A case of trisomy 5 in a Philadelphia positive leukemia.
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Biomedical subjects
Publications and source records attributed to M Krulik.
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Twenty patients with documented progression after two or three cisplatin-based regimens for advanced epithelial ovarian carcinoma were treated with high-dose folinic acid (200 mg/m2), 5-fluorouracil bolus (400 mg/m2) and continuous infusion (600 mg/m2) for two consecutive days every two weeks. One clinically complete and two partial responses were observed in 16 evaluable patients, with 5 remaining stable. Median survival was 9 months. Toxicity was mild. This combination achieved a 19% (95% confidence interval 4%-46%) response rate in heavily pretreated cisplatin-resistant patients.
The presence of an haematological cytogenetic laboratory into a clinical unit allowed to realize a close collaboration between clinicians and cytogeneticists, and to achieve a maximal exploitation of the results of the bone marrow cytogenetic studies in some haematological malignancies. It made it possible to perform sequential bone marrow karyotypes studies during the different phases of a disease: We could thus establish: The diagnostic value of cytogenetic findings for chronic myelocytic leukaemia, secondary acute leukaemia, but not for dysglobulinemias. The prognostic value of cytogenetic abnormalities in chronic myelocytic leukaemia where additional abnormalities to the Ph1 are a hallmark of blastic transformation; in primitive dysmyelopoiesis where they represent a bad prognostic factor; in dysglobulinemias, where they are a signal of terminal evolution. In all these diseases, only complex and multiple abnormalities have a prognostic significance pointing out the emergence of a malignant clone, where as rare and single abnormalities are of no significance. Nowadays, haematological cytogenetic must be bound to molecular biology.
We report an additional cytogenetic study of a metastatic Merkel cell carcinoma. Even though the cells analyzed were from a metastatic lesion, chromosomal abnormalities were not complex. Similarities between cytogenetic findings described in small-cell lung carcinoma and the present case are observed. However, further studies are needed to define the relationship between these two neuroendocrine small-cell malignancies.
Plasma cell leukemia (PCL) is a very rare disease. We report two cases of PCL with complex chromosomal abnormalities: long arm trisomy and short arm partial monosomy of chromosome 1, a marker derived from chromosome 8, and monosomy 13 were found in both cases; other additional chromosome abnormalities were also present in each case. Bastard et al. reports two similar cases in this issue. Cytogenetic studies in PCL have seldom been reported in the literature: chromosomal abnormalities are most often complex: chromosomes 1, 8, 11, 13, and 14 are those most frequently involved. Such cytogenetic findings are observed in advanced multiple myeloma. Cytogenetic, clinical, and immunological findings observed in PCL and the advanced stage of multiple myeloma are arguments for the single origin of pathogenesis.
Twenty-five patients with advanced measurable gastric cancer were treated with high-dose folinic acid (200 mg/m2), 5-fluorouracil bolus (400 mg/m2) and continuous infusion (600 mg/m2) for two consecutive days every two weeks. Fourteen patients over 65 yr old and/or with a poor general status received first-line treatment, and eleven younger patients second-line. The response rate was 43.5% in 23 evaluable patients. There were 2 complete responses (8.7%) and 8 partial responses (34.8%). Median survival was 6 months in first-line and 8 months, calculated from start of folinic acid-5FU, in second-line. Toxicity was mild without WHO Grade greater than 2 events. This combination is effective for advanced gastric cancer in poor-prognosis patients and requires further studies.
Eighteen patients with advanced gastric cancer were treated with cisplatin 80 mg/m2 d 1, doxorubicin 30 mg/m2 d 3 and mitomycin-C 12 mg/m2 d 3. One complete and 6 partial responses were observed in 17 evaluable patients (41%, confidence interval 17-65%). Median duration of response was 7 months; median survival was 8 months. One death due to toxicity was observed. This combination of 3 active drugs should not be recommended in cases of gastric cancers.
Clinical, hematologic, and cytogenetic data of nine patients with refractory anemia with excess of blasts in transformation (RAEB-t), classified according to the French-American-British Cooperative Group for myelodysplastic syndrome (MDS), are reported. At diagnosis, eight out of nine cases, had chromosomal abnormalities and three out of nine developed acute leukemia. Karyotype studies allowed individualization of two groups of patients: five with nonrandom major karyotype abnormalities (MAKA) including hypodiploidy, chromosomes 5 and 7 involvement, at least four other abnormalities, and a poor prognosis (survival always under 3.5 months); and four patients with either normal karyotypes or minor karyotype abnormalities (MIKA) (no more than three abnormalities) and a better prognosis (survival from 14 to 38 months). Karyotype appears to be a major prognostic factor among RAEB-t.
Second-look laparotomy (SLL) was performed after chemotherapy in 86 patients with advanced epithelial ovarian cancer. Seventy-one patients received cisplatin-based regimens. Median follow-up was 66 months. Negative SLL was found in 32 patients who had a 5-year survival rate of 48.3% after SLO. Microscopic residual disease was present in seven patients whose 5-year survival rate was 35.7%. Maximum residual tumor of 2 cm or less was found in 13 patients with a 5-year survival rate of 30%. Residual tumor larger than 2 cm after secondary cytoreduction was present in 20 patients; their 3-year survival rate was 19.7%. Fourteen patients with bulky residual disease who did not have cytoreduction were all dead within 17 months. Patients with initial residual tumor at first laparotomy less than 2 cm had a nearly significant advantage in survival rate over patients with residual disease greater than 2 cm and stage IV (P = 0.07). Non-responders to initial chemotherapy had a survival rate similar to that of partial responders. These findings justify discontinuation of conventional systemic chemotherapy for patients showing residual disease after SLL and secondary tumor removal in case of residual tumor at SLL. Therapeutic trials are needed in advanced ovarian cancer testing initial aggressive surgery or early debulking to avoid bulky residual disease, and consolidation therapy in patients who achieved complete pathological response or minimal residual disease.
Second-look laparotomy (SLL) was performed after chemotherapy in 106 patients with epithelial ovarian cancer. Thirteen were stage I and II and 93 stage III and IV. Seventy-eight patients received cisplatin-based regimens. Median follow-up was 60 months. Negative SLL was found in 32 patients who had a 5-year survival rate of 43.4% after SLO. Microscopy residual disease was present in 9 patients whose 5-year survival rate was 25%. Maximum residual tumor of 2 cm or less was found in 13 patients with 5-year survival rate of 30%. Residual tumor larger than 2 cm after secondary cytoreduction was present in 21 patients, their 3-year survival rate was 18.3%. Eighteen patients with bulky residual disease who did not have cytoreduction were all dead within 17 months. Patients with initial residual tumor at first laparotomy less than 2 cm had a near significant advantage in survival rate over patients with residual disease greater than 2 cm and stage IV (p = 0.07). Non-responders to initial chemotherapy had a survival rate similar to that of partial-responders. These findings justify discontinuation of conventional systemic chemotherapy for patients showing residual disease after SLL and secondary tumor removal in case of residual tumor at SLL. Therapeutic trials are needed in advanced ovarian cancer testing initial aggressive surgery or early debulking to avoid bulky residual disease and consolidation therapy in patients who achieved complete pathological response or minimal residual intraperitoneal disease.
We report here the case of a patient with refractory anemia with excess of blasts (RAEB) which evolved into RAEB in transformation. The standard Philadelphia (Ph) chromosome was found by cytogenetic study at diagnosis and during evolution. Southern blot analysis showed breakpoint cluster region (bcr) rearrangement as observed in chronic myelogenous leukemia (CML).
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An enhanced antineoplastic effect of 5-fluorouracil in patients with advanced colorectal cancer has been produced either by combination with folinic acid or administration by continuous infusion. Thirty-seven patients with advanced measurable colorectal cancer received high-dose folinic acid (LV 200 mg/m2) followed by 5-fluorouracil i.v. bolus (300 mg/m2) and continuous infusion (300 mg/m2) on days 1 and 2 then 14 and 15 every 4 weeks. In the absence of toxicity, 5-FU was increased to 400 mg/m2 i.v. bolus and continuous infusion at course 2 and to 500 mg/m2 at course 3 and from course 4 maintained at 500 mg/m2. Responses were: complete responses: 1 (2.7%), partial responses: 19 (51.4%), no change: 8 (21.6%) and progressive disease: 9 (24.3%). CEA decrease was correlated with response. Median duration of response was 11 months. Median survival was 18 months, 21% of the patients were alive at 2 years. Toxicity was low, with diarrhea in 17% and nausea in 11.5% of the patients. LV-5-FU bolus and continuous infusion is safe and has definite activity in metastatic colorectal cancer.
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Twenty-eight patients with Ph-positive chronic myelocytic leukemia (CML), who all died of the disease, had cytogenetic studies throughout the progression of the disease: at diagnosis, during chronic phase (CP), accelerated phase (AP), and blastic transformation (BT). The aim of this sequential study was to appreciate the frequency and the significance of additional chromosomal abnormalities (ACA) during CML evolution, especially in the CP. In our series ACA were rare (five of 28 patients) and simple (four of five) in CP. They were much more frequent and complex in AP (11 of 16) and in BT (22 of 24) with complex abnormalities (13 of 24). In CP, ACA predictive value for metamorphosis was poor: only three of 13 patients had ACA within 1 year before BT, and only two of 11 within 1 year before AP. ACA were mainly observed during the last period before BT: ten of 17 patients studied within 6 months prior BT had ACA, but by then two of three were in AP. ACA, especially when complex, appear to be a hallmark of CML metamorphosis.
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