On the origin of extraordinary cyclic strengthening of the austenitic stainless steel Sanicro 25 during fatigue at 700°C.

The origin of the extraordinary strengthening of the highly-alloyed austenitic stainless steel Sanicro 25 during cyclic loading at 700°C was investigated by use of advanced scanning transmission electron microscopy (STEM). Along with substantial change of dislocation structure, nucleation of two distinct populations of nanoparticles was revealed. Fully coherent Cu-rich nanoparticles were observed homogeneously dispersed with high density along with nanometer-sized incoherent NbC carbides precipitating on dislocations during cyclic loading. Probe-corrected HAADF STEM imaging was used to characterize the atomic structure of nanoparticles. Compositional analysis was conducted using both EELS and high spatial resolution EDS. High temperature exposure induced precipitation of a high density of coherent Cu-rich nanoparticles while strain-induced nucleation of incoherent NbC nanoparticles leads to retardation of dislocation movement. The pinning effects and associated obstacles to dislocation motion prevent recovery and formation of the localized low-energy cellular structures. As a consequence, the alloy exhibits remarkable cyclic hardening at elevated temperature.

ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥ 4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial.

BACKGROUND: Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma. However, recent clinical trials have failed to confirm BEACOPP overall survival (OS) superiority over ABVD. In addition, the gain in low-risk patients is still a matter of debate. PATIENTS AND METHODS: We randomly compared ABVD (8 cycles) with BEACOPP (escalated 4 cycles ≥ baseline 4 cycles) in low-risk patients with an International Prognostic Score (IPS) of 0-2. The primary end point was event-free survival (EFS). This parallel group, open-label phase 3 trial was registered under #RECF0219 at French National Cancer Institute. RESULTS: One hundred and fifty patients were randomized in this trial (ABVD 80, BEACOPP 70): 28 years was the median age, 50% were male and IPS was 0-1 for 64%. Complete remission rate was 85% for ABVD and 90% for BEACOPP. Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients (17 versus 5 patients). With a median follow-up period of 5.5 years, seven patients died: six in the ABVD arm and one in the BEACOPP arm (HL 3 and 0, 2nd cancer 2 and 1, accident 1 and 0). The EFS at 5 years was estimated at 62% for ABVD versus 77%, for BEACOPP [hazards ratio (HR) = 0.6, P = 0.07]. The progression-free survival (PFS) at 5 years was 75% versus 93% (HR = 0.3, P = 0.007). The OS at 5 years was 92% versus 99% (HR = 0.18, P = 0.06). CONCLUSION: Fewer progressions/relapses were observed with BEACOPP, demonstrating the high efficacy of the more intensive regimen, even in low-risk patients. However, additional considerations, balancing treatment-related toxicity and late morbidity due to salvage may help with decision-making with regard to treatment with ABVD or BEACOPP.

[Importance of determination of serum beta-2-microglobulin levels in patients with Hodgkin's lymphoma]. / Význam stanovení sérové hladiny beta-2-mikroglobulinu u nemocných s Hodgkinovým lymfomem.

The authors evaluated retrospectively in a group of 69 adult patients with Hodgkin's lymphoma the relationship between the beta-2-microglobulin serum level, basic demographic parameters (age, sex) and factors characterizing the extent (stage III and IV, "bulk" or mediastinal mass, number of affected areas of lymph nodes) and activity of the tumour (presence of B-symptoms, red cell sedimentation rate, haemoglobin, albumin and lactate dehydrogenase level, number of leucocytes and lymphocytes). They analyzed also the possible prognostic impact of beta-2-microglobulin on the therapeutic response risk of relapse and patient's survival. Methods of univariant statistical analysis confirmed the correlation of beta-2-microglobulin level with all investigated metric parameters of patients (advanced age, number of affected nodes, red cell sedimentation rate and lactate dehydrogenase level, lower albumin, haemoglobin level, numbers of leucocytes and lymphocytes). In multivariant analysis however the only independent metric markers significantly associated with an elevated protein level were more advanced age of the patients (P = 0.0002) and a lower number of leucocytes (P = 0.05). The values of beta-2-microglobulin was not influenced by the extent of the tumour (stage III and IV, "bulk" or mediastinal mass, higher number of affected areas of lymph nodes). Significantly more frequently elevated protein values were recorded in patients with manifestations of B symptoms associated with the diagnosis (P = 0.0003). Multivariant analysis did not prove the importance of the serum level of beta-2-microglobulin as a prognostic factor in the sense of predicted remission, development of a relapse or death in conjunction with progression of Hodgkin's lymphoma.

[Mantle cell lymphoma as a diagnostic and therapeutic problem]. / Mantle cell lymfom jako diagnostický a lécebný problém.

The authors present the characteristics of a group of 23 patients with mantle cell lymphoma. In the group only a slight predominance of men over women was found (1.1:1), the median age was 63 years. Twenty-one (91%) of the patients were diagnosed in stage IV (Ann Arbor). In all these patients the bone marrow was affected. In 19 of them immunoflowcytometric analysis revealed the typical clone of B lymphocytes (CD5 positive)/CD 23 negative). The majority of patients had at the time of diagnosis a large tumourous mass with massive splenomegaly (61%), hepatomegaly (57%) and bulky disease (52%). The node was excised in 17 patients, but in four patients (24%) during the first session the diagnosis was not assessed correctly. In the laboratory findings an inclination to anaemia, thrombocytopenia, lymphocytosis and in particular to high levels of serological indicators of activity of the disease dominated--lactate dehydrogenase, beta-2-microglobulin and serum thymidine kinase. All patients were treated by chemotherapy. Complete remission was achieved by the date of evaluation in one patient (4%), partial remission in seven patients (30%) but 48% patients did not respond to first line treatment. Nine patients of the group died, their median of survival was 14 months (0-24), the median of the follow up of the remaining patients was 133 months (2-31). Two female patients had large-dose treatment with subsequent administration of autologous stem cells. The first one is after 370 days of treatment in complete remission, the second one developed a relapse 100 days after the procedure. From the results and analysis of the literature ensues that mantle cell lymphoma is one of the aggressive malignant B-lymphoproliferations with a very adverse prognosis and it deserves therefore special diagnostic and intense therapeutic attention.

[Interferon-alpha in the treatment of patients with chronic myeloid leukemia]. / Interferon alfa v lécbe nemocných s chronickou myeloidní leukémií.

A retrospective analysis of the treatment with Interferon alpha in 18 patients with Ph positive chronic myeloid leukaemia is presented and compared with the results of peroral chemotherapy with Hydroxyurea or Busulphan in 20 patients. Patients treated with Interferon were significantly younger than the control group (median age 40.5 versus 55.5) (p = 0.01) and were followed-up for shorter period of time (median 10.5 months versus 36.5 months) ( p = 0.002), but did not differ in other parameters. Despite the shorter period of observation and treatment, significantly more complete haematological remissions were achieved with Interferon (86%) than with peroral chemotherapy (25%) (p = 0.03). 6 major and 2 minor (44%) cytogenetic responses were observed after Interferon, despite the fact that 8 patients had been treated for less than one year. Interferon was not the optimal therapy in the patients with additional or complex cytogenetic abnormalities at the time of diagnosis, which were the most significant negative prognostic factor. In general, our short-term results confirm the importance and effectiveness of Interferon in the patient with CML providing the therapy was started early, with an effective dose and with simultaneous cytogenetic monitoring. Longer observation of the patients is needed to confirm the impact of Interferon on the survival of patients.

[Fludarabine monophosphate in the treatment of patients with advanced stages of chronic B-cell lymphatic leukemia resistant to conventional chemotherapy]. / Fludarabin monofosfát v lécbe nemocných s pokrocilým stupnem B-chronické lymfatické leukémie rezistentní ke konvencní chemoterapii.

The authors evaluated retrospectively a group of 12 patients with B-chronic lymphatic leukaemia to whom fludarabine was administered. All patients had been treated in the past by combined chemotherapy (1-4 regimes, median 3). Fludarabine was administered in amounts of 30 mg/m2/day for 5 days to 4 patients and for 3 days to patients. The median of the number of administered cycles was 3. Only two patients achieved partial remission of the disease, the reminder did not respond to therapy. All patients had complications which very probably were associated with the administered treatment. A total of 21 episodes were recorded in the course of 36 cycles, 1 complication per 1.7 cycles. The most frequent complications were infections, a total of 14 episodes, incl. 3 invasive aspergilloses. Infections were more frequent in patients with a 5-day cycle, the majority was recorded after the first two cycles. Eight patients (67%) died from complications which developed in the course of treatment or after its termination. The author's experience with the administration of fludarabine in intensively pretreated patients with advanced forms of B-chronic lymphatic leukaemia indicates that this treatment is associated with a large number of serious complications, which are not compensated by a corresponding therapeutic effect.