Journal of hematology最新文献

Background: Treatment with non-anthracycline (ANT)-based chemotherapy has increased survival in patients with extranodal natural killer/T-cell lymphoma (ENKTCL). However, the relative efficacy of various drug combinations has been contentious. We aimed to identify the most effective chemotherapy regimens for newly diagnosed ENKTCL.

Methods: A network meta-analysis was performed to evaluate the differences in survival and treatment responses across various regimens. The primary objective was overall survival (OS), while secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and complete response (CR). We utilized a Bayesian framework to perform the network meta-analysis. Rank probabilities were assessed by the surface under the cumulative ranking curve (SUCRA). Node-splitting method was used to assess the inconsistency.

Results: A total of 1,113 patients were enrolled across 10 studies. Chemotherapy regimens were grouped into five modalities, for which six types of direct comparisons were available. We identified the asparaginase (ASP)/gemcitabine (GEM)-based regimens superiority over ANT-based, non-ASP/ANT-based and ASP/methotrexate (MTX)-based regimens on OS. Although no significant differences were observed compared with ASP/not otherwise specified-based, ASP/GEM-based regimens were still the best option chemotherapy for OS. Moreover, the ASP/GEM-based regimens demonstrated advantages in PFS, ORR and CR.

Conclusions: According to our network meta-analysis, it appears that ASP/GEM-based regimens could potentially serve as the most effective frontline chemotherapy option for ENKTCL.

Cyclic thrombocytopenia (CTP) as the name suggests presents with cyclic episodes of thrombocytopenia and is frequently initially misdiagnosed as immune thrombocytopenia. Following a lack of sustained response or abnormally increased response to common treatments used for immune thrombocytopenia, a proper diagnosis of CTP can then be made. Prior reports have shown a subset of patients who respond to cyclosporin A. Here, we present a case of CTP that was initially at another facility presumed to have and treated for immune thrombocytopenic purpura. However, after multiple attempts to treat with steroids, intravenous immunoglobulin (IVIG), rituximab, and eltrombopag, episodes of severe thrombocytopenia followed by thrombocytosis continued. The patient ultimately developed intracerebral hemorrhage (ICH) in the setting of one of the episodes of severe thrombocytopenia and developed multiple subsequent complications from which the patient unfortunately did not recover. It was only after developing ICH that the patient had been evaluated at a center with hematology consultation capabilities, at which time after a detailed review of his case and pattern recognition the proper diagnosis of CTP was made with initiation of cyclosporine. This case was further complicated by need to maintain an adequate platelet threshold post-ventriculoperitoneal shunt placement which was necessary due to his ICH and was placed before diagnosis of CTP could be made. While CTP is a rare diagnosis, this case reinforces a greater need to properly diagnose and consider cyclosporine treatment for CTP, as it has been effective in some patients and may help to prevent patient morbidity and especially catastrophic bleeding complications.

Chronic myelogenous leukemia (CML) is a hematologic malignancy with unique significance to the field of hematology and oncology, specifically due to the development of tyrosine kinase inhibitors (TKIs). CML often presents with nonspecific symptoms, and the quality of life in patients with CML has drastically improved as a result of TKIs. However, complications of CML including the risk of transforming into life-threatening blast crises continue to exist. Further, as most patients are asymptomatic in the chronic phase, patients often present with serious complications associated with noncompliance to TKIs. For example, central nervous system (CNS) manifestations of CML have been reported, both as the initial presentation of undiagnosed CML and as known complication of uncontrolled CML. Hyperleukocytosis is a manifestation of uncontrolled CML and leukostasis is a complication, occurring in cases of acute myeloid leukemia (AML). Here we present a rare case of leukostasis in a patient with known CML presenting on computed tomography (CT) as intracranial masses in the chronic phase. Our goal is to discuss this rare case of leukostasis in adult CML and describe its management.

Background: Patients with chronic lymphocytic leukemia (CLL) are vulnerable to coronavirus disease 2019 (COVID-19) and are at risk of inferior response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, especially if treated with the first-generation Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. We aimed to evaluate the impact of the third-generation BTKi, zanubrutinib, on systemic and mucosal response to SARS-CoV-2 vaccination.

Methods: Nine patients with CLL with ongoing zanubrutinib therapy were included and donated blood and saliva during SARS-CoV-2 vaccination, before vaccine doses 3 and 5 and 2 - 3 weeks after doses 3, 4, and 5. Ibrutinib-treated control patients (n = 7) and healthy aged-matched controls (n = 7) gave blood 2 - 3 weeks after vaccine dose 5. We quantified reactivity and neutralization capacity of SARS-CoV-2-specific IgG and IgA antibodies (Abs) in both serum and saliva, and reactivity of T cells activated with viral peptides.

Results: Both zanubrutinib- and ibrutinib-treated patients had significantly, up to 1,000-fold, lower total spike-specific Ab levels after dose 5 compared to healthy controls (P < 0.01). Spike-IgG levels in serum from zanubrutinib-treated patients correlated well to neutralization capacity (r = 0.68; P < 0.0001) and were thus functional. Mucosal immunity (specific IgA in serum and saliva) was practically absent in zanubrutinib-treated patients even after five vaccine doses, whereas healthy controls had significantly higher levels (tested in serum after vaccine dose 5) (P < 0.05). In contrast, T-cell reactivity against SARS-CoV-2 peptides was equally high in zanubrutinib- and ibrutinib-treated patients as in healthy control donors.

Conclusions: In our small cohort of zanubrutinib-treated CLL patients, we conclude that up to five doses of SARS-CoV-2 vaccination induced no detectable IgA mucosal immunity, which likely will impair the primary barrier defence against the infection. Systemic IgG responses were also impaired, whereas T-cell responses were normal. Further and larger studies are needed to evaluate the impact of these findings on disease protection.

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous hematological disorder with malignant potential controlled by immunological characteristics of the tumor microenvironment. Rapid breakthrough in the molecular pathways has made immunological approaches the main anchor in the management of DLBCL, with or without chemotherapeutic agents. Rituximab was the first monoclonal antibody approved for the treatment of DLBCL. Following rituximab that transformed the therapeutic landscape, other novel immunological agents including chimeric antigen T-cell therapy have reshaped the management of relapsed/refractory DLBCL. However, resistance and refractory state remain a challenge in the management of DLBCL. For this literature review, we screened articles from Medline, Embase, Cochrane databases and the European/North American guidelines from March 2010 through October 2022 for DLBCL. Here we discuss immunological agents that will significantly affect future treatment of this aggressive type of lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL); it has a cure rate of approximately 50% with standard anthracycline-based chemoimmunotherapy. However, the clinical outcomes of elderly unfit/frail DLBCL patients remain suboptimal due to poor tolerance of anthracycline-containing regimens. Herein, we report a series of seven elderly unfit patients with DLBCL who were treated with a reduced-intensity anthracycline-free chemoimmunotherapy (rituximab, cyclophosphamide, vincristine, and prednisone) regimen combined with lenalidomide (R₂-COP). Five patients received R₂-COP as first-line therapy, and two patients were treated for relapsed DLBCL. Four patients with newly diagnosed DLBCL and two with relapsed disease achieved complete remission. The R₂-COP regimen was well tolerated. Interim positron emission tomography (PET) scans in four patients after two to three cycles showed a complete metabolic response. At a median follow-up of 24 months, six patients remain in complete remission. R₂-COP is an effective anthracycline-free regimen with encouraging clinical activity in elderly DLBCL patients who are unfit for standard anthracycline-containing regimens.

Background: Secondary iron overload, alloimmunization, and increased risk of infection are common complications in patients with transfusion-dependent thalassemia (TDT). Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) play an essential role in preventing excessive immune response. This research aimed to study the interaction between Tregs and MDSCs in TDT patients and to evaluate the association of these cell types with disease severity.

Methods: This case-control study included 26 patients with TDT and 23 healthy, age- and sex-matched controls. All patients were investigated for complete blood count (CBC), serum ferritin, and flow cytometric analysis of peripheral blood to detect Tregs, MDSCs, and MDSC subsets.

Results: A significant increase was observed in the frequencies of Tregs and MDSCs, particularly monocytic MDSCs (MO-MDSCs), in TDT patients compared with controls. The frequencies of these cells showed a direct association with ferritin level and total leukocyte count and an inverse association with hemoglobin level. Furthermore, a positive correlation was observed between Tregs and each of the total MDSCs and MO-MDSCs.

Conclusions: Levels of Tregs and MDSCs increased in TDT and may probably have a role in suppressing the active immune systems of TDT patients.

Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is an extremely rare B-cell lymphoma. The disease is typically indolent and treatment with splenectomy usually results in durable remissions. Here, we present a case of an extremely aggressive course of SDRPL with transformation to diffuse large B-cell lymphoma and multiple relapses immediately following cessation of immunochemotherapy. We provide results from whole-exome sequencing from debut of SDRPL and from following transformed stages and identified a novel somatic mutation in RB1 as the possible driver of this aggressive disease, which has not been reported earlier in SDRPL.

Hyperammonemia is a rare cause of encephalopathy in multiple myeloma in the absence of hepatic involvement. This is the only reported case of a 74-year-old man who presented with multiple myeloma and achieved complete remission but developed hyperammonemia afterward. He was aggressively treated with a combination of chemotherapy and immunotherapy, with a resolution of his encephalopathy; however, within one month, he relapsed with encephalopathy. He ultimately decided to pursue comfort-care measures. The authors conclude that hyperammonemia in multiple myeloma is a rare but important differential in patients with encephalopathy of unknown causes. Aggressive treatment is of the utmost importance due to the high mortality associated with the condition.