CAR T-cell therapy in aggressive lymphomas-identifying prognostic and predictive markers
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):357-363. doi: 10.1182/hematology.2023000436.ABSTRACTWe discuss different pre-infusion, post-infusion and post-CAR T-cell relapse prognostic factors influencing the outcomes of anti-CD19 CAR T-cell therapy in patients with relapsed or refractory large B-cell lymphomas. Despite the overall positive results of anti-CD19 CAR T-cell therapy, a significant percentage of patients relapse. We summarize the efforts made to identify predictive factors for response and durable remissions and survival. In the pre-infusion setting, the patient-related factors discussed include ...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Alberto Mussetti Nicole Fabbri Anna Sureda Source Type: research
Clonal hematopoiesis in frequent whole blood donors
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):299-304. doi: 10.1182/hematology.2023000483.ABSTRACTHealthy volunteer donors are committed to contributing key medical resources. Repeated, regular donation of whole blood represents a specific trigger of hematopoietic stress. Hematopoietic stem cells (HSCs) are known to respond to environmental triggers by altering their differentiation and/or proliferative behavior. This can manifest in long-term changes in the clonal dynamics of HSCs, such as the age-associated expansion of HSCs carrying somatic mutations in genes associated with hematologic cancers-that is, clo...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Darja Karpova Source Type: research
Clonal evolution in inherited marrow failure syndromes predicts disease progression
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):125-134. doi: 10.1182/hematology.2023000469.ABSTRACTProgression to myelodysplastic syndromes (MDS) and acute myeloid leukemia is one of the most serious complications of the inherited bone marrow failure and MDS-predisposition syndromes. Given the lack of predictive markers, this risk can also be a source of great uncertainty and anxiety to patients and their providers alike. Recent data show that some acquired mutations may provide a window into this risk. While maladaptive mechanisms, such as monosomy 7, are associated with a high risk of leukemogenesis, mutation...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Kristen E Schratz Source Type: research
Understanding differential technologies for detection of MRD and how to incorporate into clinical practice
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):682-690. doi: 10.1182/hematology.2023000454.ABSTRACTPatient- and leukemia-specific factors assessed at diagnosis classify patients with acute myeloid leukemia (AML) in risk categories that are prognostic for outcome. The induction phase with intensive chemotherapy in fit patients aims to reach a complete remission (CR) of less than 5% blasts in bone marrow by morphology. To deepen and sustain the response, induction is followed by consolidation treatment. This postremission treatment of patients with AML is graduated in intensity based on this favorable, intermedia...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Jacqueline Cloos Lok Lam Ngai Michael Heuser Source Type: research
Are transplant indications changing for myelofibrosis?
Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):676-681. doi: 10.1182/hematology.2023000453.ABSTRACTMyelofibrosis is a devastating myeloid malignancy characterized by dysregulation of the JAK-STAT pathway, resulting in splenomegaly, constitutional symptoms, anemia, thrombocytopenia, leukocytosis, and an increased likelihood of progression to acute leukemia. The only curative option is allogeneic stem cell transplantation. The numbers of transplants have been increasing every year, and although there have been improvements in survival, there remain many unanswered questions. In this review, we will evaluate patie...
Source: Hematology ASH Education Program - December 9, 2023 Category: Hematology Authors: Jeanne Palmer Source Type: research
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
