RÉSUMÉ
Thrombosis is a well-recognized complication of asparaginase therapy for acute lymphoblastic leukemia (ALL), associated with the depletion of antithrombin (AT). Following a high incidence of thrombotic episodes during induction therapy for ALL in our tertiary referral center, we prospectively instituted a protocol of AT replacement. Forty-five consecutive adolescents and adults with ALL treated with asparaginase-containing phase I induction protocols were included in this observational study. Fifteen received standard therapy with no replacement; the subsequent 30 were managed with the protocol described. One or more low AT levels (<70 iu/dl) were recorded in 76% of patients in the cohort managed using the protocol, resulting them in receiving an AT replacement. There was a significant reduction in the incidence of thrombosis with this strategy (0/30 vs. 5/15, p < 0.001). We suggest that such a strategy should be studied in a prospective randomized sub-study within the context of a national ALL trial.
Sujet(s)
Antinéoplasiques/effets indésirables , Antithrombiniques/usage thérapeutique , Asparaginase/effets indésirables , Leucémie-lymphome lymphoblastique à précurseurs B et T/complications , Thrombose/traitement médicamenteux , Thrombose/étiologie , Adolescent , Adulte , Sujet âgé , Antinéoplasiques/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Asparaginase/usage thérapeutique , Association de médicaments , Femelle , Humains , Mâle , Adulte d'âge moyen , Leucémie-lymphome lymphoblastique à précurseurs B et T/diagnostic , Leucémie-lymphome lymphoblastique à précurseurs B et T/traitement médicamenteux , Études rétrospectives , Thrombose/prévention et contrôle , Résultat thérapeutique , Jeune adulteRÉSUMÉ
Optical coherence tomography (OCT) is a high-resolution, nondestructive imaging modality that enables time-serial assessment of adenoma development in the mouse model of colorectal cancer. In this study, OCT was utilized to evaluate the effectiveness of interventions with the experimental antitumor agent α-difluoromethylornithine (DFMO) and a nonsteroidal anti-inflammatory drug sulindac during early [chemoprevention (CP)] and late stages [chemotherapy (CT)] of colon tumorigenesis. Biological endpoints for drug interventions included OCT-generated tumor number and tumor burden. Immunochistochemistry was used to evaluate biochemical endpoints [Ki-67, cleaved caspase-3, cyclooxygenase (COX)-2, ß-catenin]. K-Ras codon 12 mutations were studied with polymerase chain reaction-based technique. We demonstrated that OCT imaging significantly correlated with histological analysis of both tumor number and tumor burden for all experimental groups (P < 0.0001), but allows more accurate and full characterization of tumor number and burden growth rate because of its time-serial, nondestructive nature. DFMO alone or in combination with sulindac suppressed both the tumor number and tumor burden growth rate in the CP setting because of DFMO-mediated decrease in cell proliferation (Ki-67, P < 0.001) and K-RAS mutations frequency (P = 0.04). In the CT setting, sulindac alone and DFMO/sulindac combination were effective in reducing tumor number, but not tumor burden growth rate. A decrease in COX-2 staining in DFMO/sulindac CT groups (COX-2, P < 0.01) confirmed the treatment effect. Use of nondestructive OCT enabled repeated, quantitative evaluation of tumor number and burden, allowing changes in these parameters to be measured during CP and as a result of CT. In conclusion, OCT is a robust minimally invasive method for monitoring colorectal cancer disease and effectiveness of therapies in mouse models.
Sujet(s)
Antimétabolites antinéoplasiques/administration et posologie , Cytarabine/administration et posologie , Mobilisation de cellules souches hématopoïétiques , Lymphome à cellules du manteau/traitement médicamenteux , Antimétabolites antinéoplasiques/effets indésirables , Cytarabine/effets indésirables , Transplantation de cellules souches hématopoïétiques , Humains , Lymphome à cellules du manteau/thérapie , Transplantation homologue , Résultat thérapeutiqueSujet(s)
Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Lymphome à cellules du manteau/traitement médicamenteux , Anticorps monoclonaux d'origine murine/usage thérapeutique , Cyclophosphamide/usage thérapeutique , Doxorubicine/usage thérapeutique , Femelle , Humains , Mâle , Prednisone/usage thérapeutique , Rituximab , Vincristine/usage thérapeutiqueRÉSUMÉ
Clinically and biologically, nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) has much more in common with germinal-center derived B-cell non-Hodgkin lymphoma (NHL) than with classical Hodgkin lymphoma (cHL). Management of NLPHL remains controversial. In a 14-year multicenter series, 69 cases were analyzed, and the median follow-up was 53 months (range 11-165.) B-symptoms were present in only 4.3% of patients, and 81.1% of patients had stage I/II disease. Treatment was with radiotherapy (53.6%), chemotherapy (21.7%), combined modality (17.4%), and observation (7.2%). In all, 10.1% of patients relapsed and 2.9% of patients developed high-grade transformation to DLBCL. All relapses and transformations were salvageable. No patient died of their disease. The 5-year relapse-free survival was 92%, transformation-free survival 98.4%, and overall survival 100%. We conclude that NLPHL behaves as a distinct clinical entity, often presenting at an early stage without risk factors. It has an excellent outcome. It may be possible, in early-stage disease, to reduce the intensity of therapy in NLPHL, to single-modality radiotherapy, without affecting OS.
Sujet(s)
Maladie de Hodgkin/anatomopathologie , Maladie de Hodgkin/thérapie , Noeuds lymphatiques/anatomopathologie , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Enfant , Association thérapeutique , Femelle , Études de suivi , Maladie de Hodgkin/classification , Maladie de Hodgkin/mortalité , Humains , Lymphocytes/anatomopathologie , Mâle , Adulte d'âge moyen , Pronostic , Radiothérapie , Écosse , Analyse de survie , Résultat thérapeutique , Jeune adulteSujet(s)
Amyloïdose/traitement médicamenteux , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Vertèbres cervicales , Tumeurs du rachis/traitement médicamenteux , Sujet âgé , Acides boroniques/administration et posologie , Bortézomib , Dexaméthasone/administration et posologie , Humains , Imagerie par résonance magnétique , Mâle , Pyrazines/administration et posologieRÉSUMÉ
Hodgkin lymphoma (HL) is an unusual malignancy in that the tumour cells, the Hodgkin and Reed-Sternberg (HRS) cells, are a minor component of the tumour mass, the bulk of which is a mixed cellular infiltrate. There is compelling evidence that HRS cells are clonal B cells that have lost their B cell phenotype. Mature B cells lacking B cell receptors would normally die by apoptosis, and therefore HRS cells must have developed mechanisms to facilitate survival. The escape from apoptosis and transcriptional reprogramming of HRS cells are interlinked and appear central to disease pathogenesis. Epstein-Barr virus (EBV) is present in the HRS cells of a proportion of cases and expresses genes with a plausible oncogenic function. It is likely that EBV plays a role in reprogramming and survival through dysregulation of several signalling networks and transcription factors, including nuclear factor (NF)-κB. Activation of NF-κB is a feature of all HRS cells and gene mutations affecting this pathway appear common in EBV-negative HL. The HRS cell furthers its own survival by attracting a supportive microenvironment of immune and stromal cells, and suppressing local immune responsiveness. Although many questions remain unanswered, the last two decades have witnessed a considerable increase in our knowledge of this complex disease.