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Objective: To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenström macroglobulinemia (WM) . Methods: Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety. Results: A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion: Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

Objective: To investigate the presence of a distinct stem cell populations different from mesenchymal stem cells in the mandibular periosteum of both human and non-human primates (macaca mulatta), to explore its properties during intramembranous osteogenesis and to establish standard protocols for the isolation, culturing and expanding of mandibular periosteal stem cells (PSC) distinguished from other PSCs in other anatomical regions. Methods: Periosteum was harvested from the bone surface during flap bone removal in patients aged 18-24 years undergoing third molar extraction and from the buccal side of the mandibular premolar region of 6-year-old macaca mulatta respectively, and then subjected to single-cell sequencing using the Illumina platform Novaseq 6000 sequencer. Cross-species single-cell transcriptome sequencing results were compared using homologous gene matching. PSC were isolated from primary tissues using two digestion methods with body temperature and low temperature, and their surface markers (CD200, CD31, CD45 and CD90) were identified by cell flow cytometry. The ability of cell proliferation and three-lineage differentiation of PSC expanded to the third generation in vitro in different species were evaluated. Finally, the similarities and differences in osteogenic properties of PSC and bone marrow mesenchymal stem cells (BMSC) were compared. Results: The single-cell sequencing results indicated that 18 clusters of cell populations were identified after homologous gene matching for dimensionality reduction, and manual cellular annotation was conducted for each cluster based on cell marker databases. The comparison of different digestion protocols proved that the low-temperature overnight digestion protocol can stably isolate PSC from the human and m. mulatta mandibular periosteum and the cells exhibited a fibroblast-like morphology. This research confirmed that PSC of human and m. mulatta had similar proliferation capabilities through the cell counting kit-8 assay. Flow cytometry analysis was then used to identify the cells isolated from the periosteum expressed CD200(+), CD31(-), CD45(-), CD90(-). Then, human and m. mulatta PSC were induced into osteogenesis, adipogenesis, and chondrogenesis to demonstrate their corresponding multi-lineage differentiation capabilities. Finally, comparison with BMSC further clarified the oesteogenesis characteristics of PSC. The above experiments proved that the cells isolated from the periosteum were peiosteal cells with characteristics of stem cells evidenced by their cell morphology, proliferation ability, surface markers, and differentiation ability, and that this group of PSC possessed characteristics different from traditional mesenchymal stem cells. Conclusions: In this study, normal mandibular PSC from humans and m. mulatta were stably isolated and identified for the first time, providing a cellular foundation for investigating the mechanism of mandibular intramembranous osteogenesis, exploring ideal non-human primate models and establishing innovative strategies for clinically mandibular injury repair.

This article summarizes and organizes relevant publications in journals, along with a review of medical history, systematically summarizing the development process of dental alveolar surgery in China. The initial establishment phase (1935-1952) marked the starting point of Chinese Alveolar Surgery. Despite the impact of wars, it laid the foundation for subsequent research and practice. During the early development phase (1953-1966), the "Chinese Journal of Stomatology" was founded, which promoted the development of Alveolar Surgery. Research focused on tooth extraction methods and complications. Tooth Transplantation and Preprosthetic Surgery gradually began to take off. The stagnant phase (1967-1977) occurred due to the interruption of international exchanges, leading to an almost complete halt in the development of Alveolar Surgery. Entering the rapid catch-up phase (1978-1985), Alveolar Surgery scholars in China began striving to overcome the stagnation of the previous decade. While some progress was made, no significant innovative achievements emerged. In the scientific development phase (1986-2010), clinical research, basic experiments, and paper writing in modern Chinese Alveolar Surgery began to adhere to scientific standards with the rise of experimental medicine. The exploration and innovation stage (2011-2023) is the current development phase, during which Chinese Aveolar Surgery has reached its peak, making substantial progress in technology, clinical practices, and basic research, gradually reaching or even surpassing international advanced levels. Looking back at the development history in China, we can find the wisdom and hard work of the older generation of Alveolar Surgery scholars. However, contemporary challenges and issues, such as standardizing technology, promoting clinical practices, and talent cultivation, need to be addressed by present-day Alveolar Surgery professionals as they forge ahead.

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.

Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P =0.001; 5-year PFS: 8.9% vs 54.2%, P <0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups ( P =0.271, P =0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases ( P =0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% ( P >0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P =0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P =0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes ( P <0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.

Objective: To investigate the clinical and pathological features, treatment, and prognosis of gray zone lymphoma (GZL) . Methods: From July 2, 2013, to February 10, 2021, the clinical and pathological features, treatment, and outcomes of five patients with GZL at the Blood Diseases Hospital, Chinese Academy of Medical Sciences were studied retrospectively. Results: There were one male and 4 females, with a median age of 28 (16-51) years at diagnosis. Four patients had mediastinal (thymic) involvement, two of which had superior vena cava obstruction syndrome, and 3 patients had extra-nodal involvement. There was one case with a limited Ann Arbor stage and 4 cases with a progressive stage. Three patients had cHL-like pathomorphology with scattered Hodgkin-like cells, strongly positive for CD20, positive for CD30, and CD15 was negative; the other two patients had both cHL and DLBCL morphology, with some areas resembling Hodgkin cells and some areas resembling immunoblasts, strongly positive for CD30, and CD15 but negative CD20. Two patients were treated with cHL-like regimens for induction and achieved only partial remission; after salvage therapy with enhanced DLBCL-like regimens, all achieved complete remission (CR) . Three patients were treated with enhanced DLBCL-like immunochemotherapy regimens for induction, and two patients were effective, one of whom achieved CR. Four patients who did not achieve CR were given second or third-line salvage therapy, and all of them recovered. One patient lost parity, one died of disease progression at 35.9 months after diagnosis, and the remaining three maintained sustained remission. Conclusions: GZL is uncommon, usually affects younger patients, is mediastinal and is diagnosed using path morphology and immunophenotype. Patients with newly diagnosed GZL appear to be more sensitive to DLBCL-like immunochemotherapy regimens; relapsed or refractory patients were tended with non-cross-resistant combination chemotherapy or with new drugs.

Objective: The study aims to explore the clinical and biological characteristics of patients with non-IgM lymphoplasmacytic lymphoma (LPL) . Methods: The clinical data of 340 patients with LPL admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were collected retrospectively, including 23 cases of the non-IgM LPL and 317 cases of the Waldenström's macroglobulinemia (WM) , from July 1993 to August 2020. The clinical and biological characteristics of the two groups were compared. Results: Among 23 patients with the non-IgM type LPL, two patients secreted monoclonal IgA, 14 patients secreted monoclonal IgG, and seven patients did not secrete monoclonal immunoglobulin. The median age of the non-IgM LPL and WM were both 62 (35-81) years old. Compared with the WM group, the proportion of women (56.5% vs 27.3%, P =0.007) , the proportion of splenomegaly (60.1% vs 43.8%, P =0.100) , and the proportion of extranodal invasion (21.7% vs 12.3%, P =0.672) in non-IgM LPL group were higher. Eighteen patients were tested for MYD88 gene mutation, and the overall mutation rate of MYD88 was 55.6%. In the non-IgM LPL group, a total of 17 patients received treatment, which had a comparable proportion (94.4% vs 92.7%, P =0.488) to the WM group. Sixteen patients were evaluated for efficacy, and the overall remission rate of the first-line treatment was 87.5%. The median follow-up time was 33.9 (3.5-125.1) months, and the median PFS and OS were both not reached. The 3-year PFS and OS rates were 71.4% and 68.9%, respectively. In the WM group, the median PFS was 66.2 months and the median OS was 78.1 months. Compared with the WM group, in the non-IgM group no significant differences in PFS ( P =0.340) and OS ( P =0.544) were seen. Conclusion: The clinical and biological characteristics of the non-IgM LPL and WM patients were similar. However, the proportion of women and extranodal involvement were higher in the non-IgM LPL group. The survival and prognosis of the non-IgM LPL patients were similar to those of the WM patients.

Objective: To study the clinical, histopathological, and genetic features of large B-cell lymphoma (LBCL) with IRF4 rearrangement. Methods: Six patients presenting at our center between December 2017 and October 2021 were evaluated by pathological examination, fluorescence in situ hybridization, and next-generation sequencing. The relevant literature was reviewed. Results: ①The study sample included three males and three females with a median age of 33 years. Three tumors were in the tonsils, two in the lymphoid nodes, and one in the dorsal lump. All patients were treated using the RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone) regimen. All of them were alive at the time of follow-up in November 2021. ②Microscopic examination showed an entirely follicular pattern in one case and an entirely diffused pattern in 5 cases. The tumor cells were medium to large, and most of the lesions were dilatative with brisk mitotic activity ( n =five cases) and no starry sky pattern ( n =6 cases) . ③Four cases exhibited a GCB phenotype, and the other two exhibited a non-GCB phenotype. All of the cases were positive for CD20, PAX-5, MUM, and BCL6, and negative for CD5. Moreover, CD10, BCL2, and c-MYC were positive in 4, 3, and 2 cases, respectively.④IRF4 gene rearrangement was identified in all cases, BCL6 gene rearrangement was detected in 5 cases, and 2 cases were positive. BCL2 and MYC gene rearrangement were performed in 5 cases, all negative. ⑤Three paraffin tissue samples were used for next-generation sequencing, and lymphoma-related gene mutations such as IRF4, TP53, IGLL5, and MYD88 were detected in 3 cases. Conclusions: LBCL with IRF4 rearrangement is a rare entity with unique clinical, pathological, and genetic characteristics. This entity's pathogenesis, treatment options, and long-term prognosis still need to be explored further.

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.

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.

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.

Objective: To explore the feasibility of graphene oxide (GO)-chitosan (CS) guided bone regeneration composite membrane being used as a new guided bone regeneration (GBR) membrane by testing its tensile strength and its effect on the proliferation of human gingival fibroblasts (HGF). Methods: The CS solution and GO solution were mixed in following ratios, ultrasonically crushed and dispersed, and formed into membranes by self-evaporation. Composite membrane with 0.5%, 1.0%, 2.0%, 4.0%, 6.0%, 8.0% GO in CS was prepared. The tensile strength of the composite membranes was tested by mechanical universal testing machine ( n= 6). The microstructure of the composite membrane with the best tensile strength was observed by scanning electron microscopy and transmission electron microscopy. X-ray diffraction was used to characterize the ingredients of the material. A group of samples was prepared again with the proportion of the highest tensile strength composite membrane, and were immersed in a sodium hydroxide solution for acid removal. The tensile strength of the new group of samples was tested. The newly extracted impacted teeth were collected from the Department of Oral and Maxillofacial Surgery, Stomatologic Hospital and College, Anhui Medical University, and the gingival tissues remained on the teeth were taken for primary HGF and were cultured to P2 generation, which were identified by immunocytochemical staining methods. Cell counting kit-8 (CCK-8) was applied to detect cell counts in the blank control group, the pure CS membrane group, and the composite membrane group with the highest tensile strength ( n= 5) and all groups co-cultured with the HGF for 24 h and 48 h. Results: After adding GO, the cross-section of the composite membrane was in an ordered layer structure. X-ray diffraction analysis showed that GO could be found in the composite membrane. The tensile strength increased with the increase of GO ratio. When the mass fraction of GO in CS was 4.0%, the tensile strength reached (134.8±7.3) MPa and the tensile strength reached (144.6±8.1) MPa after deacidification of the composite membrane. The CCK-8 test of HGF showed that there was no significant difference in absorbance between the pure CS membrane group and the GO/CS composite membrane group when they were compared with the blank control group ( P> 0.05). Conclusions: When the mass fraction of GO in CS is 4.0%, the composite membrane has the best tensile strength. The composite membrane showes good cytocompatibility, which lays a foundation for further in vivo experiments and the development of a new generation of GBR membrane.

Objective: To investigate the prognostic significance of detection of minimal residual disease after first induction treatment (MRD(1)) in adult acute lymphoblastic leukemia (ALL) patients treated with autologous stem cell transplantation (auto-HSCT). Methods: The clinical data of 87 ALL patients who underwent auto-HSCT during February 2006 to April 2017 with MRD(1) detection data by flow cytometry were analyzed retrospectively. The relationship between MRD(1) and relapse and survival of ALL patients after auto-HSCT was studied. Results: Of 87 patients, 26 (29.9%) were MRD(1) positive. The proportion of high-risk immunophenotype (pro-B, pro-T, pre-T, mature T) was significantly higher in MRD(1)-positive patients than that in MRD(1) negative patients (34.6% vs 14.5%, P =0.038). There was no significant difference between positive and negative MRD(1) patients at age, sex, lineage (T/B), immunophenotype (standard risk/high risk), high white blood cell count (B-ALL>30×10(9)/L or T-ALL>100×10(9)/L), high-risk chromosome/gene ratio, the time from first complete remission to transplantation and pre-treatment regimen. The 5-year overall survival (OS) and leukemia-free survival (LFS) in MRD(1) negative and positive patients were 72.7% vs 47.3% ( P =0.004) and 75.7% vs 29.6% ( P <0.001), respectively. Multivariate analysis showed that positive MRD(1) was an independent risk factor for OS ( HR =3.007, 95% CI 1.256-7.200, P =0.013) , and positive MRD(1) and high-risk immunophenotype were risk factors for LFS ( HR =3.986, 95% CI 1.813-8.764, P =0.001; HR =2.981, 95% CI 1.373-6.473, P =0.006) . Conclusions: Auto-HSCT could not reverse the poor prognosis of MRD(1) positive patients. Auto-HSCT treatment is optional for patients with MRD(1) negative and maintaining MRD(1) negative status during intensive therapy.

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.

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.

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion: During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.

Objective: To evaluate efficacy of the BiRd regimen, a combination of clarithromycin, lenalidomide, and dexamethasone, in the treatment of patients with relapsed/refractory multiple myeloma (RRMM) . Methods: Patients with RRMM treated with BiRd between September 11, 2013 and August 1, 2016 at six centers were included to evaluate overall survival rate (ORR) , clinical benefit rate (CBR) , progression-free survival (PFS) , overall survival (OS) , as well as adverse events. Results: Of 30 patients with RRMM, 27 patients were evaluable, and ORR and CBR were 51.9% (14/27) and 66.7% (18/27) respectively, including 1 sCR (3.7%) , 3 CR (11.1%) , 3 VGPR (11.1%) , and 7 PR (25.6%) . In 13 patients with prior Rd, ORR and CBR were 38.5% (5/13) and 61.5% (8/13) respectively, of which 5 patients with ≥MR carried high-risk cytogenetic[ (e.g.17p- or t (4;14) ] together with at least one of other adverse-prognostic cytogenetic (e.g.13q- and/or 1q21+) . In 24 patients with prior bortezomib-based therapy, ORR and CBR were 45.8 and 62.5%, respectively. With a median follow-up time of 14.9 (range 1.0-33.8) months, the median PFS and OS were 12.0 (95% CI 11.6-12.4) and 27.6 (95% CI 15.1-40.1) months, respectively. The BiRd regimen was well tolerated. Conclusion: The BiRd regimen is an effective and safety protocol for RRMM, including those carrying high-risk cytogenetic markers.

Objective: To evaluate the efficacy and long-term outcome of a combined protocol for multiple myeloma (MM) , including induction therapy, autologous hematopoietic stem cell transplantation (ASCT) and consolidation and maintenance therapy. Methods: Clinical records of 144 patients with MM from January 1, 2005 to February 1, 2016 were retrospectively analyzed. Results: The overall response rate (ORR) after ASCT was 100.0%, in which the complete remission (CR) was 64.1% and the best treatment response rate of superior to PR was 89.4%. During a median follow-up of 47 months, patients with an overall survival (OS) and progression free survival (PFS) was 120.9 and 56.9 months respectively. 5y-OS (73.7±4.7) %, 7y-OS (60.5±6.3) %; 3y-PFS (69.2±4.2) %, 5y-PFS (47.8±5.3) %. The median OS and PFS between the first line transplantation group and salvage transplantation group were 120.9 months vs 50.1 months and 60.2 months vs 16.7 months (all P =0.000). In 127 patients with R-ISS staging, the median survival of Ⅰ, Ⅱ, Ⅲ stage was 120.9 months ( n =43) , 88.4 months ( n =64) , 35.6 months ( n =20) , respectively ( P =0.000). For subgroup analysis of survival in early and late ASCT, the median OS of patients with R-ISS stage Ⅲ (35.6 months vs 15.8 months, P =0.031) and the median PFS of two groups (phase Ⅰ: 72.1 months vs 18.9 months, P =0.000; Ⅱ: 53.4 months vs 16.7 months, P =0.012; Ⅲ: 28.5 months vs 5.9 months, P =0.001) were different. Multivariate analysis showed that only R-ISS and the degree of remission before transplantation had impact on OS ( HR =8.486, 95% CI 2.549-28.255, P =0.003) and PFS ( HR =2.412, 95% CI 1.364-4.266, P =0.002) , respectively. Conclusion: The combined protocol containing ASCT is effective for MM patients, improving remission rate and remission depth, prolonging PFS and OS. First line transplantation could significantly prolong the OS and PFS as compared with salvage transplantation. R-ISS and pre-transplantation remission depth are prognostic factors for survival.

Objective: To investigate the clinical efficacy and safety of lenalidomide (Revlimid, R) -based chemotherapy in the treatment of relapsed/refractory multiple myeloma (MM) patients. Methods: 57 consecutively relapsed/refractory MM patients were retrospectively analyzed from June 2013 to February 2016. All the patients received lenalidomide-based chemotherapy. Results: ① 60.4% patients had international staging system (ISS) stage Ⅲ, 37.9% patients had revised international staging system (R-ISS) stage Ⅲ, and 53.3% patients harbored at least one of the high-risk cytogenetic abnormalities[del (17p) and/or t (4;14) and/or t (14;16) ]. ②The patients received median 6 cycles of R (range: 1-32). The overall response rate (ORR) was 58.9% (33/56) , among which 8.9% was complete response (CR) , 19.8% was very good partial response (VGPR) , and 30.4% was partial response (PR). In addition, 10.7% patients attained minor response (MR). Total clinical benefit was 69.6%. Patients with more than 1 line of prior therapy, or previously thalidomide-resistance, or R-ISS stage Ⅲ disease showed significantly lower ORR. ③With a median follow-up of 27 months, the median progression free survival (PFS) , the median interval to PR, the median duration of response (DOR) , and the median overall survival (OS) was 8 months, 2 months, 8 months, and 19 months, respectively. Univariate prognostic analysis showed that abnormal karyotype, R-ISS stage Ⅲ and response inferior to PR were negative prognostic factors for PFS and OS. While the multivariate prognostic analysis showed that abnormal karyotype and R-ISS stage Ⅲ were independent prognostic factors. ④In the safety aspect, the most common grade 3-4 non-hematology adverse events (AEs) were infection (17.5%) , rash (1.8%) and thromboembolism (1.8%) , and the most common grade 3-4 hematology AEs were neutropenia (7.0%) and thrombocytopenia (3.5%). Totally 3 patients (5.3%) discontinued R because of AEs, and 2 cases (3.5%) of secondary primary malignancies were observed. Conclusion: The R-based treatment is effective and safe in the treatment of relapsed/refractory MM patients in China. Abnormal karyotype and R-ISS stage Ⅲ were independent negative prognosis factors in this cohort.

Objective: To explore the risk factors of acute lymphoblastic leukemia (ALL) recurrence in adult patients and establish a prognosis index (PI) calculation model in order to improve the prevention strategy of ALL in adults., Methods: 104 adult ALL patients from Blood Diseases Hospital & Chinese Academy of Medical Sciences between August 2008 and November 2011 were enrolled. COX proportional hazards regression stratified by Dummy variable was used to set up the prediction model; Kaplan-Meier method and Log-rank test were used to estimate and compare the survival. After calculated individual PI value, patients' expected survival should be estimated by groups., Results: The overall median survival of adult ALL patients was 22.00 months (95% CI 17.00-27.00). COX regression analysis showed that chemotherapy group patients had a higher risk of recurrence than of ASCT group while setting treatment as the dummy variable (RR=2.052, 95%CI 0.877-4.799, P=0.007). Stratified Analysis showed that the risk factors of B-ALL recurrence in adult patients included HGB <100 g/L (RR=0.186, 95% CI 0.068-0.512, P=0.001), CNSL (RR=7.767,95% CI 2.951- 20.433, P=0.001), number of consolidation chemotherapy<3 (RR=0.445, 95% CI 0.211-0.940, P=0.034) and Ph chromosome positive (RR=2.771, 95% CI 1.353-5.674, P=0.005). Grouped by the PI value, the expected survival of each individual patient could be estimated as PI=0.58 base., Conclusion: HGB, CNSL, number of consolidation chemotherapy and Ph chromosome were independent risk factors of B-ALL recurrence in adult patients. PI value could predict the survival of adult ALL patients and provide reference for individual therapy and prognostic evaluation.

Objective: To investigate the clinical and laboratory characteristics and survival of Chinese patients with T- cell prolymphocytic leukemia (T-PLL)., Methods: Eleven patients with T-PLL admitted in our hospital from Jan 2006 to Oct 2012 were retrospectively analyzed., Results: Of the 11 patients, nine were males and two females, with the median age of 56.0(19-69) years old. All the patients, except for three, presented with leukocytosis. The incidence of hyperleukocytosis (1/11) was less frequent than that in the British series (75%) (P=0.000). Lymphocyte counts in peripheral blood were increased in 9 of the 11 patients with the median absolute lymphocyte count (ALC) of 17.22(0.58-148.83)×10⁹/L. Superficial lymphadenopathy and splenomegaly were the most common physical signs. It was common that serum lactate dehydrogenase (LDH) and beta 2 microglobulin(β2-MG)were higher than normal level. All cases were positive for CD2/CD3/CD5/TCRαβ, negative for CD1a /HLA-DR and TdT, and most of them were strong positive for CD7 expression. By chromosome analyses, most cases. (9/10) have normal chromosome. This rate is significantly higher than that of the British and American series (3% and 25%, respectively) (P=0.000, P=0.001). The 14q11 abnormality and trisomy 8q, which are common among Western cases, were not observed in any of our cases. With a median follow-up of 23.0 months, three patients died. Two year progress free survival (PFS) and overall survival (OS) were 53.3% and 50%, respectively. There were 3 patients with PFS over a number of years, whether it should be considered as the T-chronic lymphocytic leukemia (T-CLL) is worthy of further studies., Conclusion: The common clinical manifestations of T-PLL patients were increased lymphocyte counts and lymphadenopathy as well as splenomegaly. And most cases have high level of blood LDH and β2- MG and normal chromosome karyotype.

Objective: To explore the treatment options for younger than 60 years old adults with Ph /BCR-ABL positive acute lymphoblastic leukemia (Ph⁺ ALL)., Methods: From January 2001 to June 2012, 42 adult patients were enrolled in the study. All patients received standard VDCP±L ±imatinb (IM) as induction therapy followed by intensive consolidation of modified Hyper-CVAD/MA±IM. At complete remission 1 (CR1), patients with appropriate donor received allogeneic hematopoietic stem cell transplantation (allo-HSCT), the others sequentially received intensive consolidation ±IM and autologous HSCT (ASCT) at molecular CR (MCR), then MM±VP±IM as maintenance therapy. Overall survival (OS), disease free survival (DFS) and relapse rate (RR) were analyzed., Results: CR rate after 1 cycle of induction chemotherapy was 83.3%. 39(92.9%) patients achieved CR. The median DFS and OS were (22.0±3.5) and (37.0±5.3) months respectively, with cumulative RR of (43.7±9.7)% during a median follow-up of 26.5(8-75) months. All 7 patients in CT group relapsed. Two patients received IM pre- and post-ASCT maintained MCR for 35 and 12 months after ASCT. But the other 3 ASCT recipients without IM died of relapse within 1 year. The transplant-related mortality rate in allo-HSCT group was 12.5%. The estimated 3-year OS in allo-HSCT (n=16), ASCT (n=5) and CT (n=7) groups were (66.7±12.2)%, (25.0±21.7)% and (16.7±15.2)%, respectively (P=0.014); meanwhile, the estimated 3-year DFS in those groups were of (56.3±12.4)%, (26.7±22.6)% and 0, respectively (P=0.002)., Conclusion: IM combined with intensive chemotherapy significantly increased the CR rate with the improved quality of CR, which highlighted the feasibility of SCT. Allo-HSCT could decrease relapse to produce favorable OS and DFS in CR1 of young adults with Ph⁺ ALL. ASCT combined IM might be the treatment of choice for those achieved MCR but without donors.

Objective: To explore the efficacy and prognosis of first-line autologous hematopoietic stem cell transplantation (ASCT) for newly diagnosed patients with multiple myeloma(MM)., Methods: From January 2005 to December 31, 2012, 60 patients with MM were enrolled. All patients received thalidomide or/and bortezomib-based induction therapy, then received high-dose melphalan (200 mg/m²) and autologous stem cell support to get a ≥ partial response (PR), and followed by thalidomide-dexamethasone (TD) ±bortezomib as consolidation or maintenance treatment. With the follow up to December 31, 2012, the overall survival (OS), progression free survival (PFS) and the prognostic factors, including ISS stage, response and fluorescent in situ hybridization (FISH) data of cytogenetics were analyzed., Results: With a median follow up of 36.8 (12.0-102.5) months, the median OS and PFS estimate were not reached and 86.5 months, respectively. After transplantation, all (100%) patients received very good partial response (VGPR), and 34 (56.7%) patients achieved complete response (CR) after consolidation or maintenance treatment. The patients that achieved CR resulted in long term PFS (P=0.030), with no difference in OS (P=0.942). The univariate analysis showed that the abnormalities, including 13q14 deletion, 1q21 gain, IgH location and p53 deletion had the prognostic impacts. If the t(4;14) or p53 deletion was excluded, there would be no correlation between 13q14 deletion or 1q21 gain with PFS and OS. The patients with p53 deletion had a worst survival., Conclusion: There has been significant improvement in the outcome for young MM patients by using ASCT and novel drugs. Cytogenetic abnormalities and response to therapy are the main factors affecting the survival of patients.

Objective: To explore the efficacy of imatinib (IM)-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-SCT) in first complete remission (CR1) for adult Ph(+) acute lymphoblastic leukemia \[Ph(+)-ALL\]., Methods: From March 2006 to December 2010, 16 adult Ph(+)-ALL were enrolled in the study. All patients received IM combined with standard VDCP ± L as induction therapy then intensive consolidation with modified Hyper-CVAD/MA regimen plus IM, and followed by allo-SCT in CR1. Some of them received IM maintenance therapy after allo-SCT. With the follow up to March 31, 2011, the clinical parameters. overall survival (OS), disease free survival (DFS), relapse incidence (RI), non-relapse mortality (NRM) and prognostic factors were analyzed., Results: All 16 patients achieved morphological complete remission (CR), and 10 of them achieved molecular CR. After transplantation, all patients obtained successful engraftments. With a median follow-up of 27.1 (7.4 - 65.8) months, 14 patients were alive, 2 died from NRM, and 2 relapsed. The estimated OS and DFS at 3 year were (85.9 ± 9.3)% and (83.9 ± 10.5)%, and cumulative RI and NRM at 3 year were (16.1 ± 10.5)% and (14.1 ± 9.3)%, respectively. None prognostic factor was found on analysis., Conclusion: IM combined with intensive chemotherapy significantly increased the CR rate and improved the quality of CR, which prepared the feasibility of allo-SCT in CR1. IM therapy pre- and post-allo-SCT would be a promising strategy for adult Ph(+)-ALL to decrease relapse and facilitates favorable OS and DFS.

Objective: To investigate the expression of microRNA-155 and microRNA-146a in the CD19(+) B cells of chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), splenic marginal zone lymphoma (SMZL), and to analyze its clinical significance., Methods: Peripheral blood (PB) (78 cases) and bone marrow (BM) samples (9 cases) from 53 CLL patients, 13 MCL patients, 19 SMZL patients, and 12 healthy donors were collected. Mononuclear cells were isolated and B cells were purified with a CD19(+) magnetic-bead system. Total RNA was extracted from purified CD19(+) cells and microRNAs expression were measured using the TaqMan microRNA quantitative PCR. The results combined with the clinic data of patients were analysed., Results: (1) The expression of microRNA-155 in CLL (4.49 ± 0.83) was significantly higher than in MCL (3.83 ± 0.45) and SMZL (3.80 ± 0.61) (P < 0.05); (2) The level of microRNA-146a in SMZL (3.81 ± 0.59) was significantly higher than in CLL (2.58 ± 0.90) and MCL (2.27 ± 0.88) (P < 0.01); (3) The level of microRNA-155 was significantly higher in IgVH unmutated patients than in mutated patients in CLL (P = 0.012); (4) The microRNAs expression had no statistical difference between two prognostic groups in CLL., Conclusion: (1) The expression of microRNA-155 and microRNA-146a is different in malignant lymphoproliferative disorders (LPD); (2) Deregulation of the microRNAs expression might play a critical role in the pathogenesis and prognosis in the LPD.

Objective: To determine the incidence and clinical significance of chromosome 13q14 deletion in multiple myeloma (MM)., Methods: Bone marrow samples were collected from 132 newly diagnosed MM patients referred to our hospital. Interphase fluorescence in situ hybridization (i-FISH) combined with magnetic activated cell sorting (MACS) were performed on chromosome 13q14 (RB-1)., Results: (1) i-FISH was used to investigate CD138-enriched bone marrow MM cells and revealed a 13q14 deletion rate of 51.5% (68/132), while conventional cytogenetic (CC) analysis revealed 13q deletions/monosomy 13 (Δ13) only of 5.0%(6/120). (2) Univariate analysis showed that 13q14 deletion rate by i-FISH > 25%, bone marrow plasma cells > 50%, ISS stage and β(2)-MG ≥ 5.5 mg/L were associated with shorter overall survival (OS). Multivariate analysis revealed that 13q14 deletion rate by i-FISH > 25% was an independent unfavorable factor (P = 0.042). (3) Patients treated with bortezomib had a much better response than those treated with traditional chemotherapy (P = 0.001). There was no significant difference in OS between patients received bortezomib with and without 13q14 deletion (P > 0.05), indicating that bortezomib could reverse the poor prognosis of 13q14 deletion., Conclusion: (1) i-FISH followed CD138 cell sorting appears to be a highly sensitive method for detecting 13q14 deletion. (2) 13q14 deletion rate by i-FISH > 25% is an independent unfavorable factor. (3) Bortezomib could reverse the poor prognosis of 13q14 deletion.

Objective: To study the cytogenetic characteristics of B cell non-Hodgkin's lymphoma (B-NHL) with bone marrow involvement, and to explore the clinical significance and prognosis., Methods: Clinical data of 126 B-NHL patients with bone marrow involvement diagnosed in our hospital were retrospectively analyzed. Chromosome banding analysis was performed after 24 h culture., Results: (1) The B-NHLs included were diffuse large B-cell lymphoma (DLBCL) 38.9% (49 cases), lymphoplasmacytic lymphoma (LPL) 19% (24 cases), mantle cell lymphoma (MCL) 16.7% (21 cases), follicular lymphoma (FL) 9.5% (12 cases), marginal zone lymphoma (MZL) 8.7% (11 cases) and small lymphocytic lymphoma (SLL) 7.1%(9 cases). (2) Chromosome aberrations (CA) were detected in 52 of 126 patients (41.3%) by conventional cytogenetics (CC), including clonal CA 38 cases, and non-clonal CA 14 cases. Ploidy levels in 38 clonal CA cases were pseudodiploid (57.9%), hypodiploid (15.8%) and hyperdiploid (26.3%). The incidence of chromosomal abnormalities among DLBCL, MCL, MZL, LPL, FL and SLL was 73.4%, 38.1%, 36.4%, 8.3%, 8.3% and 11.1%, respectively. (3) Clonal CA, CA more than two kinds, and CA of chromosomes 2, 3, 9, 11, 17, 18 and 20 were associated with shorter overall survival (OS) in DLBCL. More than two kinds of CA and CA of chromosome 3, 13 were associated with shorter OS in MCL., Conclusions: The incidence of CA was higher in aggressive lymphoma than in indolent lymphoma. Complex CA were quite common, and some specific CA might have prognostic significance.

Objective: To investigate the role of mesenchymal stem cells (BMSCs) in multiple myeloma (MM) bone marrow (BM) microenrivonment and their effect on myeloma cells survival and bortezomib induced apoptosis., Methods: BMSCs were derived from BM of untreated myeloma patients (MM-BMSCs) and healthy donors (HD-BMSCs), respectively. The phenotype, proliferation time and cytokine secretion of MM-BMSCs were detected and compared with HD-BMSCs. Then BMSCs were co-cultured with myeloma cell line NCI-H929 and bortezomib in vitro. The NCI-H929 cells proliferation and bortezomib induced cell apoptosis were investigated., Results: MM-BMSCs and HD-BMSCs were isolated successfully. The phenotype of MM-BMSCs was similar to that of HD-BMSCs. Expressions of CD73, CD105, CD44 and CD29 were positive, but those of CD31, CD34, CD45 and HLA-DR (< 1%) negative. The proliferation time of MM-BMSCs was longer than that of HD-BMSCs (82 h vs 62 h, P < 0.05). Moreover, over-expressions of IL-6 and VEGF in MM-BMSCs culture supernatant were detected as compared with that in HD-BMSCs [(188.8 ± 9.4) pg/ml vs (115.0 ± 15.1) pg/ml and (1497.2 ± 39.7) pg/ml vs (1329.0 ± 21.1) pg/ml, respectively]. MM- BMSCs supported survival of the myeloma cells NCI-H929 and protected them from bortezomib induced cell apoptosis., Conclusions: MM-BMSCs is benefit for myeloma cells proliferation and against cell apoptosis induced by bortezomib. Over-expression of IL-6 and VEGF maybe play a critical role in these effects.

Objective: To investigate the clinical features and treatment outcomes of different regimens in Chinese patients with lymphoblastic lymphoma (LBL)., Methods: Forty-three patients with LBL were retrospectively analysed, of which 30 were T-LBL, and 13 B-LBL., Results: (1) Most patients were young men with a median age of 21, and 63.0% of the T-LBL patients had mediastinal masses. (2) Treatment outcome could be assessed in 37 cases, of which the response rate (RR) was 81.1% and complete remission (CR) rate was 67.6%. The RR and CR rates in patients treated with regimens for ALL (ALL-like group) and those treated with regimens for NHL (NHL-like group) were 94.4%, 68.4% and 83.3%, 52.6%, respectively. (3) The estimated median overall survival (OS) and progression free survival (PFS) of hematopoietic stem cell transplantation (HSCT) group were significant longer than those of ALL-like group (P=0.018, P=0.025) and NHL-like group (P=0.016, P=0.011). The OS at 5 years in NHL-like group, ALL-like group and HSCT group were (14.4+/-9.4)%, (20.2+/-12.7)% and (79.5+/-13.1 )%, respectively., Conclusion: (1) LBL is more common in young men, with less involvement of peripheral blood. Compared with B-LBL, T-LBL often has a mediastinal mass and serious cavity effusion. (2) Intensive treatment regimens for ALL should be used in LBL. HSCT at CR1 can improve outcome obviously.

Objective: To analyze the characteristics of cytogenetic aberration of adults with Philadelphia chromosome-positive (Ph+) and/or bcr-abl positive (bcr-abl+) acute lymphoblastic leukaemia (ALL), and investigate its influence on patients' outcomes., Method: Retrospective analysis of 100 adult Ph+ ALL patients from January 1, 1996 to December 31, 2007 was carried out. The type, distribution and frequency of chromosome aberration were summarized, and compared among different subgroups., Results: 1) In all cases, 72 had chromosome aberrations, including 22 with sole Ph chromosome, 44 Ph+ with additional abnormalities, which included double Ph, monosomy 7, monosomy 20, trisomy 8 trisomy 21, 9p deletion and 22 deletion. 2) Patients with pseudodiploid and hyperdiploid had higher WBC count, and inferior outcome with lower rates of overall survival (OS) and relapse free survival (RFS). 3) Ph+ group also had higher WBC counts and inferior outcome with low OS and RFS rates. There was no statistic significance between sole Ph+ group and Ph plus additional aberrations group. 4) Patients with both abnormal and normal metaphase (AN) and with solely abnormal metaphase (AA) had higher WBC count, less frequent P190 occurrence and inferior outcome than those only normal metaphase (NN) group, whereas, there was no difference between AA and AN groups. 5) Double Ph chromosome had a lower frequency of P190 and inferior OS than non-double Ph group., Conclusion: Adults with Ph+ ALL have complicated cytogenetic abnormalities, pseudodiploid and hyperdiploid indicate inferior outcome, and double Ph chromosome may be a unfavorable prognostic factor.

Objective: To explore the prognostic impact of bone marrow involvement (BMI) and therapy in diffuse large B cell lymphoma (DLBCL)., Methods: The clinical characteristics and prognosis of 83 DLBCL patients with or without BMI were retrospectively analyzed. The treatment outcome of standard CHOP regimen (CHOP group), intensive-dose regimen (intensive-dose group) and rituximab combined therapy (rituximab group) were compared., Results: The adverse prognostic factors including LDH elevation, ECOG score > or =2, higher IPI and aaIPI score, B symptom, hepatomegaly, splenomegaly, hemoglobin <110 g/L, platelet <100 x 10(9)/L and serum albumin <35 g/L were more prevalent in DLBCL patients with BMI than in those without BMI. Multivariate analysis showed that BMI was an independent prognostic factor of DLBCL. The 3-year OS and PFS rates in rituximab group were 78.1% and 64.3%, respectively, being statistically higher than that in CHOP group (23.6% and 21.8% respectively, P = 0.000 for both) and in intensive-dose group (33.3% and 25.7% respectively, P = 0.002 and 0.001, respectively). But no difference between the latter two groups (P = 0.411 and 0.694, respectively). For the patients with BMI, the 3-years OS and PFS in rituximab group (57.1% and 57.1%) were statistically higher than that in CHOP group (13.9% and 14.1%) and intensive-dose group (29.5% and 16.8%) (P = 0.029 and 0.012 respectively), respectively and also no difference in the latter two groups (P = 0.226 and 0.376 respectively). In the rituximab group, the 3-years OS and PFS were 86.7% and 67.3% respectively in patients without BMI, being higher than that in patients with BMI (57.1% and 57.1%), but the difference was not statistically significant (P = 0.645 and 0.965 respectively)., Conclusion: BMI is a negative independent prognostic factors of DLBCL patients. The rituximab combined chemotherapy can significantly improve the therapeutic effect of the DLBCL, and relieve the negative impact of BMI.

Objective: To investigate the efficacy and adverse reaction of bortezomib plus chemotherapy with or without stem cell transplantation (SCT) for treatment of multiple myeloma (MM)., Methods: Thirty-one MM patients were treated with bortezomib plus dexamethasone or thalidomide or DTPACE, followed by SCT. Response to bortezomib was evaluated according to the European Blood and Marrow Transplantation (EBMT) criteria. Adverse events were graded according to the WHO criteria., Results: 1) 5 discontinued the bortezomib therapy because of acute renal failure or acute tumor lysis syndrome and 3 died. In 26 evaluable patients received 99 courses of therapy. The overall response rate (ORR) to bortezomib was 80.8%, and was 100.0% in 15 newly diagnosed patients and 54.6% in 11 relapsed/refractory patients. All of the 6 newly diagnosed patients treated with bortezomib plus DTPACE followed by SCT achieved CR. 2) In 7 newly diagnosed patients completed 8 cycles bortezomib treatment, the diseases were improved more and more with the courses of treatment. Chromosome 13 deletion did not exert a negative impact on response. 3) 6 of 7 patients completed 8 cycles treatment without SCT relapsed in 1-3 month after discontinued therapy; only 1 of 6 such patients received SCT relapsed with the rest keeping on CR at 6-11 month follow-up. 4) The most common adverse events were 1-2 grade and tolerable 3 patients had to reduce the bortezomib dosage because of peripheral neuropathy or sinus bradycardia., Conclusion: Bortezomib in combination with chemotherapy with or without SCT is an effective therapy with manageable toxicities for MM patients.

Objective: To analyze the clinical and laboratory features of chronic lymphocytic leukemia (CLL)., Methods: Retrospective investigation of 263 patients with CLL in our hospital between Feb. 2000 and Jan. 2007., Results: The median age was 60 years with male/female ratio of 2.17 : 1. Patients who were asymptomatic at diagnosis (35.4%) had low Rai grades. Fatigue and lymphadenopathy (54.8%) were the most common features at presentation. Infections, connective tissue diseases and secondary tumors frequently occurred in CLL. WBC counts were between (10 - 100) x 10(9)/L, with lymphocytes percentages more than 0.50 in 97.1% patients. Bone marrow was normal- to hyper-cellularity with lymphocytes percentages more than 0.300 in 99.4% patients. Diffuse infiltrations in bone marrow section were found in 72.2% patients. There were lower CD5 (85.1%) and higher CD25 (78.9%) positivities in the present series as compared with that in other reports. Hypogammaglobulinemia, especially hypo-IgM, usually occurred. Chromosome abnormality were rarely found by routine chromosome examination., Conclusions: There were some clinical and laboratory characteristics different from that of abroad data. Further exploration of new markers is required for prognosis prediction and treatment choice.

Objective: To analyse the efficacy and safety of thalidomide (Thal) for patients with multiple myeloma (MM)., Methods: Effectiveness and adverse events of 102 MM patients treated with thalidomide at a median dosage of 200 mg/d. Thirteen cases were treated with Thal alone (group A), and 105 case with Thal in combination with other therapeutic agents (group B) were retrospectively analyzed., Result: 1) The response rate (RR) (CR + PR) was 65.4% for induction therapy in 52 cases and 45.5% for salvage therapy in 66 cases. RR in group B was higher than that in group A (58.1% versus 23.1/%, P= 0.017), and the non-response/progress (NR) rate was lower (15.2% versus 46.2%, P= 0.015). In group B, the NR rate was lower in 50 cases of newly diagnosed MM than in 55 cases of refractory or relapsed MM (6.0% versus 23.6%, P=0.012). In group B, RR between Thal+VAD or M, regimen (72 cases) and Thal + MP regimen (33 cases) was not statistically significant (62.5% versus 48.5%, P >0.05). 2) The median duration of response maintenance was 15.5 (1.0-58.0) months in 21 cases. 3) Among 97 patients with follow-up data, the estimated median duration of OS was 44 months in a median follow-up duration of 20 months and the accumulative time for use of Thal was 8 months. In univariate analysis,the accumulative duration for use of Thal 6 months, hemoglobin > or = 100 g/L and bone marrow megakaryocytes > 20 per smear were associated with longer OS (P = 0.0014, 0.0101, 0.019, respectively). 4) Multivariate analysis suggested that the accumulative time for use of Thal and bone marrow megakaryocytes > 20 were independent good prognostic factors for OS (P = 0.006, 0.036, respectively). 5) The adverse events of Thal were mostly endurable, the rate of thrombus events was lower than that reported in literature., Conclusion: Thalidomide alone or combined with chemotherapy is an useful therapy for MM. The accumulative time for use longer than 6 months may improve survival.

Objective: To verify applicability of the International Staging System (ISS) for multiple myeloma (MM) to 112 Chinese MM patients and compare ISS with Durie-Salmon (DS) and Intergroup Francophone du Myeloma (IFM) staging system in predicting prognosis., Methods: 112 previously untreated MM patients in Blood Diseases Hospital of CAMS were analyzed according to ISS retrospectively., Results: 1) Serum beta2-microglobulin (beta2-MG) > or = 3.5 mg/L was an independent adverse prognostic factor for overall survival (OS), and serum albumin <35 g/L predicted for time to progression (TTP), 2) In the 58 cases having cytogenetic data, chromosome 13 aberration (Delta 13) was the only independent adverse prognostic factor for OS; 3) Factors significantly related to serum beta2-MG were serum creatinine, 24h urinary protein,body mass index (BMI) and performance status (PS); and those related to serum albumin were hemoglobin level, percentage of bone marrow plasma cells, lactate dehydrogenase(LDN), fever, PS, class of M-protein, serum phosphorus and BMI; 4) All traditional prognostic factors had no statistical difference between ISS stage II and III excepting for serum beta2-MG and creatinine, and 5/6 Delta 13 patients were classified to ISS stage II; 5) The median OS of ISS stage I, II, III were 69, 23 and 26 months (m) respectively, being no statistical difference between stage II and III; for DS system, 89.5% of patients were classified in stage III, being no statistical difference for OS between the stage I/II and III; while for IFM system, the median OS of low-, intermediate- and high-risk group were 69, 40 and 8 months respectively, being statistically different between high-risk and intermediate/ low-risk groups., Conclusions: From the result of our limited analysis, the staging of ISS II and III seems unsuitable for Chinese MM patients. The IFM staging system ,which incorporates delta 13, is more effective than ISS, and DS staging system in predicting prognosis.

Objective: To investigate the efficacy of imatinib in the treatment of chronic myeloid leukemia (CML) and analyse the treatment outcome and related factors., Methods: Ninety five CML patients were treated with imatinib in our hospital from May 2002 to May 2006. The outcomes and related factors were analysed., Results: (1) One year after therapy, there were 95.5% of chronic phase (CP) patients achieved complete hematologic response (CHR). Fifty-two patients with complete cytogenetic dates were divided into primary-therapy group (n = 19) and secondary-therapy group (n = 33). The major cytogenetic responses (MCyR) at 6-, 12-, 18-, 24- and 30-months after therapy for the former group were 84.2%, 84.2%, 89.5%, 89.5% and 94.7%, and for the latter group were 36.4%, 39.4%, 39.4%, 39.4% and 39.4%, respectively (P < 0.01). The expected survival at 12-, 24-, 36- and 50-month after imatinib treatment for CP group was (98.1 +/-1.9)%, (87.8 +/- 7.1)%, (81.9 +/- 8.7)% and (81.9 +/- 8.7)%, respectively. (2) Twelve month after therapy, there are 70% of accelerated phase (AP) patients achieve CHR and 10% get MCyR. The expected survival at 12-, 24- and 36-month after imatinib treatment for AP group was (63.0 +/- 17.7)%, (15.8 +/- 14.3)% and (15.8 +/- 14.3)%, respectively. (3) Six month after therapy, 57.9% of blast crisis (BC) patients achieve CHR, with the expected survival at 12- and 24-month of (40.6 +/- 12.3)% and 0, respectively. (4) COX analysis CP group indicated that imatinib therapy administered for previously untreated was an independent favorable prognostic factor. Conclusion (1) Imatinib as a primary treatment for CP CML can significantly improve the survival time as compared with that AP or BC patients or with that used in previously treated patients. (2) Imatinib could induce hematologic, even cytogenetic response to a certain extent, in CP or BC patients and prolong the survival time.

Objective: To analyse the clinical characteristics, treatments and prognosis of patients with T-cell non-Hodgkins lymphoma (NHL) in intermediate-high and high risk., Methods: Fifty-four patients with T-cell NHL classified intermediate-high and high risk were retrospectively analyzed., Results: According to WHO classification criteria, there were 12 cases of T-lymphoblastic lymphoma (TLBL), 31 peripheral T-cell lymphoma unspecified (PTCL-U), and 11 hepatosplenic T-cell lymphoma (HSTCL). The IPI were 12 cases of intermediate-high risk and 42 high risk. Of them, 49 cases were bone marrow affected and 7 CNS affected. The response rate (RR) for the whole group was 86.5%, complete remission (CR) rate 67.3%, and 3-year survival rate 16.0%. The 3-year survival rates for haematopoietic stem cell transplantation and chemotherapy groups were 44.4% and 8.3%, respectively. Multi-factor analysis showed that choice of therapy modality, and achievement of remission were significant factors for overall survival., Conclusion: T-NHL is a group of heterogeneous malignancies. The response rate of intermediate-high and high risk T- NHL, especially PTCL-U and LTBL, is not low, but its long-term outcome is poor. New treatment modality needs to be explored for these patients, and autologous HSCT is perhaps a good choice.

Objective: To assess the prognostic value of biological features and therapy-related factors in multiple myeloma (MM)., Methods: 123 patients with newly diagnosed MM between January 1998 and May 2005 were enrolled in this retrospective study. Biological features at presentation and therapy-related factors were analysed. The overall survival (OS) and time to progression (TTP) were estimated by Kaplan-Meier analysis and the distribution of OS and TTP were compared using log-rank test. Cox regression was used to identify the independent prognostic factors., Results: (1) The univariate analysis indicated that more immature plasma cells in bone marrow biopsy, C-reactive protein >8. Omg/L, CD117 expression, serum beta2-microglobulin (beta2-MG) (3.5 approximately 5.5 mg/L), abnormal cytogenetics aberration of chromosome 13 (Delta13), hypodiploid, poor response to chemotherapy, interferon(IFN) therapy less than 6 months were associated with shorter OS(P <0.05). Lytic bone lesions at presentation, more immature plasma cells in bone marrow biopsy, serum beta2-MG (3.5 approximately 5.5 mg/L), poor response to chemotherapy, and IFN therapy less than 6 months as well as abnormal cytogenetics, hypodiploid and Delta13 were associated with shorter TTP (P <0.05). (2) Multivariable COX analysis indicated IFN therapy more than 6 months was a protective factor for OS and TTP, and more immature plasma cells in bone marrow biopsy was an independent poor prognostic factor for TTP., Conclusion: The morphology of myeloma cells is useful for assessing the prognosis. And IFN therapy more than 6 months could lengthen OS and TTP.