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What's new in hematology
Official reprint from UpToDate® ©2017 UpToDate®
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What's new in hematology
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2017. | This topic last updated: Aug 21, 2017.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.


Liposomal daunorubicin-cytarabine for treatment-related AML (August 2017)

Optimal management of treatment-related acute myeloid leukemia (t-AML) is not well defined. Based on preliminary results of a phase III trial in which liposome-encapsulated daunorubicin-cytarabine improved median overall survival compared with conventional "7+3" administration of daunorubicin and cytarabine (10 versus 6 months), and had tolerable adverse effects (eg, bleeding, infections, mucositis), the US Food and Drug Administration approved this product for patients with newly diagnosed t-AML [1]. For patients with t-AML whose performance status permits an aggressive therapeutic approach, we offer liposome-encapsulated daunorubicin and cytarabine as an alternative to conventional 7+3 therapy. (See "Therapy-related myeloid neoplasms: Acute myeloid leukemia and myelodysplastic syndrome", section on 'Treatment'.)

Updated guidelines for empiric antifungal therapy for children with fever and neutropenia (June 2017)

Updated guidelines from the International Pediatric Fever and Neutropenia Guideline Panel consider children with cancer or hematopoietic cell transplant as high risk for invasive fungal infection if they have acute myelogenous leukemia, high-risk acute lymphoblastic leukemia, relapsed acute leukemia, neutropenia for >10 days, or are receiving high-dose corticosteroids [2]. In contrast to the previous guideline, they weakly recommend against initiating empiric antifungal therapy for low-risk patients, using serial galactomannan to guide antifungal therapy, and obtaining computed tomography images of the sinuses before initiating antifungal therapy unless the patient has localizing signs or symptoms. They also now suggest abdominal imaging before initiation of antifungal therapy in high-risk patients. (See "Fever in children with chemotherapy-induced neutropenia", section on 'Antifungal therapy'.)

Midostaurin approved for induction therapy of AML with FLT3 mutations (April 2017)

Mutations of the FLT3 gene are found in approximately one-third of adults with acute myeloid leukemia (AML) and are associated with worse outcomes in patients undergoing induction therapy with cytarabine and daunorubicin. In a phase III trial of over 700 patients, the multitargeted small molecule FLT3 inhibitor midostaurin improved event-free and overall survival when added to standard induction therapy in adults with AML demonstrating FLT3 mutations [3]. Midostaurin is now approved by the US Food and Drug Administration in this setting [4], and we suggest the addition of midostaurin to induction therapy for treatment of adults with newly diagnosed AML who are FLT3 mutation-positive. (See "Induction therapy for acute myeloid leukemia in younger adults", section on 'FLT3 mutation positive AML'.)

Arsenic trioxide plus ATRA for acute promyelocytic leukemia (March 2017)

Arsenic trioxide (ATO) combined with all-trans retinoic acid (ATRA) can induce complete molecular remissions in acute promyelocytic leukemia (APL) without the use of cytotoxic chemotherapy. In longer-term follow-up of the landmark international study, APL0406, patients with low or intermediate-risk APL (white blood cell <10,000/microL) were evaluated through the consolidation and maintenance phases of therapy [5]. In this analysis, ATO plus ATRA was associated with less toxicity, fewer deaths during induction therapy, and fewer short-term and long-term relapses compared with ATRA plus conventional chemotherapy. We recommend treatment with ATO plus ATRA for patients with low or intermediate-risk APL. (See "Initial treatment of acute promyelocytic leukemia in adults", section on 'Arsenic trioxide plus ATRA'.)

Blinatumomab for relapsed/refractory ALL (March 2017)

For patients with relapsed or refractory lymphoblastic leukemia (ALL), the initial goal of treatment is achievement of complete remission, but such remissions are typically short-lived; cure generally requires allogeneic hematopoietic cell transplantation (HCT). Blinatumomab is a bispecific antibody directed against both CD19 (expressed on the leukemic blast cells) and CD3 on the patient’s own T lymphocytes. In a randomized international trial of approximately 400 patients with relapsed or refractory ALL, blinatumomab resulted in superior overall survival, event-free survival, and response rate compared with state-of-the-art cytarabine-based chemotherapy [6]. Despite substantial toxicities (which are comparable to conventional chemotherapy), we now recommend blinatumomab, rather than chemotherapy, for remission induction prior to allogeneic HCT in relapsed or refractory ALL. (See "Treatment of relapsed or refractory acute lymphoblastic leukemia in adults", section on 'Blinatumomab'.)

Decline in secondary malignancies among childhood cancer survivors (March 2017)

In addition to recurrences of primary malignancies, cancer survivors are at a higher risk for secondary malignancies as a result of their cancer treatments. In a study of over 23,000 survivors of childhood cancer, 6.9 percent of survivors experienced neoplasms, most commonly breast or thyroid cancer, over a mean follow-up of 20.5 years [7]. The frequency of subsequent malignancies decreased by decade of diagnosis (2.1, 1.7 and 1.3 percent for the 1970s, 1980s and 1990s, respectively). This decline may be related to a decrease in the proportion of individuals receiving radiation and the median radiation dose administered over time. (See "Overview of cancer survivorship care for primary care and oncology providers".)

Molecular markers of prognosis following transplant in myelodysplastic syndromes (February 2017)

Although allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelodysplastic syndromes (MDS), controversy surrounds candidate selection. Two large retrospective studies of patients with MDS reported that TP53 mutations were associated with shorter overall survival after transplant, though the effect was seen only in the context of a complex karyotype in one of the studies [8,9]. One of the studies also found that RAS signaling pathway mutations were associated with poor outcomes when reduced intensity conditioning regimens were used [8]. These studies suggest that molecular features may increasingly aid in selection of patients with MDS for HCT and influence the choice of conditioning regimen. (See "Hematopoietic cell transplantation in myelodysplastic syndromes", section on 'Cytogenetic and molecular factors'.)

2017 European LeukemiaNet (ELN) prognostic stratification scheme for AML (February 2017)

Cytogenetic and molecular features of acute myelogenous leukemia (AML) permit stratification of patients into various prognostic groups. We prefer the classification system recently updated by the European LeukemiaNet (ELN) (table 1) [10]. This revised schema distinguishes three prognostic categories and incorporates data on additional gene mutations (eg, TP53, ASXL1), biallelic mutated CEBPA, the allelic ratio of FLT3-ITD, and effects of specific combinations of such features. These prognostic variables, coupled with the patient's clinical status, often inform key therapeutic decisions regarding management of AML. (See "Prognosis of acute myeloid leukemia", section on 'European LeukemiaNet classification' and "Post-remission therapy for acute myeloid leukemia in younger adults" and "Treatment of relapsed or refractory acute myeloid leukemia".)


Oral glutamine for sickle cell disease (July 2017)

In July of 2017, the US Food and Drug Administration approved an L-glutamine formulation (Endari) for reducing vasoocclusive complications in individuals with sickle cell disease (SCD). Approval was based on a trial (as yet unpublished) in which 230 individuals with SCD who had frequent pain episodes were treated with daily oral glutamine or placebo for a year [11,12]. Compared with placebo, glutamine reduced the frequency of pain episodes, acute chest syndrome, and hospitalization. We await publication of the trial before incorporating L-glutamine into routine clinical care for individuals with SCD. (See "Vasoocclusive pain management in sickle cell disease", section on 'L-glutamine'.)

Low-dose ferrous sulfate for iron deficiency anemia (June 2017)

For infants and children with iron deficiency anemia, standard oral iron dosing is 3 to 6 mg/kg elemental iron per day, but the optimal dose and preparation have not been established. Now, a study reports that ferrous sulfate 3 mg/kg once daily without food was effective in most patients and was more effective than an equivalent dose of an iron polysaccharide complex formulation [13]. These findings support administering ferrous sulfate at the low end of the standard dose range as first-line treatment for nutritional iron deficiency in children. (See "Iron deficiency in infants and young children: Treatment", section on 'Dose and scheduling'.)

Cardiovascular risk in sickle cell trait (March 2017)

Sickle cell trait is a benign carrier state, but concerns have been raised about increased cardiovascular risk factors. Analyses from several large cohorts have now provided reassuring evidence that there are no differences in the risks of diabetes, hypertension, or heart failure in blacks with sickle cell trait compared with the general black population [14,15]. (See "Sickle cell trait", section on 'No increased risk of hypertension, diabetes, or heart failure'.)

Experimental gene therapy for sickle cell disease (March 2017)

The first case report of gene therapy for sickle cell disease (SCD) has been published [16]. The patient was a 13-year-old boy with SCD who had pain despite treatment with hydroxyurea and transfusions. He received an autologous hematopoietic cell transplant (HCT) using his own hematopoietic cells that had been transduced with a vector to express a modified beta globin gene with anti-sickling properties. After HCT, he became free of pain and independent of transfusions and analgesics. Additional studies of this approach are underway. (See "Investigational therapies for sickle cell disease", section on 'Gene therapy'.)

Glycated hemoglobin (A1C) in sickle cell trait (March 2017)

In a retrospective cohort study evaluating glycated hemoglobin (A1C) in African Americans with and without sickle cell trait, A1C was lower at any fasting glucose value in patients with sickle cell trait compared with controls [17]. However, the study is limited by its methodology, as mean glucose levels were estimated on the basis of very few measurements, usually a single fasting glucose level or oral glucose tolerance test. A1C correlates best with mean blood glucose over 8 to 12 weeks, raising the possibility that if measured appropriately with frequent glucose measurements over time (multiple daily measurements or continuous glucose monitoring), mean glucose levels may actually have been different between the study populations, with the putative different A1C levels accurately reflecting these different mean glucose levels. We continue to use A1C as one option to diagnose diabetes in patients with sickle cell trait. (See "Estimation of blood glucose control in diabetes mellitus", section on 'Racial variation'.)


Addition of idelalisib to bendamustine plus rituximab in CLL (March 2017)

The combination of idelalisib plus rituximab is one of our preferred treatments for patients with refractory or early relapsing chronic lymphocytic leukemia (CLL). In a multicenter phase III trial of over 400 patients with relapsed/refractory CLL, the addition of idelalisib to the combination of bendamustine plus rituximab (BR) improved progression-free and overall survival, with moderate increases in infection and other toxicities [18]. These results provide further support for the efficacy of idelalisib plus rituximab in relapsed/refractory CLL. We do not usually incorporate bendamustine since the contribution of this agent to the regimen's efficacy is not clear. (See "Treatment of relapsed or refractory chronic lymphocytic leukemia", section on 'Idelalisib'.)

Long-term follow-up of imatinib in CML (March 2017)

Imatinib was the first tyrosine kinase inhibitor (TKI) that specifically targeted BCR-ABL1, the fusion protein that underlies chronic myeloid leukemia (CML). In an analysis of long-term outcomes from the landmark IRIS trial, 83 percent of patients with chronic phase CML treated with imatinib were alive at 10 years [19]. Serious adverse events were uncommon and most frequently occurred in the first year of treatment. These excellent outcomes and favorable toxicity profile support our recommendation to use a BCR-ABL1 TKI (eg, imatinib, dasatinib, or nilotinib) for initial treatment of chronic phase CML. (See "Initial treatment of chronic myeloid leukemia in chronic phase", section on 'IRIS trial'.)


Ibrutinib for treatment of chronic GVHD (August 2017)

Optimal management of patients with steroid-refractory (SR) chronic graft-versus-host disease (GVHD) is poorly defined. Preliminary results of a phase II trial of ibrutinib in 42 such patients reported multiorgan responses (eg, skin, mouth, gastrointestinal tract, liver) in two-thirds, which, for the majority of patients, permitted reduction in steroid dose and improved quality of life [20]. Reported side effects included fatigue, bruising, stomatitis, nausea, diarrhea, cytopenias, and infections. Ibrutinib was approved by the US Food and Drug Administration for treatment of chronic GVHD [21] and is an acceptable alternative to calcineurin inhibitors (eg, cyclosporin, tacrolimus) and other agents for treatment of SR-chronic GVHD. (See "Treatment of chronic graft-versus-host disease", section on 'Ibrutinib'.)

Molecular markers of prognosis following transplant in myelodysplastic syndromes (February 2017)

Although allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelodysplastic syndromes (MDS), controversy surrounds candidate selection. Two large retrospective studies of patients with MDS reported that TP53 mutations were associated with shorter overall survival after transplant, though the effect was seen only in the context of a complex karyotype in one of the studies [8,9]. One of the studies also found that RAS signaling pathway mutations were associated with poor outcomes when reduced intensity conditioning regimens were used [8]. These studies suggest that molecular features may increasingly aid in selection of patients with MDS for HCT and influence the choice of conditioning regimen. (See "Hematopoietic cell transplantation in myelodysplastic syndromes", section on 'Cytogenetic and molecular factors'.)

Palliative care during hematopoietic cell transplantation (February 2017)

For patients with serious life-threatening illness, comprehensive palliative care can be successfully integrated with disease-modifying treatment. The benefits of delivering palliative care alongside potentially curative treatment were shown in a randomized trial of inpatient palliative care consultation versus usual transplant care in 160 adults with hematologic malignancies undergoing autologous or allogeneic hematopoietic cell transplantation [22]. At two weeks posttransplant, the increase in depression, anxiety, and overall symptom burden was less in the intervention group, and the decrease in quality of life (QOL) was also smaller. Depression and QOL benefits persisted at three months. (See "Benefits, services, and models of subspecialty palliative care", section on 'Rationale for palliative care'.)


Underdosing of direct oral anticoagulants (August 2017)

The oral direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban (collectively called direct oral anticoagulants [DOACs] or newer oral anticoagulants [NOACs]) have been available for several years. Two real-world studies in two populations (venous thromboembolism and atrial fibrillation) have now demonstrated that DOACs are frequently given at doses other than that recommended in guidelines and prescribing information [23,24]. Underdosing is more frequent than overdosing (approximately 35 to 50 percent and approximately 10 to 20 percent, respectively). Both studies found that deviations from recommended dosing correlated with increased frequency of thrombotic events. Clinicians should familiarize themselves with prescribing information to avoid adverse outcomes. (See "Direct oral anticoagulants and parenteral direct thrombin inhibitors: Dosing and adverse effects", section on 'Clinician familiarity with dosing'.)

Two new investigational therapies for hemophilia (July 2017)

Prophylaxis to reduce bleeding in hemophilia currently relies on administration of the deficient clotting factor. Two new investigational strategies have been demonstrated to reduce bleeding:

Emicizumab, a bifunctional monoclonal antibody that substitutes for the function of factor VIII, was demonstrated to reduce bleeding in people with factor VIII deficiency (hemophilia A) with factor VIII inhibitors (annualized bleeding rate reduced from 23 to 3 events) [25].

Fitusiran, an antisense oligonucleotide that reduces levels of antithrombin, was demonstrated to reduce bleeding in people with hemophilia A or hemophilia B (annualized bleeding rate reduced from 3 to 0 events) [26].

These therapies are not yet available for clinical use. (See "Hemophilia A and B: Routine management including prophylaxis", section on 'Prophylactic therapies under development'.)

Confirmatory data on idarucizumab for dabigatran reversal (July 2017)

Idarucizumab (pronounced "I-dare-you-cizumab") is a monoclonal antibody fragment against dabigatran that can reverse the anticoagulant effect within minutes. A preliminary report suggested good efficacy in patients with dabigatran-associated bleeding or those undergoing emergency surgery. In a new report of over 500 patients treated with idarucizumab, most had cessation of bleeding or underwent surgery without abnormal bleeding [27]. We continue to suggest idarucizumab for clinically significant bleeding or emergency surgery in patients on dabigatran with a history or laboratory testing that suggest they are actively anticoagulated. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Dabigatran reversal'.)

New oral direct factor Xa inhibitor betrixaban approved (June 2017)

The US Food and Drug administration has approved a new oral direct factor Xa inhibitor, betrixaban, for venous thromboembolism prophylaxis in acutely ill medical patients [28]. Betrixaban (brand name Bevyxxa) is taken at a dose of 160 mg on day 1 followed by 80 mg once daily for the duration of thromboprophylaxis. In a trial in which over 7500 patients hospitalized for an acute medical illness were randomly assigned to receive betrixaban or the low molecular weight heparin enoxaparin for 35 to 42 days, betrixaban was associated with a trend towards greater efficacy and a similar risk of bleeding compared with enoxaparin. (See "Direct oral anticoagulants and parenteral direct thrombin inhibitors: Dosing and adverse effects" and "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults".)

Neuraxial anesthesia in parturients with thrombocytopenia (June 2017)

The risk of spinal epidural hematoma (SEH) associated with neuraxial anesthesia (NA) techniques in patients with thrombocytopenia is poorly defined because SEH is rare. In a systematic review of over 1500 NA procedures in parturients with platelet counts less than 100,000 /microL, no cases of epidural hematoma requiring decompressive laminectomy were identified [29]. A statistical analysis based on data from this cohort suggests that the incidence of epidural hematoma may range from 0.2 percent (for platelet counts 70 to 100,000/microL) to 11 percent (for platelet counts <49,000/microL). These estimates may inform clinical decision-making regarding performance of NA in parturients with thrombocytopenia. (See "Adverse effects of neuraxial analgesia and anesthesia for obstetrics", section on 'Neuraxial analgesia and low platelets'.)

Tranexamic acid for management of postpartum hemorrhage (May 2017)

Tranexamic acid, an antifibrinolytic drug, reduces bleeding in surgical and trauma patients. In a pragmatic randomized trial involving over 20,000 women with postpartum hemorrhage in over 20 countries (the World Maternal Antifibrinolytic Randomized Trial [WOMAN]), tranexamic acid, compared with placebo, reduced the relative risk of death due to bleeding by 20 to 30 percent, reduced the incidence of laparotomy to control bleeding, and was not associated with an increase in adverse effects [30]. Overall mortality was not reduced. We now recommend administration of tranexamic acid as a component of the treatment for postpartum hemorrhage. (See "Postpartum hemorrhage: Medical and minimally invasive management".)

Rivaroxaban for treatment of superficial vein thrombosis (May 2017)

Short-term anticoagulation is recommended for treatment of superficial vein thrombosis (SVT) in patients at high risk for venous thromboembolism (VTE). The phase 3b SURPRISE trial randomly assigned over 400 patients with SVT to oral rivaroxaban (a direct factor Xa inhibitor) or subcutaneous fondaparinux and found that both groups had similar rates of symptomatic VTE, progression or recurrence of SVT, and all-cause mortality at 45 days [31]. There were no major bleeds in either group, but clinically relevant nonmajor bleeding occurred more often in the rivaroxaban group. Thus, rivaroxaban appears to be an effective anticoagulant for patients with SVT and may be a more convenient and less expensive option than subcutaneous therapy. (See "Phlebitis and thrombosis of the superficial lower extremity veins", section on 'Increased risk for thromboembolism'.)

PLASMIC score for TTP (March 2017)

Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening condition in which platelet microthrombi can cause organ injury and infarction. Most patients with TTP have severely reduced activity of the von Willebrand factor cleaving protease ADAMTS13, but results of ADAMTS13 testing may take days to receive. The PLASMIC score was developed to predict the likelihood of ADAMTS13 activity <10 percent in adults with suspected TTP. In three cohorts involving over 500 patients, a high PLASMIC score was predictive of ADAMTS13 <10 percent [32,33]. This score cannot be used to confirm or exclude the diagnosis of TTP, but it may be helpful when there is lack of clarity regarding the most likely diagnosis and/or the need to initiate TTP therapy. (See "Acquired TTP: Clinical manifestations and diagnosis", section on 'Diagnostic evaluation'.)

Aspirin for prevention of preeclampsia (February 2017)

Low-dose aspirin therapy during pregnancy reduces the occurrence of preeclampsia in high-risk women, but questions remain about optimum dosing and timing. In one recent meta-analysis, the optimum aspirin dose appeared to be 100 to 150 mg, with favorable effects limited to initiation before 16 weeks of gestation [34]. In another recent meta-analysis with a different design, aspirin was similarly effective whether initiated before or after 16 weeks of gestation; optimum dosing was not assessed [35]. For women at high risk of developing preeclampsia, we continue to suggest initiating aspirin 81 mg daily at the end of the first trimester because this dose is readily available and early initiation is both safe and effective. If aspirin is not initiated at this time, initiation after 16 weeks, but before symptoms develop, also appears to be effective. (See "Preeclampsia: Prevention", section on 'Meta-analysis'.)


Brentuximab vedotin for CD30-expressing cutaneous lymphomas (July 2017)

Mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (PC-ALCL) are CD30-expressing tumors that frequently relapse after surgical resection, radiation therapy, and/or topical therapies. In an international, phase III trial of 128 patients with MF or PC-ALCL that had progressed despite earlier methotrexate or radiation, brentuximab vedotin (BV; anti-CD30 monoclonal antibody conjugated with chemotherapy) was more effective at controlling skin disease, achieving durable responses (at least four months), maintaining progression-free survival, and providing symptomatic relief than the physician’s choice of bexarotene or methotrexate [36]. Peripheral neuropathy occurred in two-thirds of patients. BV is now an acceptable alternative for treatment of MF or PC-ALCL that relapses after initial systemic treatment. (See "Primary cutaneous anaplastic large cell lymphoma", section on 'Brentuximab vedotin' and "Treatment of advanced stage (IIB to IV) mycosis fungoides", section on 'Brentuximab vedotin'.)

Subcutaneous formulation of rituximab for certain lymphomas (June 2017)

Most studies evaluating the efficacy of the anti-CD20 monoclonal antibody rituximab in the treatment of B-cell lymphomas have utilized intravenous administration. A subcutaneous formulation (rituximab-hyaluronidase) has been developed, which can be administered over a shorter time and uses a fixed dose that varies with histology and chemotherapy regimen. Randomized trials have demonstrated comparable efficacy and safety of the two formulations in patients with follicular lymphoma, diffuse large B cell lymphoma, or chronic lymphocytic leukemia [37-39]. The subcutaneous formulation (rituximab-hyaluronidase) is now an option for patients with these lymphoma subtypes who have tolerated at least one full dose of intravenous rituximab [40]. (See "Initial treatment of advanced stage (III/IV) follicular lymphoma", section on 'Immunotherapy-based treatment'.)

Bendamustine plus rituximab in mantle cell or clinically indolent lymphoma (June 2017)

The preferred initial chemotherapy regimen for patients with mantle cell lymphoma (MCL) or clinically indolent lymphoma is not known, and clinical practice varies. Initial reports of two randomized trials that together included over 900 patients suggested that bendamustine plus rituximab (BR) is less toxic than and at least equally efficacious to cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP). Long-term follow-up confirms these results with no new toxicity signals [41,42]. In the StiL trial, BR demonstrates a clear progression-free survival (PFS) advantage with 10-year follow-up [41]. In the BRIGHT trial, PFS with BR is at least equivalent, and may be superior to, R-CHOP in those with MCL [42]. Neither study demonstrates a survival difference between arms. These results support our preference for the off-label use of BR in clinically indolent lymphoma or MCL. (See "Initial treatment of mantle cell lymphoma", section on 'Conventional chemoimmunotherapy' and "Initial treatment of advanced stage (III/IV) follicular lymphoma", section on 'Chemoimmunotherapy'.)


Post-transplant lenalidomide maintenance in multiple myeloma (August 2017)

Three large randomized trials have shown a progression-free survival (PFS) benefit with lenalidomide maintenance versus placebo or observation in patients undergoing autologous hematopoietic cell transplantation (HCT) for newly diagnosed multiple myeloma (MM), but in each, estimates in overall survival (OS) were imprecise. In a meta-analysis using data from the >1200 patients enrolled in these three trials, post-transplant maintenance with lenalidomide improved both PFS and OS [43]. Although lenalidomide maintenance showed a survival benefit in most subgroups, a survival benefit could not be demonstrated in patients with high-risk cytogenetics. These results support our preference for post-HCT lenalidomide maintenance in patients with standard-risk MM; in contrast, we offer post-HCT bortezomib maintenance to patients with intermediate- or high-risk MM. (See "Autologous hematopoietic cell transplantation in multiple myeloma", section on 'Standard-risk disease'.)

Daratumumab, pomalidomide, and dexamethasone for relapsed multiple myeloma (August 2017)

The anti-CD38 monoclonal antibody daratumumab is one of our preferred agents for the treatment of patients with relapsed or refractory multiple myeloma (MM). In a prospective trial of daratumumab, pomalidomide, and dexamethasone in multiply relapsed MM, this regimen had an overall response rate of 60 percent and a median progression-free survival of 8.8 months, and was well tolerated [44]. Based on this and other data, the US Food and Drug Administration has approved this regimen for patients with MM who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. We reserve this regimen for patients with multiply relapsed disease unresponsive to lenalidomide (table 2). (See "Treatment of relapsed or refractory multiple myeloma", section on 'Efficacy'.)

Denosumab versus zoledronic acid in multiple myeloma (June 2017)

Denosumab is a monoclonal antibody used for the treatment of solid tumor bone metastases. Its efficacy in patients with multiple myeloma (MM) is unclear. In preliminary results of a trial of 1700 patients with previously untreated MM and measurable bone lesions, those randomly assigned to denosumab versus zoledronic acid experienced similar time to first skeletal-related event and overall survival, longer median progression-free survival, and lower rates of renal toxicity, but had higher rates of osteonecrosis of the jaw [45]. Despite these data, further follow-up is needed to determine the role of denosumab for patients with MM. (See "The use of osteoclast inhibitors in patients with multiple myeloma", section on 'Denosumab'.)

Early versus delayed transplant for multiple myeloma (April 2017)

Autologous hematopoietic cell transplantation (HCT) extends the survival of, though does not cure, patients with multiple myeloma. Timing for HCT was evaluated in a trial of 700 adults ≤65 years of age who had completed induction therapy with bortezomib, lenalidomide, and dexamethasone (VRD) [46]. Early transplant, following induction with VRD, was compared with delayed transplant (consolidation VRD and transplant at the time of first relapse). Approximately 80 percent of patients assigned to further VRD underwent HCT at relapse. With a median follow-up of 44 months, early HCT resulted in a longer progression-free survival, but no difference in overall survival. We take patient preference, age, genetic risk profile, and logistic factors into account to individualize the timing of HCT. (See "Autologous hematopoietic cell transplantation in multiple myeloma", section on 'Timing of first HCT'.)

Chemotherapy for C3 glomerulopathy with monoclonal gammopathy (March 2017)

C3 glomerulopathy with monoclonal gammopathy is a form of monoclonal gammopathy of renal significance (MGRS), a group of kidney disorders caused by a monoclonal immunoglobulin that is secreted by a nonmalignant or premalignant B cell or plasma cell clone. A retrospective analysis compared renal outcomes among 50 patients with C3 glomerulopathy with monoclonal gammopathy who were treated with or without chemotherapy directed against the underlying plasma or B cell clone [47]. Treatment with clone-directed chemotherapy was associated with a higher rate of renal response and improved renal survival at a median of 24 months. Importantly, renal survival was significantly higher among patients who achieved a hematologic response with chemotherapy. We typically treat patients who have C3 glomerulopathy with monoclonal gammopathy using chemotherapy based upon the isotype of the circulating monoclonal protein detected in the serum or urine. (See "Diagnosis and treatment of monoclonal gammopathy of renal significance", section on 'Patients with C3 glomerulopathy with monoclonal gammopathy'.)


Opana ER withdrawn from the US market (July 2017)

A long-acting abuse-deterrent formulation of oxymorphone, Opana ER, is being voluntarily withdrawn from the United States (US) market at the request of the US Food and Drug Administration due to concerns related to injection abuse, including reports of thrombotic microangiopathy (TMA) when the oral formulation is injected intravenously (IV) [48-50]. The TMA is thought to be due to an inert component that was added to the formulation to make it crush-resistant and thus deter IV injection. Generic extended-release oxymorphone products remain on the US market. (See "Cancer pain management with opioids: Optimizing analgesia", section on 'Oxycodone, hydrocodone, hydromorphone, and oxymorphone' and "Drug-induced thrombotic microangiopathy", section on 'Drugs of abuse'.)

Discontinuation of eculizumab in complement-mediated hemolytic uremic syndrome (June 2017)

Eculizumab is an effective treatment for complement-mediated hemolytic uremic syndrome (HUS). Monthly intravenous maintenance administration has been the standard of care for patients attaining complete remission. Now, two case series have reported successful discontinuation of eculizumab in most patients, with successful remission after early resumption of therapy in those who relapsed [51,52]. Although these results are promising, further studies are needed to determine the optimal time to discontinue eculizumab therapy and the patient population in whom therapy can be safely discontinued. Until these data are available, the decision to withdraw eculizumab therapy should be made in conjunction with a clinician with expertise in managing patients with complement-mediated HUS. Close monitoring after withdrawal is required so eculizumab can be reinitiated if relapse occurs. (See "Complement-mediated hemolytic uremic syndrome", section on 'Discontinuation'.)

Subcutaneous C1 inhibitor for hereditary angioedema (April 2017, Modified June 2017)

Patients with hereditary angioedema (C1 inhibitor deficiency) develop attacks of angioedema affecting the skin, gastrointestinal tract, and airway, which can be prevented with intravenous infusions of C1 inhibitor, typically given twice weekly. Subcutaneous administration should significantly facilitate self-treatment. In a randomized multicenter trial of 90 children and adults, participants injected a subcutaneous formulation of C1 inhibitor or placebo twice weekly for 16 weeks [53]. Therapy was well tolerated and participants receiving active drug had fewer attacks per month (mean 0.5 versus 4.0 attacks). This formulation was approved by the US Food and Drug Administration (FDA) in June 2017, and approval in Europe is anticipated in the near future. However, it is not yet available for clinical use. (See "Hereditary angioedema: General care and long-term prophylaxis", section on 'Subcutaneous C1 inhibitor'.)

Eltrombopag for adults with acquired severe aplastic anemia unable to undergo HCT (May 2017)

Acquired aplastic anemia (AA) has a high morbidity, and allogeneic hematopoietic cell transplantation (HCT) is suggested as therapy for patients healthy enough to tolerate HCT who have a suitable donor. Immunosuppressive therapy (IST) is offered to those for whom HCT is not an option but is often ineffective in improving outcomes over the long term. A prospective cohort study in adults with acquired severe AA evaluated the effectiveness of IST plus eltrombopag, a thrombopoietin receptor agonist that acts on platelet precursors and hematopoietic stem cells [54]. Eltrombopag plus IST produced higher rates of overall hematologic response at six months compared with responses in a historical cohort (80 to 94 percent versus 66 percent for the historical group). Based on these findings, we now suggest administration of eltrombopag plus IST for individuals with acquired severe AA who are not candidates for allogeneic HCT. (See "Treatment of aplastic anemia in adults", section on 'Evidence for efficacy'.)

Autoimmune hemolytic anemia after recovery from babesiosis (March 2017)

Babesiosis is known to cause hemolysis from direct parasite-mediated lysis of red blood cells in the circulation. A new association of Babesia infection with autoimmune (autoantibody-mediated) hemolytic anemia (AIHA) has been reported [55]. In a series of 86 patients treated for Babesia, 7 percent developed this complication. AIHA was diagnosed two to four weeks after recovery from the infection and was restricted to individuals who were asplenic due to a prior splenectomy. (See "Warm autoimmune hemolytic anemia: Clinical features and diagnosis", section on 'Underlying causes'.)

E. coli O157:H7 outbreak associated with soy nut butter (March 2017)

Escherichia coli O157:H7, which causes bloody diarrhea and is associated with the hemolytic-uremic syndrome, is typically transmitted through contaminated beef products and produce, but other foods have also been implicated in outbreaks. In the United States, a particular brand of soy nut butter (I.M. Healthy) has been linked to a multistate E. coli O157:H7 outbreak that has affected mainly children [56]. Although the soy nut butter products have been recalled, individuals should be advised to avoid and discard any remaining product, and the possibility of E. coli O157:H7 infection should be considered in exposed patients with diarrheal illnesses. Details on the outbreak can be found on the Centers for Disease Control and Prevention website. (See "Microbiology, pathogenesis, epidemiology, and prevention of enterohemorrhagic Escherichia coli (EHEC)", section on 'Other foods'.)

Masitinib in indolent and smoldering systemic mastocytosis (February 2017)

There are limited treatment options for indolent and smoldering systemic mastocytosis (ISM and SSM, respectively). Masitinib is a tyrosine kinase with activity against at least three mast cell signaling molecules. In a phase III trial of 135 severely symptomatic patients with ISM or SSM, oral masitinib reduced symptoms, tryptase levels, and urticaria pigmentosa lesions compared with placebo, although it was associated with side effects requiring discontinuation in 24 percent [57]. The drug is under regulatory review, and further data about the safety and efficacy are needed before its use can be recommended. (See "Systemic mastocytosis: Management and prognosis", section on 'Clinical trials'.)

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