Cancer patients' needs for virtues and physicians' characteristics in physician-patient communication: a survey among patient representatives.

BACKGROUND: Data on patients' needs with respect to physicians' ethical behavior and virtues are important but not available in most cases. PATIENTS AND METHODS: In an iterative process together with patients' representatives, we developed a standardized questionnaire which was distributed to the representatives of the Women's Self-Help after Cancer in Germany. We started with the classical ethical virtues and clustered them to characteristics. The patients' representatives were asked to rate in different communications settings. RESULTS: One hundred eighty-six patients' representatives took part in the survey. For four communication situations (first communication on symptoms, diagnosis of cancer, choice of therapy, doubts on therapy), competence was rated as very important by 80-89% and as important by 6-7%; honesty as very important by 78-89% and as important by 5-12%; respect as very important by 66-71% and as important by 19-21%; and patience as very important by 55-68% and as important by 6-24%. Compassion was rated as less important, with only 24-31% rating it as very important and another 26-32% as important. Additional desires expressed by the participants were physicians having more time (9.1%) and a better relationship between physician and patient (7.0%). CONCLUSION: Competence, honesty, respect, and patience are important characteristics which should be focused on in communication training of medical students and physicians. In spite of compassion being rated as less important, training on compassion/empathy might help doctors to improve coping with the continuous confrontation with complications, progress, suffering, and death of their patients.

Influenza virus infections in patients with malignancies -- characteristics and outcome of the season 2014/15. A survey conducted by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO).

Influenza virus infections (IVI) may pose a vital threat to immunocompromised patients such as those suffering from malignancies, but specific data on epidemiology and outcome in these patients are scarce. In this study, we collected data on patients with active cancer or with a history of cancer, presenting with documented IVI in eight centres in Germany. Two hundred and three patients were identified, suffering from haematological malignancies or solid tumours; 109 (54 %) patients had active malignant disease. Influenza A was detected in 155 (77 %) and Influenza B in 46 (23 %) of patients (genera not determined in two patients). Clinical symptoms were consistent with upper respiratory tract infection in 55/203 (27 %), influenza-like illness in 82/203 (40 %), and pneumonia in 67/203 (33 %). Anti-viral treatment with oseltamivir was received by 116/195 (59 %). Superinfections occurred in 37/203 (18 %), and admission on an intensive care unit was required in 26/203 (13 %). Seventeen patients (9 %) died. Independent risk factors for death were delayed diagnosis of IVI and bacterial or fungal superinfection, but not underlying malignancy or ongoing immunosuppression. In conclusion, patients with IVI show high rates of pneumonia and mortality. Early and rapid diagnosis is essential. The high rate of pneumonia and superinfections should be taken into account when managing IVI in these patients.

A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias.

BACKGROUND: Ponatinib is a potent oral tyrosine kinase inhibitor of unmutated and mutated BCR-ABL, including BCR-ABL with the tyrosine kinase inhibitor-refractory threonine-to-isoleucine mutation at position 315 (T315I). We conducted a phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). METHODS: We enrolled 449 heavily pretreated patients who had CML or Ph-positive ALL with resistance to or unacceptable side effects from dasatinib or nilotinib or who had the BCR-ABL T315I mutation. Ponatinib was administered at an initial dose of 45 mg once daily. The median follow-up was 15 months. RESULTS: Among 267 patients with chronic-phase CML, 56% had a major cytogenetic response (51% of patients with resistance to or unacceptable side effects from dasatinib or nilotinib and 70% of patients with the T315I mutation), 46% had a complete cytogenetic response (40% and 66% in the two subgroups, respectively), and 34% had a major molecular response (27% and 56% in the two subgroups, respectively). Responses were observed regardless of the baseline BCR-ABL kinase domain mutation status and were durable; the estimated rate of a sustained major cytogenetic response of at least 12 months was 91%. No single BCR-ABL mutation conferring resistance to ponatinib was detected. Among 83 patients with accelerated-phase CML, 55% had a major hematologic response and 39% had a major cytogenetic response. Among 62 patients with blast-phase CML, 31% had a major hematologic response and 23% had a major cytogenetic response. Among 32 patients with Ph-positive ALL, 41% had a major hematologic response and 47% had a major cytogenetic response. Common adverse events were thrombocytopenia (in 37% of patients), rash (in 34%), dry skin (in 32%), and abdominal pain (in 22%). Serious arterial thrombotic events were observed in 9% of patients; these events were considered to be treatment-related in 3%. A total of 12% of patients discontinued treatment because of an adverse event. CONCLUSIONS: Ponatinib had significant antileukemic activity across categories of disease stage and mutation status. (Funded by Ariad Pharmaceuticals and others; PACE ClinicalTrials.gov number, NCT01207440 .).

Polymorphisms of Toll-like receptors (TLR2 and TLR4) are associated with the risk of infectious complications in acute myeloid leukemia.

Infectious complications continue to be one of the major causes of morbidity and mortality in patients with acute myeloid leukemia (AML). Several single-nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) can affect the genetic susceptibility to infections or even sepsis. We sought to investigate the impact of different SNPs on the incidence of developing sepsis and pneumonia in patients with newly diagnosed AML following induction chemotherapy. We analyzed three SNPs in the TLR2 (Arg753Gln) and TLR4 (Asp299Gly and Thr399Ile) gene in a cohort of 155 patients with AML who received induction chemotherapy. The risk of developing sepsis and pneumonia was assessed by multiple logistic regression analyses. The presence of the TLR2 Arg753Gln polymorphism was significantly associated with pneumonia in AML patients (odds ratio (OR): 10.78; 95% confidence interval (CI): 2.0-58.23; P=0.006). Furthermore, the cosegregating TLR4 polymorphisms Asp299Gly and Thr399Ile were independent risk factors for the development of both sepsis and pneumonia (OR: 3.55; 95% CI: 1.21-10.4, P=0.021 and OR: 3.57, 95% CI: 1.3-9.86, P=0.014, respectively). To our best knowledge, this study represents the first analysis demonstrating that polymorphisms of TLR2 and TLR4 influence the risk of infectious complications in patients with AML undergoing induction chemotherapy.

[Acute leukemia in adults]. / Akute Leukämien des Erwachsenen.

BACKGROUND: The prognosis of adult patients with acute leukemia has continuously improved over the years due to the introduction of new diagnostic and therapeutic procedures and progress in the field of supportive therapy. METHODS: This article gives an overview of the currently available options and the clinical approach to the diagnostics and therapy of acute leukemia. RESULTS: The standardization as well as improvements in diagnostic procedures, in particular by immunocytological and genetic procedures, allow a more rapid determination of the exact diagnosis. In addition to age and performance status of patients, an established panel of cytogenetic and molecular markers allows an individual risk stratification for selecting the most appropriate therapeutic procedure for each patient. In acute myeloid leukemia (AML) younger patients with genetically determined intermediate and poor risk status benefit from allogeneic stem cell transplantation whereas patients in the low risk group are still primarily treated with conventional induction chemotherapy with anthracycline and cytarabine. The poor prognosis of elderly patients with AML has been improved by the development of stem cell transplantation procedures with reduced intensity conditioning and for patients not suitable for stem cell transplantation, the introduction of less toxic demethylating substances allows a substantial improvement in outcome and quality of life compared to cytoreductive therapy alone. The additional role of targeted therapies in AML is still under investigation. In adult patients with acute lymphoblastic leukemia (ALL), the standard systemic therapy still consists of complex cytotoxic regimens which have been modified from pediatric protocols. Biologically and genetically determined subgroups of ALL patients as well as poor responders, who can be identified by the detection of significant molecular determined residual disease (MRD) after standard therapy, benefit from allogeneic transplantation in first remission. In patients with bcr-abl positive ALL, the implementation of first and second generation tyrosine kinase inhibitors has led to rapidly rising response rates and less toxicity. Patients with relapsed ALL may benefit from new molecular options, e.g. bispecific antibodies. Additionally, improved standardization and supportive care, particularly due to the introduction of modern antimycotic agents, increase the treatment options and improve the prognosis of patients with acute leukemia. CONCLUSION: The improved diagnostic and therapeutic options for patients with acute leukemia require a complex management. Currently only subgroups of patients benefit from molecular targeted therapeutic strategies. Due to this increasing complexity in the management, patients with acute leukemia should be treated in academic centers and within clinical trials.

A classic improved: minor tweaks yield major benefits in crayfish slow-flexor preparations.

Action potentials and the postsynaptic potentials they evoke fill the pages of neuroscience textbooks, but students have relatively few opportunities to record these phenomena on their own. However, the act of making such recordings can be key events in a student's scientific education. The crayfish abdominal slow flexor muscle system is a well-established platform for recording spikes and PSPs. It enables students to see nerves and the muscles they innervate, record spontaneous spikes from several motor axons in these nerves as well as PSPs in their postsynaptic muscle fibers, and interpret these recordings quantitatively. Here we describe an improved method for preparing the slow-flexor system for recording that employs transmitted illumination through the stereo microscope's conventional substage lighting. Oblique transmitted lighting allows students to see the nerve and muscles fibers in each segment clearly and position recording electrodes accurately under visual control. Because students can see the nerves, muscles, and recording electrodes, broken electrode tips are relatively uncommon and the first successful recordings come more quickly. Many kinds of neurons in the CNS have the same pattern of multineuronal, multiterminal innervation that occurs on these muscle fibers. To visualize these innervation patterns on these fibers, we describe an immunohistochemical protocol that labels the GABAergic inhibitory motor axon and all the synaptic vesicles in the synaptic terminals on these muscle fibers. Dual-color images reveal extensive branching of the axons and fields of presynaptic terminals, only some of which are double-labeled for GABA.

[Chronic myelogenous leukemia]. / Chronische myeloische Leukämie.

The advent of tyrosine kinase inhibitors (TKI) has improved the prognosis and outcome of patients with chronic myelogenous leukemia (CML) considerably. Compared with imatinib, the first-line use of second-generation inhibitors nilotinib and dasatinib has led to faster and deeper molecular remissions accompanied by a differential adverse effect profile. An essential part of the management of CML patients is the guideline-based application of cytogenetics and standardized polymerase chain reaction techniques to regularly assess the remission status. Long-lasting treatment-free remission in a minority of patients led to hopes for the curability of CML in a significant minority of patients. The use of interferon alpha combined with or after TKI therapy is associated with the induction of an immune response toward the leukemic clone. This innovative treatment approach is currently under prospective investigation to improve long-term response. The coordinated cooperation of academic and regional hospitals, office-based hematologists, laboratories, and patient representatives allows for up-to-date patient care and the early use of new therapeutic options in patients at risk.

Patients with malignant hematological disorders treated on a palliative care unit: prognostic impact of clinical factors.

A reliable estimation of prognosis in patients receiving palliative care is desirable in order to facilitate clinical decision finding. For patients with advanced hematological malignancies, only few data are available to estimate prognosis of the individual's remaining life span. Here, we sought to investigate potential clinical prognostic parameters in patients with hematological malignancies admitted to a palliative care unit. Using a prospectively collected database, we analyzed clinical and laboratory parameters regarding their prognostic impact in 290 patients with malignant hematological diseases. The parameters included patient-related factors such as Eastern Cooperative Oncology Group (ECOG) performance status, need for transfusions, parenteral nutrition or analgetics, and laboratory values (hemoglobin, platelet count, lactic dehydrogenase (LDH), albumin, total protein, calcium, and C-reactive protein (CRP)) as well as referral symptoms (including anemia, infection, fever, fatigue, and dyspnea). In univariate analyses, LDH (>248 U/l), albumin corrected calcium (>2.55 mmol/l), CRP (>50 mg/l), albumin (<30 g/l), platelet count (<90 × 10(9)/l), total protein (≤60 g/l), hemoglobin (<10 g/dl), opioid treatment, performance status (ECOG >2), and need for parenteral nutrition or blood transfusion significantly correlated with impaired survival. Multivariate analysis showed that low performance status, low platelet count, opioid based pain therapy, high LDH, and low albumin were associated with poor prognosis. Using these five parameters, patients were divided into three "risk groups": low risk (presence of zero to one factor), intermediate risk (two to three factors), and high risk. Median survival for the poor risk patients was 10 days, and the intermediate and low risk patients survived a median of 63 and 440 days, respectively (p < 0.0001). Several clinical and laboratory parameters were associated with a poor prognosis of patients with hematological malignancies treated on a palliative care unit. These parameters might help clinicians to estimate prognosis of remaining life span and individualize treatment and/or end-of-life care options for patients.

Phase I/II trial of capecitabine and oxaliplatin in combination with bevacizumab and imatinib in patients with metastatic colorectal cancer: AIO KRK 0205.

BACKGROUND: Combined inhibition of platelet-derived growth factor receptor beta signalling and vascular endothelial growth factor promotes vascular normalisation in preclinical models and may lead to increased delivery of chemotherapy to tumour tissue. This phase I/II trial assessed the safety and efficacy of capecitabine plus oxaliplatin (XELOX) plus bevacizumab and imatinib in the first-line treatment of patients with metastatic colorectal cancer. METHODS: Two dose levels (I/II) were defined: capecitabine 850/1000 mg m(-2) twice daily on days 1-14; oxaliplatin 100/130 mg m(-2) on day 1; bevacizumab 7.5 mg kg(-1) on day 1; imatinib 300 mg day(-1) on days 1-21 every 21 days. The primary study endpoint was safety. The phase II secondary endpoint was 6-month progression-free survival (PFS). RESULTS: Dose level I was chosen for phase II testing because, even though further dose escalation was permitted by the protocol, gastrointestinal toxicities were considered to be clinically significant. A total of 49 patients were evaluated. The 6-month PFS rate was 76%, median PFS was 10.6 months and median overall survival was 23.2 months. Haematological toxicities were generally mild. Sensory neuropathy and diarrhoea were the most common grade 3 toxicities. CONCLUSION: The combination of XELOX with bevacizumab and imatinib is tolerable and has promising efficacy.

Adjuvant IMRT/XELOX radiochemotherapy improves long-term overall- and disease-free survival in advanced gastric cancer.

PURPOSE: In a retrospective analysis, adjuvant intensity-modulated radiation therapy (IMRT) combined with modern chemotherapy improved advanced gastric cancer survival rates compared to a combination of three-dimensional conformal radiation therapy (3D-CRT) and conventional chemotherapy. We report on the long-term outcomes of two consecutive patient cohorts that were treated with either IMRT and intensive chemotherapy, or 3D-CRT and conventional chemotherapy. PATIENTS AND METHODS: Between 2001 and 2008, 65 consecutive gastric cancer patients received either 3D-CRT (n = 27) or IMRT (n = 38) following tumor resection. Chemotherapy comprised predominantly 5-fluorouracil/folinic acid (5-FU/FA) in the earlier cohort and capecitabine plus oxaliplatin (XELOX) in the latter. The primary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: Median OS times were 18 and 43 months in the 3D-CRT and IMRT groups, respectively (p = 0.0602). Actuarial 5-year OS rates were 26 and 47 %, respectively. Within the IMRT group, XELOX gave better results than 5-FU/FA in terms of OS, but this difference was not statistically significant. The primary cause of death in both groups was distant metastasis. Median DFS times were 14 and 35 months in the 3D-CRT and IMRT groups, respectively (p = 0.0693). Actuarial 5-year DFS rates were 22 and 44 %, respectively. Among patients receiving 5-FU/FA, DFS tended to be better in the IMRT group, but this was not statistically significant. A similar analysis for the XELOX group was not possible as 3D-CRT was almost never used to treat these patients. No late toxicity exceeding grade 3 or secondary tumors were observed. CONCLUSION: After a median follow-up period of over 5 years, OS and DFS were improved in the IMRT/XELOX treated patients compared to the 3D-CRT/5-FU/FA group. Long-term observation revealed no clinical indications of therapy-induced secondary tumors or renal toxicity.

Phase 2 study of subcutaneous omacetaxine mepesuccinate for chronic-phase chronic myeloid leukemia patients resistant to or intolerant of tyrosine kinase inhibitors.

Omacetaxine mepesuccinate (omacetaxine) is a first-in-class cephalotaxine with a unique mode of action, independent of BCR-ABL, that has shown promising activity in patients with chronic myeloid leukemia (CML). This multicenter, noncomparative, open-label phase 2 study evaluated the efficacy and safety of subcutaneous omacetaxine in CML patients with resistance or intolerance to two or more tyrosine kinase inhibitors (TKIs); results in patients in chronic phase are reported here. Patients received subcutaneous omacetaxine 1.25 mg/m² twice daily days 1-14 every 28 days until hematologic response (up to a maximum of six cycles), then days 1-7 every 28 days as maintenance. Primary endpoints were rates of hematologic response lasting >8 weeks and major cytogenetic response (MCyR). Forty-six patients were enrolled: all had received imatinib, 83% had received dasatinib, and 57% nilotinib. A median 4.5 cycles of omacetaxine were administered (range, 1-36). Hematologic response was achieved or maintained in 31 patients (67%); median response duration was 7.0 months. Ten patients (22%) achieved MCyR, including 2 (4%) complete cytogenetic responses. Median progression-free survival was 7.0 months [95% confidence interval (CI), 5.9-8.9 months], and overall survival was 30.1 months (95% CI, 20.3 months-not reached). Grade 3/4 hematologic toxicity included thrombocytopenia (54%), neutropenia (48%), and anemia (33%). Nonhematologic adverse events were predominantly grade 1/2 and included diarrhea (44%), nausea (30%), fatigue (24%), pyrexia (20%), headache (20%), and asthenia (20%). Subcutaneous omacetaxine may offer clinical benefit to patients with chronic-phase CML with resistance or intolerance to multiple TKI therapies.

[Tailored management of chronic myeloid leukemia]. / Maßgeschneiderte Therapie der chronischen myeloischen Leukämie.

State of the art management of chronic myeloid leukemia (CML) patients with the selection of best available treatment options requires systematic cytogenetic and molecular monitoring. The choice of the first-line tyrosine kinase inhibitor depends on integration of comorbidities and individual treatment goals. Clinical prognostic scores should be used for cohort comparison and for stratification in randomized trials. Their relevance for individual treatment decisions has not yet been established. Essential for therapeutic decision-making is the achievement of predefined cytogenetic and molecular milestones in the course of the disease. In cases of treatment resistance or relapse the analysis of potential causes is required. After exclusion of compliance issues bone marrow analysis for the accurate characterization of the hematologic disease state and exclusion of clonal evolution is recommended. In parallel, BCR-ABL mutation analysis should be performed. The choice of second-line treatment depends on the predicted sensitivity of any BCR-ABL mutation detected and the clinical history of the patient. Most important is prevention of disease progression as treatment results in advanced disease are still not satisfying. Therefore, allogeneic stem cell transplantation should be considered early in resistant disease, when high-risk parameters (e.g. multiresistant mutations) have been detected.

The JAK1/2 inhibitor ruxolitinib in patients with COVID-19 triggered hyperinflammation: the RuxCoFlam trial.

Dysregulated hyperinflammatory response is key in the pathogenesis in patients with severe COVID-19 leading to acute respiratory distress syndrome and multiorgan failure. Whilst immunosuppression has been proven to be effective, potential biological targets and optimal timing of treatment are still conflicting. We sought to evaluate efficacy and safety of the Janus Kinase 1/2 inhibitor ruxolitinib, employing the previously developed COVID-19 Inflammation Score (CIS) in a prospective multicenter open label phase II trial (NCT04338958). Primary objective was reversal of hyperinflammation (CIS reduction of ≥25% at day 7 in ≥20% of patients). In 184 patients with a CIS of ≥10 (median 12) ruxolitinib was commenced at an initial dose of 10 mg twice daily and applied over a median of 14 days (range, 2-31). On day 7, median CIS declined to 6 (range, 1-13); 71% of patients (CI 64-77%) achieved a ≥25% CIS reduction accompanied by a reduction of markers of inflammation. Median cumulative dose was 272.5 mg/d. Treatment was well tolerated without any grade 3-5 adverse events related to ruxolitinib. Forty-four patients (23.9%) died, all without reported association to study drug. In conclusion, ruxolitinib proved to be safe and effective in a cohort of COVID-19 patients with defined hyperinflammation.

Capecitabine-associated hand-foot-skin reaction is an independent clinical predictor of improved survival in patients with colorectal cancer.

BACKGROUND: Hand-foot-skin reaction (HFSR) is an adverse event frequently observed during treatment with capecitabine (cape). In the present analysis, we sought to evaluate the potential association of HFSR and survival in German patients with metastatic colorectal cancer and locally advanced rectal cancer treated with cape in clinical trials. METHODS: Patients of the Arbeitsgemeinschaft für Internistische Onkologie (AIO) KRK-0104 and the Mannheim rectal cancer trial were evaluated. HFSR was graded according to NCI-CTC criteria in both trials. Time to first occurrence of HFSR was described per cycle and HFSR developing during cycles 1 and 2 was defined as 'early HFSR'. Baseline characteristics between the patient groups with or without HFSR were compared using Mann-Whitney-U, Fisher's exact or χ(2)-test, as appropriate. Haematological and non-haematological toxicities observed in both groups were compared using Fisher's exact test. Progression-free (PFS) or disease-free (DFS) as well as overall survival (OS) data from both trials were pooled and the HFSR group was compared with the non-HFSR using Kaplan-Meier analysis. RESULTS: A total of 374 patients were included, of whom 29.3% developed any HFSR. Of these, 51% had early HFSR. Baseline characteristics were comparable between both HFSR groups concerning age, gender, ECOG performance status and UICC stage. On multivariate analysis none of these factors had influence on the occurrence of HFSR. The percentage of all-grade (and grade 3-4) haematological toxicities did not differ between both the groups. By contrast, patients exhibiting HFSR had a significantly higher rate of all-grade (but not grade 3-4) diarrhoea, stomatitis/mucositis and fatigue (P<0.01, respectively). Patients with HFSR had improved PFS/DFS (29.0 vs 11.4 months; P=0.015, HR 0.69) and OS (75.8 vs 41.0 months; P=0.001, HR=0.56). Within the HFSR group, PFS/DFS and OS were comparable between patients with early vs late HFSR. INTERPRETATION: The present analysis provides evidence for the association of HFSR and survival in patients with colorectal cancer. Baseline characteristics, with the exception of UICC stage, older age and ECOG performance status, and the time of occurrence of HFSR had no impact on survival. Patients with HFSR had a higher probability of developing any-grade gastrointestinal toxicity and fatigue while no correlation with haematological toxicity was found.

[Interdisciplinary COVID board for patients with SARS-CoV-2-triggered hyperferritinemic Inflammation]. / Interdisziplinäres COVID-Board bei SARS-CoV-2-getriggerter hyperferritinämischer Inflammation.

BACKGROUND: Patients with severe COVID-19 develop hyperferritinemic inflammation, a rare sepsis-like immune dysregulation syndrome. METHODS: Stratified treatment decisions in a cross-location telemedical interdisciplinary case conference were assessed in this retrospective cohort study. A standardized treatment algorithm including continuous positive airway pressure and noninvasive ventilation was implemented. A locally developed COVID inflammation score (CIS) defined patients at risk for severe disease. Patients with life-threatening inflammation were offered off-label treatment with the immune modulator ruxolitinib. RESULTS: Between 4 March 2020 and 26 June 2020 COVID-19 patients (n = 196) were treated. Median patient age (70 years) and comorbidity were high in interstudy comparison. Mortality in all patients was 17.3%. However, advance care planning statements and physician directives limited treatment intensity in 50% of the deceased patients. CIS monitoring of ruxolitinib-treated high-risk patients (n = 20) on days 5, 7, and15 resulted in suppression of inflammation by 42% (15-70), 54% (15-77) and 60% (15-80). Here, mortality was 20% (4/20). Adjusted for patients with a maximum care directive including ICU, total mortality was 8.7% (17/196). CONCLUSION: Severe COVID-19 pneumonia with hyperferritinemic inflammation is related to macrophage activation syndrome-like sepsis. An interdisciplinary intensive care teleconference as a quality tool for ICUs is proposed to detect patients with rare sepsis-like syndromes.

The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation.

A subgroup of patients with severe COVID-19 suffers from progression to acute respiratory distress syndrome and multiorgan failure. These patients present with progressive hyperinflammation governed by proinflammatory cytokines. An interdisciplinary COVID-19 work flow was established to detect patients with imminent or full blown hyperinflammation. Using a newly developed COVID-19 Inflammation Score (CIS), patients were prospectively stratified for targeted inhibition of cytokine signalling by the Janus Kinase 1/2 inhibitor ruxolitinib (Rux). Patients were treated with efficacy/toxicity guided step up dosing up to 14 days. Retrospective analysis of CIS reduction and clinical outcome was performed. Out of 105 patients treated between March 30th and April 15th, 2020, 14 patients with a CIS ≥ 10 out of 16 points received Rux over a median of 9 days with a median cumulative dose of 135 mg. A total of 12/14 patients achieved significant reduction of CIS by ≥25% on day 7 with sustained clinical improvement in 11/14 patients without short term red flag warnings of Rux-induced toxicity. Rux treatment for COVID-19 in patients with hyperinflammation is shown to be safe with signals of efficacy in this pilot case series for CRS-intervention to prevent or overcome multiorgan failure. A multicenter phase-II clinical trial has been initiated (NCT04338958).

European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia.

The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.

Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (mGemOx): final results of a multicenter randomized phase II trial in advanced pancreatic cancer.

BACKGROUND: To compare the efficacy and safety of three different chemotherapy doublets in the treatment of advanced pancreatic cancer (PC). PATIENTS AND METHODS: At total of 190 patients were randomly assigned to receive capecitabine 1000 mg/m(2) twice daily on days 1-14 plus oxaliplatin 130 mg/m(2) on day 1 (CapOx), capecitabine 825 mg/m(2) twice daily on days 1-14 plus gemcitabine 1000 mg/m(2) on days 1 and 8 (CapGem) or gemcitabine 1000 mg/m(2) on days 1 and 8 plus oxaliplatin 130 mg/m(2) on day 8 (mGemOx). Treatment cycles were repeated every three weeks. The primary end point was progression-free survival (PFS) rate at 3 months; secondary end points included objective response rate, carbohydrate antigen 19-9 response, clinical benefit response, overall survival and toxicity. RESULTS: The PFS rate after 3 months was 51% in the CapOx arm, 64% in the CapGem arm and 60% in the mGemOx arm. Median PFS was estimated with 4.2 months, 5.7 months and 3.9 months, respectively (P = 0.67). Corresponding median survival times were: 8.1 months (CapOx), 9.0 months (CapGem) and 6.9 months (mGemOx) (P = 0.56). Grade 3/4 hematological toxicities were more frequent in the two Gem-containing arms; grade 3/4 non-hematological toxicity rates did not exceed 15% in any arm. CONCLUSION: CapOx, CapGem and mGemOx have similar clinical efficacy in advanced PC. Each regimen has a distinct but manageable tolerability profile.