Significantly longer time to deterioration of quality of life due to CANKADO PRO-React eHealth support in HR+ HER2- metastatic breast cancer patients receiving palbociclib and endocrine therapy: primary outcome analysis of the multicenter randomized AGO-B WSG PreCycle trial.

BACKGROUND: The multicenter, randomized, phase IV, intergroup AGO-B WSG PreCycle trial (NCT03220178) evaluated the impact of CANKADO-based electronic patient-reported outcome (ePRO) assessment on quality of life (QoL) in hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer (MBC) patients receiving palbociclib and an aromatase inhibitor or palbociclib + fulvestrant. CANKADO PRO-React, a European Union-registered medical device, is an interactive autonomous application reacting to patient self-reported observations. PATIENTS AND METHODS: Between 2017 and 2021, 499 patients (median age 59 years) from 71 centers were randomized (2 : 1, stratified by therapy line) between an active version of CANKADO PRO-React (CANKADO-active arm) and a version with limited functionality (CANKADO-inform arm). A total of 412 patients (271 CANKADO-active; 141 CANKADO-inform) were available for analysis of the primary endpoint, time to deterioration (TTD) of QoL [10-point drop on the Functional Assessment of Cancer Therapy-General (FACT-G) score], using an Aalen-Johansen estimator for cumulative incidence function of TTD DQoL (QoL deterioration) with 95% pointwise confidence intervals (CIs). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and DQoL. RESULTS: In all patients [intention-to-treat (ITT)-ePRO], cumulative incidence of DQoL was significantly more favorable (lower) in the CANKADO-active arm (hazard ratio 0.698, 95% CI 0.506-0.963). Among first-line patients (n = 295), the corresponding hazard ratio was 0.716 (0.484-1.060; P = 0.09), and in second-line patients (n = 117) it was 0.661 (0.374-1.168; P = 0.2). Absolute patient numbers declined in later visits; FACT-G completion rates were 80% and higher until about visit 30. Mean FACT-G scores showed a steady decline from baseline and an offset in favor of CANKADO-active. No significant differences in clinical outcome were observed between arms: median PFS (ITT population) was 21.4 (95% CI 19.4-23.7) (CANKADO-active) and 18.7 (15.1-23.5) months (CANKADO-inform); median OS was not reached (CANKADO-active) and 42.6 months (CANKADO-inform). CONCLUSIONS: PreCycle is the first multicenter randomized eHealth trial demonstrating a significant benefit for MBC patients receiving oral tumor therapy when using an interactive autonomous patient empowerment application.

Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response.

BACKGROUND: Addition of immune checkpoint inhibitors to neoadjuvant chemotherapy (NACT) is a promising strategy in early breast cancer, but the optimal duration of therapy is currently unknown. In the GeparNuevo (NCT02685059) trial, addition of durvalumab to NACT as previously reported led to a moderate increase in pathological complete response (pCR) rate by an absolute 9% (P = 0.287). PATIENTS AND METHODS: Patients with cT1b-cT4a-d triple-negative breast cancer (TNBC) received durvalumab 1.5 g or placebo every 4 weeks added to nab-paclitaxel 125 mg/m2 weekly for 12 weeks, followed by durvalumab/placebo every 4 weeks plus epirubicin/cyclophosphamide every 2 weeks followed by surgery. Durvalumab was not continued after surgery. The primary objective was pCR. Secondary endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS). RESULTS: A total of 174 patients were randomised between June 2016 and October 2017. After a median follow-up of 43.7 months, 34 events had occurred. Despite a non-significant increase in the pCR rate, significant differences were observed for 3-year iDFS, DDFS and OS: iDFS was 85.6% with durvalumab versus 77.2% with placebo [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.24-0.97, stratified log-rank P = 0.036]; DDFS 91.7% versus 78.4% (HR 0.31, 95% CI 0.13-0.74, P = 0.005); OS 95.2% versus 83.5% (HR 0.24, 95% CI 0.08-0.72, P = 0.006). pCR patients had 3-year iDFS of 95.5% with durvalumab and 86.1% without (HR 0.22, 95% CI 0.05-1.06). In the non-pCR cohort 3-year iDFS was 76.3% versus 69.7% (HR 0.67, 95% CI 0.29-1.54). Multivariable analysis confirmed a durvalumab effect independent of the pCR effect. No new safety signals occurred. CONCLUSIONS: Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional studies are needed to clarify the optimal duration and sequence of checkpoint inhibitors in the treatment of early TNBC.

Deposition of plant lipids after single application of a lip care product determined by confocal raman spectroscopy, corneometry and transepidermal water-loss.

OBJECTIVE: Lip treatment products often incorporate oils and waxes in their formulations, and a desired outcome of their use is to prevent lip dryness and roughness as well as help to repair this condition. The objective of this study was to combine confocal Raman spectroscopy with skin capacitance (corneometry) and transepidermal water loss (closed chamber Aquaflux system) measurements, in the evaluation of the degree of moisturization and lip skin penetration of a fruit wax (Rhus vernicula peel cera) and natural oil-based (Cocos nucifera fruit oil and Olea europea oil) lip care product, following a single application. METHODS: The study was conducted on a total of 15 healthy female volunteers. Instrumental measurements were performed before and 30 min, 2 h and 6 h after a single application of the product. RESULTS: Lip skin barrier function as well as lip hydration were significantly improved and penetration of olive oil was maintained for at least 6 h post product application. The deposition of the three component lipids (berry fruit wax, coconut oil and olive oil) into the stratum corneum after a single application of the lip care product was maintained and data significant for 2-6 h post product application. Lipid deposition was regarded as a positive long-lasting skin care (depot-) effect combined with a profound hydrating effect for about 6 h. CONCLUSION: The tri-method approach taken in this study is deemed relevant and valid for measuring lip hydration offering a complimentary assessment of the barrier function of lip skin and interactive effects of cosmetic ingredients.

OBJECTIFS: Les formulations des produits de soins des lèvres contiennent souvent des huiles et des cires. En outre, la prévention, voire la réparation de la sécheresse et de la rugosité des lèvres font partie des résultats attendus de l'utilisation de ces produits. Cette étude avait pour objectif d'associer une spectroscopie confocale Raman à des mesures de la capacitance de la peau (cornéométrie) et de la perte d'eau transépidermique (système à chambre fermée Aquaflux), dans l'évaluation du niveau d'hydratation et de pénétration cutanées des lèvres d'une cire à base de fruits (cire d'écorce de Vernis du Japon) et d'un produit de soins des lèvres à base d'huiles naturelles (huile de coco et huile d'olive), après une seule application. MÉTHODES: Au total, l'étude a été menée auprès de 15 volontaires en bonne santé de sexe féminin. Des mesures instrumentales ont été réalisées avant, puis 30 minutes, 2 heures et 6 heures après une seule application du produit. RÉSULTATS: Une amélioration significative de la fonction barrière et de l'hydratation de la peau des lèvres a été observée, et la pénétration cutanée de l'huile d'olive est demeurée stable pendant au moins 6 heures après l'application du produit. Le dépôt des trois lipides entrant dans sa composition (la cire de baies, l'huile de coco et l'huile d'olive) dans la couche cornée s'est prolongé pendant 2 à 6 heures après une seule application du produit de soins des lèvres, présentant ainsi un intérêt significatif pour le recueil de données. Les résultats concernant le dépôt lipidique ont décrit un effet positif et durable dans le soin de la peau associé à une hydratation intense pendant environ 6 heures. CONCLUSION: L'approche à trois méthodes adoptée dans le cadre de cette étude pour mesurer l'hydratation des lèvres est jugée pertinente et valable, car elle offre une évaluation complémentaire de la fonction barrière de la peau des lèvres et des effets interactifs des ingrédients entrant dans la composition des cosmétiques.

Erlotinib in routine clinical practice for first-line maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC).

PURPOSE: The controlled phase III trial SATURN demonstrated that maintenance therapy with erlotinib after the first-line platinum-based chemotherapy prolonged progression-free survival (PFS) and overall survival (OS) of non-small cell lung cancer (NSCLC) patients with advanced, non-progressive disease. We conducted the non-interventional study SATURN NIS to investigate the effectiveness and tolerability of erlotinib maintenance in daily clinical practice. METHODS: This single-arm NIS screened 290 patients with locally advanced or metastatic NSCLC (stage IIIB or IV) and stable disease after standard platinum-based first-line chemotherapy in 95 institutions across Germany. Erlotinib was dosed and administered corresponding to the terms of the marketing authorization at the time of recruitment. The main effectiveness endpoint was subjects' OS at 1 year. Subgroup analyses of survival estimates of OS and PFS were performed. RESULTS: 272 patients were eligible for analysis (median age 66 years, 37.1% females, 99.6% Caucasian, median ECOG performance status 1, 61.8% adenocarcinoma, 96.3% of patients with stable disease). Maintenance therapy with erlotinib resulted in median OS comparable to that of the SATURN phase III trial 10.4 months [95% CI: (8.8; 12.5) vs. 11.9 months]. The 1-year survival rate was 45.6% [95% CI: (37.5%; 53.6%)]. No new safety signals were observed. As expected, patients with epidermal growth factor receptor (EGFR) mutations derived a greater benefit concerning OS and PFS than EGFR-wild-type patients. Moreover, a significant association of OS and PFS and the smoking status was observed. CONCLUSIONS: The results of this non-interventional study support the current clinical practice of erlotinib switch maintenance in EGFR-mutation-positive patients.

Observer-blind randomized controlled study of a cosmetic blend of safflower, olive and other plant oils in the improvement of scar and striae appearance.

OBJECTIVE: The normal process of skin tissue repair following injury invariably results in visual scarring. It is known that topical treatment with hydrophobic cosmetics rich in silicone and mineral oil content can improve the appearance of scars and striae. Given lifestyle preferences of many cosmetic consumers towards so-called natural treatments, the objective of this controlled randomized study was to investigate the efficacy of a plant body oil rich in oleic and linoleic acids (Bio Skin Oil® ) for improving the appearance of scars and striae. METHODS: A panel of 80 volunteers with non-hypertrophic scars (40) or stretch marks (40) not older than 3 years applied a cosmetic face and body oil for 8 weeks. Compared to an untreated scar/stretch mark region, a blinded investigator as well as volunteer assessments with given observed parameters demonstrated the efficacy of the oil under test. RESULTS: On the Observer Scar Assessment Scale (OSAS), the mean score was reduced on the product-treated area by approximately 5% (P = 0.006). The untreated area remained unchanged. Observed effects by volunteers were more pronounced - Patient Scar Assessment Scale (PSAS) giving a reduction of approximately 20% on the treated area, and on the control untreated area a reduction of approximately 6%. The overall product effect of 14% was shown to be clearly significant (P = 0.001). All statements relating to product traits achieved higher frequencies of agreements than of non-agreements and were therefore assessed positively by the volunteers. Highest frequencies of agreements occurred in statements that the test product provides a long-lasting, soft and supple skin feeling (93%); caring effect (87%); and quick absorbance (84%). Agreement was also found for statements that the product improves the skin appearance (61%) and that scars/striae appear less pronounced (51%). Only 17% of volunteers felt the oil had no benefit to the appearance of their scars/striae. CONCLUSIONS: The oil blend under test is effective in improving the appearance of non-keloid scars and striae. Further work is required to understand the mechanisms of how plant oil fatty acids ameliorate scar and striae appearance.

A plant oil-containing pH 4 emulsion improves epidermal barrier structure and enhances ceramide levels in aged skin.

OBJECTIVE: Xerosis is a serious problem among the very old. It is a dermatological challenge caused by significant alterations in stratum corneum (SC) function and structure. Two negative changes in aged skin are (i) the enhanced skin surface pH and (ii) the altered SC lipid content, composition and ordering. METHODS: Therefore, we investigated the way in which an acidic skin care product with different plant oils affects SC function, structure and lipid profile in older subjects with dry skin. Before and after a 3-week application period, different biophysical measurements were performed: transepidermal water loss, SC hydration and skin surface pH. In addition, the SC lipid matrix was evaluated by analysis of the intercellular lipid lamellae and the SC lipid profile. RESULTS: After treatment, a significant increase in lipid lamellae in the intercellular space of the SC was observed in the area treated with the test product compared to the untreated area. Furthermore, the ceramide level was found to be increased, although ceramides were not provided by the acidic test formulation. CONCLUSION: In summary, topical application of a pH 4.0 product containing plant oils improves epidermal barrier formation and SC lipid ordering and ratio in aged dry skin.

Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia.

We randomized 3375 adults with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome to test whether increasingly intensive chemotherapies assigned at study-entry and analyzed on an intent-to-treat basis improved outcomes. In total, 1529 subjects <60 years were randomized to receive: (1) a first course of induction therapy with high-dose cytarabine and mitoxantrone (HAM) or with standard-dose cytarabine, daunorubicin and 6-thioguanine (TAD) followed by a second course of HAM; (2) granulocyte-colony stimulating factor (G-CSF) or no G-CSF before induction and consolidation courses; and (3) high-dose therapy and an autotransplant or maintenance chemotherapy. In total, 1846 subjects ⩾60 years were randomized to receive: (1) a first induction course of HAM or TAD and second induction course of HAM (if they had bone marrow blasts ⩾5% after the first course); and (2) G-CSF or no G-CSF as above. Median follow-up was 7.4 years (range, 1 day to 14.7 years). Five-year event-free survivals (EFSs) for subjects receiving a first induction course of HAM vs TAD were 17% (95% confidence interval, 15, 18%) vs 16% (95% confidence interval 14, 18%; P=0.719). Five-year EFSs for subjects randomized to receive or not receive G-CSF were 19% (95% confidence interval 16, 21%) vs 16% (95% confidence interval 14, 19%; P=0.266). Five-year relapse-free survivals (RFSs) for subjects <60 years receiving an autotransplant vs maintenance therapy were 43% (95% confidence interval 40, 47%) vs 40 (95% confidence interval 35, 44%; P=0.535). Many subjects never achieved pre-specified landmarks and consequently did not receive their assigned therapies. These data indicate the limited impact of more intensive therapies on outcomes of adults with AML. Moreover, none of the more intensive therapies we tested improved 5-year EFS, RFS or any other outcomes.

Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment.

Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.

Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG.

Chemomodulation of cytarabine by fludarabine has been attributed with a higher antileukemic efficacy, but randomized trials to address this question are rare. We therefore conducted a multicenter, randomized phase III study to evaluate the antileukemic efficacy of adding fludarabine to sequential high-dose cytarabine+idarubicin (SHAI) re-induction chemotherapy in relapsed or refractory acute myeloid leukemia (AML). Patients (n=326, of which 281 were evaluable) were randomly assigned to SHAI (cytarabine, 1 g/m(2) bid, days 1-2 and 8-9 (3 g/m(2) for patients ≤ 60 years with refractory AML or ≥ 2nd relapse); idarubicin 10 mg/m(2) daily, days 3-4 and 10-11) or F-SHAI (SHAI with fludarabine, 15 mg/m(2), 4 h before cytarabine). Although complete remission (CR) rates (35% SHAI and 44% F-SHAI) and overall survival did not differ between both regimens, fludarabine prolonged time to treatment failure from 2.04 to 3.38 months (median, P<0.05). Twenty-seven percent of patients proceeded to allogeneic stem cell transplantation, with a significantly higher number of patients in CR or incomplete remission in the F-SHAI group (22 vs 10%, P<0.01). In conclusion, fludarabine has a beneficial, although moderate, impact on the antileukemic efficacy of high-dose cytarabine-based salvage therapy for relapsed and refractory AML.

ASXL1 exon 12 mutations are frequent in AML with intermediate risk karyotype and are independently associated with an adverse outcome.

We aimed at evaluating ASXL1mut in 740 AML with intermediate risk karyotype for frequency, association with other mutations and impact on outcome. Five hundred fifty-three cases had a normal karyotype (NK) and 187 had intermediate risk aberrant cytogenetics. Overall, ASXL1mut were detected in 127/740 patients (17.2%). ASXL1mut were more frequent in males than in females (23.5% vs 9.9%, P<0.001). They were associated with higher age (median: 71.8 vs 61.8, P<0.001), a history of preceding myelodysplastic syndromes, and with a more immature immunophenotype compared with patients with wild-type ASXL1 (ASXL1wt). ASXL1mut were more frequent in patients with aberrant karyotype (58/187; 31.0%), especially in cases with trisomy 8 (39/74; 52.7%), than in those with NK (69/553; 12.5%; P<0.001). ASXL1mut were observed more frequent in RUNX1mut (P<0.001), and less frequent in NPM1mut (P<0.001), FLT3-internal tandem duplication (ITD) (P<0.001), FLT3-TKD (P=0.001) and DNMT3Amut (P<0.001). Patients with ASXL1mut had a shorter overall survival (OS) (P<0.001) and event free survival (P=0.012) compared with ASXL1wt. In multivariable analysis, ASXL1mut was an independent adverse factor for OS (P=0.032, relative risk: 1.70). In conclusion, ASXL1mut belong to the most frequent mutations in intermediate risk group AML. Their strong and independent dismal prognostic impact suggests the inclusion into the diagnostic work-up of AML.

Differentiation of Candida dubliniensis from Candida albicans by means of MALDI-TOF mass spectrometry.

BACKGROUND: Species specific differentiation of the two closely related yeasts, Candida albicans and C. dubliniensis, is difficult in routine diagnosis. METHODS AND RESULTS: Here we show that MALDI-TOF MS is a practical and useful tool for the discrimination of C. albicans and C. dubliniensis, demonstrated by the analysis of reference strains from type culture collections and other well characterized isolates. The spectra of C. albicans and C. dubliniensis further revealed that each species consists of several clades. CONCLUSIONS: Reliable, routinely applicable methods for species specific differentiation of C. albicans and C. dubliniensis appear to be of particular importance to better understand the epidemiology and virulence of C. dubliniensis.

[Percutaneous coronary intervention in a patient with acute myeloid leukemia]. / Koronarintervention bei einer Patientin mit akuter myeloischer Leukämie.

HISTORY AND ADMISSION FINDINGS: A 63-year-old woman was referred to our hospital for evaluation of leukocytopenia and blast cells in the peripheral blood smear. The general condition was reduced, a maculo-papulous exanthema of the face and upper body as well as a general lymphadenopathy were found. INVESTIGATIONS: Bone marrow examination revealed the diagnosis of acute myeloid leukemia (AML) FAB M1 and a normal karyotype. Extramedullary manifestations of AML were demonstrated in skin and lymphnode biopsies. ECG showed no signs of ischemia, echocardiography a normal left-ventricular function. TREATMENT AND COURSE: The patient received induction treatment using sequential high-dose cytosinarabinosid and mitoxantrone, which rapidly resolved the extramedullary skin- and lymphnode-manifestations of the AML. During the chemotherapy-associated bone marrow aplasia a non-ST-elevation infarction (NSTEMI) developed combined with severe ischemic cardiomyopathy, high-grade mitral valve deficiency and serious congestive heart failure with respiratory failure. Coronary artery angiography showed a complete occlusion of the proximal ramus circumflexus. Percutanous coronary intervention (PCI) with implantation of a bare-metal stent was performed, which resulted in prompt improvement of the condition. Despite the transfusion-dependent thrombocytopenia a dual antiplatelet therapy with acetylsalicylic acid and clopidogrel was given. After each unit of platelets transfused a loading dose of 600 mg clopidogrel was given to prevent stent thrombosis. The patient did not experience major bleeding and was discharged in complete remission of AML and completely cardially recompensated. CONCLUSION: Coronary angiography and stenting can generally be safely performed in patients with transfusion-dependent thrombocytopenia. Despite a higher risk of bleeding an oral dual antiplatelet therapy with aspirin and e. g. clopidogrel according to the guidelines should be performed, but its duration should be adapted to the individual patient circumstances.

Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial.

BACKGROUND: On the basis of promising results that were reported in several phase 2 trials, we investigated whether the addition of the monoclonal antibody rituximab to first-line chemotherapy with fludarabine and cyclophosphamide would improve the outcome of patients with chronic lymphocytic leukaemia. METHODS: Treatment-naive, physically fit patients (aged 30-81 years) with CD20-positive chronic lymphocytic leukaemia were randomly assigned in a one-to-one ratio to receive six courses of intravenous fludarabine (25 mg/m(2) per day) and cyclophosphamide (250 mg/m(2) per day) for the first 3 days of each 28-day treatment course with or without rituximab (375 mg/m(2) on day 0 of first course, and 500 mg/m(2) on day 1 of second to sixth courses) in 190 centres in 11 countries. Investigators and patients were not masked to the computer-generated treatment assignment. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00281918. FINDINGS: 408 patients were assigned to fludarabine, cyclophosphamide, and rituximab (chemoimmunotherapy group) and 409 to fludarabine and cyclophosphamide (chemotherapy group); all patients were analysed. At 3 years after randomisation, 65% of patients in the chemoimmunotherapy group were free of progression compared with 45% in the chemotherapy group (hazard ratio 0·56 [95% CI 0·46-0·69], p<0·0001); 87% were alive versus 83%, respectively (0·67 [0·48-0·92]; p=0·01). Chemoimmunotherapy was more frequently associated with grade 3 and 4 neutropenia (136 [34%] of 404 vs 83 [21%] of 396; p<0·0001) and leucocytopenia (97 [24%] vs 48 [12%]; p<0·0001). Other side-effects, including severe infections, were not increased. There were eight (2%) treatment-related deaths in the chemoimmunotherapy group compared with ten (3%) in the chemotherapy group. INTERPRETATION: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab improves progression-free survival and overall survival in patients with chronic lymphocytic leukaemia. Moreover, the results suggest that the choice of a specific first-line treatment changes the natural course of chronic lymphocytic leukaemia. FUNDING: F Hoffmann-La Roche.

High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG.

The objective of this study for newly diagnosed acute promyelocytic leukemia (APL) was to evaluate the efficacy of an intensified double induction chemotherapy including high dose ara-C (HD) and all-trans retinoic acid (ATRA) followed by consolidation and 3 years maintenance therapy. In contrast to APL studies stratifying therapy according to pretreatment white blood cell (WBC) count < and > or =10 x 10(9)/l (low/intermediate and high risk according to the Sanz score), our patients received uniform therapy. From 1994 to 2005, 142 patients (age, 16-60 years) were enrolled. In the low/intermediate (n=105) vs high (n=37) WBC group, the rates of complete remission were 95.2 vs 83.8%, of induction death were 4.8 vs 16.2% (P=0.05) and of molecular remission were 87.5 vs 91.3% (P=1). Long-term overall survival was 84.4 vs 73.0% (P=0.12), event free survival was 78.3 vs 67.3% (P=0.11), relapse free survival was 82.1 vs 80.0% (P=0.83) and the cumulative incidence of relapse was 7.4 vs 11.4% (P=0.46). No relapse or death occurred after 4.7 years. ATRA and intensified chemotherapy including HD ara-C followed by prolonged maintenance therapy reduced the relapse risk in high risk patients. Pretreatment WBC count > or =10 x 10(9)/l count was no relevant prognostic factor for relapse.

Modification of surface antigens in blood CD8+ T-lymphocytes in COPD: effects of smoking.

In contrast to the effects of cigarette smoke on T-lymphocyte subsets in the airways, it has not yet been determined whether smoking has immunomodulatory effects on surface antigens of peripheral blood T-lymphocytes and, if that is the case, whether these effects differ in smokers with and without chronic obstructive pulmonary disease (COPD). The present authors have, therefore, examined the expression of the surface activation marker CD28, the levels of cytotoxic effector lymphocytes (CD27-/CD45RA+) and the expression of the lung type (Tc)1-specific chemokine receptor CXCR(3)+ on peripheral blood CD8+ T-lymphocytes. The present authors have also studied the chemotactic activity of CD8+ T-lymphocytes on monocyte chemotactic protein (MCP)-1 and compared 13 nonsmoking controls, 12 smokers with COPD and 14 smokers without airflow limitation. There was a decrease in the total count of CD8+ T-cells and an increase in the CD4+/CD8+ ratio in smokers with COPD compared with smokers without COPD and controls. Expression of the Tc1-specific chemokine receptor CXCR(3)+ by CD8+ T-cells was increased in smokers with COPD compared with smokers without COPD and controls. The expression of activated and of cytotoxic effector CD8+ T-cells in smokers with and without COPD showed an increase compared with controls. CD8+ T-cells from smokers with and without COPD showed a decrease in chemotactic activity to MCP-1 compared with controls. In conclusion, chronic obstructive pulmonary disease may be a systemic immunomodulatory disease associated with the modification of surface antigens in blood CD8+ T-lymphocytes.