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V617F JAK2 mutation is a reliable molecular marker of polycythemia vera (PV), potentially useful to monitor the effect of treatments in this disease. In a phase 2 study of pegylated (peg) IFN-alpha-2a in PV, we performed prospective sequential quantitative evaluation of the percentage of mutated JAK2 allele (%V617F) by real-time polymerase chain reaction (PCR). The %V617F decreased in 24 (89%) of 27 treated patients, from a mean of 49% to a mean of 27% (mean decrease of 44%; P < .001), and no evidence for a plateau was observed. In one patient, mutant JAK2 was no longer detectable after 12 months. In 3 patients homozygous for the mutation, reappearance of 50% of wild-type allele was observed during treatment. The results seem to confirm the hypothesis that IFN-alpha preferentially targets the malignant clone in PV and show that %V617F assessment using a quantitative method may provide the first tool to monitor minimal residual disease in PV. This trial was registered at www.clinicaltrials.gov as #NCT00241241.

Unlabelled: Uterine sarcoma is a poor prognosis disease, with a high risk of metastatic relapse. We conducted a study of adjuvant chemotherapy with cisplatin, ifosfamide, and doxorubicin followed by radiotherapy (n=18). The results were then compared in a matched case-controlled study to radiotherapy alone (n=16) or no therapy at all (n=2). Chemotherapy consisted in three cycles of adriamyein-platinum-ifosfamide (API) (doxorubicin 60 mg /m2 on day 1; cisplatin 100 mg /m2 on day 2; ifosfamide 5 g /m2 on day 1+mesna 5 g /m2 on day 1+granulocyte colony-stimulating factor; q 3 weeks). Drug doses were reduced (20% for ifosfamide and cisplatin) four times (four patients) due to hematologic toxicity. Compared to a case-control study of adjuvant radiotherapy alone, results were not decreased by the addition of a toxic chemotherapy., Conclusion: Adjuvant API chemotherapy followed by radiotherapy is a feasible protocol; a multicenter phase III study comparing radiotherapy alone versus API chemotherapy followed by radiotherapy just began in France.

A 22-year-old woman was admitted in August 2001 for loss of consciousness due to hypoglycemia. Her serum insulin level during the hypoglycemic episode was high at 121 mU/l (normal range: 5-25 mU/l). She had never received an insulin injection. Insulin antibodies by radioimmunoassay were positive. During hospitalisation, the patient presented clinical and biological features of systemic lupus erythematosus (SLE). Treatment with high-dose corticosteroids and cyclophosphamide resulted in restoration of euglycemia associated with resolution of circulating anti-insulin antibodies and parallel improvement in clinical and laboratory features of SLE.

Optimal treatment of non operable localized non small cell lung carcinoma (NSCLC) continues to evolve. Increasing overall survival must evolute through improving local tumoral control and eradication of probable occult metastasis. Historically, median survival varies between 7 and 10 months with a standard conventional fractionated radiotherapy (RT). Induction chemotherapy (CT) followed by RT has demonstrated its superiority over RT alone, modality which is widely utilised. Other studies revealed best results with decreasing metastatic relapses. Three independent meta-analysis confirmed benefit obtained with cisplatin based CT followed by RT that allowed to consider this association as a gold standard. Other authors demonstrated an improvement of local control and survival with concomitant RT-CT or hyperfractionated accelerated RT. Results of all of these new therapeutic modalities still poor. Implication of new CT drugs has conducted for an emergence of new studies finding to demonstrate more encouraging results. Randomized trials are conducted in this way.

Chronic lymphocytic leukemia cell (CLL) usually (95%) express B-phenotype and the CD5 antigen which is usually present on the surface of normal T cells. However, among B CLL, 7 to 20% do not express CD5. The significance of the lack of CD5 expression remains unclear. We reviewed 42 consecutive CD5- B CLL seen in three French medical centers from 1985 to 1991 and compared them with 79 CD5+ B CLL. Immunophenotype studies were performed using indirect immunofluorescence under light microscopy as well as flow cytometry after 1988. B CLL was considered to be CD5 negative when less than 5% of mononuclear cells expressed CD5 after subtraction of the number of T-cells. Cases with CD5- B CLL had isolated splenomegaly more frequently (p = 2.10(-7)). They frequently expressed a higher level of surface immunoglobulin (S-Ig) or the switch mu/delta phenotype (p = 4.7 10(-2)). The median survival time was not reached but no significant difference between CD5 negative and positive B CLL was observed at the time of our data analysis (p = 0.97). Clinical presentation of CD5- B CLL seems to be different from other forms of B CLL. Although, no conclusion can be reached in terms of prognosis, CLL with low expression of CD5 should be regarded as a subtype of CLL with a different clinical presentation than CD5+ CLL.

We report the cytogenetic results obtained in 81 multiple myeloma (MM) patients with abnormal karyotypes. Most karyotypes were complex with numerical and structural abnormalities but the analysis of chromosomal abnormalities allowed identification of two cytogenetic patterns depending on the chromosome number: a first hyperdiploid pattern (54%) with recurrent trisomies 3, 5, 7, 9, 11, 15 and 19 and a second pattern (46%) showing either pseudodiploid, hypodiploid or near-tetraploid karyotypes. Structural abnormalities were present in all but five hyperdiploid karyotypes, and frequently involved lymphoid breakpoints: immunoglobulin gene regions (36 cases) or chromosome 11q13 region (21 cases). Numerous other structural aberrations were detected; the most frequent involved chromosome 1 and chromosome 13. Structural abnormalities were significantly more frequent in the second hypodiploid group. When analyzing the results obtained in the 60 patients studied at the time of diagnosis, a prognostic correlation was found between the cytogenetic pattern and overall survival: hyperdiploid patients had a longer survival than patients belonging to the pseudo/hypo/near-tetraploid group (median survival 36.8 vs 18.2 months, P < 0.04). These results suggest that MM could correspond to two closely related diseases.

Background: Systemic capillary leak syndrome (SCLS) is a rare condition characterized by unexplained episodic capillary hyperpermeability due to a shift of fluid and protein from the intravascular to the interstitial space. This results in diffuse swelling, weight gain, and renal shut-down. From the first publication in 1960, only 34 cases have been reported., Objective: To collate enough patients to observe the natural history of the disease and evaluate the efficacy of empiric treatments., Design: Multicentric retrospective study., Results: Thirteen patients (6 women and 7 men) were collated with a mean follow-up of 6.4 years. Eight patients are still alive after a mean of 5.6 years (range 1 to 15). Three patients out of the 11 who were not lost to follow-up died; 1 during an attack and 2 because of a progression towards multiple myeloma., Conclusions: Our series shows an improvement in the prognosis of SCLS due most likely to improved management during attacks. Some patients' disease could evolve into a multiple myeloma. Treatment is still empiric and no prophylactic therapy, including terbutaline associated with aminophylline, has clearly proven its efficacy.

Cytogenetic studies in multiple myeloma (MM) have been disappointing due to the low mitotic index of plasma cells. Recently the detection of clonal chromosomal abnormalities at diagnosis seemed to be improved by addition of cytokines (IL-6 and GM-CSF) in the culture medium. We performed two parallel total bone marrow cells culture types in 33 stage I, II and III multiple myeloma patients at diagnosis: 3 d without any cytokine, and 4-7 days stimulated with IL-6 and GM-CSF. No clonal chromosomal abnormality was detected in the 12 stage I and II patients either in 3 d or in 4-7 d culture. In stage II patients, abnormalities were observed in 18/21 (85.7%) and in 8/18 (44.4%) in the 3 d culture and the 4-7 d stimulated cultures respectively. Our results suggest that in stage III multiple myeloma at diagnosis, 3 d culture without cytokine may be the better technique to detect clonal chromosomal abnormalities, and, before using cytokines as a reference condition, this 3 d unstimulated culture should be considered.

The authors report a documented case of hyperphosphatemia-induced nephrocalcinosis after chemotherapy of an acute lymphoblastic leukemia (ALL). Microscopic examination of the kidney showed numerous calcium deposits with concentric structure in the calyces and in the tubules. Electronic microsound analysis proved the deposits to be composed of calcium phosphate. The nephropathy mechanism is studied, and a review of the 34 similar cases of this acute tumor lysis syndrome is made. Some suggestions are put forward to present the consequences of this therapy-induced syndrome.

Nephrocalcinosis due to hyperphosphataemia with hypocalcaemia is a rare cause of ARF during chemotherapy of ALL. Three cases are reported, one with renal anatomopathological studies and microanalysis of the intratubular calculi. All possible preventive measures should be taken against this complication which is related to acute tumoral lysis, especially in the hyperleukocytic and/or tumoral forms of ALL.

Cases of two newborns with acute lymphoblastic leukemia (ALL) L2 type, are reported. In each case, some chromosomal abnormalities can be found. In the first case, a translocation t (4;11) is noticed. It has to be compared with already published patients' cases and so the non randomly occuring character of those alterations in ALL and poor pronostic factor can be confirmed. In the second observation, a complex translocation t (5;6;X) never described before in literature, was observed. Chromosomal findings in ALL are not only a help to diagnosis but, by cytogenetic data, are also a help to accurate prognosis and adequate treatment.

Lipoproteins have previously, been studied in various myeloproliferative disorders. This study focused only on agnogenic myeloid metaplasia (AMM). Total cholesterol (TC), phospholipids (PL) and triglycerides (TG) were measured not only in serum but also in HDL, VLDL and LDL with in the same time total apolipoproteins A1 and B. Besides hypocholesterolemia (p less than 0.01) HDL-TC were significantly diminished in mmol/l (p less than 0.01) and in percentage (p less than 0.01) while LDL.TC was decreased in mmol/l (p less than 0.01). The whole lipid moity (TC + PL + TG) of VLDL was increased (p less than 0.05). Cardiovascular diseases occur frequently in these hypocholesterolemic patients. Atherogenic ratios: LDL.TC on HDL.TC or VLDL.TC + LDL.TC on HDL.TC were not significantly higher than matching age and sex controls. Atherogenic risks could be partly related to the significant decrease of HDL.TC.