Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

27 patients (aged 15-55 years) with relapsed acute myelogenous (AML) and lymphoblastic leukaemia (ALL), and with lymphoblastic non Hodgkin's lymphoma (NHL) have been treated with intermediate dose cytosine arabinoside (AraC, 1 g/m2 q 12 h X 12) and 3 d of m-AMSA (20 patients), 90-115 mg/m2 daily, or daunorubicin (7 patients). 18 of them attained a complete remission (AML 10/14, ALL 3/5, NHL 5/8). 7 patients received consolidation treatment with 1-2 courses comprising 4 d of AraC (3 g/m2 q 12 h X 8) and m-AMSA (90-115 mg/m2) on d 5 of each course. 2 patients underwent allogeneic bone marrow transplantation and 9 received no further treatment after remission induction. In addition to vomiting, fever and conjunctivitis, toxicity in 6 patients included a combination of severe diarrhoea, fever and signs of paralytic ileus. 3 of them died during the pancytopenic phase. The pancytopenic period ranged from 16-25 d (median 21 d) after the remission induction and 14-21 d (median 19 d) after the consolidation course. Median remission duration was 5 months for those patients who received no treatment after remission induction and greater than 9 months (4+ - 16+ months) for the patients who received consolidation courses. Increased dosages of AraC are active in relapsed leukaemia and lymphoma, although optimal dose and schedule are still undetermined.
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PMID:Intermediate and high-dose ARA-C and m-AMSA (or daunorubicin) as remission and consolidation treatment for patients with relapsed acute leukaemia and lymphoblastic non-Hodgkin lymphoma. 385 71

A 73-year-old man with acute myelomonocytic leukemia developed a severe paralytic ileus after amsacrine and etoposide treatment. The ileus did not respond to treatment with gastric suction and intravenous fluids. Autonomic neuropathy induced by anti-neoplastic drugs may lead to this life-threatening condition.
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PMID:Amsacrine and etoposide induced paralytic ileus in a patient with acute myelomonocytic leukemia. 385 83

XK-469 is advancing to Phase I clinical trials. Preclinical studies were carried out to assist in clinical applications. DOSE-SCHEDULE ROUTE TESTING: Single dose i.v. treatment with XK-469 produced lethality (LD20 to LD100) above 142 mg/kg. Optimum treatment required total dosages of 350 to 600 mg/kg. Furthermore, high individual i.v. dosages (100 to 142 mg/kg) were poorly tolerated, producing substantial weight loss (8 to 18% of body weight), poor appearance, and slow recovery (8 to 12 days). A 1-hour infusion of dosages more than 140 mg/kg, or BID injections 6 hrs apart, did not reduce lethality. However, lower individual dosages of 40 to 50 mg/kg/injection i.v. were well tolerated and could be given daily to reach an optimum total dose with minimal toxicities. Likewise, 75 mg/kg/injection i.v. could be used every other day to reach optimal treatment. The necropsy profiles of deaths from toxic dosages were essentially identical regardless of schedule (deaths 4 to 7 days post treatment). The profiles were: paralytic ileus or gastroparesis; GI epithelial damage; and marrow toxicity. Interestingly, the key lethal events were rapidly reversible and simple to overcome with lower dosages given daily or every other day. Based on these results, the high dose, Q21 day schedule should be avoided in clinical applications. Instead, a split dose regimen is recommended (e.g., daily, every other day, or twice weekly). XK-469 was also well tolerated by the oral route, requiring 35% higher dosages p.o. to reach the same efficacy and toxicity as produced i.v.. CROSS-RESISTANCE STUDIES: XK-469 resistance was produced by optimum treatments of i.v. implanted L1210 leukemia over seven passage generations. This leukemia subline (L1210/XK469) had reduced sensitivity to VP-16 (with a 4.0 log kill in i.v. implanted L1210/XK469 compared to an 8.0 log kill against i.v. implanted L1210/0). It also had a reduction in the sensitivity to 5-FU (with a 2.0 log kill in the implanted L1210/XK469 compared to a 4.0 log kill against i.v. implanted L1210/0). Other agents were approximately as active against the resistant tumor, including: Ara-C, Gemzar, Cytoxan, BCNU, DTIC, and CisDDPT. No case of collateral sensitivity was observed; i.e., no agent was markedly more active against the resistant subline L1210/XK-469 than against the parent tumor in mice.
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PMID:Preclinical efficacy evaluations of XK-469: dose schedule, route and cross-resistance behavior in tumor bearing mice. 1200 90

We present an interesting case of recurrent paralytic ileus due to strongyloidiasis in a woman who was being treated with corticosteroids and immunosuppressants for systemic lupus erythematosus (SLE). She was also a carrier of human T-cell leukemia virus type I. She had a history of strongyloidiasis 8 years earlier. Recurrent episodes of paralytic ileus due to strongyloidiasis occurred during treatment of her SLE with corticosteroids. Ivermectin was given and improved the symptoms. This case shows that symptomatic strongyloidiasis can be induced in immunocompromised hosts by immunosuppressive therapy. It is important to rule out strongyloidiasis prior to starting immunosuppressive therapy in patients from endemic areas.
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PMID:Recurrent paralytic ileus associated with strongyloidiasis in a patient with systemic lupus erythematosus. 1662 24

We report a 49-year-old man who was a human T-cell leukemia virus type 1 (HTLV-1) carrier, born in Okinawa prefecture where both strongyloidiasis and HTLV-1 are endemic. He presented with fever, headache and urinary retention. On the basis of CSF examination and MRI findings, his condition was diagnosed as myelitis. He received methylprednisolone pulse therapy. He was transferred to our hospital due to severe paralytic ileus. Strongyloides stercoralis (S. stercoralis) was found in the duodenal stained tissue of a biopsy specimen. Ivermectin applied both orally and through enema were ineffective because of severe ileus and intestinal bleeding. Nine mg (200 microg/kg) of ivermectin solution was administered subcutaneously every other day for five days (total amount 45 mg). The S. stercoralis burden in the stool decreased and paralytic ileus gradually resolved. Three weeks after the resolution of S. stercoralis infection, purulent meningitis developed and acute obstructive hydrocephalus appeared. The hydrocephalus improved by ventricular drainage. Approximately three months after drainage, he died of incidental aspiratory pneumonia. Autopsy showed neither eggs nor larvae of S. stercoralis in the organs. In this case, the fourth reported case in the world, subcutaneous ivermectin injection was dramatically effective. We should consider a diagnosis of strongyloidiasis for any patient from Okinawa prefecture who was an HTLV-1 carrier presenting with unknown origin ileus after treatment of steroid therapy.
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PMID:[Fulminant strongyloidiasis successfully treated by subcutaneous ivermectin: an autopsy case]. 1838 29

The first patient with influenza A/H1N1-related pneumonia was admitted to an Italian ICU at the end of August 2009. Until then, despite the international alarm, the level of awareness was low and very few Italian hospitals were equipped with ECMOs. Moreover the PCR test for A H1N1 virus was sporadically available and the emergency departments of even the largest institutions could rely only on the rapid test for the urgent screening of patients with pneumonia and respiratory failure. On September 5th, a young and "apparently" previously healthy man, was admitted to our ICU because of a severe ARDS caused by influenza A H1N1 virus. As there was no ECMO available, he was treated with prolonged cycles of prone positioning ventilation. Antiviral treatment was started with Oseltamivir, but as enteral absorption was impaired by paralytic ileus and tube feeding intolerance, Oseltamivir had to be discontinued. Intravenous Zanamivir 1200 mg/day for ten days was therefore prescribed as "off label" antiviral therapy. A bone marrow biopsy allowed the diagnosis of an initial stage of "hairy cells leukaemia." ARDS related to A/H1N1 influenza was the first sign of the disease in our patient. He did well with complete clearance of the infection from the BAL after 10 days of Zanamivir, although the nasopharyngeal swabs remained positive for ten more days. Prone positioning ventilation may be a life-saver strategy in patients with severe ARDS when ECMO is not immediately available. However, prone positioning ventilation is often associated with severe impairment of the absorption of drugs that require enteral administration via the nasogastric tube. In these cases, intravenous Zanamivir may be an effective alternative strategy.
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PMID:Prone Positioning and Intravenous Zanamivir may Represent Effective Alternatives for Patients with Severe ARDS Virus A (H1N1) Related Pneumonia in Hospitals with no Access to ECMO. 2119 75

Posterior reversible encephalopathy syndrome (PRES) has been reported in childhood leukemia patients increasingly frequently. However, the development of PRES in adult leukemia patients during chemotherapy is very rare. We present a case of PRES in an adult patient with acute lymphoblastic leukemia (ALL) after remission induction chemotherapy. A 28-year-old woman with ALL was administered remission induction chemotherapy consisting of cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase. After initiation of chemotherapy, the patient developed paralytic ileus and hypertension, and on day 30, she suddenly developed generalized convulsions, loss of visual acuity, and muscle weakness in the legs. Magnetic resonance imaging findings and her signs and symptoms were typical of PRES. The symptoms gradually improved following treatment with an anticonvulsant and an antihypertensive agent, and the patient underwent allogeneic bone marrow transplantation. She has completely recovered from PRES and has been asymptomatic without leukemia relapse. During remission induction chemotherapy for ALL, PRES may be caused by multiple drugs, such as L-asparaginase, vincristine, and corticosteroids, with different mechanisms of action. PRES should be recognized as an important complication, which will occur more frequently with the increased intensity of chemotherapy for adult ALL patients.
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PMID:Posterior reversible encephalopathy syndrome in an adult patient with acute lymphoblastic leukemia after remission induction chemotherapy. 2216 Aug 36

Adult T cell leukemia- lymphoma is a rare aggressive malignancy of the peripheral T lymphocytes, caused by human T cell lymphotropic virus -1 (HTLV-1) infection. Hypercalcemia occurs in about 70% of patients with acute adult T cell leukemia. However, there are very few case reports of adult T cell leukemia presenting as a hypercalcemic crisis. We report a case of a 54-year-old male who presented with abdominal pain, constipation and altered sensorium. On examination he had generalized lymphadenopathy, hepatosplenomegaly and paralytic ileus. Investigation revealed hypercalcemic crisis with low parathormone (PTH) levels. Peripheral smear and bone marrow aspirate were consistent with adult T cell leukemia. HTLV-1 serology was positive. Despite the corrective measures for hypercalcemia and chemotherapy, he succumbed to the illness in a week.
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PMID:Hypercalcemic crisis due to adult T cell leukemia: a rare cause of paralytic ileus. 2471 44

Hyperechogenic bowel (HB) is a nonspecific ultrasound finding that can be associated with human cytomegalovirus (CMV) congenital infection. In this study, we investigated HB pathophysiology in CMV-infected fetuses. We examined small and large intestine as well as pancreas in 8 fetuses at 22 weeks of gestation with congenital CMV infection. Ultrasound findings showed 4 fetuses with HB and 4 without. As negative group, 4 fetuses without CMV infection and without HB were studied. Immunohistochemistry for CMV, lymphocytic infiltrate, B-cell leukemia/lymphoma-2 (bcl-2), CD-117, cystic fibrosis transmembrane regulator (CFTR) were performed. HB fetuses showed multiple and sequential CMV-positive ganglion cells of Auerbach's myenteric plexus. In the ganglia, bcl-2 was weakly expressed representing a reduced neuronal functionality. CD-117 revealed a regular distribution of Cajal cells, the pacemakers of intestinal contractility. Pancreas showed normal CFTR staining, indicating a preserved exocrine secretion, thus unlikely a contributory factor in HB. In CMV-infected fetuses without HB, CMV-positive cells were scatteredly found in ganglion cells and bcl-2 was strongly expressed. Intestinal CD-117 and pancreatic CFTR expression were similar to fetuses with HB. In conclusion, fetal CMV infection of the bowel may lead to peristalsis impairment (paralytic ileus) due to intestinal plexus involvement, which at ultrasound appeared as HB.
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PMID:Pathophysiology of Hyperechogenic Bowel in Congenitally Human Cytomegalovirus Infected Fetuses. 3245 64