Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO).

Sepsis and septic shock are major causes of mortality during chemotherapy-induced neutropenia for malignancies requiring urgent treatment. Thus, awareness of the presenting characteristics and prompt management is most important. Improved management of sepsis during neutropenia may reduce the mortality of cancer therapies. However, optimal management may differ between neutropenic and non-neutropenic patients. The aim of the current guideline is to give evidence-based recommendations for hematologists, oncologists, and intensive care physicians on how to manage adult patients with neutropenia and sepsis.

Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors-Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO).

Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria.

Diagnosis and management of gastrointestinal complications in adult cancer patients: 2017 updated evidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

Cancer patients frequently suffer from gastrointestinal complications. In this manuscript, we update our 2013 guideline on the diagnosis and management of gastrointestinal complications in adult cancer patients by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). An expert group was put together by the AGIHO to update the existing guideline. For each sub-topic, a literature search was performed in PubMed, Medline, and Cochrane databases, and strengths of recommendation and the quality of the published evidence for major therapeutic strategies were categorized using the 2015 European Society for Clinical Microbiology and Infectious Diseases (ESCMID) criteria. Final recommendations were approved by the AGIHO plenary conference. Recommendations were made with respect to non-infectious and infectious gastrointestinal complications. Strengths of recommendation and levels of evidence are presented. A multidisciplinary approach to the diagnosis and management of gastrointestinal complications in cancer patients is mandatory. Evidence-based recommendations are provided in this updated guideline.

[Neuroendocrine prostate cancer]. / Neuroendokrines Prostatakarzinom.

Neuroendocrine prostate cancer (NEPC) mostly occurs as a treatment-emergent adaptive response under the pressure of intensive androgen deprivation treatment (t-NEPC). Approximately 30-40% of patients with metastatic castration-resistant prostate cancer (mCRPC) also have neuroendocrine involvement. In contrast primary small cell prostate cancer is very rare (<1%). A t­NEPC should be clinically suspected in patients who have particularly aggressive mCRPC but a disproportionately low prostate-specific antigen (PSA) level and elevated neuroendocrine tumor markers, such as chromogranin A and neuron-specific enolase. The initial Gleason score was shown to be an independent factor correlated to the risk of development of t­NEPC. Treatment is oriented to that of small cell lung cancer. In patients with negative PSA levels, chemotherapy with cisplatin and etoposide is the first line treatment, for which response rates in the range of 30-60% with a median survival time of usually less than 1 year can be achieved. In patients with much higher serum PSA levels, chemotherapy with carboplatin plus docetaxel should be considered.

A randomized trial on chlorhexidine dressings for the prevention of catheter-related bloodstream infections in neutropenic patients.

BACKGROUND: Central venous catheter (CVC)-related bloodstream infections (CRBSI) are a frequent cause of morbidity and mortality in patients with chemotherapy-induced neutropenia. Chlorhexidine containing catheter securement dressings may prevent CRBSI. PATIENTS AND METHODS: A multicenter randomized, controlled trial was conducted at 10 German hematology departments. We compared chlorhexidine-containing dressings with non-chlorhexidine control dressings in neutropenic patients. The primary end point was the incidence of definite CRBSI within the first 14 days (dCRBSI14) of CVC placement. Secondary end points included combined incidence of definite or probable CRBSI within 14 days (dpCRBSI14), overall (dpCRBSI), incidence of unscheduled dressing changes and adverse events. RESULTS: From February 2012 to September 2014, 613 assessable patients were included in the study. The incidence of dCRBSI14 was 2.6% (8/307) in the chlorhexidine and 3.9% (12/306) in the control group (P = 0.375). Both dpCRBSI14 and dpCRBSI were significantly less frequent in the study group with dpCRBSI14 in 6.5% (20/307) of the chlorhexidine group when compared with 11% (34/306) in the control group (P = 0.047), and dpCRBSI in 10.4% (32/307) versus 17% (52/306), respectively (P = 0.019). The frequency of dressing intolerance with cutaneous and soft tissue abnormalities at the contact area was similar in both groups (12.4% and 11.8%; P = 0.901). CONCLUSIONS: Although the trial failed its primary end point, the application of chlorhexidine containing catheter securement dressings reduces the incidence of definite or probable CRBSI in neutropenic patients. CLINICAL TRIALS NUMBER: NCT01544686 (Clinicaltrials.gov).

Hodgkin lymphoma is as common as non-Hodgkin lymphoma in HIV-positive patients with sustained viral suppression and limited immune deficiency: a prospective cohort study.

OBJECTIVES: The incidence of HIV-related non-Hodgkin lymphoma (NHL) but not that of Hodgkin lymphoma (HL) has been declining. The aim of the study was to compare HIV-infected patients with NHL and HL with respect to antiretroviral therapy (ART) exposure at the time of lymphoma diagnosis. METHODS: HIV-infected patients with NHL and HL included in a prospective multicentre cohort study since January 2005 were compared with respect to ART exposure and viral load at the time of lymphoma diagnosis. RESULTS: As of 31 December 2012, data for 329 patients with NHL and 86 patients with HL from 31 participating centres were available. Patients with HL were more likely to be on ART (73.5% vs. 39.1%, respectively; P < 0.001) and more frequently had a viral load below the detection limit (57.3% vs. 27.9%, respectively; P < 0.001) than patients with NHL. The proportion of patients with HL was 8.0% in ART-naïve patients, 34.8% in patients with current HIV RNA < 50 HIV-1 RNA copies/mL, and 50.0% in patients with both HIV RNA < 50 copies/mL for > 12 months and a CD4 cell count of > 200 cells/µL. Of note, 45.8% of all patients with NHL were not currently on ART and had a CD4 count of < 350 cells/µL. CONCLUSIONS: This prospective cohort study shows that HL was as common as NHL in patients with sustained viral suppression and limited immune deficiency. In contrast to NHL, the majority of patients with HL were on effective ART, suggesting that ART provides insufficient protection from developing HL. The high proportion of untreated patients with NHL suggests missed opportunities for earlier initiation of ART.

Central venous catheter-related infections in hematology and oncology: 2012 updated guidelines on diagnosis, management and prevention by the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology.

BACKGROUND: Cancer patients are at increased risk for central venous catheter-related infections (CRIs). Thus, a comprehensive, practical and evidence-based guideline on CRI in patients with malignancies is warranted. PATIENTS AND METHODS: A panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) has developed a guideline on CRI in cancer patients. Literature searches of the PubMed, Medline and Cochrane databases were carried out and consensus discussions were held. RESULTS: Recommendations on diagnosis, management and prevention of CRI in cancer patients are made, and the strength of the recommendation and the level of evidence are presented. CONCLUSION: This guideline is an evidence-based approach to the diagnosis, management and prevention of CRI in cancer patients.

Efficacy and safety of high-dose chemotherapy as the first or subsequent salvage treatment line in patients with relapsed or refractory germ cell cancer: an international multicentric analysis.

BACKGROUND: In relapsed or refractory (RR) metastatic germ cell cancer (GCC), high-dose (HD) chemotherapy (CTX) plus autologous stem cell transplantation is considered the standard of care. Limited data exist regarding the efficacy of HD-CTX following conventionally dosed salvage regimens (CDRs). This analysis explores and contrasts the efficacy of HD-CTX as the first or subsequent salvage regimen. PATIENTS AND METHODS: Data were retrospectively collected to explore the efficacy of HD-CTX administered as the first (group A) or subsequent salvage CTX (group B) after a CDR. The primary endpoint was OS from the time of HD-CTX. Associations of survival, overall response rate (ORR), and toxicity with clinical characteristics were explored using stratified Kaplan-Meier and Cox regression models. RESULTS: Overall, 283 patients with GCC were included from 11 international centers, with 159 patients (56%) in group A and 124 patients (44%) in group B. The first salvage treatment was administered between 1998 and 2022, with a median follow-up of 27.0 [standard deviation (SD) 46.2] months for group A and 17.0 (SD 48.5) months for group B. The median OS from HD-CTX treatment initiation was not reached in group A, compared with 25 months in group B (P = 0.00027), associated with 2- and 5-year OS rates of 74% and 63% (group A) versus 53% and 37% (group B), respectively. When administered as the first salvage treatment, HD-CTX was associated with a higher ORR (79% versus 60%; P = 0.013) and lower nonhematologic grade ≥3 toxicity rate (78% versus 97%; P < 0.001). Concerning risk factor analysis for the total cohort, the International Prognostic Factors Study Group score was the only independent predictor of OS in multivariable analysis (P = 0.006). CONCLUSIONS: When administered as the initial salvage treatment or after CDR, HD-CTX exhibits curative potential for patients with RR GCC. The efficacy and safety outcomes were more favorable when HD-CTX was conducted as the first salvage treatment line.

Diagnosis and management of gastrointestinal complications in adult cancer patients: evidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

BACKGROUND: Cancer patients frequently suffer from gastrointestinal complications. However, a comprehensive, practical and evidence-based guideline on this issue is not yet available. PATIENTS AND METHODS: An expert group was put together by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) to develop a guideline on gastrointestinal complications in cancer patients. For each subtopic, a literature search was carried out in PubMed, Medline and Cochrane databases and the strength of recommendation and the quality of the published evidence for major therapeutic strategies were categorized using a modification of the 'Infectious Diseases Society of America' criteria. Consensus discussions were held on each of the topics. RESULTS: Recommendations were made with respect to non-infectious and infectious gastrointestinal complications. For all recommendations, the strength of the recommendation and the level of evidence are presented. CONCLUSION: This guideline is an evidence-based approach to the diagnosis and management of gastrointestinal complications in cancer patients.

Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer.

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.

Existential behavioural therapy for informal caregivers of palliative patients: a randomised controlled trial.

BACKGROUND: Existential behavioural therapy (EBT) was developed to support informal caregivers of palliative patients in the last stage of life and during bereavement as a manualised group psychotherapy comprising six sessions. We tested the effectiveness of EBT on mental stress and quality of life (QOL). METHODS: Informal caregivers were randomly assigned (1:1) to EBT or a treatment-as-usual control group using computer-generated numbers in blocks of 10. Primary outcomes were assessed with the Brief Symptom Inventory (subscales somatisation, anxiety and depression), the Satisfaction with Life Scale (SWLS), the WHOQOL-BREF and a numeric rating scale for QOL (QOL-NRS, range 0-10). Data were collected at baseline, pre-treatment, post-treatment and follow-ups after 3 and 12 months. Treatment effects were assessed with a multivariate analysis of covariance. RESULTS: Out of 160 relatives, 81 were assigned to EBT and 79 to the control group. Participants were 54.5 ± 13.2 years old; 69.9% were female. The multivariate model was significant for the pre-/post-comparison (p=0.005) and the pre-/12-month comparison (p=0.05) but not for the pre-/3-month comparison. Medium to large effects on anxiety and QOL (SWLS, WHOQOL-BREF, QOL-NRS) were found at post-treatment; medium effects on depression and QOL (QOL-NRS) emerged in the 12-month follow-up. No adverse effects of the intervention were observed. CONCLUSION: Existential behavioural therapy appears to exert beneficial effects on distress and QOL of informal caregivers of palliative patients. Further longitudinal evidence is needed to confirm these findings.

Management of sepsis in neutropenic patients: guidelines from the infectious diseases working party of the German Society of Hematology and Oncology.

Sepsis is a leading cause of mortality in neutropenic cancer patients. Early initiation of effective causative therapy as well as intensive adjunctive therapy is mandatory to improve outcome. We give recommendations for the management of adults with neutropenia and sepsis. The guidelines are written for clinicians involved in care of cancer patients and focus on pathophysiology, diagnosis and treatment of sepsis during neutropenia.

High antileukemic efficacy of an intermediate intensity conditioning regimen for allogeneic stem cell transplantation in patients with high-risk acute myeloid leukemia in first complete remission.

The goal of this analysis was to define the role of the moderate-intensity fludarabin Ara-C amsacrin (FLAMSA)-reduced intensity conditioning (RIC) regimen for patients with high-risk AML undergoing allogeneic SCT (alloSCT) in first CR1. High-risk was defined by (1) AML secondary to MDS or radio/chemotherapy, (2) unfavorable cytogenetics or (3) delayed response to induction chemotherapy. A total of 23 of 44 AML patients referred to the University of Munich for alloSCT in CR1 between 1999 and 2006 fulfilled these criteria and received FLAMSA chemotherapy, followed by RIC (4 Gy TBI/cyclophosphamide/ATG) for alloSCT. Twenty-two patients engrafted, one died in aplasia. Two-year cumulative incidences for relapse and nonrelapse mortality (NRM) were 4.6 and 22.5%, respectively. Four-year overall and leukemia-free survival was 72.7% (median follow-up among survivors: 35 months). The results of this high-risk cohort were compared to the outcome of 21 consecutive standard-risk patients <55 years, who had received standard, myeloablative sibling SCT in CR1 AML within the same center and time period. Survival and cumulative incidences of relapse and NRM were identical in both groups. In conclusion, the FLAMSA-RIC regimen produces long-term remission in a high proportion of patients with high-risk AML transplanted in CR1. In this cohort, FLAMSA-RIC showed equivalent antileukemic activity as compared to the standard protocols.

Split-dose docetaxel, cisplatin and leucovorin/fluorouracil as first-line therapy in advanced gastric cancer and adenocarcinoma of the gastroesophageal junction: results of a phase II trial.

BACKGROUND: Phase II and III trials of docetaxel, cisplatin and fluorouracil (DCF) have shown superior efficacy versus cisplatin and fluorouracil alone but high rates of hematologic toxicity in advanced gastric cancer. To reduce toxicity while maintaining the efficacy of DCF, we investigated split doses of docetaxel (T), cisplatin (P), leucovorin (L) and fluorouracil (F). PATIENTS AND METHODS: Chemotherapy-naive patients with advanced gastric-/esophageal adenocarcinomas received T 50 mg/m(2) and P 50 mg/m(2) on days 1, 15 and 29 and L 500 mg/m(2) plus F 2000 mg/m(2) weekly, every 8 weeks. Because significant dose reductions to <80% became necessary in 80% of patients, the regimen was amended after the first 15 patients to T 40 mg/m(2), P 40 mg/m(2), L 200 mg/m(2) and F 2000 mg/m(2). The primary endpoint was response rate. RESULTS: Sixty patients were enrolled: 24 had locally advanced (LA) tumors and 36 had metastatic disease. Grade 3/4 toxicities included neutropenia (22%), febrile neutropenia (5%), diarrhea (20%) and lethargy (18%). The overall response rate was 47%. Twenty-three LA patients underwent secondary surgical resection (96%); complete resection was achieved in 87%. Overall, median time to progression and overall survival were 9.4 and 17.9 months, respectively (8.1 and 15.1 months, respectively, for patients with metastatic disease). CONCLUSION: T-PLF regimen is highly active and has a favorable toxicity profile.

[Neuroendocrine prostate cancer]. / Neuroendokrines Prostatakarzinom.

Neuroendocrine prostate cancer (NEPC) mostly occurs as a treatment-emergent adaptive response under the pressure of intensive androgen deprivation treatment (t-NEPC). Approximately 30-40% of patients with metastatic castration-resistant prostate cancer (mCRPC) also have neuroendocrine involvement. In contrast primary small cell prostate cancer is very rare (<1%). A t­NEPC should be clinically suspected in patients who have particularly aggressive mCRPC but a disproportionately low prostate-specific antigen (PSA) level and elevated neuroendocrine tumor markers, such as chromogranin A and neuron-specific enolase. The initial Gleason score was shown to be an independent factor correlated to the risk of development of t­NEPC. Treatment is oriented to that of small cell lung cancer. In patients with negative PSA levels, chemotherapy with cisplatin and etoposide is the first line treatment, for which response rates in the range of 30-60% with a median survival time of usually less than 1 year can be achieved. In patients with much higher serum PSA levels, chemotherapy with carboplatin plus docetaxel should be considered.

Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and long-term course.

In order to evaluate the efficacy, time-course of action and predictors of response to topical capsaicin, 39 patients with chronic post-herpetic neuralgia (PHN), median duration 24 months, were treated with 0.025% capsaicin cream for 8 weeks. During therapy the patients rated their pain on a visual analogue scale (VAS) and a verbal outcome scale. A follow-up investigation was performed 10-12 months after study onset on the patients who had improved. Nineteen patients (48.7%) substantially improved after the 8-week trial; 5 (12.8%) discontinued therapy due to side-effects such as intolerable capsaicin-induced burning sensations (4) or mastitis (1); 15 (38.5%) reported no benefit. The decrease in VAS ratings was significant after 2 weeks of continuous application. Of the responders 72.2% were still improved at the follow-up; only one-third of them had continued application irregularly. Treatment effect was not dependent on patient's age, duration or localization of PHN (trigeminal involvement was excluded), sensory disturbance or pain character. Treatment response was not correlated with the incidence, time-course or severity of capsaicin-induced burning. If confirmed in controlled trials, the long-term results of this open, non-randomized study might indicate that the analgesic effect of capsaicin in PHN is mediated by both interference with neuropeptide metabolism and morphological changes (perhaps degeneration) of nociceptive afferents.

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.

[Peripheral T-cell lymphoma: diagnosis and treatment]. / Periphere T-Zell-Lymphome--Diagnostik und Therapie.

Peripheral T/NK-cell lymphomas (PTCL) comprise a heterogeneous group of rare diseases accounting for approximately 10-15% of all non-Hodgkin"s lymphomas. Compared to B-cell lymphomas, PTCL more frequently involve extranodal sites and have a worse prognosis. Because of their usually indolent course, primary cutaneous T/NK-cell lymphomas should be distinguished from the other PTCL. Staging of PTCL is done according to the Ann Arbor staging system. The International Prognostic Index, established for aggressive B-cell lymphomas, has also proved relevant for PTCL. Standard therapy for PTCL has not been defined, yet. First line anthracycline-based chemotherapy brings about long-term remissions in 15 to 42% of patients. Apart from (ALK-positive) anaplastic large cell lymphoma it thus gives poorer results than those obtained in patients with aggressive B-cell lymphomas. Data for high-dosage therapy with autologous stem cell transplantation (autoSCT) for relapsing and refractory PTCL are similar to those reported for aggressive B-cell lymphomas. Thus this treatment seems to constitute a sensible salvage strategy. Allogeneic stem cell transplantation following reduced conditioning regimens has also given promising results in patients with relapse. However, the impact of high-dosage strategies and the implementation of newer agents, such as alemtuzumab, in first-line treatment are still uncertain. Hence patients with PTCL should be treated within clinical trials.