Objective To study the clinical features and risk factors of invasive fungal infection (IFI) in multiple myeloma ( MM) . Methods Three hundred and fifty-seven cases of MM were retrospectively analyzed for IFI, clinical features, complicating diseases, treatment of fungus and side effect of anti-fungal drugs. Results Forty-four cases ( 12. 3% ) of IFI were diagnosed. Three of them were diagnosed definitely, 8 clinically and 33 probably. Ten cases incurred IFI in (he induction therapy, 4 in platform, 27 in progress and 3 in the treatment with autologous stem cell transplantation. The lung was the commonest site of infection ( 50. 0% ) . The total effective rates of amphotericin B liposome, voriconazole, itraconazole, caspofungin and fluconazol were 83. 3% , 75. 0% , 78. 9% , 75. 0% and 57. 1% respectively (P= 0.493). In a multivariate analysis, independent factors significantly associated with IFI were diabetes (P=0.035, OR 2. 527, 95%CI 1.005-6.052), dialysis (P=0. 022,OR 2. 768, 95%CI 1. 161-6. 600), persistent agranulocytosis (P = 0.019, OR 3.215, 95% CI 1.200-7.407), broad-spectrum antibiotic therapy (P = 0.009,OR 3. 350,95% CI 1.353-8.295) and fludarabine treatment( P = 0. 001,0R 4. 669, 95% CI 1.813-12.023). Conclusions Patients with MM are in high risk of IFI. The lung is the commonest site of infection. The therapeutic effect was similar with itraconazole, voriconazole, caspofungin and amphotericin B liposome in MM patients with complicating IFI. The risk factors for IFI in MM were diabetes, dialysis, persistent agranulocytosis and the use of broad-spectrum antibiotics and fludarabine.

Objective To investigate the efficacy and safety of bortezomib-based induction regimen followed by autologous hematopoietic stem cell transplantation (ASCT) in pationts with multiple myeloma (MM). Methods A retrospective analysis was performed upon clinical data of 62 MM patients who received bortezomib-based induction regimen followed by ASCT from June 2006 to June 2011.All patients were followed up to September 30,2011.Results Overall response rate [ complete remission (CR) + near complete remission (nCR) + partial remission (PR) ],≥ nCR rate (CR/nCR) and CR rate of postinduction with bortezomib-based regimen were 88.7％,66.1％ and 24.2％,respectively.After ASCT,CR rate and CR/nCR rate were increased to 50.0％ and 82.3％,respectively,with significant differences (P =0.003 and P =0.032).The median time of neutrophil and platelet engraftment was 12.0 (9-43) days and 13.5 (0-120) days,respectively. Significances were found in neutrophil and platelet engraftment between MM patients with and without prior exposure to alkylating agents. Furthermore,engraftment of neutrophil and platelet in patients receiving peripheral blood stem cell transplantation were faster than those receiving bone marrow transplantation.No unexpected side effects occurred.The median time of follow-up was 26.5 (7-61) months.The median overall survival (OS) was not reached and the median progression-free survival (PFS) was 30 months.There were significant differences in OS and PFS between patients obtaining CR/nCR and those with ≤ PR before ASCT.Conclusions Bortezomib-based induction regimen can improve the efficacy of ASCT in MM patients.The side effects are tolerant.Higher response quality before ASCT can translate to high rates of OS and PFS following high-dose therapy and stem cell transplantation.

Objective To compare effects and toxicities of DVd and VAdM regimen for newly diagnosed multiple myeloma.nethods 17 newly diagnosed active multiple myeloma received DVd treatment,dexamethasone(20 mg/d)on days 1～4 as an intravenous infusion.16 newly diagnosed active multiple myeloma on days 1～4 plus melphalan(12 mg/d)as an intravenous infusion.Results Objective response rates(DVd,76.5%;VAd,81.3%,P=0.737)were similar between the two treatment groups.In the DVd group,the mean time to max response was shorter than the VAdM group[(3.2±1.7)months vs.(4.6±1.0)months,P=0.039].DVd was associated with low Grade 3/4 neutropenia(23.5% vs.68.8%,P=0.015),less use of G-CSF(11.8% vs.62.5%,P=0.004),less use antibiotic(11.8% vs.37.5%,P=0.118),lower incidence of hospitalization for adverse events(37.5% vs.17.6%,P=0.259),but more hand-foot syndrome.Coilcinsion The DVd regimen demonstrated similar efficacy compared with VAdM,while with less toxicity and supportive care,which might be used as a modified VAd regimen for newly diagnosed myeloma.

Objective To explore the clinical features of infection in multiple myeloma (MM)undergoing autologous hematopoietic stem cell transplantation (ASCT). Methods Thirty-seven patients with MM undergoing ASCT were retrospectively analyzed for type and time of infection, pathogen, and outcome. Results Fifty-nine cases of infectious complications occurred in 33 patients (89. 2% ) after ASCT, with 34 cases (57.6%) of bacterial infections in 30 patients, 15 cases (25.4%) of fungal infections in 12 patients, 4 cases (6. 8% ) of cytomegalovirus (CMV) infection, 3 cases (5. 1% ) of herpes zoster virus infection and 3 cases (5. 1% ) of HBV reactivation. The proportion of bacterial infection, fungal infection and virus infection were 62. 8%, 28.6% and 8. 6% respectively in the early stage after ASCT, and 50. 0%, 20. 8% and 29. 3% respectively in the median stage. Response to first-line antibiotic therapy was seen in 38 cases (64. 4% ). Infection-related mortality was 8. 1% (3 cases). Conclusions The incidence of infection in MM patients undergoing ASCT is high and they are susceptible to all pathogens. It is important to choose the right antifungal agents as quickly as possible to reduce infection-related mortality.

Objective: To compare the efficacy, response and survival between high-dose melphalan (HDM) and cyclophosphamide+ etoposide+ busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) . Methods: Retrospectively enrolled 123 consecutive NDMM patients who had received PAD induction with subsequent ASCT from Jan 2011 to Aug 2017. The CVB group and HDM group had 82 and 41 patients respectively. Results: ①No differences existed between these 2 groups in non-hematological side effects. ②Patients of CVB group had faster neutrophil and platelet engraftment time, with the median neutrophil engraftment time of 10 (9-35) day vs 11 (9-12) day for patients of HDM group (z=-3.433, P=0.001) , and with median platelet engraftment time of 11 (7-55) day vs 13 (10-35) day for patients of HDM group (z=-3.506, P<0.001) . CVB group entered neutropenia and severe thrombocytopenia more earlier than the HDM group, resulting similar neutropenia duration and severe thrombocytopenia duration between the CVB group and HDM group. However, patients of CVB group had significantly longer fever persistent time and antibiotic administration time. ③The response rate was significantly lower in patients of CVB group vs. patients of HDM group (9/46 vs 14/28, P=0.021) . Further, the minimal residual disease (MRD) negative rate at 3^rd month post-transplantation seemed to be lower in CVB group than that in HDM group (31.7%vs 48.8%, P=0.065) . ④Both the univariate and multivariate analysis showed that HDM and CVB groups had similar duration to progression (TTP) (P=0.619) and overall survival (OS) (P=0.295) . Conclusion HDM conditioning regimen is superior to CVB regimen in hematological side effects, tumor burden reduction and administration convenience. However, these two regimen had similar TTP and OS in MM patients receiving ASCT.

Objective:To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients.Methods:In the follow-up cohort of patients with newly diagnosed MM and who received “novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy” in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results:The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions:The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.