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Background: B-cell chronic lymphoproliferative disorders (B-CLPDs) are characterized by the sustained accumulation of monoclonal B cells. Limited studies have systematically described the clinical features and outcomes of the whole patient group, especially in Eastern populations., Patients and Methods: A total of 1592 patients with newly diagnosed B-CLPD were enrolled. Chronic lymphocytic leukemia (CLL) accounted for 39%, and Waldenström macroglobulinemia (WM), leukemic marginal zone lymphoma, follicular lymphoma (FL), and mantle cell lymphoma (MCL) constituted 13%, 13%, 9%, and 8% of cases, respectively., Results: The median age at diagnosis was 58 years, and the male/female ratio was 1.8:1. The 17p and 11q deletions were most common in MCL (36% and 17%, respectively), and 13q deletion and trisomy 12 were most frequent in CLL (35% and 21%, respectively). Patients with leukemic MCL had significantly worse survival than that of patients with other disease entities, with a 3-year overall survival (OS) of 58%, followed by 68.2% for WM/lymphoplasmacytic lymphoma. Those with CLL, leukemic marginal zone lymphoma, and FL had relatively favorable outcomes, with a 5-year OS > 80%. The survival of patients with B-CLPDs has improved over time with the emergence of novel drugs (3-year OS improvement from 82.1% to 92.2%). The improvement in survival mainly resulted from improvement among patients with MCL, WM/lymphoplasmacytic lymphoma, and FL. On multivariate analysis, only hemoglobin, lactate dehydrogenase, and 17p deletion were independently associated with survival (hazard ratio, 1.6, 2.0, and 3.1, respectively)., Conclusions: Comprehensive analysis of the clinical characteristics, immunophenotypic profiles, and cytogenetic features can be helpful in the differential diagnosis, especially for patients without a non-bone marrow biopsy specimen available. Universal prognostic factors could help with the early detection of high-risk patients and stratification for risk-adapted therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Recent attempts have focused on identifying fewer magnitude of minimal residual disease (MRD) rather than exploring the biological and genetic features of the residual plasma cells (PCs). Here, a cohort of 193 patients with at least one cytogenetic abnormalities (CA) at diagnosis were analyzed, and interphase fluorescence in situ hybridization (iFISH) analyses were performed in patient-paired diagnostic and posttherapy samples. Persistent CA in residual PCs were observed for the majority of patients (63%), even detectable in 28/63 (44%) patients with MRD negativity (<10 -4 ). The absence of CA in residual PCs was associated with prolonged survival regardless of MRD status. According to the change of the clonal size of specific CA, patients were clustered into five groups, reflecting different patterns of clone selection under therapy pressure. Therapy-induced clonal selection exerted a significant impact on survival (HR = 4.0; P < 0.001). According to the longitudinal cytogenetic studies at relapse, sequential cytogenetic dynamics were observed in most patients, and cytogenetic architecture of residual PCs could to some extent predict the evolutional pattern at relapse. Collectively, the repeat cytogenetic evaluation in residual PCs could not only serves as a good complementary tool for MRD detection, but also provides a better understanding of clinical response and clonal evolution.

Rapid remission by induction therapy has long been recognized as an important predictor for long-time survival in acute leukemia. However, the impact of response kinetics on multiple myeloma (MM) seems to be different and remains unexplored. The relationship between response kinetics and outcome were assessed in 626 patients with newly diagnosed MM who were included in a prospective, nonrandomized clinical trial (BDH 2008/02). Patients were assigned to either immunomodulatory drug- or proteasome inhibitor-based therapy. The response depth, time to best response (T BR ) and duration of best response (D BR ) were collected. Depth of response was associated with superior outcomes, consistent with findings from other studies. However, the early responders (defined as T BR ≤3 months) showed significantly worse survival compared with late responders. We found that patients with rapid complete remission experienced inferior survivals comparable to those attaining a gradual partial remission. Moreover, 4 distinct response kinetics patterns were identified. Patients with gradual and sustained remission ("U-valley" pattern) experienced superior outcomes, whereas poor outcomes were observed in rapid and transient responders ("roller coaster" pattern) (median overall survival, 126 vs 30 months). The effects of response patterns on survival were confirmed in patients at different stages of disease and cytogenetic risk, including transplant-eligible patients and those attaining different extents of response depth. Collectively, our data indicated that slow and gradual response is a favorable prognostic factor in MM. In addition to response depth, the kinetic pattern of response is a simple and powerful predictor for survival even in the era of novel agents., (© 2019 by The American Society of Hematology.)

Background: Peripheral neuropathy (PN) is an important toxicity that limits the use of bortezomib (Btz). Attempts to reduce PN have included its subcutaneous (SC) administration., Patients and Methods: We retrospectively analyzed 307 patients with newly diagnosed multiple myeloma from a single Chinese center, receiving Btz-based regimens administered either via SC injection (SC group, n = 167) or intravenous (IV) infusion (IV group, n = 140). The efficacy and safety of Btz administration via SC and IV were then compared., Results: Most baseline characteristics were similar between these 2 groups. A lower frequency of adverse events, especially grade ≥ 3 PN (P = .002), was observed in the SC group compared with the IV group. The estimated median Btz dosage when PN developed was higher (20.8 mg/m 2 vs. 15.6 mg/m 2 ), and fewer patients reduced or discontinued Btz owing to adverse events in the SC group compared with the IV group. The overall response rate (≥ partial response [PR]) was comparable (94.8% vs. 96.2%). However, patients in the IV group required fewer cycles to achieve PR, whereas a larger proportion of patients in the IV group achieved ≥ very good PR. After a median follow-up of 23 months (range, 1-84 months), no significant difference in median progression-free survival (not arrived vs. 33.0 ± 2.735 months) and overall survival (not arrived vs. 56.0 months) was noted., Conclusion: SC Btz is associated with better tolerance; however, IV administration achieves a faster and deeper response in Chinese patients with newly-diagnosed multiple myeloma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To investigate the clinical characteristics and prognosis of very young patients with multiple myeloma (MM)., Methods: We retrospectively analyzed the clinical characteristics and outcome of 35 newly diagnosed MM patients 40 years old or younger during a period of 15 years and compared with published data from western countries., Results: Our study demonstrated that these very young patients were more likely to be in advanced stage of International staging system, IgD isotype, hemoglobin<100 g/L, decreased platelets and deletion of 17p13. With a median follow-up of 17 months (1- 89 months), the median overall survival (OS) of this cohort was 33 months and progression-free survival (PFS) was 13 months, moreover 8 of 17 deaths occurred in the first year after diagnosis. In the univariate analysis, extramedullary infiltration, del (17p13）and renal impairment were associated with reduced PFS (P=0.031, P=0.015, P=000, respectively), while the last two factors also predicted inferior OS (P=0.015, P=0.001), but multivariate analysis showed that only renal impairment independently associated with inferior survival in COX model（PFS: HR=3.953, 95% CI 1.263-12.371, P=0.018; OS: HR=5.769, 95% CI 1.602- 20.771, P=0.007)., Conclusion: Our research showed for the first time that the clinical characteristics and survival of MM patients ≤ 40 years old in China were different from that in western countries. The special attention should be paid to the patients with their diagnosis and treatment.

Objective: To study the association between the level of serum DKK1 and disease course of multiple myeloma（MM）as well as myeloma bone disease., Methods: This study enrolled 145 cases of MM（including 79 newly diagnosed MM, 19 responded MM, 47 relapsed or progressive MM） whose lytic bone disease were evaluated by conventional radiography, ELISA was used to detect the concentration of serum DKK1., Results: Serum DKK-1 elevated in newly diagnosed MM compared with normal donors［2 155（646-35 251）vs 1 487（646-2 577） ng/L, P=0.000］, those responded［1 136（431- 3 582） ng/L, P=0.001］and relapsed/progressive MM［1 695（431-3 582） ng/L, P=0.037］, and the level of relapsed/progressive MM was marginally higher than the responded ones. Moreover, MM patients without lytic lesions in conventional radiography had significantly lower DKK- 1 levels than those with lytic bone disease［1 910（660-26 925）vs 2 519（646-35 251） ng/L, P=0.005］. Notably serum DKK-1 correlated with the number of bone lesions［0 vs 1-3 vs >3 lesions: 1 910（660-26 925）vs 2 155（1 369-5 974）vs 2 547（646-35 251）ng/L, P=0.018]., Conclusion: DKK-1 serum concentration correlated with disease course of MM and myeloma bone disease, indicating that DKK-1 was an important factor for the extent of bone disease, which supporting the hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.

Objective: To evaluate the results of autologous hematopoietic stem cell transplantation (auto-HSCT) in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-ALL)., Methods: From January 2000 to December 2007, the clinical data of auto-HSCT in adults Ph-ALL with complete remession (CR) 1 according to BDHALL2000/02 protocol were analyzed., Results: A total of 56 patients were enrolled and the probabilities of standard risk, intermediated risk and high-risk group were 41.1%, 33.9%, and 25.0%, respectively. After a median follow-up of 75 months (range 7-177 months), the 5-year overall survival (OS), events free survival (EFS) and relapse free survival (RFS) were (51.8 ± 6.7)%, (51.8 ± 6.7)%, and (60.5 ± 6.9)%, respectively. And the 5-year accumulative relapse rate was (39.1 ± 6.9)%. The 5-year OS of standard risk, intermediate risk, high-risk group were (60.9 ± 10.2)%, (52.6 ± 11.5)%, and (35.7 ± 2.8)%, respectively. The 5-year RFS among three groups were (68.3 ± 9.9)%, (62.5 ± 12.1)%, and (44.9 ± 14.1)%, respectively. The 5-year EFS among three groups were (60.9 ± 10.2)%, (52.6 ± 11.5)%, and (35.7 ± 12.8)%, respectively. The 5-year accumulative relapse rate among three groups were (31.7 ± 9.9)%, (37.5 ± 12.1)%, and (55.1 ± 14.1)%, respectively. There was no statistical significance of any survival rates between standard and intermediate risk groups, just as intermediate and high-risk groups. The OS and EFS in standard risk group were superior to those in high-risk group (P=0.040 and P=0.029, respectively), while there was no statistical significance of RFS and accumulative relapse rate between the two groups. The clinical factors listed below did not influenced the prognosis in the univariate analysis (P>0.05), including more than 5 weeks reaching to CR, WBC count at diagnosis, different immunophenotype (T or B cells), myeloid antigen expression, hyperdiploid chromosome karyotype, complex chromosome abnormality, conditioning regimen with or without TBI, duration between transplantation and diagnosis., Conclusion: Ph-ALL adults could achieve a satisfactory CR and better survial according to BDHALL2000/02 protocol followed by auto-HSCT, especially for the standard or intermediate risk group, and no-donors high-risk patients.

Objective: To analyse the incidence, clinical features, prognosis of bone-related extramedullary disease （bEMD） and its relationship with strict EMD (sEMD) in MM patients., Methods: The records of 834 consecutive newly diagnosed patients with MM in our hospital between 1993 and 2013 were retrospectively reviewed., Results: ①Among 834 patients at diagnosis, 32 cases (3.8%) showed bEMD, and 40 cases (4.8%) showed sEMD. Patients with bEMD at presentation showed significant lower level of lactate dehydrogenase (180.9 U/L vs 299.2 U/L, P=0.034) and higher overall response rate (ORR) (95.7% vs 66.7%, P=0.009) compared with sEMD patients. While the above two parameters were comparable between patients with bEMD and without EMD. ②As to the prognosis of patients without autologous hematopoietic stem cell transplantation (auto-HSCT), the overall survival (OS) of patients with sEMD, bEMD and without EMD was 14.0, 37.5, and 38.0 months, respectively. The time to progression (TTP) of the three groups was 11.5, 27.0, and 22.0 months, respectively. Compared to the patients with sEMD, the outcomes (both OS and TTP) of the other two groups was significantly better (P<0.05). Patients with bEMD at presentation was comparable to the patients without EMD, but the two groups were better than the patients with sEMD. ③The incidence of bEMD during follow-up was 0.5%. The OS of patients with sEMD, bEMD and without EMD during follow-up was 26.0, 17.0, and 40.0 months, respectively. The TTP of the three groups was 13.0, 11.0, and 25.0 months, respectively. The outcomes (both OS and TTP) of patients with bEMD at relapse/progression showed no significant difference as compared with the other two groups (P>0.05)., Conclusion: The clinical features of MM patients with bEMD are different from the patients with sEMD. Outcomes of this population is significantly better than the latter, and is comparable to the patients without EMD. It suggests that bEMD alone has no negative prognostic significance in MM patients.

Objective: To investigate the outcomes of autologous stem cell transplantation (ASCT) for patients with aggressive peripheral T-cell lymphoma (PTCLs) in advanced stage., Methods: The clinical data of 25 patients in complete remission (CR) with aggressive PTCLs received ASCT from May 1997 to June 2013 were retrospectively analyzed., Results: ① Of the 25 cases, 16 were unspecified PTCL (PTCL-U), 4 with angioimmunoblastic T cell lymphoma (AITL), 3 with anaplastic large cell lymphoma (ALCL) and 2 with hepatosplenic T cell lymphoma (HSTL), with a median age of 30(12-54) years old. Ratio of male to female is 16∶9. The distribution of stages was 8 cases with stage Ⅲ and 17 patients with stage Ⅳ. Nine patients presented with bone marrow involvement. Before ASCT, 18 patients were in CR1 and 7 patients were in CR2. ②Two patients with HSTL in stage ⅣB and IPI score 4/5 in CR1 relapsed and died within 12 months after ASCT. At a median follow-up of 38 (range 14-110) months, the estimated 3-year probability of PFS and OS for the other 23 patients was (63.1 ± 10.5)% and (71.8 ± 9.9)%, respectively. The patients in first CR had a better survival than the patients in second CR. The 3-year probability of PFS were (74.9 ± 11.0)% vs (33.3 ± 19.2)% (P=0.092) and OS were (80.2 ± 10.4)% vs (50.0 ± 20.4)% (P=0.043), respectively. The 3-year probability of PFS and OS were (40.0 ± 17.4)% and (53.3 ± 17.3)% in bone marrow involvement patients and the corresponding figure were (77.9 ± 11.3)% and (84.4 ± 10.2)% in non- bone marrow involvement patients., Conclusion: ASCT could improve the survival of aggressive PTCLs. Non CR1 status and bone marrow involvement had negative influence on OS in patients with aggressive PTCLs treated by ASCT. The prognosis was very poor in patients with HSTL and satisfactory regimens should be investigated.

Objective: To investigate the influence of renal function on the level of β₂-microglobulin (β₂-MG) as prognostic factor in newly diagnosed multiple myeloma (MM) patients, and to analyze the overall survival (OS) in different level of β₂-MG with relatively normal or abnormal renal function in MM patients., Methods: According to the level of β₂-MG, 666 newly diagnosed MM patients were divided into three groups as β₂-MG<3.5, 3.5-<5.5, ≥5.5 mg/L. According to the level of serum creatinine, these patients were divided into two groups:serum creatinine <177 μmol/L as relatively normal group, serum creatinine ≥177 μmol/L as abnormal group., Results: Among 666 patients, there were 416 male and 250 female, the median age was 58 (25-86) years old. Comparison of OS among β₂-MG<3.5, 3.5-<5.5, ≥5.5 mg/L groups indicated that the median OS of the three groups were 85.75 (95% CI 70.99-100.50), 47.25 (95% CI 40.98-53.53) and 35.05 (95% CI 30.75-39.35) months, respectively (P<0.01). Comparison of OS between serum creatinine <177 and ≥177 mmol/L groups, the median OS of the two groups were 64.67 (95% CI 56.57-72.77) and 32.74 (95% CI 27.74-37.73) months, respectively (P<0.01). In β₂-MG≥5.5 mg/L, the median OS of relatively normal and abnormal groups were 37.25 (95% CI 31.45-43.06) and 32.55 (95% CI 26.26-38.83) months, respectively (P=0.142)., Conclusion: High level of β₂-MG and renal function correlated with shorter survival of MM patients. Higher level of β₂-MG with abnormal renal function can't change the prognostic value of β₂-microglobulin on MM.

Objective: To assess the efficacy of dose-intensive immunochemotherapy with or without autologous hematopoietic stem cell transplantation (ASCT) for newly diagnosed young patients with medium/high risk diffuse large B-cell lymphoma (DLBCL)., Methods: The retrospective study was performed in 29 cases of young patients (≤ 60 years) with newly diagnosed DLBCL and an age-adjusted International Prognostic Index (aaIPI) score of 2 or 3. All of them were treated with dose-intensive regimens (DA-EPOCH or Hyper-CVAD/MA) combined with Rituximab and some were consolidated with first-line ASCT. The efficacy and the potential predictors were evaluated., Results: The median age of 29 patients was 43 years old. Of them, 12 patients were consolidated with high-dose chemotherapy and ASCT. The complete remission (CR) rate was 69%, the partial remission (PR) rate 21% and the overall response rate 90%. After a median follow-up of 14 months, the estimated progression-free survival (PFS) and overall survival (OS) at two years were 64% and 70%, respectively. The median PFS and OS were significantly longer in CR patients than that in PR patients (P=0.015 and 0.061, respectively). Two patients achieved PR after induction therapy converted to CR after ASCT and were in continuous CR after follow-up above three years. In multivariate analysis, only bone marrow involvement (BMI) at diagnosis had an adverse influence in PFS (P=0.009), but not in OS. Based on whether there was BMI or not and the extent of BMI at diagnosis, the patients were divided into three groups as BM-0 (without BMI), BM-1 (the extent of BMI ≤ 10%) and BM-2 (the extent of BMI>10%). Patients in BM-2 group had significantly shorter PFS and OS than those in BM-0 and BM-1 groups (P=0.001 and 0.045, respectively). In multivariate analysis, the extent of BMI>10% was the independent poor prognostic factor for PFS and CNS relapse or prognosis., Conclusion: Dose-intensive immunochemotherapy followed by ASCT or not has significant effect on efficacy of first-line treatment for young and untreated patients with medium/high risk DLBCL. The extent of BMI>10% at diagnosis is an independent risk factor associated with poor PFS and increased CNS relapse or progression.

Objective: To investigate the treatment outcomes of autologous stem cell transplantation (ASCT) as first-line treatment in patients with high risk lymphoblastic lymphoma (LBL) and compare the effect of different induction regimen on prognosis., Methods: Thirty LBL patients in complete remission received ASCT from 1996 to 2012 in our hospital were retrospectively analyzed., Results: (1)Of the 30 patients, 25 were T-LBL and 5 B-LBL with a median age of 19(7-53) years old. Ratio of male to female is 23:7. Fourteen (46.7%) patients presented with bulky mediastinal masses and 15(50.0%) with bone marrow involvement. The distribution of stages was 2(6.7%), 5(16.7%) and 23 (76.6%)patients with stages II, III, and IV, respectively. The distribution according to age-adjusted international prognostic index (aaIPI) was 5(16.7%) patients in 1 score, 14(46.6%) in 2 scores and 11(36.7%) in 3 scores. (2)At a median follow-up of 32(range, 10-171) months, 17 patients were alive and 13 relapsed and died from LBL after ASCT. The estimated 5-year probability of DFS and OS was (50.4±10.7) % and (53.9 ±10.2)% for all the patients. (3)According to the treatment regimens before ASCT, the patients were divided into NHL-type group (n=12) and ALL-type group (n=18). In NHL-type group, 9 patients relapsed and died, the estimated 5-year probability of DFS and OS was (22.2 ±12.8) % and (33.3 ±13.6) %, respectively. Median DFS and OS time were 24 months and 36 months. In ALL-type group, 4 patients relapsed and died from lymphoma, the estimated 5-year probability of DFS and OS was (77.8 ± 9.8) % and (77.8 ± 9.8) %, respectively. Median DFS and OS time were not reached. For DFS and OS, ALL-type group were better than that of NHL-type group and the difference was significant (P=0.022 and P=0.049)., Conclusion: The results showed that complete remission with intensive first-line ALL-type regimens and followed by ASCT consolidation may significantly improve long-term outcome for high risk LBL patients.

Chromosome 1q21 aberrations have not been yet been made part of routine clinical tests and their effect in multiple myeloma is still under investigation. The prognostic value of copy number variation and percentage of plasma cells involved have remained unclear. In the present study, we analyzed the prognostic value of 1q21 in a series of 290 cases of newly diagnosed multiple myeloma treated in a prospective, non-randomized clinical trial (BDH 2008/02). We found that incidence of 1q21 aberration increased at relapse, but its copy numbers and proportion of cells involved did not change. Gains of 1q21 had no impact on survival in patients receiving thalidomide-based treatment but conferred a significantly inferior prognosis in patients under bortezomib-based chemotherapy and was an independent adverse prognostic factor for progression free survival (HR 3.831; 95%CI: 2.125-6.907; P<0.001) and overall survival (HR 3.245; 95%CI: 1.555-6.773; P=0.002). Strikingly, our results showed that the copy number variation and clone size harboring 1q21 gains carried no additional prognostic value and patients with 1q21 gains did not benefit significantly from regimens incorporating bortezomib. Our results indicate that three copies of 1q21 and 20% of plasma cells with this abnormality were enough to confer bortezomib resistance. Therefore, chromosome 1q21 gains should be considered a high-risk feature in multiple myeloma receiving bortezomib therapy.