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The remission rate in the observation group were higher than that in control group (P < 0.05); The PFS rate (1 year) in observation group was higher than that in control group (P < 0.05); the PFS rate (2 years, 3 years) was not significantly different (P > 0.05). The OS rate (1 year, 2 years, 3 years) did not show difference (P > 0.05); the number of patients with neutropenia in observation group was higher than that in control group (P < 0.05); the levels of CD4(+) CD45RA(+), CD4(+) CD45RO(+) in observation group were lower than those in control group (P < 0.05); the levels of CD4(+) and CD4(+)/CD8(+) in observation group was lower than those in control group (P < 0.05); the level of CD8(+) in observation group was higher than that in control group (P < 0.05); the incidence of pneumonia, cardiotoxicity, severe anemia, and thrombopenia were not significantly different (P > 0.05).
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Based on the treatment results of 300 Hodgkin lymphoma patients the authors formulated the basic approaches for radiation treatment in ABVD and BEACOPP-21 chemotherapy regimens recipients. In patients with complete response to chemotherapy any dose regimen (26 to 44 Gr) leads to 100% local disease control. In patients with major response to chemotherapy (PR> or =80%) the 36 Gr total focal dose allows an adequate local control, more intensive local control doesn't yield better results. In patients with PR 0-79% the implication of total focal doses less than 40 Gr leads to statistically significant increase of nodal relapse rate. These treatment approaches may be implied by specialists conducting chemotherapy and radiation therapy in Hodgkin lymphoma patients.
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Mantle cell lymphoma (MCL) is an aggressive type of B-cell non-Hodgkin lymphoma associated with poor prognosis. Implementation of high-dose cytarabine (araC) into induction therapy became standard-of-care for all newly diagnosed younger MCL patients. However, many patients relapse even after araC-based regimen. Molecular mechanisms responsible for araC resistance in MCL are unknown and optimal treatment strategy for relapsed/refractory MCL patients remains elusive.
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Transitions between progression-free first-line treatment (PF1), progression-free second-line treatment (PF2), progression, and death health states were simulated with a probabilistic Markov model with half-cycle correction. At first, patients were assumed to be receiving rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) induction. The first-line RCHOP induction responders continued without (RCHOP) or with (RCHOPR) the first-line rituximab-maintenance treatment. In the case of PF1 failure, patients received RCOPR/bendamustine or RCOPR/COP according to the European Society for Medical Oncology guidance. In the case of PF2 failure, patients were expected to receive the best supportive care (BSC). The survivals and adverse events were estimated with direct and indirect comparisons. Health outcomes and Finnish payer (drug, drug administration, monitoring, test, progression, serious adverse event) costs valued in 2010 euros were discounted with 3% per annum.
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Acetylcholinesterase (AChE)-inhibition is an area of priority research as various roles have been attributed to AChE in neurodegenerative disorders and cancer as well. In the present study, a comparative multiple 4 dimensional (4D)-approach was applied to analyze human platelet AChE-inhibition by cyclophosphamide (CP). AChE activity was assessed by measuring the hydrolysis of acetylthiocholine iodide (ASChI). The different perspective of analysis was based on two classical (Lineweaver-Burk as well as Dixon) plots, built-in equations of GOSA and a recently introduced graphical approach. Thus, various kinetic constants such as KI, Ks, Km, ksl, Vmao, Ki, ksli, Slmax, �Ks, K1/2, kcat and ksp were estimated. Previous findings of AChE (from different sources) inhibition by CP were also compared. This study extends the elucidation of the kinetic approach of analysis and quantifying enzyme-substrate and enzyme-inhibitor interactions, which is crucial to bringing any drug from bench to bedside. The acyl pocket of human AChE was found to interact with CP through the amino acid residues Y70, Y121, W233, F288, F290, Y334, F408 and Y442, while the anionic sub-site of catalytic site (CAS) interacted with the ligand through residues W84, N85, G116, G117, Y121, S122, G123, L127, Y130, E198, Y334, H443 and G444. CP displayed variable docking poses with the peripheral anionic site (PAS) of human AChE. The findings of kinetic analysis were reinforced by the results of docking experiments. Both the applied approaches strongly indicate partial mixed type of inhibition pattern for the study enzyme (AChE) and its inhibitor (CP).
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The aim of this study was to verify the effect of immunosuppression by cyclophosphamide (Cy) on susceptibility of BALB/c mice subjected to challenge with recombinant strains of Toxoplasma gondii. Animals were prime infected with the D8 (recombinant I/III) or the ME49 (type II) non-virulent strains, weekly immunosuppressed with Cy and challenged with the CH3 or EGS virulent strains (I/III). Parasites recovered from surviving mice were submitted to PCR-RFLP analysis to confirm co-infection. Prime-infection with the D8 strain conferred more protection against challenge with the CH3 and EGS strains when compared with ME49 prime infection. Cy treatment caused significant leukopenia in the infected mice, what probably favors reinfection after challenge. Reinfection was associated with increased levels of IgA. Otherwise, Cy-treated mice presented significantly lower IgA levels after challenge, suggesting involvement of this immunoglobulin on protection against reinfection. In conclusion, BALB/c mice susceptibility to reinfection by T. gondii is related to genetic differences among the strains used for primary and challenge infections. Alteration of the host's immune integrity by Cy probably compromises the protection previously established by primary infection.
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Proinflammatory markers, including neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR), are associated with many aspects of different malignancies. The aim of this study was to assess the associations of NLR and PLR with estrogen receptor (ER) and progesterone receptor (PR) expression in locally advanced breast cancer patients and their changes after neoadjuvant chemotherapy (NAC). Whether these parameters were predictive for the response to NAC in breast cancer patients was also evaluated.
Bendamustine in combination with rituximab (BR) has been associated with high response rates and acceptable toxicity in older patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Evaluation of BR is warranted in the front-line setting for DLBCL patients not eligible for anthracyclines or for the elderly. In this phase II study, we enrolled DLBCL patients aged ≥65 years who were poor candidates for R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) to determine the efficacy and safety of BR in previously untreated stage II-IV DLBCL. Twenty-three patients were enrolled with a median age of 80 years. 52% of patients presented with poor functional status (Eastern Cooperative Oncology Group performance score of ≥2). The overall response rate was 78% with 12 complete responses (52%). At a median follow up of 29 months, the median overall survival was 10·2 months and the median progression-free survival was 5·4 months. The most common grade 3/4 adverse events were haematological. Combination therapy with BR demonstrates high response rates as front-line therapy in frail older patients with DLBCL, but survival rates were low. BR should be used with caution in future clinical trials involving older DLBCL patients with poor functional status.
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Systemic sclerosis (SSc) is a rare disease requiring multicentre collaboration to reveal comprehensive details of disease-related causes for morbidity and mortality.
Dogs received toceranib at 2.75 mg/kg once every other day. After 2 weeks, oral CYC was added at 15 mg/m(2) daily. Numbers of Treg and lymphocyte subsets were measured in blood by flow cytometry during the 8-week study period. Serum concentrations of IFN-γ were measured by ELISA.
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Changing the neoadjuvant chemotherapy regimen in insufficiently responding breast cancer is not a standard policy. We analysed a series of patients with 'luminal'-type breast cancer in whom the second half of neoadjuvant chemotherapy was selected based on the response to the first half.
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Primary pericardial synovial sarcoma is a rare disease. We herein report a case of synovial sarcoma that originated in the epicardium. A 13-year-old male visited our hospital with a fever and chest pain. Copious pericardial effusion and a large intrapericardial tumor were detected. An open-chest tumor resection was performed. A solid nodular tumor was observed in the pericardial cavity. The tumor was a polypoid mass that was pedunculated and grew from the inner surface of the pericardium near the origin of the SVC and ascending aorta. Histologically, the tumor cells were uniformly spindle shaped, with an ovoid or oval nucleus, and formed solid, compact sheets and fascicles. A storiform pattern was also observed. Based on the histopathological and immunohistochemical findings, and the fluorescence in situ hybridization detection of rearrangement of the SYT gene, a monophasic synovial sarcoma was diagnosed. We discuss the diagnosis and treatment of this case and review the pertinent literature.
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Standardization of doses of chemotherapy was deemed interesting if > or =60% of the doses were standardisable with a maximum of five SRD and a minimum of one delivery per week, in order to guarantee a good turnover of the batch. A maximum of 5% standard deviation is added to those three criteria, the deviation currently accepted among our medical staff. After analyzing 3506 prescriptions, 7 molecules are eligible: Doxorubicine, 5-Fluorouracil infusion, 5-Fluorouracil pump, Gemcitabine, Paclitaxel, Rituximab, Trastuzumab and Vinorelbine, with a percentage of standardisation of 77% [SRD: 30 mg), 61% [SRD: 700 mg, 750 mg, 800 mgl, 75% (SRD: 4000 mg, 4500 mg, 5000 mg), 72% [SRD: 1600 mg, 1800 mg, 2000 mg), 61% [SRD: 140 mg, 150 mg, 160 mgl, 64% (SRD: 600 mg, 700 mg, 750 mg], 71% (SRD: 350 mg, 400 mg. 450 mgl et 62% [SRD: 40 mg, 50 mg] respectively.
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Reduced-intensity-conditioned allogeneic stem cell transplantation (SCT) remains a potentially curative approach for patients with relapsed/refractory Hodgkin lymphoma (HL) after an autologous stem cell transplantation. In the absence of an HLA-identical donor, haploidentical SCT (haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy) has been evaluated with favorable preliminary results. We evaluated 24 patients who underwent haplo-SCT for relapsed/refractory HL. The conditioning regimen consisted of cyclophosphamide, fludarabine, and total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of a calcineurin inhibitor, mycophenolate mofetil, and PT-Cy (50 mg/kg/day for 2 days) for all patients. After a median follow-up of 2 years, the cumulative incidence (CI) of nonrelapse mortality was 26% and the CI of grades II to IV acute GVHD and chronic GVHD were 17% and 24%, respectively. Estimation of progression-free and overall survival at 2 years were 54% and 66%%, respectively. Haplo-SCT is a valuable option for relapsed/refractory HL patients after a failed autologous SCT, with favorable survival and relatively low risk of GVHD.
Immunosuppressive agents may induce hepatitis B flares. The minimal corticosteroid dose and duration of therapy leading to HBV reactivation is unknown.
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Rolling of leukocytes increased ~3-fold in the postcapillary vessels in the protamine sulphate-treated group and the increase in this parameter was ~5 and ~6.5-fold in cyclophosphamide and IR groups, respectively. The increase in leukocyte adherence reached similar, approx. 7-fold increase in each of the challenged groups. The red blood cell velocity in the capillaries decreased in the protamine sulphate and IR groups, while the velocity increased moderately in the cyclophosphamide-treated group.
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A few recent studies investigated the prognostic impact of CD30 expression in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. No study has evaluated the significance of CD30 expression in DLBCL patients treated with rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH). In a group of 97 patients with DLBCL and high-risk features who received R-EPOCH induction therapy, we studied CD30 expression by immunohistochemistry using different cutoff values (>0% and ≥20% of lymphoma cells, respectively) and correlated with prognosis. CD30 expression was detected in 24 (25%) cases using a cutoff greater than 0% and in 12 (12%) cases using a cutoff of 20% or greater. The clinicopathological features were similar between CD30+ and CD30-negative groups. A major difference was that MYC rearrangement was infrequent in the CD30+ group: 2 (9%) of 23 in CD30+ versus 25 (35%) of 72 in CD30-negative group (P=.02). CD30 expression was not associated with germinal center B-cell-like (GCB) or non-GCB type. Overall survival (OS) was not significantly different between patients with CD30+ and patients with CD30-negative DLBCL, either for all patients or for the subset of patients without MYC rearrangement, regardless of cutoff (P>.05). CD30 expression was not associated with OS in either GCB or non-GCB subtype (P>.05, > 0% cutoff). In conclusion, CD30 expression was detected in up to 25% of cases of DLBCL and was more frequent in tumors without MYC rearrangement. CD30 expression was not associated with OS in R-EPOCH-treated de novo DLBCL patients.
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Forty patients (median age, 57 years; range, 27 to 71 years) were enrolled. The median follow-up was 28.7 months. In the intention-to-treat analysis, the median PFS and overall survival were 15.1 (95% CI, 8.4; -) and 36.3 (95% CI, 25.6; -) months, respectively. The overall response rate to induction was 69%. One patient underwent a syngeneic allograft and 25 HDM/ASCT (16 of whom subsequently received a reduced-intensity conditioning allograft and seven a second ASCT followed by maintenance).
Occupational exposure to anticancer drugs is recognized as a risk for healthcare workers. Reducing anticancer drugs in the environment is important to prevent the exposure of individuals to anticancer drugs. However, there are currently no effective degrading agents for all anticancer drugs used in clinical settings. We previously reported the resolution of an anticancer drug with the use of a photocatalyst (TiO2), which acts by absorbing ultraviolet light to degrade organic compounds. In this study, we evaluated anticancer drug degradation using a visible light-driven photocatalyst (Cu/WO3). Anticancer drugs [cyclophosphamide (CPA), paclitaxel (PTX), methotrexate (MTX), irinotecan (CPT-11), cytarabine (Ara-C), and 5-fluorouracil (5-FU)], were experimentally deposited on a stainless steel plate. The visible light-driven photocatalytic agent (0.075% Cu/WO3 solution) was sprayed onto the plate, and the plate was then left under a fluorescent lamp for 12 h. The anticancer drugs remaining on the plate were assayed by high-performance liquid chromatography (HPLC). CPA, PTX, MTX, CPT-11, Ara-C, and 5-FU were found to be degraded by up to 37.7%, >99.0%, 57.1%, 54.6%, 69.5%, and 36.3%, respectively. The visible light-driven photocatalyst was therefore confirmed to degrade anticancer drugs under a fluorescent lamp. The ability of the visible light-driven photocatalyst to degrade multiple chemotherapeutic agents without the need for altering the light source could make it a useful tool for reducing anticancer drug pollution in clinical settings.
As the patient`s condition deteriorated from day to day a diagnosis had to be enforced. Splenectomy was thus performed which confirmed the CT findings of numerous infarcted areas. A marginal zone lymphoma was found within the splenic hilar lymph nodes. High titer serum antibodies against cardiolipin confirmed the diagnosis of secondary antiphospholipid syndrome (APS).
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Most patients with anti-NMDAR encephalitis respond to immunotherapy. Second-line immunotherapy is usually effective when first-line treatments fail. In this cohort, the recovery of some patients took up to 18 months.
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The combination of fludarabine, cyclophosphamide and rituximab (FCR) has been widely used in the treatment of lymphoproliferative disorders, and is now considered as the standard first-line therapy for fit, young patients with chronic lymphocytic leukemia (CLL). However, in routine practice, the majority of patients with lymphoproliferative disease are over the age of 70 years, and most studies involving FCR have included younger, "fitter" patients, on average in their sixth decade of life. It is not easy to extrapolate the results of these studies to routine practice. In general, the impression is that FCR is less well tolerated in more elderly patients (> 70 years) with good organ function. However, there is a relative paucity of evidence to support this. In this review we aimed to critically examine evidence of the efficacy and toxicity of FCR in the elderly patient.