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Practice Changing UpDates
Official reprint from UpToDate® ©2017 UpToDate®
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
Practice Changing UpDates
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2017. | This topic last updated: Mar 21, 2017.

INTRODUCTION — This section highlights selected specific new recommendations and/or updates that we anticipate may change usual clinical practice. Practice Changing UpDates focus on changes that may have significant and broad impact on practice, and therefore do not represent all updates that affect practice. These Practice Changing UpDates, reflecting important changes to UpToDate over the past year, are presented chronologically, and are discussed in greater detail in the identified topic reviews.

ONCOLOGY (March 2017)

Scalp hypothermia to prevent chemotherapy-induced alopecia

For women with breast cancer who are receiving chemotherapy that is expected to result in significant alopecia, and who place a high value on avoiding chemotherapy-induced alopecia, we suggest the use of a scalp cooling device (Grade 2A). Although the evidence base is less robust, scalp hypothermia could also be discussed as a potential option for patients with other solid tumors who are receiving chemotherapy that is expected to result in significant alopecia.

Two prospective studies have evaluated the efficacy of two different automated scalp cooling devices in women with early stage breast cancer [1,2]:

In an interim analysis of a randomized trial comparing the Paxman Scalp Cooling device and no scalp hypothermia for women with breast cancer receiving adjuvant chemotherapy (one-third anthracycline-based, the remainder taxane-based), one-half of the hypothermia group had limited hair loss (to less than 50 percent, not requiring a wig) compared with none in the control group [1]. Adverse events were all grade 1 and 2, including primarily headache and feeling cold. The success rate was higher with taxane-containing regimens.

In a multicenter prospective cohort study, 101 patients receiving non-anthracycline taxane-based chemotherapy and who used the DigniCap Scalp Cooling device were compared with 16 concurrently treated controls who did not use the device [2]. Hair loss of 50 percent or less one month after the end of chemotherapy was demonstrated in two-thirds of the intervention group compared with none of the control group. At a median follow-up of 2.5 years, no patient developed scalp metastases.

These results confirm prior studies on the efficacy and safety of scalp hypothermia to reduce chemotherapy-induced alopecia. One of these devices (DigniCap) is FDA-cleared for this use in the United States. (See "Chemotherapy-induced alopecia", section on 'Efficacy and safety'.)


Immunotherapy for stinging insect hypersensitivity in adults

We suggest not giving venom immunotherapy (VIT) to patients with reactions to stinging insects limited to cutaneous systemic symptoms and not involving other organ systems (Grade 2C). However, VIT is effective in reducing the severity of future reactions and may still be offered in selected situations.

Venom immunotherapy (VIT) for the treatment of patients with anaphylactic reactions to stings of Hymenoptera insects (eg, bees, yellow jackets, wasps, hornets, and fire ants) is highly effective in preventing future anaphylactic reactions. However, in an updated practice parameter from the American Joint Task Force, VIT is no longer suggested for adults with systemic reactions limited to the skin (ie, generalized erythema, pruritus, urticaria, or angioedema) as studies suggest these patients are at low risk for serious future systemic reactions [3]. This change brings the American approach into closer alignment with guidelines of other countries and is similar to the existing recommendation for children. Despite this revision, VIT may be appropriate for certain adults with cutaneous systemic reactions (eg, those with underlying medical conditions or medications that could affect the outcome of a systemic reaction, frequent unavoidable exposure to Hymenoptera, or impaired quality of life due to fear of future stings). (See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action", section on 'Patients with past cutaneous systemic reactions'.)

ONCOLOGY, ADULT PRIMARY CARE (July 2016, Modified February 2017)

Duration of adjuvant endocrine therapy for breast cancer

For postmenopausal women with nonmetastatic hormone receptor-positive breast cancer who have completed a five-year course of an aromatase inhibitor (AI) and who have higher-risk disease (eg, node-positive or ≥T3 disease), we suggest continuing the AI for an additional five years (Grade 2B).

For postmenopausal women receiving adjuvant treatment with an aromatase inhibitor (AI) for hormone-positive breast cancer, the minimum duration of treatment is five years. While data from the MA17R trial demonstrated that extending the duration from 5 to 10 years improved recurrence-free survival [4], preliminary results from the NSABP-B42, DATA, and IDEAL trials, reported at the San Antonio Breast Cancer Symposium, have not confirmed this benefit [5-7]. No study has demonstrated a benefit in overall survival with extended adjuvant AI therapy, and bone-related toxic effects are more frequent among those receiving extended treatment. While variations in methodology likely account for the differences in recurrence-free survival between the studies, the magnitude of any potential benefit is likely to be greatest for those at highest risk for recurrence. While we previously had recommended an extended course of AI adjuvant therapy for most postmenopausal women with nonmetastatic hormone-positive disease, based on the new data, we now suggest offering extended adjuvant aromatase inhibitor therapy to those with high-risk disease (eg, node-positive or ≥T3 disease). (See "Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer", section on 'Duration of endocrine treatment'.)


Tenofovir alafenamide for the treatment of chronic hepatitis B virus infection

For most patients with chronic HBV infection who initiate therapy with tenofovir, we recommend tenofovir alafenamide rather than tenofovir disoproxil fumarate (tenofovir DF) (Grade 1B). We also suggest that those initially started on tenofovir DF switch to tenofovir alafenamide (Grade 2B).

Tenofovir disoproxil fumarate is a first-line therapy for chronic hepatitis B virus (HBV) infection. A newer formulation of tenofovir, tenofovir alafenamide, was approved by the US Food and Drug Administration in November 2016 for the treatment of chronic HBV in patients with compensated liver disease [8]. In two large randomized noninferiority trials among patients with chronic HBV infection (both treatment-naive and experienced, and including patients positive or negative for HBV e antigen), tenofovir alafenamide resulted in similar rates of HBV suppression and fewer adverse effects on renal function and bone density at 48 weeks compared with tenofovir disoproxil fumarate [9,10]. Given these findings, tenofovir alafenamide is our preferred formulation for patients with chronic HBV who initiate therapy with tenofovir. We also favor switching those initially started on tenofovir disoproxil fumarate to tenofovir alafenamide. Given limited available safety data, we do not currently use tenofovir alafenamide in pregnant women. (See "Hepatitis B virus: Overview of management", section on 'Nucleos(t)ide analogues'.)


Meningococcal conjugate vaccination for HIV-infected patients

For all HIV-infected individuals older than two months, we suggest meningococcal conjugate vaccination (Menactra or Menveo) (Grade 2C).

Growing evidence has suggested that HIV-infected individuals have a disproportionate incidence of invasive meningococcal disease, with an estimated risk 5 to 13 times that of the general population. Because of this, the Centers for Disease Control and Prevention in the United States now recommends meningococcal conjugate vaccination (with MenACWY-CRM [Menveo] or MenACWY-D [Menactra]) for all HIV-infected individuals older than two months [11]. This includes a primary vaccine series for those who have not previously received it and interval booster doses every several years; the precise schedule depends on the age of the patient (table 1). Individuals may also have separate indications for serogroup B meningococcal vaccination. Evidence of vaccine efficacy in HIV-infected patients is limited to immunologic outcomes. (See "Immunizations in HIV-infected patients", section on 'Meningococcal vaccine' and "Meningococcal vaccines".)


HPV vaccine dosing for individuals younger than 15 years

For individuals younger than 15 years, we advise administration of human papillomavirus (HPV) vaccine in two doses separated by six months. Those 15 years and older should continue to receive a three-dose vaccine series.

For individuals younger than 15 years receiving human papillomavirus (HPV) vaccination, two vaccine doses administered at least six months apart are now recommended by the Centers for Disease Control and Prevention in the United States [12]. This new vaccine schedule is similar to schedules used in other countries and is supported by data demonstrating that two vaccine doses in young females have similar immunogenicity to three doses. However, the efficacy of fewer than three doses for prevention of cervical neoplastic disease has not been directly established. Three doses are still recommended for individuals older than 15 years because they have lower immunologic responses to HPV vaccination. (See "Recommendations for the use of human papillomavirus vaccines", section on 'Immunization schedule'.)

HEMATOLOGY (October 2016, Modified October 2016)

Daratumumab-based regimens in relapsed multiple myeloma

Subject to availability, we recommend a daratumumab-based regimen for the treatment of first relapse in myeloma (Grade 1B).

Two recent multicenter randomized trials including over 1000 patients have demonstrated large improvements in progression-free survival (PFS) when the anti-CD38 monoclonal antibody daratumumab is added to standard regimens in relapsed multiple myeloma. The addition of daratumumab to either lenalidomide plus dexamethasone (POLLUX trial) or to bortezomib plus dexamethasone (CASTOR trial) resulted in substantially improved response rates and PFS with a mild to moderate increase in toxicity [13,14]. Mostly mild infusion reactions were common with the first infusion, but rarely resulted in drug discontinuation. Overall survival data are not yet mature. Based on these results we now recommend a daratumumab-based regimen for the treatment of first relapse in myeloma. (See "Treatment of relapsed or refractory multiple myeloma", section on 'Daratumumab'.)


Mycophenolate mofetil for scleroderma lung disease

For patients with systemic sclerosis who have respiratory symptoms, abnormal and/or declining pulmonary function, imaging evidence of interstitial lung disease, and no active infection, we suggest initiating treatment with mycophenolate mofetil (MMF) (Grade 2B).

Cyclophosphamide has been the suggested treatment for moderate-to-severe interstitial lung disease complicating systemic sclerosis (SSc-ILD) but has well-known toxicity. A recent randomized trial compared mycophenolate mofetil (MMF) with oral cyclophosphamide in 142 patients with SSc-ILD, exertional dyspnea, and features of progressive disease [15]. Pulmonary function and dyspnea improved in both groups, without a significant difference between groups. MMF was better tolerated than cyclophosphamide based on a longer time to patient withdrawal and lower incidence of leukopenia and thrombocytopenia. We now suggest initiating treatment for symptomatic progressive SSc-ILD with mycophenolate, rather than cyclophosphamide, due to comparable efficacy, better safety profile, and the option for longer-term therapy. (See "Treatment and prognosis of interstitial lung disease in systemic sclerosis (scleroderma)", section on 'Choice of an agent'.)

ONCOLOGY (October 2016)

Pembrolizumab for PD-L1 high non-small cell lung cancer

For patients with treatment-naïve advanced non-small cell lung cancer that lacks EGFR or ALK genetic aberrations and expresses PD-L1 on at least 50 percent of tumor cells, we recommend pembrolizumab for initial therapy (Grade 1A).

In a phase III trial enrolling 305 patients with treatment-naïve advanced non- small cell lung cancer (NSCLC) lacking a driver mutation and expressing PD-L1 in at least 50 percent of tumor cells, pembrolizumab monotherapy improved progression-free survival, overall survival, and objective response rate compared with standard platinum-doublet chemotherapy [16]. It was also associated with lower treatment-related adverse effects. These data support our recommendation for frontline pembrolizumab in patients with a tumor that has at least 50 percent tumor cell staining for PD-L1 and lacks a driver mutation. (See "Immunotherapy of non-small cell lung cancer with immune checkpoint inhibition", section on 'First-line setting'.)


Olanzapine for prevention of nausea and vomiting induced by highly emetogenic chemotherapy regimens

For patients receiving cisplatin and other highly emetogenic chemotherapy regimens, we suggest the addition of olanzapine on days 1 through 4 to standard antiemetic therapy (a combination of a 5-HT3 receptor antagonist, dexamethasone, and an NK1R antagonist) (Grade 2B).

The antipsychotic olanzapine may be a particularly useful agent for preventing delayed chemotherapy-induced nausea and vomiting, which is often poorly controlled with conventional antiemetics. The effectiveness of adding olanzapine to a standard antiemetic regimen was shown in a trial in which 380 patients receiving highly emetogenic chemotherapy (cisplatin or doxorubicin/cyclophosphamide for breast cancer) were randomly assigned to dexamethasone, an NK1R antagonist, and a 5-HT3 receptor antagonist plus either olanzapine (10 mg daily orally on days 1 through 4) or placebo [17]. The proportion of patients with no chemotherapy-induced nausea (the primary endpoint) was higher with olanzapine both in the first 24 hours after chemotherapy and in the delayed period. Rates of complete response (no emesis and no use of rescue medication) were also higher with olanzapine over a five-day period. Patients receiving olanzapine had more sedation on day 2 (severe in 5 percent), which resolved despite continued olanzapine. On the basis of this trial, we now suggest the addition of olanzapine on days 1 through 4 to standard antiemetic therapy for patients receiving highly emetogenic chemotherapy. (See "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults", section on 'Olanzapine'.)


Inactivated influenza vaccine for 2016-2017 season in the northern hemisphere

For the 2016-2017 influenza season in the northern hemisphere, we suggest inactivated influenza vaccine (IIV) rather than live attenuated influenza vaccine (LAIV) for the prevention of influenza in both children and adults (Grade 2B).

The effectiveness of seasonal influenza vaccines varies from season to season and is determined by a number of factors, including the match between circulating influenza strains and influenza strains in the vaccine. During the 2015-2016 influenza season, data from the United States Influenza Vaccine Effectiveness Network indicated that inactivated influenza vaccine (IIV) was 63 percent effective in preventing influenza in children, but live attenuated influenza vaccine (LAIV) was not effective [18]. Findings of poor or lower than expected LAIV effectiveness were also noted during the 2013-2014 and 2014-2015 seasons in the United States. These findings are inconsistent with studies sponsored by the manufacturer and studies from other countries that found LAIV was effective (ranging from 46 to 58 percent) during the 2015-2016 season [19-22]; however, LAIV was less effective than IIV in all of these studies [23]. In August 2016, the United States Centers for Disease Control and Prevention recommended that LAIV not be used during the 2016-2017 influenza season [24]. While some countries have elected to continue using LAIV [19], we suggest IIV rather than LAIV for the 2016-2017 influenza season in the northern hemisphere. (See "Seasonal influenza in children: Prevention with vaccines", section on 'IIV versus LAIV' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation'.)


Sofosbuvir-velpatasvir for all genotypes of chronic HCV infection

For patients with chronic genotype 1 or 4 hepatitis C virus (HCV) infection, we suggest ledipasvir-sofosbuvir or sofosbuvir-velpatasvir (Grade 2B). For patients with chronic genotype 2 or 3 HCV infection, we suggest sofosbuvir-velpatasvir (Grade 2B). Depending on clinical factors, some patients with genotype 3 infection may also warrant the addition of ribavirin.

All-oral, direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have proliferated over the past two years. Sofosbuvir-velpatasvir, a coformulated combination of an NS5B and an NS5A inhibitor, is the first such regimen that has high, well-established efficacy for all genotypes, even in patients with cirrhosis or prior treatment failure with interferon-based regimens [25-27]. This agent was approved by the US Food and Drug Administration in June 2016 and is now our preferred or one of our preferred regimens for adults with chronic HCV infection of any genotype because of its efficacy, simplicity of administration, and limited drug interactions (algorithm 1 and algorithm 2 and algorithm 3 and algorithm 4). Sofosbuvir-velpatasvir is given for 12 weeks for all genotypes. For genotype 3 infection, the addition of ribavirin may be warranted, depending on the presence of cirrhosis, the prior treatment history, and the presence of mutations associated with NS5A resistance. (See "Treatment regimens for chronic hepatitis C virus genotype 1 infection in adults", section on 'Selection of treatment regimens' and "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults", section on 'Selection of treatment regimen' and "Treatment regimens for chronic hepatitis C virus genotypes 4, 5, and 6 infection in adults", section on 'Selection of treatment regimens'.)

ONCOLOGY (June 2016)

Choice of adjuvant chemotherapy for resected pancreatic cancer

Following resection of pancreatic cancer, we suggest six months of combination chemotherapy with gemcitabine plus capecitabine rather than gemcitabine monotherapy for most patients (Grade 2B). However, therapy with gemcitabine alone (or, where available, S-1) is a reasonable option, particularly for patients with a borderline performance status or a comorbidity profile that precludes intensive therapy.

Adjuvant chemotherapy is recommended for all patients with resected pancreatic cancer. The standard approach has been gemcitabine monotherapy or, where available, S-1 alone. The benefit of a two-drug regimen was tested in the ESPAC-4 trial, which randomly assigned 730 patients with resected pancreatic adenocarcinoma to six months of gemcitabine with or without capecitabine [28]. Combination therapy was associated with significantly longer median overall survival (28 versus 25.5 months) and twice as many patients remaining alive at five years (19 versus 9). Severe diarrhea, hand-foot syndrome, and neutropenia were all significantly more common with combined therapy.

For most patients we suggest six months of combination chemotherapy with gemcitabine plus capecitabine rather than gemcitabine monotherapy after resection of pancreatic cancer. However, therapy with gemcitabine or S-1 alone remains a reasonable option, particularly for patients with a borderline performance status or a comorbidity profile that precludes intensive therapy. (See "Treatment for potentially resectable exocrine pancreatic cancer", section on 'Gemcitabine plus capecitabine'.)

ONCOLOGY (May 2016)

No survival benefit from chemoradiotherapy after initial chemotherapy for locally advanced pancreatic cancer

For most patients with locally advanced pancreatic cancer who are not considered candidates for surgical exploration after initial chemotherapy, we suggest continued chemotherapy rather than chemoradiotherapy (Grade 2B). However, for patients in whom resection is being considered, chemoradiotherapy is still advised in an attempt to increase the likelihood of a complete resection.

There is no consensus as to the best approach for patients with locally advanced pancreatic cancer. Given that initial chemoradiotherapy (CRT) has not demonstrated a consistent survival benefit, and that up to one-third of patients develop overt metastases during the initial phase of treatment, it had been hoped that reserving CRT for patients without metastases after initial chemotherapy would improve survival. However, data from the randomized LAP-07 trial suggest no survival benefit from CRT compared with continued systemic chemotherapy alone, at least for patients treated initially with gemcitabine monotherapy [29].

For patients who do not progress following initial chemotherapy, subsequent therapy depends on whether the patient is a candidate for resection. For patients in whom resection is being considered, we continue to suggest combined treatment with external beam radiotherapy plus concomitant low-dose fluorouracil (eg, 200 mg/m2 daily), in an attempt to increase the rate of complete (R0) resection. For most patients with truly unresectable tumors following initial chemotherapy, we now suggest continued chemotherapy rather than CRT. However, CRT may be appropriate for selected patients, such as those with localized disease and a good performance status who cannot tolerate further chemotherapy. (See "Initial chemotherapy and radiation for nonmetastatic locally advanced unresectable and borderline resectable exocrine pancreatic cancer".)


Option for shortened MDR-TB regimen in updated WHO guidelines

Consistent with WHO updated guidelines for patients with multidrug-resistant tuberculosis (MDR-TB), we suggest a shortened 9 to 12-month MDR-TB regimen for nonpregnant patients who have no extrapulmonary disease, an isolate known to be susceptible to fluoroquinolones and injectable antituberculous agents, and no prior exposure to second-line agents for more than one month (Grade 2C).

The conventional treatment regimen for multidrug-resistant tuberculosis (MDR-TB) consists of a fluoroquinolone, an injectable agent, and at least two other core second-line agents for a total duration of 20 to 26 months. Updated World Health Organization (WHO) guidelines present the option of a shortened regimen for nonpregnant patients with MDR-TB who have no extrapulmonary disease, an isolate known to be susceptible to fluoroquinolones and injectable antituberculous agents, and no prior exposure to second-line agents for more than one month [30]. The shortened regimen consists of an intensive phase (four to six months of high-dose isoniazid, ethambutol, pyrazinamide, gatifloxacin [or moxifloxacin], kanamycin, prothionamide, and clofazimine) followed by a continuation phase (five months of ethambutol, pyrazinamide, gatifloxacin [or moxifloxacin], and clofazimine). Support for this regimen comes in part from a large study from Bangladesh that reported high rates of favorable bacteriologic outcomes with a similar 9 to 12-month regimen [31]. The new WHO guidance also indicates that patients with rifampin monoresistance should be treated as for MDR-TB. Patients with known or suspected MDR-TB who do not meet criteria for the shortened MDR-TB regimen should be treated with the conventional regimen. (See "Treatment and prevention of drug-resistant tuberculosis", section on 'General principles'.)


Surgical revascularization in patients with coronary disease and left ventricular systolic dysfunction

For patients with ischemic cardiomyopathy (LVEF 35 percent or less) and coronary artery disease that is amenable to surgical revascularization, we suggest the combination of surgical revascularization and medical therapy rather than medical therapy alone (Grade 2B). Medical therapy alone is a reasonable option for patients who prioritize concerns about early CABG-associated morbidity and a small risk of early mortality over an overall decrease in longer-term mortality.

Most observational studies suggest that surgical revascularization in patients with ischemic cardiomyopathy (left ventricular ejection fraction [LVEF] of 35 percent or less) improves survival compared with medical therapy. Previously reported five-year outcomes of the randomized Surgical Treatment for Ischemic Heart Failure (STICH) trial comparing surgical revascularization with medical therapy alone showed a trend toward reduced mortality following surgical revascularization, but this primary outcome did not achieve statistical significance. An updated report, the STICH Extension Study (STICHES), extended the follow-up to a median of 9.8 years and found a significant 7 percent absolute reduction in total mortality for patients who underwent surgical revascularization [32]. On the basis of this new evidence, we have revised our previous suggestion for initial management with medical therapy alone for most patients with LVEF 35 percent or less and coronary artery disease amenable to coronary artery bypass graft (CABG) surgery. For such patients, we now suggest the combination of surgical revascularization and medical therapy rather than medical therapy alone. This suggestion is based primarily on the long-term absolute reduction in mortality over the 10 years following CABG surgery. Based on the small but nontrivial early mortality risk associated with CABG surgery as well as other post-CABG morbidities, patients may also reasonably choose medical therapy as the initial treatment option. (See "Ischemic cardiomyopathy: Treatment and prognosis", section on 'Randomized trials'.)


Indications for antibiotics in the management of skin abscess

We suggest antibiotic therapy as adjunctive therapy to incision and drainage for patients with a skin abscess that is ≥2 cm (Grade 2B).

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has raised uncertainty regarding the role of antimicrobial therapy for treatment of skin abscess following incision and drainage. In a randomized trial including 1220 patients >12 years of age (median 35 years) with drained skin abscess (≥2 cm in diameter) comparing trimethoprim sulfamethoxazole (TMP-SMX, 320 mg/1600 mg twice daily) with placebo, the cure rate 7 to 14 days after treatment was higher in the TMP-SMX group (80.5 versus 73.6 percent); wound cultures were positive for MRSA in 45 percent of cases [33]. Based on these findings, abscess size ≥2 cm in diameter is a useful threshold for guiding decisions regarding use of antibiotic therapy for adjunctive treatment of skin abscess.

Additional factors for which we recommend antibiotic therapy include the presence of multiple lesions, extensive surrounding cellulitis, associated comorbidities or immunosuppression, signs of systemic infection, or inadequate clinical response to incision and drainage alone; we suggest antibiotic therapy for patients with an indwelling device or high risk for transmission of S. aureus to others. For otherwise healthy patients with none of these factors, we suggest not administering antimicrobial therapy. (See "Cellulitis and skin abscess: Treatment".)

HEMATOLOGY (March 2016, Modified March 2016)

Ibrutinib in older adults with newly diagnosed CLL

For older adults with symptomatic CLL, we suggest single agent ibrutinib as initial treatment, rather than chlorambucil plus a novel anti-CD20 monoclonal antibody (obinutuzumab or ofatumumab) (Grade 2B).

Ibrutinib is commonly used for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and for the initial treatment of patients with CLL who carry a deletion in chromosome 17. Until now, there was little data regarding its use in other patients with previously untreated disease. In a phase III trial (RESONATE-2), 269 older adults with previously untreated CLL were randomly assigned to initial therapy with ibrutinib or chlorambucil [34]. Ibrutinib was better tolerated and resulted in higher response rates and superior rates of progression-free and overall survival at two years. These results led to the approval of ibrutinib by the US Food and Drug Administration for the initial treatment of CLL [35]. Ibrutinib is now our preferred therapy for previously untreated older adults with CLL. We continue to use fludarabine-based therapies for younger patients. (See "Selection of initial therapy for symptomatic or advanced chronic lymphocytic leukemia", section on 'Ibrutinib'.)


Agent selection for anticoagulation in venous thromboembolism

For long-term anticoagulation for venous thromboembolism in most nonpregnant patients who do not have severe renal insufficiency or active cancer, we suggest a direct oral anticoagulant (ie, apixaban, edoxaban, rivaroxaban, or dabigatran) rather than other agents (Grade 2B).

Guidelines for the treatment of acute venous thromboembolism (VTE) were issued by The American College of Chest Physicians (ACCP) [36]. Compared with earlier versions of the guidelines, the direct oral anticoagulants (DOACs) apixaban, edoxaban, rivaroxaban, or dabigatran are now the preferred agents for long-term anticoagulation in patients who are not pregnant and do not have active cancer or severe renal insufficiency. This preference was based upon randomized trials that consistently reported similar efficacy, a lower bleeding risk, and improved convenience when compared with warfarin. We agree with this preference for DOACs in patients with acute VTE, understanding that choosing among anticoagulants frequently depends upon availability and cost as well as patient comorbidities and preferences. (See "Venous thromboembolism: Anticoagulation after initial management", section on 'Selection of agent'.)


Stroke prevention in sickle cell disease

For children with sickle cell disease and increased risk for a first ischemic stroke based on transcranial Doppler measurements, who have received chronic transfusion therapy for at least two years and who meet criteria for hydroxyurea therapy based on the TWiTCH trial, we suggest transition to hydroxyurea (Grade 2C).

Individuals with sickle cell disease (SCD) are at risk for ischemic and hemorrhagic stroke. Transcranial Doppler (TCD) measures blood flow rate in intracranial arteries and is used to assess stroke risk in children with SCD. Children with increased TCD velocities are treated with chronic prophylactic transfusions to reduce the risk of ischemic stroke. The recently published TWiTCH trial (TCD With Transfusions Changing to Hydroxyurea) randomly assigned 121 children who had completed a period of chronic transfusions and who met study criteria (related to hemoglobin S levels with transfusion, TCD velocities, magnetic resonance angiographic findings, ability to comply with treatment and monitoring, and response to hydroxyurea) to transition to hydroxyurea therapy or to continue transfusions [37]. After approximately two years of follow-up, TCD velocities were similar in both groups and there were no strokes in either group. For children who would have met criteria for the TWiTCH trial, we suggest transitioning to hydroxyurea after two or more years of chronic transfusion, with transfusions tapered and hydroxyurea dosing gradually increased during the transition, as done in the trial. We continue to recommend chronic transfusions for all patients with SCD who have had an ischemic stroke (ie, for secondary prevention). (See "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Chronic transfusion followed by transition to hydroxyurea'.)

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