What's new in hematology

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'.)

CHRONIC LEUKEMIAS AND MYELOPROLIFERATIVE NEOPLASMS

CAR-T cell therapy for multiply relapsed CLL (April 2024)

The US Food and Drug Administration recently granted accelerated approval of the CD19-directed chimeric antigen receptor T (CAR-T) cell therapy lisocabtagene maraleucel for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) after two or more lines of systemic therapy including a Bruton tyrosine kinase inhibitor and a BCL2 inhibitor [2]. Approval was based on accumulating evidence from single-arm prospective trials that show variable response rates and duration of response; remissions have lasted over a decade in some patients with persistent CAR-T cells. This population has few therapeutic alternatives, and we consider CAR-T cell therapy an option for fit patients who meet these criteria. However, given the toxicity, complexity, and cost, the decision is individualized and highly dependent on an estimation of complication risk and the needs and wishes of the patient. (See "Treatment of relapsed or refractory chronic lymphocytic leukemia", section on 'Chimeric antigen receptor T cells'.)

Rusfertide for reducing therapeutic phlebotomy in polycythemia vera (February 2024)

In patients with polycythemia vera (PV), maintaining the hematocrit <45 percent decreases mortality, reduces thromboses, and alleviates pruritus, but the need for ongoing phlebotomy is inconvenient. In a small placebo-controlled randomized trial in patients with PV, rusfertide, a novel injectable hepcidin mimic that induces iron deficiency, effectively controlled erythrocytosis, eliminated the need for therapeutic phlebotomy, and caused only minor injection site reactions [3]. Rusfertide is not yet approved by the US Food and Drug Administration, but it appears promising for controlling erythrocytosis in patients with PV. (See "Polycythemia vera and secondary polycythemia: Treatment and prognosis", section on 'Other agents'.)

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 [4,5]. 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'.)

LYMPHOMAS

Zanubrutinib plus obinutuzumab in multiply relapsed follicular lymphoma (April 2024)

Zanubrutinib, a Bruton tyrosine kinase inhibitor, has received regulatory approval by the US Food and Drug Administration for use with obinutuzumab in patients with multiply relapsed follicular lymphoma (FL) [6]. Approval was based on results from a randomized trial in which >200 patients who had received two or more prior systemic therapies for FL experienced improved overall response rates and progression-free survival with the addition of zanubrutinib to obinutuzumab. Toxicities with zanubrutinib were modest. Although we prefer other combinations, including lenalidomide with either rituximab or obinutuzumab, for multiply relapsed FL, we consider zanubrutinib plus obinutuzumab to be an acceptable alternative or later-line option. (See "Treatment of relapsed or refractory follicular lymphoma", section on 'Zanubrutinib plus obinutuzumab'.)

Three-year follow-up of CAR-T cell therapy in follicular lymphoma (April 2024)

CD19-directed chimeric antigen receptor T (CAR-T) cell therapies were originally approved for use in follicular lymphoma (FL) based on single-arm trials with limited follow-up. In an update of one such trial that expanded results to include 127 patients with FL treated with axicabtagene ciloleucel (axi-cel), the vast majority of patients had an objective response and approximately one-half were alive and free of progression at 36 months [7]. In addition, all 13 patients who were retreated with axi-cel at relapse had a second response. These results provide further support for the efficacy of CAR-T cell therapy in FL. The decision to pursue CAR-T therapy is individualized, weighing disease tempo, availability of other treatments, and expected toxicity. (See "Treatment of relapsed or refractory follicular lymphoma", section on 'Chimeric antigen receptor T cells'.)

No role for central nervous system prophylaxis with high-dose methotrexate in diffuse large B cell lymphoma (February 2024)

Patients with diffuse large B cell lymphoma (DLBCL) are at substantial risk for central nervous system (CNS) relapse, but there is controversy about whether adding high-dose methotrexate (HD-MTX) prophylaxis to CD20-based induction chemoimmunotherapy can reduce this risk. In a recent observational study that included 2418 patients, administration of HD-MTX prophylaxis (at the discretion of the treating physician) was not associated with a clinically meaningful reduction in two-year risk of CNS relapse [8]. Toxicity with HD-MTX includes encephalopathy, hepatotoxicity, and kidney toxicity. Based on this and other studies, we do not routinely add HD-MTX prophylaxis to induction chemoimmunotherapy for DLBCL. (See "Initial treatment of advanced stage diffuse large B cell lymphoma", section on 'CNS management'.)

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 [9]. 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) [10]. 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 [11]. 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

No association between monoclonal gammopathy of undetermined significance and autoimmune diseases or immune-related conditions (May 2024)

Studies have evaluated whether a relationship exists between monoclonal gammopathy of undetermined significance (MGUS) and autoimmune diseases or immune-related conditions. Although several retrospective studies had suggested an increased risk of MGUS among patients with these conditions, a large Icelandic prospective population-based screening study did not find an association [12]. The increased prevalence in prior retrospective studies likely reflects a sampling bias as testing was likely preferentially performed in patients with autoimmune diseases or immune-related conditions due to a perceived association. (See "Diagnosis of monoclonal gammopathy of undetermined significance", section on 'Associated conditions'.)

BCMA-directed CAR-T cell therapy for relapsed multiple myeloma (May 2024)

The US Food and Drug Administration has expanded the indications for B cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy in relapsed or refractory multiple myeloma (MM), to allow use earlier in the disease course given progression-free survival benefits:

● Ciltacabtagene autoleucel is now approved after at least one line of systemic therapy, including an immunomodulatory agent and a proteasome inhibitor, that is refractory to lenalidomide [13].

● Idecabtagene vicleucel is now approved after two or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody [14].

However, we do not typically offer CAR-T cell therapy after just one line of systemic therapy, given risks that include neurotoxicity and T cell lymphoma. A possible exception is high-risk MM with progression without response to a four-drug combination that includes an anti-CD38 monoclonal antibody. (See "Multiple myeloma: Treatment of second or later relapse", section on 'Chimeric antigen receptor T cells'.)

Using iStopMM risk model to defer bone marrow evaluation in suspected MGUS (April 2024)

Bone marrow aspiration and biopsy are frequently performed as part of the evaluation of patients with suspected monoclonal gammopathy of undetermined significance (MGUS) to confirm <10 percent clonal bone marrow plasma cells. The iStopMM risk model has been proposed as an alternative method of estimating the risk of bone marrow involvement [15]. When applied to a large Icelandic cohort without clinical evidence of multiple myeloma (MM), the model had high sensitivity and negative predictive value. If biopsy were pursued only in patients in whom the model estimated ≥10 percent bone marrow involvement, 60 percent of patients could defer biopsy, only a small percentage of whom would actually have more advanced disease. In individuals with no clinical evidence of MM (eg, anemia, lymphadenopathy, or organomegaly), we consider <10 percent bone marrow involvement estimated by the iStopMM risk model to be a low-risk scenario in which bone marrow evaluation may be deferred. (See "Diagnosis of monoclonal gammopathy of undetermined significance", section on 'Bone marrow aspiration and biopsy'.)

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 [16,17]. In a third trial, deeper responses were seen when isatuximab was added to carfilzomib, lenalidomide, and dexamethasone [18]. 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'.)

RED BLOOD CELL DISORDERS AND ANEMIAS

Gene editing in sickle cell disease (May 2024)

A gene editing therapy that increases production of fetal hemoglobin (Hb F) in autologous hematopoietic stem cells was approved for sickle cell disease in late 2023. A new report describes outcomes in 44 patients with sickle cell disease who underwent myeloablative autologous transplantation using this therapy [19]. At 6 months, the mean hemoglobin was 12.5 g/dL and the mean Hb F was 44 percent. Of the 30 participants who had follow-up of at least 12 months, only 1 had a vaso-occlusive event, and none were hospitalized for vaso-occlusive events. One person with preexisting lung disease and busulfan-induced lung injury died of COVID-19 at day 268. Other gene editing approaches are under investigation. (See "Curative therapies in sickle cell disease including hematopoietic stem cell transplantation and gene therapy", section on 'Gamma globin upregulation (including exa-cel, Casgevy)'.)

Gene editing in transfusion-dependent beta thalassemia (May 2024)

Exagamglogene autotemcel, a gene editing construct that increases production of fetal hemoglobin (Hb F), was approved for transfusion-dependent beta thalassemia in January 2024. A new report describes outcomes in 52 individuals who underwent myeloablative autologous transplantation using this therapy [20]. There were no deaths or cancers, and toxicity was as expected from the conditioning regimen. For the 35 individuals with follow-up of at least 12 months, 32 (91 percent) became transfusion independent, with mean total hemoglobin of 13.1 g/dL and mean Hb F of 11.9 g/dL. Any transplantation strategy in thalassemia requires reduction (or prevention) of iron overload and individualized decision-making. (See "Management of thalassemia", section on 'Gene therapy and gene editing'.)

Haploidentical transplantation in sickle cell disease (May 2024)

Allogeneic hematopoietic stem cell transplantation can cure sickle cell disease, but most patients do not have a matched sibling donor. Haploidentical donors (parents, siblings, or children who share one haplotype with the recipient) can substantially increase the donor pool. In a new series of 70 individuals with sickle cell disease undergoing allogeneic transplantation with a haploidentical donor and modifications such as adding thiotepa to reduce graft failure and using posttransplant cyclophosphamide to reduce graft-versus-host disease, overall survival was 96 percent at one year and 94 percent at two years, with all five deaths due to infections [21]. While the decision to pursue curative therapies is highly individualized, this approach appears to be the most promising for individuals who lack a matched sibling donor. (See "Curative therapies in sickle cell disease including hematopoietic stem cell transplantation and gene therapy", section on 'Haploidentical related donor'.)

Intravenous iron in heart failure (April 2024)

Individuals with heart failure (HF) and iron deficiency should be treated, but expert groups differ on the perceived benefits. In a new meta-analysis that included over 4500 patients participating in randomized trials, intravenous iron reduced the rate of cardiovascular hospitalizations compared with placebo; all-cause mortality was not reduced [22]. This supports our suggested approach of using intravenous iron, although oral iron may be reasonable. Iron supplementation should be stopped once stores are repleted, as excess iron deposition is cardiotoxic. (See "Evaluation and management of anemia and iron deficiency in adults with heart failure", section on 'Iron supplementation'.)

Association of preoperative anemia with adverse outcomes after cardiac surgery (March 2024)

Studies continue to show a high rate of preoperative anemia in patients undergoing cardiac surgery and an association with adverse surgical outcomes. In a retrospective study of >4000 patients undergoing coronary artery bypass grafting surgery, 30 percent had preoperative anemia, which was associated with dose-dependent increases in postoperative acute kidney injury (AKI) and longer hospital stay [23]. In a 2024 meta-analysis with nearly 160,000 patients who underwent cardiac surgery, 28 percent had preoperative anemia, which was associated with increased mortality, AKI, other morbidities, and longer hospital stay [24]. When feasible, we postpone major surgery in patients with anemia to diagnose the cause and provide treatment. (See "Perioperative blood management: Strategies to minimize transfusions", section on 'Treatment of anemia'.)

New international guideline for PK deficiency (March 2024)

A new international expert guideline for diagnosis and treatment of pyruvate kinase (PK) deficiency has been published [25]. Key recommendations include testing in any individual with nonimmune hemolytic anemia after exclusion of hemoglobin and red blood cell (RBC) membrane disorders, acceptance of genetic testing alone for diagnosis, regular RBC transfusions for children <5 years with symptomatic anemia, monitoring for iron overload and its complications, use of mitapivat for symptomatic anemia in adults who are not receiving transfusions and do not have two nonmissense mutations, and discontinuing mitapivat for lack of efficacy. These guidelines are consistent with the advice in UpToDate. (See "Pyruvate kinase deficiency", section on 'Treatment'.)

Hemoglobin nadir in transfusion-dependent thalassemia (March 2024)

Thalassemia experts generally target a nadir hemoglobin of 9.5 to 10.5 in patients with transfusion-dependent thalassemia (TDT), but supporting evidence for this has been very limited. A new retrospective study evaluated outcomes in 779 patients with TDT and reported that higher pretransfusion hemoglobin (the nadir between regular transfusions) correlated with improved 10-year survival [26]. The survival benefit was not seen with ferritin >1000 ng/mL, emphasizing the importance of addressing iron overload. While several caveats apply to interpretation, this study supports our practice of targeting a nadir of 9.5 to 10.5 g/dL in TDT. (See "Management of thalassemia", section on 'Supporting evidence'.)

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 [27]. 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)'.)

THROMBOSIS AND HEMOSTASIS

Reversal strategy for intracerebral hemorrhage associated with direct factor Xa inhibitors (May 2024)

The optimal reversal strategy for direct factor Xa inhibitors (apixaban, edoxaban, rivaroxaban) in acute intracerebral hemorrhage (ICH) is uncertain. In the ANNEXA-I trial, which randomly assigned 530 patients with factor Xa inhibitor-associated ICH to andexanet alfa or standard care (typically including a prothrombin complex concentrate [PCC]), patients assigned to andexanet had higher rates of hemostasis than those assigned to standard therapy (67 versus 53 percent) [28]. However, thrombotic events, including ischemic stroke and myocardial infarction, were more common with andexanet (10.3 versus 5.6 percent). Mortality and functional outcomes at 30 days were similar. Based on these results, we individualize selection of andexanet alfa or PCC for direct factor Xa inhibitor reversal in acute ICH and other life-threatening bleeding; previously, we favored andexanet in most cases. Andexanet may restore hemostasis more effectively than PCC but is associated with higher thrombotic risk. (See "Reversal of anticoagulation in intracranial hemorrhage", section on 'Reversal agent options'.)

Recombinant ADAMTS13 prophylaxis in hereditary thrombotic thrombocytopenic purpura (May 2024)

In patients with hereditary thrombotic thrombocytopenic purpura (TTP), prophylaxis against acute exacerbations can be done with plasma or recombinant ADAMTS13 (rADAMTS13), which was approved by the US Food and Drug Administration (FDA) in late 2023. In a new randomized crossover trial in 48 individuals with hereditary TTP, prophylaxis with rADAMTS13 was associated with fewer TTP episodes, fewer adverse events, and higher ADAMTS13 activity levels than with plasma or plasma-derived factor VIII-von Willebrand factor complex containing ADAMTS13 [29]. These results support our approach of suggesting regular prophylaxis for individuals with frequent exacerbations and suggesting rADAMTS13 over plasma. Some patients may reasonably make other choices. (See "Hereditary thrombotic thrombocytopenic purpura (hTTP)", section on 'Prophylaxis/prevention of future exacerbations'.)

Emicizumab in infants with hemophilia A (April 2024)

Emicizumab is a monoclonal antibody that substitutes for the function of factor VIII; initial use has focused on older patients with factor VIII inhibitors. Now, two new studies report safety and efficacy in infants, most of whom did not have inhibitors. In HAVEN 7, there were no spontaneous bleeds or intracerebral bleeds [30]. In the second study, annualized bleeding rate decreased from 2 to 1 [31]. Neither study observed serious adverse events. Emicizumab is an attractive option due to its efficacy, lower rate of factor VIII exposure, and maintenance dosing schedule (subcutaneously once every other week), but use requires specialized knowledge of monitoring, risks, and treatment of breakthrough bleeding. (See "Hemophilia A and B: Routine management including prophylaxis", section on 'Emicizumab efficacy and adverse events'.)

Anti-factor Xa levels 24 hours after the last therapeutic enoxaparin dose (April 2024)

Guidelines recommend waiting 24 hours after a therapeutic dose of low molecular weight heparin (LMWH) before performing neuraxial anesthesia, to minimize the risk of spinal epidural hematoma (SEH). However, anti-factor Xa levels (which test LMWH activity) may still be elevated 24 hours after the last dose. In a study of 103 patients taking therapeutic dose enoxaparin, 23 percent had an anti-factor Xa level ≥0.2 international units/mL at ≥24 hours after the last dose [32]. The implications of these findings are unclear, as a safe anti-factor Xa level for performing neuraxial procedures has not been determined and there has not been a noticeable increase in SEH in patients who have withheld LMWH according to current guidelines. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication", section on 'Therapeutic LMWH'.)

Updates on congenital fibrinogen disorders (April 2024)

Congenital fibrinogen disorders are rare and remain underdiagnosed. New publications address the clinical manifestations of these disorders and provide obstetric guidance:

●A new report from the Rare Bleeding Disorders database described 123 patients with afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia and characterized bleeding and thrombotic manifestations [33]. (See "Disorders of fibrinogen", section on 'Clinical manifestations'.)

●New guidelines from the International Society on Thrombosis and Hemostasis (ISTH) provide target fibrinogen levels and advice for managing postpartum bleeding and thromboprophylaxis in individuals with congenital fibrin disorders [34]. (See "Disorders of fibrinogen", section on 'Conception and pregnancy'.)

A high index of suspicion for these disorders and multidisciplinary management are required.

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 [35]. 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'.)

TRANSFUSION MEDICINE

Incidence of transfusion-related acute lung injury (April 2024)

Transfusion-related acute lung injury (TRALI) is a potentially fatal complication of transfusion characterized by rapid-onset noncardiogenic pulmonary edema. The incidence is challenging to determine due to differing case definitions and reliance on passive reporting (requiring the clinician to notify the transfusion medicine service). A new meta-analysis that included approximately 176 million transfused blood components provides estimates from active surveillance studies [36]. For red blood cells, TRALI occurred with 0.17 of 10,000 units; for platelets, 0.31 of 10,000 units; and for plasma, 3.19 of 10,000 units (the incidence for plasma was much lower when two outlier studies were removed). TRALI remains rare and has been significantly reduced by mitigation measures such as excluding plasma from multiparous female donors; nevertheless, these numbers suggest it is more common than estimated by passive surveillance. (See "Transfusion-related acute lung injury (TRALI)", section on 'Epidemiology'.)

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) [37]. 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 [38]. 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'.)

OTHER HEMATOLOGY

Pemivibart for prevention of COVID-19 in selected immunocompromised patients (April 2024)

Monoclonal antibodies have been used as adjunctive pre-exposure prophylaxis to reduce the risk of COVID-19 in individuals expected to have suboptimal response to vaccination, although emergence of variants that escape neutralization limit their utility. In March 2024 in the United States, the novel monoclonal antibody pemivibart received emergency use authorization (EUA) to prevent COVID-19 in individuals age 12 years or older (weighing at least 40 kg) who have moderate-to-severe immunocompromising conditions (table 1) [39]. Pemivibart is active against JN.1, the dominant SARS-CoV-2 variant. We suggest pemivibart in individuals at the highest risk for vaccine nonresponse (eg, those with hematologic malignancy or recent history of transplantation) as long as it remains active against the main circulating variants. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Limited role for monoclonal antibodies in selected patients'.)

New guidelines for protoporphyria (March 2024)

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare cutaneous porphyrias that cause severe, nonblistering photosensitivity and liver disease; their rarity makes evidence-based management challenging. Two new guidelines from the Rare Diseases Clinical Research Network are available to help guide diagnosis and management of EPP and XLP:

●Consensus guidelines discuss use of biochemical and genetic testing, use of afamelanotide, avoidance of ineffective therapies, methods of sun protection, and prevention of liver disease [40].

●Liver-specific guidelines discuss screening, prevention, and treatment of liver disease, including liver and hematopoietic stem cell transplantation for advanced disease [41].

●(See "Erythropoietic protoporphyria and X-linked protoporphyria", section on 'Management'.)

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 [42]. 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'.)