Myelodysplastic Syndrome Secondary to Multiple Myeloma: A Case Report and Literature Review

Background: With the prolongation of survival in recent years, the accumulation of toxic and side effects of therapeutic drugs and the concomitant drug-related adverse reactions were reported in recent years. However, myelodysplastic syndrome secondary to multiple myeloma is rare. Objective: To improve the understanding of myelodysplastic syndrome secondary to multiple myeloma. Methods: The clinical data of a patient with myelodysplastic syndrome secondary to multiple myeloma after treatment were analyzed, and the related literature was reviewed. Results: A 54-year-old male patient was diagnosed as multiple myeloma in February 2014. After three courses of first-line induction chemotherapy, he achieved complete remission and received two courses of consolidation treatment. After that, he continued to take thalidomide orally. The disease recurred 13 months after complete remission (CR) with 6q+ karyotype change in 37 months. 21q− karyotype change was found in 39 months. The patient was finally diagnosed as treatment-related secondary myelodysplastic syndrome. Due to the poor effect of chemotherapy, the disease continued to deteriorate. Conclusion: In the course of multiple drug treatment, clinicians should pay attention to the changes of molecular genetics and the treatment-related secondary tumor.

Journal of Biosciences and Medicines tection of monoclonal protein in blood or urine, leading to the dysfunction of related organs [1]. MM is the second most common malignant tumor, accounting for about 1% of tumor diseases [2]. At present, the main treatment methods of MM were increasing, including proteasome inhibitors, immunomodulators, alkylating agents and hematopoietic stem cell transplantation. With the prolongation of survival, the accumulation of toxic and side effects of therapeutic drugs and the concomitant drug-related adverse reactions were reported in recent years.
However, myelodysplastic syndrome secondary to multiple myeloma is rare. The increased risk of secondary MDS (s-MDS) seriously threatens the long-term prognosis and quality of life of MM patients. Therefore, early detection of patients who are at high risk of secondary tumor will have important guiding significance for the follow-up diagnosis and treatment of patients.
In this study, we report a case of MM with normal karyotype of bone marrow at the initial diagnosis. During the treatment, there were 6q+ and 21q− chromosome changes. Two months later, s-MDS was diagnosed.

Case Presentation
A 59-year-old man was admitted to our hospital in February 2014 due to "chest and back pain for 20 days". After hospitalization, blood routine examination show hemoglobin was 62 g/L. Immunoglobulin shows IgA was 63.51 g/L. β2 microglobulin was 13.80 mg/L. blood light chain show κ chain was 322 mg/L, λ chain was 2090 mg/L, κ/λ ratio was 0.154. Blood immunoprotein fixed 39 months after CR, the blood routine showed white blood cell (WBC) count was 1.88 × 10 9 /L, neutrophil count was 0.43 × 10 9 /L, hemoglobin was 75 g/L, After that, the patient refused further treatment and discharged automatically.
After that, the patient was lost to follow-up.
The course of the disease was 48 months from diagnosis to final deterioration.
Abnormal karyotype was found in the 42 months after diagnosis. 16% of myeloid progenitor cells were found months after diagnosis. From the diagnosis of MM to the diagnosis of secondary MDS, the total dose of thalidomide was gradually increased from 100 mg/d to 400 mg/d within the tolerable range of patients.

Discussion
A large number of literatures have reported that the risk of secondary hematological tumors in tumor patients is significantly higher than that in ordinary people [3] [4] [5]. In recent years, with the prolongation of the survival time in MM patients, the incidence rate of MM related second tumors was increased [6].
Studies show that there is a causal relationship between the treatment of primary malignant tumors and the incidence of secondary tumors. The alkylating agent based therapy combined with immunomodulatory drugs will increase the risk of secondary tumor, among which lenalidomide is the most reported [7] [8]. In the evaluation and analysis of MM patients receiving various chemical regimens, the risk factors of secondary MDS or AML included male patients, old age and using thalidomide or lenalidomide [9].
In this study, the patient was treated with cyclophosphamide, ifosfamide and etoposide, and the patients had been taking thalidomide orally almost all the time during the course of the disease. The dose gradually increased from 100 mg/d to 400 mg/d at the maximum, and there was no obvious adverse reaction.
It has been reported that alkylating agent combined with thalidomide may in- In this study, the patient was diagnosed with MDS two months after karyotype changed. A study [10]  In conclusion, patients with multiple myeloma should be monitored blood routine test and chromosome karyotype during the treatment. Patients with unexplained abnormal blood and abnormal chromosome karyotype should be alert to the occurrence of secondary hematological second tumor.

Consent
Written informed consent was obtained from the patient for publication of this article and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.