Cases Of Myelosuppression Research Articles

A case of myelosuppression in patients with lupus nephritis caused by azathioprine

A case of myelosuppression in patients with lupus nephritis caused by azathioprine

Local and systemic diffusion of antineoplastic drugs following vertebroplasty using acrylic cement mixed with cisplatin or methotrexate: experimental study in pigs.

To determine the efficacy of cisplatin- or methotrexate-containing acrylic cement for local and systemic antineoplastic drug diffusion. Among the uses of acrylic cement or Polymethylmethacrylate (PMMA), there is the possibility to employ it as vehicle for drug diffusion. This capability is of interest in the treatment of pathological fractures: The curative effects of the cement (cytotoxicity of the monomer and increased temperature) are added to the antineoplastic effect of the drugs. In the experimental study, two groups of ten pigs underwent vertebroplasty using cement mixed with 500mg of powder cisplatin or 1000mg of powder methotrexate. Vertebroplasty was performed in two non-consecutive lumbar vertebrae with bipedicular cement injection. Transpedicular bone biopsy was performed weekly to measure levels of antineoplastic agent in bone tissue and blood plasma. Cisplatin was studied by atomic absorption spectrometry and methotrexate by fluorescence polarization immunoassay. Renal and hepatic function and blood analysis were performed weekly. Cisplatin and methotrexate levels were found in bone tissue at more than 5weeks following surgery. The cisplatin peak occurred at week 3 (mean 1269μg/g bone) and the methotrexate peak at week 1 (mean 862.76μg/g bone). Plasma drug levels were found 72h after surgery, with a peak at 24h for cisplatin (mean 0.23μmol/L) and at 30min for methotrexate (mean 0.92μmol/L). None of the animals died during the study. Animals with intracanal cement leaks showed no neurological involvement. Renal, hepatic and hemogram studies remained within normal limits. There is local diffusion of antineoplastic agents from the cement to bone and plasma. We found methotrexate and cisplatin levels in bone at up to 5weeks, comparable to previous in vitro reports. At the doses administered, there were no cases of myelosuppression, hepatotoxicity, or nephrotoxicity.

P-107: Effect of exclusive enteral nutrition on the course of CD and intestinal microbiota

P-107: Effect of exclusive enteral nutrition on the course of CD and intestinal microbiota

P-106: The clinical relevance of tacrolimus for ulcerative colitis in children: a national survey of the treatments for pediatric inflammatory bowel disease in Japan

P-106: The clinical relevance of tacrolimus for ulcerative colitis in children: a national survey of the treatments for pediatric inflammatory bowel disease in Japan

Acquired Bone Marrow Failure After Diphtheria

Acquired bone marrow failure can result after infections caused by viruses, exposure to toxins, or chemicals. Majority of acquired cases of marrow failure labeled as "idiopathic" are probably immune mediated through activated T-cells and cytokines. We observed pancytopenia in the second week, after pharyngeal diphtheria in a 14-year-old child. Bone marrow examination showed reduced marrow precursors affecting all 3 cell lines. There are no clinical cases of myelosuppression reported in diphtheria infection and this is probably the first reported case of bone marrow failure after diphtheria infection. However, such observations merit further evaluation and confirmation by experimental studies.

Beyond TPMT: genetic influences on thiopurine drug responses in inflammatory bowel disease.

Azathioprine and 6-mercaptopurine are widely used in the management of inflammatory bowel disease (IBD). However, approximately 25% of IBD patients experience toxicity, and up to 10% show resistance to these thiopurine drugs. The importance of genetic variability in determining thiopurine toxicity was first recognized over 25 years ago with the discovery of the thiopurine S-methyltransferase (TPMT) polymorphism and the occurrence of azathioprine-induced myelosuppression in TPMT-deficient patients. In the intervening period, TPMT has become the foremost example of pharmacogenetics, and TPMT deficiency represents one of the few pharmacogenetic phenomena that have successfully made the transition from the research laboratory to diagnostics. While TPMT activity predicts some cases of myelosuppression, deficiency in this enzyme is neither predictive of other adverse drug reactions, nor resistance to thiopurine therapy. As myelosuppression only accounts for approximately 2.5% of adverse reactions in IBD patients, researchers are increasingly turning their attention to other enzymes involved in thiopurine metabolism to find molecular explanations for intolerance and resistance to azathioprine and 6-mercaptopurine. In this review, we summarize the current state of knowledge with regards to TPMT, and also explore genetic variability, beyond TPMT, that may contribute to thiopurine response in IBD patients.

Efecto terapéutico de Mitomicina C en el postoperatorio inmediato de pacientes con tumores vesicales no músculo invasores de riesgo intermedio

IntroductionApproximately 70-85% of transitional bladder cell carcinomas are non-muscle-invasive. After an initial surgery, around 60-90% will have a recurrence, being the highest risk period the first two years. Urothelium instability could be the main reason for recurrence in mid grade tumours, reason why a single dose of a chemotherapy after transurethral resection of the bladder (TURB) might be insufficient. That is why a deferred therapy in occasions associated with maintenance is recommended. Patients and methodsA prospective, controlled and randomized study was performed. We included non-muscle-invasive mid risk bladder tumours. All patients had initially a TURB performed and were randomized to receive a single dose of mitomycin C (MMC), in the immediate postoperative period. ResultsA total of 105 patients were included. Mean follow-up was 22, 70±8, 15 months. MMC was administered to 53 patients. Of these 66, 0% had no recurrence and 34,0% had a non-muscle-invasive recurrence. Of the 52 patients in the non MMC group, 53,8% had no recurrence and 44,2% had a non-muscle-invasive recurrence and only 1 patient had a muscleinvasive progression. We did not find significantly differences in time to recurrence in mid risk tumours when using immediate postoperative single dose of MMC or deferred therapy. There was only one case of myelosuppression. DiscussionIn mid risk non-muscle-invasive tumors, some studies suggest that early intravesical instillation of chemotherapy reduces the risk of recurrence after TURB. We could not show significantly differences when comparing postoperatorive MMC versus traditional deferred instillations.

Clinical and Preclinical Pharmacology of Liposomal Vincristine

Vincristine is one of the most commonly administered anticancer drugs and is active in a wide range of indications including non-Hodgkin's lymphomas, acute lymphocytic leukemias and lung cancer. Administration of vincristine in long-circulating liposomes may be expected to result in increased accumulation of drug at tumor sites due to “passive targeting” or “disease-site targeting” effects arising from the more permeable vasculature in these regions. Further, for liposomes with appropriate drug release characteristics, extended exposure of tumor cells to vincristine would result from liposomal delivery. The combination of increased drug delivery and extended duration of drug exposure may be expected to result in increased efficacy, particularly because vincristine is a cell-cycle specific drug. It is shown that vincristine can be encapsulated in large unilamellar vesicles (diameter β 100 nm) using a pH gradient (interior acidic) approach. Further, the efficacy of liposomal formulations of vincristine in animal models is highly sensitive to the drug release rate in vivo. A liposomal formulation with drug retention characteristics such that more than 50% of the vincristine is retained in the carrier 24 h following i.v. injection exhibits significantly improved antitumor efficacy in A431 xenograft and P388 murine tumor models in comparison to either free drug or leakier liposomal formulations. The clinical activity of liposomal vincristine has been investigated in relapsed or refractory non-Hodgkin's lymphoma patients at a dose level of 2 mg/m2 every two weeks. Of 83 registered patients, there were 24 responses in 68 evaluable patients. The responses according to histology are: Indolent-13%; Transformed-42%; Aggressive-45%. There were no serious cases of myelosuppression or any toxic deaths. It is concluded that liposomal vincristine can be given at high doses, is active and well tolerated and is rarely neurotoxic or myelosuppressive in these heavily pretreated patients. It appears that the benefits of low toxicity and enhanced efficacy noted in the tumor models are also observed in the clinical setting. A multicenter pivotal Phase II trial of liposomal vincristine in relapsed and refractory non-Hodgkin's lymphoma has been approved by the US FDA and is ongoing.