Journal of hematology最新文献

Multiple myeloma (MM) is classically associated with organ dysfunction leading to hypercalcemia, renal insufficiency, anemia and bone disease, known as the CRAB criteria. More than 70% of patients with MM present with anemia. Few rare case reports, however, have demonstrated the presentation of MM associated with polycythemia. We present an interesting case of a 65-year-old female who was initially diagnosed with monoclonal gammopathy of undetermined significance (MGUS) which progressed to smoldering myeloma and later developed into MM. The patient also had coexisting polycythemia vera (PCV). We discuss the typical patient presentations as well as the expanded diagnostic criteria for MM. The pathophysiology explaining the coexistence of polycythemia and MM will be explored as well.

Background: There are no standard renal dose adjustments for melphalan conditioning for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. The objective of this study was to evaluate the effect of melphalan dosing and chronic kidney disease (CKD) on transplant-related outcomes, progression-free survival (PFS), and overall survival (OS).

Methods: A retrospective chart review was performed, and MM patients who underwent ASCT between February 2016 and September 2021 were included. Melphalan 200 mg/m² (Mel200) or 140 mg/m² (Mel140) was administered. The cohort was divided based on renal function: creatinine clearance (CrCl) ≥ 60 mL/min (no-CKD) and CrCl < 60 mL/min (CKD). Outcomes measured include PFS, OS, treatment-related mortality (TRM), incidence of adverse events, hospitalization duration, and hospital readmission within 30 days. Statistical analysis included Chi-square test, t-test, and Kaplan-Meier method. Logistic regression model was used to account for melphalan dose adjustment.

Results: A total of 124 patients were included (n = 108 no-CKD, and n = 16 CKD). Median age was 62 years, majority (62%) were male, and 97% had at least a partial response at time of ASCT. Of the 124 patients, nine (7%) received Mel140. Five of these patients had CKD (CrCl range: 26 - 58 mL/min), with one on hemodialysis. Median time to neutrophil engraftment was 13.6 vs. 14.9 days and median time to platelet engraftment was 18.3 vs. 18.5 days in the CKD group vs. no-CKD group, respectively (P = 0.03 and P = 0.8). When adjusting for melphalan dose reduction, the median time to neutrophil engraftment was not statistically significant (P = 0.11). At a median follow-up of 28.7 months, the median PFS for the CKD vs. no-CKD group was 60 vs. 46 months (P = 0.3). One-year OS was 93.8% in the CKD group vs. 97% in the no-CKD group. There was a higher incidence of grade 3 or 4 mucositis in the CKD group vs. no-CKD group (P = 0.013).

Conclusions: There is no significant difference in engraftment, PFS, or OS for MM patients with CKD vs. no-CKD receiving melphalan conditioning for ASCT. Severe mucositis was significantly more common in the CKD group, including when accounting for melphalan dose reduction.

Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is an uncommon subtype of non-Hodgkin lymphoma, with pancreatic involvement being exceedingly rare and documented in only a handful of case reports. We present a unique case of a 31-year-old human immunodeficiency virus (HIV)-positive male with multisite ALK-negative ALCL, who initially presented with a buttock ulcer, leading to a suspicion of primary cutaneous ALCL or lymphomatoid papulosis. However, the discovery of multiple extracutaneous sites, including an atypical pancreatic head involvement, confirmed the diagnosis of systemic ALK-negative ALCL with cutaneous manifestation. The patient received six cycles of brentuximab vedotin + cyclophosphamide-doxorubicin-prednisone (BV + CHP) treatment, achieving a substantial reduction in the size of the pancreatic head mass and no detectable fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan. This case underscores the diagnostic challenges of ALK-negative ALCL in HIV-positive patients with extranodal presentations and demonstrates the potential effectiveness of targeted therapeutic strategies for such cases.

Background: Erythrocyte sedimentation rate (ESR) indirectly measures blood fibrinogen, and it is altered by all those pathological conditions that modify the aggregation of red blood cells. The international guidelines by the International Council for Standardization in Hematology (ICSH) define the Westergren method as the gold standard for ESR, although it is completely operator-dependent, time-consuming, and requires a patient's blood consumption. Therefore, the validation of new ESR analyzers is needed. The aim of this study is the validation of a new automated ESR analyzer, MINI-CUBE (DIESSE, Diagnostica Senese, Italy).

Methods: The samples (n = 270) were collected at the University Hospital of the University of Rome Tor Vergata. A comparison between the automated instrument and the gold standard was performed. Statistical analyses were processed by MedCalc software.

Results: The comparison analysis performed on the overall samples reported a good agreement, showing a Spearman rank correlation coefficient of 0.94 (P < 0.001), compared to the Westergren test. The Bland-Altman analysis showed a mean bias of 1.5 (maximum (max.):19.6; minimum (min.): -16.6). Inter-run (level 1 coefficient of variation (CV): 4.9%; level 2 CV: 0.8%), intra-run (level 1 CV: 21.1%; level 2 CV: 3.2%), and inter-instrument (level 1 CV: 27.1%; level 2 CV: 5.6%) precision were also assessed. The hematocrit value did not interfere with the analysis: Spearman rank correlation coefficient of 0.929 (P < 0.001); mean bias of 1.3 (max.:18.3; min.: -15.6).

Conclusions: Overall results from MINI-CUBE asserted a good correlation rate with the gold standard, and it could be considered an accurate, and objective alternative for the Westergren test.

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.