Yi Sh

[Dose-intensive immunochemotherapy with or without autologous hematopoietic stem cell transplantation in the treatment of 29 newly diagnosed young patients with medium/high risk diffuse large B-cell lymphoma].

OBJECTIVEnTo 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).nnnMETHODSnThe 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.nnnRESULTSnThe 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.nnnCONCLUSIONnDose-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.

Rituximab combined with second line regimens for treatment of seven relapsed and refractory Hodgkin lymphoma patients

目的 探讨利妥昔单抗联合二线方案治疗复发难治性霍奇金淋巴瘤（HL）患者的疗效及安全性。 方法 7例复发难治性HL患者中2例接受R-GDP(E) [利妥昔单抗、吉西他滨、顺铂、地塞米松、（依托泊苷）]方案治疗，2例接受R-IGVP（利妥昔单抗、异环磷酰胺、吉西他滨、长春瑞滨、泼尼松）方案治疗，3例接受R-BEACOPP（利妥昔单抗、博来霉素、依托泊苷、多柔比星、环磷酰胺、长春新碱、甲基苄肼、泼尼松）方案治疗。观察患者治疗过程中及其后的不良反应和疗效。 结果 7例患者中男3例，女4例，发病时中位年龄21(12~36)岁；结节性淋巴细胞为主型HL(NLPHL) 1例，经典型HL 6例（包括4例结节硬化型，1例淋巴细胞为主型和1例混合细胞型)。中位疗程数为4(1~4)个，中位随访时间为29(24~58)个月。7例患者中4例达完全缓解，2例达疾病稳定，1例死亡。2年总生存率为85.7%。不良反应均可耐受，以骨髓抑制为主。5例患者化疗后行外周血自体造血干细胞移植治疗。 结论 利妥昔单抗联合二线方案治疗复发难治性HL患者安全、有效。OBJECTIVEnTo investigate the efficacy and safety of Rituximab combined with second line regimen for treatment of relapsed and refractory Hodgkin lymphoma.nnnMETHODSnSeven patients with relapsed and refractory Hodgkin lymphoma were treated with Rituximab combined with second line regimen. Among them, two patients were treated with R-GDP (E) [rituximab, gemcitabine, cisplatin, dexamethasone (etoposide)] regimen, another two patients with R-IGVP (rituximab, ifosfamide, gemcitabine, vinorelbine, prednisone)regimen, and the left three patients with R-BEACOPP (rituximab, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)regimen. The efficacy and safety were evaluated during and after chemotherapy.nnnRESULTSnTherere three male and four female patients, whose median age was 21 years (range 12-36 years) old. One patient was diagnosed as nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), and the other six patients as classical HL (four nodular sclerosis HL, one lymphocyte-rich classical HL and one hmixed cellularity HL). The median cycles of salvage therapy were 4(1-4), and the median follow-up was 29 months (24-58 months). Among these 7 patients, the complete remission was observed in 4 patients, stable disease in 2 patients, but one patient died during salvage therapy. The two-year survival rates were 85.7% and the major toxic effects were bone marrow suppression.nnnCONCLUSIONnThese results indicate that the Rituximab combined with second line regimen is an effective therapy for relapsed and refractory Hodgkin lymphoma.

[Clinical and biological characteristics of non-IgM lymphoplasmacytic lymphoma].

目的 探索非IgM型淋巴浆细胞淋巴瘤（LPL）患者的临床及生物学特征，并与华氏巨球蛋白血症（WM）进行比较，探索两者的异同。 方法 对2000年1月至2013年12月收治的13例非IgM型LPL患者临床资料进行回顾性分析，应用荧光原位杂交技术（FISH）对其中7例患者标本进行检查。 结果 13例患者中，男7例，女6例，中位发病年龄63(43~74）岁。2例分泌单克隆IgA, 6例分泌单克隆IgG，5例不分泌单克隆性免疫球蛋白。以贫血为主要表现者7例，以皮肤黏膜出血和浅表淋巴结肿大为主要表现者各2例，出现B症状（发热、盗汗、体重减轻）者8例。所有患者均骨髓受累并表现贫血，10例患者为血常规2系或以上减少。行流式细胞术检查的5例患者中CD19、CD20、CD22和CD25均阳性，CD10、CD38和CD103均阴性，CD5弱阳性1例（该患者CD23阴性），sIgM阳性1例，CD23和CD11c阳性各2例，FMC7阳性3例。7例患者行细胞遗传学检查，未见异常核型，应用FISH检查发现其中2例患者伴有6q缺失。 结论 结合文献报道，非IgM型LPL与WM患者临床及生物学特征相似。OBJECTIVEnTo observe the clinical and biological characteristics of Non-IgM-secreting lymphoplasmacytic lymphoma (LPL) and draw the differences between non-IgM LPL and Waldenström macroglobulinemia (WM).nnnMETHODSnRecords of 13 patients with non-IgM LPL were retrospectively analyzed between January 2000 and December 2013. The cytogenetic aberrations were detected by fluorescence in situ hybridisation (FISH).nnnRESULTSnIn the cohort, 7 males and 6 females with a median age of 63 years (range 43 to 74), two patients were IgA secreting, 6 with IgG secreting and 5 patients without monoclonal globulin. The major complaint at diagnosis included anemia associated symptom (53.8%), mucocutaneous hemorrhage and superficial lymphadenopathy (15.4%). Eight patients had B symptom at diagnosis. All of the 13 patients had bone marrow involvement and anemia, and 10 patients had 2 or 3 lineage cytopenia. In 5 patients with available immunophenotypic data, all expressed CD19, CD20, CD22 and CD25, but missed the expression of CD10, CD103 and CD38. Two cases had CD5 or sIgM positive alone. Another 2 patients were CD23 or CD11c positive and 3 patients were FMC7 positive. Cytogenetic aberrations had been detected by FISH in 7 patients, but only two (28.6%) patients had aberrations with del(6q).nnnCONCLUSIONnThe clinical and biological characteristics had no significantly difference between non-IgM LPL and WM.

[The impact of renal function on prognostic value of β₂-microglobulin of ISS stage system in multiple myeloma patients--Clinical data analysis of 666 patients in a single center].

OBJECTIVEnTo 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.nnnMETHODSnAccording 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.nnnRESULTSnAmong 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).nnnCONCLUSIONnHigh level of β₂-MG and renal function correlated with shorter survival of MM patients. Higher level of β₂-MG with abnormal renal function cant change the prognostic value of β₂-microglobulin on MM.目的 分析不同β2微球蛋白(β2-MG)水平合并或不合并肾功能异常的初诊多发性骨髓瘤(MM)患者的生存情况，探讨肾功能对β2微球蛋白作为MM预后因素的影响。 方法 对1999年2月至2013年10月666例初诊MM患者临床资料进行回顾性分析，以血肌酐<177 µmol/L为肾功能相对正常组，血肌酐≥177 µmol/L为肾功能异常组，分析不同β2-MG水平及肾功能状态患者总生存（OS)情况。 结果 666例患者中男416例，女250例，中位年龄58(25~86)岁。β2-MG<3.5、3.5~<5.5及≥5.5 mg/L患者分别为208、173及285例，其OS时间分别为85.75(95%CI 70.99~100.50)、47.25(95%CI 40.98~53.53)及35.05(95%CI 30.75~39.35)个月，差异有统计学意义(P<0.01)。肾功能相对正常与肾功能异常患者OS时间分别为64.67(95%CI 56.57~72.77)及32.74(95%CI 27.74~37.73)个月，差异有统计学意义(P<0.01)。在β2-MG≥5.5 mg/L的患者中，肾功能相对正常与肾功能异常患者OS时间分别为37.25 (95%CI 31.45~43.06)、32.55(95%CI 26.26~38.83)个月，差异无统计学意义(P=0.142)。 结论 高水平β2-MG、肾功能异常MM患者生存时间较短，是否合并肾功能异常并未改变β2-MG作为MM国际分期系统预后因素的影响。

[Primary bone marrow diffuse large B cell lymphoma: three case reports and literature review].

OBJECTIVEnTo report the diagnosis, differential diagnosis and treatment of three rare cases of primary bone marrow diffuse large B cell lymphoma (DLBCL), and to improve the recognition of this disease.nnnMETHODSnThe clinical characteristics, therapeutic course and the outcome of these patients were reviewed. Meanwhile, a series of examinations including morphology, flow cytometry, immunohistochemistry and molecular biology of bone marrow samples were also performed.nnnRESULTSnThese three patients who were old at the onset age (56, 60 and 70 years old), primarily revealed as abnormal blood count and experienced an aggressive course of disease. Physical and imaging examination showed no enlargement of lymph node, liver and spleen, the patients were finally diagnosed as primary bone marrow DLBCL by bone marrow morphology, flow cytometry and immunohistochemistry analyses. They were treated with rituximab combined chemotherapy, which achieved a complete response, but still need longer follow-up to further evaluate their survival.nnnCONCLUSIONnPrimary bone marrow DLBCL was encountered rarely in clinical practice, and this is the first report in China. Further investigation of pathogenesis and therapeutic strategies of this rare disease was warranted.

[The immunophenotypic characteristics of 260 patients with CD5 + B cell lymphoproliferative disorders].

OBJECTIVEnTo explore the immunophenotypic characteristics of CD5⁺ B cell lymphoproliferative disorders (B-LPD) of Chinese patients.nnnMETHODSnImmunophenotyping of bone marrow and (or) of peripheral blood was performed in patients with B-LPD by four color multiparameter flow cytometry analysis using a panel of monoclonal antibodies, and the patients clinical data were retrospectively analyzed. The difference in immunophenotypes and the related clinical features were retrospectively analyzed. Fluorescence in situ hybridization (FISH) for t(11;14) detection was applied to diagnose or exclude mantle cell lymphoma.nnnRESULTSn(1)A total 260 CD5⁺ B-LPD patients were enrolled in this study, including 186 chronic lymphocytic leukemia (CLL), 40 mantle cell lymphoma (MCL), other B-LPD including 5 splenic marginal zone lymphoma (SMZL), 2 B-cell prolymphocytic leukemia (B-PLL), 3 hairy cell leukemia (HCL). The other 26 cases (10%)were not classified and defined as unclassified B-LPD (BLPD-U). MCL patients were all positive for t(11;14) detected by FISH, while all the BLPD-U patients were negative for t(11;14). (2) All patients expressed CD19, CD20 and CD5. According to the immunophenotypic score system, 186 CLL patients scored 4-5, 99.5% of patients with CD23⁺, 11.3% with sIgM⁺, 10.2% with FMC7⁺, 44.1% with CD22⁺ and 51.1% with CD11c⁺. MCL patients scored 2-3, with 50% expressing CD23 and sIgM, 81.6% expressing FMC7, 92.1% expressing CD22 and 5.3% expressing CD11c. In aspect of BLPD-U and other B-LPD, the expression of CD23, sIgM, FMC7, CD22 and CD11c were 73.1% and 50%, 34.6% and 50%, 88.5% and 100%, 92.3% and 90%, 69.2% and 70%, respectively. (3)In comparison of CLL with MCL, there was a significant difference in the expression of CD23, sIgM, FMC7, CD22 and CD11c between the two groups (P<0.01). Between MCL and BLPD-U, similar expression type of CD23, sIgM, FMC7 and CD22 was found except CD11c, which was highly expressed in BLPD-U (P<0.001). The difference of CD11c expression was also statistically significant between MCL and other B-LPD (P<0.01). In comparison of MCL with other B-LPD, there was a significant difference in the expression of CD11c (P<0.01). The expression of CD23 and sIgM in MCL are 7%-21% and 82%-100% respectively in Western population, while the expression of other immunophenotypic markers is similar with our study.nnnCONCLUSIONnThe significant high incidence of CD23 and low incidence of sIgM compared to the Western population was observed in Chinese patients, and CD11c coud serve as a useful marker to distinguish MCL from CLL and other CD5⁺ B-LPD.

[Clinical and laboratory features of T-cell prolymphocytic leukemia in China].

OBJECTIVEnTo investigate the clinical and laboratory characteristics and survival of Chinese patients with T- cell prolymphocytic leukemia (T-PLL).nnnMETHODSnEleven patients with T-PLL admitted in our hospital from Jan 2006 to Oct 2012 were retrospectively analyzed.nnnRESULTSnOf 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.nnnCONCLUSIONnThe 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.

[Clinical efficacy and safety of chemoimmunotherapy with rituximab,fludarabine and cyclophosphamide for chronic lymphocytic leukemia].

OBJECTIVEnTo evaluate the efficacy and safety of a chemoimmunotherapy regimen of rituximab, fludarabine and cyclophosphamide (FCR) for patients with chronic lymphocytic leukemia(CLL).nnnMETHODSnThe clinical data of 26 CLL patients receiving FCR regimen in our hospital from April 2003 to January 2012 were analyzed retrospectively. Patients were grouped according to indicators including Rai risk stratification, β(2)-MG, LDH, ZAP-70, CD38, cytogenetics and immunoglobulin heavy chain variable region gene (IgVH) mutation status. Therapy efficacy and survival were evaluated and the safety of FCR regimen was assessed.nnnRESULTSnAmong 26 patients, the overall response rate ( ORR ) was 76.9%, 10 patients (38.5%) achieved complete remission(CR) and 10(38.5%) partial remission(PR). With a median follow-up time of 30 ( 3-98 ) months, the median estimated progression-free survival(PFS) for all patients was 42(16-68) months and median overall survival(OS) was 63(41-85)months. Clinical parameters associated with higher CR rates were ＜2 courses of prior treatment regimens, proportions of bone marrow lymphocytes declining ≥ 50% after 2 courses of FCR, low LDH, low β(2)-MG and ZAP-70 negative (P = 0.014, 0.008, 0.027, 0.035 and 0.013, retrospectively). PFS and OS time in minimal residual disease(MRD)-negative, normal LDH and proportions of bone marrow lymphocytes declining ≥ 50% after 2 courses of FCR patients were significantly better than that of the control group (P＜0.05), PFS in the non-high-risk genetics group was significantly better than that in the high-risk genetics group (P = 0.005), while OS between two groups showed no statistically significant difference. The most common toxicities were gastrointestinal reactions (88.5%), followed by bone marrow suppression (80.8%): including neutropenia, anemia and thrombocytopenia. Infections accounted for 30.8%, mainly lung infection.nnnCONCLUSIONnFCR is an effective and well-tolerated therapy for patients with CLL. Patients with MRD-positive, elevated LDH, proportions of bone marrow lymphocytes declining＜50% after 2 courses of FCR and high risk genetics patients are suitable for more effective treatment after achieving treatment response.