Clinical and prognostic differences between ALK-negative anaplastic large cell lymphoma and peripheral T cell lymphoma, not otherwise specified: a single institution experience.

Clinical differences between anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALK(-) ALCL) and peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), remain unclear. The aim of this study was to compare the clinical and prognostic features of these two lymphoma types. We retrospectively analyzed 167 patients with ALK(-) ALCL (n = 48) and PTCL-NOS (n = 119). Compared with ALK(-) ALCL patients, PTCL-NOS patients exhibited distinct differences in clinical features with a propensity for more advanced stages, frequent extranodal involvement, and a poor performance status, leading to a higher risk group according to the International Prognostic Index or Prognostic Index for PTCL-NOS. Patients with ALK(-) ALCL were associated with a higher complete response rate (47.9 vs. 31.0 %; P = 0.041) after initial chemotherapy than patients with PTCL-NOS. The prognosis was significantly different between two subtypes, with a 5-year overall survival (OS) rate of 57.9 % for ALK(-) ALCL and 23.9 % for PTCL-NOS (P = 0.002). The subgroup analysis showed significant differences in OS and progression-free survival between the two subtypes in early-stage diseases, but not in advanced-stage diseases. We conclude that patients with ALK(-) ALCL showed favorable clinical features, higher chemosensitivity, and a superior outcome than those with PTCL-NOS.

Pegylated filgrastim is comparable with filgrastim as support for commonly used chemotherapy regimens: a multicenter, randomized, crossover phase 3 study.

The purpose of this study was to compare the efficacy and safety of a single subcutaneous injection of pegylated filgrastim with daily filgrastim as a prophylaxis for neutropenia induced by commonly used chemotherapy regimens. Fifteen centers enrolled 337 chemotherapy-naive cancer patients with normal bone marrow function. All patients randomized into AOB and BOA arms received two cycles of chemotherapy. Patients received a single dose of pegylated filgrastim 100 µg/kg in cycle 1 (AOB) or cycle 2 (BOA) and daily doses of filgrastim 5 µg/kg/day in cycle 1 (BOA) or cycle 2 (AOB). Efficacy and safety parameters were recorded. The primary end point was the rate of protection against grade 4 neutropenia after chemotherapy [defined as the rate at which the absolute neutrophil count (ANC) remained >0.5×10(9)/l throughout the entire cycle]. Ninety-four percent of patients receiving pegylated filgrastim or filgrastim did not develop grade 4 neutropenia. The incidence of ANC<1.0×10(9)/l was 16.0% (50/313) after support with either pegylated filgrastim or filgrastim. The incidences of febrile neutropenia and antibiotic administration were similar in both groups. Notably, faster ANC recovery was observed with pegylated filgrastim support. The ANC nadir was also earlier with pegylated filgrastim (day 7) support than with filgrastim support (day 9), although the depth of nadir was not significantly different. A single subcutaneous injection of pegylated filgrastim 100 µg/kg provided adequate and safe neutrophil support comparable with daily subcutaneous injections of unmodified filgrastim 5 µg/kg/day in patients receiving commonly used standard-dose mild-to-moderate myelosuppressive chemotherapy regimens.

[Association between different EGFR mutation status and survival in pemetrexed-based chemotherapy for advanced non-small cell lung cancer].

OBJECTIVE: To explore the association between different epidermal growth factor receptor (EGFR) mutation status and survival in pemetrexed-based chemotherapy for advanced non-small-cell lung cancer (NSCLC). METHODS: A retrospective cohort study was performed to assess 146 patients with advanced NSCLC at Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The first-line regimens included pemetrexed based chemotherapy (pemetrexed first-line therapy group, n = 79), pemetrexed based chemotherapy plus pemetrexed maintenance chemotherapy (pemetrexed maintenance therapy group, n = 38) and pemetrexed based chemotherapy plus tyrosine kinase inhibitors (TKI) maintenance therapy (TKI maintenance therapy group, n = 29). Median progression-free survival (PFS) was determined.For comparison, median PFS was evaluated for EGFR-positive,EGFR-negative versus EGFR mutation unknown NSCLC patients in first-line pemetrexed therapy and pemetrexed maintenance therapy groups. RESULTS: The median PFS was 4.6 (95%CI: 2.8-6.4), 9.8 (95%CI: 6.1-13.5) and 14.5 (95%CI: 11.8-17.2) months in pemetrexed first-line therapy, pemetrexed maintenance therapy and TKI maintenance therapy groups respectively (P = 0.000). No difference existed in PFS for pemetrexed first-line therapy group with a median PFS of 5.2 (95%CI: 2.8-7.7), 4.0 (95%CI: 0-10.8) and 4.6 (95%CI: 3.4-5.8) months respectively (P = 0.661). Among EGFR-positive,EGFR-negative and EGFR mutation status unknown patients in pemetrexed maintenance therapy group, the median PFS was 8.5 (95%CI: 4.0-13.1), 12.6 (95%CI: 11.6-13.7) and 8.0 (95%CI: 5.8-10.3) months with no significant statistical difference (P = 0.468). CONCLUSIONS: No significant difference exists in survival between different EGFR mutation status for pemetrexed based first-line chemotherapy. And TKI maintenance therapy is associated with better survival than pemetrexed maintenance therapy regardless of EGFR status.

[Clinical analysis of childhood and adolescent Hodgkin's lymphoma: a report of 88 cases].

OBJECTIVE: The aim of this study was to investigate the clinicopathological characteristics, effective treatment and prognosis in childhood and adolescent Hodgkin's lymphoma. METHODS: A total of 88 patients with childhood and adolescent Hodgkin's lymphoma were treated in the Cancer Hospital of CAMS from 1998 to 2005. The clinicopathological and follow-up data of the patients were retrospectively reviewed. The survival rate was calculated by Kaplan-Meier method and compared by log-rank test. COX multivariate prognosis analysis was performed. RESULTS: The 2-year event-free survival rate of the 88 patients was 86.4%, the 5-year event-free survival rate was 61.4%, and the 5-year overall survival rate was 95.5%. Univariate analysis showed that the stage of disease (P = 0.033), "B" symptoms (P = 0.028), bulky disease (P = 0.007), splenomegaly (P = 0.050), LDH elevation (P = 0.020), chemotherapy regimen (P = 0.003) were prognostic factors in the 5-year event-free survival rate. Splenomegaly (P = 0.039), LDH elevation (P = 0.033), chemotherapy regimen (P = 0.008) were prognostic factors of 5-year overall survival rate. Multivariate analysis showed that chemotherapy regimen (P = 0.033), stage of disease (P = 0.023), LDH elevation (P = 0.008), "B" symptoms (P = 0.044), bulky disease (P = 0.009) were independent prognostic factors of 5-year event-free survival rate. The chemotherapy regimen (P = 0.012) and LDH elevation (P = 0.046) were independent prognostic factors of 5-year overall survival rate. CONCLUSIONS: The non-ABVD chemotherapy regimen, stage IV disease, LDH elevation, associated with "B" symptoms and bulky disease are independent prognostic factors of 5-year event-free survival rate. LDH elevation and non-ABVD chemotherapy regimen are independent prognostic factors of 5-year overall survival rate.

[Comparative analysis of liver function in HBsAg-/HBcAb+ patients with diffuse large B-cell lymphoma treated with CHOP and R-CHOP regimens].

OBJECTIVE: To analyze the liver function in patients with diffuse large B-cell lymphoma(DLBCL), who are hepatitis B surface antigen negative/antibody to hepatitis B core antigen positive (HBsAg-/HBcAb+), treated with CHOP and R-CHOP regimens. METHODS: In this retrospective study, 86 DLBCL patients, who were HBsAg-/HBcAb+, were collected from Cancer Hospital of Chinese Academy of Medical Sciences between January 2005 and December 2008. The patients were given at least two cycles of chemotherapy using CHOP-like or R-CHOP-like regimen without anti-HBV treatment, and followed-up for at least 12 months after completion of therapy. RESULTS: Forty-seven patients received CHOP-like regimen while 39 patients received R-CHOP-like regimen. There were no significant differences in the degree of liver dysfunction between CHOP group and R-CHOP group after the 1st, 2nd, 3rd, 4th and 6th cycles (22.7% - 46.7% with CHOP and 17.6% - 34.2% with R-CHOP, respectively, (all P > 0.05), except for the 5th cycles (28.6% vs. 6.2%, P = 0.026). Liver function in most patients in CHOP group and R-CHOP group was normal after every cycle (53.3% - 77.3% and 65.8%-93.8%, respectively). Meanwhile, there were no significant differences in the degree of liver dysfunction between CHOP group and R-CHOP group in the 1st-3rd month, 4th-6th month, 7th-9th month and 10th-12th month after completion of therapy (7.7% - 40.0% with CHOP and 7.4% - 32.0% with R-CHOP, respectively, all P > 0.05). CONCLUSIONS: The present study reveals a low incidence of liver dysfunction in HBsAg-/HBcAb+ DLBCL patients, both in CHOP group and in R-CHOP group. It may indicate a potential low incidence of HBV reactivation in these groups, and Rituximab do not increase the rate of liver dysfunction. Therefore, these data may not support regularly prophylactic antiviral therapy during chemotherapy, but close monitoring of liver function, HBV serum markers and HBV DNA level are demanded.

[Evaluation of the role of rhIL-11 on hematological recovery in lymphoma patients after autologous hematopoietic stem cell transplantation].

OBJECTIVE: To evaluate the effect of recombinant human interleukin 11 (rhIL-11) on hematological recovery after autologous hematopoietic stem cell transplantation (AHSCT) in patients with lymphoma. METHODS: A retrospective study was carried out on 73 patients with lymphoma after AHSCT. The patients were divided into two groups. The study group (n = 35) received rhIL-11 1.5 mg daily from the fifth day after AHSCT to the day when platelets recovering to 80.0×109/L. The control group (n = 38) did not receive rhIL-11 after AHSCT. RESULTS: All the 73 patients finished AHSCT from Mar 2003 to Dec 2008 in our department. Thirty-five patients received rhIL-11 and 38 patients did not. In the rhIL-11 group and control group, the nadir of platelet was (18.9 ± 5.0)×109/L and (21.5 ± 6.0)×109/L, respectively, with a significant difference (P = 0.04). The median time of platelet recovering to 50.0×109/L was (14.3 ± 5.5) d and (13.2 ± 4.5) d (P = 0.37) in the two groups. There was no significant difference (P = 0.82) in the median numbers of platelet transfusion in the two groups. The curves of the mean of daily absolute platelet counts of the two groups were similar (P = 0.22). Adverse events related to rhIL-11 were not found in the rhIL-11 group. CONCLUSION: The results of this study do not show obviously accelerating effect of rhIL-11 on the platelet recovery in lymphoma patients after AHSCT and obvious increase of adverse events after rhIL-11 administration.

Efficacy of peripheral blood stem cell transplantation versus conventional chemotherapy on anaplastic large-cell lymphoma:a retrospective study of 64 patients from a single center.

Anaplastic large-cell lymphoma (ALCL) is characterized by frequently presenting adverse factors at diagnosis. Many groups believed aggressive treatment strategies such as autologous stem cell transplantation brought survival benefit for ALCL patients. However, few compared these approaches with conventional chemotherapy to validate their superiority. Here, we report a study comparing the efficacy of peripheral blood stem cell transplantation (PBSCT) and conventional chemotherapy on ALCL. A total of 64 patients with primary systemic ALCL were studied retrospectively. The median follow-up period was 51 months (range, 1-167 months). For 48 patients undergoing conventional chemotherapy only, the 4-year event-free survival (EFS) and overall survival (OS) rates were 70.7% and 88.3%, respectively. Altogether, 16 patients underwent PBSCT, including 11 at first remission (CR1/PR1), 3 at second remission, and 2 with disease progression during first-line chemotherapy. The 4-year EFS and OS rates for patients underwent PBSCT at first remission were 81.8% and 90.9%, respectively. Compared with conventional chemotherapy, PBSCT did not show superiority either in EFS (P = 0.240) or in OS (P = 0.580) when applied at first remission. Univariate analysis showed that patients with B symptoms (P = 0.001), stage III/IV disease (P = 0.008), bulky disease (P = 0.075), negative anaplastic lymphoma kinase (ALK) expression (P = 0.059), and age ≤ 60 years (P = 0.054) had lower EFS. Furthermore, PBSCT significantly improved EFS in patients with B symptoms (100% vs. 50.8%, P = 0.027) or bulky disease (100% vs. 52.8%, P = 0.045) when applied as an up-front strategy. Based on these results, we conclude that, for patients with specific adverse factors such as B symptoms and bulky disease, PBSCT was superior to conventional chemotherapy in terms of EFS.

R-CHOP regimen can significantly decrease the risk of disease relapse and progression in patients with non-germinal center B-cell subtype diffuse large B-cell lymphoma.

To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma(DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen(R-CHOP regimen) significantly decreased the risk of disease relapse and progression in CD10-negative patients (P=0.001), Bcl-6-negative patients (P=0.01), and MUM-1-positive patients (P=0.003). The risk of disease relapse in patients with non-GCB subtype (P=0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P=0.042). Although univariate analysis found that both Bcl-2-positive and -negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P=0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.

Leaf chlorophyll parameters and photosynthetic characteristic variations with stand age in a typical desert species (Haloxylon ammodendron).

As a desert shrub, Haloxylon ammodendron combines ecological, economic, and social benefits and plays an important role in the ecological conservation of arid desert areas. Understanding its physiological characteristics and its mechanism of light energy utilization is important for the conservation and utilization of H. ammodendron. Therefore, we selected five stands (5-, 11-, 22-, 34-, and 46-year-old) of H. ammodendron as research objects in the study and measured their photosynthetic light response curves by a portable open photosynthesis system (Li-6400) with a red-blue light source (6400-02B). Then, we measured the leaf chlorophyll parameters in the laboratory, calculated the photosynthetic characteristics by using Ye Zipiao's photosynthetic model, analyzed their variation patterns across stand ages, and explored the relationships between leaf chlorophyll parameters and photosynthetic characteristics. The results showed that leaf chlorophyll parameters and photosynthetic characteristics of H. ammodendron at different stand ages were significantly different. Chl content, P nmax, and LUEmax of H. ammodendron were V-shaped with the increase of stand age. The 5-year-old H. ammodendron was in the rapid growth period, synthesized more Chl a+b content (8.47 mg g-1) only by using a narrower range of light, and the Pnmax and LUEmax were the highest with values of 36.21 µmol m-2 s-1 and 0.0344, respectively. For the 22-year-old H. ammodendron, due to environmental stress, the values of Chl a+b content, P nmax, and LUEmax were the smallest and were 2.64 mg g-1, 25.73 µmol m-2 s-1, and 0.0264, respectively. For the older H. ammodendron, its Chl content, P nmax, and LUEmax were not significantly different and tended to stabilize but were slightly higher than those of the middle-aged H. ammodendron. On the other hand, the other photosynthetic parameters did not show significant variation patterns with stand age, such as R d, AQE, LSP, LCP, and I L-sat. In addition, we found that the relationships between Chl a+b content and P nmax and between Chl a+b content and LUEmax were highly correlated, except for the older H. ammodendron. Thus, using leaf chlorophyll content as a proxy for photosynthetic capacity and light use efficiency should be considered with caution. This work will provide a scientific reference for the sustainable management of desert ecosystems and vegetation restoration in sandy areas.

[Phase I study of anti-EGFR monoclonal antibody (CMAB009) in patients with advanced cancer].

OBJECTIVE: To characterize the safety profiles and serum pharmacokinetic effects of anti-epidermal growth factor receptor monoclonal antibody (CMAB009) in advanced cancer patients and evaluate the preliminary evidence of its anti-tumor activity. METHODS: This phase I, single-center clinical trial had 2 phases of treatment: single-dose phase, followed by a fixed weekly dose. Subjects meeting the inclusion criteria were enrolled. The subjects were randomly assigned to receive 1 of 3 initial doses of CMAB009 (100, 250 & 400 mg/m(2)) for the purpose of single-dose pharmacokinetic evaluation. After a 28-day washout period of allowing for the characterization of pharmacokinetic end points, the eligible patients were permitted to undergo a successive multi-dose phase study. They were divided into 2 dose groups, group A with 4 weekly doses of 250 mg/m(2), group B with the initial dose of 400 mg/m(2), followed by 3 weekly doses of 250 mg/m(2). The subjects were closely monitored for adverse events throughout the trial. RESULTS: A total of 18 subjects were recruited, including colorectal cancer (n = 10), non-small cell lung cancer (n = 7) and gastric cancer (n = 1). CMAB009-associated toxicity was minimal. And the most commonly reported Grade 1/2 adverse events were skin rashes, fever, nausea and headache. Two patients with colorectal cancer achieved partial remission and the time to progression (TTP) was 24 and 16 weeks respectively. CONCLUSION: As a well-tolerated antitumor agent, CMAB009 may be safely administered by the above multi-dosing protocol.

A Comparison of Safety and Effectiveness Between Wingspan and Neuroform Stents in Patients With Middle Cerebral Artery Stenosis.

Background: Percutaneous transluminal angioplasty and stenting with the Wingspan stent has proven safe and effective in patients with middle cerebral artery stenosis (MCAS), but the off-label use of the Neuroform stent might be an alternative treatment. This study aimed to compare the safety and effectiveness of the above two intracranial stents in patients with MCAS. Methods: We retrospectively analyzed consecutive patients with symptomatic MCAS who had been treated with the Neuroform EZ or the Wingspan stent. A propensity score was generated to control for differences in baseline characteristics. The endpoints were the rate of peri-procedural complications within 30 days after stenting, the in-stent restenosis rate, and any target-vessel-related stroke or deaths during follow-up. Results: After matching for propensity score, the peri-procedural complication rate in the Wingspan group was 7.4% compared with 5.6% in the Neuroform group (p = 1.00), while the follow-up in-stent restenosis rates were 23.3 vs. 14.3%, respectively (p = 0.41). In the restenosis group, the patients tended to be younger (p < 0.01) and the degree of artery stenosis before stenting was higher (p < 0.01). Conclusion: This study indicated that in patients with symptomatic MCAS, Neuroform EZ stents are an alternative to Wingspan. Moreover, younger age and higher degree of artery stenosis before stenting might be a risk factor of in-stent restenosis.

5-Hydroxymethylcytosine profiles of cfDNA are highly predictive of R-CHOP treatment response in diffuse large B cell lymphoma patients.

BACKGROUND: Although R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard chemotherapy regimen for diffuse large B cell lymphoma (DLBCL) patients, not all patients are responsive to the scheme, and there is no effective method to predict treatment response. METHODS: We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) from 86 DLBCL patients before they received R-CHOP chemotherapy. To investigate the correlation between 5hmC modifications and curative effectiveness, we separated patients into training (n = 56) and validation (n = 30) cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict the treatment response in the validation cohort. RESULTS: In this study, we identified thirteen 5hmC markers associated with treatment response. The prediction performance of the logistic regression model, achieving 0.82 sensitivity and 0.75 specificity (AUC = 0.78), was superior to existing clinical indicators, such as LDH and stage. CONCLUSIONS: Our findings suggest that the 5hmC modifications in cfDNA at the time before R-CHOP treatment are associated with treatment response and that 5hmC-Seal may potentially serve as a clinical-applicable, minimally invasive approach to predict R-CHOP treatment response for DLBCL patients.

Survival and pretreatment prognostic factors for extensive-stage small cell lung cancer: A comprehensive analysis of 358 patients.

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is deemed as a fatal malignancy with a poor prognosis. Although immunotherapy has gradually played an important role in the treatment of ES-SCLC since 2018, ES-SCLC treatment data and patient outcome before 2018, when chemotherapy served as a fundamental therapeutic strategy, is still meaningful as a summary of the situation regarding previous medical treatment and is a baseline for comparative data. In addition, the prognostic factors of ES-SCLC have failed to reach a consensus until now. Therefore, this study aimed to evaluate survival and identify the prognostic factors in an ES-SCLC population. METHODS: We retrospectively collected the detailed medical records of 358 patients with ES-SCLC from January 1, 2011 to December 31, 2018 in a Chinese top-level cancer hospital. The prognostic factors were evaluated by Cox univariate and multivariate analysis. RESULTS: The median overall survival (OS) of ES-SCLC patients (N = 358) was 14.0 months, the one- and two-year OS rates were 56.2% and 21.7%, respectively. Moreover, we identified two demographic characters (age ≥ 70, smoking index ≥ 400), one tumor burden factor (bone multimetastasis), two tumor biomarkers (cyfra211, CA125) and two laboratory indexes (decreased Na, PLR < 76) as independent prognostic factors for OS in this patient population. Progression-free survival (PFS) data of 238 patients was obtained for further analysis, and the median PFS was 6.2 months, and six-month and one-year PFS rates were 51.7% and 14.3%, respectively. Elevated cyfra211, decreased Hb and Na were identified as independent prognostic factors for PFS. CONCLUSIONS: This study provides real-world evidence of the survival and prognosis of ES-SCLC patients which will enable better evaluation and clinical decision-making in the future.

[Clinical features and prognostic factors of angioimmunoblastic T cell lymphoma].

OBJECTIVE: To retrospectively analyze the clinical features and prognostic factors of patients with angioimmunoblastic T-cell lymphoma (AITL). METHODS: The clinicopathological and follow-up data of 18 AITL patients undergoing integrated treatment from Feb. 1998 to April 2009 in our department were retrospectively analyzed. All of the patients received CHOP-like regimens as initial chemotherapy, including 4 once treated with radiotherapy and 1 with high dose therapy followed by autologous stem cell transplantation (HDT-ASCT) as upfront consolidation therapy. B-cell, T-cell and NK-cell subgroup proportions in the peripheral blood were tested by flow cytometry in 6 patients. RESULTS: The median age of the 18 patients was 55 years, male and female ratio was 2.6:1. Seventy-two percent of the patients were in an advanced stage. 72% of them had B symptoms, 69% hypergammaglobulinemia, 60% elevated LDH and 47% anemia. Forty-four percent achieved CR after initial treatment with CHOP-like regimens. With the median follow-up of 26 months, the overall 2-year survival and disease free survival (DFS) rates were 62.2% and 44.4%, respectively. In the univariate analysis, only age > 30 years and primary refractory disease adversely affected overall survival (OS); age > 30 years, advanced stage, B symptoms and splenomegaly adversely affected DFS. Four patients suffered from severe pneumonia during treatment, 2 of them died of respiratory failure. Flow cytometry of peripheral blood lymphocytes showed that 5 of the 6 tested cases had decreasing proportion of CD3(+)CD4(+) T cells, B cells and NK cells but elevated CD3(+)CD8(+) T cells. Two heavily treated patients achieved partial and complete response by thalidomide therapy, with a progression free survival (PFS) of 2 and 6+ months, respectively. CONCLUSION: AITL patients do not response well to CHOP-like regimens chemotherapy. Age < 30 years and sensitive to initial chemotherapy are associated with prolonged OS. Effectiveness of thalidomide in the treatment of AITL deserves further investigation. Peripheral blood lymphocytes test indicates that AITL patients suffered from both natural and acquired immune defects.

[Primary cutaneous anaplastic large cell lymphoma: clinical presentation, therapy and prognosis study of 10 cases].

OBJECTIVE: To explore the clinical presentation, therapy and prognosis study of primary cutaneous anaplastic large cell lymphoma (PCALCL). METHODS: We reviewed and analyzed ten cases of PCALCL receiving treatment at our hospital from January 1999 to January 2009. RESULTS: There were 8 males and 2 females with a median age of 48 years old (range: 22 - 69). There were single subcutaneous nodule (n = 7) and multiple nodules (n = 3). And the lesions could be found on head and neck (n = 5), trunk (n = 3) and all over body (n = 2). The lesions appeared red, solid and stable subcutaneous nodules. Partial lesions had a spontaneous regression and new nodules appeared at the same or different sites. Two patients had lymphadenopathy and one had bone involvement with anaplastic lymphoma kinase (ALK) positive and high cell proliferation ratio index (ki-67 > 80%). Seven cases with single lesion received surgical excision plus radiotherapy, chemotherapy or radiochemotherapy, one case recurred, six cases survived without disease. Three cases with multiple lesions received systemic chemotherapy mainly in combination with radiotherapy or biotherapy, two cases recurred and one case survived without disease. The median follow-up was 44 months (range: 9 - 95), progression free survival 89% and overall survival 100%. CONCLUSION: PCALCL is found more commonly in males. Visceral and lymph node involvement are rare. The patients with single lesion have a longer disease-free survival than those with multiple lesions after surgical excision in combination with chemotherapy or radiotherapy. Multiple lesions can not be cured.

[A clinical report on modified Hyper-CVAD regimen in patients with lymphoblastic lymphoma].

OBJECTIVE: The efficacy of standard chemotherapy regimen on lymphoblastic lymphoma (LBL) is unsatisfied. This study was to evaluate the efficacy and safety of modified Hyper-CVAD regimen on Chinese patients with LBL. METHODS: Clinical records of 20 LBL patients who received modified Hyper-CVAD regimen in Cancer Hospital of Chinese Academy of Medical Sciences, from June 2004 to June 2008, were retrospectively analyzed in terms of response and toxicity. RESULTS: By May. 2009, the median follow-up time was 17 (4-36) months. The 20 patients totally received 62 cycles regimen A and 29 cycles regimen B. 17 patients were assessable in efficacy, the total response rate (RR) was 88.2% with complete response (CR) rate of 41.2%. 15 patients received modified Hyper-CVAD regimen as first-line therapy (75.0%), and RR was 100% with CR rate of 50.0% (7/14). The RR of salvage therapy was 33% without CR achieved. The major toxicity was myelosuppression, the incidence of grades 3-4 neutropenia, thrombocytopenia and anemia was 95.0%, 75.0% and 40.0%, respectively. No treatment-related death was observed. CONCLUSIONS: Modified Hyper-CVAD regimen was a promising regimen for the patients with LBL, and toxicity was within acceptable limits.

[Newest Reaserch Advance in treatment of Plasmablastic lymphoma--Review].

Plasmablastic lymphoma(PBL) shows a low incidence and poor prognosis, moreover, there is no standard treatment regimen for PBL. The treatment effect and value of CHOP regimen and radiotherapy are limited. Some studies showed that intensive chemotherapy alone or its combination with proteasome inhibitors or immune regulator can improve the overall survival of patients with PBL, which can be used as the first-line therapy for PBL patients. CAR-T and immunocheckpoint inhibitors showed treatment effect for the patients with refractory and relapsed plasmablastic lymphoma. The clinical value of potential targets in treating tumour worth to be studied further.

[Effect of Jin's three-needle combined with MyoTrac biostimulation therapy on upper limb function in children with spastic hemiplegia].

OBJECTIVE: To compare the therapeutic effect among Jin 's three-needle combined with MyoTrac biostimulation therapy, simple Jin's three-needle and simple MyoTrac biostimulation therapy on upper limb function in children with spastic hemiplegia. METHODS: A total of 120 children with spastic hemiplegia were randomized into an observation group, a control group 1 and a control group 2, 40 cases in each group. Conventional occupational therapy was adopted in each group. Additionally, Jin's three-needle therapy was applied in the control group 1, scalp acupuncture and body acupuncture were sustained for 1 h and 30 min respectively, once a day, 5 times a week; MyoTrac biostimulation therapy was adopted in the control group 2, once a day, 15 min each time, 5 times a week; Jin 's three-needle combined with MyoTrac biostimulation therapy were given in the observation group. Two months were as one course, and totally 3 courses were required in the 3 groups. Before treatment and 2, 4, 6 months into treatment, the standard grasping score (sGr) and the standard visual-motor integration score (sVI) of Peabody developmental motor scales-2 (PDMS-2), the modified Ashworth scale (MAS) grade and active range of movement (AROM) of wrist joints were recorded in the 3 groups. RESULTS: Compared before treatment, sGr of 4, 6 months into treatment was increased in the observation group (P<0.05), sGr of 6 months into treatment was increased in the control group 1 and the control group 2 (P<0.05); sVI of 2, 4, 6 months into treatment was increased in the observation group (P<0.05), sVI of 6 months into treatment was increased in the control group 1 and the control group 2 (P<0.05). sGr and sVI of 6 months into treatment in the observation group were higher than those in the control group 1 and the control group 2 (P<0.05). Compared before treatment, the MAS grade of 6 months into treatment was improved in the 3 groups (P<0.05), and that in the observation group was superior to the control group 1 and the control group 2 (P<0.05). CONCLUSION: Jin 's three-needle combined with MyoTrac biostimulation therapy can effectively improve the fine function and muscle tone of upper limbs in children with spastic hemiplegia, and the improvement is superior to the simple Jin 's three-needle and the MyoTrac biostimulation therapy.

Actin-related protein Arp4 regulates euchromatic gene expression and development through H2A.Z deposition in blood-stage Plasmodium falciparum.

BACKGROUND: Malaria caused by Plasmodium spp. is still a major threat to public health globally. The various approaches to developing new antimalarial agents rely on the understanding of the complex regulatory mechanisms of dynamic gene expression in the life-cycle of these malaria parasites. The nuclear members of the evolutionarily conserved actin-related protein nuclear (ARP) superfamily are the major components of nucleosome remodelling complexes. In the human malaria parasite Plasmodium falciparum, bioinformatics analysis has predicted three ARP orthologues: PfArp1, PfArp4 and PfArp6. However, little is known about the biological functions of putative PfArp4. In this study, we aimed to investigate the function and the underlying mechanisms of PfArp4 gene regulation. METHODS: A conditional gene knockdown approach was adopted by incorporating the glucosamine-inducible glmS ribozyme sequence into the 3' UTR of the PfArp4 and PfArp6 genes. The transgenic parasites PfArp4-Ty1-Ribo, PfArp6-Ty1-Ribo and pL6-PfArp4-Ty1::PfArp6-HA were generated by the CRISPR-Cas9 technique. The knockdown effect in the transgenic parasite was measured by growth curve assay and western blot (WB) analysis. The direct interaction between PfArp4 and PfArp6 was validated by co-IFA and co-IP assays. The euchromatic gene expression mediated through H2A.Z (histone H2A variant) deposition and H3K9ac modification at promoters and regulated by PfArp4, was determined by RNA-seq and ChIP-seq. RESULTS: The inducible knockdown of PfArp4 inhibited blood-stage development of P. falciparum. PfArp4 and PfArp6 were colocalized in the nucleus of P. falciparum parasites. PfArp4 gene knockdown altered the global transcriptome. PfArp4 protein colocalized with the histone variant H2A.Z and euchromatic marker H3K9ac in intergenic regions. The inducible downregulation of PfArp4 resulted in the depletion of H2A.Z and lower H3K9ac levels at the upstream regions of eukaryotic genes, thereby repressing the transcriptional abundance of H2A.Z-dependent genes. CONCLUSIONS: Our findings suggest that PfArp4 regulates the cell cycle by controlling H2A.Z deposition and affecting centromere function, contributing to the understanding the complex epigenetic regulation of gene expression and the development of P. falciparum.

[Comparison of the efficiency of CHOP-based regimen with or without high dose consolidation treatment combined with hematopoietic stem cell transplantation in 63 lymphoblastic lymphoma patients].

OBJECTIVE: To retrospectively analyze and compare the treatment efficiency of CHOP-based regimens with or without high-dose consolidation treatment combined with hematopoietic stem cell transplantation (HDT-HSCT) in the patients with lymphoblastic lymphoma (LBL). METHODS: From 1989 to 2004, totally 63 patients with LBL were initially treated with a standard CHOP-based regimen. Forty-two of the 63 patients achieved complete response (CR), 26 of those subsequently received consolidation HDT-HSCT, while the other 16 had 6-8 cycles of standard CHOP-based treatment only. RESULTS: Of the 63 patients, 57 had a T-LBL and 6 B-LBL, with a median age of 20 years, 19 (30.2%) had a stage I-II diseases and 44 (69.8%) stage III-IV diseases, 61.9% presented with a mediastinal mass. Bone marrow involvement presented in 28.6% of the patients. Fourteen percent had central nervous system involvement. The median follow-up period was 24 months, and the estimated 5-year overall survival and disease-free survival of this series was 31.2% and 29.3%, respectively. Of the 42 patients who achieved CR, the 5-year OS rate of the patients who received HDT-HSCT as a consolidation therapy was 59.8% versus 14.6% of the patients treated by CHOP-based regimens alone (P=0.004). Bone marrow involvement, age > or =20 years, short response duration and primary refractory disease were factors significantly associated with poor outcome. Among the 18 patients with bone marrow involvement, 3 received allogeneic HSCT and were all still alive at the follow up time of 22, 32 and 37 months, respectively, while another 4 received auto-HSCT and all died of the disease within 14 months. CONCLUSION: Short term treatment with a CHOP-based regimen is not sufficient for the patients with lymphoblastic lymphoma. High-dose consolidation treatment and hematopoietic stem cell transplantation may improve overall survival and disease free survival. Bone marrow involvement, age >20 years, and short response duration and primary refractory disease are all the factors significantly associated with poor outcome. For the patients with bone marrow involvement, allohematopoietic stem cell transplantation is superior to auto-hematopoietic stem cell transplantation.