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Objective To explore the clinical value of a novel CD45-negative cell sorting technology in sorting and enriching tumor plasma cells in multiple myeloma (MM). Methods A total of 60 newly diagnosed MM patients from 3 hospitals in Chongqing from July 2018 to December 2019 were recruited in this study. Bone marrow samples of 3~4 mL were taken from each patient and divided into 2 parts. One part (direct detection group) was directly detected by flow cytometry and FISH, and the other part (CD45 sorting group) was subjected to the novel CD45-negative cell sorting, followed by flow cytometry and FISH. The proportion of plasma cells in bone marrow, detection rate of cytogenetic abnormalities and risk stratification were compared in every patient before and after sorting. Results The proportion of plasma cells in bone marrow samples was (14.5±13.8)% and (51.5±30.3)%, respectively, in the direct detection group and CD45 sorting group, with that of the latter group 7.69 times higher than that of the former group (P＜0.001). Direct FISH indicated 17 cases of cytogenetic abnormality, while FISH after CD45 sorting found 39 patients having cytogenetic abnormalities (P＜0.001). The positive rates of IgH rearrangement, 13q14 deletion, 1q21 amplification and 17p deletion were all increased significantly after sorting. According to mSMRAT3.0 standard, only 28.3% of the patients were identified at high risk before sorting, but the number was increased significantly after sorting (accounting for 53.3%, P=0.002). Conclusion The new CD45 negative cell sorting technology is simple and easy to operate, and can improve the detection rate of cytogenetic abnormalities and accurately carry out risk stratification for guiding treatment in MM patients. Thus, this technology is worthy of promotion in primary hospitals.

Objective: To analyze the frequency and composition of risk-related cytogenetic abnormalities (CAs) in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The frequency and composition of risk-related CAs from a cohort of 1 015 Chinese patients with NDMM were determined by interphase fluorescence in situ hybridization (iFISH) , individually or in combination. Results: Of the cohort of 1 015 Chinese patients with NDMM, the frequencies of IgH arrangement, del (13q) /13q14, 1q gain and del (17p) were 54.0%, 46.4%, 46.1% (35.8% and 12. 7% for 3 or more than 3 copies) and 9.9%, respectively. Among 454 patients who had the baseline information for all risk-related CAs [except t (14;20) , which was not covered by the FISH panels performed routinely at all five centers], the frequencies of t (4;14) , t (11;14) or t (14;20) were 14.1%, 11.2% and 4.8%, respectively; of them, 44.3% patients carried 2 or more CAs (28.0%, 13.4% and 2.9% for 2, 3 or ≥4 CAs) ; 83.3%, 95.0% or 68.6% patients with 1q gain, del (17p) or IgH rearrangement had 1 or more additional CA (s) , with del (13q) /13q14 as the most frequently accompanied CA; 57.7% patients carried at least 1 HRCA; the incidences of double-hit (DH) MM (DHMM) (=2 HRCAs) and triple-hit (TH) (THMM) (≥3 HRCAs) were 14.3% and 2.9%, respectively. Conclusions: Our results provided an up-to-date profile of CAs in Chinese NDMM patients, which revealed that approximately 58% patients might carry at least 1 HRCA, and 17% could experience so-called DHMM or THMM who presumably had the worst outcome.

Objective: To evaluate the prognostic significance of combining ISS-Ⅲ and high risk cytogenetic abnormalities [HRCAs, including 1q gain/amplification and del (17p) ] in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The clinical characteristics and relevant variables were retrospectively analyzed in a total of 270 NDMM patients diagnosed between November 2009 and May 2018. ISS-Ⅲ stage and HRCAs [detected by FISH, including 1q gain/amplification and del (17p) ] were defined as risk factors (hit) . Based to the number of hit per case, these patients were divided into four groups carrying 0 to 3 risk factors, respectively. Progress-free survival (PFS) and overall survival (OS) were then analyzed using the Kaplan-Meier estimator. Results: Patients who carried single hit ( n =120, 44.4%) had shorter median PFS (23.0 vs 28.9 months; P >0.05) and OS (42.3 vs 53.7 months; P >0.05) than those with no risk factors ( n =66, 24.4%) . Of note, the outcome of patients who had two or more risk factors (double/triple, n =84, 31.1%) was much worse than those with either no or one risk factor, indicated by significantly reduced median PFS (14.5 months; HR =1.584, 95% CI 1.082-2.319; P =0.003 for double/triple vs single hit) and OS (18.4 months, HR =2.299, 95% CI 1.485-3.560; P <0.001 for double/triple vs single hit) . Strikingly, patients who had three risk factor (triple hit, n =5, 1.9%) displayed the poorest survival with extraordinarily shorter PFS (0.9-15.1 months) and OS (0.9-18.9 months) compared to those carrying two risk factors (double hit) . Analogous results were obtained when different combinations of ISS stages and HRCAs were analyzed. Conclusion: These results suggest a potential but rather important role of combining multiple (e.g. double or triple) adverse factors determined via the routine ISS staging and FISH detection of cytogenetic abnormalities in risk stratification and prognostic prediction, which might be helpful to identify high risk patients more precisely at diagnosis. It also raised a possibility that a small group of ISS-Ⅲ patients carrying both 1q gain/amplification and del (17p) might represent an "extremely-high risk" subset of MM.

Objectives: To evaluate the clinical characteristics and prognosis of high risk cytogenetic abnormalities (HRCA) and various combinations of cytogenetic abnormality in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: This retrospective study collected 182 NDMM patients in the First Affiliated Hospital of Jilin University between Nov. 2009 and May 2018. HRCA included 1q+, del (17p) , t (4;14) , and t (14;16) detected by FISH, and non-HRCA included del (13q) , t (11;14) detected by FISH. The clinical characteristics among three groups, including cases who carrying a single HRCA, 1 HRCA in combination with non-HRCA and cases carrying two or more HRCAs (double/triple-hit) were observed. Kaplan-Meier curve was used to analyze both progression-free survival (PFS) and overall survival (OS) for the three groups. Results: The survivals of patients with 1 HRCA in combination with non-HRCA were similar to those with two or more HRCAs (double/triple-hit) , the median PFS (mPFS) was 19.1 m vs 12.1 m ( P =0.248) and median OS (mOS) was 29.6 m vs 29.3 m ( P =0.774) . Furthermore, the prognosis of these two groups were both inferior to patients with a single HRCA, respectively. (mPFS: 32.2 m, P =0.040, P =0.001; mOS: 42.3 m, P =0.021, P =0.041) . Strikingly, both the mPFS and the mOS of patients with 1 HRCA in combination with non-HRCA (regardless of high risk or not) were significantly shorter than that of cases with a single HRCA (mPFS: 15.1 m vs 32.2 m, HR =2.126, 95% CI 1.176-3.843, P =0.005; mOS: 29.3 m vs 42.3 m, HR =1.442, 95% CI 0.705-2.950, P =0.011) . Conclusion: It is of prognostic significance value for detecting double/triple-hit based on FISH cytogenetics in NDMM.