[Efficacy and safety of programmed death-1 inhibitor in the treatment of relapsed/refractory classical Hodgkin's lymphoma].

Objective: This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) . Methods: A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model. Results: The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions: PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.

[Clinicopathological features and prognostic analysis of papillary renal cell carcinoma].

OBJECTIVE: To investigate the clinicopathological features and prognostic characteristics of papillary renal cell carcinoma (pRCC). METHODS: The clinical data of 114 patients with pRCC, including 91 males and 23 females, admitted to the Department of Urology, Peking University Third Hospital from May 2012 to May 2021 were retrospectively analyzed. All the cases were operated patients with clear pathological diagnosis and complete follow-up data. The log-rank test was used to analyze the relationship between the patients' clinicopathological characteristics and survival time, the Kaplan-Meier method to draw survival curves, and the Cox regression model for univariate and multifactorial analysis. RESULTS: The mean age of the 114 patients was (57.3±12.6) years. The tumors were located in the left kidney in 49 cases and in the right kidney in 65 cases. In the study, 48 radical nephrectomies and 66 partial nephrectomies were performed, 42 cases were type 1 and 72 cases were type 2, and the mean maximum tumor diameter was (5.5±3.6) cm. pT1a stage 52 cases, pT1b stage 22 cases, pT2 stage 4 cases, pT3 stage 33 cases, and pT4 stage 3 cases were staged. According to the World Health Organization / International Society of Urological Pathology (WHO/ISUP), there were 13 cases of gradeⅠ, 44 cases of grade Ⅱ, 51 cases of grade Ⅲ, and 6 cases of grade Ⅳ. And 34 of the 114 patients had vascular cancer embolism, 30 cases had lymph node metastasis, and 3 cases had adrenal metastasis. The median follow-up time after surgery was 22 months, and the 3-year progression-free survival rate was 95.6%. The patients with type 1 and type 2 pRCC showed statistically significant differences in age (P=0.046), body mass index (P=0.008), surgical approach (P=0.001), maximum tumor diameter (P < 0.001), vascular cancer embolism (P < 0.001), lymph node metastasis (P < 0.001), pT stage (P < 0.001), and nuclear grade (P < 0.001). The 3-year progression-free survival rates for type 1 and type 2 pRCC were 100% and 69.4%, respectively, with type 1 having a significantly better prognosis than with type 2 (P=0.003). Univariate analysis of the patients with type 2 pRCC showed that pT stage (P < 0.001), vascular cancer embolism (P < 0.001) and lymph node metastasis (P < 0.001) were strongly associated with their prognosis. Multifactorial analysis showed that vascular cancer embolism was an independent prognostic factor for progression-free survival in type 2 pRCC (P=0.001). Univariate analysis of the pRCC patients undergoing radical nephrectomy showed that pT stage (P=0.006), vascular cancer embolism (P=0.001), and lymph node metastasis (P=0.008) were significant factors affecting their prognosis, and further multifactorial analysis showed that only vascular cancer embolism was an indepen-dent prognostic factor for their progression-free survival (P=0.006). CONCLUSION: Type 2 pRCC has more morbidity, more lymph node metastases, more advanced pT stage, and higher pathologic grading than type 1 pRCC. The presence of vascular cancer embolism is an independent prognostic factor in patients with type 2 pRCC and pRCC undergoing radical nephrectomy.

[Efficacy and prognosis of newly diagnosed multiple myeloma patients treated with bortezomib, lenalidomide and dexamethasone].

Objective: To evaluate the efficacy of VRD (bortezomib+lenalidomide+dexamethasone) in newly diagnosed multiple myeloma (NDMM) patients as well as the effect of the regimen on the long-term prognosis. Methods: The clinical characteristics, survival rates, response rates and minimal residual disease (MRD) of patients with NDMM at Institute of Hematology & Blood Diseases Hospital from January 1, 2013 to January 1, 2020 were retrospectively analyzed. Subgroup analysis was also performed among groups according to the cytogenetics and autologous stem cell transplantation (ASCT) of patients. Results: A total of 87 patients were retrospectively analyzed. The age[M(Q1,Q3)] of all patients was 56 (51, 61) years and males and females accounted for 58.6% (51/87) and 41.4% (36/87), respectively. The overall response rate (ORR) was 95.9% (71/74) after 2 courses of induction therapy, with 13.5% (10/74) achieving the deep response [complete response (CR) or better] and 51.3% (38/74) of patients achieving a very good partial response (VGPR) or better. After 4 courses of induction therapy, the ORR achieved 95.2% (60/63), and the proportions of the deep response and VGPR or better grew up to 46.0% (29/63) and 77.7% (49/63). According to the treatment, the patients (≤65 years old) were divided into transplantation group and non-transplantation group. After the induction therapy, 88.8% (32/36) of patients in the transplantation group achieved VGPR or better, and 55.5% (20/36) reached the deep response. After the transplantation, the proportion increased to 97.1% (34/35) and 77.2% (27/35), respectively(88.8% vs 97.1%,P=0.174;55.5% vs 77.2%,P=0.055), with the rate of undetectable MRD increasing from 44.4% (16/36) to 77.8% (28/36) (P=0.004). In the non-transplantation group, 74.2% (23/31) of patients achieved VGPR or better after 4 courses of induction therapy, 35.5% (11/31) of the patients achieved deep response and the rate of undetectable MRD was 37.0% (10/27). Compared with the non-transplantation group, transplantation was associated with a higher rate of complete response (89.5% vs 53.1%, P<0.001) and a lower rate of MRD detection(78.4% vs 55.2%, P=0.045). The median follow-up time of all patients was 26.3 months (20.8, 33.8). The median progression-free survival and overall survival were not reached. The three-year PFS and OS rates were 78.4% and 87.2%, respectively. None of the standard-risk group, the high-risk group, the transplantation group and non-transplantation group achieved the median PFS and OS. Conclusions: VRD regimen has a promising efficacy and results in a substantial survival benefit. ASCT after VRD induction therapy is associated with higher rate of deep response, higher rate of undetectable MRD and longer survival.

[Clinical characteristics and prognosis of 46 patients with macrofocal multiple myeloma].

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

[Dose-enhanced immunochemotherapy followed by first-line autologous peripheral blood stem cell transplantation for young patients with high-risk aggressive B-cell lymphoma: an efficacy and prognostic factor analysis].

Objective: This study aimed to determine the efficacy of dose-enhanced immunochemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT) in young patients with newly diagnosed high-risk aggressive B-cell lymphoma. Methods: A retrospective study was conducted to examine the clinical and survival data of young patients with high-risk aggressive B-cell lymphoma who received dose-enhanced immunochemotherapy and ASCT as first-line treatment between January 2011 and December 2018 in Blood Diseases Hospital. Results: A total of 63 patients were included in the study. The median age range was 40 (14-63) years old. In terms of the induction therapy regimen, 52 cases received R-DA-EP (D) OCH, and the remaining 11 received R-HyperCVAD/R-MA. Sixteen (25.4% ) patients achieved partial response in the mid-term efficacy assessment, and ten of them were evaluated as complete response after transplantation. The median follow-up was 50 (8-112) months, and the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were (83.9±4.7) % and (90.4±3.7) % , respectively. Univariate analysis demonstrated that age-adjusted international prognostic index ≥2 scores was a negative prognostic factor for OS (P=0.039) , and bone marrow involvement (BMI) was an adverse prognostic factor for OS (P<0.001) and PFS (P=0.001) . However, multivariate analysis confirmed that BMI was the only independent negative predictor of OS (P=0.016) and PFS (P=0.001) . Conclusions: The use of dose-enhanced immunochemotherapy in combination with ASCT as first-line therapy in the treatment of young, high-risk aggressive B-cell lymphoma results in good long-term outcomes, and BMI remains an adverse prognostic factor.

[Primary application of Gerota's fascia suspension device in retroperitoneal laparoscopic partial nephrectom].

OBJECTIVE: To evaluate the value of Gerota's fascia suspension device in retroperitoneal laparoscopic partial nephrectomy, and to share the operation experience. METHODS: From October 2018 to December 2020, 6 cases of tumor located in the ventral side of the kidney were selected, including 3 males and 3 females, with 3 cases on the right side and 3 cases on the left side, aged 38-60 years, with an average of 52 years. The body mass index (BMI) was 18.3-30.2 kg/m2, with an average of 22.9 kg/m2. One patient with diabetes mellitus, three patients with renal cysts, and two patients underwent cholecystectomy before. All the patients were found by physical examinations. The course of disease was 7 days to 20 years, with a median time of 1 month. The tumor was in the ventral side of the kidney, 2 cases located in the upper pole, 1 case in the lower pole and 3 cases near the renal hilum. The tumor size was 1.2-7.8 cm, with an average of 4.5 cm. The R.E.N.A.L score was 7 in 1 case, 8 in 3 cases and 9 in 2 cases. After the preoperative examination completed, retroperitoneal laparoscopic partial nephrectomy (Gerota's fascia suspension device) was performed. RESULTS: All the operations were successfully completed. The operation time ranged from 139 to 193 min, with an average of 172 min. The renal artery occlusion time was 7-43 min, with an average of 19 min, only one case was more than 30 min. The blood loss ranged from 10 to 500 mL, with an average of 128 mL. The postoperative hospital stay ranged from 4 to 13 days, with an average of 6.5 days. Postoperative pathology revealed 4 cases of renal angiomyolipoma and 2 cases of renal clear cell carcinoma. The patients were followed up for 2-27 months, with an average of 17 months, without recurrence. CONCLUSION: In the operation of retroperitoneal laparoscopic partial nephrectomy, Gerota's fascia suspension device is beneficial to expose the ventral surgical field, and it is convenient for the surgeon to operate with both hands. This technique is an effective method to deal with the ventral renal tumor, which is worthy of promotion.

[Clinical analysis of fludarabine and cyclophosphamide combined with rituximab in the first-line treatment of 43 cases of chronic lymphoblastic leukemia].

Objective: To investigate the efficacy of fludarabine and cyclophosphamide combined with rituximab (FCR) in previously untreated patients with chronic lymphocytic leukemia (CLL) . Methods: The clinical data of 43 enrolled patients from May 2004 to December 2017 were analyzed the efficacy and survival results. Results: A total of 43 patients with 31 males and 12 females, and the median age was 58 years old (range 36 to72) before treatment. There were 8 patients with symptom B. The median number of peripheral blood lymphocyte was 26 (3-550) ×10(9)/L. IGHV unmutated was detected in 62.1% (18/29) patients, P53 deletion in 14% (6/43) patients, RB1 deletion in 18.6% (8/43) patients, Trisomy 12 in 25.6% (11/33) patients, ATM deletion in 16.7% (7/42) patients, respectively. The median number of treatment courses administered was 4 (range 2-6) . Twenty patients obtained CR (46.5%) , 18 patients obtained PR, 4 patients were SD, 1 patient was PD. The overall response rate (ORR) was 88.37%. Seven patients obtained MRD negative. After the median follow-up time of 51 (6-167) months, median PFS was 67 (29-105) months, median OS was not reach, 5-year PFS was (62.1±8.6) %, 10-year PFS was (31±14.3) %, 5-year OS was (70.5±8.3) %, and 10-year OS was (51.3±13.8) %. Less than 4 courses predicted adverse OS (P<0.05) . P53 deletion and less than 4 courses were associated with poor PFS (P<0.001) , and the prognostic value still remained after multivariate analysis[HR=7.65 (95%CI 1.74-33.60) , P=0.007; HR=3.75 (95%CI 1.19-11.80) , P=0.025]. Eighteen patients (41.9%) appeared grade 2-3 infection after chemotherapy, and 19 patients (44.2%) appeared grade 3-4 hematological adverse reactions. One patient (2.3%) was developed tumor lysis syndrome. All adverse reactions were controlled or recovered spontaneously. Conclusion: Previously untreated CLL patients treated with FCR had a high response rate and good survival rate, which is an important treatment choice for fit patients.

[Central nervous system toxicity caused by bortezomib: five case reports and a review of literature].

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

[Immunoglobulin M multiple myeloma: a six-case report and literature review].

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

[Usefulness of the indocyanine green fluorescence imaging technique in laparoscopic partial nephrectomy].

OBJECTIVE: To detail a novel technique for marking renal tumors with intravenous indocyanine green (ICG) during laparoscopic partial nephrectomy, and to investigate the feasibility and safety of this technique with the use of near-infrared fluorescence imaging. METHODS: Between July 2019 and January 2020, 25 consecutive cases with renal masses underwent intraoperative ICG tumor marking laparoscopic partial nephrectomy, at the department of urology in Peking University Third Hospital by the same surgeon. The key benefits included quick intraoperative identification of the mass with improved visualization and real-time control of resection margins by the ICG Immunofluorescence imaging technique. Clinical data were prospectively collected in our institutional database. Perioperative, pathological, and clinical outcomes of the partial nephrectomy were assessed. Measurement data with normal distribution and count data were respectively described as M(range) and percentage. Among these cases, 16 cases were male and 9 cases female, The median body mass index was 25.4 (20.0-35.4) kg/m2. The average age was 54 (29-77) years. The maximum tumor diameter was 2.75(1.30-5.20) cm. The R.E.N.A.L score was 7.5 (5.0-10.0).The tumor locations were distributed with upper pole (11, 42%), middle (6, 23%), and lower pole (9, 35%).The clinical stages of the tumor were described as follows: T1aN0M0 (23, 88.5%), T1bN0M0(2, 7.7%), T2aN0M0 (1, 3.8%). RESULTS: All the 25 cases were performed 26 times with intraoperative ICG tumor marking laparoscopic partial nephrectomy. There were no allergy, infection and other complications with intravenous indocyanine green. The surgical procedure was successful in all the patients. No conversion and blood transfusion were needed. All the cases of the surgical margin were negative. Overall the operative time was 136 (50-247) min and warm ischemia time was 14 (7-30) min.The estimated blood loss was 50 (10-400) mL and the hospital stay was 5.5 (3.0-31.0) days. One case with perirenal hematoma, one case with urine leak, one with respiratory failure and deep venous thrombosis. All of these cases were cured by the corresponding treatment. The others had no severe complications. There was no tumor recurrence and metastasis during the follow up with 4 to 10 months. CONCLUSION: ICG marking and near-infrared fluorescence imaging technology has now emerged as a safe, feasible and useful tool that may facilitate laparoscopic partial nephrectomy.

[Analysis of self-control trial results of narrow band imaging and white light in transurethral resection of bladder tumor].

OBJECTIVE: To investigate the effect of NBI assisted white light transurethral resection of bladder tumor (TURBT) in the treatment of bladder urothelial carcinoma and to summarize the experience of narrow band imaging (NBI) operation. METHODS: Patients with bladder urothelial carcinoma were selected, and TURBT was performed after anesthesia. First of all, the bladder tumor was found and resected under white light. Then we replaced with NBI, looked for suspicious lesions and resected them, The specimens excised under white light and NBI were collected separately. The number, location and pathological results of the lesions under white light were recorded, and the residual lesions under NBI were also recorded. To evaluate the effect of NBI, the ratio of residual bladder tumor was calculated. The cases were divided into three groups according to the time sequence. The clinical data of each group were collected and the learning curve of TURBT under NBI assisted white light was observed. RESULTS: A prospective study of 45 patients with bladder tumor from April 2018 to January 2020, including 32 males and 13 females, aged from 23 to 89 years, with an average age of 65.2 years. All the operations were successfully completed, without obvious complications after operation. Nine cases were single and 36 cases were multiple. The maximum diameter of the tumors was 0.5 to 4.0 cm, with an average of 2.2 cm. The histopathology of the resected tissue under white light was urothelial carcinoma, and 19 cases (42.2%) were pathologically positive by NBI resection. The 45 cases were divided into three groups according to the time sequence, 15 cases in each group. The true positive rate of NBI was 33.3%, 46.7% and 46.7%, respectively, and the false positive rate was 60.0%, 46.7% and 26.7%, respectively in the three groups. CONCLUSION: TURBT is an effective way to treat bladder urothelial cancer, NBI is an effective supplement of white light, which can increase the detection rate of bladder cancer and reduce post-operative recurrence. The NBI light source has a certain learning curve. With the increase of cases, the false-positive rate of NBI is gradually reduced. After the NBI operator has rich experience, the recognition degree of flat tumor is gradually improved under white light, and the residual rate of NBI is reduced after the removal under white light.

[Cdc37 Contributes to bortezomib resistance in multiple myeloma via autophagy].

Objective: To explore the role of cell division cycle protein 37 (Cdc37) mediating bortezomib (BTZ) resistance in multiple myeloma (MM) via the regulation of autophagy activity to provide a novel strategy for MM therapy. Methods: The expressions of Cdc37 and LC3b were investigated in BTZ-resistant MM cell line ANBL-6.BR using quantitative real-time PCR (qRT-PCR) and western blot (WB) analysis. Cdc37 was upregulated in ANBL-6.BR cells owing to lentivirus transfection. The LC3b expression was detected with WB, and BTZ-induced apoptosis was explored using flow cytometry. Cdc37 was then down-regulated by shRNA in the MM cell line NCI-H929. Sensitivity of BTZ was evaluated using CCK-8 analysis. WB analysis was performed to check the expression of the AKT/mTOR pathway and autophagy-associated proteins. The sensitivity of NCI-H929 cells to BTZ in the presence of autophagy inhibitor chloroquine (CQ) was analyzed using flow cytometry. Results: Cdc37 was down-regulated, while autophagy-associated gene LC3b was upregulated in BTZ-resistant cell line ANBL-6.BR. Up-regulated Cdc37 in ANBL-6.BR cells could inhibit LC3b expression and increase the sensitivity of MM to BTZ. Suppressing Cdc37 expression in MM cell line NCI-H929 induced BTZ resistance and autophagy activation, while CQ could rescue BTZ resistance caused by Cdc37 inhibition. Conclusion: Cdc37 may participate in BTZ resistance in MM via the regulation of autophagy activity.

[The prognostic significance of POD24 in 106 cases with splenic marginal lymphoma with bone marrow invasion].

Objective: To explore the effect of progression of disease within 24 months (POD24) on overall survival (OS) of splenic marginal lymphoma (SMZL) with bone marrow invasion, and to compare the clinical characteristics between POD24 SMZL with non-POD24 SMZL patients. Methods: The SMZL patients with bone marrow invasions were retrospectively analyzed between January 2002 and January 2017 treated in our institute, and the patients with sufficient follow-up time to judge POD24 were evaluated the clinical characteristics and prognosis, patients who died of non-progressive factors were excluded. Results: 106 patients were enrolled with a median age of 57 (25-79) years old. ①Clinical characteristics: All patients presented with bone marrow invasion and splenomegaly, 59.4% (63/106) with huge spleen, 14.8% (15/101) with hepatomegaly. Complex karyotype were found in 22.7% (18/79) patients; 13q deletion, 11q (ATM) deletion, 17p (TP53) deletion, and CEP12 abnormality patients presented with the percentage of 5.1% (4/78) , 1.3% (1/72) , 2.5% (2/80) , and 7.5% (4/53) , respectively.②Survival analysis: Univariate analysis showed that POD24, HGB less than 100 g/L and FISH detection of trisomy 12 were poor prognostic factors of OS. Multivariate analysis showed that only POD24 had independent prognostic significance[HR=20.116 (95%CI 2.226-181.820) , P=0.008]. ③Subgroup features: Patients with POD24 had significantly higher rates of mediastinal lymphadenopathy (63.6%vs 18.9%, P=0.005) and complex karyotype (50.0%vs 17.9%, P=0.024) than those without POD24. While the incidence of abdominal lymphadenopathy, anemia, thrombocytopenia, the lower albumin, and the increasing lactate dehydrogenase were higher in POD24 patients, but with no statistically difference. Conclusion: POD24 is an independent prognostic factor of the OS in SMZL. SMZL patients with mediastinal lymphadenopathy and complex karyotypes when diagnosed have a higher risk of POD24.

[Retrospective study of diagnosis and treatment of renal oncocytoma].

OBJECTIVE: To summarize the experience of diagnosis and surgical treatment of renal oncocytoma, and to evaluate the surgical results based on follow-up results, in order to find the best strategy. METHODS: In the study, 21 cases with renal oncocytoma from December 2003 to April 2016 in Peking University Third Hospital were retrospectively analyzed, including 4 males, and 17 females, with 10 cases on the right side and 11 cases on the left side. Their age was between 15 to 80 years (average: 58 years). Ultrasound or CT examination after admission was conducted. Ultrasound examination showed solid nodules. CT manifestations were solid masses with enhancement, and the tumor size was between 1.5 cm to 6.5 cm (average: 3.3 cm). Of the 21 cases, 9 were located in the middle of kidney, 7 were located in the upper pole, and 5 were located in the lower pole. After preoperative examination, according to the size and location of the tumor, laparoscopic partial nephrectomy or laparoscopic nephrectomy was performed, respectively. RESULTS: All the operations were successful, in which 17 cases underwent laparoscopic partial nephrectomy (including 3 cases which were converted to open surgery), and 4 cases underwent laparoscopic radical nephrectomy. The operation time ranged from 75 to 274 min (mean: 144 min), and the blood loss ranged from 10 to 1 000 mL (mean: 115 mL). The postoperative hospital stay time ranged from 6 to 13 d (average: 8.2 d). The pathological results were all renal oncocytoma. In the study, 17 cases were followed up while 4 cases were lost to follow-up. The follow-up time ranged from 12 to 175 months (mean: 44 months). One case died in 20 months after operation with unknown reason, and there were no recurrence or metastasis in the other 16 cases. CONCLUSION: Renal oncocytoma is a benign tumor with good prognosis. Enhanced CT is an effective diagnostic method in assistant examination, but it is difficult to differentiate clear cell carcinoma only from the naked eye. It is worthwhile to measure CT value at different stages of the tumor by picture archiving and communication systems (PACS), and to compare with CT value of adjacent kidney tissue may improve the diagnostic efficiency of CT. Laparoscopic surgery is an effective treatment for renal oncocytoma. We recommend laparoscopic partial nephrectomy for the patients with renal oncocytoma as the best choice if conditions permit.

Genetic and morphology analysis among the pentaploid F1 hybrid fishes (Schizothorax wangchiachii ♀ × Percocypris pingi ♂) and their parents.

Triploid and pentaploid breeding is of great importance in agricultural production, but it is not always easy to obtain double ploidy parents. However, in fishes, chromosome ploidy is diversiform, which may provide natural parental resources for triploid and pentaploid breeding. Both tetraploid and hexaploid exist in Schizothorax fishes, which were thought to belong to different subfamilies with tetraploid Percocypris fishes in morphology, but they are sister genera in molecule. Fortunately, the pentaploid hybrid fishes have been successfully obtained by hybridization of Schizothorax wangchiachii (♀, 2n = 6X = 148) × Percocypris pingi (♂, 2n = 4X = 98). To understand the genetic and morphological difference among the hybrid fishes and their parents, four methods were used in this study: morphology, karyotype, red blood cell (RBC) DNA content determination and inter-simple sequence repeat (ISSR). In morphology, the hybrid fishes were steady, and between their parents with no obvious preference. The chromosome numbers of P. pingi have been reported as 2n = 4X = 98. In this study, the karyotype of S. wangchiachii was 2n = 6X = 148 = 36m + 34sm + 12st + 66t, while that the hybrid fishes was 2n = 5X = 123 = 39m + 28sm + 5st + 51t. Similarly, the RBC DNA content of the hybrid fishes was intermediate among their parents. In ISSR, the within-group genetic diversity of hybrid fishes was higher than that of their parents. Moreover, the genetic distance of hybrid fishes between P. pingi and S.wangchiachii was closely related to that of their parental ploidy, suggesting that parental genetic material stably coexisted in the hybrid fishes. This is the first report to show a stable pentaploid F1 hybrids produced by hybridization of a hexaploid and a tetraploid in aquaculture.

[The correlation between findings of whole-body diffusion weighted imaging and clinical result in patients with multiple myeloma].

Objective: To explore the relationship between the findings of whole body diffusion weighted imaging (WBDWI) and the clinical result in patients with multiple myeloma. Methods: A total of 43 cases of multiple myeloma patients were retrospectively collected from May 2015 to May 2017 in Tianjin First Central Hospital.Twenty-nine cases were male and 14 were female. The median age was 54 years old with a range from 36 to 73 years old. The patients were divided into two groups with and without abnormal findings pending on whole body diffusion weighted imaging. The clinical data and the ADC value were compared between the two groups, as well as comparison in patients with abnormal findings between pre-and post-treatment. Results: In 43 patients, normal findings on WBDWI were found in 10 cases, 7 males, 3 females, age (59±9) years old, and abnormal findings in 33 cases, 22 males, 11 females, age (57±10) years old.No statistical differences of age and gender were found between two groups (P>0.05) .The ratio of plasma cells and the proportion of ß(2) microspheres in patients with abnormal WBDWI (50.0% (14.0%, 78.0%) , 4.8 (2.7, 7.7) mg/L)were significantly higher than those in the normal group(5.0% (2.5%, 15.0%) , 2.4 (2.0, 3.7) mg/L) (P<0.05).ADC value in different body parts of abnormal group including costal ((0.66±0.15)×10(-3) mm(2)/s), sternal bone((0.71±0.20)×10(-3) mm(2)/s), clavicles((0.67±0.17)×10(-3) mm(2)/s), thoracic vertebra((0.63±0.17)×10(-3) mm(2)/s), lumber vertebra((0.69±0.20)×10(-3) mm(2)/s), pelvic((0.83±0.36)×10(-3) mm(2)/s), proximal humerus((0.76±0.13)×10(-3) mm(2)/s), proximal femur((0.64±0.17)×10(-3) mm(2)/s), shaft of femur((0.70±0.22)×10(-3) mm(2)/s), proximal tibia((0.97±0.18)×10(-3) mm(2)/s), shaft of tibia((0.83±0.18)×10(-3) mm(2)/s) which were significantly higher than those of normal group (all P<0.05). The albumin concentration of the patients after treatment was significantly higher than those before treatment (P<0.05). Conclusion: Different imaging findings on WBDWI can reflect clinical different result in patients with multiple myeloma, and when WBDWI is normal, the clinical symptoms are mild. When abnormal findings detected on WBDWI, the clinical symptoms are still severe although albumin concentration increased after treatment.

[Clinical analysis of 24 patients of hairy cell leukemia treated by cladribine].

Objective: To investigate the curative effect of hairy cell leukemia by clatabine. Methods: The clinical data of 24 patients with hairy cell leukemia treated by cladribine from November 2006 to October 2017 were analyzed retrospectively, then the curative effect and adverse drug reaction were analyzed. Results: ① A total of 24 patients including 22 male and 2 female, and the median age was 49.5 years (range 33 to 76) at diagnosis. There were 20 patients with of splenomegaly (4 patients with mild splenomegaly, 4 moderate splenomegaly, and 12 massive splenomegaly), 3 patients with enlargement of lymph nodes, and 1 patients who had undergone splenectomy. Five patients were pancytopenia, 15 were cytopenia in 2 lineages, and 4 patients were cytopenia only in one lineage. The median ratio of HCL cells detected by flow cytometry in bone marrow was 21.79% (0.69%-68.96%). BRAF mutation was detected in 15 patients by first generation or next generation sequencing technology. ② Among 24 patients, 20 were treated with cladribine alone (one course in 19 patients, 2 courses in 1 patient), and 4 patients were treated with cladribine combined with rituximab (one course in 3 patients, 2 courses in 1 patient). Excepting 5 patients whose follow-up time was not reaching 6 months, 19 patients were evaluated for efficacy in 6-12 months after treatment: 9 patients obtained CR, 9 obtained unconfirmed CR (Cru), the other 1 obtained PR, the CR/CRu rate was 94.7%, the overall response rate (ORR) was 100.0%. ③ All the 24 patients appeared 2-4 grade hematological adverse reactions after cladribine treatment, which were mainly grade 3/4 neutropenia (66.67%) and grade 3/4 thrombocytopenia (29.2%). All the adverse reactions were controlled or recovered spontaneously. ④ After the median follow-up time of 15 (3-133) months, no progression, recurrence or death occurred in the patients. Both median OS and PFS were not reached. Conclusion: This study suggests that treatment of HCL with cladribine has high response rate, controllable adverse reactions and the good prognosis.

[Prognostic factors in newly diagnosed multiple myeloma patients with 1q21 amplification/gain treated with bortezomib-based regimens followed by autologous hematopoietic stem cell transplantation].

Objective: To explore the prognostic factors in newly diagnosed multiple myeloma (NDMM) patients with 1q21 amplification/gain treated with bortezomib-based regimens followed by autologous hematopoietic stem cell transplantation (ASCT) . Methods: We retrospectively assayed 35 NDMM patients with 1q21 amplification/gain who received bortezomib-based chemotherapy followed by ASCT and maintenance therapy between January 2008 and August 2015. Results: ①The median age of 35 patients were 49(33-63)years old. Ratio of male to female was 22∶13. Monosomy1q21 amplification/gain was only seen in 3(8.6%) patients, the other 32 patients were with additional cytogenetic abnormalities including 13q14 deletion, t(11,14), t(4,14), t(14,16), 17p deletion and complex karyotype aberrations. ②The complete remission (CR) rate was 57.0% (20/35), the very good partial remission(VGPR) rate was 37.1%(13/35) and the partial remission (PR) rate was 5.7%(2/35) after ASCT. At a median follow-up of 24 (8-85) months, 3-year estimated progression free survival (PFS) and overall survival (OS) rate were (66.5±9.7)% and (69.6±9.9)%, respectively. ③As 13 patients with high-risk cytogenetic abnormalities, the median PFS and OS time was 26 and 28 months. The 3-year estimated PFS and OS was (28.0±15.9)% and (36.5±16.4)%, respectively. Another 22 patients without other high-risk cytogenetic abnormalities, the median PFS and OS time was 54 months and not reached. The 3-year estimated PFS and OS was (71.5±12.7)% and (92.3±7.4)% in this group, respectively. The presence of additional other high-risk cytogenetic abnormalities resulted in significantly shortened PFS (χ(2)=5.404, P=0.020) and OS (χ(2)=7.596, P=0.006) compared with no high-risk cytogenetic patients. Conclusion: NDMM patients with isolated1q21 amplification/gain were rarely and usually had additional other cytogenetic abnormalities. The outcomes in this group treated with bortezomib-based chemotherapy followed by ASCT and maintenance therapy were satisfied, additional other high-risk cytogenetic abnormalities made PFS and OS further shortened.

[Role of minimal residual disease detection by multiparameter flow cytometry in newly diagnosed multiple myeloma: an analysis of 106 patients].

Objective: To assess the feasibility and prognostic value of the minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in the newly diagnosed multiple myeloma (MM) patients of China. Methods: Clinical data of 106 consecutively newly diagnosed MM patients with MRD data were retrospectively analyzed in a single center in China from June 2013 to June 2015. Results: ① Of 106 patients, 48 (45.3%) achieved MRD negativity. The median time to MRD-negative was 3 months. More patients undergoing autologous stem cell transplantation (ASCT) achieved MRD negativity compared with non-ASCT patients (62.2% vs 36.2%, χ(2)=6.536, P=0.011). ② Of 48 patients in complete remission (CR), 7 (14.6%) was MRD positive, 5 of them showed disease progression (PD) during the follow-up, and 3 died. The median progression free survival (PFS) was 19 months, and the median overall survival (OS) was 28 months, both were significantly shorter than the CR patients with MRD-negative (P<0.05). ③At a median follow-up of 38 months, MRD-negative patients showed significantly superior outcomes compared with MRD positive ones, the PFS was not reach versus 17 months and the OS was not reach for both (P<0.001). Patients were grouped into 4 categories according to their MRD levels: 1% or higher, 0.1% to less than 1%, 0.01% to less than 0.1%, or negative. It showed that the outcomes (PFS and OS) tended to be improved along with the tumor depletion. ④ Multivariate prognostic analysis showed that MRD was a powerful independent prognostic factor for PFS[HR=0.133 (95% CI 0.062-0.288) , P<0.001] and OS[HR=0.156 (95% CI 0.050-0.484) , P=0.001]. According to MRD and cytogenetics, the patients were classified into 4 groups. High risk patients with MRD negative presented a significantly better outcome than high risk patients with MRD-positive, and a similar one to the standard risk patients with MRD-negative. Conclusions: MRD negativity by MFC was more popular in MM patients undergoing ASCT. MRD was an independent prognostic factor in MM. And the prognosis of MM patients can be stratified according to the level of MRD. MRD-negative patients with high risk cytogenetics presented a similar outcome to the standard risk ones. MRD by MFC should therefore be considered more widely applied in the clinic.