Mitoxantrone: An anthracenedione-derived antineoplastic agent.Anthraquinones: Compounds based on ANTHRACENES which contain two KETONES in any position. Substitutions can be in any position except on the ketone groups.Cytarabine: A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Antineoplastic Combined Chemotherapy Protocols: The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Prednisone: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.Vidarabine: A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the VACCINIA VIRUS and varicella zoster virus.Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.Etoposide: A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.Idarubicin: An orally administered anthracycline antineoplastic. The compound has shown activity against BREAST NEOPLASMS; LYMPHOMA; and LEUKEMIA.P-Glycoprotein: A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).Amsacrine: An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Razoxane: An antimitotic agent with immunosuppressive properties.Topoisomerase Inhibitors: Compounds that inhibit the activity of DNA TOPOISOMERASES.Remission Induction: Therapeutic act or process that initiates a response to a complete or partial remission level.Intercalating Agents: Agents that are capable of inserting themselves between the successive bases in DNA, thus kinking, uncoiling or otherwise deforming it and therefore preventing its proper functioning. They are used in the study of DNA.Taxoids: A group of diterpenoid CYCLODECANES named for the taxanes that were discovered in the TAXUS tree. The action on MICROTUBULES has made some of them useful as ANTINEOPLASTIC AGENTS.Estramustine: A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties.Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA TOPOISOMERASES, TYPE I.Cardiotoxins: Agents that have a damaging effect on the HEART. Such damage can occur from ALKYLATING AGENTS; FREE RADICALS; or metabolites from OXIDATIVE STRESS and in some cases is countered by CARDIOTONIC AGENTS. Induction of LONG QT SYNDROME or TORSADES DE POINTES has been the reason for viewing some drugs as cardiotoxins.Drug Evaluation: Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals.Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.Leukemia, Myeloid: Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.Prostatic Neoplasms: Tumors or cancer of the PROSTATE.DNA Topoisomerases, Type II: DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex.Leukemia, Myeloid, Acute: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Multiple Sclerosis, Chronic Progressive: A form of multiple sclerosis characterized by a progressive deterioration in neurologic function which is in contrast to the more typical relapsing remitting form. If the clinical course is free of distinct remissions, it is referred to as primary progressive multiple sclerosis. When the progressive decline is punctuated by acute exacerbations, it is referred to as progressive relapsing multiple sclerosis. The term secondary progressive multiple sclerosis is used when relapsing remitting multiple sclerosis evolves into the chronic progressive form. (From Ann Neurol 1994;36 Suppl:S73-S79; Adams et al., Principles of Neurology, 6th ed, pp903-914)Multiple Sclerosis: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)Multiple Sclerosis, Relapsing-Remitting: The most common clinical variant of MULTIPLE SCLEROSIS, characterized by recurrent acute exacerbations of neurologic dysfunction followed by partial or complete recovery. Common clinical manifestations include loss of visual (see OPTIC NEURITIS), motor, sensory, or bladder function. Acute episodes of demyelination may occur at any site in the central nervous system, and commonly involve the optic nerves, spinal cord, brain stem, and cerebellum. (Adams et al., Principles of Neurology, 6th ed, pp903-914)Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Myelodysplastic Syndromes: Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.Hong Kong: The former British crown colony located off the southeast coast of China, comprised of Hong Kong Island, Kowloon Peninsula, and New Territories. The three sites were ceded to the British by the Chinese respectively in 1841, 1860, and 1898. Hong Kong reverted to China in July 1997. The name represents the Cantonese pronunciation of the Chinese xianggang, fragrant port, from xiang, perfume and gang, port or harbor, with reference to its currents sweetened by fresh water from a river west of it.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Thirst: A drive stemming from a physiological need for WATER.Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness.Hair: A filament-like structure consisting of a shaft which projects to the surface of the SKIN from a root which is softer than the shaft and lodges in the cavity of a HAIR FOLLICLE. It is found on most surfaces of the body.Urination: Discharge of URINE, liquid waste processed by the KIDNEY, from the body.Diarrhea: An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.Prostate: A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM.Prescription Drugs: Drugs that cannot be sold legally without a prescription.Canada: The largest country in North America, comprising 10 provinces and three territories. Its capital is Ottawa.Insurance, Pharmaceutical Services: Insurance providing for payment of services rendered by the pharmacist. Services include the preparation and distribution of medical products.Hypopituitarism: Diminution or cessation of secretion of one or more hormones from the anterior pituitary gland (including LH; FOLLICLE STIMULATING HORMONE; SOMATOTROPIN; and CORTICOTROPIN). This may result from surgical or radiation ablation, non-secretory PITUITARY NEOPLASMS, metastatic tumors, infarction, PITUITARY APOPLEXY, infiltrative or granulomatous processes, and other conditions.Drug Prescriptions: Directions written for the obtaining and use of DRUGS.Human Growth Hormone: A 191-amino acid polypeptide hormone secreted by the human adenohypophysis (PITUITARY GLAND, ANTERIOR), also known as GH or somatotropin. Synthetic growth hormone, termed somatropin, has replaced the natural form in therapeutic usage such as treatment of dwarfism in children with growth hormone deficiency.

Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines. (1/750)

BACKGROUND: Human cancer cell lines grown in the presence of the cytotoxic agent mitoxantrone frequently develop resistance associated with a reduction in intracellular drug accumulation without increased expression of the known drug resistance transporters P-glycoprotein and multidrug resistance protein (also known as multidrug resistance-associated protein). Breast cancer resistance protein (BCRP) is a recently described adenosine triphosphate-binding cassette transporter associated with resistance to mitoxantrone and anthracyclines. This study was undertaken to test the prevalence of BCRP overexpression in cell lines selected for growth in the presence of mitoxantrone. METHODS: Total cellular RNA or poly A+ RNA and genomic DNA were isolated from parental and drug-selected cell lines. Expression of BCRP messenger RNA (mRNA) and amplification of the BCRP gene were analyzed by northern and Southern blot hybridization, respectively. RESULTS: A variety of drug-resistant human cancer cell lines derived by selection with mitoxantrone markedly overexpressed BCRP mRNA; these cell lines included sublines of human breast carcinoma (MCF-7), colon carcinoma (S1 and HT29), gastric carcinoma (EPG85-257), fibrosarcoma (EPF86-079), and myeloma (8226) origins. Analysis of genomic DNA from BCRP-overexpressing MCF-7/MX cells demonstrated that the BCRP gene was also amplified in these cells. CONCLUSIONS: Overexpression of BCRP mRNA is frequently observed in multidrug-resistant cell lines selected with mitoxantrone, suggesting that BCRP is likely to be a major cellular defense mechanism elicited in response to exposure to this drug. It is likely that BCRP is the putative "mitoxantrone transporter" hypothesized to be present in these cell lines.  (+info)

Multiple mechanisms confer drug resistance to mitoxantrone in the human 8226 myeloma cell line. (2/750)

Selection for in vitro drug resistance can result in a complex phenotype with more than one mechanism of resistance emerging concurrently or sequentially. We examined emerging mechanisms of drug resistance during selection with mitoxantrone in the human myeloma cell line 8226. A novel transport mechanism appeared early in the selection process that was associated with a 10-fold resistance to mitoxantrone in the 8226/MR4 cell line. The reduction in intracellular drug concentration was ATP-dependent and ouabain-insensitive. The 8226/MR4 cell line was 34-fold cross-resistant to the fluorescent aza-anthrapyrazole BBR 3390. The resistance to BBR 3390 coincided with a 50% reduction in intracellular drug concentration. Confocal microscopy using BBR 3390 revealed a 64% decrease in the nuclear:cytoplasmic ratio in the drug-resistant cell line. The reduction in intracellular drug concentration of both mitoxantrone and BBR 3390 was reversed by a novel chemosensitizing agent, fumitremorgin C. In contrast, fumitremorgin C had no effect on resistance to mitoxantrone or BBR 3390 in the P-glycoprotein-positive 8226/DOX6 cell line. Increasing the degree of resistance to mitoxantrone in the 8226 cell line from 10 to 37 times (8226/MR20) did not further reduce the intracellular drug concentration. However, the 8226/MR20 cell line exhibited 88 and 70% reductions in topoisomerase II beta and alpha expression, respectively, compared with the parental drug sensitive cell line. This decrease in topoisomerase expression and activity was not observed in the low-level drug-resistant, 8226/MR4 cell line. These data demonstrate that low-level mitoxantrone resistance is due to the presence of a novel, energy-dependent drug efflux pump similar to P-glycoprotein and multidrug resistance-associated protein. Reversal of resistance by blocking drug efflux with fumitremorgin C should allow for functional analysis of this novel transporter in cancer cell lines or clinical tumor samples. Increased resistance to mitoxantrone may result from reduced intracellular drug accumulation, altered nuclear/cytoplasmic drug distribution, and alterations in topoisomerase II activity.  (+info)

Dose-escalation study of docetaxel in combination with mitoxantrone as first-line treatment in patients with metastatic breast cancer. (3/750)

PURPOSE: To define the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of docetaxel in combination with mitoxantrone in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-one chemotherapy-naive patients with MBC (median age, 61 years) were enrolled. Thirty-eight (93%) had performance status (World Health Organization [WHO]) 0, 29 (71%) were postmenopausal, and 21 (51%) had estrogen receptor-negative tumors. Patients received escalated doses of docetaxel (75 to 100 mg/m2) on day 1 and mitoxantrone (8 to 22 mg/m2) on day 8. Treatment was repeated every 3 weeks. RESULTS: A total of 217 chemotherapy cycles were administered. Without recombinant human granulocyte colony-stimulating factor (rhG-CSF) support, the MTD1 occurred at the first dose level (docetaxel 75 mg/m2 and mitoxantrone 8 mg/m2); DLTs were febrile neutropenia, grade 4 neutropenia lasting more than 5 days, and grade 3 diarrhea. With prophylactic rhG-CSF, the MTD2 was docetaxel 100 mg/m2 and mitoxantrone 20 mg/m2; DLTs were febrile neutropenia and grade 4 neutropenia. Nine (22%) patients developed neutropenia after the first cycle of treatment. A total of 19 episodes of febrile neutropenia (9% of the cycles) occurred during the whole period of the study; there were no toxic deaths. At high docetaxel (100 mg/m2) and mitoxantrone (> 12 mg/m2) dose levels, a significant decrease of the absolute lymphocyte number was observed; immunophenotyping revealed that all lymphocyte subpopulations were reduced. Grades 2 and 3 neurosensory toxicity occurred in six patients (15%) and one patient (2%), respectively. No cardiac toxicity was observed. Nine complete responses (22%) and 23 partial responses (56%) were achieved (overall response rate, 78%; 95% confidence interval, 62.5% to 88.8%). The median duration of response was 12.5 months, and the median time to tumor progression was 14.5 months. CONCLUSION: The reported combination of docetaxel and mitoxantrone with G-CSF support is a safe, intensified, well-tolerated, and effective regimen as first-line treatment in patients with MBC.  (+info)

Autologous transplantation of chemotherapy-purged PBSC collections from high-risk leukemia patients: a pilot study. (4/750)

We have recently demonstrated that the combination of the alkylating agent nitrogen mustard (NM) and etoposide (VP-16) is capable of eliminating, ex vivo, leukemic cells contaminating PBSC collections and this is associated with a significant recovery of primitive and committed hematopoietic progenitor cells. Based on these data a pilot study on autologous transplantation of NM/VP-16 purged PBSC for high-risk leukemic patients was recently initiated. Twelve patients (seven females and five males) with a median age of 46 years (range 18-57) have been treated. Two patients had acute myeloblastic leukemia (AML) resistant to conventional induction treatment, four patients had secondary AML in I complete remission (CR), one patient was in II CR after failing a previous autologous BM transplantation, while two additional AML individuals were in I CR achieved after three or more cycles of induction treatment. Two patients with high-risk acute lymphoblastic leukemia (ALL) in I CR and one patient with mantle cell lymphoma and leukemic dissemination were also included. Eight patients showed karyotypic abnormalities associated with a poor clinical outcome. The mobilizing regimens included cytosine arabinoside and mitoxantrone with (n = 6) or without fludarabine (n = 3) followed by subcutaneous administration of G-CSF (5 microg/kg/day until the completion of PBSC collection) and G-CSF alone (n = 3) (15 microg/kg/day). A median of two aphereses (range 1-3) allowed the collection of 7.2 x 10(8) TNC/kg (range 3.4-11.5), 5 x 10(6) CD34+ cells/kg (range 2.1-15.3) and 9.2 x 10(4) CFU-GM/kg (0.3-236). PBSC were treated with a constant dose of 20 microg of VP-16/ml and a median individual-adjusted dose (survival < or = 5% of steady-state BM CFU-GM) of NM of 0.7 microg/ml (range 0.25-1.25). Eleven patients were reinfused after busulfan (16 mg/kg) and Cy (120 mg/kg) conditioning with a median residual dose of 0.3 x 10(4) CFU-GM/kg (0-11.5). The median time to neutrophil engraftment (>0.5 x 10(9)/l) for evaluable patients was 25 days (range 12-59); the median time to platelet transfusion independence (>20 and >50 x 10(9)/l) was 40 days (18-95) and 69 days (29-235), respectively. Hospital discharge occurred at a median of 25 days (18-58) after stem cell reinfusion. Four individuals are alive in CR (n = 3) or with residual nodal disease (n = 1 lymphoma patient) with a follow-up of 32, 26, 3 and 14 months, respectively. Seven patients died due to disease progression or relapse (n = 5) or extrahematological transplant toxicity (n = 2). Our data suggest that pharmacological purging of leukapheresis collections of leukemic patients at high-risk of relapse is feasible and ex vivo treated cells reconstitute autologous hematopoiesis.  (+info)

Follicular large cell lymphoma: an aggressive lymphoma that often presents with favorable prognostic features. (5/750)

It is debated whether follicular large cell lymphoma (FLCL) has a clinical behavior that is distinct from indolent follicular lymphomas, and whether there is a subset of patients who can be potentially cured. We report here our experience with 100 FLCL patients treated at our institution since 1984 with three successive programs. We evaluated the predictive value of pretreatment clinical features, including two risk models, the Tumor Score System and the International Prognostic Index (IPI). With a median follow-up of 67 months, the 5-year survival is 72% and the failure-free survival (FFS) is 67%, with a possible plateau in the FFS curve, particularly for patients with stage I-III disease. Features associated with shorter survival included age >/=60, elevated lactic dehydrogenase (LDH) or beta-2-microglobulin (beta2M), advanced stage, and bone marrow involvement. Stage III patients had significantly better survival than stage IV patients (P <.05). By the IPI and Tumor Score System, 80% of the patients were in the lower risk groups; both systems stratified patients into prognostic groups. Patients with FLCL have clinical features and response to treatment similar to that reported for diffuse large cell lymphoma. Prognostic risk systems for aggressive lymphomas are useful for FLCL. A meaningful fraction of patients may possibly be cured when treated as aggressive lymphomas.  (+info)

Early detection of anthracycline induced cardiotoxicity in asymptomatic patients with normal left ventricular systolic function: autonomic versus echocardiographic variables. (6/750)

OBJECTIVE: To investigate left ventricular dysfunction in patients who had been treated with anthracycline based chemotherapy. METHODS: Autonomic function was compared with left ventricular diastolic function in 20 asymptomatic women with normal systolic function (left ventricular ejection fraction (LVEF) > 0.50) treated for breast cancer with high dose anthracycline based chemotherapy, and 20 age matched healthy controls. Left ventricular diastolic function was assessed echocardiographically by measuring the early peak flow velocity to atrial peak flow velocity ratio, isovolumic relaxation time, and deceleration time. Heart rate variability analysis was assessed for time domain and frequency domain parameters. RESULTS: The mean (SD) age of the patients was 45 (7) years and the mean LVEF was 0.59 (0.06). The time interval after the end of chemotherapy was 29 (27) months. One or more diastolic variables were abnormal in 50% of the patients. Heart rate variability was abnormal in 85% of patients. Mean values of both time domain and frequency domain parameters were decreased (p < 0.05), in particular the parasympathetic indices. CONCLUSIONS: Autonomic impairment occurs in a large proportion of asymptomatic patients with normal systolic left ventricular function after high dose anthracycline based chemotherapy. In particular, heart rate variability analysis may be a sensitive tool to identify the first signs of cardiotoxicity in these patients.  (+info)

Time sequential chemotherapy for primary refractory or relapsed adult acute myeloid leukemia: results of the phase II Gemia protocol. (7/750)

BACKGROUND AND OBJECTIVE: High-dose cytarabine (HDAra-C), mitoxantrone and etoposide are the mainstay of several active regimens against relapsed or refractory acute myelogenous leukemia (AML). We designed a phase II study to assess the efficacy and side effects of a time sequential application of mitoxantrone plus intermediate-dose Ara-C followed by HDAra-C plus etoposide (GEMIA) in adult patients with refractory or relapsed AML. DESIGN AND METHODS: Patients with refractory or relapsed AML were eligible for GEMIA salvage therapy, which comprised mitoxantrone 12 mg/m2/day on days 1-3, Ara-C 500 mg/m2/day as a 24-hour continuous infusion on days 1-3, followed by HDAra-C 2 g/m2/12-hourly on days 6-8 and etoposide 100 mg/m2/12-hourly on days 6-8. Granulocyte colony-stimulating factor was started on day 14. In patients above the age of 55 the dose of Ara-C in the first sequence (days 1-3) was reduced to 250 mg/m2. RESULTS: Twenty patients were included, of whom 12 achieved complete remission after GEMIA (60%, 95% CI 40-80%), one was refractory and five died early from infection. Two additional patients achieved partial remission after GEMIA and complete remission after consolidation chemotherapy, for a final CR rate of 70% (95% CI 48-88%). Neutrophils recovered at a median of 27 days (range, 22-43) and platelets 46 days (range, 25-59) after the start of treatment. The median duration of remission was 133 days (range, 36-417+) whereas overall survival time lasted for a median of 153 days (range, 13-554+). Treatment-associated toxicity was comprised predominantly of infection, mucositis and diarrhea that reached World Health Organization grades III-V in 40%, 40% and 30% of patients, respectively. Despite the intention to rapidly proceed to a hematopoietic stem cell transplant in patients in remission, only five patients reached the transplant. INTERPRETATION AND CONCLUSIONS: The GEMIA time sequential chemotherapy regimen appears effective in obtaining remissions in refractory and relapsed adult AML. The high toxicity seen, however, suggests that its design is amenable to further improvements, especially in more elderly patients. Since remissions are short-lived, more innovative post-remission strategies are needed.  (+info)

Trisomy 21 associated transient neonatal myeloproliferation in the absence of Down's syndrome. (8/750)

Although usually associated with Down's syndrome, transient neonatal myeloproliferation (TMD) can occur in the absence of a constitutional trisomy 21. This report describes two such cases, both of whom had a trisomy 21 restricted to clonal cells. Unlike in previous such reported cases, spontaneous morphological, cytogenetic, and molecular remission in both cases was followed by re-emergence, in one case, of an evolved clone with a more malignant phenotype which required pharmacological intervention. Awareness that trisomy 21 bearing leukaemia in the neonatal period can be transient even in the absence of Down's syndrome is important to prevent unnecessary treatment. Equally, such cases require indefinite follow up as a proportion may have a recurrence which may require treatment.  (+info)

  • Mitoxantrone (Novantrone) is an FDAapproved drug used to treat the secondary-progressive form ofMS due to its demonstrated immunosuppressive properties. (
  • The risk of heart damage may depend on the total amount of mitoxantrone given to a person over a lifetime, so your doctor will probably limit the total number of doses you receive if you are using this medication for MS. If you experience any of the following symptoms, call your doctor immediately: difficulty breathing, chest pain, swelling of the legs or ankles, or irregular or fast heartbeat. (
  • Tell your doctor and pharmacist if you are taking or have ever received certain cancer chemotherapy medications such as daunorubicin (Cerubidine), doxorubicin (Doxil), epirubicin (Ellence), or idarubicin (Idamycin), or if you have ever been treated with mitoxantrone in the past. (
  • All patients were allocated to receive either idarubicin or mitoxantrone in induction by stratified concealed randomisation. (
  • FINDINGS: Of 239 registered patients, 216 were randomly assigned to either idarubicin (109 analysed) or mitoxantrone (103 analysed). (
  • INTERPRETATION: As compared with idarubicin, mitoxantrone conferred a significant benefit in progression-free and overall survival in children with relapsed acute lymphobastic leukaemia, a potentially useful clinical finding that warrants further investigation. (
  • The most common is side effect of Mitoxantrone in patient with MS are nausea, hair thinning, loss of menstrual periods, bladder infections and mouth ulcers or sores. (
  • Because of the risk of cardiomyopathy, mitoxantrone carries a limit on the cumulative lifetime dose (based on body surface area) in MS patients. (
  • We may have to adjust the dose of mitoxantrone depending on your blood counts. (
  • Mitoxantrone is dark blue in colour, so it may turn your urine a blue-green colour for a few days after each dose. (
  • You should not use this medication if you are allergic to mitoxantrone. (
  • Currently, the pharmacodynamic properties of mitoxantrone have not been investigated to any extent in patients with MS. In one study, 6 months' treatment with intravenous mitoxantrone generally had no effect on the distribution of cytokine-positive peripheral blood monocyte cells in patients with MS. In an animal model of the disease, mitoxantrone suppressed the development and progression of both actively and passively induced acute experimental allergic encephalomyelitis (EAE). (
  • Your heart rate may need to be checked using an electrocardiograph or ECG (sometimes called an EKG) before, during, and after your treatment with mitoxantrone. (
  • Please note all mitoxantrone-treated patients need to go onto a maintenance therapy once the 6 or 24 months of treatment are over. (
  • Your doctor will examine you and perform certain tests to check how well your heart is working before beginning treatment with mitoxantrone and if you show any signs of heart problems. (
  • Intravenous mitoxantrone treatment improved neurological disability and delayed progression of MS in patients with worsening relapsing-remitting (RR) [also termed progressive-relapsing (PR) MS] or secondary-progressive (SP) disease. (
  • Post hoc analyses suggest that the benefits associated with mitoxantrone treatment may be sustained for at least 12 months after cessation of treatment, mean changes from baseline at 36 months in EDSS, AI and SNS scores of 0.10, 0.61 and 0.19, respectively, in the mitoxantrone group versus 0.46, 1.13 and 3.38 with placebo. (
  • I tend to avoid using mitoxantrone in patients who are permanently catherised, or who have recurrent urinary tract infections, because of the risk of sepsis. (
  • Concomitant intravenous mitoxantrone 20mg plus intravenous methylprednisolone 1g once every month for 6 months was more effective than intravenous methylprednisolone monotherapy in preventing the development of new gadolinium-enhanced lesions in patients with very active RRMS or SPMS. (
  • Currently, there are no published pharmacokinetic data for intravenous mitoxantrone in pitoxantrone in patients with MS, paediatric patients or in those with renal impairment. (
  • All studies, to date, have been in patients with cancer receiving a single, approximately 30-minute intravenous infusion of mitoxantrone 5-14 mg/m(2). (
  • At the recommended dosage, mitoxantrone appears to have a low potential to cause cardiotoxicity. (
  • Clearly female MSers who are pregnant, are trying to become pregnant, or are breastfeeding should not be treated with mitoxantrone because it may harm the baby. (
  • You should use birth control while taking mitoxantrone to avoid becoming pregnant. (
  • While the mechanism of action of mitoxantrone is not yet well understood, and is limited in its use due to cardiotoxicity, the aim of this study was to determine the effect of mitoxantrone on microglial and astrocyte activation as a measure of the inflammatory response. (
  • Whilst receiving mitoxantrone the chances of you getting an infection are increased. (
  • Mitoxantrone causes your white blood cell count to go down, which increases your chance of getting an infection. (
  • Mitoxantrone Injection, USP (concentrate) should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents. (
  • More powerful approaches to disease modification in MS include the so-called "biological therapies" or monoclonal antibodies (natalizumab, alemtuzumab, daclizumab, rituximab, and ocrelizumab) and cytotoxic drugs (cladribine and mitoxantrone) [ 3 - 6 ]. (
  • Tell your doctor and pharmacist if you are taking or have ever received certain cancer chemotherapy medications such as daunorubicin (Cerubidine), doxorubicin (Doxil), epirubicin (Ellence), or idarubicin (Idamycin), or if you have ever been treated with mitoxantrone in the past. (
  • Using DOXOrubicin together with mitoXANTRONE or other chemotherapy drugs may increase the risk of side effects, especially those that affect the bone marrow or gastrointestinal tract. (
  • Inevitably, mitoxantrone must be compared with doxorubicin,which remains the standard against which anthracycline analogs are evaluated.Dr. Armitage reviews the pertinent literature concerning the cardiotoxicpotential of these agents, as well as the literature that defines the doses ofdoxorubicin and mitoxantrone that have equivalent myelosuppressive toxicity. (
  • While the toxicities associated with its use are significantly less than those observed following treatment with the widely used doxorubicin, mitoxantrone cardiotoxicity is clearly a substantial clinical problem. (
  • Similar protection is observed against doxorubicin and the oxidized form of mitoxantrone, but not against the non-hydroxylated analog of mitoxantrone, ametantrone. (
  • Who Should Not Take This Medication You should not take this medication if you are allergic to mitoxantrone, any of its components, or other medications that are similar to mitoxantrone, including doxorubicin, epirubicin, daunorubicin, idarubicin. (
  • Post hoc analyses suggest that the benefits associated with mitoxantrone treatment may be sustained for at least 12 months after cessation of treatment, mean changes from baseline at 36 months in EDSS, AI and SNS scores of 0.10, 0.61 and 0.19, respectively, in the mitoxantrone group versus 0.46, 1.13 and 3.38 with placebo. (
  • Mitoxantrone also displays broad immunosuppressive activity inhibiting proliferation of all classes of lymphocytes and inducing apoptosis of antigen-presenting T cells. (
  • Mitoxantrone also has immunosuppressive activity, inhibiting B cell, T cell and macrophage proliferation and decreasing tumor necrosis factor alpha and interleukin-2 secretion. (
  • When mitoxantrone injection is used to treat MS, it is usually given once every 3 months for about 2 to 3 years (for a total of 8 to 12 doses). (
  • Mitoxantrone therapy is often accompanied by mild to moderate elevations in serum aminotransferase levels, but in typical doses it rarely causes clinically apparent, acute liver injury. (
  • In high doses, mitoxantrone has been associated with a high rate of jaundice, but the degree of hyperbilirubinemia has been mild, transient and not associated with significant serum enzyme elevations or evidence of hepatitis. (
  • Some of the possible side effects of mitoxantrone include fatigue, nausea, and upper respiratory tract infections. (
  • Some side effects of mitoxantrone should be reported immediately to your healthcare provider. (
  • Herein we describe how the drug mitoxantrone can bind, induce folding of and stabilise i-motif forming DNA sequences, even at physiological pH. (
  • Mitoxantrone ability to induce premature senescence in human dental pulp stem cells and human dermal fibroblasts. (
  • mitoxantrone can induce clinical responses in adults with relapsed or refractory acute leukemias and high-risk MDS 1. (
  • Mitoxantrone should be given only under the supervision of a doctor with experience in the use of chemotherapy medications. (
  • 3-For patients with recurrent lymphoma, mitoxantrone fitnicely into an evolving series of ifosfamide(Ifex)/etoposide regimens,[8,9,ulminating in the MINE-ESHAP* strategy cited by Dr. Armitage. (
  • Patients failing to enter remission may receive 4 days of therapy with Etoposide 100 mg/m2 on days 1-4,Mitoxantrone 8 mg/m2 days 1-2 or 1-4,and Clofarabine at 20-30 mg/m2 IV on days 1-4. (
  • article{2a3edb89-6fb5-406f-87d5-bb309003c418, abstract = {30 patients with malignant pleuritis were randomised to be treated, either with intrapleural instillation of mepacrine chloride or with mitoxantrone. (
  • Initial experiments aimed at defining mitoxantrone mechanism of action showed that mitoxantrone likely does not stimulate a significant production of active oxygen species, or have a specific effect on mitochondrial function. (
  • If you miss an appointment to receive mitoxantrone, contact your doctor as soon as possible to reschedule your appointment. (
  • Congestive heart failure (CHF), potentially fatal, may occur either during therapy with mitoxantrone or months to years after termination of therapy. (
  • Mitoxantrone can cause heart problems, including congestive heart failure , which can be severe enough to lead to death. (
  • Mitoxantrone can cause heart problems, including congestive heart failure. (
  • One compound, A18 (1,4-bis(diethylamino)-5,8- dihydroxy anthraquinon) was a mitoxantrone derivative and significantly decreased viability in most of the cells comparable to the to the level of FAK kinase inhibitors TAE-226 (Novartis, Inc) and PF-573,228 (Pfizer). (
  • ut the overall simplicity of the FND regimen, its efficacy, and the substantialencouraging confirmatory data from other institutions have made thefludarabine/mitoxantrone (FN) combination (with or without steroids) anappealing option for patients with indolent lymphoma. (
  • This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. (
  • Second-line treatment with mitoxantrone and retreatment with docetaxel are commonly used despite limited data on safety and efficacy. (
  • However, the patients treated with mepacrine chloride experienced greater discomfort with fever and pain, and those treated with mitoxantrone reported significantly less dyspnoea and less asthenia after 4 weeks. (
RCSB PDB - 4RC4: Crystal structure of Ser/Thr kinase Pim1 in complex with Mitoxantrone derivatives
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