With the wide clinical application of proteasome inhibitors (PI), immunomodulary drugs (IMiD) and autologous stem cell transplantation (ASCT), the prognosis of multiple myeloma (MM) patients has been dramatically improved. However, MM is still an incurable disease, becoming relapse or disease progression finally. Therefore, the development of new drugs with varying mechanisms and the improvement of treatment regimens can help to eradicate the tumor clone and deepen the degree of disease remission. Although most new agents are in different stages of clinical trials, the emerging development of novel agents abroad currently has made MM patients obtain deeper and more enduring remission according to the early experimental data, adding the good safety and efficacy of the new drugs, which could bring the promising clinical application. Varieties of novel drugs combined with PI or IMiD could provide new treatment regimens for MM. This paper reviews the recent progress of the targeted novel drugs of MM.

Objective:To investigate the diagnosis and treatment of histiocytic necrotizing lymphadenitis (HNL) complicated with hemophagocytic syndrome (HPS).Methods:The clinical characteristics, diagnosis, treatment process, and therapy response of a patient with HNL complicated with HPS admitted to the Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences in March 2019 were retrospectively analyzed, and the literature was reviewed.Results:This 17-year-old female patient had fever with bilateral cervical lymphadenopathy as the first presentation, accompanied by cough and expectoration. After admission, the disease progressed rapidly, and the serum ferritin increased progressively.The regimen of hormone and etoposide was used to control the disease condition. The bone marrow smear revealed atypical lymphocytes and hemophagocytic phenomenon, and the pathological features of HNL in lymph node biopsy were observed. This patient was finally diagnosed as HNL complicated with HPS. The patient's condition was stable at 3-month follow-up after discharge.Conclusions:The clinical manifestations of HNL patients complicated with HPS are similar to other hematologic malignant diseases, and application of multiple laboratory and pathological examination methods can help with early diagnosis. In the event of a progressive rise in serum ferritin, timely application of hormone therapy combined with etoposide if necessary can rapidly control the progression of the disease.

Objective:To investigate the clinical features, diagnosis, and treatment of the central nervous system (CNS) toxicity caused by bortezomib.Methods:This study reports five new cases of CNS toxicity caused by bortezomib to elucidate its characteristics along with a review of the literature.Results:CNS toxicity caused by bortezomib presents in three clinical forms: syndrome of inappropriate antidiuresis (SIAD) , posterior reversible encephalopathy syndrome (PRES) , and central fever, which is the most common clinical manifestation. Four of our five patients developed central fever after the administration of bortezomib, manifested as persistent high fever, anhidrosis, and absence of infective foci; the symptom could be improved by discontinuance of bortezomib. Of these patients, three concurrently presented with refractory hyponatremia and one was clearly diagnosed with SIAD. The bortezomib could have caused damages to the hypothalamus and induced both central fever and SIAD. In addition, one patient was diagnosed with PRES due to disturbance of consciousness and epilepsy after taking bortezomib. After discontinuation of bortezomib, the symptoms disappeared and did not recur. We also found that thrombocytopenia may be related to the severity of the CNS toxicity of bortezomib.Conclusion:Cases of CNS toxicity of bortezomib are extremely rare and present as SIAD, PRES and central fever. Early detection and treatment of bortezomib are very important to prevent irreversible neurological complications.

Objective:To investigate the clinical characteristics, responses, and prognosis of immunoglobulin M multiple myeloma (IgM MM) .Methods:The clinical characteristics, laboratory results, bone marrow biopsy results, response, and prognosis of six cases of IgM MM in the Blood Diseases Hospital, Chinese Academy of Medical Sciences, from December 18, 2009 to October 29, 2020 were collected and analyzed.Results:All six cases met the diagnosis criteria of IgM MM. There were four males and two females. The median age at first diagnosis was 70 (59-81) years. According to Durie-Salmon (DS) staging, 2 cases were in ⅠA, and 4 cases were in ⅢA. According to the International Staging System (ISS) , 4 cases were in Ⅱ, and 2 cases were in Ⅲ. The initial symptoms were as follows: 4 cases of bone pain, 3 cases of hyperviscosity, and 2 cases of lymphadenopathy or hepatosplenomegaly. Laboratory results showed the following: median blood M protein: 39.11 (3.61-75.56) g/L; median serum IgM: 69.35 (4.35-137.00) g/L; median hemoglobin: 87.0 (70-131) g/L; median blood creatinine: 83.6 (53.0-129.6) μmol/L; median blood calcium: 2.12 (2.11-2.50) mmol/L. The median ratio of bone marrow plasma cells was 0.390 (0.255-0.590) , and in four cases, plasma cells were observed in blood smears. Karyotype analysis and fluorescence in situ hybridization (FISH) examination showed the following: 1 case of hypodiploidy, 2 cases of P53 gene deletion, 1 case of 1q21 amplification positive, and 4 cases of RB-1 gene deletion positive. The immunoglobulin heavy chain (IgH) rearrangement was positive in all cases, of which 3 cases were CCND1/IgH fusion gene-positive identified with t (11;14) rearrangement. Immunophenotyping revealed that all cases were positive for CD38, CD138, and monoclonal light chain and four cases were weakly positive for CD20. All cases accepted proteasome inhibitor-based regimens and attained the response of partial remission to strict complete remission.Conclusion:In addition to the typical clinical manifestations of myeloma, IgM MM is also characterized by hyperviscosity, lymphadenopathy, or hepatosplenomegaly, and t (11;14) is the most frequent cytogenetics aberration. Furthermore, the response and prognosis of IgM MM are similar to other common myeloma subtypes.

The clinical characteristics, laboratory results, response to treatment, and prognosis of 46 macrofocal multiple myeloma(MFMM) patients at our center from January 2013 to December 2019 were analyzed retrospectively. The other 92 patients were selected as matched-controls based on diagnostic period and treatment. Among the 1 137 MM patients, 46 patients met the definition criteria of MFMM (4.0%), with median age 56 years, which was not statistically different from whole MM population ( P=0.066). According to the international staging system (ISS) and Revised ISS, the proportion of patients with advanced stage in MFMM group was less common than that of controls ( P<0.05). More plasmacytomas in MFMM patients were presented (43.5% vs. 18.5%, P<0.05). Regarding cytogenetic abnormalities, there were minor patients manifesting high-risk features in MFMM group (15.8% vs. 32.2%, P=0.058). Translocation(11;14) could be detected in 32.4% MFMM patients and 9.4% typical myeloma patients ( P<0.05). The treatment regimens were comparable. As to the best response of treatment, the complete response (CR) rate in MFMM group was significantly higher than that of controls (78.3% vs. 60.9%, P<0.05). The median follow-up time was 37.9 months. The median progression-free survival in MFMM and control groups were 77.5 vs. 39.8 months, respectively ( P<0.05). The overall survival (OS) of MFMM patients was significantly longer (not reached vs. 68.2 months, P<0.05).

Humans ; Prognosis ; Multiple Myeloma/diagnosis* ; Neoplasm Staging ; Hematopoietic Stem Cell Transplantation ; Patients ; Retrospective Studies