The dos, don'ts, and nuances of thrombophilia testing
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):593-599. doi: 10.1182/hematology.2023000491.ABSTRACTConsiderable progress has been made in elucidating genetic and biologic risk factors for venous thromboembolism (VTE). Despite being able to identify heritable defects in a substantial proportion of patients with VTE, testing has not, in general, proven useful in management. Despite efforts to reduce inappropriate testing, it often falls to the hematologist to consult on patients having undergone thrombophilia testing. Through a series of cases, we discuss how D-dimer testing can be helpful in VTE recurrence risk ...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Thita Chiasakul Kenneth A Bauer Source Type: research
Acute lymphoblastic leukemia in young adults: which treatment?
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):587-592. doi: 10.1182/hematology.2023000512.ABSTRACTDespite improvements in survival among pediatric patients with acute lymphoblastic leukemia (ALL), survival outcomes for adolescents and young adults (AYAs) with ALL have lagged. The reasons for the inferior outcomes among AYAs are multifactorial, each presenting unique challenges and requiring novel solutions. First, adverse disease biology is more common among AYAs with ALL. Ongoing trials are investigating novel approaches to treatment, such as incorporating JAK inhibitors for Philadelphia chromosome-like ALL, ...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Annabelle Anandappa Emily Curran Source Type: research
Atypical CML: diagnosis and treatment
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):476-482. doi: 10.1182/hematology.2023000448.ABSTRACTAtypical chronic myeloid leukemia (aCML) is included in the group of myelodysplastic/myeloproliferative neoplasms by the International Consensus Classification and has been renamed as MDS/MPN with neutrophilia by the fifth edition of World Health Organization classification. It is always characterized by morphologic identification of granulocytic dysplasia with >10% circulating immature myeloid cells, 2 distinguished features that differentiate this disease among the others. Somatic mutations may help to diagno...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Massimo Breccia Source Type: research
Resistance mutations in CML and how we approach them
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):469-475. doi: 10.1182/hematology.2023000447.ABSTRACTAmong the variety of resistance mechanisms that may underlie a non-optimal response to tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia patients, secondary point mutations in the BCR::ABL1 kinase domain (KD) represent the only actionable one. Each of the 5 ATP-competitive inhibitors (imatinib, dasatinib, nilotinib, bosutinib, ponatinib) has a well-defined spectrum of resistance mutations. Growing clinical experience will soon allow to also elucidate the full spectrum of mutations conferring resi...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Simona Soverini Source Type: research
Dual-targeted regimens for the frontline treatment of CLL
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):421-426. doi: 10.1182/hematology.2023000506.ABSTRACTThe treatment landscape of chronic lymphocytic leukemia (CLL) has evolved considerably over the past decade due to the development of effective novel agents with varying mechanisms of action, including Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL2) inhibitors. Extrapolating upon the success of anti-CD20-directed chemoimmunotherapy, a dual-targeted approach has been explored in treatment-naive patients with CLL. Anti-CD20 monoclonal antibody combinations with BTK inhibitors as well as BCL2 inhibitors hav...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Chaitra Ujjani Source Type: research
Multiple myeloma: a paradigm for blending community and academic care
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):318-323. doi: 10.1182/hematology.2023000431.ABSTRACTThe care of the multiple myeloma (MM) patient is complex, with most patients requiring multiple lines of therapy over a span of many years to decades. Since the days when autologous stem cell transplantation became the standard of care for a large subset of patients, it was imperative that community practices and specialized academic centers work together to optimize the initial care of patients. Now, with the unprecedented number of treatment options and the introduction of chimeric antigen receptor T-cell therap...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Jes ús G Berdeja Source Type: research
Diagnosis and laboratory monitoring of hemophilia A
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):11-18. doi: 10.1182/hematology.2023000460.ABSTRACTAcquired hemophilia A (AHA) is a rare disorder in which autoantibodies against factor VIII (FVIII) lead to a bleeding phenotype that varies from life-threatening to no bleeding at all. Prolonged activated partial thromboplastin times (APTT) in patients with a bleeding phenotype should be investigated to rule out AHA and should never be ignored in a preprocedure patient. Most inhibitors in AHA are heat and time dependent, so mixing studies performed only on an immediate mix are not useful: both lupus anticoagulants a...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Sean Platton Suthesh Sivapalaratnam Priyanka Raheja Source Type: research
Incidence, mechanism, and consequences of IV iron-induced hypophosphatemia
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):636-639. doi: 10.1182/hematology.2023000521.NO ABSTRACTPMID:38066924 | PMC:PMC10727077 | DOI:10.1182/hematology.2023000521 (Source: Hematology ASH Education Program)
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Kylee L Martens Myles Wolf Source Type: research
Intravenous iron therapy in pediatrics: who should get it and when is the right time?
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):630-635. doi: 10.1182/hematology.2023000496.ABSTRACTIron-deficiency anemia occurs most commonly in young children due to a low-iron diet and adolescent girls due to menstrual blood loss. However, children with gastrointestinal conditions such as intestinal failure, inflammatory bowel disease, celiac disease, and/or other chronic conditions, including chronic kidney disease and heart failure, also commonly have iron deficiency. Many patients with classic iron-deficiency anemia will improve with oral iron therapy. However, in children who have an incomplete response ...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Clay T Cohen Jacquelyn M Powers Source Type: research
When to consider inherited marrow failure syndromes in adults
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):548-555. doi: 10.1182/hematology.2023000488.ABSTRACTThe inherited bone marrow failure syndromes (IBMFS) are a heterogenous group of disorders caused by germline mutations in related genes and characterized by bone marrow failure (BMF), disease specific organ involvement, and, in most cases, predisposition to malignancy. Their distinction from immune marrow failure can often be challenging, particularly when presentations occur in adulthood or are atypical. A combination of functional (disease specific assays) and genetic testing is optimal in assessing all new BMF ...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Fernanda Gutierrez-Rodrigues Bhavisha A Patel Emma M Groarke Source Type: research
Gene therapy for sickle cell disease
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):542-547. doi: 10.1182/hematology.2023000487.ABSTRACTSickle cell disease (SCD) is potentially curable after allogeneic hematopoietic stem cell transplantation (HSCT) or autologous HSCT after ex vivo genetic modification. Autologous HSCT with gene therapy has the potential to overcome many of the limitations of allogeneic HSCT that include the lack of suitable donors, graft-versus-host disease, the need for immune suppression, and the potential for graft rejection. Significant progress in gene therapy for SCD has been made over the past several decades, now with a gr...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Alexis Leonard John F Tisdale Source Type: research
MRD-directed therapy in CLL: ready for prime time?
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):413-420. doi: 10.1182/hematology.2023000441.ABSTRACTIn recent years, the treatment paradigm for patients with chronic lymphocytic leukemia (CLL) has moved away from chemoimmunotherapy (CIT) toward the use of novel targeted agents. Commercially available drugs, including Bruton's tyrosine kinase inhibitors and the BCL2 inhibitor venetoclax, often used in combination with anti-CD20 monoclonal antibodies, are now the mainstay of therapy both in the frontline and in relapsed settings. As the landscape for CLL management evolves, therapeutic endpoints need to be redefin...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Joanna M Rhodes Carlos A Lopez Jacqueline C Barrientos Source Type: research
Amyloid consults do not have to be vexing
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):407-412. doi: 10.1182/hematology.2023000440.ABSTRACTDiagnosing amyloidosis can be challenging due to its clinical heterogeneity, need for multiple specialists to make a diagnosis, and lack of a single diagnostic test for the disease. Patients are often diagnosed late, in advanced stage, and after exhibiting multiple symptoms and signs for a long period. It is important to develop a clinical suspicion of amyloidosis, particularly in those with multisystemic symptoms and high-risk patient populations such as those with precursor hematologic conditions. A systematic a...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Anita D'Souza Source Type: research
IV iron formulations and use in adults
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):622-629. doi: 10.1182/hematology.2023000495.ABSTRACTIntravenous iron has become a major component of the therapeutic armamentarium for iron deficiency and iron deficiency anemia. The earliest formulations were associated with unacceptable toxicity. Newer formulations, with complex carbohydrate cores that bind elemental iron more tightly, allow the administration of full therapeutic doses in 15 to 60 minutes. Nonetheless, a folklore of danger, fueled by earlier formulations no longer available, continues to foment caution. Complement-mediated minor infusion reaction...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Layla Van Doren Michael Auerbach Source Type: research
Sex, lies, and iron deficiency: a call to change ferritin reference ranges
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):617-621. doi: 10.1182/hematology.2023000494.ABSTRACTIron deficiency is a very common and treatable disorder. Of all the tests available to diagnose iron deficiency, the serum ferritin is the most able to discriminate iron deficiency from other disorders. However, the reference range for ferritin in many laboratories will lead to underdiagnosis of iron deficiency in women. Studies have shown that 30%-50% of healthy women will have no marrow iron stores, so basing ferritin cutoffs on the lowest 2.5% of sampled ferritins is not appropriate. In addition, several lines ...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Kylee Martens Thomas G DeLoughery Source Type: research
