Second Course Of Chemotherapy Research Articles

IMPACT OF CHEMOTHERAPY ON PROOXIDANT-ANTIOXIDANT STATUS IN PATIENTS WITH MULTIPLE MYELOMA AND CONCOMITANT CORONARY ARTERY DISEASE

Introduction. Multiple myeloma, an oncopathology that remains challenging to treat, is characterized by a 54% 5-year survival rate despite advancements in modern treatment strategies. Numerous studies have substantiated the correlation between high prooxidant concentrations and the progression of multiple myeloma. This progression is often associated with alterations in antioxidant defense mechanisms. Patients with coronary artery disease also experience changes in their antioxidant defense that may enhance the deleterious effects of active oxygen species and elevate the risk of chemotherapy-related organotoxic effects.
 The aim of this study is to investigate the specificities of the prooxidant-antioxidant status in patients with multiple myeloma and concomitant coronary artery disease during chemotherapy.
 Materials and methods. 42 patients with multiple myeloma were examined, 22 (52,5%) of them had concomitant coronary artery disease. According to the coronary artery disease, patients with multiple myeloma were divided into two groups. All patients obtain standard chemotherapy schemes. Assessment of the patients was performed four times: before and after the 1st and 5th chemotherapy course. TBA-reactants and catalase activity were measured in blood serum.
 Results. Both in I and II group of patients, TBA-reactants concentration in blood serum was increased in 1.85 (р1<0,0001) and in 2.35 (р1<0,0001) times respectively compare to healthy people before chemotherapy. Although in the patients with concomitant coronary artery disease TBA-reactants concentration in blood serum was increased in 1,28 (р2<0,0001) times compare to I group of patients. Simultaneously in II group of patients catalase activity was decreased in 1.28 (р4 <0,0001) times compare to healthy people and in 1,37 (р5 <0,0001) times compare to I group patients. Before the second course of chemotherapy in II group of patients, TBA-reactants level was increased in 1.03 (р<0.05) times compared to the first examination and in 1.27 (р<0.05) times compared to I group. In II group of patients, catalase activity was decreased in 1.24 (р<0.05) times compared to the first examination and in 1.38 (р<0.001) times compared to the II group. In II group of patients level of TBA-reactants was decreased in 1,13 (p<0,01) times compare to the first examination, but it was in 1,17(р<0,05) higher than TBA-reactants level in I group. Simultaneously catalase activity was decreased in 1.4 (р<0.05) times compare to the first examination.
 Conclusions. The progression of multiple myeloma is marked by the development of a prooxidant-antioxidant imbalance. In both the I and II patient groups, the level of TBA-reactants increased significantly by 1.85 (p<0.0001) and 2.35 (p<0.0001) times, respectively, compared to the reference value. The presence of concomitant coronary artery disease in multiple myeloma patients led to a 1.28-fold elevation in TBA-reactants levels (p<0.0001) compared to those without cardiovascular diseases. Simultaneously, catalase activity decreased by 1.37 times (p<0.0001) compared to patients without cardiovascular diseases.
 During chemotherapy, a progressive increase in the prooxidant-antioxidant imbalance was observed in multiple myeloma patients. This was evidenced by a 1.4-fold decrease in catalase activity (p<0.05) compared to the initial examination.

Neutrophil extracellular traps-associated markers in malignant neoplasms of the female reproductive system after surgical treatment and adjuvant chemotherapy

Introduction. Studies evidence about a relation between increased circulating free DNA (cfDNA) concentrations and chemotherapy, the majority of which have been focused on considering a tumor as a source of cfDNA. It has been suggested that neutrophils also contribute to this process, as cancer-related cfDNA characteristics resemble those of neutrophil extracellular traps (NETs). Therefore, the elevated concentration of cfDNA observed in chemotherapy patients may be associated with NETosis.Aim: assessment of NETosis markers in surgical treatment and adjuvant chemotherapy of patients with malignant neoplasms of the female reproductive system.Materials and Methods. A prospective non-randomized interventional controlled study was carried out by enrolling 111 patients with malignant breast diseases and female genital organs of various localizations and stages hospitalized for elective surgical treatment or chemotherapy course. The control group included 33 healthy women. 69 patients underwent surgical treatment. Adjuvant chemotherapy with paclitaxel and carboplatin was performed in 25 patients with ovarian cancer and 17 patients with breast cancer. In cancer patients, citrullinated histone H3 (citH3) and myeloperoxidase (MPO) were chosen as NETosis biomarkers allowing to distinguish NETs from other tumor-derived cfDNA thereby improving quality of research study. The concentration of NETosis markers was assessed before surgery or onset of chemotherapy upon admission to hospital and 14 days after surgery or 14 days after the second course of chemotherapy.Results. In all patients, the concentrations of NETosis markers before the start of therapy were significantly increased compared to the control group as well as 14 days after surgical treatment and 14 days after the second course of chemotherapy. However, in surgical patients, no significantly increased concentration of NETosis markers postvs. pre-surgery magnitude was observed. Upon that, patients underwent 2 courses of chemotherapy vs. baseline level were found to have significantly elevated magnitude of NETosis markers.Conclusion. The study revealed the relationship between administration of paclitaxel-containing chemotherapy in patients with ovarian cancer and breast cancer and a rise in NETs level. Chemotherapy is an essential component for management of patients with malignant neoplasms of the female reproductive system, therefore, development of new strategies to lower a risk of thrombosis and resistance to it is of crucial importance.

MYOCARDIAL INFARCTION UNDER METHOTREXATE IN A PATIENT WITH LOW RISK GESTATIONAL TROPHO BLASTIC NEOPLASIA: A CASE REPORT

Background: Methotrexate, an antifolateantimetabolite, finds extensive application in the field of oncology as well as for managingvariousautoimmunediseases. It isconsidered as backbone treatment for bothlow and high risk, trophoblasticgestationalneoplasia, as mono therapy or in combination withothercytotoxic agents.Whileitisconsideredcardioprotective, datas regardingmethotrexate-inducedcardiomyopathy are rare. we report the case of a woman, initiallydiagnosedwithlow-risk trophoblasticgestationalneoplasia, whosuffered a myocardial infraction after the second course of methotrexate. Case Presentation:A 47-year-old woman, with no othercomorbidities, wasinitiallydiagnosedwith a low-risktrophoblasticgestationalneoplasia, characterized by a Bhcg value of 12,022. Shewasundergoingmethotrexatemonotherapy for the condition. Following the second course of chemotherapy, the patient experiencedchest pain, and an electrocardiogramrevealed an elevation of the ST segment. As a result, thrombolytictreatmentwasadministered at H9 of pain onset.Due to the uncertaintysurrounding the relationbetween Methotrexate and the myocardialinfarction and consideringpotential interactions betweennonsteroidal anti-inflammatorydrugs (NSAIDs) and methotrexate, a decisionwas made to switch to Actinomycin D.The evolutionwas favorable, the patient isstillunder surveillance aftertwoyears of follow up. Conclusion:This case report highlights a possible methotrexateinducedmyocardial infraction. Inthis setting our attitude was to switch for anotherdrug, whichwasverywelltolerated, withgood oncologicincome for our patient.

Mitochondrial apoptosis-related gene polymorphisms are associated with responses to anthracycline-based chemotherapy in acute myeloid leukaemia.

Although anthracyclines are the first-line chemotherapy drugs for treating non-M3 acute myeloid leukaemia (AML), their efficacy remains limited. It is important to identify factors that influence the efficacy of anthracyclines against AML. Mitochondrial apoptosis-related genes play significant roles in the pathogenesis, treatment, and prognosis of AML. We utilized the CRISPR/Cas9 screening system to find AML anthracyclines resistance related genes and several mitochondrial apoptosis-related genes, such as BCL2L11, CASP8, TP63, TP53BP2, PLAUR, SOD2, BNIP3L, and MMP9, were screened out. Then, DNA from 279 patients with AML and 321 healthy individuals were extracted and the contributions of single nucleotide polymorphisms (SNPs) within these genes to the patient's chemotherapy response, susceptibility to AML, and overall survival were investigated. Our findings indicated that SNP rs4251864 in the PLAUR gene was associated with an increase in complete remission after anthracycline-based induction chemotherapy. rs4880 in SOD2 was associated with the response to the second course of chemotherapy, whereas rs3789068 in BCL2L11 was associated with susceptibility to AML. Our results about the association of SNPs in mitochondrial apoptosis-related genes with the response to anthracycline-based chemotherapy in AML provide an important reference for predicting the treatment outcomes in patients with this disease.

Restratifying the prognosis of acute myeloid leukemia patients with CEBPA double mutations based on CSF3R mutations and measurable residual disease

Objective: This investigation aims to assess the impact of CSF3R mutations and the presence of measurable residual disease (MRD) on the prognosis of patients with CEBPA double mutations who have acute myeloid leukemia (AML) . Methods: The prognostic significance of these two factors was examined in the present study, which included 66 patients with complete genetic mutations and sequential MRD information. Results: Following the second course of chemotherapy, the MRD status and CSF3R mutations of these patients were linked to their long-term prognosis. CSF3R mutated patients showed inferior relapse-free survival (RFS) (5-year RFS: 15.2% vs 38.7% , P=0.006) and overall survival (OS) (5-year OS: 18.2% vs 60.6% , P=0.038) compared with those with wild-type CSF3R. After the second course of chemotherapy, patients with negative MRD had an RFS of 64 months and an OS of not reaching, which was significantly longer than that of patients with positive MRD (15 and 48 months, and the P value were 0.004 and 0.050, respectively) . CSF3R mutations (HR=0.317, 95% CI 0.129-0.779, P=0.012) , WT1 mutations (HR=0.304, 95% CI 0.115-0.804, P=0.016) , and NRAS mutations (HR=0.153, 95% CI 0.061-0.385, P<0.001) were all independently associated with a poor prognosis for RFS, and CSF3R mutations and positive MRD tended to be independently associated with a poor prognosis for OS, according to the results of a Cox proportional-hazards model analysis (P values were 0.071 and 0.088, respectively) . The patients were divided into three groups based on their CSF3R mutation status and MRD status following treatment: wide-type CSF3R and negative MRD, mutated CSF3R or positive MRD, and mutated CSF3R and positive MRD, which showed significantly different RFS (P<0.001) and OS (P=0.006) . Conclusion: Both CSF3R mutations and positive MRD were associated with poor outcome in AML patients with CEBPA double mutations. An integrity model based on these two factors may be beneficial for accurately evaluating the prognosis of these patients.

The effect of the surgical treatment in the complex management on life expectancy of thymic Hodgkin's lymphoma

The result of treatment of primary Hodgkin's lymphoma lesion of the thymus gland of a 26-year-old patient is presented. At the preoperative stage of examination, tumor maligna cells were obtained during puncture of mediastinal formation. The diagnosis is malignant tumor of the mediastinum. Considering this, a surgical treatment was performed-radical removal of the mediastinal tumor. After the study of the postoperative drug, a clinical diagnosis was made: lymphogranulomatosis, a massive (bulky) tumor lesion of the mediastinum, stage IIХ, after surgical treatment. First course of ABVD chemotherapy was performed 28 days after the operation. When performing the second course of chemotherapy according to the same scheme, the patient developed complications in the form of moderate leukocytopenia (leukocytes, 0.9109/l) and stomatitis. Special treatment was discontinued, and the patient was observed by an oncologist in the polyclinic of an oncological dispensary.&#x0D; At the next examination, which was performed 11 months later, a relapse of the disease was identified. Considering the preservation of persistent leukopenia (leukocytes, 3.0109/l), it was decided to conduct six courses of ABVD polychemotherapy with prednisone, against the background of G-CSF. At this stage of oncology, the main method of treating Hodgkin's lymphoma is chemo-hormone therapy in combination with radiation therapy. The performed non-standard complex treatment is radical surgical removal of a mediastinal tumor followed by polychemotherapy. It allowed 4 years after the completion of treatment to know motherhood, which did not affect the patient's health. As indicated by the long relapse, free period of the disease is 16 years, and life expectancy is 18 years.

Une cause originale d’insuffisance rénale aiguë au cours du myélome multiple : néphrite interstitielle aiguë induite par le lénalidomide

IntroductionLenalidomide is an immunomodulatory drug widely used in the treatment of multiple myeloma. Several cases of nephrotoxicity have been reported, but few have been documented histologically. Case presentationWe report a case of acute interstitial nephritis to lenalidomide in a 62-year-old patient with multiple myeloma after administration of the second course of chemotherapy according to the protocol combining bortezomib, lenalidomide and dexamethasone. The outcome was quickly favorable after stopping lenalidomide, with corticosteroid therapy. ConclusionLenalidomide may be responsible for acute interstitial nephritis. When acute kidney injury occurs in myeloma, the nephrotoxicity of therapeutic agents should be considered in addition to the common causes of kidney failure. The chronology of events and the histological data are essential and guide the specific management.

Phase II study of S‐1 plus cisplatin with concurrent radiotherapy for locally advanced thymic carcinoma: Results of the LOGIK1605/JART‐1501 study

BackgroundCombination chemotherapy is used to treat advanced thymic carcinoma; however, the effects are insufficient.MethodsPreviously untreated patients with unresectable locally advanced thymic carcinoma received two cycles of 80 mg/m2/day S‐1 orally on days 1–14 plus 60 mg/m2/day cisplatin intravenously on day 1, and concurrent radiotherapy (60 Gy).ResultsThree patients were enrolled into the study. Toxicity and survival were assessable in all patients, but the treatment response was only assessable in one patient. The study was terminated because of poor case recruitment. The patients' characteristics were as follows: male/female = 2/1; PS 0/1 = 2/1; median age (range) = 59 (55–72); and stage III/IV = 2/1. The patient in which the treatment response was assessed exhibited SD (response rate: 0%). In both nonevaluable cases, the second course of chemotherapy was judged to be post‐protocol treatment because it was delayed by ≥14 days, but a CR and PR were achieved after the end of the study, respectively. G4 leukopenia/neutropenia and G3 febrile neutropenia occurred in one patient each (33%). The median time to tumor progression was 17.6 months, and the 1‐, 2‐, 3‐, and 4‐year survival rates were 67, 33, 33, and 33%, respectively. The median overall survival time was not reached, and the 1‐, 2‐, 3‐, and 4‐year survival rates were 100, 67, 67, and 67%, respectively.ConclusionsAlthough it was difficult to recruit patients, there was a long‐term survivor >4 years who appeared to have achieved a CR, indicating that such chemoradiotherapy may be effective against locally advanced thymic carcinoma.

Prolonged Surgical Interval Following Chemotherapy in a Patient With Idiopathic Subglottic Stenosis (iSGS): Case Report and Brief Review of Literature

Objective: To report a case of a patient with idiopathic subglottic stenosis (iSGS) who no longer required surgical intervention for her disease following a chemotherapy regimen of carboplatin and doxorubicin for ovarian cancer. A brief review of the literature and discussion on the possible mechanism of action of chemotherapy agents affecting fibrosis is included. Methods: Case report and review of literature. Results: A 71-year-old Caucasian woman with iSGS was managed with serial endoscopic excision and dilation (n = 5) from 2013 to 2017 with an average dilation interval of 12.3 months. After a course of doxorubicin and carboplatin to treat her ovarian cancer, we observed that her airway stenosis surprisingly stabilized, and has no longer required a surgical dilation for 45 months, which signifies an increase of 33 months when compared to her averaged dilation interval (12.3 months) prior to her second course of chemotherapy. Conclusion: We present an iSGS patient whose fibrosis was arrested following carboplatin/doxorubicin treatment. While a single case, a possible mechanism is carboplatin/doxorubicin’s inhibition of pathologic CD4 lymphocytes that propagate laryngotracheal fibrosis. Further investigation of like mechanisms may allow for translation of local agents with inhibitory effects on CD4+ cells and/or fibroblasts as a novel therapy for airway fibrosis.

DEPENDENCE OF CHANGES IN THE HYGIENIC CONDITION OF THE ORAL CAVITY AND PERIODONTIUM IN CHILDREN WITH MALIGNANT TUMORS ON THE DURATION OF POLYCHEMYTHERAPY AND QUANTITIES OF CYTOSTATIC DRUGS

It is known that the course of cancer and chemotherapy adversely affect the components of homeostasis of the oral cavity, which causes stomatotoxicity. However, scientific publications have not yet provided generalized results of research on the pathogenetic mechanisms of the dental pathology formation during chemotherapy, which constitutes the relevance of this publication.&#x0D; The aim of the research was to study the effect of different regimens of the second course of chemo- therapy on the hygienic condition of the oral cavity and periodontium in children with malignant tumors of the abdominal cavity.&#x0D; The dissatisfaction with our results obtained after the first course of chemotherapy on various regimens prompted us to further research. A survey of two previously formed clinical groups was performed. All of them resumed the treatment in the oncohematology department of the Poltava Children's City Clinical Hospital following a 3-4 week break between courses. Each patient was treated according to an individual program but in the absence of dental care.&#x0D; The dental status was assessed using the Green-Vermillion, Papillary-Marginal-Alveolar (PMA), and Pa- pilla Bleeding Index.&#x0D; The study of cytograms from the surface of the gingival margin of the frontal part of the mandible was carried out taking into account the methodology developed by our department's staff. The calculation was per- formed in 10 visual fields. Statistical processing was performed according to standard conditions.&#x0D; Research results and their discussion. It should be noted that in the comparative aspect, the indexes of Green-Vermillion, PMA, and RВI at the end of the first year were 1,8, 1,3, and 1,6 times worse than in the second observation group which received more cytostatic drugs.&#x0D; At the end of the second course of chemotherapy, the dryness of the mucous membrane accompanied by a decrease in oral fluid, which became viscous, was observed in 14 children (70,0%) of the first and 18 of the second group (85.7%). In addition, 15 people in the first group (75,0%) and 19 in the second one (90,4%) complained of pain and bleeding gums, which worsened when eating. At the same time, all children noted pain in the muscles that are adjacent to the lower jaw and involved in articulation.&#x0D; On external examination, only 2 children of the first (10,0%) and 1 of the second group (5%) had a red normal-coloured lip border, while the rest had exfoliation, cracks, and angular cheilitis. The oral mucosa mostly looked pale and pasty, except for 7 people of the second group (35,0%), who had manifestations of erythema. Localized erosions covered with fibrinous plaque were detected in 4 of these patients (20,0%) on the background of erythema. In addition, 12 children (60,0%) of the first group and 19 children of the second one (85.7%) showed swelling and redness of the gingival marginal edge, and the probing of the gingival sulcus provoked bleeding in all children of both groups.&#x0D; Green-Vermillion indexes increased by 1,5 and 1,7 times in the first and second groups, PMA increased by 1,4 times in both groups, and RВI was 1,4 and 1,5 times higher in the respective compared groups.&#x0D; The examination of cytograms revealed more pronounced changes in the second group where the epithelium with signs of intermediate stages of the differentiation prevailed. There was increased desquamation of the superficial layer of the gums and the increased number of peripheral blood elements, especially destroyed neutrophils.&#x0D; Thus, the generalization of the results obtained at the end of the second course of chemotherapy showed that the Green-Vermillion index was 1,8 times higher, and PMA and SВI indices were 1,4 times higher in the second observation group which received more cytostatics. That is, the severity of the manifestations of dental status disorders is directly proportional to the severity of the regimen.&#x0D; Conclusion. The prolongation of the second course of chemotherapy in children with abdominal malignant tumors provoked a significant deterioration of dental status. Major changes occurred in the group of children who received more cytostatic drugs simultaneously, which requires a balanced approach to designing differentiated treatment plans and prevention measures depending on the complexity of antitumor therapy regimens.&#x0D; Prospects for further research. The obtained results indicate the need to develop a set of differentiated&#x0D; treatment and prevention measures aimed at eliminating or improving changes in children that occur in the oral cavity under the influence of polychemotherapy.

The effect of serial administration of doxorubicin at the level of main female sex hormones in the experiment

Annotation. The article presents the results of an experimental study of the dynamics of changes in the main female sex hormones with serial use of doxorubicin. The experiments were performed on 45 adult female white rats. The levels of antimullerian hormone, estradiol and follicle-stimulating hormone were studied. In total, 4 courses of chemotherapy were performed with an interval of 3 weeks. After each course of chemotherapy, the hormonal status of the experimental animals was studied twice: during the first proestrus after the course (to determine the acute ovarian toxicity of the drug) and during the last proestrus before the next course of chemotherapy (to study ovarian function restoration). The obtained data were processed using the statistical software package SPSS 20.0 for Windows. The dynamics of the levels of studied sex hormones with serial administration of doxorubicin is characterized by wavy dynamics with deterioration immediately after chemotherapy and partial recovery during the period between adjacent courses. Ovariotoxicity of doxorubicin when serial administration in therapeutic doses in the experiment is manifested by significant changes in the levels of major female sex hormones after the second course of chemotherapy.

CASE REPORT OF MARGINAL ZONE LYMPHOMA DETECTED WHILE INVESTIGATING ETIOLOGY FOR HEMOSTASIS DISORDER

In this article, we wanted to present our case in which we detected SMZL during examining for defects in coagulation tests and correlated the PT and aPTT elevation with the development of inhibitors against coagulation factors related to this disease. The PT and aPTT values of the patient diagnosed with MZL did not improve in the mixing test, and no other etiology was found. With the second course of chemotherapy, the patient's values improved.

High dose and hepatobiliary dysfunction are associated with hand-foot syndrome in patients with lymphoma using pegylated liposomal doxorubicin: a retrospective study

PurposeIn clinical practice, the risk factors for pegylated liposomal doxorubicin-related hand-foot syndrome remain unclear. The purpose of this study was to determine the risk factors associated with hand-foot syndrome in patients with lymphoma using pegylated liposomal doxorubicin.MethodsThis retrospective descriptive analysis included patients with lymphoma who received PLD treatment (≥ 2 cycles of chemotherapy) at our cancer centre and had complete follow-up data from January 2016 to February 2020. Clinical, laboratory data, as well as the occurrence of hand-foot syndrome (incidence, location, severity, impact on follow-up chemotherapy) were obtained. The primary end point was the incidence of hand-foot syndrome, which was classified according to the “Common Terminology Criteria for Adverse Events” (Version 4.0). A multivariate logistic regression analysis was used to identify risk factors for hand-foot syndrome in patients with lymphoma using doxorubicin liposomes.FindingsA total of 167 patients met the inclusion criteria. 58 developed HFS, of which 45 occurred after the second course of chemotherapy. The multivariate logistic regression analysis revealed that a dose increase of pegylated liposomal doxorubicin and hepatobiliary dysfunction were significantly associated with an increased risk for hand-foot syndrome(dose intensity, OR = 6.479; 95% CI, 1.431–29.331 [P = 0.015]; history of gallstones, OR = 14.144, 95% CI, 1.512–132.346 [P = 0.020]; alanine aminotransferase, OR = 1.194, 95% CI, 1.056–1.350 [P = 0.005]; aspartate aminotransferase, OR = 1.162, 95% CI, 1.010–1.336 [P = 0.035]; and glutamine transpeptidase, OR = 1.092, 95% CI, 1.016–1.174 [P = 0.018]).ImplicationsThese findings contribute to the risk assessment of patients with lymphoma before using pegylated liposomal doxorubicin. For patients with the above risk factors, preventive measures should be taken in advance to reduce the incidence of HFS.

Prevention of Dysbiosis Complications with Autologous Fecal Microbiota Transplantation (auto-FMT) in Acute Myeloid Leukemia (AML) Patients Undergoing Intensive Treatment (ODYSSEE study): First Results of a Prospective Multicenter Trial

Introduction. There is a growing body of evidence highlighting the possible interactions between the microbiota and cancer. However, little is known about the consequence on the microbiota of the intensive chemotherapy in patients with AML. Indeed, intensive treatments of AML are known to negatively impact gut microbiota composition; it is measured by a deep shutdown of diversity indices (eg. Simpson), also called dysbiosis. Decrease in microbiota diversity may impact the immune system and may have consequences on the outcome of AML patients. Therefore, development of strategies to manipulate the gut microbiota may minimize treatment-related complications and potentially improve outcomes. With this background, we developed a single arm prospective phase I/II multicenter trial (ClinicalTrials.gov Identifier: NCT02928523) aiming to evaluate use of auto-FMT in AML patients treated with intensive chemotherapy and antibiotics.Patients and methods. For this purpose, at the time of admission and AML diagnosis, patients were requested to donate stools that were screened according to standard recommendations. If deemed appropriate according to protocol criteria, stools were conditioned, processed with a patented diluent, and stored frozen until transplantation performed after recovery from aplasia and before the second course of chemotherapy. The auto-FMT inoculum was administered as an enema, and was prepared for each individual patient according to standardized and reproducible processes developed by the sponsor of the trial. The primary endpoint was the recovery of microbiota diversity and correction of dysbiosis after auto-FMT. The microbiome diversity and richness were measured at baseline (prior to induction chemotherapy), after induction chemotherapy, and around 10 days post-auto-FMT. Microbiome restoration was assessed at the genus and species level, on the basis of metagenomic results obtained for the 3 sequential samples. Illumina TruSeq Nano Prep kit was used for sequence-library preparation and samples were sequenced on HiSeq 2500 2x125bp, 40 million reads/sample. Secondary objectives included monitoring of the immune system, safety and feasibility of auto-FMT, and a set of parameters exploring the impact of auto-FMT on different patient-related outcomes (clinical status and recovery).Results. At time of this planned intermediate analysis, 35 AML patients eligible for intensive induction chemotherapy (intermediate and unfavorable karyotype) with a median age of 53 (range, 23-67) years were screened. The current interim results concern the 9 patients who fulfilled all criteria for inclusion and were able to proceed to auto-FMT after intensive induction therapy (“3+7” induction or equivalent). Prior to the start of induction chemotherapy, the mean baseline Simpson index (measured at genus level) was 0.836 (95%CI, 0.755-0.987). At the end of induction chemotherapy, a highly significant decrease of -0.519 ([-0.677, -0.361], p<.001) was observed, highlighting the deleterious impact on the gut microbiome of intensive chemotherapy and the multiple antibiotics received during induction. Per protocol, these patients were able to receive an auto-FMT prior to receiving their subsequent consolidation chemotherapy. Auto-FMT was well tolerated, only one serious adverse event was reported: a case of E. Coli infection which resolved after appropriate antibiotherapy. After auto-FMT, the Simpson index returned back to baseline level (difference=0.023 ([-0.135, 0.181], p=0.776), and virtually identical results were obtained when Simpson was measured at species level. The ongoing immunomonitoring of these 9 patients suggested data correlated with the dysbiosis correction.Conclusions. This first multicenter prospective trial reached its primary endpoint in all analyzed cases thus far, and established the capacity of auto-FMT to correct dysbiosis and restore a normal microbiota in AML patients receiving intensive induction chemotherapy and wide-spectrum antibiotics. Correlations with clinical and immune parameters that may influence AML outcome are currently being analyzed and will be presented. The apparent modulation of the immune system through microbiota restoration is a promising venture in the treatment of AML patients warranting further investigations. (The trial was funded by MaaT Pharma whose product was tested in this protocol). DisclosuresMohty:Sanofi: Honoraria, Speakers Bureau. Recher:Celgene, Sunesis, Amgen, Novartis: Research Funding; Novartis, Celgene, Jazz, Sunesis, Amgen: Consultancy. Plantamura:Maat Pharma: Employment. Lehert:Maat Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Doré:Maat Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Chemotherapy-induced myasthenic crisis in thymoma treated with primary chemotherapy with curative intent on mechanical ventilation: a case report and review of\xa0the literature

BackgroundThymoma is an uncommon cancer often associated with myasthenia gravis, an autoimmune disorder of the neuromuscular junction characterized by muscular fatigability. In patients with advanced nonmetastatic thymoma, primary chemotherapy may be required to induce tumor shrinkage and to achieve radical resection. Cancer chemotherapy has been anecdotally reported as a trigger factor for worsening of myasthenia gravis in thymic epithelial cancers. The study of uncommon cases of chemotherapy-related myasthenic crisis is warranted to gain knowledge of clinical situations requiring intensive care support in the case of life-threatening respiratory failure.Case presentationWe report a case of an 18-year-old Caucasian woman with advanced Masaoka-Koga stage III type B2 thymoma and myasthenia gravis on treatment with pyridostigmine, steroids and intravenous immunoglobulins, who developed a myasthenic crisis 2 hours after initiation of cyclophosphamide/doxorubicin/cisplatin primary chemotherapy. Because of severe acute respiratory failure, emergency tracheal intubation, mechanical ventilation, and temporary (2 hours) discontinuation of chemotherapy were needed. Considering the curative intent of the multimodal therapeutic program, we elected to resume primary chemotherapy administration while the patient remained on mechanical ventilation. After 24 hours, the recovery of adequate respiratory function allowed successful weaning from respiratory support, and no further adverse events occurred. After 3 weeks, upon plasma exchange initiation with amelioration of myasthenic symptoms, a second course of chemotherapy was given, and in week 6, having documented partial tumor remission, the patient underwent radical surgery (R0) and then consolidation radiation therapy with 50.4 Gy in 28 fractions in weeks 15–20.ConclusionsThis case report, together with the only four available in a review of the literature, highlights that chemotherapy may carry the risk of myasthenic crisis in patients affected by thymoma and myasthenia gravis. To our knowledge, this is the first reported case of chemotherapy continuation on mechanical ventilation in a patient with chemotherapy-induced myasthenic crisis requiring tracheal intubation. The lesson learned from the present case is that, in selected cases of advanced thymoma, the paradoxical worsening of myasthenia gravis during chemotherapy should not be considered an absolute contraindication for the continuation of primary chemotherapy with curative intent.

Comparison of Autologous Bone Marrow Transplantation and Intensive Chemotherapy as Postremission Therapy in Adult Acute Myeloid Leukemia

AbstractThree intensive consolidation strategies are currently proposed to younger adults with acute myeloid leukemia (AML) in first complete remission (CR): allogeneic or autologous bone marrow transplantation (BMT) and intensive consolidation chemotherapy (ICC). Patients aged 15 to 50 years with de novo AML received an induction treatment with 7 days of cytarabine and either idarubicin or rubidazone. After achievement of a CR, patients up to the age of 40 and having an HLA-identical sibling were assigned to undergo an allogeneic BMT. All the other patients received a first course of ICC with high-dose cytarabine and the same anthracycline as for induction. They were then randomly assigned to either receive a second course of ICC with amsacrine and etoposide or a combination of busulfan and cyclosphosphamide followed by an unpurged autologous BMT. Of 517 eligible patients, 367 had a CR, but only 219 (59.5%) actually received the planned intensive postremission treatment (73 allogeneic BMT, 75 autologous BMT, and 71 ICC). With a median follow-up of 62 months, the 4-year disease-free survival (DFS) of the 367 patients in CR was 39.5%. The 4-year overall survival (OS) of the 517 eligible patients was 40.5%. In multivariate analysis, DFS and OS were influenced only by the initial white blood cell count and by the French-American-British classification. The type of postremission therapy had no significant impact on the outcome. There was no difference in the 4-year DFS and OS between 88 patients for whom an allogeneic BMT was scheduled (respectively, 44% and 53%) and 134 patients of the same age category and without an HLA-identical sibling (respectively, 38% and 53%). Similarly, there was no difference in the outcome between autologous BMT and ICC. The 4-year DFS was 44% for the 86 patients randomly assigned to autologous BMT and 40% for the 78 patients assigned to ICC (P = .41). The 4-year OS was similar in the two groups (50% v 54.5%, P = .72). The median duration of hospitalization and thrombocytopenia were longer after autologous BMT (39 v 32 days, P = .006, and 109.5 v 18.5 days, P = .0001, respectively). After a first course of ICC, a second course of chemotherapy is less myelotoxic than an unpurged autologous BMT but yields comparable DFS and OS rates.

Large B-cell lymphoma with IRF4 rearrangement: a special tonsillar lymphoma in children

ObjectiveTo identify the clinicopathological features and prognosis of large B-cell lymphoma(LBCL) with interferon regulation factor 4 (IRF4) rearrangement. MethodsWe retrospectively analyzed the medical records of four patients from Children’s Hospital of Fudan University diagnosed with LBCL with IRF4 rearrangement during Sep. 2014 to Oct. 2018, and performed a literature review. ResultsFour patients had an average age of 5.7 years. The median duration from presentation to final diagnosis was 25.7 days. All 4 patients were admitted to the hospital due to severe snoring with no causes. The patients showed enlarged lymph nodes in the neck without tenderness. All 4 cases presented as localized disease (St-jude stage II). Lactate dehydrogenase (LDH) and serum albumin were all in the normal range. Morphology showed that normal lymphoid follicles were diffusely invaded by consistent, medium-sized large cells with obvious nucleoli. CD20, CD79α, PAX5, CD10 and BCL6 were diffusely positive. Neoplastic cells were also strongly positive for MUM1 and Ki-67. IRF4 gene rearrangement was detected as positive by IRF4 dual-color break-apart probe. Four patients underwent routine chemotherapy post bilateral tonsillectomy operation. Three achieved complete remission (CR) while the newly diagnosed one is during the second course of chemotherapy. ConclusionsTonsillar LBCL with IRF4 rearrangement in children presents distinct clinicopathologic and molecular genetic features, and it usually has a favorable outcome.

A case of acute monocytic leukemia complicated with multiple myeloma

A case of acute monocytic leukemia complicated with multiple myeloma

Effect of exercise during adjuvant chemotherapy for breast cancer.

6524 Background: In 2018, an estimated 266,120 women faced the challenge of living with breast cancer and approximately 40,920 died from their disease. Nearly 100% of these women experienced significant treatment related side effects that negatively impact quality of life (QOL). Exercise has repeatedly demonstrated to alleviate many of the side effects, improve QOL, and decrease cancer recurrence and mortality. In spite of this evidence, women do not maintain exercise during treatment for breast cancer. The purpose of this randomized controlled trial was to determine the effectiveness of exercising the day chemotherapy is administered on 1) the persistence with an exercise program, 2) side effects, and 3) QOL. Methods: Eligible women were randomly assigned to a control or experimental group. As part of their treatment plan, all participants were referred to one of 14 community-based exercise centers to exercise. Experimental group also exercised at one of two cancer centers each day chemotherapy was administered. Outcome measures include exercise retention and chemotherapy, completion; cancer-related fatigue, nausea/vomiting, peripheral neuropathy, weight gain, and QOL. Outcome measures were assessed prior to every second course of chemotherapy and 3- and 6-months post-chemotherapy. Results: 273 women with Stage I-III breast cancer receiving chemotherapy were enrolled in the study. The number of participants who withdrew from exercise was higher among those in the control group (n= 16; 12.4%) compared with those in the experimental group (n = 10; 6.9%). At cycle 5, those in the experimental group reported less motor peripheral neuropathy than those in the control group (p = .018) and higher physical well-being scores than those in the control group (p = .047). Conclusions: The highest impact of the intervention was on attrition from exercise. Since participants in both the control and experimental groups exercised throughout chemotherapy, it is not surprising that the groups performed comparably with regard to side effects and QOL. Given the positive effects exercise has demonstrated on persons receiving cancer treatment in numerous studies, having patients exercise in the cancer center on the day of chemotherapy is a significant step toward engaging persons receiving chemotherapy in an exercise program.

The novel translocation of t (1;21) in multiple myeloma with poor prognosis

Objective: Multiple myeloma (MM) is characterized as the neoplastic proliferation of plasma cells producing a monoclonal paraprotein. The aim of this paper is to report complex karyotype that leads to a fatal clinical course in a patient with MM. Case: A 48-year-old male patient was diagnosed as MM free lambda. The karyotype of the patient was 46, XY, t(1;21) (p11;p11), del(3) (q25;q29), del(6) (q24;q26), t(11;14) (q13;q32), del(13) (q14;q21) in cytogenetic evaluation. Vincristine, doxorubicin and dexamethasone were started. The creatinine levels increased after the second course of chemotherapy, the chemotherapy protocol was switched to bortezomib and dexamethasone. Patient was admitted to the emergency department with pneumonia after the second chemotherapy cycle. Despite using broad spectrum antibiotics and oxygen support, he died after the development of sepsis syndrome. Conclusion: The anomaly of t (1;21) (p11;p11), that we detected in this case was detected in a case with MM for the first time and this anomaly has not been detected between these breaking points in any malignancies before. Although the prognostic impact of this unique anomaly may be unclear, further studies are needed to evaluate the effect of cytogenetic anomalies on prognosis of multiple myeloma.