Selection of maize hybrids based on genotype × yield × trait (GYT) in different environments.

This study aimed to identify the best genotypes using the genotype × yield × trait (GYT) method. To investigate the relationships was performed between yield × traits in four regions of Karaj, Birjand, Shiraz and Arak in two cropping years in a randomized complete block design (RCBD) with three replications. The average grain yield in four regions and two years of the experiment was calculated as 5966 kg/ha, and GYT was obtained based on the multiplication of grain yield with different traits. Comparing the average effect of genotype × year in different environments showed that KSC703 and KSC707 hybrids are among the most productive hybrids among the studied genotypes in grain yield. By examining the correlation coefficients between yield × traits in the tested areas, Y × TWG with Y × GW, Y × NRE, Y × NGR and Y × EL, Y × ED with Y × NGR, Y × NRE with Y × GW and the combination of Y × GW with Y × GL had a positive and significant correlation in all regions. The correlation diagrams were drawn on the evaluated areas' data and showed the correlation of most compounds except Y × GT with each other. Based on the analysis of the main components, the first three components explained the greatest diversity in the population. They were named the component ear grain profile, grain thickness component and plant height profile component.

Stability yield indices on different sweet corn hybrids based on AMMI analysis.

Currently, sweet corn is considered an important crop due to its high sugar content and low starch content. Important sugars in sweet corn include sucrose, fructose, glucose, and maltose. The purpose of the present study was to use the yield indices of the eight examined sweet corn hybrids and the correlation of the yield indices together. Concentration is important for consumers in terms of yield indices. The research site was located at the Látókép Experimental Station of the University of Debrecen. The small plot experiment had a strip plot design with four replications. The previous crop was sweet corn; the plant density was 64 thousand/ha. The obtained result indicates that Biplot AMMI based on IPCA1 showed that the DB, NO, GS, and GB hybrids had stability and high performance in terms of yield indices. At the same time, fructose and glucose had stable parameters for the hybrids involved in the study. IPCA1 AMMI biplot showed that the ME hybrid had stability and high performance in terms of iron and zinc as well. IPCA2 AMMI biplot showed that DE, GB, and GS hybrids had stability and the highest performance on yield parameters in the scope of the research. Fructose, glucose, and sucrose had stable parameters on hybrids based on IPCA2. The DB and SE hybrids had desirable performance in Lutein and Zeaxanthin based on the biplot. The DE hybrid had a maximum performance on iron and zinc parameters.

Quantitative and qualitative yield in sweet maize hybrids.

Today, sweet corn is considered an important vegetable due to its high sugar content and low starch content. Cluster analysis and variance analysis showed that hybrids had variations in yield indices. GB, DE and GS hybrids had similar performance on indices. SE hybrid that has significant performance on zeaxanthin. Biplot showed that fructose, glucose, sucrose and potassium had stability value on hybrids. All the hybrids had the best performance on fructose, glucose, sucrose and potassium factors. Factor biplot positively correlated with yield indices, including calcium, iron, zinc, magnesium, α-Carotene, 9Z-ß-Carotene, phosphorus, and ß-carotene. On the other hand, there is a positive correlation with fructose, glucose, potassium, lutein, sucrose, ß-Cryptoxanthin, and zeaxanthin. So, to evaluate or increase lutein and zeaxanthin, the other parameters like sugar content (fructose, glucose, and sucrose) are important factors and have an effect together. Factor analysis and biplot showed that ME hybrid had a maximum performance on the first factor of yield indices. Also, the second factor of yield indices had a maxi-mum effect on NO hybrids. SE hybrids had maximum performance in zeaxanthin and GS hybrid had maximum performance in zinc, phosphorus, and iron. The dry matter had stability on DB hybrid.

The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma.

BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. PATIENTS AND METHODS: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. RESULTS: A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. CONCLUSIONS: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.

Patient Attitudes Toward Transplantation as Preferred Treatment Modality in Different Stages of Renal Disease.

OBJECTIVE: Kidney transplantation is generally considered to be the best treatment for end-stage renal disease. Not every patient can be operated, but many of suitable patients refuse this possibility. We aimed to explore the attitudes of patients with chronic kidney disease towards renal replacement therapies to recognize motives, thoughts, and feelings concerning accepting or refusing the treatment. We studied the attitudes towards the illness and the treatment, the appearance of depression, and the disease burden during different stages of the disease. METHODS: For this study we implemented a questionnaire that we developed (which has been described in an earlier publication of this journal) with 99 pre-dialysis patients, 99 dialysis patients, and 87 transplantation patients. We completed the attitude questionnaire designed by our team to include disease burden and depression questionnaires. RESULTS: We used discriminant analysis to describe different stages of the disease. There was a significant difference in the following factors between the three patient groups: accepting the new kidney, lack of confidence in transplantation therapy, fear of surgery, accepting self-responsibility in recovery, dependency on the transplanted kidney, confidence in recovery, subjective burden of dialysis, and denial of personal responsibility in maintaining the transplanted kidney. Significant differences were also detected in these three groups regarding the level of depression and disease burden: we measured the highest value among the dialysis patients, and the lowest value among the pre-dialysis patients. Comparing patients accepting and refusing transplantation, we found a correlation between the refusal of transplantation and the attitudes towards the illness and treatment. CONCLUSIONS: Most patients remain unmotivated to change treatment modality and refuse transplantation. Misbelief about transplantation shows a correlation with the motive of refusal. Dissemination of information may facilitate a change in the situation.

Effects of pituitary adenylate cyclase activating polypeptide on small intestinal INT 407 cells.

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide having a widespread distribution both in the nervous system and peripheral organs including the gastrointestinal tract. It has been shown to exert actions on intestinal functions, mainly affecting glandular secretion and motility. PACAP has several different effects on cell survival depending on the cell type and the applied stimulus. Its influences on small intestinal epithelial cells are not yet elucidated, therefore the aim of the present study was to investigate the effects of PACAP on intestinal epithelial cells having high turnover (INT 407) against different harmful stimuli, such as oxidative stress, in vitro hypoxia and gamma radiation. We tested the effect of PACAP on proliferation and cell survival using MTT assay. Moreover, various cancer-related factors were evaluated by oncology array. PACAP did not influence the proliferation rate of INT 407 cells. Its cell survival-enhancing effect could be detected against oxidative stress, but not against in vitro hypoxia or gamma irradiation. Clonogenic survival assay was performed to analyze the effect of PACAP on clonogenic potential of cells exposed to gamma radiation. Surprisingly, PACAP enhanced the clone-forming ability decrease induced by irradiation. Western blot analysis of ERK1/2 phosphorylation was performed in order to obtain further information on the molecular background. Our data showed phospho-ERK1/2 suppression of PACAP in irradiated cells. Furthermore, the role of endogenous PACAP against oxidative stress was also investigated performing ADCYAP1 small interfering RNA transfection. We found significant difference in the cell vulnerability between cells undergoing silencing and cells without transfection suggesting the protective role of the endogenously present PACAP against oxidative stress in INT 407 cells. In summary, PACAP seems to be able to exert contradictory effects in INT 407 cells depending on the applied stressor, suggesting its regulatory role in the cellular household.

A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML or AML with ⩽30% blasts.

Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts. The MTD was not reached; the RP2D was PAN 30 mg plus AZA 75 mg/m2. More patients receiving PAN+AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6-43.9%)) vs AZA (14.3% (5.4-28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50-80%); AZA, 70% (50-80%)) or time to progression (PAN+AZA, 70% (40-90%); AZA, 70% (40-80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen.

Evaluation of Mannose-Binding Lectin is a Useful Approach to Predict the Risk of Infectious Complications Following Autologous Hematopoietic Stem Cell Transplantation.

Hematopoietic stem cell transplantation (HSCT) associated immunocompromised state carries high risk of infectious complications. Mannose-binding lectin (MBL) is an acute phase protein involved in innate immune response. Serum MBL level is genetically determined and quite stable. According to literature, significant association was shown between low MBL concentrations and serious infections. The association between serum MBL level and frequency and severity of infections was studied in 186 patients following autologous HSCT. Double-monoclonal antibody sandwich enzyme-linked immunosorbent assay was used to determine MBL antigen level in sera. MBL levels were measured around 100 days following transplantation, in a period without active infection. Twenty-one patients (11%) were MBL deficient. The median time of first infection and number of infections during the first year post-transplantation were not significantly different between patients with MBL deficiency and those without MBL deficiency. The occurrence and number of infections after HSCT correlated with the MBL/C-reactive protein ratio. The number of severe infections was not higher among those with MBL deficiency. The occurrence of infections after the pre-engraftment period during the first year post-transplantation was significantly different in patient groups separated by MBL cut-off level. The MBL/C-reactive protein ratio might be a useful marker of infectious complications. MBL measurement may be helpful in antibiotic treatment. In case of MBL deficiency, earlier and more intensive treatment may be indicated.

Questionnaire Development for the Measurement of Patients' Attitudes Toward Renal Transplantation.

OBJECTIVE: The aim of this work was the exploration of chronic renal insufficiency patients' attitudes toward treatment, various motifs underlying their acceptance or refusal of kidney therapy, and understanding of their psychologic content. Examinations were carried out of chronic renal insufficiency patients' attitudes toward renal treatments, and a questionnaire suitable for its assessment was developed. METHODS: Suppositions of patients before and after renal transplantation were explored by means of semistructured interviews. The content-based analysis of the interview narratives revealed the system of content-categories, which we fitted with attitude questions. Transplant patients took part in the trial of the questionnaire, and the statistical analysis of their replies revealed specific variations in patients' attitudes toward transplantations. RESULTS: The results of the principal component analysis classified the replies of transplanted patients into 8 categories for interpretation: hope of recovery, effects of dialysis in deterioration of quality of life, mistrust of transplantation, refusal, anxiety in the run-up phase to transplantation, difficulty in acceptance of the disease and transplantation as a treatment, fears of living-donor transplantations, acceptance of transplantation, and curiosity about dead donors. CONCLUSIONS: Our research explored attitude variances among patients for and against transplantations. A good understanding of patients' attitudes (the exploration of valid and invalid assumptions) might exert a positive influence on patient decisions, and might improve their attitude toward their treatment and their adherence from preparation for the operation to the postoperative phase of recovery.

Combined prognostic value of absolute lymphocyte/monocyte ratio in peripheral blood and interim PET/CT results in Hodgkin lymphoma.

Decreased absolute lymphocyte/monocyte ratio (LMR) in peripheral blood has been reported as an unfavorable prognostic marker in Hodgkin lymphoma. We aimed to investigate whether combining LMR and interim PET/CT scan result (PET2) confers stronger prognostic value than PET2 alone. 121 HL patients were investigated. LMR was calculated from a blood sample taken at the time of diagnosis. PET2 was carried out after the second chemotherapy cycle. Survival was calculated using the Kaplan-Meier method and significance was determined by log-rank test. Effect of variants on survival results was examined using univariate and multivariate analyses. Best LMR cut-off value was determined by receiver operating characteristic (ROC) curve. Best LMR cut-off value was 2.11 in the case of our patients (LMR > 2.11: favorable, LMR ≤ 2.11: unfavorable). Overall and progression-free survivals (OS/PFS) were significantly worse both in lower LMR (≤ 2.11) (OS: P = 0.041, PFS: P = 0.044) and PET2 positive groups (OS: P < 0.001, PFS: P < 0.001). In PET2 positive patient group (n = 32) the low LMR result meant a significantly worse OS (0.030) and PFS (0.001). Both LMR and PET2 proved to be independent prognostic factors on multivariate analysis, and strengthened each other's effect.

Prognostic value of interim and restaging PET/CT in Hodgkin lymphoma. Results of the CHEAP (Chemotherapy Effectiveness Assessment by PET/CT) study - long term observation.

Very few studies have determined the prognostic value of interim and restaging PET/CT in patients with Hodgkin lymphoma using current standard of care therapy outside clinical trials. We analyzed the effect of the results of interim and restaging PET/CT on the survival (overall- and relapse-free) in patients who received standard first-line treatment based on the stage of disease and risk factors. We investigated the differences between the relapse and non-relapse groups based on the clinical pathological characteristics of patients who had positive interim PET/CT results.Between January 1, 2007 and December 31, 2011, the staging, interim and restaging PET/CT scans of patients with Hodgkin lymphoma were analyzed. The Deauville criteria were used for the evaluation of interim PET/CT scans. One hundred and thirteen Hodgkin lymphoma patients underwent staging, interim and restaging PET/CT scans. None of the therapy was modified based on the interim PET/CT results. The median follow-up time was 43.5 months. A total of 62 early stage patients and 51 advanced stage patients were identified. The five-year overall survival rates were 93.4% in the interim PET negative group and 58% in the interim PET positive group (p<0.001). The five-year relapse-free survival rates for the negative and positive groups were 92.7% and 40.8%, respectively (p<0.001). The negative predictive value was 100% in the early stage group and 82.35% in the advanced stage group. By comparison, the positive predictive values were 53.8% and 58.8%, respectively, in these two groups. In the interim PET positive group, patients over 40 years of age had a significantly higher probability of relapse (p=0.057).The routine clinical use of interim PET/CT is highly recommended based on our investigation. However, patients with positive interim PET/CT results required frequent additional evaluations.

Prognostic value of FDG-PET in Hodgkin lymphoma for posttreatment evaluation. Long term follow-up results.

Determining the viability of residual tumor masses is a great challenge after primary treatment of Hodgkin lymphoma. FDG-PET may play a crucial role in this procedure. In this study, files of 128 Hodgkin lymphoma patients were reviewed, who were treated in three Hungarian hematology centers between January 1995 and February 2005. CT scan showed residual tumor mass by all of them. Their median follow-up was 75.5 months from PET examination. The number of true-positive, true-negative, false-positive, false-negative subjects were 29, 83, 10, 6, respectively. Sensitivity of post-treatment FDG-PET was 83 %, specificity 93 %, positive predictive value 74 %, negative predictive value 93 %, and accuracy 88 %. The difference between the event free survival of PET positive and negative cases is highly significant (p=0.0000), according to the Mantel-Cox test. Our results in the largest cohort of patients, in accordance with literature, clearly indicates that patients with negative FDG-PET results are unlikely to progress or relapse during the longest follow-up.

Aspects of B-cell non-Hodgkin's lymphoma development: a transition from immune-reactivity to malignancy.

The development of B-cell lymphomas is an intricate interplay among various pathogenic factors, leading to a multi-step process, encompassing various stages of B-cell maturation. Besides genetic abnormalities, a variety of environmental and microbial factors, as well as disproportional immune-regulatory processes lead to the malignant transformation. Yet, little is known about the exact chain of events, which lead from the physiological polyclonal B-cell activation as a response to exogenous antigens through oligoclonality to a monoclonal, uncontrolled, malignant B-cell proliferation. The aim of the present review was to summarize the potential harmful steps in the development of B-cell lymphomas, according to conventional and novel theories, and to depict therapeutic regimens presently in use as well as to envision future drug developments, beneficial in the battle against this lymphoid malignancy.

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)-clinicopathological features based on the data of two Hungarian lymphoma centres.

UNLABELLED: Clinicopathological features of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) differ from those of the classical Hodgkin lymphoma (cHL). Our aim was to examine clinical presentation, therapeutic and survival results of NLPHL patients in Hungary based on the data of two centres, and incidentally we analyzed the clinicopathological characteristics and differential diagnostic difficulties of this rare entity. We analyzed the clinical features, treatment and survival data of 536 Hodgkin lymphoma patients who had been diagnosed and primarily treated in our institutes between 1995 and 2004. Mean follow-up time was 82.7 (3-144) months of the total 536 HL patients. Sixteen (3%) of the patients were diagnosed with NLPHL, 93% of them presented with early-stage disease. None of the patients showed extranodal or splenic involvement or bulky disease. One patient received chemotherapy alone, six received only involved field radiotherapy while six underwent combined modality treatment. We applied watch and wait strategy in three cases. Overall response rate was 100% (93.75% complete). Two NLPHL cases transformed to non-Hodgkin's lymphoma. In contrast to the classical HL, the 10-year prognosticated overall survival rate was 100 vs. 82%, the event free survival was: 75% vs. 70%. In NLPHL group there were no late or multiple relapses and none of them died. CONCLUSIONS: NLPHL is a rare disease, thus these are limited experiences with its diagnosis and treatment. Since the disease has an excellent outcome, it is very important to prefer less toxic or local therapies to reach long term survival similar to that of the normal population.

Epidural malignant lymphomas of the spine: collected experiences with epidural malignant lymphomas of the spinal canal and their treatment.

STUDY DESIGN: Retrospective study of 13 patients treated by the authors. OBJECTIVE: To examine the course of the disease of malignant lymphoma (ML) presenting in the epidural area of the spine. SETTING: Department of Neurosurgery, Third Department of Internal Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. SUBJECTS AND METHODS: The epidural presentation in eight patients was heralded by motor signs (paraparesis and plegia), in one by a lesion of the posterior columns of the spinal cord (ataxia), and in three by pain. One patient was free of complaints and symptoms. The affected epidural area was diagnosed previously by myelography and computerized tomography (CT), and later by magnetic resonance (MR), over the course of which the location was verified as thoracic in eight patients, cervical in one, and lumbar in four. The authors recommended surgical intervention in 9 out of 13 cases, in seven cases of Hodgkin's and six cases of non-Hodgkin's lymphoma. Seven patients were treated for recognized manifestations of malignant lymphoma while six were diagnosed by intraoperative-histological examination. RESULTS AND CONCLUSION: The decompression operations for tumors resulted in limited improvement in seven patients (reduction in pain and return of ability to walk). Four patients were not operated on, two of which had significant improvement in their neurological symptoms. Paraparesis remained unchanged in one patient. One patient remained symptom-free. The authors emphasize the importance of interdisciplinary consultation and weighing individual priorities in the indications for operation on epidural ML.

Successful rituximab-CHOP treatment of systemic lupus erythematosus associated with diffuse large B-cell non-Hodgkin lymphoma.

The authors discuss the case of a 76-year-old female patient who has been suffering from subacute cutaneous lupus erythematosus since 1983. In 1999 she was diagnosed with systemic lupus erythematosus (SLE) based on her symptoms of malar rash, polyarthritis, leukopenia, autoimmune hemolytic anemia and positive anti-DNA antibody test. For this she received methylprednisolone and cyclophosphamide. After 3 years of remission, symptoms of cutaneous vasculitis appeared in 2004, which transitionally responded to treatment with azathioprin and methylprednisolone. Her cutaneous symptoms, however, progressed quickly along with generalized lymphadenopathy, splenomegaly and thrombocytopenia. Immunohistological evaluation of the lymph node biopsy showed diffuse large B-cell lymphoma. She developed complete remission after treatment with six-cycle R-CHOP (rituximab, and reduced doses of cyclophosphamide, vincristin, adriablastin, methylprednisolone). SLE became inactive and her symptoms of vasculitis resolved. The authors are bringing attention to one of the possible late complications of systemic lupus, and also underscoring that treatment with rituximab (+CHOP) was beneficial not only for the lymphoma but the SLE as well.

Investigation of monoclonal gammopathy of undetermined significance: a single-centre study.

Summary The main characteristic of monoclonal gammopathies (MG) is the presence of an increased amount of both electrophoretically and immunologically homogeneous immunoglobulins (M component). According to the WHO classification, monoclonal gammopathies are classified among the non-Hodgkin's lymphomas as 'plasma cell dyscrasias'. The unknown behaviour state, so-called MGUS (monoclonal gammopathy of undetermined significance), is distinguished from the malignant diseases. We investigated the frequency and features of MG and MGUS by reviewing the serum immunochemistry protein analyses between 1998 and 2004. Among 18,642 analyses, MG was found in 1,983 cases (10.39%) derived from one or more samples of 416 patients. Case histories of 340 patients were analysed. A malignant lymphoproliferative disease was proved in 171 cases, while in 169 cases the behaviour of the gammopathy was unknown. In 65 cases, the disease was possibly not related to MG. Mean follow-up time of the 65 patients with MGUS was 42 (9-81) months. During the follow-up period seven patients progressed into a malignant lymphoproliferative disorder-- mean probability of the malignant transformation was 3.07%/year and it occurred more frequently in the presence of immunoglobulin A isotype. There was no correlation between the progression of the disease and other laboratory findings. Besides the analyses of MG-related diseases, we focus on the malignant transformation of MGUS and on the importance of regular clinical and laboratory control examinations.

Gastroesophageal reflux disease progressing to achalasia.

Two achalasia patients with former complaints of heartburn were examined. Antisecretory drugs were used by the patients when dysphagia occurred. Barium X-ray and esophageal manometry were performed and achalasia was diagnosed in both patients. Twenty-four-hour pH-metry showed significant and long-lasting acid reflux during supine position. Prolonged reflux episodes can be explained not only by the swallow-unrelated transient relaxation of lower esophageal sphincter (LES) and mechanical damage of the esophageal body, but also by its chemical insensitivity. Thus preoperative detection of reflux should determinate either the operational procedure and the postoperative follow up of the patient.

Antibodies against extractable nuclear antigen in non-Hodgkin lymphoma patients.

Autoantibodies are found at higher frequency in malignant lymphoproliferative diseases and also the association of these diseases with autoimmunity is documented. However precise mechanisms are not yet understood beyond these findings. We measured anti-extractable nuclear antigen (ENA) antibodies in non-Hodgkin's lymphoma patients before, during and after chemotherapy and compared these values to healthy controls. Sixty six lymphoma patients' data were compared with 30 healthy patients' data. ENA levels were significantly elevated in untreated lymphoma patients compared with healthy controls (1.85 U/l versus 0.68 U/l, P < 0.05). This increase could be observed during and after treatment as well. Those patients who responded well to initial chemotherapy were demonstrated with gradually increasing ENA antibody titers compared with the rest of patients, where a gradual decrease in titer was found. These findings are not yet statistically significant, but may help us further understand immunological reactions beyond the treatment of malignant lymphomas.

Phase III double-blind placebo-controlled study of farnesyl transferase inhibitor R115777 in patients with refractory advanced colorectal cancer.

PURPOSE: To determine whether R115777 improves survival in patients with refractory advanced colorectal cancer (CRC) in a multicenter, double-blind, prospective randomized study. PATIENTS AND METHODS: Three hundred sixty-eight patients were randomly assigned to R115777 (300 mg twice daily) orally for 21 days every 28 days or placebo in a 2:1 ratio. All patients received best supportive care. The primary end point was overall survival; secondary end points were progression free survival, tumor response, toxicity, and quality of life. RESULTS: The two treatment groups were well balanced for baseline demographics, including previous chemotherapy for advanced CRC. The median overall survival for R115777 was 174 days (95% CI, 157 to 198 days), and 185 days (95% CI, 158 to 238 days) for those patients receiving placebo (P =.376). One patient achieved a partial response in the R115777 arm. Stable disease (> 3 months) was observed in 24.3% patients in the R115777 group compared to 12.8% in the placebo arm. This did not translate into a statistically significant increase in progression-free survival. Overall, treatment was well tolerated. There was an increased incidence of reversible myelosuppression (neutropenia, thrombocytopenia), rash, and grade 1 to 2 diarrhea in the R115777 arm. There was no statistically significant difference in quality of life between arms. CONCLUSION: Single agent R115777, given at this dose and schedule, has an acceptable toxicity profile, but does not improve overall survival compared to best supportive care alone in refractory advanced CRC.