Azacitidine Post-transplant Maintenance Improves Disease Progression in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome.

BACKGROUND: Maintenance after allogeneic hematopoietic cell transplantation (alloHCT) with hypomethylating agents has yielded conflicting results. MATERIALS AND METHODS: We conducted a single center retrospective matched-control analysis with the study group (5-azacitidine [AZA] group) including adults with FLT3-negative acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who received post-transplant AZA maintenance off clinical trial (n = 93). A matched control group was comprised of contemporaneous AML/MDS patients who did not receive any maintenance (n = 357). Primary endpoint was disease progression. RESULTS: The AZA and control groups had comparable patient and disease characteristics except for older age (median: 61 vs. 57 years, P = .01) and lower hematopoietic comorbidity index (median: 2 vs. 3, P = .04) in the AZA group. The 3-year cumulative incidence of progression in the AZA and control groups was 29% vs. 33% (P = .09). The protective effect of AZA on progression was limited to patients with high-risk AML/MDS (HR = 0.4, 95% CI = 0.2-0.8, P = .009). This led to improved progression-free survival both in high-risk AML and MDS patients with maintenance (HR = 0.2, 95% CI = 0.1-0.6, P = .004 and HR = 0.4, 95% CI = 0.2-0.9, P = .04). CONCLUSION: AZA maintenance was associated with a lower progression rate in patients with high-risk FLT3-negative AML or MDS, and AZA maintenance should be considered for post-alloHCT maintenance in this subset.

Topical Treatment of Psoriasis Vulgaris: The Swiss Treatment Pathway.

Topical treatment is crucial for the successful management of plaque psoriasis. Topicals are used either as a stand-alone therapy for mild psoriasis or else in combination with UV or systemic treatment for moderate-to-severe disease. For the choice of a suitable topical treatment, the formulation matters and not just the active substances. This expert opinion paper was developed via a non-structured consensus process by Swiss dermatologists in hospitals and private practices to illustrate the current treatment options to general practitioners and dermatologists in Switzerland. Defining treatment goals together with the patient is crucial and increases treatment adherence. Patients' personal preferences and pre-existing experiences should be considered and their satisfaction with treatment and outcome regularly assessed. During the induction phase of "classical" mild-to-moderate psoriasis, the fixed combination of topical calcipotriol (Cal) 50 µg/g and betamethasone dipropionate (BD) 0.5 mg/g once daily is frequently used for 4-8 weeks. During the maintenance phase, a twice weekly (proactive) management has proved to reduce the risk of relapse. Of the fixed combinations, Cal/BD aerosol foam is the most effective formulation. However, the individual choice of formulation should be based on a patient's preference and the location of the psoriatic plaques. Tailored recommendations are given for the topical management of specific areas (scalp, facial, intertriginous/genital, or palmoplantar lesions), certain symptoms (hyperkeratotic or hyperinflammatory forms) as well as during pregnancy or a period of breastfeeding. As concomitant basic therapy, several emollients are recommended. If topical treatment alone does not appear to be sufficient, the regimen should be escalated according to the Swiss S1-guideline for the systemic treatment of psoriasis.

Variation in immunosuppression practices among pediatric liver transplant centers-Society of Pediatric Liver Transplantation survey results.

BACKGROUND: Variation in IS exists among pediatric liver transplant centers. While individual centers may publish their practice paradigms, current data on practices as a whole are lacking. This study sought to ascertain the IS protocols of pediatric liver transplant centers within the SPLIT to better understand variability and similarities among peer institutions. METHODS: A 27-item questionnaire was developed within the SPLIT Quality Improvement and Clinical Care Committee. The survey collected data regarding center demographics, IS practices, and treatment of acute cellular rejection. RESULTS: Twenty-eight (64%) SPLIT centers responded with 22 (79%) centers performing more than 10 transplants per year and 17 (61%) following more than 100 post-transplant recipients. All centers use a written protocol, and 25 (89%) have a dedicated transplant pharmacist/PharmD. Twenty-five (89%) centers use steroids for induction alone or in combination with thymoglobulin/interleukin-2 antibodies. All centers use tacrolimus for initial maintenance therapy. Most centers have specialized protocols for ABO-incompatible transplants, recipients with renal dysfunction, autoimmune liver diseases, and liver tumors. Treatment of rejection varied but was associated with escalation in IS. CONCLUSION: IS practices among pediatric liver transplant centers are similar including the use of written protocols, pharmacy involvement, steroids for induction, tacrolimus as initial IS, tacrolimus reduction/delay for renal dysfunction, and escalation of IS with rejection severity. However, other IS practices show wide variability including treatment for ABO-incompatible grafts and presumed rejection. This study serves as a foundation to guide prospective research linking IS practice to outcomes to determine best practice.

Best Practice Guidance for Adult Infusion Centres during the COVID-19 Pandemic: Report from the COVID-19 International Organization for the Study of IBD [IOIBD] Task Force.

Infusion centres are a central part in the management of patients with inflammatory bowel disease [IBD] and could be a source of transmission of SARS-COV-2. Here we aimed to develop global guidance for best practices of infusion centres for IBD patients and to determine the impact of the COVID-19 pandemic on these centres. Under the auspices of the International Organization for the Study of Inflammatory Bowel Disease [IOIBD], a task force [TF] was formed, an online survey was developed to query infusion centre protocols during COVID-19, and recommendations were made, based on TF experience and opinion. Recommendations focus mainly on patients screening, infusion centres re-organization, personnel protection, and protocol modifications such as shortening infusion duration or replacing it with subcutaneous alternatives. Implementing these recommendations will hopefully reduce exposure of both IBD patients and care givers to SARS-COV-2 and improve the function and safety of infusion centres during the COVID-19 pandemic as well as potential future threats.

Frontline PARP inhibitor maintenance therapy in ovarian cancer: A Society of Gynecologic Oncology practice statement.

PARP inhibitors (PARPi) have shown have activity in the treatment of ovarian cancer. Previous studies documented activity in patients with germline (gBRCA) and tumor (tBRCA) BRCA mutations (BRCAm) for treatment in lieu of chemotherapy as well as in recurrent ovarian cancer as maintenance therapy. The recent data from four randomized phase 3 trials have established an important role for frontline PARPi maintenance therapy in ovarian cancer. While SOLO-1 only included BRCAm patients, PRIMA, VELIA, and PAOLA-1 enrolled broader patient populations. The magnitude of benefit of PARPi in these studies was consistently greatest in the BRCAm patients (germline or tumor). PARPi treatment also improved PFS in the HRD cohort but to a lesser degree than in patients with BRCAm. In secondary analyses, the overall impact of PARPi treatment in HR proficient patients, which comprise about 50% of ovarian cancers, was more limited than in the other subgroups. Data for overall survival, also a secondary endpoint, is currently immature for these four trials. Fatigue, hematologic, and GI toxicities are the most commonly noted adverse events with PARPi therapy. The recent FDA approvals of PARPi in the maintenance setting will enable clinicians to incorporate these into frontline armamentarium of ovarian cancer treatment.

ANCA-associated vasculitides: Recommendations of the French Vasculitis Study Group on the use of immunosuppressants and biotherapies for remission induction and maintenance.

Treatment of vasculitides associated with anti-neutrophil cytoplasm antibodies (ANCA) (AAVs) has evolved dramatically in recent years, particularly since the demonstration of rituximab efficacy as remission induction and maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. In 2013, the French Vasculitis Study Group (FVSG) published recommendations for its use by clinicians. Since then, new data have made it possible to better specify and codify prescription of rituximab to treat AAVs. Herein, the FVSG Recommendations Committee, an expert panel comprised of physicians with extensive experience in the treatment and management of vasculitides, presents its consensus guidelines based on literature analysis, the results of prospective therapeutic trials and personal experience.

European Guideline on IgG4-related digestive disease - UEG and SGF evidence-based recommendations.

The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6-0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2-4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added.

Ovarian Cancer Maintenance: Practice-Changing Data Calls for Changing Practice.

Staying current on the rapidly evolving therapeutic landscape in oncology is challenging for clinicians. This commentary discusses exciting practice­changing data specific to ovarian cancer.

Systematic review and network meta-analysis: first- and second-line biologic therapies for moderate-severe Crohn's disease.

BACKGROUND: There are limited data to inform positioning of agents for treating moderate-severe Crohn's disease (CD). AIM: We assessed comparative efficacy and safety of first-line (biologic-naïve) and second-line (prior exposure to anti-tumour necrosis factor [TNF]-α) agents) biologic therapy for moderate-severe CD, through a systematic review and network meta-analysis, and appraised quality of evidence (QoE) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. METHODS: We identified randomised controlled trials (RCTs) in adults with moderate-severe CD treated with approved anti-TNF agents, anti-integrin agents and anti-IL12/23 agents, first-line or second-line, and compared with placebo or another active agent. Efficacy outcomes were induction and maintenance of clinical remission; safety outcomes were serious adverse events and infections. Network meta-analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities. RESULTS: No head-to-head trials were identified. In biologic-naïve patients, infliximab (SUCRA,0.93) and adalimumab (SUCRA,0.75) were ranked highest for induction of clinical remission (moderate QoE). In patients with prior anti-TNF exposure, adalimumab (SUCRA, 0.91; low QoE, in patients with prior response or intolerance to anti-TNF agents) and ustekinumab (SUCRA, 0.71) were ranked highest for induction of clinical remission. In patients with response to induction therapy, adalimumab (SUCRA, 0.97) and infliximab (SUCRA, 0.68) were ranked highest for maintenance of remission. Ustekinumab had lowest risk of serious adverse events (SUCRA, 0.72) and infection (SUCRA, 0.71; along with infliximab, SUCRA, 0.83) in maintenance trials. CONCLUSION: Indirect comparisons suggest that infliximab or adalimumab may be preferred first-line agents, and ustekinumab a preferred second-line agent, for induction of remission in patients with moderate-severe CD. Head-to-head trials are warranted.

New Therapies for Ovarian Cancer.

In the latest NCCN Guidelines for Ovarian Cancer, the histologic subtypes of ovarian cancer are described in more depth as they vary by frequency, typical age and disease stage at presentation, treatment recommendations, and survival probabilities. The less common subtypes are also discussed. The update with the greatest impact on the treatment of ovarian cancer, however, is probably the use of maintenance therapy with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, and 3 PARP inhibitors are now included in the guidelines. These drugs have made a large difference in outcome, both for patients with BRCA mutations and in unselected patients.

Efficacy of On-Demand Therapy Using 20-mg Vonoprazan for Mild Reflux Esophagitis.

BACKGROUND: The study aimed to evaluate the efficacy of on-demand therapy using 20-mg vonoprazan for mild reflux esophagitis (RE). METHODS: On-demand therapy by taking one 20-mg tablet of vonoprazan only when reflux symptoms occurred was performed for 24 weeks using 30 patients with mild RE who were receiving maintenance therapy with proton pomp inhibitors (PPIs). The presence or absence of RE, degree of overall satisfaction with the treatment, score of symptoms, and fasting gastrin level before breakfast were examined before and after on-demand therapy. The number of tablets taken during the 24-week period was also noted. RESULTS: One of the 30 patients dropped out of on-demand therapy 1 week after its initiation. Remission was maintained in 25 (86.2%) of the 29 patients (all 10 [100%] Los Angeles classification grade A patients and 15 (78.9%) of the 19 grade B patients). However, 4 grade B patients exhibited grade B relapse. There were no differences in the degree of overall satisfaction, score of symptoms or the gastrin level between PPI and on-demand therapies. The number of vonoprazan tablets taken during the observation period was 33 tablets (median)/24 weeks. CONCLUSION: On-demand therapy using 20-mg vonoprazan tablets is an effective alternative maintenance therapy for mild RE.

[Preventative and therapeutic relapse strategies after allogeneic hematopoietic stem cell transplantation: Guidelines from the Francophone society of bone marrow transplantation and cellular therapy (SFGM-TC)]. / Stratégies préventives et thérapeutiques de la rechute après allogreffe de cellules souches hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT). The risk of recurrence is elevated in patients with high-risk cytogenetic or molecular abnormalities, as well as when allo-HCT is performed in patients with refractory disease or with persistent molecular or radiological (PET-CT scan) residual disease. Within the frame of the 7th annual workshops of the francophone society for bone marrow transplantation and cellular therapy, the working group reviewed the literature in order to elaborate unified guidelines for the prevention and treatment of relapse after allo-HCT. For high risk AML and MDS, a post transplant maintenance strategy is possible, using hypomethylating agents or TKI anti-FLT3 when the target is present. For Philadelphia positive ALL, there was a consensus for the use of post-transplant TKI maintenance. For lymphomas, there are no strong data on the use of post-transplant maintenance, and hence a preemptive strategy is recommended based on modulation of immunosuppression, close follow-up of donor chimerism, and donor lymphocytes infusion. For multiple myeloma, even though the indication of allo-HCT is controversial, our recommendation is post transplant maintenance using bortezomib, due to its a good toxicity profile without increasing the risk of GVHD.

Multiple Myeloma, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology.

Multiple myeloma (MM) is caused by the neoplastic proliferation of plasma cells. These neoplastic plasma cells proliferate and produce monoclonal immunoglobulin in the bone marrow causing skeletal damage, a hallmark of multiple myeloma. Other MM-related complications include hypercalcemia, renal insufficiency, anemia, and infections. The NCCN Multiple Myeloma Panel members have developed guidelines for the management of patients with various plasma cell dyscrasias, including solitary plasmacytoma, smoldering myeloma, multiple myeloma, systemic light chain amyloidosis, and Waldenström's macroglobulinemia. The recommendations specific to the diagnosis and treatment of patients with newly diagnosed MM are discussed in this article.

Stem Cell Harvesting after Bortezomib-Based Reinduction for Myeloma Relapsing after Autologous Transplantation: Results from the British Society of Blood and Marrow Transplantation/United Kingdom Myeloma Forum Myeloma X (Intensive) Trial.

The phase III British Society of Blood and Marrow Transplantation/United Kingdom Myeloma Forum Myeloma X trial (MMX) demonstrated prospectively, for the first time, superiority of salvage autologous stem cell transplantation over chemotherapy maintenance for multiple myeloma (MM) in first relapse after previous ASCT. However, many patients have stored insufficient stem cells (PBSC) for second ASCT and robust evidence for remobilization after first ASCT is lacking. We report the feasibility, safety, and efficacy of remobilization after bortezomib-doxorubicin-dexamethasone reinduction in MMX and outcomes of second ASCT with these cells. One hundred ten patients underwent ≥1 remobilization with 32 and 4, undergoing second and third attempts, respectively. Toxicities of remobilization were similar to those seen in first-line mobilization. After all attempts, 52% of those with insufficient previously stored PBSC had harvested a sufficient quantity to proceed to second ASCT. Median PBSC doses infused, neutrophil engraftment, and time to discharge after second ASCT were similar regardless of stem cell source, as were the toxicities of second ASCT. No significant differences between PBSC sources were noted in depth of response to ASCT or time to progression. Harvesting after bortezomib-doxorubicin-dexamethasone reinduction for MM at first relapse is safe and feasible and yields a reliable cell product for second ASCT. The study is registered with ClinicalTrials.gov (NCT00747877) and EudraCT (2006-005890-24).

Role of Maintenance Therapy after High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation in Aggressive Lymphomas: A Systematic Review.

Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials [RCT], 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas.

Task shifting from doctors to non-doctors for initiation and maintenance of antiretroviral therapy.

BACKGROUND: The high levels of healthcare worker shortage is recognised as a severe impediment to increasing patients' access to antiretroviral therapy. This is particularly of concern where the burden of disease is greatest and the access to trained doctors is limited.This review aims to better inform HIV care programmes that are currently underway, and those planned, by assessing if task-shifting care from doctors to non-doctors provides both high quality and safe care for all patients requiring antiretroviral treatment. OBJECTIVES: To evaluate the quality of initiation and maintenance of HIV/AIDS care in models that task shift care from doctors to non-doctors. SEARCH METHODS: We conducted a comprehensive search to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress) from 1 January 1996 to 28 March 2014, with major HIV/AIDS conferences searched 23 May 2014. We had also contacted relevant organizations and researchers. Key words included MeSH terms and free-text terms relevant to 'task shifting', 'skill mix', 'integration of tasks', 'service delivery' and 'health services accessibility'. SELECTION CRITERIA: We included controlled trials (randomised or non-randomised), controlled-before and after studies, and cohort studies (prospective or retrospective) comparing doctor-led antiretroviral therapy delivery to delivery that included another cadre of health worker other than a doctor, for initiating treatment, continuing treatment, or both, in HIV infected patients. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles, abstracts and descriptor terms of the results of the electronic search and applied our eligibility criteria using a standardized eligibility form to full texts of potentially eligible or uncertain abstracts. Two reviewers independently extracted data on standardized data extraction forms. Where possible, data were pooled using random effects meta-analysis. We assessed evidence quality with GRADE methodology. MAIN RESULTS: Ten studies met our inclusion criteria, all of which were conducted in Africa. Of these four were randomised controlled trials while the remaining six were cohort studies.From the trial data, when nurses initiated and provided follow-up HIV therapy, there was high quality evidence of no difference in death at one year, unadjusted risk ratio was 0.96 (95% CI 0.82 to 1.12), one trial, cluster adjusted n = 2770. There was moderate quality evidence of lower rates of losses to follow-up at one year, relative risk of 0.73 (95% CI 0.55 to 0.97). From the cohort data, there was low quality evidence that there may be an increased risk of death in the task shifting group, relative risk 1.23 (95% CI 1.14 to 1.33, two cohorts, n = 39 160) and very low quality data reporting no difference in patients lost to follow-up between groups, relative risk 0.30 (95% CI 0.05 to 1.94).From the trial data, when doctors initiated therapy and nurses provided follow-up, there was moderate quality evidence that there is probably no difference in death compared with doctor-led care at one year, relative risk of 0.89 (95% CI 0.59 to 1.32), two trials, cluster adjusted n = 4332. There was moderate quality evidence that there is probably no difference in the numbers of patients lost to follow-up at one year, relative risk 1.27 (95% CI 0.92 to 1.77), P = 0.15. From the cohort data, there is very low quality data that death at one year may be lower in the task shifting group, relative risk 0.19 (95% CI 0.05 to 0.78), one cohort, n = 2772, and very low quality evidence that loss to follow-up was reduced, relative risk 0.34 (95% CI 0.18 to 0.66).From the trial data, for maintenance therapy delivered in the community there was moderate quality evidence that there is probably no difference in mortality when doctors deliver care in the hospital or specially trained field workers provide home-based maintenance care and antiretroviral therapy at one year, relative risk 1.0 (95% CI 0.62 to 1.62), 1 trial, cluster adjusted n = 559. There is moderate quality evidence from this trial that losses to follow-up are probably no different at one year, relative risk 0.52 (0.12 to 2.3), P = 0.39. The cohort studies did not report on one year follow-up for these outcomes.Across the studies that reported on virological and immunological outcomes, there was no clear evidence of difference whether a doctor or nurse or clinical officer delivered therapy. Three studies report on costs to patients, indicating a reduction in travel costs to treatment facilities where task shifting was occurring closer to patients homes. There is conflicting evidence regarding the relative cost to the health system, as implementation of the strategy may increase costs. The two studies reporting the patient and staff perceptions of the quality of care, report good acceptability of the service by patients, and general acceptance by doctors of the shifting of roles. One trial reported on the time to initiation of antiretroviral therapy, finding no clear evidence of a difference between groups. The same trial reports on new diagnosis of tuberculosis which favours nurse initiation of HIV care for increasing the numbers of diagnoses of tuberculosis made. AUTHORS' CONCLUSIONS: Our review found moderate quality evidence that shifting responsibility from doctors to adequately trained and supported nurses or community health workers for managing HIV patients probably does not decrease the quality of care and, in the case of nurse initiated care, may decrease the numbers of patients lost to follow-up.

2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease.

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on first line/second and further lines of treatment in advanced disease.