Andreas Rank

Intensified Chemotherapy and Dose-Reduced Involved-Field Radiotherapy in Patients With Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD11 Trial

PURPOSEnCombined-modality treatment consisting of four to six cycles of chemotherapy followed by involved-field radiotherapy (IFRT) is the standard of care for patients with early unfavorable Hodgkins lymphoma (HL). It is unclear whether treatment results can be improved with more intensive chemotherapy and which radiation dose needs to be applied.nnnPATIENTS AND METHODSnPatients age 16 to 75 years with newly diagnosed early unfavorable HL were randomly assigned in a 2 × 2 factorial design to one of the following treatment arms: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) + 30 Gy of IFRT; four cycles of ABVD + 20 Gy of IFRT; four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP(baseline)) + 30 Gy of IFRT; or four cycles of BEACOPP(baseline) + 20 Gy of IFRT.nnnRESULTSnWith a total of 1,395 patients included, the freedom from treatment failure (FFTF) at 5 years was 85.0%, overall survival was 94.5%, and progression-free survival was 86.0%. BEACOPP(baseline) was more effective than ABVD when followed by 20 Gy of IFRT (5-year FFTF difference, 5.7%; 95% CI, 0.1% to 11.3%). However, there was no difference between BEACOPP(baseline) and ABVD when followed by 30 Gy of IFRT (5-year FFTF difference, 1.6%; 95% CI, -3.6% to 6.9%). Similar results were observed for the radiotherapy question; after four cycles of BEACOPP(baseline), 20 Gy was not inferior to 30 Gy (5-year FFTF difference, -0.8%; 95% CI, -5.8% to 4.2%), whereas inferiority of 20 Gy cannot be excluded after four cycles of ABVD (5-year FFTF difference, -4.7%; 95% CI, -10.3% to 0.8%). Treatment-related toxicity occurred more often in the arms with more intensive therapy.nnnCONCLUSIONnModerate dose escalation using BEACOPP(baseline) did not significantly improve outcome in early unfavorable HL. Four cycles of ABVD should be followed by 30 Gy of IFRT.

Epoetin Alfa in Patients With Advanced-Stage Hodgkin's Lymphoma: Results of the Randomized Placebo-Controlled GHSG HD15EPO Trial

PURPOSEnTo determine whether epoetin alfa reduces anemia-related fatigue, improves other aspects of health-related patient-recorded outcomes (PROs), reduces the number of RBC transfusions, and has an impact on freedom from treatment failure (FFTF) and overall survival (OS) in patients with advanced-stage Hodgkins lymphoma (HL).nnnPATIENTS AND METHODSnThe prospectively randomized HD15EPO study performed by the German Hodgkin Study Group investigated epoetin alfa administered at doses of 40,000 U weekly during and after chemotherapy (six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPP]) in a double-blind, placebo-controlled setting. The study accrued 1,379 patients, of whom 1,328 were assessable for safety, 1,303 were assessable for clinical outcome, and 930 were assessable for PROs.nnnRESULTSnPROs were not different in patients receiving placebo or epoetin alfa, both after the end of chemotherapy and 6 months thereafter. There was no difference between patients treated with epoetin alfa or placebo with respect to FFTF and OS. There were also no differences in the numbers of deaths, progressions, relapses, and thromboembolic events. The median number of RBC transfusions was reduced from four per patient in the placebo group to two per patient in the epoetin alfa group (P < .001), with 27.4% of patients needing no RBC transfusion in the placebo group compared with 36.7% of patients in the epoetin alfa group (P < .001).nnnCONCLUSIONnEpoetin alfa administered at 40,000 U weekly parallel to BEACOPP chemotherapy was safe in patients with advanced-stage HL and reduced the number of RBC transfusions but had no impact on fatigue and other PRO domains.

Prevention, management and extent of adverse pregnancy outcomes in women with hereditary antithrombin deficiency.

Antithrombin (AT) deficiency is a rare hereditary thrombophilia with a mean prevalence of 0.02xa0% in the general population, associated with a more than ten-fold increased risk of venous thromboembolism (VTE). Within this multicenter retrospective clinical analysis, female patients with inherited AT deficiency were evaluated concerning the type of inheritance and extent of AT deficiency, medical treatment during pregnancy and postpartally, VTE risk as well as maternal and neonatal outcome. Statistical analysis was performed with SPPS for Windows (19.0). A total of 18 pregnancies in 7 patients were evaluated, including 11 healthy newborns ≥37th gestational weeks (gw), one small for gestational age premature infant (25th gw), two late-pregnancy losses (21st and 28th gw) and four early miscarriages. Despite low molecular weight heparin (LMWH) administration, three VTE occurred during pregnancy and one postpartally. Several adverse pregnancy outcomes occurred including fetal and neonatal death, as well as severe maternal neurologic disorders occurred. Patients with substitution of AT during pregnancy in addition to LMWH showed the best maternal and neonatal outcome. Close monitoring with appropriate anticoagulant treatment including surveillance of AT levels might help to optimize maternal and fetal outcome in patients with hereditary AT deficiency.

Hormone replacement therapy leads to increased plasma levels of platelet derived microparticles in postmenopausal women

BackgroundWhereas prevention of cardiovascular diseases by hormonal replacement therapy is still part of an ongoing debate, well-defined data are available relating hormonal replacement therapy to an elevated risk of venous thrombosis and embolism. Although it seems that venous thrombosis in patients treated with hormonal replacement therapy is linked to changes in plasmatic coagulation, less is known about the role of platelet-derived microparticles, as well as endothelial cell-derived microparticles.Patients and methodsIn this prospective case–control study, levels of microparticles were investigated in postmenopausal women receiving hormone replacement therapy (nxa0=xa015) and compared to age-matched controls (nxa0=xa015).ResultsTotal count of microparticles and the subgroup of microparticles derived from endothelial cells did not differ in the investigated groups. In contrast, median levels of microparticles derived from platelet/megacaryocyte were higher in women taking hormonal replacement therapy (5,244xa0×xa0106/l) than in controls (2,803xa0×xa0106/l; pxa0=xa00.040). Furthermore, hormonal replacement therapy led to a higher plasma level of microparticles derived from activated platelets, exposing P-selectin (136xa0×xa0106/l vs. 58xa0×xa0106/l; pxa0=xa00.011), or exposing CD63 (171xa0×xa0106 vs. 91xa0×xa0106/l; pxa0=xa00.011) compared to the control group.ConclusionHigher concentrations of microparticles derived from (activated) platelets/megacaryocytes were present in postmenopausal women taking hormonal replacement therapy. This finding indicates a procoagulant state in these women and might play a role in the development of venous side effects. In contrast, levels of endothelial cell-derived microparticles did not differ.

Climacteric Lowers Plasma Levels of Platelet-Derived Microparticles: A Pilot Study in Pre- versus Postmenopausal Women

Background: Climacteric increases the risk of thrombotic events by alteration of plasmatic coagulation. Up to now, less is known about changes in platelet- (PMP) and endothelial cell-derived microparticles (EMP). Methods: In this prospective study, plasma levels of microparticles (MP) were compared in 21 premenopausal and 19 postmenopausal women. Results: No altered numbers of total MP or EMP were measured within the study groups. However, the plasma values of CD61-exposing MP from platelets/megakaryocytes were higher in premenopausal women (5,364 × 106/l, range 4,384–17,167) as compared to postmenopausal women (3,808 × 106/l, range 2,009–8,850; p = 0.020). This differentiation was also significant for the subgroup of premenopausal women without hormonal contraceptives (5,364 × 106/l, range 4,223–15,916; p = 0.047; n = 15). Furthermore, in premenopausal women, higher plasma levels of PMP exposing CD62P were also present as compared to postmenopausal women (288 × 106/l, range 139–462, vs. 121 × 106/l, range 74–284; p = 0.024). This difference was also true for CD63+ PMP levels (281 × 106/l, range 182–551, vs. 137 × 106/l, range 64–432; p = 0.015). Conclusion: Climacteric lowers the level of PMP but has no impact on the number of EMP in women. These data suggest that PMP and EMP do not play a significant role in enhancing the risk of thrombotic events in healthy, postmenopausal women.

Incidence, outcome and risk stratification tools for venous thromboembolism in advanced pancreatic cancer – A retrospective cohort study

INTRODUCTIONnVenous thromboembolism (VTE) is frequent in advanced pancreatic cancer (APC). Recent studies demonstrated that the Khorana score - an established risk stratification tool for VTE in cancer - performs poorly in identifying pancreatic cancer patients at high risk for VTE.nnnMATERIALS AND METHODSnWe performed a retrospective cohort study in order to define incidence, treatment and outcome of VTE as well as the performance of VTE risk stratification tools (Khorana score, CONKO score and aPTT ratio) in a real life clinical cohort of APC patients undergoing palliative chemotherapy.nnnRESULTS AND CONCLUSIONSnOne hundred and seventy-two eligible APC patients from our comprehensive cancer center were identified. VTE after start of palliative chemotherapy was diagnosed in 71 patients (41.3%). Most VTE events were asymptomatic (n=50, 29.1%) with only 21 symptomatic events (12.2%). On multivariate analysis - including age, performance status and carbohydrate antigen 19-9 (CA 19-9) - symptomatic VTE was an independent risk factor for death (hazard ratio [HR]: 2.22, 95% CI: 1.05-2.60, p<0.05). Khorana score, CONKO score and aPTT ratio alone were not able to predict the risk for symptomatic VTE. High risk patients could only be identified by using a combination of either Khorana or CONKO score with aPTT ratio (30% vs. 10% symptomatic VTE events in high vs. low risk patients, p<0.05). The combination of Khorana or CONKO score with aPTT thus may represent a novel risk stratification tool for symptomatic VTE in APC and should further be validated within prospective clinical trials.

Brain abscess caused by Ureaplasma urealyticum in an adult patient.

ABSTRACT Ureaplasma urealyticum is a fastidious bacterium usually residing in the female genitourinary tract. We present an exceedingly complicated case of a brain abscess secondary to mastoiditis by U. urealyticum in an adult hypogammaglobulinemic patient after rituximab treatment 3 years earlier.