[Successive myeloblastic and megakaryoblastic transformations of chronic myeloid leukemia].
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Biomedical subjects
Publications and source records attributed to A Thyss.
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Thirteen patients with cancer being treated with high-dose methotrexate (MTX) chemotherapy (350-5,000 mg/6 h IV were entered in this study. Plasma levels of MTX and 7-OHMTX, its main circulating metabolite, were measured by an HPLC technique. 7-OHMTX appears rapidly in the blood, reaching a maximum 6-12 h after the beginning of treatment. The elimination of 7-OHMTX is slower than that of MTX, but the elimination half-lives (24-48 h) are not significantly different: 25.2 h for 7-OHMTX versus 20.3 h for MTX. In all cases, 24 h after starting infusion plasma levels of 7-OHMTX exceeded those of MTX. There was a positive and significant correlation between the dose administered and peak plasma 7-OHMTX. Finally, 7-OHMTX formation was shown to be relatively stable throughout the treatment.
In connection with six cases of colorectal lymphomas, including five cases of non-Hodgkin lymphomas (3 primary, 2 secondary), and one case of Hodgkin's disease, the authors review the literature concerning the general features and radiological aspects of these pathologies. The radiological signs observed during barium enemas for non-Hodgkin lymphomas are as follows: a small nodular pattern, frequently with multiple lesions (45.7% of cases), a diffuse or infiltrating pattern (25.4%), a filling defect (22.9%), endo- and exo-luminal images (17.8%), ulcerating patterns (3.4%) and a pure mesenteric form (0.8%). Thus, associated radiological forms are present in 16% of cases. The preferential site is the caecum (52.5% of cases), followed by the rectum (21.2%). Colonic or rectal involvement by Hodgkin's disease is extremely rare. From a radiological viewpoint, the most frequently described pattern in the literature is an infiltrating lesion which may or may not cause stenosis; the most frequent site is the caecum.
Of the various prognostic factors for cancer, biological parameters of the Host/Tumour relationship allow objective evaluation of the conflict between the organism and the disease. Alpha 1-acid glycoprotein (Orosomucoïd), which belongs to the Acute Phase Reactant's Proteins, and prealbumin, a highly sensitive nutritional protein, are two compounds whose blood levels vary in inverse proportion during perceptible-stage cancers: alpha 1-acid glycoprotein concentrations increase while prealbumin values drop. The ratio of the blood levels of these two parameters provides a more sensitive index than either parameter taken alone. Study of the orosomucoïd/prealbumin ratio (ROP) in a population of 132 patients and 63 controls revealed a good association between the ratio values and the different stages of the disease. The highest values corresponded to patients with active disease; normal levels were obtained for patients in partial or complete remission. During the course of disease, the orosomucoïd/prealbumin ratio is more reliable than the sedimentation rate. Furthermore, when measured at the onset of the disease, this ratio is an undeniable prognostic element, independent of the stage of disease extension.
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The urinary polyamines putrescine (PU) and spermidine (SPD) were measured for 67 patients with lymphomas: 48 non-Hodgkin (NHL) and 18 Hodgkin's disease (HD). Monthly repeat measurements were obtained over an average follow-up period of 12.5 months. For NHL, a good association was observed between polyamine levels and the severity of the the stage; the distribution of values between nodular and diffuse forms was also significantly different. No such correlations were seen for HD. The evolution of PU values in time has been shown to reflect disease activity for NHL. Non-specific fluctuating Pu values were found in the case of HD. In the case of 20 patients with NHL undergoing chemotherapy, comparison of polyamine levels before and after chemotherapy allowed differentiation between the population of complete responders to treatment and those with only partial or no response.
Biological detection of liver metastases represents an important factor in the surveillance of the course of cancerous affections. The authors present a report on a potential new indicator, the isoenzyme of alkaline phosphatase migrating to the alpha 1 region (alpha 1 ALP). In comparison to those tests considered the most sensitive at present-gamma glutamyl transferase and total alkaline phosphatase-this alpha 1 isoenzyme appears more sensitive and more specific, capable of detecting 97% of liver metastases with a specificity of 90%.
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From September 1983 to September 1987, 238 patients with squamous cell carcinoma of the upper aerodigestive tract were given 3 cycles of chemotherapy [cisplatinum (cis-DDP), 100 mg/m2 on day 1; 5-fluorouracil (5-FU), 1,000 mg/m2 on days 2-6] before any local treatment. Eighty-one of these patients had pharyngolaryngeal cancer. Of the 45 of 50 laryngeal cancers and 26 of 31 hypopharyngeal cancers suitable for evaluation, complete responses (CR) were obtained in 51.1% and 53.8%, respectively. These response rates led to changes in the postchemotherapy protocols. For CRs, multilating surgical protocols were replaced by definitive radiotherapy: one local recurrence has been observed among the 9 laryngeal cancers, and 3 of 10 hypopharyngeal cancer patients, who had an initial indication of total laryngectomy or total pharyngolaryngectomy replaced by radiotherapy. In the group of CR, survival rates at 2 years were 93% and 69%, respectively, for the larynx and hypopharynx vs 65.6% and 40% for non-CR patients. The possibility of conservative treatment sparing vocal function with a high degree of reliability would in itself appear to be justification for induction chemotherapy in pharyngolaryngeal cancers, even though its long-term effects remain controversial.
Systemic delivery of mitomycin C (MMC) was studied in 6 patients administered microencapsulated MMC (MMC-mc) by an intra-arterial route (IA): 3 IA liver infusions, 3 IA pelvic infusions. Pharmacokinetic data revealed a lower blood MMC availability (peak plasma levels, AUC 0-4 hours) for the pelvis than for the liver; this was attributed to differences in the blood flow infusion rates at these two sites of administration. Direct comparison of systemic MMC exposure was possible for one patient, who received both IA liver MMC (10 mg in standard form, which served as the control) and IA liver MMC-mc (20 mg the day after). The 65% reduction in MMC-mc bioavailability observed for this patient indicates a quantitative local improvement in exposure to the drug and correlates well with the low incidence of systemic side effects noted in preliminary clinical studies.
Primary lung sarcomas are uncommon histologic types of primary lung cancer and presents a wide spectrum of clinical behaviour. Nine patients treated at Antoine Lacassagne Cancer Center between 1982 and 1995 were studied. The median age was 63 years (range, 35-73 years) and the most common histologic types were malignant fibrous histiocytoma (four) and leiomyosarcoma (three). All of them underwent surgery, six patients had a complete surgery and three patients incomplete resections. The median overall survival for all patients was 36 months. In the subgroup of patients with initial complete resection, the median survival was significantly longer (47 months) than in the subgroup of patients with incomplete resection (6 months) (P<0.05, log-rank test). Moreover, two patients had a second complete resection for ipsilateral lung relapse and were long survivors (overall survival of 58 and 83 months, respectively). The ability to achieve a complete second surgery stress the possible benefit of an early detection of local recurrence. Because no specific symptom was linked with the local relapse, a systematic CT scan every 2 or 3 months could be required.
Ondansetron, a highly selective 5-HT3 receptor antagonist, is available in an intravenous (IV) formulation and tables, but syrup would be particularly useful in children. As chemotherapy can affect taste perceptions, this study was undertaken to determine the preference between two flavors of ondansetron syrup in children undergoing chemotherapy. Fifty-nine children, randomized into a multicenter, double-blind, crossover study, each received 5 mg/m2 of IV ondansetron daily before chemotherapy. The syrup was then randomly given in two doses, one of each flavor, strawberry and grape, 30 minutes apart. The preference was assessed 30 minutes after the second dose of syrup had been administered. Taste was assessed by the child against a panel of five faces. Of those children expressing any preference, 70% preferred the strawberry flavor. Overall, 59% of children preferred the strawberry flavor, whilst 25% preferred grape (P = 0.005) and 15% expressed no preference. The only adverse event assessed as drug related by the investigator was constipation, which occurred in one patient. In conclusion, a strong preference was found for the strawberry formulation. The ondansetron syrup was safe and well tolerated.
The present study was designed to address the question of the early identification of patients at risk of developing cisplatin (CP)-related delayed emesis. This study included demographic, clinical, biological and pharmacological data and was conducted on 110 consecutive patients treated by CP-based chemotherapy. A previously validated single-point CP pharmacokinetic evaluation was performed in all patients. A total of 110 cycles was analyzed. Delayed vomiting (i.e., occurring between day 3 and day 7 following CP administration) was observed in 36.4% of cycles. Among the tested variables, the occurrence of delayed emesis was significantly related to elevated ultrafilterable (UF) platinum concentration (measured 16 h after the end of CP administration) and to low plasma magnesium concentration (measured 48 h before CP administration). Risk-thresholds for delayed emesis were established for UF platinum and magnesemia, at 60 ng/ml and 58 mmol/l, respectively. In the sub-group of patients with magnesemia determination, this later parameter was the only significant predictor of delayed emesis. Gender, cycle number, primary cancer location and age were not associated with the risk of developing delayed emesis. The ability to select patients at risk of delayed vomiting may offer a practical means of targeting administration of specific treatments.
In a prospective, multicenter study, we evaluated the incidence of adverse cardiac effects in 1097 patients receiving 5-FU as a short i.v. perfusion or as a continuous perfusion over 3 to 5 days. There were 29 cardiac events (incidence 1.6%; 4.5% in patients with a history of cardiovascular disease, 1.1% in the remainder). Adverse effects were more frequent in the patients with advanced WHO (WHO = OMS) stage (2 or 3) primary tumors of the upper respiratory or digestive tract, or of the gastrointestinal tract, when 5-FU was given as a continuous perfusion. They also appeared to be more frequent in patients with a history of cardiovascular disease, and mainly occurred during the second or third day of the first course of treatment. Retreatment of eight patients with 5-FU led to the recurrence of symptoms in five. The outcome of these adverse cardiac effects was generally favorable, but 11.5% of the patients died.
The authors describe 10 cases of malignant non Hodgkin's lymphoma in a mammary site in women aged 38 to 82 years. The clinical examination and the sometimes suggest an adenocarcinomatous lesion, thus leading to a useless surgical exeresis. An initial histological study provides the diagnosis. A complete assessment of extension allows an accurate staging and the refinement of the therapeutic schedule. Exclusive radiation therapy seems to be justified in low-malignancy forms remaining strictly confined to the breast. For the high- and medium-malignancy forms, the essential weapon is chemotherapy, which seems to improve the duration and rate of remission.
Two cases occurred of granulocytic sarcoma with cerebrospinal fluid involvement but no associated leukemia on presentation. Both cases were difficult to identify by histology and were initially misdiagnosed as malignant lymphoma. The characteristic cerebrospinal fluid cytologic picture allowed the diagnosis. These cases underscore the value of cytologic examination of tumor imprints and the use of myeloid markers in panels for immunophenotyping lymphomas.
Patients with lymphoma frequently develop neurologic abnormalities mainly due to nervous system infiltration but also direct drug toxicity. Moreover Guillain-Barré syndrome (GBS) remains a possible neuropathy, rarely described in non-Hodgkin's lymphoma. We describe a case of GBS in a patient with non-Hodgkin's high grade lymphoma. A 74-year old man with a newly diagnosed stage I high-grade lymphoma (precursor B-cell Burkitt like type according to the R.E.A.L. Classification) develop flaccid quadriparesis, 7 days after the end of the third course of CHOP treatment. The clinical course and neurological examination were consistent with GBS. The patient was in tumoral complete response. Despite appropriate treatment and a transfer in a reanimation unit, the patient died 3 days after the beginning of neurologic symptoms. The low number of cases described in the international literature doesn't permit to understand the association of this neurologic disease with non-Hodgkin's lymphoma. Collecting more data could lead interesting information to know the place of malignant hematological disease in the natural history of GBS.
The authors report on 3 cases of malignant lymphoma associated with well-defined lytic lesions of the skull and limbs that were identical to lesions observed in patients with multiple myeloma. In two patients, subcutaneous nodules were found opposite the site of bone lysis. Histologic examination diagnosed centrofollicular cell malignant lymphoma in all 3 cases. The exceptional nature of such lesions in patients with malignant lymphoma is discussed in connection with literature data. The suggested physiopathologic mechanism is secretion of an "osteoclast activation factor" (OAF) by malignant lymphoid B cells.