Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi.

BACKGROUND: Tumor regression after antiviral therapy (AT) is in favor of an etiological role of hepatitis C virus (HCV) in non-Hodgkin's B-cell lymphomas (NHL). PATIENTS AND METHODS: We carried out a cohort study of 704 consecutive HIV-negative, HCV-positive patients with indolent NHL diagnosed and treated from 1993 to 2009 in 39 centers of the Fondazione Italiana Linfomi; 134 patients were managed with AT for lymphoma control. RESULTS: For entire cohort, 5-year overall survival (OS) was 78% [95% confidence interval (CI): 74%-82%] and 5-year progression-free survival (PFS) was 48% (95% CI: 44%-53%). In multivariate analysis, the use of AT during the patients' life had positive impact on OS. Forty-four of the 100 patients treated with first-line AT achieved a complete remission (CR) and 33 a partial response (PR). HCV-RNA clearance was achieved in 80 patients and was related to lymphoma response. At a median follow-up of 3.6 years, 5-year PFS was 63% (95% CI: 50%-73%). CR + PR rate was 85% with AT as second-line treatment. CONCLUSION: AT produces HCV-RNA clearance and consequent tumor regression in most patients with HCV-related indolent NHL. AT used at any time is associated with improved OS. Consequently, AT can be considered an option for patients with indolent lymphomas who do not need immediate cytoreductive treatment.

Pegfilgrastim versus filgrastim after high-dose chemotherapy and autologous peripheral blood stem cell support.

BACKGROUND: American Society of Clinical Oncology guidelines recommend the use of growth factor after high-dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) support. This randomized trial aims to demonstrate the noninferiority of pegfilgrastim (PEG) compared with filgrastim (FIL) after HDC. PATIENTS AND METHODS: Eighty patients were assigned to FIL at a daily dose of 5 mug/kg or a single fixed dose of PEG (6 mg) 1 day after PBSC. The primary end point was the duration of neutropenia both in terms of absolute neutrophil count (ANC) <0.5 x 10(9)/l and of days to reach an ANC >0.5 x 10(9)/l. RESULTS: The mean duration of neutropenia was 6 and 6.2 days and the mean time to reach an ANC >0.5 x 10(9)/l was 11.5 and 10.8 in the FIL and PEG group, respectively. No differences were observed in the mean time to reach an ANC >1.0 x 10(9)/l (12.2 versus 12.0 days) in the incidence of fever (62% versus 56%) and of documented infections (31% versus 25%). The mean duration of antibiotic therapy was 5.7 and 4.0 days in FIL and PEG group, respectively. CONCLUSION: PEG is not inferior to FIL in hematological reconstitution and represents an effective alternative after HDC and PBSC.

ABVD plus radiotherapy versus EVE plus radiotherapy in unfavorable stage IA and IIA Hodgkin's lymphoma: results from an Intergruppo Italiano Linfomi randomized study.

BACKGROUND: In 1997, the Intergruppo Italiano Linfomi started a randomized trial to evaluate, in unfavorable stage IA and IIA Hodgkin's lymphoma (HL) patients, the efficacy and toxicity of the low toxic epirubicin, vinblastine and etoposide (EVE) regimen followed by involved field radiotherapy in comparison to the gold standard doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) regimen followed by the same radiotherapy program. PATIENTS AND METHODS: Patients should be younger than 65 years with unfavorable stage IA and IIA HL (i.e. stage IA or IIA with bulky disease and/or subdiaphragmatic disease, erythrocyte sedimentation rate higher than 40, extranodal (E) involvement, hilar involvement and more than three involved lymph node areas). RESULTS: Ninety-two patients were allocated to the ABVD arm and 89 to the EVE arm. Complete remission (CR) rates at the end of treatment program [chemotherapy (CT) + RT] were 93% and 92% for ABVD and EVE arms, respectively (P = NS). The 5-year relapse-free survival (RFS) rate was 95% for ABVD and 78% for EVE (P < 0.05). As a consequence of the different relapse rate, the 5-year failure-free survival (FFS) rate was significantly better for ABVD (90%) than for EVE (73%) arm (P < 0.05). No differences in terms of overall survival (OS) were observed for the two study arms. CONCLUSIONS: In unfavorable stage IA and IIA HL patients, no differences were observed between ABVD and EVE arms in terms of CR rate and OS. EVE CT, however, was significantly worse than ABVD in terms of RFS and FFS and cannot be recommended as initial treatment for HL.

A phase II, multicentre trial of decitabine in higher-risk chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a complex clonal hematological disorder classified among myelodysplastic (MDS)/myeloproliferative neoplasms. Prognosis is poor and there is a lack of effective treatments. The hypomethylating agent decitabine has shown activity against MDS and elderly acute myeloid leukemia, but there is little data focusing specifically on its efficacy in CMML. In this prospective, phase 2 Italian study, CMML patients received intravenous decitabine 20 mg/m2 per day on Days 1-5 of a 28-day treatment cycle. Response was evaluated after four and six cycles; patients responding at the end of six cycles could continue treatment with decitabine. Forty-three patients were enrolled; >50% were high-risk according to four CMML-specific scoring systems. In the intent-to-treat population (n=42), the overall response rate after six cycles was 47.6%, with seven complete responses (16.6%), eight marrow responses (19%), one partial response (2.4%) and four hematological improvements (9.5%). After a median follow-up of 51.5 months (range: 44.4-57.2), median overall survival was 17 months, with responders having a significantly longer survival than non-responders (P=0.02). Grade 3/4 anemia, neutropenia and thrombocytopenia occurred in 28.6%, 50% and 38% of patients, respectively. Decitabine appears to be an effective and well-tolerated treatment for patients with high-risk CMML.

Establishment of a Ph1-positive human cell line (BV173).

A new cell line (BV173) derived from a patient with Philadelphia chromosome (Ph1)-positive acute leukemia was compared with the Ph1-positive K562 and NALM-1 lines, which display the phenotypic characteristics of erythroid and pre-B cells, respectively. BV173 cells retained the Ph1 chromosome and had the morphologic and cytochemical features of undifferentiated blast cells. They lacked the membrane characteristics of mature B- or T-lymphocytes and did not react with monoclonal antibodies to the myelomonocytic cell lineage. Although they reacted with anti-glycophorin A antiserum, they failed to produce hemoglobin after butyric acid treatment. This line was similar to NALM-1 in that it bore common acute lymphoblastic leukemia antigen and la-like antigen, reacted with monoclonal antibodies directed against early stages of hematopoietic cell differentiation, and presented the nuclear enzyme terminal deoxynucleotidyl transferase. However, it differed from NALM-1 because it did not express cytoplasmic IgM, a marker of pre-B-cells. The new line can be considered a clonal expansion of leukemia cells blocked at an earlier differentiation stage than that for the other Ph1-positive cell lines.

Effects of potassium dichromate on nucleic acid and protein syntheses and on precursor uptake in BHK fibroblasts.

Treatments for 1 to 4 hr with 10-4 m potassium dichromate, a soluble hexavalent chromium salt with a strong oxidizing power, markedly reduce DNA and RNA accumulation rates in hamster fibroblasts grown in vitro (BHK line), as shown by quantitative spectrophotometric determinations. Such inhibitory action is not immediately evident on the basis of the incorporation rates of labeled nucleosides into DNA and RNA, as dichromate affects also the relative concentrations of labeled precursors in the intracellular pool. Dichromate first stimulates and then inhibits nucleoside (mostly thymidine) uptake, whereas amino acid uptake is immediately inhibited. Actual rates of macromolecular syntheses have been calculated by taking into account the induced changes of soluble precursor concentrations; sucn normalized rates point out that dichromate induces a sudden blockage of DNA replication, whereas RNA and protein syntheses are secondarily inhibited. The observed cytotoxic effects of dichromate are tentatively referred to the oxidation of cell components by hexavalent chromium and thereby to the interaction of reduced trivalent chromium with specific biological ligands on cell membrane and on DNA.

Does the use of a university lecturer as a visiting tutor support learning and assessment during physiotherapy students' clinical placements? A survey of higher education institution providers.

OBJECTIVES: To establish the rationale for using a lecturer as a visiting tutor, and to identify the activities undertaken during clinical placements to support student learning and assessment in practice. DESIGN: A secure electronic survey was used to incorporate qualitative and quantitative data collection procedures. SETTING: Thirty-three higher education institution (HEI) providers of physiotherapy education in the UK, registered with the Chartered Society of Physiotherapy. PARTICIPANTS: UK HEI physiotherapy placement coordinators. MAIN OUTCOME MEASURES: A questionnaire was used to examine HEI perceptions. A pilot focus group consultation informed the questionnaire content. Surveys were analysed based on the proportion of responses to closed questions on an adapted Likert scale, with further thematic analysis of open questions. RESULTS: All 25 respondents (25/33, 76%) indicated their provision of support for students and clinical educators throughout their clinical placements. 'Face-to-face' engagement during the placement visit was viewed as essential to guide the clinical educator to provide a consistent approach to learning and assessment strategies; ensuring cohesion between theoretical and clinical components of the curriculum was viewed as a core objective by visiting academic tutors. However, the emergent themes highlighted key differences between HEIs' perspectives of what this support for clinical placement learning should entail. CONCLUSIONS: The majority of HEIs endorse the use of a lecturer as a visiting tutor to inform and maintain the standard of learning and assessment within the clinical placement. However, the value of this interaction requires confirmation via other stakeholders, and exploration of other forms of non-face-to-face support processes warrant further investigation.

PO-03 - Khorana score and histotype predict the incidence of early venous thromboembolism (VTE) in Non Hodgkin Lymphoma (NHL). A pooled data analysis of twelve clinical trials of Fondazione Italiana Linfomi (FIL).

BACKGROUND: Recent studies show that the risk of VTE in NHL pts is similar to that observed in high risk solid tumors (i.e. pancreatic, ovarian cancer). VTE in NHL occurs in most cases within three months from diagnosis and can have substantial impact on treatment delivery and outcome as well as on quality of life. However few data are available on potential predictors. AIMS: To better clarify the epidemiology of early (within six months from treatment start) VTE in NHL we conducted a pooled data analysis of 12 clinical trials from FIL. Our analysis included basic demographic features, lymphoma-related characteristics as well the Khorana score (based on histology, BMI, platelets WBC and HB counts) which is extensively used in solid tumors to predict VTE risk. PATIENTS AND METHODS: From Jan. 2010 to Dec. 2014, all pts with B-cell NHL enrolled in prospective clinical trials from FIL for frontline treatment were included. For 9 studies study period included the entire trial population was included. The analyses were conducted based on CRFs as well as pharmacovigilance reports. VTE definition and grading was stated according to standard criteria of toxicity (CTCAE V4.0). Cumulative incidence of VTE from the study enrollment was estimated using the method described by Gooley et al. accounting for death from any causes as a competing risk. The Fine & Gray survival model was used to identify predictors of VTE among NHL pts. Factors predicting the grade of VTE were investigated using an ordinal logistic regression model. This pooled data analysis was approved by local IRB. RESULTS: Overall, 1,717 patients belonging to 12 studies were evaluated. Eight were phase I/II or II (25% of pts) and 4 phase III (75% of pts). M/F ratio was 1.41, Median age was 57, (IQ range (IQR) 49-66). Histologies were: DLCL-B 34%, FL 41%, MCL 18%, other 6%. Median BMI was 25 (IQR 22-28). Median Hb, WBC and platelets counts were 13g/dl) (IQR 11.5-14.2), 7.1*10^(9)/l (IQR 5.6-10.3), 224*10^(9)/l (IQR 169-298), respectively. 1189 pts were evaluable Khorana score: 58% low risk, 30% intermediate risk, 12% were high risk. Human erythropoetin support was given to 9% of patients. All pts received Rituximab. Planned therapeutic programs included ASCT in 27% of pts, conventional chemotherapy in 67% a conventional chemotherapy plus lenalidomide in 6%. Overall 59 any grade VTE episodes occurred in 51 pts (2.9%), including 21 grade III-IV VTE (18 pts). None was fatal. Median time from study enrolment to VTE was 63 days (IQR: 35-110). Considering death as a competitive event the 6 months cumulative incidence of VTE was 2,2% in low risk Khorana score, 4.5% (95%IC: 2.3-6.7) in intermediate and 6.6% (95%IC: 2.4-10.8) in high risk (p=0.012) (figure 1). Khorana score was predictive also for grade III-IV events as they were 0,7% (95% CI:0.1-1.4) in low risk and 2.0% (95% CI:0.8-3.3) in intermediate-high risk (p=0.048). The results were similar also after excluding lenalidomide containing studies. The Fine and Gray multivariate analyses, adjusted for age and stage, showed that Khorana score (intermediate risk adjHR=1.96; 95%IC: 0.84-4.56 and high risk adjHR=3.81; 95%IC: 1.51-9.58) and DLCL-B histotype (adjHR=2.58; 95% CI: 1.01-6.55) were independently associated to an increased risk of VTE. Moreover an ordinal logistical regression model indicated that the increase of one point in the Khorana score resulted in an increased risk of VTE (OR=1.85; 95% CI: 1.23-2.79). CONCLUSIONS: Our results suggest that DLCL-B histotype and Khorana score are predictors of VTE in NHL. The latter might become a simple and effective tool to assess the risk of VTE in NHL. Prospective validation including also patients not eligible for clinical trials is needed.

PML-RARα kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy.

The APL0406 study showed that arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are not inferior to standard ATRA and chemotherapy (CHT) in newly diagnosed, low-intermediaterisk acute promyelocytic leukaemia (APL). We analysed the kinetics of promyelocytic leukaemia-retinoic acid receptor-α (PML-RARα) transcripts by real-time quantitative PCR (RQ-PCR) in bone marrow samples from 184 patients and assessed the prognostic impact of fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 159 patients enrolled in this trial in Italy. After induction therapy, the reduction of PML-RARα transcripts was significantly greater in patients receiving ATRA-CHT as compared with those treated with ATRA-ATO (3.4 vs 2.9 logs; P=0.0182). Conversely, at the end of consolidation, a greater log reduction of PML-RARα transcripts was detected in the ATRA-ATO as compared with the ATRA-CHT group (6.3 vs 5.3 logs; P=0.0024). FLT3-ITD mutations had no significant impact on either event-free survival (EFS) or cumulative incidence of relapse in patients receiving ATRA-ATO, whereas a trend for inferior EFS was observed in FLT3-ITD-positive patients receiving ATRA-CHT. Our study shows at the molecular level that ATRA-ATO exerts at least equal and probably superior antileukaemic efficacy compared with ATRA-CHT in low-intermediaterisk APL. The data also suggest that ATRA-ATO may abrogate the negative prognostic impact of FLT3-ITD.

MACOP-B treatment in diffuse large-cell lymphoma: identification of prognostic groups in an Italian multicenter study.

PURPOSE: The prognosis of advanced-stage diffuse large-cell lymphoma (DLCL) has improved with the use of the third-generation regimens such as methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B). However, different results have been reported. Therefore, we started a cooperative study to confirm the efficacy of MACOP-B. An analysis of prognostic factors was also performed to identify poor-prognosis patients. PATIENTS AND METHODS: Between June 1986 and March 1989, 180 patients with advanced-stage DLCL were treated with MACOP-B. MACOP-B was given according to the original scheme. Numerous clinical features possibly predictive for complete response (CR), disease-free survival (DFS), and survival were analyzed in univariate and multivariate analyses. RESULTS: One hundred twenty-seven patients (71%) achieved a complete remission, 20 (11%) achieved a partial remission, 24 (13%) had unchanged or progressive disease, and nine (5%) died due to toxicity. With a median follow-up of 28 months, 71% of 127 CRs remain in first remission. Predicted 3-year survival for all 180 patients is 60%, and 3-year DFS for the 127 CRs is 67%. Overall toxicity was acceptable, with mucositis being the most frequent severe side effect. A multivariate regression analysis identified lactate dehydrogenase (LDH) level, bone marrow involvement, and tumor burden as independent risk factors for survival. These factors were also important for achievement of remission and DFS and allowed us to identify three distinct risk groups of patients with good, intermediate, and poor prognosis, with 3-year survival rates of 80%, 59%, and %29, respectively. CONCLUSIONS: These results confirm the effectiveness of MACOP-B in advanced-stage DLCL at low or intermediate risk; however, high-risk patients are in urgent need of new therapeutic approaches. A better definition of prognostic features would allow a more reliable comparison of different treatment regimens, as well as an effective tailoring of therapy by prognostic groups.

Image-aided estimate of tumor burden in Hodgkin's disease: evidence of its primary prognostic importance.

PURPOSE: To explore a more direct method for evaluating tumor burden (TB) in Hodgkin's disease (HD) and to verify its prognostic importance. PATIENTS AND METHODS: The volume of TB at diagnosis was directly and retrospectively measured in 121 HD patients through images of the lesions recorded by computed tomographic (CT) scan of the thorax, abdomen, and pelvis for all deep sites of involvement and many superficial ones, and by ultrasonography (US) for the remaining superficial lesions. RESULTS: The TB, which was obtained from the sum of the volumes of all the lesions measured on CT scans and US and normalized to body-surface area (relative TB [rTB]), showed a median value of 102.6 cm(3)/m(2) (range, 2.2 to 582.8). At multivariate analysis for prognostic value, rTB was the parameter that statistically correlated best with time to treatment failure (P = 2.2 x 10(-6)), followed by erythrocyte sedimentation rate (ESR) (P =.0003), and serum fibrinogen (P =.0112). The prognostic discrimination allowed by rTB alone proved to be clearly superior to that obtained with the score of the International Prognostic Factor Project. The rTB was found to be correlated with many clinical staging parameters (bulky disease, number of involved lymph node regions, serum lactate dehydrogenase, ESR, hemoglobin, Karnofsky index), but its predictability from these variables was low (R(2) =.668). CONCLUSION: Relative TB is emerging as a strong prognostic factor in HD, more powerful than and largely independent of those hitherto known and used. Further studies are needed to confirm these results and exploit their clinical value, particularly the relationship among rTB, drug doses, and response.

Intensified and high-dose chemotherapy with granulocyte colony-stimulating factor and autologous stem-cell transplantation support as first-line therapy in high-risk diffuse large-cell lymphoma.

PURPOSE: In our previous study with MACOPB, we identified a high-risk group of patients with a poor 3-year survival rate of 29%. These patients were defined as having at diagnosis advanced-stage disease with high tumor burden (TB) and elevated lactate dehydrogenase (LDH) level or bone marrow (BM) involvement. A novel therapeutic scheme was investigated to improve the outcome of these patients. PATIENTS AND METHODS: Fifty patients with high-risk diffuse large-cell lymphoma (DLCL) were enrolled. The therapeutic scheme includes three phases: induction with 8 weeks of MACOPB; intensification with a 3-day course of mitoxantrone 8 mg/m2 plus high-dose cytarabine (HDARA-C) 2 g/m2 every 12 hours plus dexamethasone 4 mg/m2 every 12 hours (MAD protocol) and granulocyte colony-stimulating factor (G-CSF) 5 microg/kg on days 4 to 17 to harvest peripheral-blood progenitor cells (PBPC); consolidation with carmustine (BCNU), etoposide, ARA-C, and melphalan (BEAM) regimen; plus autologous stem-cell transplantation (ASCT) with PBPC, marrow, or both. RESULTS: Thirty-six patients (72%) achieved a complete response (CR), 11 (22%) showed no response (NR), and three (6%) died of toxicity. Among the 22 PRs or NRs after the induction phase, 56% of patients achieved a CR with subsequent intensified therapy. With a median follow-up duration of 32 months, the overall survival and failure-free survival rates were 56% and 50%, respectively. The disease-free survival rate is 69% at 32 months. Leukapheresis after MAD and G-CSF yielded a median of 32 x 10(6)/kg CD34+ cells and 80 x 10(4)/kg granulocyte-macrophage colony-forming units (CFU-GM). Thirty-nine patients were autografted and 11 did not undergo ASCT: six because of disease progression, four due to toxicity, and one because of patient refusal. The median times to achieve engrafment were 11 days (range, 7 to 19) to a neutrophil count greater than 0.5 x 10(9)/L and 12 days (range, 8 to 60) to a platelet count greater than 50 x 10(9)/L. CONCLUSION: This sequential scheme with intensified and high-dose chemotherapy with ASCT is feasible with moderate toxicity and may improve the outcome in high-risk DLCL.

Chromosome damage induced in cord blood T-lymphocytes infected in vitro by HTLV-I.

Experiments were carried out to investigate whether the human T-lymphotropic virus type I (HTLV-I), alone or in combination with a chemical mutagen such as mitomycin C (MMC), has the capacity to damage host chromosomes. Cord-blood T lymphocytes (CBL) were infected by co-cultivation with lethally irradiated HTLV-I-producing cells. Infected and immortalized CBL were then studied for frequencies of sister chromatid exchanges (SCE), chromosome breaks and micronuclei. HTLV-I-infected cells had statistically higher baseline SCE, chromosome aberrations and micronucleus values than the uninfected control CBL. While MMC treatment further augmented these values both in control and in infected lymphocytes, the latter did not show dose-related increases, most likely because of the more pronounced MMC-induced delaying effect on cell progression to mitosis. In view of similar previous observations in mouse lymphocytes carrying the Moloney murine leukemia virus, it is suggested that expression of a common retrovirus gene product, such as the pol endonuclease, might be responsible for the cytogenetic abnormalities observed. In addition to the IL-2 autocrine loop, the direct induction of chromosome damage by HTLV-I in target lymphocytes may be related to the pathogenesis of malignancies associated with HTLV-I infection.

Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM).

A risk-adapted treatment strategy is mandatory for myelodysplastic syndromes (MDS). We refined the World Health Organization (WHO)-classification-based Prognostic Scoring System (WPSS) by determining the impact of the newer clinical and cytogenetic features, and we compared its prognostic power to that of the revised International Prognostic Scoring System (IPSS-R). A population of 5326 untreated MDS was considered. We analyzed single WPSS parameters and confirmed that the WHO classification and severe anemia provide important prognostic information in MDS. A strong correlation was found between the WPSS including the new cytogenetic risk stratification and WPSS adopting original criteria. We then compared WPSS with the IPSS-R prognostic system. A highly significant correlation was found between the WPSS and IPSS-R risk classifications. Discrepancies did occur among lower-risk patients in whom the number of dysplastic hematopoietic lineages as assessed by morphology did not reflect the severity of peripheral blood cytopenias and/or increased marrow blast count. Moreover, severe anemia has higher prognostic weight in the WPSS versus IPSS-R model. Overall, both systems well represent the prognostic risk of MDS patients defined by WHO morphologic criteria. This study provides relevant in formation for the implementation of risk-adapted strategies in MDS.

Induction of DNA repair synthesis by ultraviolet radiation and methylmethanesulphonate in cultured mouse lymphocytes.

The induction of DNA repair synthesis by UV-radiation and methyl-methanesulphonate (MMS) was studied in mouse lymphocytes and leukemic cells by means of autoradiography and scintillation counting, after labelling in vitro with tritiated thymidine ([3H]dThd). Repair stimulation was detected by both procedures in LSTRA and YC8 leukemic cell lines as well as in primary fibroblasts of BALB/c and BALB/Mo mice. No stimulation was observed in primary cultures of lymphocytes from the spleen, thymus and lymph-nodes of the same mice. In primary lymphocytes neither stimulation with concanavalin A (Con A) nor pre-incubation with 5-bromodeoxyuridine (BUdR) were effective in making evident DNA repair. The data put into question the reliability of the repair test for the prediction of carcinogenic potential of chemicals.

Human peripheral blood lymphocytes as a cell model to evaluate the genotoxic effect of coal tar treatment.

Peripheral blood lymphocytes (PBL) from psoriatic patients therapeutically exposed to polycyclic aromatic hydrocarbons (PAH) during coal tar (CT) treatment were used to evaluate the in vivo formation of benzo[a]pyrene diol epoxide(BaPDE)-DNA adducts by an ELISA technique and by the 32P-postlabeling method. Moreover, we controlled if the pretreatment with CT influences the formation of BaP-DNA adducts and the BaP metabolism in the PBL obtained from psoriatic patients, treated in vitro with BaP. Our data did not show any significant influence of the CT treatment on the levels of PAH-DNA adducts. Moreover, the use of PBL from psoriatic patients, treated in vitro with BaP, did not allow to detect significant modifications of the metabolic activation of BaP and of the ability of its metabolites to bind to DNA, before and after CT treatment. Thus, PBL do not seem to represent an useful cell model to evaluate the possible genotoxic effect of the exposure through the skin of psoriatic patients to the PAH contained in CT.

Immunologic cell markers of peripheral blood and lymph node lymphocytes in chronic lymphocytic leukemia.

The immunologic phenotype of the lymphocytes of 100 patients with chronic lymphocytic leukaemia (CLL) was investigated. Peripheral blood lymphocytes (PBL) were examined in all cases; in 46 patients with lymphadenopathy, a lymph node was biopsied and the histologic and immunologic patterns were assessed: 24 had a lymphocytic-lymphoplasmocytoid histology and 22 the follicular variant of lymphocytic lymphoma (mantle zone lymphoma, MZL). For comparison, lymph node suspensions from 19 patients with non-leukemic centrocytic lymphoma (CCL) were also studied. Significant differences in the PBL immunologic features were found between stage O and stage I patients. The phenotype of the lymphocytes of patients with lymphocytic histology was similar to that of stage 0 CLL patients, whereas major differences were found between these patients and those with mantle zone histology. This enables these patients to be recognized easily on immunologic grounds.

Myeloid leukemias and myelodysplastic syndromes: chemical exposure, histologic subtype and cytogenetics in a case-control study.

We conducted a case control study of 50 acute myeloid leukemias (AML), 17 chronic myeloid leukemias (CML), 19 myelodysplastic syndromes (MDS), and 246 controls. The cases were classified according to the French-American-British (FAB) classification, and chromosome aberrations were recorded according to the International System for Human Cytogenetic Nomenclature. Exposure to suspected leukemogenic agents was assessed blindly by an industrial hygienist. Increased risks were noted for mechanics, welders, electricians, and drivers among men and among farmers and textile workers among women. Increased SMRs for leukemias in a census-based cohort study conducted in the same area (Torino) were previously reported for electricians and drivers among men and for textile workers among women. We detected nonstatistically significant increased relative risks for exposure to benzene (odds ratio, OR = 1.7), petrol refining products (1.9), polycyclic aromatic hydrocarbons (1.7), and electromagnetic fields (1.6) in men; in women, a statistically significant association with exposure to pesticides was detected [OR = 4.4; 95% confidence interval (CI) 1.7-11.5]. Although exposure to pesticides was confined to AML, MDS cases included a high proportion of subjects exposed to benzene and electromagnetic fields. No particular histologic subtype of AML was associated with chemical exposures except for that of pesticides with the M4 category. Chromosome aberrations were not associated with chemical exposures (OR = 1.0), but a nonstatistically significant excess was noted in association with electromagnetic fields (OR = 2.1).

The treatment of elderly patients with aggressive non-Hodgkin's lymphomas: feasibility and efficacy of an intensive multidrug regimen.

The results of a prospective trial of an 8 week treatment for elderly patients with advanced intermediate-high grade NHL are reported. Our aim was to reduce general toxicity without losing an antilymphoma effect. For this reason the use of growth factor was studied. We also analysed the behavior of different histological groups (E + F vs G + H). From November 1991 to November 1993 100 patients older than 65 years with combination intermediate-high grade advanced stage NHL were treated with the P-VEBEC regimen, an original including epirubicin 50 mg/sqm, cyclophosphamide 300 mg/sqm and etoposide 100 mg/sqm on weeks 1, 3, 5, 7; vinblastine 5 mg/sqm and bleomycin 5 mg/sqm on weeks 2, 4, 6, 8; prednisone 50 mg/sqm/day per os in the first two weeks and thereafter every other day .46 pts received rG-CSF 5 micrograms/Kg/day throughout the treatment starting on day 2 of every week for 4 consecutive days. Twenty eight pts had B symptoms, 41 had bulky disease, 37 LDH levels above normal, 50 stage IV patients and 30 had bone marrow involvement. Sixty two percent achieved a complete remission (CR). Adverse prognostic factors for CR were E and F histology, stage IV disease, bone marrow infiltration, serum LDH levels above normal, international Prognostic Index (I.I.) intermediate-high and high risk categories and relative dose intensity (RDI) less than 0.80. Severe toxicity was rarely recorded and only one toxic death was observed. With a median follow-up of 33 months OS, DFS and EFS were 44%, 60% and 30% respectively. EFS was influenced by stage, BM involvement, level of LDH and I.I. intermediate-high and high risks. The 52 patients with DLCL (diffuse large cell lymphomas--G + H according to WF) did better with a higher CR, OS, DFS and EFS rates, than the other WF subtypes. In conclusion P-VEBEC is a feasible combination to use in elderly patients, mainly in DLCL. The use of rG-CSF improves the RDI. A RDI > 0.80 could play a role in improving the outcome, especially in patients with adverse prognostic factors. For other subgroups another schedule is probably justified.