Early M-protein immune reconstitution after autologous haematopoietic stem cell transplantation is a good prognostic marker for patients with high-risk cytogenetic multiple myeloma.

The presence of transient abnormal protein banding (M-protein immune reconstitution) in serum immunofixation electrophoresis after autologous haematopoietic stem cell transplantation in patients with multiple myeloma has been reported. The purpose of this study was to investigate the impact of post-transplant M-protein immune reconstitution on the prognosis of patients with multiple myeloma. M-protein immune reconstitution was observed in 25.9% (75/290) of patients. The CR rate and MRD negativity were higher in the M-protein immune reconstitution group (85.3% vs. 69.3%, p = 0.013, 81.9% vs. 66.5%, p = 0.014). Although there were no significant differences between the groups, the overall median survival time was longer in the M-protein immune reconstruction group (80 vs. 72 m, p = 0.076; not reached vs. 105 m, p = 0.312). Among patients in the cytogenetic high-risk group, the occurrence of M-protein immune reconstitution predicted better PFS and OS (80 vs. 31 m, p = 0.010; not reached vs. 91 m, p = 0.026). Additionally, in revised-International Staging System stage III patients, PFS and OS were better in those who achieved M-protein immune reconstitution (80 vs. 20 m, p = 0.025; 57 vs. 32 m, p = 0.103). The better prognosis of M-protein immune reconstitution patients may be associated with the acquisition of a deeper response. In high-risk patients, early acquisition of M-protein immune reconstitution may suggest a better prognosis.

Efficacy of prophylactic antibiotics for the prevention of neutropenic fever in patients with multiple myeloma receiving high-dose cyclophosphamide for stem cell mobilization.

High-dose cyclophosphamide (HD-Cy) (3 g/m2) plus granulocyte colony-stimulating factor (G-CSF) is a very effective regimen for peripheral blood stem cell (PBSC) mobilization. Unfortunately, it is associated with an increased risk of neutropenic fever (NF). We analyzed the effect of NF on PBSC apheresis results and the efficacy of prophylactic antibiotics for the prevention of NF associated with HD-Cy plus G-CSF for PBSC mobilization in patients with newly diagnosed multiple myeloma (MM). First, patients were divided into NF ( +) and NF ( -) groups according to whether they suffered from NF during mobilization. Second, we divided patients into an antibiotic prophylaxis group and a nonantibiotic prophylaxis group according to whether antibiotic prophylaxis was used during the mobilization period. Our study showed that NF( +) patients (n = 44) had lower CD34 + cell dose collection (median 2.60 versus 5.34 × 106/kg, P < 0.001) and slower neutrophil engraftment and platelet engraftment (median 11 versus 10 days, P = 0.002, and median 13 versus 11 days, P = 0.043, respectively) than NF( -) patients (n = 234). Of note, the nonantibiotic prophylaxis group patients (n = 30) had a 26.7% incidence of NF. In the patients receiving antibiotic prophylaxis (n = 227), the incidence was reduced to 9.3% (P = 0.01). The antibiotic prophylaxis patients had higher CD34 + cell collection (median 5.41 versus 2.27 × 106/kg, P < 0.001) and lower hospitalization cost of mobilization ($ median 3108.02 versus 3702.39, p = 0.012). Thus, our results demonstrate that NF is associated with lower CD34 + cell collection and that antibiotic prophylaxis can reduce the incidence of NF and improve stem cell mobilization and collection outcomes, which reduces the hospitalization cost of mobilization.

Prolonged infusion time of cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) as a mobilization regimen may improve mobilization efficiency in newly diagnosed multiple myeloma patients: a single center experience.

OBJECTIVES: This study aimed to clarify the effectiveness and safety of two different infusion durations of cyclophosphamide (CTX) plus granulocyte colony-stimulating factor (G-CSF) for peripheral blood stem cell mobilization in patients with newly diagnosed multiple myeloma (NDMM). METHODS: One hundred and fifty-six consecutive NDMM patients receiving CTX plus G-CSF mobilization and autologous stem cell transplantation during the period of September 2008 to May 2020 were selected for retrospective analysis. According to differences in prolonged infusion time of CTX, they were divided into a 24-h group (24-h continuous infusion) and a control group (4-6 h of infusion). Mobilization and safety of infusion were analyzed. Flow cytometry was used to detect the peripheral blood CD34+ cell count. Multivariate analysis was performed to determine the factors influencing the number of CD34+ cells. RESULTS: The mean CD34+ cell counts collected in 24-h and control groups were 6.78 (interquartile range [IQR] 3.59-11.69) and 4.48 (IQR 2.39-6.30) ×106/kg, respectively (p < 0.001). Meanwhile, the target number of CD34+ cells/kg (defined as ≥4 × 106/kg) was collected from 51 (75%) of cases in 24-h group vs. 45 (51%) in the control group (p = 0.002). Multivariate analysis identified the independence of CTX infusion time as a factor influencing the target number of CD34+ cells/kg [odds ratio OR, 4.045; 95% CI: 1.630-10.038, p = 0.003]. The post-transplantation time to neutrophil engraftment was 10 (IQR 9-11) in 24-h group and 11 (IQR 10-12) in control group (p < 0.001). Finally, no statistical differences were identified between groups in terms of hematologic and non-hematologic toxicities. CONCLUSIONS: For patients with NDMM, 24-h continuous infusion of CTX plus G-CSF contributes to improved mobilization efficiency and equivalent toxicity as a stem cell mobilization regimen.

Clinical Characteristics and Prognosis of Secondary Acute Lymphoblastic Leukemia in Patients with Multiple Myeloma during Long-Term Thalidomide Maintenance.

Background: Secondary primary malignancies (SPM) have attracted increasing attention with the application of autologous hematopoietic stem cell transplantation (ASCT) and novel agents in multiple myeloma (MM). Secondary acute lymphoblastic leukemia (sALL) has rarely been reported, and the clinical characteristics and prognosis of sALL have not been described in detail. Methods: We retrospectively enrolled 179 consecutive newly diagnosed multiple myeloma (NDMM) patients undergoing bortezomib-based induction regimens followed by upfront ASCT and maintenance therapy from December 2006 to April 2018 in our center. Results: The median follow-up interval was 69.1 months, and 12 patients (6.7%) developed sALL during maintenance therapy. The median time from the diagnosis of MM to the occurrence of sALL was 51.1 (31.7-91.5) months. All sALL patients received thalidomide as maintenance therapy before the onset of sALL, and the median duration of thalidomide maintenance was 39.5 (24-74) months. The cumulative incidence of sALL was 6.6% and 11.2% at 5 and 10 years after the diagnosis of MM, respectively. All sALL patients presented with a B-cell immunophenotype accompanied by myeloid antigen expression according to flow cytometry analysis, and the BCR/ABL fusion gene was all negative. Only one patient had evidence of active MM, and the other patients were in stable status at the time of the diagnosis of sALL. The prognosis of most sALL patients was very poor, and the median overall survival time was 11.9 (1.1-51.2) months since the diagnosis of sALL. Conclusions: sALL should be considered for MM patients who developed unexplained persistent cytopenia while on long-term thalidomide maintenance treatment, particularly if it has been more than 3 years. With the increasing availability of new drugs for MM, thalidomide may be recommended for no more than 3 years. Sequential allogeneic hematopoietic stem cell transplantation was considered as soon as possible after achieving remission in order to achieve a longer survival.

RUNX2 promotes the suppression of osteoblast function and enhancement of osteoclast activity by multiple myeloma cells.

RUNX2 is a transcription factor that participates in osteoblast differentiation and chondrocyte maturation and plays an important role in the invasion and metastasis of cancers. With the deepening of research, evidence has indicated the correlation between RUNX2 and bone destruction in cancers. However, the mechanisms underlying its role in multiple myeloma remain unclear. By observing the induction effects of conditioned medium from myeloma cells on preosteoblasts (MC3T3-E1) and preosteoclasts (RAW264.7) and constructing myeloma-bearing mice, we found that RUNX2 promotes bone destruction in multiple myeloma. In vitro, conditioned medium from RUNX2-overexpressing myeloma cells reduced osteoblast activity and increased osteoclast activity. In vivo, RUNX2 expression was positively correlated with bone loss in myeloma-bearing mice. These results suggest that therapeutic inhibition of RUNX2 may protect against bone destruction by maintaining the balance between osteoblast and osteoclast activity in multiple myeloma.

Development and validation of a chemotherapy tolerance prediction model for Chinese multiple myeloma patients: The TM frailty score.

Objective: The physical fitness of older individuals is heterogeneous, making it difficult to know their chemotherapy tolerance. The toxicities may offset the benefits of anti-myeloma therapy in frail patients. The accurate evaluation of frailty status before chemotherapy is essential. We aimed to explore the applicability of the IMWG GA and develop a new frailty screening tool more suitable for Chinese MM patients. Cases and methods: We performed the IMWG GA and the full CGA in 167 MM patients and validated the applicability of the IMWG GA to chemotherapy and prognosis. The CGA domains were screened for their predictive value to improve IMWG GA and develop new frailty screening tools. Results: The results showed that the IMWG GA had limitations in distinguishing the risk of grade ≥3 adverse events (AEs) between fit and int-fit patients. Of the CGA domains, TUG and MNA-SF were independent prognostic factors for grade ≥3 AEs and OS and further stratified the risk of grade ≥3 AEs in the IMWG GA int-fit subgroup (P< 0.05). We combined TUG and MNA-SF to construct the TM frailty score. The frail subgroup had a higher proportion of adverse outcomes, a higher hazard ratio (HR) in Cox regression and a higher Harrell's C-index for distinguishing the risk of grade ≥3 AEs and OS than the IMWG GA frail subgroup. Conclusion: The TM frailty score is more suitable than the IMWG GA for evaluating chemotherapy tolerance and prognosis in the Chinese population.

On-demand plerixafor added to high-dose cyclophosphamide and pegylated recombinant human granulocyte colony-stimulating factor in the mobilization of patients with multiple myeloma: a treatment with high effectiveness, convenient, and affordable cost.

Objective: The combination of high-dose cyclophosphamide (HD-Cy) (3g/m2) plus granulocyte colony-stimulating factor (G-CSF) and on-demand plerixafor (PXF) has been considered an effective mobilization regimen of patients with multiple myeloma(MM). However, the daily multi-injection regimen of G-CSF poses challenges. This study delves into the efficiency and cost implications of a novel approach, using HD-Cy alongside pegylated G-CSF (PEG G-CSF) and on-demand PXF. Unlike G-CSF, which necessitates daily injections, the half-life of PEG G-CSF extended allows for a single injection. Methods: A retrospective analysis was conducted on 350 MM patients, which were categorized based on their mobilization regimens: Cy+PEG G-CSF+/-PXF (n=66), Cy+PEG G-CSF (n=91), Cy+ G-CSF (n=169), and G-CSF+PXF (n=24). Results: Mobilization with Cy+PEG G-CSF+/-PXF(8.79)yielded a notably higher median CD34+ cell count compared to the other regimens: Cy+PEG G-CSF(4.96), Cy+G-CSF (4.65), and G-CSF+PXF (2.99) (P<0.001). The percentage of patients who achieved >6×106/kg CD34+ cells was significantly higher in the Cy+PEG G-CSF+/-PXF group (77.3%) than in the other mobilization regimens: Cy+PEG G-CSF (41.8%), Cy+ G-CSF (37.3%), and G-CSF+PXF (8.3%) (P<0.001). From a cost perspective, the Cy+PEG G-CSF+/-PXF approach was more economical than the G-CSF+PXF strategy but was marginally costlier than the other two methods. A multivariate assessment highlighted that the combination of Cy+PEG G-CSF with on-demand PXF had a superior potential to achieve the desired harvest (6×106/kg) compared to the Cy+PEG G-CSF protocol without PXF. The incremental cost-effectiveness ratio for each 1% increase in the probability of achieving a successful optimal harvest was $ 97.02 per patient. The incidence of neutropenic fever was 3.0% in the Cy+PEG G-CSF+/-PXF group. Conclusion: The combination of on-demand PXF with HD-Cy and PEG G-CSF offers a cost-effective approach with a high mobilization success rate, manageable side effects, and the convenience of fewer injections. It stands as a promising mobilization strategy for MM patients.

Prognostic Significance of the Stage at Which an MRD-Negative Status Is Achieved for Patients With Multiple Myeloma Who Received ASCT.

Objective: To explore the prognostic significance of the stage at which a minimal residual disease (MRD)-negative status is achieved for patients with newly diagnosed multiple myeloma (NDMM) who received autologous hematopoietic stem cell transplantation (ASCT). Cases and Methods: A retrospective analysis of 186 NDMM patients who received "induction therapy-ASCT-maintenance therapy" in our center and achieved an MRD-negative status was performed. Patients were divided into three groups, A (induction therapy), B (3 months after ASCT), and C (maintenance therapy), according to the stage at which an MRD-negative status was achieved. Results: The median time to progression (TTP) of 186 patients was not reached; the median overall survival (OS) was 113.8 months. The median TTP of the patients in three groups was not reached (P=0.013), and the median OS of the patients in three groups was not reached, not reached, and 71.2 months, respectively (P=0.026). Among patients with standard-risk cytogenetics, the median TTP of those in all three groups was not reached (P=0.121), and the median OS of the patients in three groups was not reached, not reached, and 99.6 months, respectively (P=0.091). Among patients with high-risk cytogenetics, the median TTP of those in three groups was not reached, 53.9 months, and 35.8 months (P=0.060), and the median OS was not reached, 71.2 months, and 60.2 months, respectively (P=0.625). Among patients with R-ISS stage I-II, the median TTP of those in three groups was not reached (P=0.174), and the median OS of the patients in three groups was not reached, not reached, and 99.6 months, respectively (P=0.186). Among the 29 patients with R-ISS stage III, the median TTP of those in the 3 groups were unreached, unreached, and 35.1 months (P<0.001), and the median OS was unreached, unreached, and 48.5 months, respectively (P=0.020). In all enrolled patients, the stage of reaching MRD-negative was an independent prognostic factor for TTP, rather than a prognostic factor for OS. The stage of reaching MRD-negative in patients with R-ISS III was an independent prognostic factor for OS. Conclusion: For the same patients who are MRD-negative, the prognoses of those who achieve an MRD-negative status at different groups are different. The stage at which an MRD-negative status is achieved can predict the prognosis of patients with R-ISS stage III.

Clinical value of minimal residual disease assessed by multiparameter flow cytometry in amyloid light chain amyloidosis.

PURPOSE: To assess the feasibility and prognostic value of minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in newly diagnosed amyloid light chain (AL) amyloidosis. METHODS: Clinical data from 25 consecutive newly diagnosed AL amyloidosis patients with MRD data tested at 3 months after first-line therapy completion were retrospectively analysed in a single centre from 2012 to 2019. First-line therapy included 8 courses of VD or 4 courses of VD plus sequential autologous stem cell transplantation (ASCT), both without maintenance therapy. RESULTS: Of 25 patients with very good partial response (VGPR) or better, 19 (76%) achieved MRD negativity. Baseline characteristics were not different between MRD-negative and MRD-positive patients. More ASCT patients than non-ASCT patients (90.0% vs 53.3%, p = 0.043) achieved MRD negativity. In the MRD-negative and MRD-positive groups, cardiac response was observed in 93% and 25% (p = 0.019) and any organ response in 94% and 50%, respectively (p = 0.023). At a median follow-up of 25.1 months, MRD-negative patients showed significantly longer progression-free survival (PFS) from diagnosis than MRD-positive patients (24.52 vs 76.39 months, p = 0.004). CONCLUSIONS: MRD negativity measured by MFC at 3 months after first-line therapy completion in patients with AL amyloidosis is measurable and associated with improved organ response rates and PFS over a long follow-up.

Recombinant human thrombopoietin improved platelet engraftment after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma.

BACKGROUND: To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) for hematopoietic reconstitution after autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (NDMM). METHOD: Thirty-five cases with NDMM had been enrolled into a prospective clinical trial from March 2014. The hematopoietic reconstitution was compared between these 35 cases (rhTPO group) and 98 historic cases not receiving rhTPO (control group) after stem cell reinfusion. RESULTS: Thirty-five (100%) cases receiving rhTPO achieved both neutrophil and platelet engraftment within 30 days post-transplant. The median time to neutrophil and platelet engraftment was the 10th day and 11th day after stem cell reinfusion, respectively. Multivariate analysis showed that rhTPO administration was an independent factor for accelerating platelet engraftment (HR 2.013, 95% CI 1.336-3.034, p = 0.001). Subgroup analysis showed that rhTPO improved platelet engraftment and alleviated platelet transfusion needs in patients with inadequate re-infused CD34+ cell counts of <2 × 109 /L. All the 35 patients tolerated rhTPO well. Survival analysis showed no decrease in time to progression (TTP) or overall survival (OS) by rhTPO administration. CONCLUSION: rhTPO accelerated the platelet engraftment after ASCT in patients with NDMM with good tolerability and long-term safety, especially for those patients with poor CD34+ cell reinfusion. rhTPO might be recommended to be used early after ASCT for patients with NDMM.

Mechanism of megaloblastic anemia combined with hemolysis.

Megaloblastic anemia (MA) patients often exhibit hemolysis, but it is not clear whether there are other hemolytic mechanisms in addition to intramedullary hemolysis. We retrospectively analyzed the clinical characteristics of 124 MA patients, measured erythrocyte physical parameters in two patients with hemolysis and one healthy volunteer by atomic force microscopy, and measured 18F-FDG uptake in one MA patient with hemolysis. In multivariate analysis, hemolysis was associated with mean corpuscular volume (MCV) and indirect bilirubin. A receiver operating characteristic curve analysis, with sensitivity of 83.1% and specificity of 68.7%, suggested that the MCV cutoff value that predicts hemolysis is 116.4 fL. Hb was negatively correlated with MCV in the hemolysis group (r = -0.317, P = 0.007) but not in the nonhemolysis group. The erythrocyte peak-valley value, average cell surface roughness and surface area in the MA patients with hemolysis were significantly lower than those in controls (P < 0.05). 18F-FDG uptake by the liver and spleen was diffuse and increased in MA patients undergoing hemolysis. MA combined with extramedullary hemolysis could be caused by macrophages removing mechanically damaged erythrocytes and the retention of erythrocytes with decreased deformability when blood circulates through narrow spaces in the liver and spleen.

Comparison of efficacy, safety, patients' quality of life, and doctors' occupational stress between lenalidomide-based and bortezomib-based induction in patients with newly diagnosed multiple myeloma.

BACKGROUND: In the new therapeutic era, comparisons between regimens containing lenalidomide and bortezomib are needed. METHODS: In this single-center, prospective study, patients received four to six cycles of lenalidomide+liposomal doxorubicin+dexamethasone (RAD) or bortezomib+liposomal doxorubicin+dexamethasone (PAD) every 4 weeks, with subsequent autologous stem cell transplantation (ASCT) and maintenance therapy. We compared the efficacy, safety, patients' quality of life, and doctors' occupational stress between RAD and PAD induction in newly diagnosed MM patients. RESULTS: The complete response (CR) rate was comparable between the RAD and PAD groups after induction (30.8% vs. 32.0%, p = 0.92). Common adverse events, including infections, peripheral neuropathy, and gastrointestinal disturbances, were more frequent in the PAD group, while leukopenia and rashes were more common in the RAD group. Compared with PAD, RAD improved patients' quality of life more quickly and caused less occupational stress for doctors. However, only 31.6% of patients collected adequate CD34+ cells (≥2 × 106 /kg) in the RAD group, which was significantly lower than that in the PAD group (95.5%, p < 0.001). The number of CD34+ cells collected was significantly higher in patients within three courses of RAD than in patients with four or five to six courses (14.18 ± 13.57 vs. 2.07 ± 2.42 vs. 1.51 ± 1.81 × 106 /kg, p = 0.028). The median progression-free survival and overall survival of the two groups were not reached by the end of follow-up. CONCLUSION: Compared to PAD, RAD induction had comparable efficacy and a significantly better safety profile, improved quality of life for patients, and reduced occupational stress for doctors. However, RAD induction may need to be limited to four cycles to avoid irreversible damage to hematopoietic stem cells. CLINICAL TRIAL REGISTRATION: This study was registered at www.chictr.org.cn (ChiCTR1900021558).

Health-related quality of life of patients with multiple myeloma: A real-world study in China.

PURPOSE: This study aimed to assess the health-related quality of life (HRQOL) of Chinese patients with different stages of multiple myeloma (MM) who received various treatments and identify the factors associated with a lower quality of life in China. METHODS: A cross-sectional, anonymous questionnaire was distributed to adults with MM. The measures of quality of life included the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30, QLQ-myeloma-specific module 20 (MY20), and EuroQoL EQ-5D. The data, including patient factors, difficulties experienced during the diagnosis and treatment processes, psychosocial factors and disease- or treatment-related effects, were collected. RESULTS: Four hundred and thirty patients with MM were recruited from all 27 provinces of China, and their average age was 55.7 years. Many variables were significantly associated with the HRQOL of the patients with MM. In the multivariate analyses, performance status, psychosocial factors, disease phase, and an early diagnosis were significantly associated with the HRQOL. In the subgroup analysis, the HRQOL of the patients who underwent autologous stem cell transplantation (ASCT) was significantly higher than that of the non-ASCT patients. Treatment-related toxicities had a significant impact on the quality of life of the patients with MM, and 91.5% of the patients intended to stop the maintenance treatment. CONCLUSIONS: The quality of life of patients with MM in China is affected by patient factors, difficulties experienced during the diagnosis and treatment processes, psychosocial factors, and disease- or treatment-related effects. Efforts should be exerted to improve the overall quality of life of these patients in China.

Cystathionine ß Synthase/Hydrogen Sulfide Signaling in Multiple Myeloma Regulates Cell Proliferation and Apoptosis.

Objective-To investigate cystathionine ß synthase (CBS)/hydrogen sulfide (H2S) signaling in multiple myeloma (MM) patients and to identify its effect on the proliferation of U266 cells. Methods-Bone marrow samples of 19 MM patients and 23 healthy donors were collected. qRT-PCR was performed to measure the mRNA expression levels of H2S synthases, cystathionine ß synthase, and cystathionine γ lyase. ELISA assays quantified the amount of H2S produced by the two enzymes CBS and CSE. CCK-8 experiment was used to investigate the influence of the CBS inhibitor amino oxyacetic acid and the CSE inhibitor propargylglycine on the proliferation of U266 cells. Flow cytometry and western blotting were performed to determine the effects of AOAA, PAG, and NaHS on cell cycle distribution as well as Caspase-3 and Bcl-2 expression. Results-Patients with MM had higher level of CBS compared with healthy donors. AOAA significantly inhibited cell proliferation in both a time and concentration dependent characteristic, whereas PAG does not. After 24 hours of treatment, AOAA significantly elevated the G0/G1 phase proportion of cells, and reduced the cell distribution in both S and G2/M phases, while NaHS accelerated cell cycle progression by reducing the relative number of cells in G0/G1 phase and increasing the proportion of cells in the G2/M phase. Moreover, AOAA abolished the impact of NaHS on cell cycle progression of U266 cells. AOAA treatment also led to a significant decrease in Bcl-2 expression and dramatic increase in Caspase-3 expression, though NaHS reversed these effects. Conclusion-CBS/H2S system might have a certain effect on the proliferation and apoptosis of MM cells.

Early monoclonal protein decline pattern is an independent prognostic factor in patients with multiple myeloma.

Patients always have different responses to the same treatment due to the heterogeneity of multiple myeloma (MM). However, the relationship between monoclonal protein (M-protein) reduction rates during treatment and survival prognosis in MM patients remains controversial. We retrospectively analyzed 198 newly diagnosed MM patients who received regular bortezomib-based chemotherapy for at least 2 cycles and subsequent autologous stem cell transplantation (ASCT) plus continuous maintenance. The relationship between the early M-protein reduction rates and survival prognosis was evaluated. This study is the first to divide patients into three patterns, namely, A, B, and C, according to the M-protein reduction rate during the first two therapy cycles. The results showed that pattern B patients with progressive reduction in M-protein had better progression-free survival (PFS) and overall survival (OS) than did pattern A or C patients with precipitating or slow M-protein reduction (75.33 ± 18.81 versus 41.23 ± 9.13 or 26.60 ± 6.67 months; P < 0.001; 117.33 ± 18.44 versus 71.00 ± 10.06 or 39.73 ± 24.10 months; P = 0.003, respectively). In addition, biological analysis showed that pattern A + C patients had higher international staging system (ISS) stage III proportions (P = 0.008) and lactate dehydrogenase (LDH) elevations (P = 0.044) than pattern B patients. Furthermore, pattern A + C was a significant independent adverse parameter for PFS and OS (HR = 2.62, P = 0.001; HR = 2.15, P = 0.022, respectively). Thus, our results demonstrate that pattern A + C indicates an inferior survival prognosis in MM.

Fecal Microbiota Taxonomic Shifts in Chinese Multiple Myeloma Patients Analyzed by Quantitative Polimerase Chain Reaction (QPCR) and 16S rRNA High-Throughput Sequencing.

BACKGROUND Increasing evidence has suggested that gut flora play an important role in tumor progression and prognosis. However, the relationship between fecal microbiota and hematologic malignancy requires further investigation. This study aimed to characterize the relationship of the fecal microbial community in multiple myeloma (MM) patients. MATERIAL AND METHODS A total of 40 MM patients and healthy controls (n=17) were retrospectively collected from the First Affiliated Hospital of Sun Yat-sen University between October 2018 and May 2019. The fecal samples were collected for 16S rRNA high-throughput sequencing for the fecal microbial community, as well as diversity and correlation analysis. Furthermore, 21 MM patients and their family members were selected for the matched pair analysis to confirm the fecal microbiota taxonomic changes by qRT-PCR assay. RESULTS Diversity analysis showed that diversity measured by Shannon index was lower in MM patients compared with healthy controls. At the phylum level, higher abundances of Proteobacteria but lower abundances of Actinobacteria were identified in the MM group in comparison with the healthy control group. At the genus level, the proportion of Bacteroides, Faecalibacterium, and Roseburia was significantly higher in the MM group. The matched pair analysis showed that Pseudomonas aeruginosa and Faecalibacterium were significantly more abundant in the MM group. Further analysis on prognostic risk factors revealed that the Faecalibacterium prausnitzii level was significantly correlated with ISS stage. CONCLUSIONS Our study highlights the imbalanced composition and diversity of the gastrointestinal microbiome in MM patients, which could be further used as a potential biomarker for MM risk screening, therapeutic strategies, and prognostic prediction.

1q21 Gain Combined with High-Risk Factors Is a Heterogeneous Prognostic Factor in Newly Diagnosed Multiple Myeloma: A Multicenter Study in China.

BACKGROUND: The prognostic value of 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Our aim was to investigate the prognostic value of 1q21 gain in a Chinese population. MATERIALS AND METHODS: We retrospectively identified 565 patients with NDMM from multiple centers in China. RESULTS: We detected 1q21 gain in 222 (39.3%) patients, among whom 144 had three copies of 1q21, 57 had four copies of 1q21, and 21 had at least five copies of 1q21. Copy number variation did not show any effect on the disease outcome. Multivariate analysis indicated that 1q21 gain was an independent factor for poor prognosis, but we found that 1q21 gain was strongly associated with other high-risk factors, such as del(17p), t(4;14), t(14;16), lactate dehydrogenase (LDH) level >300 U/L and International Scoring System (ISS) stage II-III (p < .001). Further analysis revealed that in the absence of other high-risk factors, isolated 1q21 gain resulted in similar progression-free survival (PFS; 52.0 vs. 52.8 months, p = .810) and overall survival (OS; not reached vs. not reached, p = .833); additionally, when present with other high-risk cytogenetic abnormalities or increased LDH levels, 1q21 gain lost its prognostic power. However, the presence of 1q21 gain increased the adverse impact of ISS stage. Furthermore, 1q21 gain predicted poor PFS and OS in patients who received bortezomib-based regimens. Moreover, autologous stem cell transplantation reversed the poor prognosis in patients with 1q21 gain. CONCLUSION: Our results show that heterogeneity exists among patients with 1q21 gain and suggest that we should assess the impact of 1q21 gain on prognosis according to different treatment regimens and accompanying high-risk factors. IMPLICATIONS FOR PRACTICE: 1q21 gain is one of the most common chromosomal aberrations in multiple myeloma (MM); however, the prognostic value of 1q21 gain remains controversial. This study investigated the prognostic value of 1q21 gain in a Chinese population with newly diagnosed MM. The results showed that heterogeneity exists among patients with 1q21 gain and suggested that the impact of 1q21 gain on prognosis should be assessed according to different treatment regimens and accompanying high-risk factors. These results could help stratify risk in patients with MM and guide treatment decisions.

A favorable inductive remission rate for decitabine combined with chemotherapy as a first course in <60-year-old acute myeloid leukemia patients with myelodysplasia syndrome features.

In acute myeloid leukemia (AML), myelodysplasia-related changes contribute to a poor prognosis. This retrospective, propensity score-matched study analyzed 108 newly diagnosed AML patients with features of myelodysplasia syndrome (MDS) (aged 14-60 years) from 2014 to 2018, who received either idarubicin and cytarabine (IA) or decitabine, idarubicin and cytarabine (DAC+IA), and compared efficacy and toxicity between the two regimens. After propensity score matching, there were 54 patients in each group. The rate of complete remission (CR) was higher in the DAC+IA group than in the IA group (85.2% vs 68.5%, P = .040) after the first course, and toxicities were comparable in both groups. Multivariate analysis indicated that the combination with DAC was independent factor for CR rate after the first induction therapy (OR = 2.978, 95% CI:1.090-8.137, P = .033). Subgroup analysis showed a CR advantage for DAC+IA (vs IA) for patients of intermediate-high risk status according to National Comprehensive Cancer Network prognostic stratification. In conclusion, DAC+IA is therefore offered as a new induction choice for newly diagnosed AML patients with features of MDS, aged <60 years old, especially in intermediate-high risk status.

Longitudinal Flow Cytometry Identified "Minimal Residual Disease" (MRD) Evolution Patterns for Predicting the Prognosis of Patients with Transplant-Eligible Multiple Myeloma.

Many questions about minimal residual disease (MRD) still need to be answered for multiple myeloma (MM). Flow MRD was monitored in 104 consecutive patients with MM after induction and at the 3rd, 6th, 9th, 12th, 18th, and 24th months post-transplant. Four MRD evolution patterns were revealed: Pattern 1 patients had persistent MRD-negative status after post-induction with no progression; pattern 2 patients had MRD-positive status postinduction but became MRD negative within 24 months post-transplant; pattern 3 patients had MRD-negative status postinduction but became MRD positive within 24 months post-transplant; and pattern 4 patients had persistent MRD-positive status after postinduction. Patients with MRD evolution pattern 1 had a better time to progression than did patients with the other evolution patterns (not reached versus not reached, versus 15.4 ± 2.4 months, versus 16.9 ± 3.0 months; log-rank test, P = .003, P = .000, and P = .000, respectively). Patients with MRD pattern 1 had a significantly longer overall survival than did patients with pattern 3 (not reached versus 35.2 ± 18.6 months; log-rank test, P = .000) and pattern 4 (not reached versus 23.8 ± 15.0 months, log-rank test, P = .000) but had a similar overall survival as pattern 2 patients (not reached versus not reached; log-rank test, P = .229). For progressing patients with MRD evolution pattern 2 or 3, the median interval of a sustained MRD-negative status was only 17 months and the median time from MRD reappearance to disease progression was only 4.6 months. A more complete MRD evolution pattern was developed to predict the outcomes for patients with MM. The optimal time of MRD assessment should include postinduction and 3rd and 24th month post-transplant. Regular MRD assessments will help detect relapse early. A sustained negative MRD status should last for at least 24 months.