Effects of extramedullary disease on patients with newly diagnosed multiple myeloma / 中华血液学杂志

Objective: To summarize the characteristics of patients with newly diagnosed multiple myeloma (NDMM) admitted at Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine. We compared the clinical characteristics and prognoses among patients with non-extramedullary disease (EMD), bone-related extramedullary (EM-B) disease, and extraosseous extramedullary (EM-E) disease and further explored the effects of autologous hematopoietic stem cell transplantation (ASCT) for EMD. Methods: From January 2015 to January 2022, data of 114 patients (22%) with EMD out of 515 patients with NDMM were retrospectively analyzed; 91 (18%) and 23 (4%) patients comprised the EM-B and EM-E groups, respectively. The clinical characteristics of patients in all groups were compared with the Chi-square test. Progression-free survival (PFS) and overall survival (OS) of patients were analyzed by the Kaplan-Meier method. Independent prognostic factors were determined using multivariate Cox proportional hazard model. Results: There were no significant differences in age, gender, ISS stage, light chain, creatinine clearance, cytogenetic risk, 17p deletion, ASCT, and induction regimens among the three groups. Overall, 13% of EM-E patients had IgD-type M protein, which was significantly higher than that in EM-B patients (P=0.021). The median PFS of patients in the non-EMD, EM-B, and EM-E groups was 27.4, 23.1, and 14.0 months; the median OS was not reached, 76.8 months, and 25.6 months, respectively. The PFS (vs non-EMD, P=0.004; vs EM-B, P=0.036) and OS (vs non-EMD, P<0.001; vs EM-B, P=0.002) were significantly worse in patients with EM-E, while those were not significantly different between patients with EM-B and those with non-EMD. In the multivariate analysis, EM-E was an independent prognostic factor for OS in patients with NDMM (HR=8.779, P<0.001) and negatively impacted PFS (HR=1.874, P=0.050). In those who did not undergo ASCT, patients with EM-B had significantly worse OS than those with non-EMD (median 76.8 months vs. not reached, P=0.029). However, no significant difference was observed in the PFS and OS of patients with EM-B and those with non-EMD who underwent ASCT. Conclusions: Compared to patients with either non-EMD or EM-B, those with EM-E had the worst prognosis. EM-E was an independent risk factor for OS in patients with NDMM. ASCT can overcome the poor prognosis of EM-B.

Construction of NKG2D CAR-NK92 cells and its killing effect on multiple myeloma cells / 细胞与分子免疫学杂志

Objective This study aims to construct and identify the chimeric antigen receptor NK92 (CAR-NK92) cells targeting NKG2D ligand (NKG2DL) (secreting IL-15Ra-IL-15) and verify the killing activity of NKG2D CAR-NK92 cells against multiple myeloma cells. Methods The extracellular segment of NKG2D was employed to connect 4-1BB and CD3Z, as well as IL-15Ra-IL-15 sequence to obtain a CAR expression framework. The lentivirus was packaged and transduced into NK92 cells to obtain NKG2D CAR-NK92 cells. The proliferation of NKG2D CAR-NK92 cells was detected by CCK-8 assay, IL-15Ra secretion was detected by ELISA and killing efficiency was detected by lactate dehydrogenase (LDH) assay. The molecular markers of NKp30, NKp44, NKp46, the ratio of apoptotic cell population, CD107a, and the secretion level of granzyme B and perforin were detected using flow cytometry. In addition, the cytotoxic mechanism of NKG2D CAR-NK92 cells on the tumor was verified by measuring the degranulation ability. Moreover, after NKG2D antibody inhibited effector cells and histamine inhibited tumor cells, LDH assay was utilized to detect the effect on cell-killing efficiency. Finally, the multiple myeloma tumor xenograft model was constructed to verify its anti-tumor activity in vivo. Results Lentiviral transduction significantly increased NKG2D expression in NK92 cells. Compared with NK92 cells, the proliferation ability of NKG2D CAR-NK92 cells was weaker. The early apoptotic cell population of NKG2D CAR-NK92 cells was less, and NKG2D CAR-NK92 cells had stronger cytotoxicity to multiple myeloma cells. Additionally, IL-15Ra secretion could be detected in its culture supernatant. NKp44 protein expression in NKG2D CAR-NK92 cells was clearly increased, demonstrating an enhanced activation level. Inhibition test revealed that the cytotoxicity of CAR-NK92 cells to MHC-I chain-related protein A (MICA) and MICB-positive tumor cells was more dependent on the interaction between NKG2D CAR and NKG2DL. After stimulating NKG2D CAR-NK92 cells with tumor cells, granzyme B and perforin expression increased, and NK cells obviously upregulated CD107α. Furthermore, multiple myeloma tumor xenograft model revealed that the tumors of mice treated with NKG2D CAR-NK92 cells were significantly reduced, and the cell therapy did not sensibly affect the weight of the mice. Conclusion A type of CAR-NK92 cell targeting NKG2DL (secreting IL-15Ra-IL-15) is successfully constructed, indicating the effective killing of multiple myeloid cells.

Diagnosis and treatment of multiple myeloma in Hunan Province / 中南大学学报(医学版)

OBJECTIVES@#There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM.@*METHODS@#The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0.@*RESULTS@#Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%).@*CONCLUSIONS@#In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.

The Value of Serum HMGB1 and sRAGE in the Diagnosis, Efficacy Monitoring and Prognosis of Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the value of high mobility group protein B1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the diagnosis, efficacy monitoring and prognosis of newly diagnosed multiple myeloma (MM) patients.@*METHODS@#Fifty newly diagnosed MM patients before and after chemotherapy and 50 hematological outpatients from October 2018 to May 2020 were selected. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum HMGB1 and sRAGE levels of the patients. ROC was used to further analyze the efficacy of serum HMGB1 and sRAGE levels on the diagnosis of MM. At the same time, the serum levels of HMGB1 and sRAGE before and after chemotherapy were compared, and their values in the evaluation of curative effect of MM patients were analyzed. According to the mean values of serum HMGB1 and sRAGE, all the patients were divided into different groups, the clinical characteristics and survival status of the patients were compared.@*RESULTS@#Before treatment the serum HMGB1 level of the patients in MM group was higher than that in control group, while sRAGE level was lower (t=11.363,6.127, P<0.001). The AUC of serum HMGB1 and sRAGE in the MM patients was 0.955 and 0.811, respectively. After 3 courses of chemotherapy, HMGB1 level of the patients in CR group was lower than before chemotherapy, while in PD group was higher, as well as sRAGE level of the patients in PR group (P<0.05). There were significant differences in R-ISS stage, HGB, CRP, ESR, CD56, CD117, D13S319 deletion between HMGB1 high expression group and HMGB1 low expression group (χ2=3.920, 6.522, 6.65, 4.16, 3.945, 6.65, 4.16, P<0.05), while there were significant differences in ISS stage, CRP and CD56 between sRAGE low expression group (28 cases) and sRAGE high expression group (22 cases) (χ2=4.565, 4.711, 5.547, P<0.05). Kaplan-Meier survival analysis showed that the patients in HMGB1 low expression group had better survival condition, for PFS Tlow>Thigh (χ2=9.470, P<0.05), and for OS Tlow>Thigh (χ2=7.808, P<0.05); there was no difference in the survival of sRAGE high expression group and low expression group, for PFS Tlow<Thigh (χ2=1.661, P>0.05), and for OS Tlow<Thigh (χ2=2.048, P>0.05). Cox analysis showed that LDH and HMGB1 were the factors affecting the prognosis of the patients, and both of them affected PFS (HR=2.771, 95% CI: 1.002-7.662, P=0.049; HR=6.022, 95% CI: 1.689-21.470, P=0.006), while HMGB1 also affected OS (HR=4.275, 95% CI: 1.183-15.451, P=0.027).@*CONCLUSION@#The serum HMGB1 and sRAGE have certain auxiliary value for the diagnosis and curative effect monitoring of newly diagnosed MM patients, and serum HMGB1 is expected to be an auxiliary detection index for the prognosis of MM.

Toxicity Management and Efficacy Evaluation of BCMA-CART in the Treatment of Relapsed and Refractory Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM).@*METHODS@#The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated.@*RESULTS@#After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity.@*CONCLUSION@#BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.

A clinical retrospective analysis of newly diagnosed multiple myeloma patients with systemic light chain amyloidosis / 中华血液学杂志

Objective: To analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group (P=0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7%vs 79.7%, P<0.05) and higher excellent partial response (76.2%vs 55.1%, P<0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups (P>0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group (P<0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement (P<0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.

Young age and autologous stem cell transplantation are associated with improved survival in newly diagnosed multiple myeloma

ABSTRACT Background: Multiple myeloma is a disease of the elderly. However, 40% of patients are diagnosed before 65 years old. Outcomes regarding age as a prognostic factor in MM are heterogeneous. Method: We retrospectively analyzed clinical characteristics, response to treatment and survival of 282 patients with active newly-diagnosed multiple myeloma, comparing results between patients younger and older than 65 years. Main results: The frequency of multiple myeloma in those younger than 66 years was 53.2%. Younger patients presented with a more aggressive disease, more advanced Durie-Salmon stage (85.3% vs 73.5%; p = 0.013), extramedullary disease (12.7% vs 0%; p < 0.001), osteolytic lesions (78.7% vs 57.6%; p < 0.001) and bone plasmacytoma (25.3% vs 11.4%; p = 0.003). In spite of this, the overall response rate was similar between groups (80.6% vs 81.4%; p = 0.866). The overall survival was significantly longer in young patients (median, 65 months vs 41 months; p = 0.001) and higher in those who received autologous hematopoietic stem cell transplantation. The main cause of death was disease progression in both groups. Multivariable analysis revealed that creatinine ≥2 mg/dl, extramedullary disease, ≤very good partial remission and non-autologous hematopoietic stem cell transplantation are independent risk factors for shorter survival. Conclusion: Although multiple myeloma patients younger than 66 years of age have an aggressive presentation, this did not translate into an inferior overall survival, particularly in those undergoing autologous hematopoietic stem cell transplantation.

Do cytomegalovirus infections affect the daratumumab treatment course in multiple myeloma patients? - Literature review

ABSTRACT Introduction Multiple myeloma is a progressive and incurable hematological disease characterized by disordered and clonal multiplication of plasmacytes in the bone marrow. The main clinical manifestations are caused by the presence of neoplastic cells in bone tissue, as well as the excessive production of immunoglobulins and normal humoral immunity suppression. Daratumumab is an anti-CD38 monoclonal antibody that has promising results in managing the multiple myeloma disease. Objective This study aimed to investigate the scientific evidence concerning the impact of the cytomegalovirus infections in the daratumumab treatment course in extensively pretreated multiple myeloma patients. Method To this end, an integrative literature review was performed in different databases, comprising a 5-year period. Results The studies analysis revealed that the cytomegalovirus infection reactivation can occur during the use of daratumumab in multiple myeloma patients previously treated, which led to treatment discontinuation, compromised the drug efficacy and favored the disease progression. Moreover, it was observed that even with prophylactic antiviral therapy there was an infection reactivation in some cases, as well as deaths, in more severe situations. Conclusion Thus, even considering that few reports on such a topic are available in the scientific literature, the present review showed that cytomegalovirus reactivation can impair daratumumab therapy, mainly in multiple myeloma patients heavily pretreated. In addition, this study could contribute as a tool for the clinical decision and management of adverse effects in medical practices, demonstrating the importance of patient monitoring for the possibility of cytomegalovirus reactivation in heavily pretreated myeloma patients.

Analysis of Related Early Warning Indexes of Cytokine Release Syndrome in Multiple Myeloma Patients after CAR-T Treatment / 中国实验血液学杂志

OBJECTIVE@#To investigate the relationship between the levels of ferritin, C-reactive protein (CRP), lactate dehydrogenase (LDH) and interleukin-6 (IL-6) in peripheral serum and cytokine release syndrome (CRS) in patients with relapse and/or refractory multiple myeloma (R/R MM) after receiving chimeric antigen receptor T cells (CAR-T) immunotherapy.@*METHODS@#Twenty-eight patients with R/R MM were treated with 1×10@*RESULTS@#Among the 28 patients, 27 cases (96.4%) developed CRS, 24 cases (85.7%) in 1-2 grade CRS and 3 cases (10.7%) in 3-5 grade. The severity grade of CRS of 27 patients was positively correlated with the peak values of ferritin, CRP, LDH, and IL-6 in peripheral blood (r@*CONCLUSION@#After receiving CAR-T cellular immunotherapy, the incidence of CRS in patients with R/R MM is higher, but most of them are in grade 1 or 2. The severity of CRS is positively correlated with the levels of ferritin, CRP, LDH and IL-6 in peripheral blood.

Clinical Features and Prognostic Factors of Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To summarize the clinical and Laboratory characteristics of patients with multiple myeloma (MM) and analyze the prognostic factors.@*METHODS@#Two hundred MM patients were retrospectively analyzed for the following parameters, including peripheral blood, bone marrow morphology, cytogenetics, clinical staging, and response to the chemotherapy in order to summarize related factors affecting overall survival (OS). The prognostic factors were also analyzed.@*RESULTS@#200 patients with MM were divided into 3 groups according to bone marrow plasma cell percentage (BMPC%) in bone marrow smears: ＜10% group (74 cases, 37.0%), 10%-50% group (75 cases, 37.5%), ＞50% group (51 cases, 25.5%). Compared with the other two groups, patients in BMPC%<10% group were characterized by lower clinical staging levels, lower rates of 13q14 deletion and t(11;14) positive, better response to chemotherapy and favorable three-year OS rate. The univariate analysis showed that prognostic factors indicating favorable outcome as evaluated by OS included age≤55 years old, BMPC%＜10%, WBC＜7.5×10@*CONCLUSION@#The clinical characteristics are different among MM patients with different BMPC% in bone marrow smears at initial diagnosis, and prognostic analysis shows that the BMPC% in bone marrow smears has an effect on OS rate. BMPC% in bone marrow smears at initial diagnosis, age, WBC, Hb, response to the fourth chemotherapy are also the main factors impacting the prognosis of patients.

Application of Conditioning Regimen with Busulfan and Cyclophosphamide in Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the safety and efficacy of BUCY (busulfan and cyclophosphamide) conditioning regimen for autologous hematopoietic stem cell transplantation (ASCT) in patients with multiple myeloma (MM).@*METHODS@#The clinical data of 72 MM patients received transplantation in the Hematology Department of the First Affiliated Hospital of Soochow University from May 2012 to June 2015 were retrospectively analyzed. Among them, 36 patients received BUCY conditioning regimen while the others received high-dose melphalan (HDM) conditioning regimen. The complication, post-transplantation hematopoietic reconstitution and efficacy between the two groups were compared.@*RESULTS@#There were no significant differences in sex, age, isotype, stage, induction therapy, mobilization method and proportion of conditioning regimen with Bortezomib between the two groups. The median time of neutrophil engraftment for the patients in BUCY and HDM groups was 10 (8-17) and 10 (9-13) d (P=0.046), and the median time of platelet engraftment was 10 (8-18) and 11 (9-47) d (P=0.017), respectively. The transplant related mortality of the patients in both groups was 2.7%. The CR rates of the patients after ASCT (38.9% and 50.0%) were higher than those before ASCT (27.8% and 19.4%) in the two groups. For the patients in BUCY group, the median follow-up time was 45 (0-61) months. Fifteen patients (41.7%) achieved disease progression. While for the patients in HDM group, the median follow-up time was 52(0-75) months. Twenty-two patients (61.1%) achieved disease progression.@*CONCLUSION@#The BUCY conditioning regimen is a safe and effective therapy for ASCT in patients with MM. Besides, in terms of safety and efficacy, BUCY regimen is not inferior to HDM regimen. BUCY regimen may replace HDM regimen as a standard conditioning regimen for ASCT in MM.

Predictive Value of Newly Diagnosed IgG Level in Patients with IgG-type Multiple Myeloma after Initial Treatment / 中国实验血液学杂志

OBJECTIVE@#To explore the predictive value of newly diagnosed IgG levels in the recurrence of IgG-type multiple myeloma (MM) patients after initial treatment.@*METHODS@#The clinical and pathological data of 91 patients newly diagnosed IgG-type MM who were hospitalized in the Department of Hematology of the Second People's Hospital of Yichang and Department of Oncology of The Affiliated Hospital of Jianghan University from April 2010 to March 2019 were collected. According to the median IgG level at the time of initial diagnosis, patients were divided into high IgG group and low IgG group. The recurrence time after initial treatment was followed up, and the correlation between newly diagnosed IgG level and recurrence was analyzed by univariate and multivariate analysis, as well as the influencing factors of IgG levels in order to predict furtherly the potential mechanism of recurrence.@*RESULTS@#Univariate survival analysis showed that high revised international staging system (R-ISS) staging, high level of bone marrow plasma cell (BMPC), lactate dehydrogenase (LDH), creatinine, β@*CONCLUSION@#The higher the serum IgG concentration of IgG-type MM patients at first diagnosis, the earlier the recurrence, which is related to the low level of serum albumin, and can be used as a potential recurrence predictor after complete remission of IgG-type MM patients.

Pre-Transfusion Testing and Transfusion Strategy in Patients with Multiple Myeloma after Daratumumab Treatment / 中国实验血液学杂志

OBJECTIVE@#To investigate the procedure of pre-transfusion testing and transfusion strategy of patients with multiple myeloma (MM) treated by daratumumab (DarA).@*METHODS@#The blood samples of MM patients before and after DarA treatment from the Fifth Affiliated Hospital of Sun Yat-sen University were collected, and the ABO/Rh blood group antigen identification and DAT test results were compared. The results of antibody screening and cross matching of the patients before and after inactivation of red blood cells with 0.2 mol/L dithiothreitol (DTT) were compared and analyzed.@*RESULTS@#ABO/Rh blood group antigen typing showed no affecting in patients after treated by DarA; the result of DAT test showed negative. Irregular antibody screening showed that all the three cells(Ⅰ, Ⅱ and Ⅲ) were positive(1+~2+) and the self-control was negative. By microcolumn agglutination method, the main side of the multi-bag of blood showed no matched, while the secondary side showed all identical. After treated by DTT solution, the cross matching results in reagent red blood cells and the red blood cells of blood donors were both consistent, and the irregular antibody screening was negative. The K(+)O type erythrocytes used in parallel control were transformed into K(-)O type erythrocytes after DTT treatment. However, there was no significant changes in E(+) O type erythrocytes before and after DTT treatment. There was no condensation on the primary and secondary side of the condensed amine method. The primary and secondary sides of blood matching by saline method showed negative.@*CONCLUSION@#After treated by DarA, cross matching results from microcolumn agglutination method can be interfered by the residual drug antibody in MM patients, while the interference was eliminated in the presence of 0.2 mol/L DTT solution. However, no disturbance was observed when using condensed amine method or saline method. Therefore, corresponding transfusion procedures should be selected according to the emergency degree of blood transfusion to ensure the safety and timeliness of blood transfusion.

Analysis of Factors Influencing Autologous Peripheral Blood Stem Cells Mobilization in Patients with Lymphoma and Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To analyze the factors influencing the mobilization of autologous peripheral blood stem cells (auto-PBSCs) in patients with lymphoma and multiple myeloma, and provide reference for optimizing the autologous stem cell mobilization regimen.@*METHODS@#Clinical data of 33 multiple myeloma and lymphoma patients received auto-PBSCs mobilization in our center from January 2015 to December 2018 were collected, the correlation of mobilization failure rate with gender, age, courses of chemotherapy before mobilization, does of recombinant human granulocyte colony stimulating factor (rhG-CSF), type of disease, and chemotherapy regimen were retrospectively analyzed.@*RESULTS@#Type of disease and course of pre-mobilization chemotherapy could affect the mobilization failure rate (P0.05).@*CONCLUSION@#Multi-course chemotherapy before collection and lymphoma patients are poor factors negatively impacting on auto-PBSCs mobilization.

Managing patients with multiple myeloma during the COVID-19 pandemic: recommendations from an expert panel - ABHH monoclonal gammopathies committe

ABSTRACT Since the World has been facing the COVID-19 pandemic, special attention has been taken concerning cancer patients; related to their immunosuppression status, adding risk for more aggressive COVID-19 and mortality, but also concerns about the access and the quality of care in cancer therapy. The COVID-19 pandemic impacts the number of infected, its related mortality, as well as the care of cancer patients. Multiple myeloma patients are a particular group with several important aspects to be considered during pandemic times. In essence, they are immunosuppressed in different intensities during their treatment. Most of them are elderly and all of them require long-term therapy, with prolonged contact with the health care system, possibly including a stem cell transplant during the treatment. A panel of experts in multiple myeloma and infectious diseases discusses pieces of evidence and the lack of the same in the scenario of COVID-19 in myeloma patients, while also exposing what is expected for the next phases of the COVID-19 pandemic.

Construction of CAR-T cells targeting CS1 and analysis of their antitumor activity in vitro / 生物工程学报

We constructed the CS1-targeted second- and third-generation CAR-T cells with genetic engineered 4-1BB or/and ICOS as a costimulatory signaling molecule by use of lentiviral platform. The CS1-targeted second-generation CAR-T cells with ICOS or 4-1BB had similar anti-neoplastic activity. When effector/target ratio was 1:1, the CAR-T cells with ICOS showed better killing effect on IM9-lucgfp cells than those with 4-1BB. However, The CS1-targeted third-generation CAR-T cells exihibited lower cytolytic capacity against IM9-lucgfp cells than the CS1-targeted second-generation CAR-T cells when the ratio of effector/target was 1:1, 2:1 or 5:1. When the ratio of effector/target was 10:1, the killing efficacy of both the second- and third-generation CAR-T cells against IM9-lucgfp cells was more than 85%, significantly higher than that of the control T cells. Taken together, both the CS1-targeted second- and third-generation CAR-T cells with ICOS or/and 4-1BB could efficiently kill CS1-positive multiple myeloma cells, but the CS1-targeted second-generation CAR-T cells had more potent killing effect on CS1-positive multiple myeloma cells than the CS1-targeted third-generation CAR-T cells.

Infections in patients with multiple myeloma treated with conventional chemotherapy: a single-center, 10-year experience in Pakistan

ABSTRACT Introduction: Multiple myeloma (MM) is a common hematologic malignancy with variable degrees of immunodeficiency. Disease- and treatment-related compromise of the immune system predisposes patients to infections, which are a major cause of morbidity and mortality. Objective: We aimed to establish the incidence and main characteristics of infections in MM patients treated at our center over a 10-year period. Method and results: Of the 412 patients retrospectively analyzed, 154 (37.4%) were documented to have at least one episode of infection and were included in this study. A total of 244 infectious episodes were documented. The most common site of infection was the lung, followed by the genitourinary system. The most common infections were bacterial, followed by viral. Escherichia coli were the most common organism. In 160 (65.5%) episodes, the organism was not isolated. Thalidomide with dexamethasone was the most common treatment regimen, followed by melphalan with dexamethasone. Infection was the main cause of death in 26 (6.3%) out of all 412 patients. Conclusion: Infections are a notable cause of morbidity and mortality in the clinical course of MM patients. By considering patient and disease characteristics, a risk-adapted selection of the MM treatment should be employed, with special attention toward patient age and disease-associated organ dysfunction. Patient education, access to healthcare and physician vigilance are also essential. Vaccination and antimicrobial prophylaxis may be considered prior to or during therapy.

Trasplante de progenitores hematopoyéticos autólogo en gammapatías monoclonales: primeros resultados del Hospital "Hermanos Ameijeiras" / Autologous stem cell transplantation in monoclonal gammopathies: first results from the "Hermanos Ameijeiras" Hospital

Introducción: Los avances en el manejo del mieloma múltiple (MM) durante los últimos años incluyen la incorporación del trasplante de progenitores hematopoyéticos autólogo (TPHa) a la estrategia de tratamiento de estos pacientes. Objetivo: Dar a conocer los primeros resultados en el hospital Hermanos Ameijeiras (HHA) con la aplicación del TPHa en pacientes con gammapatías monoclonales (GM), empleando las altas dosis de melfalán (AD-Mel) como tratamiento acondicionante (TA) y su impacto en la sobrevida global (SG). Métodos: Se hizo un estudio retrospectivo de todos los pacientes con GM sometidos a TPHa en el Servicio de Hematología del HHA en el período comprendido entre 2009 y 2018. La muestra final comprendió 14 casos. Resultados: La edad promedio fue de 53,5 años; la mayoría tenía como diagnóstico MM (85,7 por ciento) y todos ellos debutaron en estadio III de Durie-Salmon; como TA el 64,2 por ciento recibió AD-mel, en dosis de 200 mg/m2. La recuperación de las cifras de neutrófilos y plaquetas ocurrieron como promedio a los 11,4 y 12 días, respectivamente. La mortalidad relacionada con el trasplante (MRT) al día +30 fue del 7,1 por ciento. La probabilidad de SG a los 2 años fue superior al 90 por ciento y a los 5 años del 68 por ciento. Conclusiones: Se comprobó que la realización del TPHa con el empleo de AD-Mel como TA en pacientes con GM es un proceder realizable en nuestro país con una MRT relativamente baja. Se logró demostrar que la inclusión del TPH en el tratamiento mejora considerablemente las expectativas de sobrevida de estos pacientes(AU)

Introduction: The recent advances in the management of multiple myeloma (MM) during the last years have included the autologous hematopoietic stem cell transplantation (auto-HSCT) to the treatment strategy of these patients. Objective: To present the first results in the Hermanos Ameijeiras hospital (HAH) with the application of auto-HSCT in patients with monoclonal gammopathies (MG) using high doses of melphalan (HD-Mel) as conditioning regimen (CR) and its impacton overall survival (OS). Methods: A retrospective study of all patients with MG who underwent auto-HSCT in the Hematology Service of the HAH in the period between 2009 and 2018 wasmade. The final sample comprised 14 cases. Results: The average age was 53.5 years; the majority had diagnosis of MM (85.7percent) and all of them were diagnosed in stage III of Durie-Salmon; as CR 64.2 percent received HD-mel, at 200 mg/m2. The recovery of neutrophil and platelet counts occurred on average at 11.4 and 12 days respectively. Transplant related mortality (TRM) at day +30 was 7.1 percent. The probability of OS at 2 years was higher than 90 percent and at 5 years of 68 percent. Conclusions: It was verified that the performance of auto-HSCT with the use of HD-Mel as CR in patients with MG is a feasible procedure in our country with a relatively low TRM. It was possible to demonstrate that the inclusion of auto-HSCT in the treatment considerably improves the survival expectations of these patients(AU)

Mieloma múltiple en Chile: Respuesta a tratamiento en pacientes con mieloma múltiple elegibles para trasplante autólogo de progenitores hematopoyéticos / Response rates to first-line treatment in eligible patients to autologous stem transplantation in Chile

Background The treatment of choice of newly diagnosed multiple myeloma (NDMM) is an induction with proteasome inhibitors followed autologous stem cell transplantation (HSCT). Since 2013, the treatment of these patients in the public system is based on CTD (cyclophosphamide, thalidomide, and dexamethasone). Aim To evaluate the response rates achieved with CTD, and the results of HSCT in patients with NDMM in the public setting. Material and Methods Data from patients considered as candidates for HSCT from different centers of the National Adult Antineoplastic Drug Program (PANDA, for its acronym in Spanish), diagnosed between 2013 and 2017, was analyzed. The response to treatment of first and second lines of treatment was evaluated, in addition to the results of HSCT. An optimal Response was defined as the sum of strict complete remission, complete remission and very good partial response (sCR, CR and VGPR). Results One hundred and seventy-seven patients were analyzed, 54% women, and 53% with IgG multiple myeloma. Information about the international staging system was retrieved in 127 patients (71%). Seventeen percent were ISS I, 22% in ISS II and 32% ISS III. CTD was used as first treatment in 106 patients (60%), and cyclophosphamide, bortezomib and dexamethasone (CyBorD) in 13 (7%). As first line, CTD had an overall response of 50.9%, and CyBorD of 76.9%. Thirty patients were treated with bortezomib as second line treatment. Forty patients (22%) underwent HSCT. The 5-year Overall Survival (OS) in transplanted patients and non-transplanted patients was 100 and 62% respectively (p < 0.01). Conclusions The response rate achieved by CTD in these patients is suboptimal. The response to CyBorD was better.

New proteasome inhibitors in the treatment of multiple myeloma

Abstract The treatment of patients with relapsed and/or refractory multiple myeloma has improved considerably in the last 15 years, after the introduction of proteasome inhibitors and immunomodulatory drugs. The first clinical trials with new proteasome inhibitors have produced exciting results, particularly those comparing triplet regimens with standard doublet regimens, with a gain in progression-free survival accompanied by an acceptable safety profile and either similar or better health-related quality of life. New proteasome inhibitors hold the potential to fill unmet needs in multiple myeloma management regarding improvement of clinical outcomes, including delayed progression of disease in high-risk patients. This review summarizes the main pharmacological properties and clinical outcomes of these agents, and discusses their potential to change the whole multiple myeloma therapeutic landscape.