Strong magnetic exchange and frustrated ferrimagnetic order in a weberite-type inorganic-organic hybrid fluoride.

We combine powder neutron diffraction, magnetometry and 57Fe Mössbauer spectrometry to determine the nuclear and magnetic structures of a strongly interacting weberite-type inorganic-organic hybrid fluoride, Fe2F5(H taz). In this structure, Fe2+ and Fe3+ cations form magnetically frustrated hexagonal tungsten bronze layers of corner-sharing octahedra. Our powder neutron diffraction data reveal that, unlike its purely inorganic fluoride weberite counterparts which adopt a centrosymmetric Imma structure, the room-temperature nuclear structure of Fe2F5(H taz) is best described by a non-centrosymmetric Ima2 model with refined lattice parameters a = 9.1467(2) Å, b = 9.4641(2) Å and c = 7.4829(2) Å. Magnetic susceptibility and magnetization measurements reveal that strong antiferromagnetic exchange interactions prevail in Fe2F5(H taz) leading to a magnetic ordering transition at TN = 93 K. Analysis of low-temperature powder neutron diffraction data indicates that below TN, the Fe2+ sublattice is ferromagnetic, with a moment of 4.1(1) µB per Fe2+ at 2 K, but that an antiferromagnetic component of 0.6(3) µB cants the main ferromagnetic component of Fe3+, which aligns antiferromagnetically to the Fe2+ sublattice. The zero-field and in-field Mössbauer spectra give clear evidence of an excess of high-spin Fe3+ species within the structure and a non-collinear magnetic structure. This article is part of the theme issue 'Mineralomimesis: natural and synthetic frameworks in science and technology'.

Singlet ground state of the quantum antiferromagnet Ba(3)CuSb(2)O(9).

We present local probe results on the honeycomb lattice antiferromagnet Ba(3)CuSb(2)O(9). Muon spin relaxation measurements in a zero field down to 20 mK show unequivocally that there is a total absence of spin freezing in the ground state. Sb NMR measurements allow us to track the intrinsic susceptibility of the lattice, which shows a maximum at around 55 K and drops to zero in the low-temperature limit. The spin-lattice relaxation rate shows two characteristic energy scales, including a field-dependent crossover to exponential low-temperature behavior, implying gapped magnetic excitations.

First Report of Powdery Mildew Caused by Podosphaera pannosa on Prunus cerasus in France.

Podosphaera pannosa (Wallr.:Fr.) de Bary (anamorph Oïdium leucoconium Desm.) is described as the most frequent species causing powdery mildew of members of the Rosaceae family, especially on Rosa spp. and Prunus spp. P. pannosa is reported as cosmopolitan, but its occurrence on Prunus cerasus (cherry) is limited to Hungary (3). During spring 2011, typical symptoms of powdery mildew were observed in a Prunus cerasus orchard located in La Roche de Glun (southeastern France). On average, 25% of the shoots per individual tree were affected by this disease. Although several different cultivars were grown in the orchard, cultivar Bigalise alone displayed powdery mildew symptoms. The lower surface of the leaves was covered with superficial, white, dense mycelium, whereas the upper side showed discoloration, necrosing patches, and blisters. Microscopic slides were prepared from fresh material by gently pressing a clear adhesive tape onto the lower surface covered by mycelium, which was further stained with lactic acid/methyl blue. The presence of powdery mildew was confirmed by the observation of typical microscopic features of the anamorphic stage of the fungus (2). Conidiophores were erect. Conidia (oïdia) were hyaline and keg-shaped, and developed basipetally in chains of six to eight conidia. Conidial dimensions were 17 to 29 (23) × 9 to 17 (14) µm. No cleistothecia (teleomorphic state of the fungus) were observed. Species identity was determined by sequencing the ITS region of the rDNA followed by comparison with reference sequences available on GenBank (1). Fungal material was collected from infected leaves by scraping the mycelium with a sterile needle, and was transferred into 2-ml microtubes. Fungal total DNA was then extracted using a commercial plant DNA extraction kit and the ITS region was amplified by PCR using the ITS1-ITS4 primer pair (4). Nucleotide sequence was determined and deposited in GenBank (Accession No. JN654341). Analysis of the sequence by BLAST showed 100% identity with Podosphaera pannosa. To our knowledge, this is the first report of Podosphaera pannosa on Prunus cerasus in France. This species was hitherto scarcely reported on cherry trees, and may deserve more attention in the future. References: (1) M. Gàbor et al. Eur. J. Plant Pathol. 131:135, 2011. (2) G. Grove et al. Page 12 in: Compendium of Stone Fruit Diseases. American Phytopathological Society, St Paul, MN, 1995. (3) L. Vajna et al. New Dis. Rep. 12:15, 2005. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications, 1990.

User trial of Easypod, an electronic autoinjector for growth hormone.

OBJECTIVE: A new electronic injection device, the Easypod, has been developed to administer growth hormone (GH). This study assessed the use of this device in common practice. MATERIALS AND METHODS: Results are from the French arm (one centre) of an international, open-label, uncontrolled study. Subjects were children already using, or about to start, GH therapy. Children used the Easypod device for 60 days. The main outcome measures were patients' or, if appropriate, their parents' qualitative overall impression of the device and the usefulness of its features after 15 days' use, as evaluated by questionnaire. RESULTS: At day 15, all participants (20/20) described their overall impression of the Easypod device as "good" or "very good". All participants rated the display of the remaining drug in the cartridge, the preprogrammed dosing, the onscreen instructions and the automatic-needle attachment as "useful" or "very useful". The device's audible/visible signals and customisable injection depth and speed were each rated as "useful" or "very useful" by 19/20 participants and the skin sensor, customisable needle-insertion speed and dose-injection confirmation were each rated as such by 18/20 participants. Electronic display of the date and time of the last injection and the dose history were considered "useful" or "very useful" by 17/20 and 15/20 participants, respectively. At day 60, 17/17 respondents expressed a preference for continuing to use the device. CONCLUSION: These results show that the features of Easypod are considered useful in routine practice and the majority of participants expressed a desire to continue using the device.

A magnetisation and Mössbauer study of triazole (M1-x2+Mx3+)M3+F5(Htaz)1-x(taz)x weberites (M = Fe, Co, Mn, Zn, Ga, V).

A series of triazole fluoride weberites (M1-x2+Mx3+)M3+F5(Htaz)1-x(taz)x is obtained by hydrothermal synthesis. All phases are found to be isostructural to ZnAlF5(Htaz) by powder X-ray diffraction. Weberite structures are prone to induce the magnetic frustration of antiferromagnetic interactions originating from the cationic topology of HTB layers. The (nD) magnetic properties of (0D) Co-Ga, (1D) Zn-Fe, (3D) Fe-Ga, Mn-Fe, Co-Fe and Co-V couples are thus reported. Co2+ or Fe2+ magnetic anisotropy induces a negative magnetisation below TN and compensation temperatures for Mn-Fe and Co-Fe couples. All iron 3D magnetic phases exhibit high Néel temperatures, between 81 K and 102 K, and large |θP/TN| ratios, signalling strong magnetic frustration. Their cation site occupancies and the deduced (de)protonation states of the amine are accurately determined by 57Fe Mössbauer spectrometry. In addition, this spectroscopy evidences a subtle effect of the atmosphere that surrounds the samples: the magnetic ordering temperatures TN decrease significantly when the samples are cooled under vacuum with respect to samples that are cooled at ambient pressure. This novel phenomenon, which is highlighted for all studied (3D) triazole iron weberites, is reversible, and thus provides promising perspectives for understanding the underlying mechanism.

First-principles calculations within periodic boundary conditions of the NMR shielding tensor for a transition metal nucleus in a solid state system: The example of 51V in AlVO4.

We present the first density functional theory based calculations of NMR shielding parameters for a transition metal nucleus using periodic boundary conditions. These calculations employ the gauge-including projected augmented-wave pseudopotential approach. The quality of this method is discussed by comparing experimental and calculated chemical shift tensor eigenvalues for the quadrupolar 51V nucleus in the diamagnetic solid-state compound AlVO4. Furthermore, the combination of shielding tensor with fast and accurate projector augmented-wave electric field gradient tensor calculations allows us to determine the relative orientation of these two tensors.

Increased risk of secondary acute nonlymphocytic leukemia after extended-field radiation therapy combined with MOPP chemotherapy for Hodgkin's disease.

The purpose of this study was to evaluate the influence of the number of mechlorethamine, vincristine, procarbazine, and prednisolone (MOPP) cycles and the extent of irradiation on the risk of secondary acute nonlymphocytic leukemia (SANLL) after a single combined treatment for Hodgkin's disease (HD). Between April 1972 and May 1980, 462 patients with HD clinical stage (CS) I, II, and III were prospectively treated with three or six cycles of MOPP and supra- and/or infradiaphragmatic irradiation (40 Gy). Four hundred forty-one patients achieved complete remission (CR). By January 1988, 237 patients had been followed-up in first CR for at least 10 years. Ten patients developed SANLL between the 34th and 123rd month of CR. The 15-year SANLL risk is 3.5% +/- 2.7%. Cox's stepwise regression analysis performed with all initial and treatment covariates (sex, age, histology, splenectomy, MOPP chemotherapy, and irradiation extent) showed that the only significant explanatory variable of SANLL risk was the irradiation extent (P less than .002). Using the log-rank test, SANLL risk ranged from 2.2% for supradiaphragmatic irradiation alone to 9.1% for subtotal (STNI) or total nodal irradiation (TNI) (P less than .001). These results strongly suggest that extended high-dose irradiation and MOPP chemotherapy should not be combined for the treatment of HD.

Escalating dose of mitoxantrone with high-dose cyclophosphamide, carmustine, and etoposide in patients with refractory lymphoma undergoing autologous bone marrow transplantation.

PURPOSE: We conducted a dose-finding study of mitoxantrone (MITO) in combination with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (CBV) in refractory lymphoma undergoing autologous bone marrow transplantation (ABMT). The objective were to determine the following: (1) the maximum-tolerated dose of MITO, (2) the extramedullary toxicity of this regimen, (3) its antitumor activity, and (4) the pharmacokinetic characteristics of MITO at each dose level. PATIENTS AND METHODS: Escalating doses of MITO (15 to 90 mg/m2, single bolus infusion on day -8) followed by CBV were administered to 20 patients (mean age, 38.5 years) with refractory lymphoma. MITO concentrations were determined by high-performance liquid chromatography (HPLC). RESULTS: No toxic death occurred. The maximum-tolerated dose appears to be 75 mg/m2. Two of five patients treated with 90 mg/m2 developed severe organ toxicity, versus zero of 15 treated with doses up to 75 mg/m2. Duration of neutropenia was longer for patients treated with 90 mg/m2 (31.7 days) than for patients treated with doses up to 75 mg/m2 (22.1 days) (P < .05). A linear relationship was observed between administered dose of MITO and (1) plasma peak value, (2) area under the curve (AUC), and (3) plasma concentration on the day of marrow infusion (day 0). Hematologic toxicity was related to the terminal half-life (T1/2) of MITO, and day-0 plasma concentration. A high complete response (CR) rate was observed (60%), and eight of 11 (73%) patients treated with MITO > or = 60 mg/m2 achieved a CR. CONCLUSION: MITO (up to 75 mg/m2) and CBV can be administered with acceptable toxicity and a promising CR rate in this poor-risk population, justifying further phase II studies.

Immunotherapy by non-myeloablative allogeneic stem cell transplantation in multiple myeloma: results of a pilot study as salvage therapy after autologous transplantation.

Non-myeloablative allogeneic stem cell transplantation has been reported to induce sustained complete remission even in advanced diseases (acute leukemia, lymphomas). The tolerance of this procedure allows treatment of poor candidates to conventional allogeneic transplantation with persisting or relapsing myeloma patients. Twelve patients previously treated with at least VAD regimen and autologous transplantation were included. All patients had a serum beta2 microglobuline >3 mg/l at diagnosis. The conditioning regimen consisted of fludarabine 25 mg/m/day x 5, antithymoglobulin 2.5 mg/kg/day x 5, busulphan 2 mg/kg/day x 2; the transplant was peripheral stem cells (except one) from an HLA-matched sibling and was followed by cyclosporin for 45 to 90 days. This treatment results in a well-tolerated procedure (no mucositis, duration of aplasia <7 days). A dramatic graft anti-myeloma effect is documented even in progressive disease (11/12 PR + CR, 4/12 CR). However, five patients underwent CMV disease, one died of CMV encephalitis (UPN 3) and delayed severe GVHD occurred in four patients. Our data suggest that a better survival could be achieved when patients are transplanted with a controlled disease. In high risk patients, we now propose a non-myeloablative transplantation in addition to the conventional and intensive chemotherapy as first-line of treatment.

Prognostic significance of karyotype in de novo adult acute myeloid leukemia. The BGMT group.

A group of 201 adult patients, 127 younger and 74 older than 55 years, with de novo acute myeloid leukemia were investigated to determine the prognostic significance of karyotype on early death (toxic or aplastic death occurring before hematopoietic recovery), drug resistance, continuous complete remission (CCR) and survival probabilities at 5 years. A good prognostic impact was found for t(8;21), t(15;17) and inv(16). The best factor proved to be t(8;21) (5-year survival probability: 50%), followed by t(15;17) (5-year survival probability: 39%) and by inv(16) (5-year survival probability: 43%). An intermediate outcome was found in patients with trisomy 8 (27% alive at 5 years) and in patients with numerical abnormalities other than -7 and +8 (33% in CCR and 62% alive at 5 years). Normal karyotypes had a different prognostic impact according to age: intermediate in young and good in older patients. A poor outcome was observed among patients with del(5q)/-5 (median survival: 1 month), with 11q23 rearrangements (median survival: 1.5 months) and with del(7q)/-7 (median survival: 10 months). The 'other structural change' group was also found to be a poor risk population (5-year survival probability: 5%) whereas complex karyotypes were predictive of short survivals only in older patients. Conversely, del(7q)/-7 and +8 as secondary changes, had no prognostic impact.

[Preparation and administration of cytotoxic drugs: prickly innovation]. / Préparation et administration des cytotoxiques: du piquant dans l'innovation.

The requirement for safe and optimal administration of cytotoxic drugs led us to test a new product manufactured by Codan. The transfer set (CONNECT SET) and the administration set (CYTO-AD-SET) were assessed successively by pharmacist assistance within a centralized unit for cytotoxic drug preparation and by the nursing staff in an ambulatory unit. Transfer sets can be handled in the centralized units without using needles, but with an increased sterilization load and production cost. Assessment of the administration sets demonstrated time saving for the nursing staff. These materials require significant expenditures, careful training, and a change in treatment routine, but provide important time savings for the nursing staff and considerable improvement in the safety of handling cytotoxic drugs.

Epstein-Barr virus (EBV) replicative gene expression in tumour cells of AIDS-related non-Hodgkin's lymphoma in relation to CD4 cell number and antibody titres to EBV.

OBJECTIVE: To determine whether activation of Epstein-Barr virus (EBV) replication in tumour cells of AIDS-related non-Hodgkin's lymphoma (ARNHL) is correlated with CD4+ cell counts and influences antibody response to EBV [anti-Z Epstein-Barr replicative activator (ZEBRA), anti-early antigen (EA), anti-viral capsid antigen (VCA)]. DESIGN: Retrospective study based on immunohistochemistry and in situ hybridization to detect EBV replicative gene products in tissue samples from patients affected by ARNHL and correlation with CD4+ cell counts and results of EBV serology (including anti-ZEBRA activity) in sera from the same patients. METHODS: Seventeen out of 22 cases of ARNHL were selected for the presence of EBV [Epstein-Barr early region (EBER) RNA-positive]. Immunohistochemistry was performed with anti-ZEBRA, anti-EA-restricted, anti-VCA antibodies and in situ hybridization with BHLF1/NotI oligoprobes on tumour samples. Results were statistically correlated with those of CD4+ cell counts (17 out of 17) and with anti-EBV antibody titres (13 out of 17) assessed using standard immunofluorescence method and enzyme-linked immunosorbent assay procedure using recombinant ZEBRA protein and synthetic peptides as antigens. RESULTS: BZLF1 (ZEBRA) or early gene products (EA-R and EA-D/BHLF1/NotI) were detected in a small proportion (< 0.01-5%) of tumour cells in eight of these 17 cases by immunohistochemistry and in situ hybridization. Demonstration of replicative gene expression did not correlate with either low CD4+ cell counts (P > 0.05) or anti-EBV antibody titres (P > 0.05). Anti-ZEBRA activity was not significantly increased in patients affected with ARNHL, the cells of which expressed replicative gene products (P > 0.05). CONCLUSION: The degree of immunodeficiency does not clearly enhance replicative gene expression in tumour cells of ARNHL. EBV serology, including anti-ZEBRA activity, is not a reliable tool for predicting the occurrence of such proliferations.

Risk factors for cytomegalovirus infection in BMT recipients transfused exclusively with seronegative blood products.

Risk factors for developing cytomegalovirus (CMV) infection and pneumonitis were analysed in 100 unselected consecutive patients undergoing allogenic BMT. This series is homogeneous because of the same diagnostic procedures, BMT technique and supportive care (exclusive seronegative blood products, no CMV immunoglobulin, no prophylactic antiviral). The incidence of CMV infection and CMV interstitial pneumonitis (CMV-IP) were 44% and 13% respectively, of whom five patients died. Variables such as age, sex, underlying disease, conditioning regimen and occurrence of GVHD were not found as significant risk factors. We confirm that the only major factor was recipient's serology as CMV infection and IP occurred in 4% and 0% respectively among negative recipients (R-) compared with 79% and 25% among positive R. In contrast to some studies among R+, neither donor's immunity nor recipient's CMV humoral response improved the clinical outcome. This study validates the good predictive value of viremia and urinary virus excretion for the occurrence of CMV-IP (respectively positive in 11 and 13 patients out of 13 with IP), always preceding IP by a median of 37 and 27 days. The highest risk patients for lethal CMV-IP were older recipients (> 30 years). Thus, prospective prophylactic trials with antiviral agents are suggested in such viremic or viruric patients. Furthermore, the use of seronegative blood products is highly effective and sufficient to prevent CMV infection in R-patients.

Maintenance treatment with recombinant alpha interferon after autologous bone marrow transplantation for aggressive myeloma in first remission after conventional induction chemotherapy.

Twenty patients (median age 57 years) with high tumor mass myeloma in first remission after conventional chemotherapy received a two-phase treatment: autologous bone marrow transplantation (ABMT) using a preparative regimen of high dose melphalan plus total body irradiation followed by maintenance treatment with recombinant alpha interferon. Before ABMT all patients were in partial remission, while after ABMT 10 (50%) achieved complete remission, and 10 remained in partial remission (with a 90% decrease in measurable paraprotein in 7/10). With a median follow-up of 19.8 months (12.2-33.5) after diagnosis and 13 months (4-25) after ABMT, the Kaplan-Meier 2-year post-ABMT probability of progression-free survival was 85% (95% CI = 58.7-95.8%). None of the 10 patients in complete remission has relapsed. No toxic death occurred. Alpha interferon was introduced early after ABMT (2.7 months) and was well tolerated. This strategy may represent an advance in the management of aggressive myeloma.

Thalidomide in patients with advanced multiple myeloma.

INTRODUCTION: Recently, a report has suggested the efficacy and safety of thalidomide in refractory multiple myeloma. In an attempt to assess the efficacy and tolerance of thalidomide in advanced multiple myeloma (on behalf of the Intergroupe Franchophone dy Myelome (IFM)), we report the preliminary experience of the IFM with this drug. MATERIALS AND METHODS: Patients with advanced multiple myeloma (n=27) were treated with an oral dose of thalidomide (median 400 mg/day). At the start of treatment, all patients had active disease and 20 patients had received at least one autologous transplantation. RESULTS: Median follow-up was 105 days from the first administration. The serum and/or urine levels of the M-component were reduced by at least 75% in four patients including one patient with a >90% reduction, by at least 50% in five patients and by at least 25% in three patients, giving a total response rate of 45% (12 out of 27 patients). Nine patients had stable disease and six patients had progressed disease. Short-term side-effects of thalidomide were generally moderate. CONCLUSION: This study confirms that thalidomide is an effective agent in patients with advanced myeloma.

Bone marrow involvement in anaplastic large cell lymphoma. Immunohistochemical detection of minimal disease and its prognostic significance.

Bone marrow involvement by anaplastic large cell anaplastic large cell (ALC) lymphoma can be difficult to detect on routine morphologic examination alone. In a series of 42 patients with ALC lymphoma, the authors analyzed: (1) the usefulness of a limited panel of monoclonal antibodies directed against CD30 (Ber-H2, HRS4) and epithelial marrow involvement on routinely processed biopsy specimens; and (2) the prognostic significance of bone marrow involvement as detected on both morphologic and immunohistochemical grounds. On conventional examination, 17% of the patients were found to have bone marrow involvement at diagnosis. However, after immunohistochemical analysis, occult malignant cells were detected in 23% of the patients with negative bone marrow biopsy on routine histology. The low percentage of positive cases on routine morphologic examination compared to immunohistochemical examination was related to: (1) the scarcity of neoplastic cells which were scattered among hematopoietic cells; (2) the difficulty of distinguishing malignant cells from immature hematopoietic elements; and (3) the absence of alteration of the reticulin network. The authors observed a significant association between marrow infiltration and the presence of hematologic abnormalities (mostly anemia or cytopenias) at diagnosis, both in children and adult patients. More importantly, a significant lower survival was seen in patients with bone marrow involvement compared to those without bone marrow involvement. Immunohistochemistry with anti-CD30 and anti-EMA antibodies should be performed systematically in bone marrow biopsies from patients with ALC lymphoma to reliably identify the presence of bone marrow involvement that appears to carry a poor prognosis.

Prognostic significance of karyotype in a twelve-year follow-up in childhood acute lymphoblastic leukemia.

We report a follow-up of 49 children with acute lymphoblastic leukemia (ALL) diagnosed between 1972 and 1978 (follow-up 12-18 years). This series allowed us to analyze the predictive value of karyotype in a long-term follow-up. Karyotypes were abnormal in 33 cases (67.3%): pseudodiploidy in 11 (22.4%), hyperdiploidy > 50 chromosomes in 8 (16.3%), hyperdiploidy 47-50 chromosomes in 11 (22.4%), and hypodiploidy in 3 cases (6.1%). Event-free survival (EFS) and survival studies showed that the outcome of patients was determined only by treatment and karyotype. Eleven patients have survived, nine in first remission (6 years 5 months to 15 years 2 months), and two are in second remission (3 years 8 months and 8 years 2 months). All ploidy groups are represented in these patients. Late relapses can occur in the hyperdiploid > 50 group, thus accounting for shorter EFS than expected, but because of the unusually long second remission of one patient, the rate of surviving patients was higher for this ploidy group than for all other ploidy groups together. Conversely, patients with only numerical abnormalities (no matter which ploidy group they belonged to), had a better outcome than did patients with structural changes or normal karyotypes and no discrepancy between EFS and survival curves was observed in this chromosomal group. Thus, our results suggest that numerical changes only should be considered an indicator of low risk factor, but our results, based on partially banded karyotypes, need to be verified by a current method and therapy.

Vincristine degradation by serum from leukemic patients: role of myeloperoxidase.

Myeloperoxidase (MPO) has been shown to catalyze the in vitro degradation of vincristine (VCR). Given that MPO is a lysosomal enzyme that can be released into the circulation by both normal activated and leukemic myeloid cells, we investigated the possibility that sera from patients with acute myeloblastic leukemia (AML) might exhibit an increased capacity to degrade VCR. 31 serum samples (23 from patients with acute myeloblastic leukemia and 8 from patients with other conditions) were analyzed after incubation with ((3)H)VCR by using HPLC. Sera from patients with AML demonstrated an increased ability to breakdown VCR when compared to either normal sera or to sera from patients with lymphoid leukemias. VCR degradation was significantly increased by adding hydrogen peroxide, an electron donor for MPO, to the sera and was almost completely inhibited by adding 1 mM acetaminophen, an inhibitor of MPO. VCR peroxidation in the presence of hydrogen peroxide correlated both with the number of leukemic blasts in the circulation at the time the sera were obtained and with serum MPO concentrations determined by an immunoassay. These data suggest that the inactivity of VCR in AML may be due in part to its rapid peroxidation to inactive species by the MPO of leukemic myeloblasts.

Randomized study of recombinant interleukin-2 after autologous bone marrow transplantation for acute leukemia in first complete remission.

Immunological control of acute leukemia may be achieved after allogeneic transplant. Despite promising preliminary results, the impact of immunotherapy with interleukin-2 (r-IL-2) on patients with acute leukemia (AL), in first complete remission (CR1) remains unclear. We conducted a prospective multicenter randomized trial to compare outcome in patients with AL in CR1, treated with autologous bone marrow transplantation (BMT) with or without postgraft r-IL-2. One hundred and thirty patients with AL in CR1 (myeloblastic (AML): N = 78; lymphoblastic (ALL): N = 52) were randomized at time of BMT to receive (N = 65) or not (N = 65) r-IL-2. r-IL-2 (RU 49637 from Roussel Uclaf) was started after hematological recovery, as a five cycle regimen (12 M IU/m2/day continuous infusion on day 1-5, 15-17, 29-31,43-45 and 57-59). The two groups were balanced for patient and transplant characteristics. Analysis was based on an intent to treat. Thirty-eight (59%) of the 65 patients randomized into the study group started r-IL-2 at a median of sixty-eight days (23-140) after transplant and received 77% (16-100) of the scheduled dosage. They received a median of 120 x 10(6) IU/m2 (25-156) over 10 (3-13) days during a total median period of 56 (3-78) days. With a median follow-up of 7 years (5.4-8.1 years), 79 patients relapsed (study group: 43 (66%); control group: 36 (55%): p = NS). Survival and leukemia-free survival estimates were 33% (23-45) versus 43% (22-52) and 29% (19-41) versus 36% (24-51) respectively for study and control groups (all p = NS). These results show that leukemic control after autologous BMT is not increased by r-IL-2 therapy. Further studies should investigate more appropriate r-IL-2 schedules and the possibilities offered by better antigen recognition and activated effector cells.

[Deep venous thrombosis on implantable infusion devices. A prospective study of 72 patients with Doppler ultrasonography of veins of the neck (jugular, subclavian and brachiocephalic trunk)]. / Thromboses veineuses profondes sur dispositifs de perfusion implantables. Etude prospective de 72 patients par échotomographie-Doppler des veines du cou (jugulaire, sous-clavière et tronc brachio-céphalique veineux).

Seventy-two consecutive patients with totally implanted catheters for administration of chemotherapy for solid tumours or lymphomas were studied prospectively to assess the prevalence of venous thrombosis. During the follow-up period of 343 (6-1,177) days, 11 cases of venous thrombosis (15.2%), of which 45% were partial and only 36% symptomatic were observed. Venous thrombosis was an early complication, 6/11 cases being observed within 1 month of implantation. No clinical or biological predisposing factor, apart from the presence of malignant disease, could be identified. Doppler ultrasonography is a good method of following-up these patients. This method should become an essential diagnostic tool in this field.