Mycophenolate mofetil was recently accepted as the effective induction treatment of lupus nephritis, with the potential to replace cyclophosphamide or at least expand our therapeutic armamentarium in patients with this lifelong disease often requiring repeated induction treatment of its relapses. Compared with cyclophosphamide, mycophenolate may be more effective in black patients, and the risk of gonadotoxicity may be significantly lower in mycophenolate-treated subjects. However, experience with mycophenolate in severe lupus nephritis is still limited and we also have insufficient data on the long-term outcome of mycophenolate-treated patients. Treatment with mycophenolate is more expensive than with cyclophosphamide, which may limit its use, especially in low- and middle-income countries. The efficacy of mycophenolate mofetil may be more dependent on the patient's compliance compared with intravenous cyclophosphamide pulses. Low-dose cyclophosphamide remains an effective and relatively safe induction treatment of active lupus nephritis, but to decrease its cumulative toxicity, repeated exposure to cyclophosphamide in relapsing patients should be (if possible) avoided.

• Klíčová slova
• cyclophosphamide, lupus nephritis, mycophenolate, treatment,
• MeSH
• adherence pacienta * MeSH
• antitumorózní látky alkylující terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• indukce remise MeSH
• klinické protokoly normy   MeSH
• lidé MeSH
• nefritida při lupus erythematodes farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH
• Názvy látek
• antitumorózní látky alkylující MeSH
• cyklofosfamid MeSH

INTRODUCTION: Macrocrystalline oxides of alkaline earth metals (Mg and Ca) or light metals (Al and Ti) can respond to standard warfare agents such as sulfur mustard, soman, or agent VX. In this paper, we compared the decontamination ability of sodium hydroxide (NaOH) and sodium hypochlorite (NaClO) for nitrogen mustards (cyclophosphamide [CP] and ifosfamide [IFOS]) with a new procedure using a destructive sorbent based on nanocrystalline and nanodispersive titanium dioxide (TiO2) as a new efficient and cheap material for complete decontamination of surfaces. METHODS: Titanium (IV) dioxide nanoparticles were prepared by the homogeneous hydrolysis of titanium(IV) oxysulfate (TiOSO4) with urea. The as-prepared TiO2 nanoparticles were used for the fast and safe decontamination of cytostatics from the nitrogen mustard family (CP and IFOS) in water. The adsorption-degradation process of cytostatics in the presence of TiO2 was compared with decontamination agents (0.01 M solution of sodium hydroxide and 5% solution of sodium hypochlorite). The mechanism of the decontamination process and the degradation efficiency were determined by high-performance liquid chromatography with mass spectrometry. RESULTS: It was demonstrated that a 0.01 M solution of sodium hydroxide (NaOH) decomposes CP to 3-((amino(bis(2-chloroethyl)amino)phosphoryl)oxy)propanoic acid and sodium hypochlorite formed two reaction products, namely, IFOS and 4-hydroxy-cyclophosphamide. IFOS is cytotoxic, and 4-hydroxy-cyclophosphamide is a known metabolite of CP after its partial metabolism by CYP/CYP450. IFOS degrades in the pres¬ence of NaOH to toxic IFOS mustard. Titanium(IV) dioxide nanoparticles adsorbed on its surface CP after 5 minutes and on IFOS after 10 minutes. The adsorption-degradation process of CP in water and in the presence of TiO2 led to 4-hydroxy-cyclophosphamide and IFOS, respectively, which decayed to oxidation product 4-hydroxy-ifosfamide. CONCLUSION: Nanodispersive TiO2 is an effective degradation agent for decontamination of surfaces from cytostatics in medical facilities.

• Klíčová slova
• cyclophosphamide, decontamination agents, degradation, ifosfamide, ifosfamide mustard, titanium(IV) dioxide,
• MeSH
• antitumorózní látky alkylující chemie   metabolismus   MeSH
• cyklofosfamid chemie   metabolismus   MeSH
• cytostatické látky chemie   metabolismus   MeSH
• dekontaminace metody   MeSH
• ifosfamid chemie   metabolismus   MeSH
• lidé MeSH
• nanočástice chemie   MeSH
• titan chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky alkylující MeSH
• cyklofosfamid MeSH
• cytostatické látky MeSH
• ifosfamid MeSH
• titan MeSH
• titanium dioxide MeSH Prohlížeč

Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300)

• MeSH
• cyklofosfamid * aplikace a dávkování   terapeutické užití   MeSH
• cyklosporin terapeutické užití   MeSH
• dospělí MeSH
• imunosupresiva * aplikace a dávkování   terapeutické užití   MeSH
• intravenózní infuze MeSH
• lidé MeSH
• míra přežití MeSH
• mladý dospělý MeSH
• nefritida při lupus erythematodes diagnóza   farmakoterapie   MeSH
• vyšetření funkce ledvin MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• cyklofosfamid * MeSH
• cyklosporin MeSH
• imunosupresiva * MeSH

High doses of corticosteroids in combination with rituximab remain an alternative in the treatment in relapsed or refractory chronic lymphocytic leukaemia (CLL) in the current era of targeted therapies. This study retrospectively evaluates the efficacy of an RCD (rituximab, cyclophosphamide and dexamethasone) regimen in the treatment of 51 patients with relapsed CLL (median age, 72 years). Unfavourable prognostic features, such as Rai stage III/IV, unmutated IGHV, del11q, TP53 mutation/deletion, complex karyotype and bulky lymphadenopathy, were frequent. The overall response or complete remission was of 57% and 7%, respectively, and the median progression-free survival (PFS) was of 12.3 months, median time to next treatment 23.1 months and median overall survival 39.2 months. Significant independent predictors of shorter PFS were TP53 deletion/mutation, advanced Rai stage and ≥2 previous lines of treatment. The incidence of neutropenia grade ≥ 3 was of 13%. Serious (CTCAE grade 3-5) infections were found in 20% of patients. Steroid-induced diabetes or diabetes decompensation occurred in 20% patients. Treatment-related adverse events resulted in RCD dose reduction in 35% of patients. In comparison with a historical R-Dex patient group, the treatment response and/or toxicity in our group was largely similar. However, the substantial differences in the baseline clinical characteristics of the groups may affect this comparison. In conclusion, the RCD regimen is an active, time-limited therapeutic strategy for elderly patients with relapsed CLL. Further, the results of our analysis indicate that the addition of cyclophosphamide to the R-Dex regimen maintains a similar efficacy, even after 50% reduction in the dexamethasone dose.

• Klíčová slova
• chemoimmunotherapy, chronic lymphocytic leukaemia, cyclophosphamide, dexamethasone, rituximab,
• MeSH
• chronická lymfatická leukemie farmakoterapie   genetika   patologie   MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• dexamethason aplikace a dávkování   MeSH
• diabetes mellitus chemicky indukované   epidemiologie   MeSH
• doba přežití bez progrese choroby MeSH
• indukce remise MeSH
• infekce epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   genetika   patologie   MeSH
• míra přežití MeSH
• nádorový supresorový protein p53 genetika   MeSH
• neutropenie chemicky indukované   epidemiologie   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• retrospektivní studie MeSH
• rituximab aplikace a dávkování   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• vysazování léků MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklofosfamid MeSH
• dexamethason MeSH
• nádorový supresorový protein p53 MeSH
• rituximab MeSH
• TP53 protein, human MeSH Prohlížeč

The median survival time of DBA/2Wf or CD2F1 hybrid mice increased after administration of 10(3) cells of lymphoid leukaemia L 1210 when the recipient mice were injected earlier with L 1210 cells pretreated in vivo with cyclophosphamide. To achieve this effect, at least 10(5) cells treated with cyclophosphamide should be used per mouse. This effect was immunologically specific and could not be induced by L-1 cells treated with cyclophosphamide, and was transferable by means of splenocytes. Such immunoprophylaxis was efficient for at least 100 days. Attempts at immunoprevention by means of the same cells treated with mitomycin C or killed by osmotic shock were unsuccessful.

• MeSH
• antibiotika antitumorózní terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• experimentální sarkom farmakoterapie   imunologie   MeSH
• imunologická tolerance účinky léků   MeSH
• inbrední kmeny myší MeSH
• leukemie L1210 farmakoterapie   imunologie   MeSH
• mitomycin MeSH
• mitomyciny terapeutické užití   MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibiotika antitumorózní MeSH
• cyklofosfamid MeSH
• mitomycin MeSH
• mitomyciny MeSH

OBJECTIVES: Cyclophosphamide induction regimens are effective for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but are associated with infections, malignancies and infertility. Mycophenolate mofetil (MMF) has shown high remission rates in small studies of AAV. METHODS: We conducted a randomised controlled trial to investigate whether MMF was non-inferior to cyclophosphamide for remission induction in AAV. 140 newly diagnosed patients were randomly assigned to MMF or pulsed cyclophosphamide. All patients received the same oral glucocorticoid regimen and were switched to azathioprine following remission. The primary endpoint was remission by 6 months requiring compliance with the tapering glucocorticoid regimen. Patients with an eGFR <15 mL/min were excluded from the study. RESULTS: At baseline, ANCA subtype, disease activity and organ involvement were similar between groups. Non-inferiority was demonstrated for the primary remission endpoint, which occurred in 47 patients (67%) in the MMF group and 43 patients (61%) in the cyclophosphamide group (risk difference 5.7%, 90% CI -7.5% to 19%). Following remission, more relapses occurred in the MMF group (23 patients, 33%) compared with the cyclophosphamide group (13 patients, 19%) (incidence rate ratio 1.97, 95% CI 0.96 to 4.23, p=0.049). In MPO-ANCA patients, relapses occurred in 12% of the cyclophosphamide group and 15% of the MMF group. In PR3-ANCA patients, relapses occurred in 24% of the cyclophosphamide group and 48% of the MMF group. Serious infections were similar between groups (26% MMF group, 17% cyclophosphamide group) (OR 1.67, 95% CI 0.68 to 4.19, p=0.3). CONCLUSION: MMF was non-inferior to cyclophosphamide for remission induction in AAV, but resulted in higher relapse rate. TRIAL REGISTRATION NUMBER: NCT00414128.

• Klíčová slova
• ANCA-associated vasculitis, cyclophosphamide, induction therapy, mycophenolate, randomised trial,
• MeSH
• ANCA-asociované vaskulitidy farmakoterapie   MeSH
• azathioprin terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• dítě MeSH
• dospělí MeSH
• imunosupresiva terapeutické užití   MeSH
• indukční chemoterapie metody   MeSH
• kyselina mykofenolová terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• recidiva MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• azathioprin MeSH
• cyklofosfamid MeSH
• imunosupresiva MeSH
• kyselina mykofenolová MeSH

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused the dysregulation of host inflammatory response and immunosuppression to infection Early recognition and intervention are hence of paramount importance. In this respect the "sepsis bundle" was proposed in 2004 to be instituted in cases of suspected sepsis. OBJECTIVE AND HYPOTHESIS: We hypothesised that a combination treatment of the sepsis bundle with cyclophosphamide would improve the function of the intestinal mucosa and enhance survival in rats with induced sepsis. METHODS AND RESULTS: Sprague-Dawley rats were divided into 5 different groups: sham, cecal ligation and puncture (CLP), cyclophosphamide (CTX), imipenem+normal saline (NS) and imipenem+NS+CTX. Cecal ligation and puncture were used for inducing the polymicrobial sepsis. Western-blot was used to measure the occludin protein, and ELISA for examining the plasma level of cytokines IL-6, IL-10 and TNF-α. TUNEL assay for testing the intestinal mucosal apoptosis, and hematoxylin-eosin staining for observing the intestinal mucosal changes. The permeability of intestinal mucosa was determined by the plasma level of FD-70. The results showed that the combination treatment of the sepsis bundle with cyclophosphamide attenuated cytokine levels, inhibited epithelial cell apoptosis and improved the function of the intestinal barrier. The survival rate of the group treated with the combined therapy was significantly higher than that of the other groups. CONCLUSION: The combination treatment of sepsis bundle with cyclophosphamide improves the function of the intestinal barrier and enhances survival in septic rats.

• Klíčová slova
• cyclophosphamide, intestinal barrier, sepsis, sepsis bundle,
• MeSH
• antibakteriální látky farmakologie   MeSH
• apoptóza účinky léků   MeSH
• chlorid sodný farmakologie   MeSH
• cyklofosfamid farmakologie   MeSH
• cytokiny metabolismus   MeSH
• fixní kombinace léků MeSH
• imipenem farmakologie   MeSH
• imunosupresiva farmakologie   MeSH
• okludin metabolismus   MeSH
• permeabilita účinky léků   MeSH
• potkani Sprague-Dawley MeSH
• sepse farmakoterapie   mortalita   MeSH
• střevní sliznice účinky léků   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• chlorid sodný MeSH
• cyklofosfamid MeSH
• cytokiny MeSH
• fixní kombinace léků MeSH
• imipenem MeSH
• imunosupresiva MeSH
• okludin MeSH

BACKGROUND: Cyclophosphamide (CP) embryotoxicity was documented in several studies on different experimental models. We investigate quantitatively the relationship between the embryotoxic effect of CP and the disturbance of the cell-cycle using flow cytometry. METHODS: Chick embryos on Days 2-4 were treated with 0.5, 1, 2, 4, 8, and 16 microg doses of pure substance of CP by intraamniotic or subgerminal administration routes. Cell-cycle analysis was carried out in the brain, limb buds, hearts, and facial outgrowths dissected from the embryos 6 hr after administration. Samples of nuclear suspensions were obtained by enzymatic and mechanical disintegration of solid tissues in collagenase-dispase, followed by detergent and RNA-ase mediated cytolysis. Nuclei were stained by ethidium bromide. RESULTS: A dose-dependent increase of S-phase cells followed by decrement of G2M cell compartment was observed. The significant block of S-phase cells, however, was not always associated with malformations. The degree of cell-cycle disturbance was expressed more readily by the ratio G2M/S that demonstrated consistently the threshold character of both teratogenic and lethal effects. CONCLUSION: CP-induced cytotoxicity manifested by dose-dependent disturbance of cell-cycle resulted in an overall depression of proliferation activity clearly associated with the occurrence of malformations and embryonic death. Although a non-significant depression of mitotic activity appeared sufficient to produce malformations on Day 2, remarkably deeper disturbance was needed to interfere with the development of the embryos in more advanced stages. Changes in proliferation rate appear to be a primary and most important event in teratogenesis induced by general toxic agents.

• MeSH
• abnormality vyvolané léky * MeSH
• antitumorózní látky alkylující toxicita   MeSH
• buněčné dělení účinky léků   MeSH
• buněčný cyklus účinky léků   MeSH
• cyklofosfamid toxicita   MeSH
• embryo nesavčí cytologie   účinky léků   embryologie   MeSH
• kuřecí embryo MeSH
• teratogeny toxicita   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky alkylující MeSH
• cyklofosfamid MeSH
• teratogeny MeSH

Pre-transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo-HCT). The impact of MRD on the outcomes of post-transplant cyclophosphamide (PTCy)-based allo-HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD-], n = 165; MRD positive [MRD+], n = 107) with a median follow-up of 19 (range: 16-24) months were studied. The incidence of grades II-IV and grades III-IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2-year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD- cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39-4.72), lower leukaemia-free survival (LFS) (HR = 2.04, 95% CI: 1.23-3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04-3.25) and GVHD-free, relapse-free survival (GRFS) (HR = 1.69, 95% CI: 1.10-2.58). MRD status did not have a significant impact on non-relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo-HCT with PTCy, pre-transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS.

• Klíčová slova
• acute myeloid leukaemia, allogeneic haematopoietic cell transplantation, measurable residual disease, post-transplant cyclophosphamide, unrelated donor,
• MeSH
• akutní myeloidní leukemie * komplikace   MeSH
• cyklofosfamid terapeutické užití   MeSH
• lidé MeSH
• lokální recidiva nádoru etiologie   MeSH
• nemoc štěpu proti hostiteli * MeSH
• nepříbuzný dárce MeSH
• retrospektivní studie MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklofosfamid MeSH

Single and repeated intravenous administration of cyclophosphamide significantly decreased the candidacidal activity of rabbit peritoneal macrophages. Using higher doses of the drug, a more pronounced decrease, persisting up to 10 d, was observed. The phagocytic index has not changed significantly 10 d after cyclophosphamide injection as compared with controls. No changes in the phagocytic activity were recorded. The decreased candidacidal activity may be one of the causes of serious microbial infections in cyclophosphamide-treated patients.

• MeSH
• Candida albicans účinky léků   imunologie   MeSH
• cyklofosfamid farmakologie   MeSH
• fagocytóza účinky léků   MeSH
• králíci MeSH
• makrofágy účinky léků   imunologie   MeSH
• peritoneální dutina MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklofosfamid MeSH