Molecular Iodine Improves the Efficacy and Reduces the Side Effects of Metronomic Cyclophosphamide Treatment against Mammary Cancer Progression.

Metronomic chemotherapy with cyclophosphamide (Cpp) has shown promising results in cancer protocols. These lower and prolonged doses have antiangiogenic, pro-cytotoxic, and moderate secondary effects. Molecular iodine (I2) reduces the viability of cancer cells and, with chemotherapeutic agents, activates the antitumoral immune response and diminishes side effects. The present work evaluates the adjuvant of oral I2 with Cpp using a murine model of mammary cancer. Female Sprague Dawley rats with 7,12-dimethylbenzantracene-induced tumors received Cpp intraperitoneal (50 and 70 mg/kg two times/week, iCpp50 and iCpp70) and oral (0.03%; 50 mg/Kg; oCpp50) doses. I2 (0.05%, 50 mg/100 mL) and oCpp50 were offered in drinking water for three weeks. iCpp70 was the most efficient antitumoral dose but generated severe body weight loss and hemorrhagic cystitis (HC). I2 prevented body weight loss, exhibited adjuvant actions with Cpp, decreasing tumor growth, and canceled HC mechanisms, including decreases in vascular endothelial growth factor (VEGF) and Survivin expression. oCpp50 + I2 diminished angiogenic signals (CD34, vessel-length, and VEGF content) and proinflammatory cytokines (interleukin-10 and tumor necrosis factor-alpha) and increased cytotoxic (lymphocytic infiltration, CD8+ cells, Tbet, and interferon-gamma) and antioxidant markers (nuclear erythroid factor-2 and glutathione peroxidase). I2 enhances the effectiveness of oCpp, making it a compelling candidate for a clinical protocol.

Can Lacticaseibacillus rhamnosus CRL1505 postbiotic improve emergency myelopoiesis in immunocompromised mice?

We evaluated whether viable and non-viable Lacticaseibacillus rhamnosus CRL1505 (Lr05V or Lr05NV, respectively) was able to improve emergency myelopoiesis induced by Streptococcus pneumoniae (Sp) infection. Adult Swiss-mice were orally treated with Lr05V or Lr05NV during five consecutive days. The Lr05V and Lr05NV groups and untreated control group received an intraperitoneal dose of cyclophosphamide (Cy-150 mg/kg). Then, the mice were nasally challenged with Sp (107 UFC/mice) on day 3 post-Cy injection. After the pneumococcal challenge, the innate and myelopoietic responses were evaluated. The control group showed a high susceptibility to pneumococcal infection, an impaired innate immune response and a decrease of hematopoietic stem cells (HSCs: Lin-Sca-1+c-Kit+), and myeloid multipotent precursors (MMPs: Gr-1+Ly6G+Ly6C-) in bone marrow (BM). However, lactobacilli treatments were able to significantly increase blood neutrophils and peroxidase-positive cells, while improving cytokine production and phagocytic activity of alveolar macrophages. This, in turn, led to an early Sp lung clearance compared to the control group. Furthermore, Lr05V was more effective than Lr05NV to increase growth factors in BM, which allowed an early HSCs and MMPs recovery with respect to the control group. Both Lr05V and Lr05NV were able to improve BM emergency myelopiesis and protection against respiratory pathogens in mice undergoing chemotherapy.

Posttransplant cyclophosphamide beyond haploidentical transplantation.

Posttransplant cyclophosphamide (PTCy) has practically revolutionized haploidentical (Haplo) hematopoietic cell transplantation (HCT). Comparisons between Haplo with PTCy and unrelated donor (URD) with conventional graft-versus-host disease (GVHD) prophylaxis have shown comparable overall survival with lower incidences of GVHD with Haplo/PTCy and led to the following question: is it PTCy so good that can be successfully incorporated into matched related donor (MRD) and URD HCT? In this review, we discuss other ways of doing PTCy, PTCy in peripheral blood haploidentical transplants, PTCy in the context of matched related and matched unrelated donors, PTCy with mismatched unrelated donors, and PTCy following checkpoint inhibitor treatment. PTCy is emerging as a new standard GVHD prophylaxis in haploidentical, HLA-matched, and -mismatched HCT.

Melatonin prevents overproduction of reactive oxygen species and vascular dysfunction induced by cyclophosphamide.

AIMS: Overproduction of reactive oxygen species (ROS) is a pathologic hallmark of cyclophosphamide toxicity. For this reason, antioxidant compounds emerge as promising tools for preventing tissue damage induced by cyclophosphamide. We hypothesized that melatonin would display cytoprotective action in the vasculature by preventing cyclophosphamide-induced oxidative stress. MATERIALS AND METHODS: Male C57BL/6 mice (22-25 g) were injected with a single dose of cyclophosphamide (300 mg/kg; i.p.). Mice were pretreated or not with melatonin (10 mg/kg/day, i.p.), given during 4 days before cyclophosphamide injection. Functional (vascular reactivity) and oxidative/inflammatory patterns were evaluated at 24 h in resistance arteries. The antioxidant action of melatonin was assessed in vitro in cultured vascular smooth muscle cells (VSMCs) of mesenteric arteries. KEY FINDINGS: Cyclophosphamide induced ROS generation in both mesenteric arterial bed (MAB) and cultured VSMCs, and this was normalized by melatonin. Cyclophosphamide-induced ROS generation and lipoperoxidation in the bladder and kidney was also prevented by melatonin. Increased levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were detected in the MAB of cyclophosphamide-treated mice, all of which were prevented by melatonin. Functional assays using second-order mesenteric arteries of cyclophosphamide-treated mice revealed a decrease in vascular contractility. Melatonin prevented vascular hypocontractility in the cyclophosphamide group. Melatonin partially prevented the decrease in myeloperoxidase (MPO) and N-acetyl-beta-D-glucosaminidase (NAG) activities in the MAB of the cyclophosphamide group. SIGNIFICANCE: Melatonin may constitute a novel and promising therapeutic approach for management of the toxic effects induced by cyclophosphamide in the vasculature.

Protective effect of coenzyme Q10 in cyclophosphamide-induced kidney damage in rats

SUMMARY OBJECTIVE: We aimed to investigate the effect of coenzyme q10 on cyclophosphamide-induced kidney damage in rats. METHODS: A total of 30 female Wistar-Albino rats were utilized to form three groups. In group 1 (control group) (n=10), no drugs were given. In group 2 (cyclophosphamide group) (n=10), 30 mg/kg intraperitoneal cyclophosphamide was administered for 7 days. In group 3 (cyclophosphamide+coenzyme q10 group) (n=10), 30 mg/kg cyclophosphamide and 10 mg/kg coenzyme q10 were given for 7 days via intraperitoneal route. Right kidneys were removed in all groups. Blood malondialdehyde levels and activities of catalase and superoxide dismutase were measured. Histopathological damage was evaluated by examining the slides prepared from kidney tissue using a light microscope. RESULTS: Tissue damage was significantly higher in the cyclophosphamide group than in the cyclophosphamide+coenzyme q10 group (p<0.05). The malondialdehyde levels were significantly higher and the activities of superoxide dismutase and catalase were lower in the cyclophosphamide group than in the cyclophosphamide+coenzyme q10 group (p<0.05). CONCLUSION: Coenzyme q10 may be a good option to prevent cyclophosphamide-induced kidney damage.

Favorable evolution of severe paraquat poisoning. Treatment with gastric lavage, activated charcoal, cyclophosphamide + corticoids, and conventional daily hemodialysis: case study at the Franck Joly Hospital Center in French Guiana / Évolution favorable d'une intoxication grave au paraquat. Traitement par lavage gastrique, charbon activé, cyclophosphamide + corticoïdes, et hémodialyse conventionnelle quotidienne : étude des cas au centre hospitalier Franck Joly en Guyane française

We report the observations of two patients, having voluntarily ingested lethal doses of paraquat with suicidal intent, with an unfavorable prognostic score. The treatment consisted of gastric lavage, administration of activated charcoal, n-acetylcysteine and cyclophosphamide + methylprednisolone + dexamethasone. The installation of acute renal failure motivated the initiation of daily conventional hemodialysis (HD) over 10 to 14 days, with a favorable evolution. The following complications were recorded: anemia, bacteremia and deep vein thrombosis. These observations raise three questions in the treatment of paraquat intoxication: the effectiveness of HD, the interest of its association with the above therapies in the prevention of pulmonary fibrosis, and the need for infectious prevention and thromboembolism. Furthermore, the absence of a paraquatemia assay cannot constitute a limitation for management, and hemoperfusion on an inaccessible charcoal column can be replaced by an HD usually available.

Nous rapportons les observations de deux patients ayant ingéré volontairement des doses létales du paraquat à but suicidaire, avec un score pronostic défavorable. Le traitement a consisté en un lavage gastrique, une administration du charbon activé, du n-acétylcystéine et du cyclophosphamide + méthylprednisolone + dexaméthasone. L'installation d'une insuffisance rénale aiguë a motivé l'initiation d'une hémodialyse conventionnelle quotidienne (HD) sur 10 à 14 jours, avec une évolution favorable. Les complications suivantes ont été enregistrées : anémie, bactériémie et thrombose veineuse profonde. Ces observations soulèvent trois questions dans le traitement d'une intoxication au paraquat : l'efficacité de l'HD, l'intérêt de son association avec les thérapeutiques supra dans la prévention de la fibrose pulmonaire, et la nécessité d'une prévention infectieuse et thrombo-embolique. Par ailleurs, l'absence d'un dosage de la paraquatémie ne peut constituer une limite pour la prise en charge, et l'hémoperfusion sur colonne de charbon non accessible peut être remplacée par une HD habituellement disponible.

[Melatonin reverses oxidative damage in the submandibular gland of rats treated with Cyclophosphamide]. / Melatonina revierte el daño oxidativo en glándula submandibular de ratas tratadas con Ciclofosfamida.

Objetive: Cyclophosphamide (Cf) produces oxidative damage in rat submandibular gland (GSM). In the present work we evaluated the antioxidant protective effect of melatonin (MLT) in GSM of rats treated with Cf. Methods: 40 adult male Wistar rats were divided into 5 groups (G): G1: control; G2: Control+Ethanol: treated with 1% ethanol for 10 consecutive days. On days 11 and 12 they received a dose of saline; G3: Cf: treated with 1% ethanol for 12 days, days 11 and 12 they received an intraperitoneal (i.p.) dose of Cf 50 mg/Kg/kg of saline. ) of Cf 50 mg/kg bw; G4: Cf + MLT: MLT (5 mg/kg bw, intraperitoneal, dissolved in 1% ethanol) was administered daily, days 11 and 12 received Cf same as G3; G5: MLT: treated 12 consecutive days with MLT (same dose as G4). After 12 hours of fasting, animals were anesthetized to obtain both submandibular glands, then they were sacrificed. Uric acid (UA), lipid peroxides (LPs), aqueous peroxides (APs) and superoxide dismutase (SOD) activity were measured in submandibular gland homogenate. Statistical analysis: we used ANOVA and Bonferroni test pos hoc, considering significant p<0.05. Results: Cf treatment decreased AU concentration and SOD activity (AU, mg/mg prot., G1: 2.50±0.68; G2: 2.18±0.13; G3: 0.54±0.09* G4: 1.95±0.24#, G5: 2.64±0.47, *p<0.01 G3 vs G1, G2, G4; #p<0.01 G4 vs G3 and G5; SOD, U/mg prot, G1: 4.57±0.95, G2: 4.79±0.94, G3: 2.18±0.53*, G4: 5.13±1.10, G5: 5.09±0.39, *p< 0.01 G3 vs G1, G2, G4 and G5). MLT treatment prevented these effects. In addition, Cf increased PL and PA formation. Conclusion: MLT improved the redox status in GSM of Cf-treated rats. MLT could prevent oxidative processes in GSM produced by Cf.

Objetivo: Ciclofosfamida (Cf) produce daño oxidativo en glándula submandibular (GSM) de ratas. En el presente trabajo se evaluó el efecto protector antioxidante de melatonina (MLT) en GSM de ratas tratadas con Cf. Método: Se utilizaron 40 ratas Wistar machos adultas divididas en 5 grupos (G): G1: control; G2: Control+Etanol: tratados con etanol al 1% durante 10 días consecutivos. Los días 11 y 12 recibieron una dosis de solución salina; G3: Cf: tratados con etanol al 1% durante 12 días, días 11 y 12 recibieron una dosis intraperitoneal (i.p.) de Cf de 50 mg/Kg de pc; G4: Cf + MLT: se administró diariamente MLT (5 mg/Kg pc, intraperitoneal, disuelta en etanol al 1%), días 11 y 12 recibieron Cf igual que G3; G5: MLT: tratamiento 12 días consecutivos con MLT (igual dosis de G4). Los animales fueron anestesiados, extirpándose ambas GSM y sacrificados, previo ayuno 12 hs. Se midió la concentración de ácido úrico (AU), peróxidos lipídicos (PL) y acuosos (PA) y actividad de superóxido dismutasa (SOD) en homogenato de GSM. Análisis estadístico: ANOVA y test de bonferroni, considerando significativo p<0,05. Resultados: El tratamiento con Cf disminuyó la concentración de AU y la actividad de SOD (AU, mg/mg prot., G1: 2,50±0,68; G2: 2,18±0,13; G3: 0,54±0,09* G4: 1,95±0,24#, G5: 2,64±0,47, *p< 0,01 G3 vs G1, G2, G4; #p< 0,01 G4 vs G3 y G5; SOD, U/mg prot., G1: 4,57±0.95, G2: 4,79±0,94, G3: 2,18±0,53*, G4: 5,13±1,10, G5: 5,09±0,39, *p< 0,01 G3 vs G1, G2, G4 y G5). El tratamiento con MLT previno esos efectos. Además, Cf aumentó la formación PL y PA. Conclusión: MLT mejoró el estado redox en GSM de ratas tratadas con Cf. MLT podría prevenir los procesos oxidativos en GSM producidos por Cf.

Case report: Cyclophosphamide pulse therapy for chronic recalcitrant erythema nodosum leprosum.

Chronic recalcitrant erythema nodosum leprosum (ENL) or type 2 reaction (T2R) is a severe condition found in approximately 50% of multibacillary leprosy subjects. T2R is associated with important morbidities and may lead to several disabilities, not only due to nerve damage but also due to the prolonged use of corticosteroids, thalidomide, or immunosuppressors. We describe here four leprosy patients with chronic recalcitrant ENL treated with cyclophosphamide pulse therapy. All subjects had been on prednisone and thalidomide therapy for at least 30 months but showed inflammatory activity when doses were reduced. Pulse therapy with 1.0 g of cyclophosphamide was used every 4-6 weeks for a minimum of three applications. After pulse therapy, all cases presented total or partial regression of symptoms, and we were able to taper thalidomide and prednisone doses, with better control of ENL, avoiding further hospital admissions and disabilities. No side effects were observed during or after infusion therapy. Cyclophosphamide pulse therapy may be useful and safe to control chronic recalcitrant ENL.

Outcomes and challenges treating pediatric acute myeloid leukemia: a retrospective analysis of patients treated at the Fundación Valle del Lili between 2011 and 2020.

INTRODUCTION: Acute myeloid leukemia is a challenging disease, due to a poor prognosis in developing countries. Herein, we aim to describe the clinical characteristics and outcomes after chemotherapy and transplantation. METHODS: A retrospective analytic observational study was performed with patients under 18 years of age with newly diagnosed acute myeloid leukemia treated at a referral center in Colombia. Two groups were compared: induction therapy (IT) and induction therapy plus consolidation (IT + C). The survival analysis was performed using the Kaplan-Meier method. RESULTS: We analyzed 34 patients diagnosed with acute myeloid leukemia; 20 received hematopoietic stem cell transplantation. Most were French-American-British (FAB) classification types M1, M5 and M0. The transplantation was haploidentical in 65%, conditioning was myeloablative in 67% and graft-versus-host disease prophylaxis was performed with post-transplant cyclophosphamide in 70%. Overall, the 5-year survival was 52% and the overall 5-year survival in the transplanted group was 80%. There were 16 deaths; in the IT group, n = 12, and in the IT + C group, n = 4. In the former, the main cause of death was septic shock and in the latter, it was relapse. CONCLUSION: Transplantation is a safe option. Receiving treatment and supportive measures in hematopoietic stem cell transplantation units is necessary to avoid infections, especially during induction cycles.

Applicability and validation of different prognostic scores in allogeneic hematopoietic cell transplant (HCT) in the post-transplant cyclophosphamide era.

We investigated the predictive capacity of six prognostic indices [Karnofsky Performance Status (KPS), Hematopoietic Cell Transplant-Specific Comorbidity Index (HCT-CI), Disease Risk Index (DRI), European Bone Marrow Transplantation (EBMT) and Revised Pre-Transplantation Assessment of Mortality (rPAM) Scores and Endothelial Activation and Stress Index (EASIX)] in 205 adults undergoing post-transplant cyclophosphamide (PTCy)-based allo-HCT. KPS, HCT-CI, DRI and EASIX grouped patients into higher and lower risk strata. KPS and EASIX maintained appropriate discrimination for OS prediction across the first 2 years after allo-HCT [receiver operating characteristic curve (area under the curve (AUC) > 55 %)]. The discriminative capacity of DRI and HCT-CI increased during the post-transplant period, with a peak of prediction at 2 years (AUC of 61.1 % and 61.8 %). The maximum rPAM discriminative capacity was at 1 year (1-year AUC of 58.2 %). The predictive capacity of the EBMT score was not demonstrated. This study validates the discrimination capacity for OS prediction of KPS, HCT-CI, DRI and EASIX in PTCy-based allo-HCT.

Teratogen Potential Evaluation of the Aqueous and Hydroalcoholic Leaf Extracts of Crataegus oxyacantha in Pregnancy Rats.

Crataegus oxyacantha is used in the treatment of cardiovascular diseases. The aim of this study was to evaluate the transplacental genotoxicity effect of aqueous (AE) and hydroalcoholic extract (HE) of leaves C. oxyacantha in a rat model and the quantification of malondialdehyde (MDA) in the liver. Three different doses of the AE and HE of the C. oxyacantha leaf were administered orally (500, 1000 and 2000 mg/kg) to Wistar rats during 5 days through the pregnancy term (16-21 days), and sampling in rats occurred every 24 h during the last 6 days of gestation, while only one sample was taken in neonates at birth. A sample of the mother's and the neonate's liver was taken for the determination of MDA. The results show that, at the hepatic level, the evaluated doses of extracts C. oxyacantha in pregnant rats and their pups did not show cytotoxicity. However, the AE and HE generated cytotoxic and genotoxic damage in the short term. On the other hand, only the AE showed a teratogenic effect. Based on these results, the AE and HE of the C. oxyacantha leaf should not be administered during pregnancy.

Dexamethasone-cyclophosphamide pulse therapy outcomes comparing pemphigus vulgaris and pemphigus foliaceus groups in a Brazilian cohort study.

BACKGROUND: Dexamethasone-cyclophosphamide pulse (DCP) and dexamethasone pulse (DP) have been successfully used to treat pemphigus, but DCP/DP outcomes comparing pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are scarce. OBJECTIVE: To compare DCP/DP outcomes in a Brazilian cohort of PV and PF patients according to demographic and clinical data. METHODS: Retrospective analytical cohort study, reviewing medical charts of PV and PF patients (for DCP/DP Phases I‒IV consult Pasricha et al.16‒18). RESULTS: 37 PV and 41 PF patients non responsive to usual treatments were included similarly for DCP or DP therapy. Disease duration was longer among PF before DCP/DP prescription (p < 0.001); PF required a higher number of monthly pulses to acquire remission in Phase I (median 10 and 6 pulses, respectively; p = 0.005). DCP/DP outcomes were similar in both groups: remission in 37.8% of PV and 34.1% of PF after completed DCP/DP cycles following a median of 13 months (1-56 months follow-up); failure occurred in 13.5% of PV and 14.6% of PF in Phase I; relapse in 13.5% of PV and 12.2% of PF, and dropout in 27% of PV and 24.4% of PF in Phases II to IV. Mild side effects were documented. STUDY LIMITATIONS: The severity of PV and PF disease was not assessed by score indexes. CONCLUSIONS: PV and PF patients presented similar DCP/DP outcomes. DCP/DP should be initiated earlier in PF patients due to the longer duration of their disease in order to decrease the number of pulses and the duration of Phase I to acquire remission.

Membranous nephropathy / Nefropatia membranosa

ABSTRACT Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.

RESUMO A nefropatia membranosa é uma glomerulopatia, cujo principal alvo acometido é o podócito, e acarreta consequências na membrana basal glomerular. Tem maior frequência em adultos, principalmente acima dos 50 anos. A apresentação clínica é a síndrome nefrótica, mas muitos casos podem evoluir com proteinúria não nefrótica assintomática. O mecanismo consiste na deposição de complexos imunes no espaço subepitelial da alça capilar glomerular com subsequente ativação do sistema do complemento. Grandes avanços na identificação de potenciais antígenos alvo têm ocorrido nos últimos vinte anos, e o principal é a proteína "M-type phospholipase-A2 receptor" (PLA2R) com o anticorpo anti-PLA2R circulante, o que possibilita avaliar a atividade e o prognóstico dessa nefropatia. Essa via de lesão corresponde aproximadamente a 70% a 80% dos casos da nefropatia membranosa caracterizada como primária. Nos últimos 10 anos vários outros antígenos alvo potenciais têm sido identificados. Esta revisão se propõe a apresentar de modo didático aspectos clínicos, etiopatogênicos e terapêuticos da nefropatia membranosa, incluídos os casos com ocorrência no transplante renal.

The bovine dialyzable leukocyte extract, immunepotent CRP, synergically enhances cyclophosphamide-induced breast cancer cell death, through a caspase-independent mechanism.

Breast cancer (BC) is one of the leading causes of cancer death worldwide. Cyclophosphamide (CTX) remains a mainstay in cancer therapy despite harmful adverse effects and cell death-resistances. To face this, combinational therapy of chemotherapies and immunotherapies has been proposed. IMMUNEPOTENT CRP (ICRP) is an immunotherapy that has cytotoxic effects in several cancer cells without affecting peripheral blood mononuclear cells (PBMC) and CD3+ cells. The aim of this study was to evaluate cytotoxicity, the type of cytotoxic effect, and several features involved in cell death induced by the combination of CTX with ICRP (ICRP+CTX) in breast cancer cells as well as their effect on healthy cells. For this purpose, human and murine breast cancer cells, MCF-7, MDA-MB-231 and 4T1, or PBMC were treated for 24 hours with ICRP, CTX or ICRP+CTX in different combination ratios for the assessment of cell death. Flow cytometry and microscopy were used to determine biochemical and morphological characteristics of cell death. Assays showed that ICRP in combination with CTX induce potentiated cell death manifested with morphological changes, loss of mitochondrial membrane potential, reactive oxygen species (ROS) production, and caspase activation. In addition, it was determined that ICRP+CTX-cell death is caspase-independent in all the breast cancer cells assessed. On the other hand, ICRP did not affect CTX-cytotoxicity in PBMC. For all the above, we can propose that the combination of ICRP with CTX an effective combination therapy, promoting their use even in tumoral cells with defects on proteins implicated in the apoptotic pathway.

Infection-related mortality after HLA-identical and haploidentical hematopoietic cell transplantation using reduced-intensity conditioning in an outpatient setting.

BACKGROUND: Despite the improvements in supportive care for allogeneic-hematopoietic cell transplantation (allo-HCT) recipients, infectious complications and infection-related mortality (IRM) continue to be a major issue for transplantation centers. METHODS: We herein report the infectious complications and IRM of 107 and 89 patients that underwent haploidentical (haplo-HCT) or HLA-identical HCT at a tertiary referral center during 2013-2020. Patients in the haplo-HCT group received post-transplant cyclophosphamide (PT-Cy), and all received reduced-intensity conditioning regimens. RESULTS: More haplo-HCT recipients presented severe infections in the pre-engraftment period (22.4% vs. 6.7%, p = 0.003). Viral (14.9% vs. 4.5%, p = 0.016) and fungal (12.1% vs. 1.1%, p = 0.003) etiologies were more common in this period in this group. The 100-day and 2-year cumulative incidence of IRM was 15% and 21% for the haplo-HCT and 5.6% and 17% for the HLA-identical group; no significant differences were observed between the groups. Fungal pathogens mainly contributed to IRM (33.3%). Infections were the most common cause of mortality (40/81, 49.4%). There were significant differences in donor/recipient CMV serostatus between transplant groups (0.002). CONCLUSIONS: No differences in IRM were observed based on allo-HCT type, with more haplo-HCT patients suffering from severe infections in the pre-engraftment period. Studies to assess future prevention, diagnostic, and treatment strategies to reduce IRM are warranted.

Electrodegradation of cyclophosphamide in artificial urine by combined methods.

The degradation of the chemotherapeutic drug cyclophosphamide in artificial urine was evaluated by Electrochemical Advanced Oxidation Processes (EAOP). The system consisted of an electrochemical flow reactor with a commercial DSA® electrode (nominal composition Ti / Ru0,3Ti0,7O2) and Ti-mesh cathode. In order to assess the best parameters, the effect of current density, time and flow rate were analyzed using an initial 23 factorial design. The chosen response variable was the energy efficiency to produce free chlorine species (HClO/ClO-). After obtaining the most significant factors, the Central Composite Design (CCD) was performed, where the optimum conditions were determined for the current density range (11.714 mA cm-2 and 66.57 mA cm-2), flow rate (31.33 mL min-1) and time range (19 and 37 min). Under an optimized condition, the efficiency of other combined methods (photo-assisted electrochemical, photochemical, sonoelectrochemical and photo-assisted sonoelectrochemical) was evaluated. The efficiency of degradation processes was determined by removal of Chemical Oxygen Demand (COD), creatinine and urea. Analysis by HPLC demonstrates that the cyclophosphamide was substantially removed during the treatment process of ∼77%. Based on these results, it can be observed that the coupling between electrochemical and photochemical processes is a promising alternative for the treatment of this effluent, as a marked reduction of organic matter is observed (63, 94% of creatinine, 29.62% of urea, 39.1% of TOC) and a low treatment cost ratio.

Evaluation of the Efficacy of Lactobacillus acidophilus in the Treatment of Cyclophosphamide-induced Hemorrhagic Cystitis in Wistar Rats.

BACKGROUND: Hemorrhagic cystitis is an inflammatory complication that can be caused by the administration of cyclophosphamide, which is widely used as an antineoplastic agent. In the search for new therapeutic alternatives, probiotics can suppress the inflammatory process and, therefore, can be used to prevent this disease. OBJECTIVE: Thus, this study aimed to evaluate the effects of using Lactobacillus acidophilus NCFM in the treatment of cyclophosphamide-induced hemorrhagic cystitis in Wistar rats. METHODS: Lactobacillus acidophilus NCFM (2x108 CFU) was used in the treatment of cyclophosphamide- induced hemorrhagic cystitis (200 mg/kg, intraperitoneal) in 77 female Wistar rats. Rats were distributed into experimental groups (n = 9): control group (GC), zero control group (GCZ), inflammation group (GI), 24-hour acute treatment groups: 24-hour lactobacilli treatment group (GL24H) and mesna group (GM), and 30-day chronic treatment groups: lactobacilli treatment group (GTL) and mesna+lactobacilli group (GM+L). After treatment, animals were euthanized and biological materials were collected for blood count, biochemical analyses, examination of abnormal sediment elements (EAS), and histopathological analysis. RESULTS: GI results showed development of edema, macroscopic alterations, and signs of bleeding in the bladder; in addition, lesions in the urothelium and hemorrhage were also found. GL24H and GM presented intact urothelium, without inflammatory reaction and hematological or biochemical urine alterations. CONCLUSION: Therefore, this study demonstrated that L. acidophilus presented uroprotective effect against the action of cyclophosphamide in both the short and long term.

Dexamethasone-cyclophosphamide pulse therapy outcomes comparing pemphigus vulgaris and pemphigus foliaceus groups in a Brazilian cohort study

Abstract Background Dexamethasone-cyclophosphamide pulse (DCP) and dexamethasone pulse (DP) have been successfully used to treat pemphigus, but DCP/DP outcomes comparing pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are scarce. Objective To compare DCP/DP outcomes in a Brazilian cohort of PV and PF patients according to demographic and clinical data. Methods Retrospective analytical cohort study, reviewing medical charts of PV and PF patients (for DCP/DP Phases I‒IV consult Pasricha et al.16‒18). Results 37 PV and 41 PF patients non responsive to usual treatments were included similarly for DCP or DP therapy. Disease duration was longer among PF before DCP/DP prescription (p < 0.001); PF required a higher number of monthly pulses to acquire remission in Phase I (median 10 and 6 pulses, respectively; p = 0.005). DCP/DP outcomes were similar in both groups: remission in 37.8% of PV and 34.1% of PF after completed DCP/DP cycles following a median of 13 months (1-56 months follow-up); failure occurred in 13.5% of PV and 14.6% of PF in Phase I; relapse in 13.5% of PV and 12.2% of PF, and dropout in 27% of PV and 24.4% of PF in Phases II to IV. Mild side effects were documented. Study limitations The severity of PV and PF disease was not assessed by score indexes. Conclusions PV and PF patients presented similar DCP/DP outcomes. DCP/DP should be initiated earlier in PF patients due to the longer duration of their disease in order to decrease the number of pulses and the duration of Phase I to acquire remission.

Linfoma de células B de alto grado de malignidad con morfología blastoide durante el embarazo: reporte de un caso / High-grade malignant B-Cell lymphoma with blastoid during pregnancy: a case report

Resumen ANTECEDENTES: Durante el embarazo es más común el linfoma de Hodking que el no Hodking; afecta, en promedio, a mujeres de 30 años (18-44 años) y más. Suele diagnosticarse alrededor de las 28 semanas de embarazo y está documentado que puede llegarse al término. Los esquemas de tratamiento pueden iniciarse en el posparto inmediato o, incluso, antes. La incidencia mundial del linfoma no Hodking es de 0.8 por cada 100,000 mujeres; se desconoce la supervivencia durante el embarazo. CASO CLINICO: Paciente de 34 años, con antecedentes obstétricos de tres embarazos, una cesárea y un aborto y el embarazo actual en curso de las 29 semanas, referida de la ciudad de Colima debido a un reporte de BI-RADS 3 en el ultrasonido de mama y un nódulo mamario palpable, con evidencia de múltiples tumoraciones en la zona hepática, esplénica y peripancreática. La biopsia tomada de las zonas de la lesión reportó: linfoma de células B de alto grado de malignidad, con morfología blastoide y expresión de C-MYC y BCL2. Además, la paciente se encontró con: anemia, dolor abdominal, múltiples nódulos hepáticos y adenopatías abdominales. Se decidió la interrupción del embrazo a las 30 semanas, con la obtención de un recién nacido, sin complicaciones. Enseguida se inició el tratamiento con rituximab-etopósido-prednisolona-vincristina-ciclofosfamida-doxorrubicina (R-EPOCH) con adecuada adaptación por la paciente. CONCLUSION: Puesto que la información bibliográfica de linfoma y embarazo es escasa el caso aquí reportado es relevante por su aporte. La atención multidisciplinaria favorecerá siempre el pronóstico de las pacientes.

Abstract BACKGROUND: Hodking's lymphoma is more common during pregnancy than non-Hodking's lymphoma; it affects, on average, women aged 30 years (18-44 years) and older. It is usually diagnosed around 28 weeks of pregnancy and is documented to be carried to term. Treatment regimens can be initiated in the immediate postpartum period or even earlier. The worldwide incidence of non-Hodking's lymphoma is 0.8 per 100,000 women; survival during pregnancy is unknown. CLINICAL CASE: 34-year-old patient, with obstetric history of three pregnancies, one cesarean section and one abortion and the current pregnancy in progress at 29 weeks, referred from the city of Colima due to a report of BI-RADS 3 on breast ultrasound and a palpable breast nodule, with evidence of multiple tumors in the hepatic, splenic and peripancreatic area. Biopsy taken from the lesion areas reported: high grade malignant B-cell lymphoma, with blastoid morphology and expression of C-MYC and BCL2. In addition, the patient was found to have: anemia, abdominal pain, multiple hepatic nodules and abdominal adenopathies. It was decided to terminate the pregnancy at 30 weeks, with the delivery of an uncomplicated newborn. Rituximab-Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (R-EPOCH) therapy was started immediately with adequate adaptation by the patient. CONCLUSION: Since bibliographic information on lymphoma and pregnancy is scarce, the case reported here is relevant for its contribution. Multidisciplinary care will always favor the prognosis of patients.

Febrile neutropenia incidence and the variable toxicity profile between brand and generic docetaxel in the adjuvant treatment of breast cancer with docetaxel and cyclophosphamide regimen

ABSTRACT Objective To assess the incidence of febrile neutropenia without primary granulocyte colony-stimulating factor prophylaxis in patients undergoing chemotherapy with adjuvant docetaxel and cyclophosphamide, and to evaluate the toxicity profile of brand-name docetaxel (Taxotere ® ) and the generic formulation. Methods This retrospective study was conducted using data obtained from electronic medical records of patients treated at a Brazilian cancer center. Patients with breast cancer who underwent adjuvant treatment between January 2016 and June 2019 were selected. Data were analyzed using chi-square and Fisher correlation of variables, and multivariate analyses were adjusted for propensity score. Results A total of 231 patients with a mean age of 55.9 years at the time of treatment were included in the study. The majority (93.9%) had luminal histology, 84.8% were at clinical stage I, and 98.2% had a good performance status. The overall incidence of febrile neutropenia in the study population was 13.4% (31 cases). The use of brand-name docetaxel (Taxotere ® ) was the only factor associated with febrile neutropenia occurrence (OR= 3.55, 95%CI= 1.58-7.94, p=0.002). Conclusion In patients with breast cancer who require treatment with adjuvant docetaxel and cyclophosphamide regimen, the toxicity profile differs between brand-name and generic docetaxel. Regardless of the formulation used, the incidence of febrile neutropenia was less than 20%, which may allow for the omission of primary prophylactic granulocyte colony-stimulating factor use in this setting.