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Resume La viabilite de l’os est compromise dans deux situations principales au niveau du poignet : la maladie de Kienbock et l’osteonecrose du pole proximal du scaphoide fracture. La radiographie standard et la tomodensitometrie permettent une approche anatomique precise des modifications morphologiques liees a la necrose du lunatum et de la fracture du scaphoide avec ses complications. La tomodensitometrie est d’acces facile pour detecter les fractures non deplacees. En revanche, les formes precoces de necrose echappent et l’evaluation de la vitalite osseuse est impossible. En IRM, les anomalies precoces sont mieux detectees et l’injection intraveineuse de gadolinium ameliore la specificite du diagnostic de necrose. L’absence de rehaussement du fragment proximal du scaphoide pousse le chirurgien a utiliser un greffon vascularise dans le traitement de la pseudarthrose. La technique a cependant ses limites. La necrose osseuse est histologiquement complexe et la prise de contraste ne signifie pas forcement viabilite. L’IRM est neanmoins l’examen d’imagerie le plus puissant dans l’exploration de la moelle osseuse.

The functional ability of PNH reticulocytes was studied by in vitro investigations on reticulocyte-rich suspensions obtained from the blood of eight patients with PNH. The parameter used was the incorporation of 59Fe and of glycine-2-14C, and the results were related to RNA content of the reticulocytes. Iron appeared to enter the PNH cells normally but a relatively small amount was protein bound. In contrast to the behaviour of normal reticulocytes in control experiments, in the PNH reticulocytes there was little or no iron incorporation. The block of haem synthesis was also demonstrated by a four to five fold reduction in incorporation of glycine into haem. Globin synthesis appeared to be unaffected. These findings support the suggestion that in PNH there is a disturbance of the integrated process of cell maturation, demonstrable at the reticulocyte level.

MRI of the post-traumatic penis. Penile trauma, though rare, requires specialized management. Fibrotic sequelae from lesions of the tunica albuginea and corpora cavernosa must be prevented given their impact of the erectile function. Knowledge ofpenile anatomy enables acquisition and interpretation of penileMRI, preferably performed in the first few hours following injury. Tearof the tunica albuginea must be identified since it requires surgical management.Other lesions may be present at the acute (hematoma) or chronic(fibrosis, arteriocavernous fistula) phases. MRI, non-invasiveand painless, is the imaging modality of choice in the multiplanarevaluation of traumatic injuries of the penis.

The metabolism of ifosfamide is a delicate balance between a minor activation pathway (4-hydroxylation) and a mainly toxification pathway (N-dechloroethylation), and there remains uncertainty as to the optimal intravenous schedule.This study assesses ifosfamide pharmacokinetics (PK) according to two standard schedules. Using a 1:1 randomized trial design, we prospectively evaluated ifosfamide PK on two consecutive cycles of 3 g/m2/day for 3 days (9 g/m2/cycle) given in one of two schedules either by continuous infusion (CI) or short (3 h) infusion. Highly sensitive analytical methods allowed determination of concentrations of ifosfamide and the key metabolites 4-hydroxy-ifosfamide, 2- and 3-dechloroethyl-ifosfamide.Extensive PK analysis was available in 12 patients and showed equivalence between both schedules (3 h versus CI) based on area under the curves (micromol/l x h) for ifosfamide, 4-hydroxy-ifosfamide, 2- and 3-dechloroethyl-ifosfamide (9,379 +/- 2,638 versus 8,307 +/- 1,995, 152 +/- 59 versus 161 +/- 77, 1,441 +/- 405 versus 1,388 +/- 393, and 2,808 +/- 508 versus 2,634 +/- 508, respectively, all P0.2). The classical auto-induction of metabolism over the 3 days of infusion was confirmed for both schedules.This study confirms similar PK for both active and toxic metabolites of ifosfamide in adult cancer patients when 9 g/m2 of ifosfamide is administered over 3 days by CI or daily 3-h infusions.

International audience; This paper deals with portfolio optimization under different risk constraints. We use a set of hedge funds where departures from normality are significant. We optimize the expected return under standard deviation, semivariance, value-at-risk (VAR) and expected shortfall (or CVAR) constraints. As far as the VAR is concerned, we compare different estimators. While the optimization with respect to VAR constraints appears to be difficult and lengthy, there are very fast optimization algorithms for the other risk constraints. We find that the choice of a particular VAR estimator is less discriminant than the choice of the risk constraint itself. We provide financial interpretations of the optimal portfolios associated with a decomposition of risk measures.

Yondelis (trabectedin, ET-743) is a novel marine-derived anticancer compound found in the ascidian Ecteinascidia turbinata. It is currently under phase II/III development in breast cancer, hormone refractory prostate cancer, sarcomas and ovarian cancer. Activity in breast cancer experimental models has been reported, and preliminary evidence of activity in this setting during the phase I programme has also been observed. The present study assessed the activity and feasibility of trabectedin in women with advanced breast cancer previously treated with conventional therapies. Patients with advanced disease previously treated with at least one but not more than two regimens that included taxanes or anthracyclines as palliative therapy were eligible. Trabectedin 1.5 mg m(-2) was administered as a 24-h continuous infusion every 3 weeks. Patients were kept on therapy until disease progression, unacceptable toxicity or patient refusal. Twenty-seven patients were included between April 1999 and September 2000. Their median age was 54 years (range: 36-67) and 63% of them had two metastatic sites. Twenty-two patients were performance status 1. All patients had previously received anthracyclines, and 23 out of 27 patients had received taxanes. Of 21 patients with measurable disease, three confirmed partial responses, one unconfirmed partial response and two minor responses (49 and 32% tumour shrinkage) were observed; six patients had stable disease. Median survival was 10 months (95% confidence interval: 4.88-15.18). Transient and noncumulative transaminitis was observed in most of the patients. The pharmacokinetic profile of trabectedin in this patient's population is in line with the overall data available with this schedule. The policy of dose adjustments based on the intercycle peaks of bilirubin and alkaline phosphatase appears to have a positive impact in the therapeutic index of trabectedin. Trabectedin can induce response and tumour control in previously treated advanced breast cancer, with manageable toxicity, thus warranting further development as a single agent or in combination regimens.

In order to visualize and quantify dopamine transporters, the synthesis of two novel ligands labelled with technetium-99 m (99mTc) has been investigated. A multi-step synthesis afforded two target ligands with a tropane skeleton and a macrocyclic complexing moiety. The choice and the position of substituents are in adequation with dopamine transporter structure. The radiolabelling of these ligands with 99mTc has been studied and the results make them good candidates for SPECT imaging. Copyright © 2002 John Wiley & Sons, Ltd.

This comparative phase III trial of mitoxantrone+vinorelbine (MV) versus 5-fluorouracil+cyclophosphamide+either doxorubicin or epirubicin (FAC/FEC) in the treatment of metastatic breast cancer was conducted to determine whether MV would produce equivalent efficacy, while resulting in an improved tolerance in relation to alopecia and nausea/vomiting. This multicentre study recruited and randomised 281 patients with metastatic breast cancer; 280 were evaluable for response survival and toxicity (138 received FAC/FEC, 142 received MV). Patient characteristics were matched in each arm and stratification for prior exposure to adjuvant therapy was made prospectively. The overall response rate (ORR) was equivalent in the two arms (33.3% for FAC/FEC versus 34.5% for MV), but MV was more effective in patients who had received prior adjuvant therapy (13% (95% confidence interval (CI) 3-23) for FAC/FEC versus 33% (95% CI 20-47) for MV P=0.025) with a better progression-free survival (PFS) (5 months (range 1-18 months) versus 8 months (range 1-27 months); P=0.0007 for FAC/FEC versus MV, respectively) while FAC/FEC was more effective in previously untreated patients (ORR 43% (95% CI 33-53) versus 35% (95% CI 25-45), P=0.26; PFS 9 months (range 0-29 months) versus 6 months (range 0-26 months) P=0.014). Toxicity was monitored through the initial six cycles of therapy; febrile neutropenia and delayed haematological recovery was more frequent for MV (P=0.001), while nausea/vomiting of grades 3-4 was greater for FAC/FEC (P=0.031), as was alopecia (P=0.0001), cardiotoxicity was the same for the two regimens. MV represents a chemotherapy combination with equivalent efficacy to standard FAC/FEC and improved results for patients who have previously received adjuvant chemotherapy. Toxicity must be balanced to allow for increased haematological suppression and risk of febrile neutropenia with MV compared with a higher risk of subjectively unpleasant side-effects such as nausea/vomiting and alopecia with FAC/FEC.

The putative role of hepatitis C virus (HCV) infection in the pathophysiology of lymphoproliferative diseases (LPD) is supported by North American and southern European studies reporting high HCV seroprevalence in patients with B-cell-non-Hodgkin lymphoma (NHL). In order to evaluate the situation in France, we conducted a retrospective national study about the association of chronic HCV infection and LPD. 72 Internal Medicine and Infectious Diseases departments were contacted. Response rate was 51.4%. We recorded 43 LPD (19 males, 24 females): 31 B-cell-NHL, 4 Waldenstrom's macroglobulinemia, 3 chronic lymphocytic leukemia, 2 multiple myeloma, 2 lymphomas of the mucosa-associated lymphoid tissue, and 1 Hodgkin's disease. Mean age at HCV diagnosis was 62 years (range 33-84). In 16 cases, LPD occurred in patients known to be HCV-infected. For 11 patients, LPD diagnosis preceded the diagnosis of HCV infection, whereas diagnosis was done simultaneously in 11 patients. For those with accurate infection date, mean interval between both events was 15.2 years. Fourteen patients had HCV extrahepatic manifestations: 9 mixed cryoglobulinemia, including 7 with NHL, 5 sicca syndrome (5 NHL), and both in one patient. Cohort of HCV-infected patients could be accurately determined for 16 departments, totaling 1,485 patients and 37 cases. Thus, from our data the frequency of LPD among HCV-infected patients approximates 2. 49%. Despite possible bias inherent to this retrospective study, our data support the hypothesis of HCV-associated LPD and particularly B-cell-NHL. In France, this association is much lower than in Italy. Further studies are needed to assess the precise role of HCV in the multistep process leading to monoclonal proliferation.

PURPOSE The study investigated the therapeutic effects of a combination of Navelbine (vinorelbine or 5'noranhydrovinblastine; Pierre Fabre Médicament, Boulogne, France) and doxorubicin in women who had received no prior chemotherapy for locally advanced or metastatic breast cancer. PATIENTS AND METHODS Ninety-seven patients with progressive and assessable advanced or metastatic breast cancer who had received no prior chemotherapy except in an adjuvant setting were entered onto the study. Eighty-nine patients were assessable for toxicity and response by World Health Organization (WHO) criteria; the other eight patients were excluded because they did not meet entry criteria or because of protocol violations. Navelbine was administered at 25 mg/m2 by 30-minute intravenous (IV) infusion on days 1 and 8, and doxorubicin at 50 mg/m2 by slow IV infusion on day 1, with each course repeated at 3-week intervals. Patients were treated for a maximum of 11 cycles or until progression or major toxicity. RESULTS Objective responses were observed in 66 of 89 assessable patients (74%; 95% confidence interval, 63% to 85%). There were nineteen (21%) complete responses (CRs) and 47 (53%) partial responses (PRs). In addition, 20 patients (22.5%) had stable disease and three (3.5%) progressed while on treatment. Responses were observed at all sites of metastatic disease. Forty-one of 58 patients with visceral disease responded (71%) and 25 of 31 with soft tissue and bone disease experienced an objective response (81%). The median duration of response was 12 months (range, 2.4 to 40.5), and the median overall survival was 27.5 months (range, 4 to 46). Neutropenia was dose-limiting, with 36 patients (41%) experiencing grade 3 or 4 toxicity. Of 727 cycles administered, there were 20 admissions (3%) for treatment of febrile neutropenia, involving 14 of 89 patients (16%). Treatment-related cardiotoxicity at grade 2 to 4 was experienced by 10% of patients and necessitated the interruption of treatment in 1.5% of cycles. Other side effects were uncommon or manageable by conventional means. CONCLUSION The encouraging response rates and duration achieved with this combination of Navelbine/doxorubicin under the conditions of this study deserve further randomized comparative trials with standard regimens.

We present a theoretical study of the Zeeman relaxation of the magnetically trappable lowest field seeking state of MnH (${}^{7}\ensuremath{\Sigma}$) in collisions with $^{3}\mathrm{He}$. We analyze the collisional Zeeman transition mechanism as a function of the final diatomic state and its variation as a function of an applied magnetic field. We show that as a result of this mechanism the levels with $\ensuremath{\Delta}{M}_{j}g2$ give negligible contributions to the Zeemam relaxation cross section. We also compare our results to the experimental cross sections obtained from the buffer-gas cooling and magnetic trapping of this molecule and investigate the dependence of the Zeeman relaxation cross section on the accuracy of the three-body interaction at ultralow energies.

Penile trauma, though rare, requires specialized management. Fibrotic sequelae from lesions of the tunica albuginea and corpora cavernosa must be prevented given their impact of the erectile function. Knowledge of penile anatomy enables acquisition and interpretation of penile MRI, preferably performed in the first few hours following injury. Tear of the tunica albuginea must be identified since it requires surgical management. Other lesions may be present at the acute (hematoma) or chronic (fibrosis, arteriocavernous fistula) phases. MRI, non-invasive and painless, is the imaging modality of choice in the multiplanar evaluation of traumatic injuries of the penis.

Endometriosis is defined by the presence of endometrial tissue outside the uterine cavity and having the functional property of menstrual bleeding. We report a case of endometriosis involving the abdominal wall muscles and canal of Nuck in a 28 year old woman. Abdominal wall sonography showed a hypoechoic lesion at the rectus abdominis insertion. T1W and T2W MRI images showed a hemorrhagic high signal intensity lesion in the muscle. MRI also showed a similar lesion in the canal of Nuck.

Neurological complications are rare in trichinosis. A case of trichinosis involving the central nervous system documented by MRI is presented. To our knowledge, only three cases of neurotrichinosis with MRI abnormalities have been already reported. The physiopathological mechanism are discussed (transport of the parasite through the blood-stream, immuno-allergic reaction or eosinophilic neurotoxic effect).

The putative role of hepatitis C virus (HCV) infection in the pathophysiology of lymphoproliferative diseases (LPD) is supported by North American and southern European studies reporting high HCV seroprevalence in patients with B-cell-non-Hodgkin lymphoma (NHL). In order to evaluate the situation in France, we conducted a retrospective national study about the association of chronic HCV infection and LPD. 72 Internal Medicine and Infectious Diseases departments were contacted. Response rate was 51.4%. We recorded 43 LPD (19 males, 24 females): 31 B-cell-NHL, 4 Waldenström's macroglobulinemia, 3 chronic lymphocytic leukemia, 2 multiple myeloma, 2 lymphomas of the mucosa-associated lymphoid tissue, and 1 Hodgkin's disease. Mean age at HCV diagnosis was 62 years (range 33-84). In 16 cases, LPD occurred in patients known to be HCV-infected. For 11 patients, LPD diagnosis preceded the diagnosis of HCV infection, whereas diagnosis was done simultaneously in 11 patients. For those with accurate infection date, mean interval between both events was 15.2 years. Fourteen patients had HCV extrahepatic manifestations: 9 mixed cryoglobulinemia, including 7 with NHL, 5 sicca syndrome (5 NHL), and both in one patient. Cohort of HCV-infected patients could be accurately determined for 16 departments, totaling 1,485 patients and 37 cases. Thus, from our data the frequency of LPD among HCV-infected patients approximates 2. 49%. Despite possible bias inherent to this retrospective study, our data support the hypothesis of HCV-associated LPD and particularly B-cell-NHL. In France, this association is much lower than in Italy. Further studies are needed to assess the precise role of HCV in the multistep process leading to monoclonal proliferation.

Fourty-six patients (41 evaluable) were treated in second line chemotherapy of metastatic breast cancer (MBC) by an association of mitomycin (M), vinorelbine (V) (M 8 mg/m2 D1, V 25 mg/m2 D1 and DI 8 every 4 weeks). Median age was 58 years (36-78), median performance status 1 (0-3). Thirty-seven per cent of the tumors were estrogen receptors positive and 17% progesterone receptors positive. Seventeen patients received an adjuvant chemotherapy and 39 a first line chemotherapy with anthracycline (A). The median number of metastatic sites was 2 (1-4) and 27 patients (67%) had visceral metastases. Twelve patients were refractory to anthracyclines and 5 resistant. No toxic death nor hemolytic uremic syndrome were observed. Seven (3.7%) febrile neutropenias happened responsible for 4 hospitalizations. A grade 3 or 4 neutropenia was noted in 34% of the cycles but no other clinic toxicity nor grade 3 or 4 thrombopenia. The rate of objective response (OR) was 37.5% with 2 complete responses (CR) and 13 partial responses (PR). Seven patients had stable disease and 18 progressed. The rate of hepatic OR was 31%. Five (40%) A-refractory patients responded but no resistant patient. Median OR time was 10 weeks (8-12) and median OR duration was 5 months (3-6). Median survival was 11.5 months. MV association is well tolerated and effective in second line chemotherapy for MBC even with hepatic metastasis and in patients refractory to anthracyclines.

Elliptinium acetate (Celiptium R ) is an intercalating agent belonging to the ellipticine family. This agent has demonstrated clinical activity as salvage treatment in breast cancer using a weekly regimen. However, its clinical use was hampered by important toxicities such as xerostomia and immune-mediated haemolytic reactions due to development of anti-elliptinium IgM antibodies. We have studied 83 patients previously treated for metastatic breast cancer using elliptinium acetate with a different schedule: 80 mg/m 2 daily for 3 consecutive days every 21 days. In 80 evaluable patients, an objective response (complete + partial response) was obtained in 5 of 30 patients with visceral metastases (13%), in 6 of 21 patients with soft tissue metastases (29%), and in 3 of 20 patients with mixed metastases (15%). The overall objective response rate was 14/80 (18%, 95% confidence interval = 10–26%). Moderate to severe xerostomia occurred in 10% of patients, while no anti-elliptinium antibodies or haemolytic reactions were detected using this schedule. No significant haematological toxicity, as usually reported with this drug, was observed. Elliptinium acetate has modest but definite activity as salvage treatment of breast cancer. The 3-week schedule seems as active as and less toxic than the weekly schedule.

We present a quantum mechanical investigation of rotational energy transfer in cold collisions of CH+ with 4 He atoms. We use a global 3D potential energy surface obtained using the reproducing Kernel Hilbert Space (RKHS) method. Rotational deactivation transition cross-sections are performed for collision energy ranging from 10-6 to 3000 cm-1 and the corresponding rotational deactivation and excitation rate coefficients are evaluated for the transitions of levels up to j = 5 and temperatures up to 500 K. We also discuss the validity of the rigid rotor approximation for this collision.

1. A novel anticancer vinca alkaloid derivative (I) has been given as an i.v. bolus to cancer patients, using four different dosage regimens with dose levels ranging from 0.04 to 0.84 mg/m2 (equivalent to between 0.12 and 1.35 mg per dose), and the pharmacokinetics determined up to 72 h after dosing. In addition, secondary effects of leukopenia and neutropenia, were related to drug exposure using a sigmoid Emax model. 2. Plasma levels of I declined in a triphasic manner with a terminal half-life of approximately 50 h; most drug elimination (55%) being associated with the terminal phase. 3. Clearance of I was relatively low (245 +/- 160 ml/min) and remained constant with increasing doses. Initial distribution volume was low (approximately 71) but once distribution was complete, it was comparatively high (327 +/- 2121). 4. Both leukopenia and neutropenia were fitted successfully to a sigmoid Emax model showing that these effects were related to the total exposure to the drug. The Hill constant was less than 1, indicating a relatively shallow exposure/response curve and a predictable, graded increase in response with increasing I exposure, rather than a sudden quantal response. 5. Pharmacokinetically, I shows some similarities to other vinca alkaloids in its plasma level decline profile, although there are some notable differences which can be exploited clinically. In addition, the ability to model both leukopenia and neutropenia to the exposure to I, provides a valuable tool in the design of the most appropriate dosage regimen for the drug, as well as for dose adjustment taking into account inter-individual variations.

14 adult patients between 16 and 50 years old with small non-cleaved cell lymphoma (Burkitt's lymphoma) were prospectively treated from 1982 to 1990 with the LMB protocols of the Societe Francaise d'Oncologie Pediatrique (SFOP). No HIV-positive patients were included. All patients had extensive disease with bad prognosis factors, i.e. 10 patients had Murphy stage III and 4 had stage IV with bone marrow involvement. The LMB protocols were characterised by high-dose fractionated cyclophosphamide, high-dose methotrexate (HD-MTX), and cytosine arabinoside. No local or central nervous system irradiation was used. Treatment duration ranged from 5 (LMB 84) to 12 (LMB 81) months. There were no therapy-related deaths. All patients achieved complete remission (CR). 6 patients relapsed between 2 and 30 months following CR. 8 of the 14 patients (57%) are still alive and disease-free after treatment by LMB protocol alone. 2 patients were salvaged with bone marrow transplantation after relapse and a total of 10 out of 14 patients (71%) are disease-free at the time of this report. Our results showed the high curability of advanced Burkitt's lymphoma using a paediatric protocol, even in adult patients. The LMB protocol may be applied to adult patients but requires intensive care during the induction period.

Between October 1985 and October 1989, 75 previously untreated patients with stage III and IV non Hodgkin's lymphoma, large cell type, were treated with an alternating weekly chemotherapy regimen including the following drugs: week 1: Doxorubicin, vincristine, cyclophosphamide, bleomycin, and intrathecal (i.th.) methotrexate and cytarabine; week 2: Methotrexate with leucovorin rescue; week 3: Doxorubicin, ifosfamide with mesna, etoposide, and i.th. methotrexate and cytarabine; week 4: Methotrexate with leucovorin rescue. Complete responders after three cycles according to this schedule (12 weeks) were given 18 gys cranial irradiation and randomized between one additional cycle or three monthly CHOP (consolidation treatment). Among 66 evaluable patients, 53 achieved a complete remission (CR 80 per cent) and seven a partial remission (11 per cent). There were six failures, and nine early deaths during the initial phase, mostly due to septic problems. Forty-one of the 53 CR patients (77.3 per cent) have remained free of disease with a median follow-up of 15 months (1-49). Eight of the 12 relapses occurred during the first year, the four others at 13, 14, 16 and 38 months respectively. The 2-year survival was 63 per cent for the whole group, and 77 per cent for the CR group. No difference has been observed up until now between the two groups with different consolidation treatment. Therefore, this protocol seems to be able to produce a high rate of complete and durable remission. The analysis of prognostic factors suggests that some high-risk patients should be considered for intensification therapy with the support of autologous bone marrow transplantation.

8160 Background: In the next 2 decades, 70% of all cancers will occur in elderly patients (pts) above 70 . Methods : In Gerico-01, with pts 70 years or older, the primary endpoint of the study was the autonomy preservation as measured by the ADL in 6 item; 2nd objectives were toxicity (NCI-CTC v2), PK study of V, the serum PSA or CA 15–3 levels variation and the tumor targets evaluation (RECIST); the primary tumors were either metastatic disease from a primary Breast, or a lung or a prostate Ca. The treatment was Q-3 weeks an oral combination chemotherapy (CT) with C day 1–14 at a starting dose of 750 mg/m2 twice a day and oral V, days 1 and 8 at a starting dose of 45 mg/m2/d. After three cycles the dose could be escalated up to 1000 mg/m2 twice a day and 60 mg/m2 respectively. At inclusion, the creatinin clearance must be above 30 ml/min (Cokroft Formula). Dose adaptation was according to the observed toxicity. C+V was discontinued in progressive disease, or the loss of 2 or more ADL criteria, or any gra...

Following Antman's report (Sem Onc 1990; 17: 7–15) underlining a better efficacy for fractionnated bolus Ifo infusion modality than the 24 h continuous infusion, as treatment in relapsing sarcoma patients, in October 93 we began a phase II study of high dose (HD) Ifo at 4 g/m 2 (d on 3 consecutive days (12 g/m 2 /cycle) given over 1 hour/d with Mesna (doses × 1. 5) every four weeks until progression. Twelve patients (pts) were entered, their characteristics as follows: median age 40 ys (18–62); sex 5 M/7 W; PS ≤ 1 12/12 pts; histologic types: bone sarcoma (sarc) 3 (2 osteosarc, 1 fibrosarc), soft tissue sarc 9 (synovialosarc 3, liposarc 2, other types 4). Ten pts had metastatic disease and 2 a locally advanced inoperable sarcoma. All pts were pretreated with chemotherapy, (1 regimen, (rg) 6 pts, 2 reg, 6 pts), the MAID regimen in 7 of them. Four/9 pts treated previously with intermediate dose Ifo 9 g/m 2 /cy (IDIFO) had responded to it. Results 35 cycles (cy) were administered, median number of cy/pt = 2 (1–6). All pts were evaluable for response. The only PR (8 weeks duration) was a previous complete responder to IDIFO. Of the 3 minor responders observed (median duration 3 months), one had previously responded to IDIFO. Seven pts had disease progression and there was one stabilisation. Toxicity/cy included: 7 febrile neutropenia episodes during the 1st cy, 2 of them despite G-CSF prophylaxis; all following cycles were administered with G-CSF; 1 grade 3 and 1 grade 2 thrombopenia, 1 grade 3 renal insufficiency, 1 grade 2 haemorrhagic cystitis. CNS toxicity related to treatment was seen in 1 cy (1 transient confusion). There was no dose modification, and no toxic death occurred. All treatment discontinuations were caused by progressive disease, or patient refusal (l pt). Conclusion Our experience with HOIFO (12 g/m 2 Icycle) contrasts with other reports showing a good efficacy of HDIFO in refractory sarcomas (Brain ASCO 95 A1641). Our series consists of pts pretreated with 1DIFO (9 g/m 2 /cycle) and our administration modality (1 hour instead of C. I. V.) may account for the 50% decrease of AUC and half life between the 1st and 3rd treatment days observed in our pharmacokinetic study (Lokiec et al. ASCO 95).

Un cas d'erythroblastopenie primitive de l'adulte evolue sur huit ans avec des rechutes successives toujours sensibles a la corticotherapie. Aucun anticorps serique dirige contre l'erythropoietine ou les precurseurs de l'erythropoiese n'a ete mis en evidence. La presence de lymphocytes ou de monocytes ayant un role cytotoxique sur les precurseurs erythroblastiques peut etre evoquee.

In vitro differentiating agents causing little bone marrow aplasia have been proposed as a specific therapy of myelodysplastic syndromes with excess of blasts. A critical review of the published data is presented. The preliminary results of a cooperative protocol using very low dosage of clytosine arabinoside (3 mg/m2/twice daily) with or without androgens are given

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Five cases of sarcoidosis associated with malignant lymphoma are reported. In one patient, sarcoidosis was diagnosed several years after the onset of Hodgkin's disease. Of the remaining 4 patients, three developed nodular mixed lymphoma and one immunoblastic lymphoma (complicating angioimmunoblastic lymphadenopathy with dysproteinaemia) 3 months to 12 years after sarcoidosis were diagnosed. Such cases are extremely rare. They may be due to coincidence, but Danish epidemiological data suggest a relationship between the two diseases. Overstepping of humoral immunity in sarcoidosis may induce the emergence of a clone of formerly quiescent neoplastic B-cells.

The authors report a case of major acanthocytosis which regressed spontaneously in a cirrhotic patient. The usual lipid abnormalities: considerable rise in free red cell cholesterol and lesser rise in phospholipid, regressed concommitantly to the disappearance of acanthocytes. No change in the main liver function tests was, however, observed. The etiological mechanisms of acanthocytosis in cirrhosis are probably multiple, and their interactions are compplex. The exchange of abnormal lipoproteins between the plasma and the red cell membrane is the last theory to be considered. On the other hand, no argument could explain the disappearance of the acanthocytosis, this phenomenon is considered up to now irreversible and a sign of the gravity of hepatic lesions.

A case associating a systemic mastocytosis and an acquired myeloperoxidase deficiency is reported. The myeloperoxydase deficiency is studied by cytochemical techniques in optical and electron microscopy and confirmed by biochemical measures. An important defect in bactericidal and candidacidal activity is demonstrated in vitro in P.N.M. The authors discuss the links between the two anomalies which might bring one more argument for the common origin of both granulocytes and mastocytes.

A case of granulocytic breast sarcoma in a 19 year-old-girl is reported. Surgical excision of the tumor was followed by radiotherapy of the breast and lymph nodes. Then 3 months later acute M2 myelocytic leukemia was diagnosed, complete remission being attained using rubidazone-cytarabine and maintained by monthly reinduction courses. Trisomy of chromosome 22 was present in leukemic cells and disappeared during remission. Its pathogenic significance is briefly discussed.

The recent development of chemotherapy in the treatment of cancer and leukemia requires that all practitioners involved have a thorough knowledge of the sometimes life-threatening side-effects of chemotherapeutic agents. All these agents, whether used alone or in a combination, carry a risk because of their lack of specificity which make active on normal cells, especially those with a rapid turn-over such as the hematopoietic cells or the cells of the digestive tract. Prior to the prescription of a chemotherapeutic regimen, the acceptable risk must always be clearly defined, according to the seriousness of the disease and to the patient's age, physical condition and psychological status. During the course continuous monitoring adjusted to the specific toxicity of the agents used is requisite. More or less prominent asthenia and weight loss are common, as the result of various physiopathological mechanisms. Digestive disorders may consist only of nausea and emesis or include mucosal lesions with diarrhea as the main feature. Vincristine and vindesine are responsible for constipation. Hepatic toxicity, which is less common, is usually due to L-asparaginase. Transient hair loss is the most frequent cutaneous side-effect. Hyperpigmentation, photosensitivity, nail lesions, cellulitis and ulcerations may occur, as well as specific lesions with bleomycin. High fever during injection often occurs with this last agent.

Aplastic anemia is the most severe hematologic side-effect. All chemotherapeutic agents, with the exception of bleomycin and L-asparaginase, may induce aplasia, but the degree of hematotoxicity varies according to the drug. With the exception of acute leukemia in which drug-induced aplasia is part of the treatment, aplasia must be prevented through perfect knowledge of the posology and injection schedules for each drug, as well as by adjusting doses to the patient's hematological status. If aplasia develops, intensive hematological care is requisite. The most common cardiac side-effect is toxic cardiomyopathy caused by anthracyclines, which must be diagnosed early by EKG recordings before each injection and repeated ultrasonography or dynamic cardiac scintigraphy. The risk of toxic cardiomyopathy makes it requisite not to exceed the maximal doses set for each drug. Pulmonary side-effects include acute hypersensitivity pneumopathy and chronic diffuse interstitial fibrosis, the latter being more common and mainly caused by bleomycin. The risk of chronic fibrosis demands that patients be closely monitored and that the total dose be kept under 300 mg. Renal toxicity usually results in acute transient renal failure, as with cisplatinum, and requires a thorough biological study before each injection. Vesical hemorrhage, which is threatening in some instances, may occur with cyclophosphamide. VM26 and VP16 may induce anaphylactic shock. Allergic symptoms are possible with L-asparaginase and bleomycin.

We used the test-dose method to calculate the dose of methotrexate to administer to the patients to reach the therapeutic but non-toxic blood concentration of 10 −5 mol/L. Methotrexate was tested with a radioimmunoassay technique and in 19 out of 20 patients we obtained the desired plateau during 24-h infusion.

7 patients with chronic lymphatic leukemia, B type, have been treated with thymic irradiation. A full remission was achieved in 2 and a partial one in 4. No serious complications were noted during or after the irradiation. This treatment has proved efficient even after the failure of a previous chemotherapy and has permitted to resume any other therapeutic modality when the C.L.L. is no more controlled.

Three cases of metastatic malignant thymoma are reported. In all three cases the tumour was invasive and excision was only partial or impossible. Histologically, these tumours were of epithelial origin with a variable lymphocytic component. Metastases were initially present in one case and in the other two developed within the first year. Partial remission was obtained with different drug combinations in only one case, and it was of short duration. The authors emphasize the increased frequency and poor prognosis of these tumours and the need for multiple chemotherapy and loco-regional treatment in the management of invasive thymomas.

In a case of pure megaloblastic refractory anemia, a complete remission is reported. This remission has been obtained by prolonged high dose androgenotherapy and has now lasted for more than 5 years. The practical therapeutic consequences are discussed.

A case associating simultaneously a sarcoidosis and an angioimmunoblastic lymphadenopathy is reported. The disease developed into a malignant lymphoma. The immunologic features and the links between the two diseases are discussed.