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Mutational signature leading to clinically aggressive multiple myeloma: 4 case reports In a study, four men aged 53–64 years were described, who developed mutational signature leading to clinically aggressive multiple myeloma following with melphalan and cisplatin, or melphalan for multiple myeloma [dosages, routes, durations of treatment to reactions onset, outcomes and causes of death not stated]. Patient 1: A 53-year-old man, who was diagnosed with multiple myeloma (IgG Kappa type), received high-dose melphalan therapy and underwent an autologous stem cell transplantation. However, after melphalan treatment, the disease relapsed and he died. His autopsy report revealed a new mutational signature named SBSMM1, which was considered secondary to the melphalan therapy. It was concluded that the mutation was associated with clinically aggressive multiple myeloma at relapse. Patient 2: A 60-year-old man, who was diagnosed with multiple myeloma (IgG Kappa type), received first course of high-dose melphalan therapy and underwent an autologous stem cell transplantation. After melphalan therapy, he received pomalidomide, followed by cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE regimen). However, the disease relapsed. He underwent an allogeneic stem cell transplantation and received conditioning therapy with melphalan at the clinical relapse. Eventually, he died. His autopsy report revealed a new mutational signature named SBSMM1, which was considered secondary to the melphalan and cisplatin therapy. It was concluded that the mutation was associated with clinically aggressive multiple myeloma at relapse. Patient 3: A 54-year-old man, who was diagnosed with multiple myeloma (IgG Lambda type), received high-dose melphalan therapy and underwent an autologous stem cell transplantation. After the melphalan treatment, the disease relapsed. He started receiving bortezomib and lenalidomide, followed by carfilzomib and daratumumab. Eventually, he died. His autopsy report revealed a new mutational signature named SBSMM1, which was considered secondary to the melphalan therapy. It was concluded that the mutation was associated with clinically aggressive multiple myeloma at relapse. Patient 4: A 64-year-old man, who was diagnosed with multiple myeloma (IgA Kappa type), received high-dose melphalan therapy along with cisplatin, doxorubicin, cyclophosphamide, etoposide (PACE regimen) and pomalidomide. He then underwent an autologous stem cell transplantation. After melphalan therapy, his disease relapsed. Therefore, PACE regimen was started again. Eventually, he died. His autopsy report revealed a new mutational signature named SBSMM1, which was considered secondary to the melphalan and cisplatin therapy. It was concluded that the mutation was associated with clinically aggressive multiple myeloma at relapse. Landau HJ, et al. Accelerated single cell seeding in relapsed multiple myeloma. Nature Communications 11: 17 Jul 2020. Available from: URL: http://doi.org/10.1038/ 803505146 s41467-020-17459-z

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