Formation of chloroethylamine and 1,3-oxazolidine-2-one following ifosfamide administration in humans.
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Ethylamines↗
Biomedical subjects
J Mansi
Publications and source records attributed to J Mansi.
Clonal analysis of three morphologically distinct lymphomas occurring in the same patient.
AIMS: To determine whether three morphologically distinct lymphomas (mucosa associated lymphoid tissue (MALT) lymphoma, monocytoid B cell lymphoma, and large cell anaplastic lymphoma), which occurred in the same patient, were in fact three morphological variants of the same lymphoproliferative process. METHODS: Previously described methods of clonal analysis using the polymerase chain reaction (PCR) were used to determine the pattern of rearrangements of the immunoglobulin heavy chain gene and the T cell receptor beta and T cell receptor gamma chain genes in the three lymphomas. RESULTS: All three morphological entities had identical patterns of gene rearrangements. CONCLUSIONS: This finding confirms the association between MALT lymphoma and monocytoid B cell lymphoma, and also provides evidence that large cell anaplastic lymphoma may not only arise de novo but may also be an end stage morphological picture in lymphoma progression.
Colonic Neoplasms↗
Ondansetron in intractable nausea and vomiting.
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Adult↗
Gut protection by cyclophosphamide "priming" in patients receiving high-dose melphalan--effect of drug scheduling.
A "priming" injection of cyclophosphamide (400 mg/m2 given i.v. on day -7) has been shown to reduce intestinal permeability and thus gut toxicity in patients receiving high-dose melphalan. To determine the optimal timing for this injection, patients receiving 200 mg/m2 melphalan with an autologous bone marrow transplant were randomly assigned to receive cyclophosphamide at 5, 7 or 9 days before the melphalan. The median percentage of [51Cr]-ethylenediaminetetraacetic acid excretion was similar (9.1% vs 7.1% vs 7.7%, respectively), with equivalent duration of WHO grade 2-4 mucositis and diarrhoea being recorded for each group. Thus, the timing of the cyclophosphamide prime is not critical, and the priming injection may be given between 5 and 9 days prior to high-dose melphalan.
Bone Marrow Transplantation↗
High-dose chemotherapy and autologous bone marrow transplantation for relapsed and refractory Hodgkin's disease.
The results of high-dose chemotherapy with melphalan or melphalan (carmustine) etoposide for 66 consecutive patients with relapsed or resistant Hodgkin's disease are described. 55 patients were evaluable for response and 22% of these achieved complete remission and 59% partial remission. The actuarial survival at 2 years was 45% and the principal factors determining survival were the sensitivity of the disease to therapy given before high-dose chemotherapy and the type of treatment received. Intensive chemotherapy with autologous bone marrow transplantation can produce long-term survivors among patients for whom long-term survival would otherwise be improbable. However, this treatment remains toxic with an uncertain place in management.
Adolescent↗
Proliferating cell nuclear antigen and S phase fraction in endometrial stromal sarcoma.
AIMS: To investigate the value of immunohistochemical staining for the cell cycle protein proliferating cell nuclear antigen (PCNA) and flow cytometric S phase fraction in determining prognosis in endometrial stromal sarcoma, graded according to mitotic count. METHODS: Seventeen endometrial stromal sarcomas from 13 patients treated at the Royal Marsden Hospital were analysed. Serial 5 microns sections were cut for haematoxylin and eosin and immunohistochemical staining for PCNA, performed using the murine monoclonal antibody PC10. PCNA positivity was expressed as a percentage of the total number of cells (PCNA index). Flow cytometric analysis was performed on nuclei extracted from paraffin wax sections. RESULTS: In the five patients who died of disease within five years, PCNA index varied between < 1% and 60% (mean 21%) and S phase fraction ranged from 11.3 and 20.1 (mean 13.8). Four patients who were apparently cured showed PCNA indices ranging from < 1% to 5% (mean 1.75%) and S phase fraction ranging from 1.4 to 3.5 (mean 2.3); and three patients alive with disease showed PCNA indices ranging from 1% to 15% (mean 8.6%) and S phase fraction ranging from 1.4 to 3.5 (mean 2.3). One patient who died from indolent local disease after nine years showed a PCNA of 1 or less and an S phase fraction of 0.9. CONCLUSIONS: PCNA staining was variable and therefore not a reliable prognostic indicator, but a high PCNA index was only found in those patients dying of disease within five years. A stronger association was seen between S phase fraction and prognosis; this also correlated well with histological grade determined by mitotic count. In individual borderline cases that are between low and high grade categories, these procedures may be useful.
Antigens, Neoplasm↗
High-dose busulfan in patients with myeloma.
PURPOSE: To evaluate the use of high-dose busulfan (HDB) with autologous bone marrow transplantation (ABMT) in patients with myeloma. PATIENTS AND METHODS: Fifteen patients received HDB (16 mg/kg), eight of whom received high-dose melphalan (HDM) but had experienced a short remission or progression-free interval. Two patients had received HDM on two previous occasions, one had no response to low-dose melphalan, and four had impaired renal function (edathamil clearance < 40 mL/min). All patients received induction chemotherapy before HDB. RESULTS: Two patients were in complete remission (CR) after induction chemotherapy before HDB. Of the remaining 13 patients, four (31%) achieved CR and two (15%) achieved a partial remission for an overall response rate of 46%. There were three treatment-related deaths, but the toxicity was otherwise predictable and manageable. CONCLUSIONS: In heavily pretreated patients, HDB results in a relatively high response rate. It can also be used safely in patients with renal impairment who are not suitable for HDM.
Adult↗
Molecular monitoring of low grade non-Hodgkin's lymphoma by gene amplification.
Molecular monitoring by the polymerase chain reaction was used to detect and follow minimal disease in working formulation category B and C on non-Hodgkin's lymphoma. Rearrangement of the bcl-2 gene served as the target for gene amplification. Thirty patients were studied. Bone marrow histology was compared to PCR analysis of bone marrow aspirate and blood. PCR upstaged disease status in approximately 50% of patients. Results are shown from a patient whose disease was followed with PCR during chemotherapy from initial remission to relapse. We conclude that PCR of bone marrow and blood can be used to upstage disease status in low grade lymphoma and PCR of blood may be used to monitor response to treatment with obvious patient benefit. The general approach of molecular monitoring provides a means for appraising therapies in the setting of subclinical disease.
Base Sequence↗
The pharmacokinetics of oral lonidamine in breast and lung cancer patients.
The plasma levels of lonidamine have been studied in 24 breast or lung cancer patients as part of the Phase II evaluation of the drug. The pharmacokinetic studies were performed when the patients had been on oral lonidamine therapy for 27 to 47 days (mean 32 days) and the studies were conducted over a 24 hour period. Lonidamine was administered in three divided doses of 150 mg (t = 0h), 150 mg (t = 7h), and 150 mg or 300 mg (t = 14h). Plasma levels of lonidamine were determined by high-performance liquid chromatography (HPLC) with fluorescence detection. Lonidamine was detected in the plasma of all patients studied, and the absolute range for the peak plasma levels of the drug following the first and second doses were 4.6-33.8 and 4.8-33.3 micrograms/ml, respectively. The range of times after administration at which the peak occurred was 0.5 to 4.2 hours for the first dose and 0.5 to 4.1 hours for the second. The absolute range for the trough levels observed over the 24-hour study period was 1.0 to 12.6 micrograms/ml and in 19 of the patients it was possible to define the apparent half life of lonidamine that was found to be within the range 2.5 to 11.7 hours. In addition to lonidamine, a number of fluorescent components were detected in the plasma of patients following lonidamine treatment that were not detected in pretreatment plasma samples. One component, a compound that eluted from the HPLC more rapidly than lonidamine, was found in some patients to be sensitive to hydrolysis with beta-glucuronidase. Comparison of the pharmacokinetic data with patient characteristics and clinical biochemistry results failed to establish any clear relationship. Similarly there was no relationship between lonidamine pharmacokinetics and either drug-induced myalgia or testicular pain. Insufficient responses were seen in the patient group studied to allow the relationship between lonidamine pharmacokinetics and response to be evaluated.
Absorption↗
ChlVPP combination chemotherapy for Hodgkin's disease: long-term results.
Two hundred and eighty-four patients with advanced Hodgkin's disease (HD) (stage II with poor prognostic features and stage III/IV) have been treated with the ChlVPP combination chemotherapy regimen (chlorambucil, vinblastine, procarbazine and prednisolone) in a single-centre unselected series. Median follow up is 92 months. Fifty-five patients had previously received radiotherapy but none had received previous chemotherapy. Eighty-five per cent of previously untreated patients and 91% of previously irradiated patients entered complete remission (CR); 71% and 68% of these respectively remain in CR at 10 years and 65% and 64% of each group respectively are alive at 10 years. On univariate analysis, age, stage, site of visceral disease and lymphocyte count predicted survival and on multivariate analysis age, absence of symptoms, absence of lung, liver or bone marrow disease and achieving a CR remained important predictors of survival. Acute toxicity was mild. The 10 year actuarial risk of acute leukaemia was 2.7%. This study adds further support to the view that chlorambucil is as effective and less toxic than mustine in combination chemotherapy for HD. We suggest that MOPP chemotherapy is no longer routinely indicated for HD.
Adolescent↗
A dose-comparative endocrine-clinical study of leuprorelin in premenopausal breast cancer patients.
Twelve premenopausal patients with advanced breast cancer were randomised to receive 3.75 or 7.5 mg of a slow release formulation of the luteinising hormone releasing hormone agonist leuprorelin once every 4 weeks. All patients were oestrogen receptor positive or unknown. Serum levels of gonadotrophins and oestrogens were suppressed markedly by both doses. All oestrogen values during treatment were within the postmenopausal range except for a single oestradiol level (274 pmol l-1) in one patient on the lower dose. There was no other indication that this lower dose was less effective as an oestrogen suppressant. There were two objective responders to the 3.75 mg dose and three to the 7.5 mg dose. Toxicity was confined almost entirely to hot flushes which occurred in 11/12 patients. We conclude that the slow release formulation of leuprorelin is effective in breast cancer treatment and that there is no major detriment to the use of the 3.75 rather than 7.5 mg dose.
Adult↗
In-vivo 31P magnetic resonance spectroscopy for monitoring treatment response in breast cancer.
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Antineoplastic Combined Chemotherapy Protocols↗
Prognostic significance of micrometastases in bone marrow in patients with primary breast cancer.
Metastatic breast cancer cells were found in the bone marrow of 60 (23%) of 269 patients with primary breast cancer, none of whom had metastatic disease disclosed by any other investigation, including bone scanning and radiological skeletal survey. We estimated the number of cancer cells as less than or more than 20 cancer cells seen. Twenty-six patients had less than 20 cancer cells present, and 34 had 20 or more. At a median follow-up time of 22 months, 53 patients had relapsed, 19 of 60 (31.7%) in the group found to have micrometastases and 34 of 195 (17.2%) in the group that had normal bone marrow. Patients with micrometastases are relapsing at a faster rate than those without micrometastases (P = less than 0.05). Patients with less than 20 cancer cells present are relapsing faster than those with no cancer cells but slower than those with 20 or more cancer cells (P = less than 0.01). We conclude that the presence of cancer cells in the marrow at primary diagnosis is a prognostic factor in patients with primary breast cancer.
Bone Marrow Diseases↗
Decrease in clonogenic tumour cells in bone marrow aspirates from multiple myeloma patients due to the incorporation of cyclophosphamide into treatment with vincristine, adriamycin and methyl prednisolone.
A study of 32 patients receiving cyclophosphamide (CY) and verapamil (VER) in addition to the drug combination vincristine, adriamycin and methyl prednisolone (VAMP) was made in which the clinical response and growth of clonogenic myeloma cells (MY-CFUc) from bone marrow aspirates were compared. At presentation, MY-CFUc were grown from 72 per cent (23/32) of the patients. After treatment with CY-VAMP or VERCY-VAMP, MY-CFUc were grown from 25 per cent (8/32) of patients of whom only 50 per cent responded clinically. The overall clinical response rate for patients receiving CY-VAMP and VERCY-VAMP was 64 per cent (9/14) and 72 per cent (13/18) respectively of whom 14 per cent in each group achieved complete remission. There was no concomitant increase in normal tissue toxicity as measured by granulocyte-macrophage colony (GM-CFUc) formation. Comparison of these data with our previous study of patients receiving VAMP alone, suggests that the addition of CY to the regimen may increase the tumour cell kill. Further clinical studies will determine whether there is a significant increase in the complete remission rate.
Antineoplastic Combined Chemotherapy Protocols↗