Acta Haematologica最新文献

Introduction: Acute myeloid leukemia (AML) represents a significant burden for patients and their families, and to the healthcare system. This study estimated the total cost of illness associated with newly diagnosed AML patients in Canada.

Methods: The economic burden of AML was estimated using an incidence-based model, analyzing different types of AML cases in Canada. Direct and indirect costs were calculated using scientific literature and Canadian clinical experts' inputs. Patients were categorized depending on their eligibility for intensive chemotherapy (fit and unfit patients) as well as according to age and cytogenetic markers.

Results: The total average cost of AML per patient is estimated to be CAD 178,073 with a cost of CAD 210,983 and CAD 145,163 for fit and unfit patients, respectively. The costs related to treatment represent half of the total average cost (52%), followed by hematopoietic stem cell transplant (23%), best supportive care (16%), productivity loss (6%), and wastage (4%).

Conclusion: For patients with AML, the costs associated with fit patients are higher than unfit patients. Hospitalization and best supportive care costs are key cost drivers for the total costs of fit and unfit patients, respectively. This study highlights that AML is associated with a significant economic burden in Canada.

Introduction: Major histocompatibility complex II (MHC-II)-mediated antigen presentation contributes to the pathogenesis of immune thrombocytopenia (ITP). Human leukocyte antigen (HLA)-DRB5 is an MHC-II molecule and this study aims to investigate its role and mechanisms in ITP development.

Methods: Guinea pig anti-mouse platelet (PLT) serum-induced ITP mice received tail vein injection of HLA-DRB5 overexpressing adenoviral vector/immune receptor expressed on myeloid cells-1 (IREM-1) monoclonal antibody (mAb). PLT count changes in mice blood were assessed by a hematology analyzer. MHC-II/CD80/CD86 expression in mice blood was measured by quantitative real-time-PCR and immunofluorescence assay. CD8+ T-cell proportion in mice blood was detected by flow cytometry.

Results: HLA-DRB5 overexpression exacerbated PLT reduction since the 5th day of the establishment of ITP mice model and enhanced MHC-II/CD80/CD86 expression upregulation as well as CD8+ T-cell ratio elevation in the blood of ITP mice, while its effects were reversed by IREM-1 mAb.

Conclusion: HLA-DRB5 overexpression upregulates MHC-II-mediated antigen presentation to CD8+ T cells, thus lowering PLT count in the ITP mice model.

Introduction: Acute promyelocytic leukemia (APL) is genetically characterized by the fusion of promyelocytic leukemia (PML) gene with retinoic acid receptor alpha (RARα) resulting from a t(15;17)(q24;q21) chromosomal translocation. An infrequent but recurrent finding in APL is the formation of an isochromosome of the derivative chromosome 17; ider(17)(q10)t(15;17) or ider(17q). This rearrangement in APL results in an additional copy of the PML-RARα fusion gene as well as loss of 17p/TP53. Due to the infrequent occurrence of the ider(17q), the prognostic impact of this genetic finding is not well known. Case Presentation(s): Here, we describe the clinical characteristics and outcomes of our case series of 5 patients with ider(17q) APL treated at the University of Maryland and Johns Hopkins University.

Conclusion: In our series, patients with APL with ider(17q) did not have a worse prognosis.

Background: Current guidelines recommend yearly evaluation of glucose metabolism with oral glucose tolerance test (OGTT) in patients with thalassemia major (TM) from their 10th year onwards.

Aims: The aim of the study was to retrospectively evaluate all the OGTT tests performed in a single pediatric center during the last decade and assess the necessity of yearly performed OGTT in patients with TM during the second decade of life.

Results: One hundred and seventy tests performed on 39 patients (24 boys) were included in the analysis. Mean age at the time of each OGTT was 14.15 ± 2.79 years. Seventeen tests (10%) in 8 patients (5 boys) were characterized as impaired glucose tolerance (IGT), whereas in 2 tests (1.18%), fasting glucose values were above 200 mg/dL (diabetes mellitus). Acknowledging the fact that there could be sporadic technical errors, especially in fasting glucose abnormal values, we selectively separated patients with either IGT and abnormal HOMA, MATSUDA, or QUICKI indices or persistently impaired fasting glucose or IGT. With these criteria, 7 patients (4 boys) were identified. No significant differences were observed in demographic and anthropometric parameters, ferritin levels, and mean volume of blood transfused in patients with a definite abnormal glucose metabolism. In order to address selection criteria for performing OGTT without missing a single patient with a definite glucose intolerance, these criteria should include (i) a first OGTT test at the initiation of puberty, (ii) OGTT in any patient with a fasting glucose above 100 mg/dL, and (iii) OGTT in any patient with a ΗΟΜΑ-IR index above 1.85 and yearly onwards. By adopting these criteria, total OGTT tests performed could have been reduced from 170 to only 91, translating to a significant reduction of 46.47%.

Conclusions: Only a small percentage of young patients with transfusion-dependent b-thalassemia exhibit abnormal glucose metabolism during their second decade of life. By adopting specific selection criteria, one may avoid performing this time- and money-consuming test in a significant proportion of patients, albeit without sacrificing timely detection and intervention.

Introduction: Plasma cell leukemia (PCL) can occur de novo as primary PCL (pPCL), or in patients with prior diagnosis of multiple myeloma (MM) as secondary PCL (sPCL). In 2021, the diagnostic criteria have been revised, establishing a new cut-off of ≥5% plasma cells in the peripheral blood. Lacking specific clinical trials, PCL is treated similarly to MM; however, outcome for patients with PCL remains poor. Here, we report outcomes for patients with pPCL and sPCL in the era of novel agents.

Methods: We performed a retrospective analysis and identified 19 patients (11 pPCL, 8 sPCL) who have been treated for PCL between 2010 and 2022 at University Hospital Essen.

Results: Patients with pPCL had a median overall survival (OS) of 37.8 months (95% CI: [15.4; 52.3] months) from diagnosis, with a median time to next treatment (TTNT) of 18.4 (2.0; 22.9) months. All patients were treated with a proteasome-inhibitor (PI)-based induction therapy, and the majority was consolidated with an autologous stem cell transplantation (SCT). Five of these patients received a tandem transplantation. Patients with sPCL had a median OS of only 1.5 months after diagnosis of PCL. Only 1 patient achieved a remission with daratumumab and subsequent allogenic SCT.

Conclusion: With our study, we add evidence for a PI-based induction therapy followed by a consolidating autologous SCT for patients with pPCL and give further evidence that a tandem transplant concept might be beneficial. The diagnosis of sPCL remains devastating and needs new therapeutic approaches.

Introduction: Chimeric antigen receptor T (CAR-T) cell therapy, emerging as an efficient treatment option for patients with secondary central nervous system (CNS) lymphoma, is frequently complicated with immune effector cell-associated neurotoxicity syndrome (ICANS).

Case presentation: We report a case of a 64-year-old woman with transformed follicular lymphoma, developing high-grade ICANS with eosinophilic pleocytosis following third-line therapy with CAR-T cells (tisagenlecleucel). During bridging therapy, she declined neurologically and was diagnosed with secondary CNS lymphoma. She received methotrexate-cytarabine-thiotepa-rituximab regimen with clinical and radiological improvement. Post-CAR-T cell infusion she developed cytokine release syndrome grade II and ICANS grade III. Given the lack of response to steroids, anakinra was initiated with complete ICANS resolution. Cerebrospinal fluid (CSF) analysis, performed only on day +10 due to thrombocytopenia, revealed eosinophils, while infections were excluded.

Conclusion: This report emphasizes the importance of CSF analysis in individuals with CAR-T-related neurotoxicity for elucidating the role of specific immune cells in such complications.

Background: Recent advancements in cellular therapies, particularly chimeric antigen receptor T-cells (CAR-T) and T-cell-engaging bispecific antibodies have significantly altered the therapeutic landscape for multiple myeloma. There are two US FDA approved CAR-T products targeting BCMA available for commercial use at this time. Though these innovative therapies have demonstrated considerable efficacy in heavily pretreated multiple myeloma patients, many challenges remain, including accessibility, potential toxicities such as cytokine release syndrome and neurotoxicity and development of resistance through targeted antigen loss and T-cell exhaustion and various other mechanisms. CRISPR edited allogeneic CAR-T cells, CAR-NK cells, and structural makeover of autologous CART with safety switches are being studied to address current limitations in cellular therapy. Additionally, newer target antigens such as GPRC5D, FcRH5, armored CAR-T cells that resist immunosuppressive cytokines such as TGF-β are being investigated.

Summary: This review summarizes safety and efficacy of currently available CART, discusses challenges with these therapies, and ongoing research efforts aimed at addressing resistance, mitigate treatment-related toxicities, and refining for broader applicability and prolonged efficacy.

Key messages: CART cell therapy has shown significant benefit in treatment of multiple myeloma. Many challenges persist. Novel strategies with structural modifications are being incorporated to overcome the limitations.

Background: Managing cancer-associated thrombosis (CAT) is a significant clinical challenge due to several factors such as increased bleeding tendency, frailty, and drug-drug interactions. For many years, the drug of choice for treating CAT was low molecular weight heparin (LMWH). Recently, direct oral anticoagulants (DOACs) entered to the therapeutic milieu of CAT. However, due to the large diversity among patients with CAT in clinical and laboratory characteristics, not all patients will equally benefit from treatment with DOACs. Furthermore, several subgroups of patients with CAT have specific characteristics that influence the anticoagulant decision-making process.

Summary: In this review, we present four different theoretical clinical case scenarios, each representing a different challenge that is associated with thrombosis management; brain metastasis, malignancies of the gastrointestinal tract, drug-drug interactions (DDIs), and thrombocytopenia. By reviewing current literature, we suggest our clinical approach for managing these cases in the era of DOACs.

Key messages: (1) The management of patients with brain tumors and CAT is challenging due to increased risk for both intracranial hemorrhage and recurrent venous thromboembolism. Both LMWH and DOACs are optional treatment in this setting. (2) There are conflicting data regarding the bleeding risk in patients with GI malignancies. Treatment with LMWH should be considered specifically in patients with advanced disease and unresectable tumors. (3) There is a paucity of data regarding DDI in patients with CAT. However, caution should be exercised when prescribing DOACs to patients receiving concurrent medications that either affect DOAC metabolism or influence bleeding risk. (4) The management of patients with CAT and thrombocytopenia depends on the severity of thrombocytopenia and the timing of the thrombotic event.

Introduction: Waldenström macroglobulinemia (WM) is a rare indolent lymphoma. Zanubrutinib (ZAN), a second-generation BTK inhibitor, has been approved for the treatment of WM in any line of therapy in 2021. Between November 2020 and January 2022, an expanded access program of ZAN opened in Israel for the treatment of patients with relapsed/refractory (R/R)-WM or those ineligible for chemotherapy or ibrutinib in first line.

Methods: This is a multicenter retrospective study aiming to provide real-world data on ZAN in patients with WM in Israel. Demographic and clinical data were collected and coded from electronic files. Response was evaluated by the investigator's assessment. As the program closed, patients transitioned to commercial ZAN.

Results: Thirteen patients (12 R/R; 1 treatment-naive) were enrolled across 8 centers in Israel. The median age at ZAN initiation was 71 years (range, 50-85); 6 were males; 10 had high IPSS-WM. R/R patients had a median of 1 (1-4) prior lines of therapy. Other than progressive disease after chemoimmunotherapy, the most common considerations for choosing ZAN were patients' age and/or comorbidities (n = 5), as well as ibrutinib toxicity. The initial ZAN dose was reduced in 4 patients. The median time on ZAN was 19.5 months (2.9-29.5). Of 12 evaluable patients, the ORR was 83% with 3 minor responses, 6 PRs, and 1 VGPR. With a median follow-up of 19.6 months, 7 patients were still on ZAN, 5 progressed, 4 while on ZAN, and 1 after ZAN was stopped due to AE. Eighteen-month PFS and OS were 60.5% and 77%, respectively. Eight (61%) patients had AEs of any grade, and 3 (23%) of grade 3-4; 2 stopped ZAN due to congestive heart failure and extreme fatigue.

Conclusion: The results of this real-world high-risk population are consistent with prospective studies highlighting the efficacy and safety of ZAN.