reduction of 90% after the third cycle. The progression-free survival period was slightly longer in the group achieving 90% M-protein reduction after the third cycle than in the group who did not achieve this rate (3.3 vs 2.2 years, p=0.09). These findings suggest that a change from conventional to novel therapeutic drugs in refractory cases identified by the responses to the first cycle of VAD can be a beneficial treatment strategy.

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A 67-year-old man was diagnosed with multiple myeloma IgA-lambda type, Durie-Salmon classification stage IIIA in October 2001. He received five courses of induction chemotherapy consisting of vincristine, doxorubicin and dexamethasone and then underwent high dose chemotherapy followed by autologous stem cell transplantation in March 2003. He achieved partial response, but then relapsed after treatment with thalidomide and was admitted to our hospital in June 2007. The patient was complicated by tumor lysis syndrome (TLS) after receiving bortezomib therapy twice. Computed tomography after bortezomib therapy showed the rapid appearance of tumors in the right upper lobe of the lung, tail of the pancreas and the spleen. Though he was treated with antifungal agents, micafungin and voriconazole, he died eighty-five days after admission. Autopsy specimen showed fungal clumps and hemorrhagic infarction in the lung and spleen, and vegetation at the mitral valve was the same fungus as found in the lung. We diagnosed disseminated zygomycosis based on the pathological fungal morphology. This case suggested that metabolic acidosis was caused by TLS, while poorly controlled diabetes, secondary hemochromatosis due to transfusion, and breakthrough zygomycosis during antifungal therapy were thought to be factors contributing to the development of zygomycosis.

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