ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

What's new in hematology

What's new in hematology
Literature review current through: Jan 2024.
This topic last updated: Jan 31, 2024.

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.

ACUTE LEUKEMIAS AND MYELODYSPLASTIC SYNDROMES

No benefit of routine thromboprophylaxis for children with ALL (January 2024)

Whether routine thromboprophylaxis reduces the risk of thrombotic complications in patients with acute lymphoblastic leukemia (ALL) has been debated. In a multicenter randomized trial of over 500 children and adolescents with newly diagnosed pre-B or T cell ALL, patients assigned to prophylactic anticoagulation with apixaban compared with standard care alone had similar rates of symptomatic venous thrombosis (1.6 versus 2.3 percent, respectively) and asymptomatic venous thrombosis (11 versus 15 percent) [1]. Nonmajor bleeding episodes (mostly epistaxis) occurred more frequently in the apixaban group (4 versus 1 percent). These data do not support the routine use of thromboprophylaxis in children with ALL, although it may be warranted in selected patients with additional risk factors for thrombosis. (See "Thromboembolism in children with cancer", section on 'Primary prevention'.)

Quizartinib approved for AML with FLT3 internal tandem duplication (August 2023)

For acute myeloid leukemia (AML) with mutated FLT3, addition of the tyrosine kinase inhibitor (TKI) midostaurin to intensive induction therapy has improved survival outcomes; other novel TKIs are emerging. The US Food and Drug Administration has approved use of quizartinib, another TKI, with chemotherapy for patients with AML with FLT3 and internal tandem duplications (ITD) based on overall survival benefits compared with chemotherapy alone, with minimal added toxicity [2]. The cardiac QT interval should be assessed and hypokalemia and hypomagnesemia corrected before treatment, as quizartinib prolongs the QT interval and has been associated with torsade de pointes and cardiac arrest. For patients with FLT3-mutated AML, we recommend addition of either midostaurin (for any FLT3 mutation) or quizartinib (for FLT3-ITD) to intensive induction chemotherapy. (See "Acute myeloid leukemia: Induction therapy in medically fit adults", section on 'AML with mutated FLT3'.)

CHRONIC LEUKEMIAS AND MYELOPROLIFERATIVE NEOPLASMS

Ibrutinib plus venetoclax in previously untreated CLL/SLL (December 2023)

In two recent studies in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), ibrutinib plus venetoclax improved progression-free and overall survival compared with chemoimmunotherapy, with acceptable toxicity [3,4]. In one, all patients received 15 months of ibrutinib plus venetoclax, while in the other the duration of therapy was guided by measurable residual disease assessments. The two approaches have not been directly compared. These data support ibrutinib plus venetoclax as an effective initial option for CLL/SLL; fixed-duration ibrutinib plus venetoclax is approved for this indication in Europe but not the United States. (See "Selection of initial therapy for symptomatic or advanced chronic lymphocytic leukemia/small lymphocytic lymphoma", section on 'Efficacy and toxicity'.)

Pirtobrutinib in relapsed CLL/SLL (July 2023, Modified December 2023)

Noncovalent Bruton tyrosine kinase (BTK) inhibitors such as pirtobrutinib are active in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with progression on a prior covalent BTK inhibitor (eg, ibrutinib, acalabrutinib, zanubrutinib). In a phase 1/2 trial including 247 such patients, pirtobrutinib was associated with an overall response rate of 82 percent and median progression-free survival of 19.6 months [5]. Response rates were similar irrespective of prior exposure to venetoclax or presence of BTK C481 mutations, which frequently arise upon progression on a covalent BTK inhibitor. Based on these results, the US Food and Drug Administration granted accelerated approval for pirtobrutinib in adults with CLL/SLL who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL2 inhibitor. We consider pirtobrutinib an option in this setting. (See "Treatment of relapsed or refractory chronic lymphocytic leukemia", section on 'Pirtobrutinib'.)

No role for ibrutinib in early stage CLL without active disease (August 2023)

For patients with early stage chronic lymphocytic leukemia (CLL) without "active disease" (table 1), chemotherapy increases toxicity relative to observation, without clinical benefit, but there is limited evidence regarding targeted therapies. A randomized trial evaluated ibrutinib in >360 patients with early stage, asymptomatic CLL without active disease, but with prognostic markers associated with worse clinical outcomes [6]. Ibrutinib postponed the development of active disease and the need for additional CLL-directed therapy compared with placebo, but increased toxicity. The final analysis after a median observation time of 69 months did not demonstrate an overall survival benefit, with approximately 93 percent of patients in both arms alive at five years. Observation remains standard for early stage, asymptomatic CLL, with early treatment reserved for clinical trials. (See "Overview of the treatment of chronic lymphocytic leukemia", section on 'Initial observation as standard care'.)

Randomized trial of decitabine versus hydroxyurea for chronic myelomonocytic leukemia (July 2023)

Patients with chronic myelomonocytic leukemia (CMML) who are not candidates for transplantation often receive either a hypomethylating agent (HMA; eg, azacitidine or decitabine) or hydroxyurea to control symptoms, but there is no consensus. In the recent DACOTA trial, survival was similar among 170 patients with advanced CMML who were randomly assigned to decitabine versus hydroxyurea, although decitabine achieved a lower rate of disease progression/transformation [7]. Rates of serious infections and hospitalization were similar with both agents. For patients who require treatment for CMML but are not eligible for transplantation, we suggest an HMA, but hydroxyurea is a reasonable alternative. (See "Chronic myelomonocytic leukemia: Management and prognosis", section on 'Older or less-fit'.)

LYMPHOMAS

Rare secondary T cell lymphomas after chimeric antigen receptor (CAR)-T cell therapy (December 2023)

Chimeric antigen receptor (CAR)-T cell therapy is effective for treatment of relapsed or refractory B cell lymphomas, multiple myeloma, and other disorders, but it may be associated with severe and potentially fatal adverse effects (AEs). Reports are now emerging of secondary T cell lymphomas in patients treated with CD19- and B cell maturation antigen (BCMA)-directed CAR-T cell therapy, some of which have CAR-positive malignant cells [8]. Although rare, the actual incidence is not well defined and it is uncertain if they are associated with all CAR-T cell products. US Food and Drug Administration (FDA)-approved CAR-T cell products include warnings about potential secondary malignancies, but at present, no regulatory action has been taken and no product has been recalled. Patients receiving CAR-T cell therapy should be monitored for development of new malignancies, and any such events should be reported to the manufacturer and to the FDA AE Reporting System (FAERS) [9]. The overall benefits of CAR-T cell products continue to outweigh potential risks for approved uses, but patients should be monitored and events reported. (See "Diffuse large B cell lymphoma (DLBCL): Suspected first relapse or refractory disease in patients who are medically fit", section on 'Relapse <12 months or primary refractory DLBCL'.)

Copanlisib withdrawn from the market (November 2023)

While previously approved by the US Food and Drug Administration for the treatment of multiply relapsed follicular lymphoma (FL), the phosphoinositide 3-kinase (PI3K) inhibitor copanlisib has been voluntarily withdrawn from the market by its manufacturer [10]. While initial studies suggested efficacy, subsequent studies did not confirm a favorable risk-to-benefit ratio. There are now no PI3K inhibitors with regulatory approval for FL. Patients who began treatment with copanlisib and are experiencing benefit with acceptable levels of toxicity may choose to continue the drug; the manufacturer is exploring access options. (See "Treatment of relapsed or refractory follicular lymphoma", section on 'Other novel agents'.)

MULTIPLE MYELOMA AND OTHER PLASMA CELL DISORDERS

Four- versus three-drug induction for multiple myeloma (December 2023)

Several recent randomized trials evaluated adding an anti-CD38 monoclonal antibody as a fourth drug for the initial treatment of multiple myeloma (MM). In two trials, adding daratumumab to bortezomib, lenalidomide, and dexamethasone (DVRd) deepened responses and improved progression-free survival (PFS) with a moderate increase in toxicity [11,12]. In a third trial, deeper responses were seen when isatuximab was added to carfilzomib, lenalidomide, and dexamethasone [13]. For most patients with standard-risk MM, we now suggest induction with either a four- or three-drug regimen rather than a two-drug regimen. The choice between three- and four-drug regimens is largely driven by patient values and preferences related to PFS, cost, and toxicity. (See "Multiple myeloma: Initial treatment", section on 'Daratumumab, bortezomib, lenalidomide, dexamethasone'.)

Zanubrutinib versus ibrutinib in Waldenström macroglobulinemia (November 2023)

The Bruton tyrosine kinase (BTK) inhibitors ibrutinib and zanubrutinib are effective treatments for Waldenström macroglobulinemia (WM). In a multicenter, phase 3 trial of >200 patients with WM, when compared with ibrutinib, zanubrutinib resulted in faster and deeper responses and had less overall toxicity, including lower rates of diarrhea, muscle spasms, hypertension, atrial fibrillation/atrial flutter, and pneumonia [14]. Progression-free survival and overall survival were similar between the two arms. Based on these and other data, we prefer zanubrutinib over ibrutinib when using a BTK inhibitor for WM. (See "Treatment and prognosis of Waldenström macroglobulinemia", section on 'Zanubrutinib'.)

Motixafortide plus G-CSF for mobilization in patients with multiple myeloma (September 2023)

In patients undergoing autologous hematopoietic cell transplantation (HCT) for multiple myeloma (MM), granulocyte colony-stimulating factor (G-CSF) is used to mobilize peripheral blood progenitor cells (PBPCs); G-CSF is used either alone, in combination with the chemokine receptor type 4 (CXCR4) inhibitor plerixafor, or after cyclophosphamide. In a randomized trial, the addition of a new CXCR4 inhibitor motixafortide to G-CSF decreased the number of apheresis sessions required [15]. These results led to its approval by the US Food and Drug Administration for use with G-CSF for PBPC mobilization in patients with MM undergoing autologous HCT [16]. For most patients, we initiate G-CSF alone rather than with a CXCR4 inhibitor, reserving the CXCR4 inhibitor for those with a suboptimal response to single-agent G-CSF. (See "Multiple myeloma: Use of hematopoietic cell transplantation", section on 'G-CSF-based stimulation'.)

Bispecific antibodies in heavily pretreated multiple myeloma (August 2023)

Bispecific antibodies used in multiple myeloma (MM) are monoclonal antibodies directed at both CD3 on the patient's T cells and another antigen on the tumor (B cell maturation antigen [BCMA] or GPRC5D). In phase 2 trials in heavily pretreated patients with MM, the following have been observed:

The anti-BCMA bispecific antibody elranatamab was associated with a response rate of 61 percent, and one-half had not progressed at 15 months [17]. Toxicity was similar to that seen with teclistamab (another anti-BCMA bispecific antibody).

The anti-GPRC5D bispecific antibody talquetamab was associated with an overall response rate of approximately 73 percent, and most responses were maintained for at least nine months [18]. In addition to adverse reactions commonly seen with other bispecific antibodies, talquetamab was associated with oral toxicity, weight loss, skin reactions, and nail changes in most patients.

Based on these and other data, the US Food and Drug Administration approved both elranatamab and talquetamab for patients who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. An anti-BCMA therapy such as elranatamab is our preferred treatment for penta-refractory MM (algorithm 1). In contrast, we typically reserve talquetamab for penta-refractory MM that is also refractory to alkylators and anti-BCMA therapies, given uncertainties regarding administration, toxicities, and long-term efficacy. (See "Multiple myeloma: Treatment of third or later relapse", section on 'Bispecific antibodies' and "Multiple myeloma: Treatment of third or later relapse", section on 'Talquetamab'.)

RED BLOOD CELL DISORDERS AND ANEMIAS

Gene editing for beta thalassemia (January 2024)

Gene editing makes permanent changes in a cell's DNA. The gene editing construct exagamglogene autotemcel (exa-cel; brand name: Casgevy) was recently approved for transfusion-dependent beta thalassemia [19]. Exa-cel uses CRISPR/Cas9 editing to disrupt the BCL11A gene in autologous hematopoietic stem cells, which increases the percentage of fetal hemoglobin (Hb F). Preliminary studies demonstrated efficacy in patients undergoing autologous transplantation using hematopoietic stem cells treated with this construct [20]. This may be an option for patients who would otherwise choose allogeneic transplantation. (See "Management of thalassemia", section on 'Gene therapy and other stem cell modifications'.)

Methemoglobinemia in infants due to contaminated hospital water supply (January 2024)

Methemoglobinemia is a potentially life-threatening condition in which heme iron becomes oxidized, preventing oxygen delivery. A report from a hospital in Japan described methemoglobinemia in 10 neonates who were fed infant formula prepared with tap water from the general hospital water supply [21]. The cause was identified as high levels of nitrites, and the source was traced to contamination by an anticorrosion agent from the heating system that entered the water supply due to a malfunctioning valve. All 10 survived, although 3 required methylene blue therapy. Infants are especially susceptible to methemoglobinemia because they have lower baseline levels of the enzyme that converts heme iron back to its normal state. (See "Methemoglobinemia", section on 'Nitrates and nitrites (from foods, drugs, preservatives, and chemicals)'.)

Gene therapy and gene editing in sickle cell disease (September 2023, Modified December 2023)

Several strategies are under study for individuals with sickle cell disease (SCD) who are seeking curative therapy. In December 2023, the US Food and Drug Administration approved two autologous cell-based therapies [22-24]:

Lovotibeglogene autotemcel (lovo-cel) uses lentivirus-based gene therapy to introduce the antisickling beta globin variant T87Q and produce hemoglobin A with antisickling properties.

Exagamglogene autotemcel (exa-cel) uses gene editing to disrupt the BCL11A gene and reverse the gamma globin to beta globin switch.

In a previous study, three individuals with SCD who were treated with a different gene editing approach (disrupting the gamma globin promotor) had marked reduction in vaso-occlusive complications and transfusion requirements [25,26]. All current gene therapy and gene editing approaches for SCD require autologous hematopoietic cell transplantation with myeloablative conditioning. (See "Investigational therapies for sickle cell disease", section on 'Gene therapy and gene editing'.)

Racial disparities in anemia during pregnancy (October 2023)

A new study has found that racial disparities in anemia during pregnancy persist and may be increasing. This analysis involved nearly four million births in the state of California from 2011 to 2020 [27]. Antepartum anemia was most common in Black individuals (22 percent), followed by Pacific Islanders (18 percent), Native American and Alaska Native peoples (14 percent), multiracial individuals (14 percent), Hispanic individuals (13 percent), Asian individuals (11 percent), and White individuals (10 percent). Antepartum anemia is associated with an increase in severe maternal morbidity. The reasons for disparities are multifactorial. (See "Anemia in pregnancy", section on 'Racial disparities'.)

Intravenous iron supplementation in heart failure with reduced ejection fraction (September 2023)

Iron deficiency is common in patients with heart failure (HF), but it remains unclear whether iron supplementation reduces mortality or hospitalization in this population. Recently published research on the effects of intravenous (IV) iron supplementation included the following observations:

In a trial in nearly 3100 patients with HF and reduced ejection fraction (HFrEF), IV iron supplementation improved iron stores but did not clearly reduce the risk of cardiovascular mortality or HF hospitalization [28].

In a meta-analysis of randomized trials of IV iron in patients with HFrEF, IV iron reduced the risk of HF hospitalization but had an unclear effect on cardiovascular mortality [29].

These data support the use of IV iron to reduce hospitalization in patients with HFrEF who have iron deficiency. (See "Evaluation and management of anemia and iron deficiency in adults with heart failure", section on 'Iron supplementation'.)

THROMBOSIS AND HEMOSTASIS

Revised classification criteria for antiphospholipid antibody syndrome (November 2023)

Antiphospholipid antibody syndrome (APS) presents with a wide array of clinical manifestations that can cause significant morbidity, making it both an important area for research and also challenging to define in studies. The American College of Rheumatology and the European Alliance of Associations for Rheumatology have recently updated the classification criteria for APS to allow more rigorous classification in research; these criteria should not substitute for clinical judgment when diagnosing APS [30]. The new criteria include a broader range of clinical manifestations (eg, microvascular complications, cardiac valve disease, thrombocytopenia, changes to pregnancy morbidity), risk stratification of macrovascular events, and a more nuanced weighting system for antiphospholipid antibodies (eg, considering immunoglobulin G versus immunoglobulin M isotypes). (See "Diagnosis of antiphospholipid syndrome", section on 'Classification criteria'.)

Risk of pregnancy-associated venous and arterial thrombosis in sickle cell disease (November 2023)

Sickle cell disease (SCD) and pregnancy both confer an increased risk of venous thromboembolism (VTE), but the magnitude of the risk is unclear. In a new administrative claims data study involving >6000 people with SCD and >17,000 age- and race-matched controls who were followed for one year postpartum, the risk of VTE was 11.3 percent in the patients with SCD, versus 1.2 percent in controls [31]. Arterial thromboembolism was also increased (5.2 percent, versus 0.6 percent in controls). This study emphasizes the value of postpartum VTE prophylaxis in people with SCD and the need for vigilance in evaluating suggestive symptoms. (See "Sickle cell disease: Obstetric considerations", section on 'Maternal risks'.)

Investigational use of efgartigimod for immune thrombocytopenia (October 2023)

Efgartigimod is under study in several autoimmune disorders. It reduces circulating antibody levels (including autoantibodies) by binding the neonatal Fc receptor (FcRn), in turn preventing FcRn from stabilizing immunoglobulins. In a randomized trial involving 131 adults with chronic or persistent immune thrombocytopenia (ITP), efgartigimod was more effective than placebo in raising the platelet count above 50,000/microL (22 versus 5 percent) [32]. The individuals in the trial had longstanding ITP, with a mean of 10.6 years since diagnosis; two-thirds had received at least three prior ITP therapies, and slightly over one-third had a splenectomy. Therapy was well tolerated, but regular intravenous infusions are required. (See "Second-line and subsequent therapies for immune thrombocytopenia (ITP) in adults", section on 'Efgartigimod (investigational FcRn inhibitor)'.)

Bleeding in Ehlers-Danlos syndromes (September 2023)

Ehlers-Danlos syndromes (EDS) are a group of rare genetic disorders of connective tissue that may cause skin hyperextensibility, joint hypermobility, tissue fragility, and vascular abnormalities. Bruising or bleeding can also occur, but EDS may not be considered due to its rarity and uncertainty about the magnitude of the bleeding phenotype. In a new study that evaluated bleeding scores in 52 individuals with several EDS subtypes, 62 percent had an abnormal score; the mean score was 9.1, well over the threshold for diagnosing a bleeding disorder [33]. Common sites of bleeding included oral, nasal, muscular, and heavy menstrual bleeding; 14 percent of females had life-threatening bleeds. This study highlights the value of considering EDS in individuals with unexplained bleeding. (See "Approach to the adult with a suspected bleeding disorder", section on 'Vascular and connective tissue disorders' and "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes", section on 'Overview'.)

Delayed diagnosis of acquired hemophilia A (September 2023)

Acquired hemophilia A (AHA) is a potentially life-threatening bleeding disorder caused by autoantibodies against coagulation factor VIII. Risk factors include older age, cancer, autoimmune disorders, and the postpartum state. In a recent series of 34 individuals with AHA followed for 15 years, diagnostic delays were common (affecting 44 percent of the patients), with a median delay of four months between bleeding onset and diagnosis [34]. The most common reason for the delay was failure to obtain coagulation testing. This study emphasizes the importance of evaluating new-onset unexplained bleeding. (See "Acquired hemophilia A (and other acquired coagulation factor inhibitors)", section on 'Typical presentation and clinical findings'.)

More evidence for investigational therapy targeting tissue factor pathway inhibitor in hemophilia (September 2023)

Concizumab is a monoclonal antibody that blocks tissue factor pathway inhibitor (TFPI) and is under study for patients with hemophilia. Because the monoclonal antibody targets a downstream protein, it is potentially useful for hemophilia A or B, especially in individuals with factor VIII or factor IX inhibitors. Previous data suggested a reduction in bleeding rates, but concerns were raised about thrombotic complications. A new trial comparing a lower dose of concizumab with placebo in patients with hemophilia and inhibitors, along with more patients treated with concizumab, has demonstrated a reduction in annualized bleeding rate (from approximately 12 to 0) without further thrombotic complications [35]. Concizumab has been approved in Canada for hemophilia B with inhibitors and remains investigational in the United States. (See "Gene therapy and other investigational approaches for hemophilia", section on 'Concizumab'.)

Thrombocytopenia and thrombosis syndrome with adenovirus infection (August 2023)

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare, autoantibody-mediated syndrome of thrombocytopenia and thrombosis (central venous thrombosis is common) that can occur after vaccination with an adenoviral-vectored COVID-19 vaccine. The clinical syndrome is similar to heparin-induced thrombocytopenia. A new report describes two individuals with a similar syndrome and VITT-like autoantibodies following documented adenovirus infection [36]. Neither patient had COVID-19 and neither received a COVID-19 vaccine. This finding suggests that a component of the adenoviral sequence may provide the source of the neoantigen. The inflammatory response to infection could provide the "second hit" that causes the syndrome. (See "COVID-19: Vaccine-induced immune thrombotic thrombocytopenia (VITT)", section on 'Mechanisms/triggers of antibody formation'.)

Direct oral anticoagulants for cancer-related venous thromboembolism (August 2023)

In patients with cancer-related venous thromboembolism (VTE), accumulating evidence suggests that direct oral anticoagulants (DOACs) and subcutaneous low molecular weight heparin (LMWH) have similar efficacy and safety. In a recent randomized trial of over 670 patients with cancer-related VTE, there were no significant differences between rates at six months for recurrent VTE (6.1 [DOACs] versus 8.8 percent [LMWH]) and major bleeding (5.2 [DOACs] versus 5.6 percent [LMWH]) [37]. Despite limitations such as lack of blinding, late randomization, and poor adherence rates with LMWH, these data are in keeping with previous evidence and support our suggestion for DOACs rather than LMWH in patients with cancer-associated VTE. (See "Anticoagulation therapy for venous thromboembolism (lower extremity venous thrombosis and pulmonary embolism) in adult patients with malignancy", section on 'Direct oral anticoagulant mono- or dual therapy'.)

TRANSFUSION MEDICINE

Whole blood transfusion for severe traumatic hemorrhage (January 2024)

For severe traumatic hemorrhage, whole blood transfusion is an alternative to balanced component transfusion (1:1:1 ratio of packed red blood cells/plasma/platelets). In an observational study comparing these two approaches, low titer group O whole blood transfusion was associated with lower 24-hour mortality (8 versus 19 percent) and lower volume of blood products received at 72 hours (48 versus 82 mL/kg) [38]. The survival benefit was greatest in patients with shock or coagulopathy. While this study suggests improved outcomes for whole blood transfusion, randomized trials are needed to determine which transfusion strategy might be superior and which patients would benefit the most. (See "Ongoing assessment, monitoring, and resuscitation of the severely injured patient", section on 'Whole blood transfusion'.)

Liberal transfusion strategy for acute myocardial infarction (December 2023)

Restrictive transfusion (transfusing at a lower hemoglobin, typically <7 or 8 g/dL) is appropriate for most patients based on evidence from randomized trials, but trial data for patients with acute myocardial infarction (MI) have been slower to accumulate. In the MINT trial, which randomly assigned 3504 patients with acute MI and anemia to a restrictive or liberal (transfusing for hemoglobin <10 g/dL) strategy, there was a trend toward better outcomes with the liberal strategy without an increased risk of adverse events [39]. We now suggest a liberal strategy for acute MI. A slightly lower hemoglobin may be reasonable for stable, asymptomatic patients, and patients with hemodynamic instability may require a higher hemoglobin. (See "Indications and hemoglobin thresholds for RBC transfusion in adults", section on 'Acute MI'.)

Variable transfusion practices in the ICU (November 2023)

Adherence to restrictive transfusion thresholds (transfusing at a hemoglobin of <7 or <8 g/dL, depending on the indication) is an important principle of patient blood management, but clinical judgment remains important in transfusion decisions, especially for symptomatic patients. In a multicenter study involving patients in 233 intensive care units (ICUs) across six continents, most ICUs gave transfusions to individuals with hemoglobin above the restrictive threshold of 7 g/dL [40]. Common transfusion indications other than low hemoglobin were active bleeding and hemodynamic instability. Further study of the variabilities in transfusion practice are warranted, especially in critically ill individuals. (See "Use of blood products in the critically ill", section on 'Symptomatic patients may require higher hemoglobin targets'.)

Convalescent plasma in mechanically ventilated patients with COVID-19 (November 2023)

Most randomized trials have not demonstrated a benefit for convalescent plasma in hospitalized patients with COVID-19, and we do not routinely use it in this setting. However, an open-label trial of 475 patients who were mechanically ventilated for severe COVID-19 did report a reduction in 28-day mortality with high-titer convalescent plasma compared with standard care (35 versus 45 percent) [41]. The inconsistency of this finding compared with the lack of effect in most other trials decreases confidence in the mortality benefit. Furthermore, the value of convalescent plasma against Omicron variants and in the context of contemporary management remains uncertain, as only a few patients in the trial had Omicron infection and most received only dexamethasone without other immunomodulatory agents. (See "COVID-19: Management in hospitalized adults", section on 'Limited role for antibody-based therapies (monoclonal antibodies and convalescent plasma)'.)

Polymicrobial sepsis from platelet transfusion (October 2023)

The risk of transfusion-transmitted bacterial infection is exceedingly low. However, a recent report documented seven cases of polymicrobial sepsis across six different states, three of which were fatal, from platelet transfusions [42]. An investigation determined the source to be the manufacturing facility of the apheresis platelet collection sets. This report highlights the importance of reporting suspected transfusion reactions to facilitate such investigations and the need for ongoing vigilance, despite the overall high and continuously improving safety of blood products. (See "Transfusion-transmitted bacterial infection", section on 'Microbiology'.)

No benefit of Cryoprecipitate in massive transfusion protocol for trauma (October 2023)

Cryoprecipitate is a source of fibrinogen; some institutions may include it in their massive transfusion protocols for trauma patients. In a new trial, 1604 trauma patients were randomly assigned to receive or not receive Cryoprecipitate in addition to a standard massive transfusion protocol [43]. Mortality at 28 days was comparable between the no Cryoprecipitate controls and the Cryoprecipitate group (26 versus 25 percent). This finding supports the practice of reserving Cryoprecipitate for patients with low fibrinogen levels. Transfusion medicine personnel and/or individuals with hemostasis expertise can help to determine the value for specific patients. (See "Cryoprecipitate and fibrinogen concentrate", section on 'Trauma'.)

Small-volume blood collection tubes to reduce anemia in the intensive care unit (October 2023)

Patients in the intensive care unit (ICU) undergo numerous blood draws that could contribute to anemia, but the magnitude and clinical significance are unknown. In a recent trial, switching to small-volume blood collection tubes led to a smaller decline in hemoglobin and a slightly reduced need for transfusion without compromising laboratory analysis [44]. Use of smaller collection tubes may be a useful approach to minimizing anemia in ICU patients. (See "Use of blood products in the critically ill", section on 'Preventing and treating other causes of anemia'.)

Effectiveness of intraoperative blood salvage for reducing need for allogenic transfusion (October 2023)

Intraoperative blood salvage is a blood conservation technique in which autologous blood is aspirated, concentrated, washed, and reinfused. A 2023 meta-analysis of randomized trials involving >14,000 patients found that it reduced the need for allogeneic red blood cell transfusions in cardiovascular surgery with or without cardiopulmonary bypass and in major orthopedic hip, knee, or spine surgery [45]. Benefits were uncertain in vascular, cancer, and obstetric surgery. We recommend intraoperative blood salvage in surgical procedures with blood loss >750 mL, particularly if transfusion of allogeneic blood is likely. (See "Surgical blood conservation: Intraoperative blood salvage", section on 'Benefits'.)

Risk of intracerebral hemorrhage in transfusion recipients (September 2023)

In an explorative study using a database of blood donors and >100,000 individuals who received a transfusion, the risk of spontaneous intracerebral hemorrhage (ICH) was slightly more than twofold greater in transfusion recipients whose donors later developed two or more episodes of ICH [46]. ICH is the most common manifestation of cerebral amyloid angiopathy, which is seen in Alzheimer disease, and the study also found an increased risk of ICH in patients who received a transfusion from a donor with a single previous episode of ICH plus dementia. These findings do not demonstrate causality, and a plausible mechanism for transmission of ICH has not been identified. Further study is needed to confirm or refute this finding. (See "Blood donor screening: Medical history", section on 'Neurodegenerative and other neurologic disorders'.)

OTHER HEMATOLOGY

Pegcetacoplan self-injector for adults with paroxysmal nocturnal hemoglobinuria (November 2023)

Pegcetacoplan is a pegylated peptide that can inhibit both intravascular and extravascular hemolysis in adults with paroxysmal nocturnal hemoglobinuria (PNH). The US Food and Drug Administration (FDA) recently approved pegcetacoplan in a single-use self-injector for use by the patient or caregiver after training in preparation and administration [47]. As with other complement inhibitors, pegcetacoplan is contraindicated in patients with severe infections, and the FDA label has a boxed warning about increased risk for meningococcal infections. We consider the pegcetacoplan self-injector an acceptable method for treatment of adults with symptomatic PNH. (See "Treatment and prognosis of paroxysmal nocturnal hemoglobinuria", section on 'Pegcetacoplan'.)

Bevacizumab in hereditary hemorrhagic telangiectasia (September 2023)

Hereditary hemorrhagic telangiectasia (HHT) can cause severe bleeding, and the antiangiogenic agent bevacizumab is sometimes used, but supporting data are limited. In the first randomized trial of bevacizumab in 24 individuals with HHT and a high transfusion requirement, those assigned to bevacizumab were more likely to reduce transfusions (64 percent, versus 33 percent in the placebo arm), but the difference did not reach statistical significance [48]. Other outcomes (epistaxis, hemoglobin, adverse events) were similar between groups. The high percentage of patients in the control group with reduced transfusion requirements serves to emphasize the fluctuating nature of bleeding in patients with HHT. This small trial reinforces the possible benefit of bevacizumab for some individuals with severe bleeding, but others may not benefit. More randomized trial data are needed. (See "Hereditary hemorrhagic telangiectasia (HHT): Evaluation and therapy for specific vascular lesions", section on 'Bevacizumab and other systemic antiangiogenic therapies'.)

Transfusion-associated graft-versus-host disease from fetal lymphocytes (September 2023)

Transfusion-associated graft-versus-host disease (TA-GVHD) is an almost universally fatal transfusion reaction in which lymphocytes in the transfused blood product attack the recipient's tissues, including skin, gastrointestinal tract, and bone marrow. A new case report described severe pancytopenia, diarrhea, and desquamating full-body rash three weeks after delivery of twins [49]. The T lymphocytes were determined to be fetally derived. Hematopoietic stem cell transplantation was planned, but the patient recovered before transplantation was initiated, with glucocorticoid therapy alone. While rare, this case serves as a reminder that TA-GVHD can occur in susceptible patients and that not all cases are fatal. (See "Transfusion-associated graft-versus-host disease", section on '"Mild" TA-GVHD'.)

  1. O'Brien SH, Rodriguez V, Lew G, et al. Apixaban versus no anticoagulation for the prevention of venous thromboembolism in children with newly diagnosed acute lymphoblastic leukaemia or lymphoma (PREVAPIX-ALL): a phase 3, open-label, randomised, controlled trial. Lancet Haematol 2024; 11:e27.
  2. Quizartinib tablets, for oral use. US Food and Drug Administration (FDA) approved product information. Revised July 2023. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216993s000lbl.pdf (Accessed on July 21, 2023).
  3. Niemann CU, Munir T, Moreno C, et al. Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2023; 24:1423.
  4. Munir T, Cairns DA, Bloor A, et al. Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease. N Engl J Med 2023.
  5. Mato AR, Woyach JA, Brown JR, et al. Pirtobrutinib after a Covalent BTK Inhibitor in Chronic Lymphocytic Leukemia. N Engl J Med 2023; 389:33.
  6. Langerbeins P, Robrecht S, Nieper P, et al. Ibrutinib versus placebo in patients with asymptomatic, treatment-naive early stage chronic lymphocytic leukemia (CLL): Final results of the CLL12 trial (abstract). Hematol Oncol 2023; 41:56.
  7. Itzykson R, Santini V, Thepot S, et al. Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia: Results of a Randomized Phase III Trial Within the EMSCO Network. J Clin Oncol 2023; 41:1888.
  8. FDA Investigating Serious Risk of T-cell Malignancy Following BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies. US Food and Drug Administration, 2023. Available at: https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous (Accessed on December 15, 2023).
  9. MedWatch: The FDA Safety Information and Adverse Event Reporting Program. US Food and Drug Administration. Available at: https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program (Accessed on December 15, 2023).
  10. Bayer provides update on Aliqopa® (copanlisib). Bayer Corporation, 2023. Available at: https://www.bayer.com/en/us/news-stories/update-on-aliqopar (Accessed on November 27, 2023).
  11. Voorhees PM, Sborov DW, Laubach J, et al. Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone for transplantation-eligible patients with newly diagnosed multiple myeloma (GRIFFIN): final analysis of an open-label, randomised, phase 2 trial. Lancet Haematol 2023; 10:e825.
  12. Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 2023.
  13. Gay F, Roeloffzen W, Dimopoulos MA, et al. Results of the Phase III Randomized Iskia Trial: Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone Vs Carfilzomib-Lenalidomide-Dexamethasone As Pre-Transplant Induction and Post-Transplant Consolidation in Newly Diagnosed Multiple Myeloma Patients (abstract 4). Blood 2023.
  14. Dimopoulos MA, Opat S, D'Sa S, et al. Zanubrutinib Versus Ibrutinib in Symptomatic Waldenström Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study. J Clin Oncol 2023; 41:5099.
  15. Crees ZD, Rettig MP, Jayasinghe RG, et al. Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial. Nat Med 2023; 29:869.
  16. Motixafortide for injection. United States prescribing information. Revised September 2023. US Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217159s000lbl.pdf (Accessed on September 20, 2023).
  17. Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med 2023; 29:2259.
  18. talquetamab-tgvs. United States prescribing information. Revised August 2023. US Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761342s000lbl.pdf (Accessed on August 11, 2023).
  19. https://www.fda.gov/media/175481/download?attachment (Accessed on January 17, 2024).
  20. Frangoul H, Altshuler D, Cappellini MD, et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. N Engl J Med 2021; 384:252.
  21. Takahashi S, Ishige T, Takizawa T. Methemoglobinemia Outbreak in a Neonatal ICU and Maternity Ward. N Engl J Med 2023; 389:2395.
  22. FDA package insert for CASGEVY (exagamglogene autotemcel). US Food and Drug Administration. Available at: https://www.fda.gov/media/174615/download (Accessed on December 15, 2023).
  23. lovotibeglogene autotemcel (Accessed on December 15, 2023).
  24. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. US Food and Drug Administration, 2023. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease (Accessed on December 15, 2023).
  25. Sharma A, Boelens JJ, Cancio MI, et al. Treatment of Individuals with Severe Sickle Cell Disease with OTQ923, an Autologous, Ex Vivo, CRISPR/Cas9-Edited, CD34+ Hematopoietic Stem and Progenitor Cell Product, Leads to Durable Engraftment and Fetal Hemoglobin Induction. Blood 2022; 140 (Supplement 1):1906.
  26. Sharma A, Boelens JJ, Cancio M, et al. CRISPR-Cas9 Editing of the HBG1 and HBG2 Promoters to Treat Sickle Cell Disease. N Engl J Med 2023; 389:820.
  27. Igbinosa II, Leonard SA, Noelette F, et al. Racial and Ethnic Disparities in Anemia and Severe Maternal Morbidity. Obstet Gynecol 2023; 142:845.
  28. Mentz RJ, Garg J, Rockhold FW, et al. Ferric Carboxymaltose in Heart Failure with Iron Deficiency. N Engl J Med 2023; 389:975.
  29. Salah HM, Savarese G, Rosano GMC, et al. Intravenous iron infusion in patients with heart failure: a systematic review and study-level meta-analysis. ESC Heart Fail 2023; 10:1473.
  30. Barbhaiya M, Zuily S, Naden R, et al. The 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria. Arthritis Rheumatol 2023; 75:1687.
  31. Agarwal S, Stanek JR, Vesely SK, et al. Pregnancy-related thromboembolism in women with sickle cell disease: An analysis of National Medicaid Data. Am J Hematol 2023; 98:1677.
  32. Broome CM, McDonald V, Miyakawa Y, et al. Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2023; 402:1648.
  33. Kumskova M, Flora GD, Staber J, et al. Characterization of bleeding symptoms in Ehlers-Danlos syndrome. J Thromb Haemost 2023; 21:1824.
  34. Tian C, Perija B, Kotb R, et al. Acquired haemophilia A: A 15-year population-based review of incidence rate, patient demographics and treatment outcomes. Haemophilia 2023; 29:1269.
  35. Matsushita T, Shapiro A, Abraham A, et al. Phase 3 Trial of Concizumab in Hemophilia with Inhibitors. N Engl J Med 2023; 389:783.
  36. Warkentin TE, Baskin-Miller J, Raybould AL, et al. Adenovirus-Associated Thrombocytopenia, Thrombosis, and VITT-like Antibodies. N Engl J Med 2023; 389:574.
  37. Schrag D, Uno H, Rosovsky R, et al. Direct Oral Anticoagulants vs Low-Molecular-Weight Heparin and Recurrent VTE in Patients With Cancer: A Randomized Clinical Trial. JAMA 2023; 329:1924.
  38. Shea SM, Mihalko EP, Lu L, et al. Doing more with less: low-titer group O whole blood resulted in less total transfusions and an independent association with survival in adults with severe traumatic hemorrhage. J Thromb Haemost 2024; 22:140.
  39. Carson JL, Brooks MM, Hébert PC, et al. Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia. N Engl J Med 2023; 389:2446.
  40. Raasveld SJ, de Bruin S, Reuland MC, et al. Red Blood Cell Transfusion in the Intensive Care Unit. JAMA 2023; 330:1852.
  41. Misset B, Piagnerelli M, Hoste E, et al. Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients. N Engl J Med 2023; 389:1590.
  42. Kracalik I, Kent AG, Villa CH, et al. Posttransfusion Sepsis Attributable to Bacterial Contamination in Platelet Collection Set Manufacturing Facility, United States. Emerg Infect Dis 2023; 29:1979.
  43. Davenport R, Curry N, Fox EE, et al. Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury: The CRYOSTAT-2 Randomized Clinical Trial. JAMA 2023; 330:1882.
  44. Siegal DM, Belley-Côté EP, Lee SF, et al. Small-Volume Blood Collection Tubes to Reduce Transfusions in Intensive Care: The STRATUS Randomized Clinical Trial. JAMA 2023; 330:1872.
  45. Lloyd TD, Geneen LJ, Bernhardt K, et al. Cell salvage for minimising perioperative allogeneic blood transfusion in adults undergoing elective surgery. Cochrane Database Syst Rev 2023; 9:CD001888.
  46. Zhao J, Rostgaard K, Lauwers E, et al. Intracerebral Hemorrhage Among Blood Donors and Their Transfusion Recipients. JAMA 2023; 330:941.
  47. Drug label information for EMPAVELI pegcetacoplan injection and solution. DailyMed. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c23d89e9-b00b-4520-e053-2995a90a95af (Accessed on November 27, 2023).
  48. Dupuis-Girod S, Rivière S, Lavigne C, et al. Efficacy and safety of intravenous bevacizumab on severe bleeding associated with hemorrhagic hereditary telangiectasia: A national, randomized multicenter trial. J Intern Med 2023; 294:761.
  49. Schreiber AR, Santos J, McMahon B, et al. A Case of Fetal-Induced Graft-versus-Host Disease. N Engl J Med 2023; 389:668.
Topic 8359 Version 12473.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟