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Recently the World Health Organization (WHO), in collaboration with the European Association for Haematopathology and the Society for Hematopathology, published a revised and updated edition of the WHO Classification of Tumors of the Hematopoietic and Lymphoid Tissues. The 4th edition of the WHO classification incorporates new information that has...
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... [1][2][3][4] Although NPM1-mutated (NPM1 mut ) AML was initially included as provisional by the World Health Organization (WHO) in 2008, it was formally recognized as a unique entity in the revised WHO 2017 edition given the distinct clinicopathologic features and favorable responses to treatment with intensive chemotherapy. 3,5,6 NPM1 mutations are infrequently observed in the setting of myeloid neoplasms (MNs) with <20% bone marrow (BM) blasts, otherwise classified as myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) including chronic myelomonocytic leukemia (CMML). 3 Consequently, previous classifications did not consider these cases as distinct entities. ...
Introduction
NPM1‐mutated (NPM1mut) myeloid neoplasms (MNs) with <20% bone marrow (BM) blasts (NPM1mut MNs<20) are uncommon, and their classification remains inconsistent.
Methods
The clinicopathologic features of 54 patients with NPM1mut MNs <20 were evaluated and compared with wild‐type NPM1 MNs <20 and NPM1mut MNs≥20, respectively.
Results
NPM1mut MNs had similar features regardless of blast percentage, except for higher IDH2 (29% vs 7%, p = .023) and FLT3 (70% vs 11%, p < .001) frequency in patients with ≥20% BM blasts. Thirty‐three (61%) patients with NPM1mut MNs <20 received low‐intensity chemotherapy (LIC) and 12 (22%) received intensive chemotherapy (IC). Higher complete remission rates (75% vs 27%, p = .006) and median overall survival (mOS) (not reached vs 30.4 months, p = .06) were observed with IC compared to LIC. Young patients (age <60 years) did not reach mOS either when treated with LIC or IC. Stem cell transplant was associated with increased survival only in patients treated with LIC (HR, 0.24; p = .025). No differences in mOS were observed by BM blast strata (32.2 months, not reached and 46.9 months for <10%, 10%–19%, and ≥20% blasts, p = .700) regardless of treatment modality (LIC: p = .900; IC: p = .360). Twenty‐three patients (43%) with NPM1mut MNs <20 had marrow blast progression to ≥20%.
Conclusions
Overall, NPM1mut MNs define a unique entity independent of BM blast percentage.
... The decreased incidence rate of CEL may be partially attributed to modifications in its diagnostic criteria. In the 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia, a specific group of patients with eosinophilia and gene rearrangements involving PDGFRA, PDGFRB, or FGFR1 were excluded from the diagnosis of CEL and classified as a separate entity, namely "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1 (MLNE)", which have distinct clinical and molecular features and respond well to tyrosine kinase inhibitors 18 . Therefore, this reclassification may have reduced the number of cases that were previously diagnosed as CEL based on the older criteria. ...
Chronic Eosinophilic Leukemia (CEL), a rare and intricate hematological disorder characterized by uncontrolled eosinophilic proliferation, presents clinical challenges owing to its infrequency. This study aimed to investigate epidemiology and develop a prognostic nomogram for CEL patients. Utilizing the Surveillance, Epidemiology and End Results database, CEL cases diagnosed between 2001 and 2020 were analyzed for incidence rates, clinical profiles, and survival outcomes. Patients were randomly divided into training and validation cohorts (7:3 ratio). LASSO regression analysis and Cox regression analysis were performed to screen the prognostic factors for overall survival. A nomogram was then constructed and validated to predict the 3- and 5-year overall survival probability of CEL patients by incorporating these factors. The incidence rate of CEL was very low, with an average of 0.033 per 100,000 person-years from 2001 to 2020. The incidence rate significantly increased with age and was higher in males than females. The mean age at diagnosis was 57 years. Prognostic analysis identified advanced age, specific marital statuses, and secondary CEL as independent and adverse predictors of overall survival. To facilitate personalized prognostication, a nomogram was developed incorporating these factors, demonstrating good calibration and discrimination. Risk stratification using the nomogram effectively differentiated patients into low- and high-risk groups. This study enhances our understanding of CEL, offering novel insights into its epidemiology, demographics, and prognostic determinants, while providing a possible prognostication tool for clinical use. However, further research is warranted to elucidate molecular mechanisms and optimize therapeutic strategies for CEL.
... In addition to surface antigens, we identified intracellular antigens to establish the correct lineage affiliation according to the 2008 and 2016 WHO recommendations [6,18]. We used MPO in our first panel tube as best myeloid lineage determinant, Table 1. ...
The diagnosis of acute lymphoblastic leukemia (ALL), which is the most common type of cancer in children, has become more accurate with the use of flow cytometry. Here, this technology was used to immunophenotype leukemic cells in peripheral blood samples from Libyan pediatric ALL patients. We recruited 152 newly diagnosed patients at Tripoli Medical Center (Tripoli, Libya) by morphological examination of blood and bone marrow. Twenty-three surface and cytoplasmic antigen markers were used to characterize B and T cells in circulating blood cells by four-color flow cytometry. Six children (3.9%) turned out to have biphenotypic acute leukemia, 88 (57.9%) had B ALL, and 58 (38.1%) had T ALL. There were 68 cases of pro-B ALL CD10-positive (44.7%), 8 cases of pro-B ALL CD10-negative (5.2%), 6 cases of pre-B ALL (3.9%), and 6 of mature-B ALL (3.9%). CD13 was the most commonly expressed myeloid antigen in ALL. We present immunophenotypic data for the first time describing ALL cases in Libya. The reported results indicate that the most common subtype was pro-B ALL, and the frequency of T-ALL subtype was higher compared to previous studies. Six cases were positive for both myeloid and B lymphoid markers. Our findings may provide the basis for future studies to correlate immunophenotypic profile and genetic characteristics with treatment response among ALL patients.
... Although the myeloblast percentage was 11.6% in the case of this lion, promyelocytes (27.3%) were counted as blasts for the total blast percentage calculation, as it has been previously performed in humans for the diagnosis of AML. 2 AML generally results from acquired genetic abnormalities in stem cells, and cell type-specific mutations lead to a predominant cell lineage, allowing the classification of AML into subtypes. Neutrophilic (M2) differentiation has been most commonly reported in cats. ...
OBJECTIVE
To describe the clinical presentation, progression, and diagnosis of acute myeloid leukemia (AML) with neutrophilic differentiation in an African lion ( Panthera leo ).
ANIMAL
A 12-year-old male African lion kept at a zoological institution in Colombia.
CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES
The lion presented for anorexia, pale mucous membranes, and a hind limb lameness of acute onset. Feline leukemia virus testing was negative, and repeated blood samples revealed severe anemia, intermittent thrombocytopenia, lymphopenia, and neutrophilia. Coinfection with Anaplasma and Mycoplasma spp and chronic kidney disease were diagnosed based on clinicopathological findings.
TREATMENT AND OUTCOME
The lion received symptomatic treatment, doxycycline, and methylprednisolone or prednisolone. Euthanasia was elected due to clinical deterioration and unresponsive anemia, despite the resolution of Anaplasma and Mycoplasma spp infections. AML with neutrophilic differentiation was diagnosed based on bone marrow cytology, histopathology, and immunohistochemistry.
CLINICAL RELEVANCE
AML is a rare, aggressive hematopoietic disorder in domestic cats, although it has not yet been reported in nondomestic cats. This is the first description of the clinicopathological, histological, and immunohistochemical features of AML with neutrophilic differentiation in an FeLV-negative African lion that lacked circulating blasts.
... [2]. Patients with higher-risk MDS have a high risk of AML transformation and a poor prognosis, with median survival of less than 2 years [2][3][4][5]. ...
... Caregivers face many challenges when caring for patients with advanced cancer diagnoses and poor prognoses [23,24]. A patient with advanced cancer and their caregiver can experience physical, emotional, social, spiritual and functional issues [2,5]. These factors are a burden for caregivers, which might result in emotional distress, often causing them to develop depression and burnout [25]. ...
Patients with higher-risk myelodysplastic syndromes (MDS) face considerable challenges in disease management and often require caregiver support. Reports on the burden of caring for patients with advanced cancer suggest that caregivers receive insufficient support. Our research aimed to identify key challenges for caregivers of patients with higher-risk MDS.
Online bulletin board is a qualitative research methodology which enables data collection via a web-based platform. A mix of moderator-led discussion guide and interparticipant discussion provides the caregiver insights as online dialogue, which then undergo content analysis to extract key findings.
Sixteen caregivers participated from the USA (n = 5), UK (n = 6) and Canada (n = 5). Content analysis identified the caregiver experience in higher-risk MDS as multifactorial, with seven key categories of caregiver burden: caregiver role and burden, mental health, family dynamics, disease experience, treatment experience, healthcare professional (HCP) interactions and information and education.
There is significant impact and burden on caregivers of patients with higher-risk MDS, which varies depending on disease stage, choice (or lack of choice) of treatments, and the personal situation of the caregiver. Emotional stress occurs mostly at diagnosis/prognosis stage and when told to ‘watch and wait’, which is amplified when HCPs are perceived to lack knowledge/expertise about MDS. There is a need for better education about MDS for HCPs, patients, caregivers and the general community; a need for improved communication between patients/caregivers and HCPs; and a high unmet need for better mental health and emotional support for both patient and caregiver.
... This analysis included patients with de novo AML (excluding the AML-M3 subtype) who were diagnosed in the Center for Hematology of Southwest Hospital from July 2012 to June 2019. AML was diagnosed according to the 2008 World Health Organization (WHO) classification of myeloid tumors [24]. The exclusion criteria are as follows: ...
Inflammation and nutrition related proteins participate in the development of acute myeloid leukemia (AML). It has been reported that the albumin-to-fibrinogen ratio (AFR) could serve as a prognostic indicator in patients with malignancy, but the precise relevance of AML is unclear. This study aimed to evaluate the effect of AFR on survival prognosis in patients with AML. We analyzed 227 patients newly diagnosed with non-M3 AML. AFR was calculated as albumin divided by fibrinogen. Based on the cutoff point from X-tile program, patients were divided into AFR-high (38.8%) and AFR-low (61.2%) groups. AFR-low group showed a poorer complete remission rate (P < 0.001) and median time to relapse (P = 0.026), while the mortality was higher (P = 0.009) than AFR-high ones. According to the log-rank test, AFR-low group had shorter OS (P < 0.001) and DFS (P = 0.034). Multivariate analysis identified AFR, ELN risk, bone marrow transplant, and hemoglobin as independent prognostic variables associated with OS. A visualized nomogram for predicting OS was performed. The C-index (0.75), calibration plots, and decision curve analyses of new model showed better discrimination, calibration, and net benefits than the ELN risk model. The time-dependent receiver operating characteristic (ROC) curve of 1-, 2-, and 3-year also functioned well (AUC, 0.81, 0.93 and 0.90, respectively). Our study provided a comprehensive view of AFR which could be an independent prognostic indicator in AML patients. The prognostic model utilized readily available information from ordinary clinical practice to improve predictive performance, identify risks, and assist in therapeutic decision-making.
... JAKoMo is a two-arm, open-label, phase IV, non-interventional study of patients with MF who were either JAKi naïve or pretreated with JAKi. Patients ≥ 18 years with a diagnosis of PMF, according to the World Health Organization classification, or PPV-MF or PET-MF, according to the International Working Group for Myeloproliferative Neoplasms Research and Treatment criteria [14,15], who were suitable for in-label treatment with RUX were eligible. Between September 2012 and September 2019, 928 patients (Arm A: n = 464 JAKi-naïve patients; Arm B: n = 464 JAKipretreated patients) eligible for analysis were enrolled across 122 centers in Germany. ...
Ruxolitinib (RUX) is a Janus kinase 1/2 inhibitor (JAKi) approved in the EU for treating disease‑related splenomegaly or symptoms in adults patients with myelofibrosis (MF). This is an interim analysis of JAKoMo, a prospective, non‑interventional, phase IV study in MF. Between 2012–2019 (cutoff March 2021), 928 patients (JAKi-naïve and -pretreated) enrolled from 122 German centers. This analysis focuses on JAKi-naïve patients. RUX was administered according to the Summary of Product Characteristics. Compared to the COMFORT-I, -II, and JUMP trials, patients in JAKoMo were older (median 73 years), had poorer Eastern Cooperative Oncology Group (ECOG) performance statuses (16.5% had ECOG ≥ 2), and were more transfusion dependent (48.5%). JAKoMo represents the more challenging patients with MF encountered outside of interventional studies. However, patients with low-risk International Prognostic Scoring System (IPSS) scores or without palpable splenomegaly were also included. Following RUX treatment, 82.5% of patients experienced rapid (≤ 1 month), significant decreases in palpable spleen size, which remained durable for 24 months (60% patients). Symptom assessment scores improved significantly in Month 1 (median –5.2) up to Month 12 (–6.2). Common adverse events (AEs) were anemia (31.2%) and thrombocytopenia (28.6%). At cutoff, 54.3% of patients had terminated the study due to, death, AEs, or deterioration of health. No new safety signals were observed. Interim analysis of the JAKoMo study confirms RUX safety and efficacy in a representative cohort of real-world, elderly, JAKi-naïve patients with MF. Risk scores were used in less than half of the patients to initiate RUX treatment.
Trial registration: NCT05044026; September 14, 2021.
... The aim of our retrospective study was to analyze the efficacy and safety of the conditioning regimens, GVHD prophylaxis, and management of complications employed at our center for salvage transplantation, and to evaluate the prognostic factors that affect transplant outcomes. The diagnosis of AML in our study was based on the 2008 World Health Organization (WHO) criteria [13], and the risk categories were determined using the European Leukemia Net (ELN) guidelines in 2017 [14]. Refractory or relapsed AML was classified as primary refractory disease, defined as AML that fails to achieve CR after ≥2 cycles of chemotherapy, and refractory relapse, defined as relapsed AML that fails to achieve CR after 1-2 courses of salvage chemotherapy. ...
Patients with relapsed and refractory acute myeloid leukemia (R-R AML), especially those in non-remission (NR) have a poor prognosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to optimize the entire allo-HSCT process for R-R AML patients and identify potential factors affecting clinical outcomes after HSCT, we retrospectively analyzed 44 adult patients with R-R AML who underwent salvage allo-HSCT while in NR or with concomitant extramedullary leukemia at the Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2013 to 2022. The 1-year and 2-year overall survival (OS) of the 44 patients were 55.3% (95% confidence interval [CI], 41.1%-74.3%) and 44.4% (95%CI, 30.2%-65.4%), respectively. The 1-year and 2-year cumulative incidence of relapse (CIR) were 39.4% (95%CI, 38.0%-40.7%) and 53.0% (95%CI, 51.0%-55.1%), respectively, and the 1-year and 2-year leukemia-free survival (LFS) were 37.8% (95%CI, 24.8%-57.7%) and 20.3% (95%CI, 9.1%-45.3%), respectively. The 100-day, 1-year and 2-year treatment-related mortality (TRM) was 13.8% (95%CI, 13.3%-14.4%), 22.8% (95%CI, 21.9%-23.7%) and 26.7% (95%CI, 25.5%-27.8%), respectively. Multivariate analysis revealed that patients who developed chronic graft-versus-host disease (cGVHD) after transplantation had lower relapse rate. Our analysis also indicated that patients with blast counts in bone marrow (BM) <20% and those with ≥20% had comparable clinical outcomes after allo-HSCT. In conclusion, our study demonstrated that R-R AML patients in NR or with concomitant extramedullary leukemia can benefit from allo-HSCT, regardless of leukemia burden at the time of transplantation. Patients who experience cGVHD after allo-HSCT may have lower relapse rate due to enhanced graft-versus-leukemia (GVL) effects, but cGVHD should be controlled at mild to moderate level to avoid life-threatening complications.
... The DLBCL diagnosis standard follows the diagnostic criteria of the World Health Organization classification [3]. And the International Prognostic Index (IPI), which incorporates details about the age, LDH, ECOG performance status, stage, and extranodal disease, is also of great value in planning therapy. ...
Objective: Diffuse Large B-Cell Lymphoma (DLBCL) is a common and frequently occurring subtype of Non-Hodgkin Lymphoma (NHL). The effective treatment and prognosis of DLBCL are still urgently needed to be explored. This article aims to shed light on the connection between DLBCL survival and NR3C1 expression levels. Methods: First, we divided the 952 DLBCL patients into an NR3C1 high-expression group and an NR3C1 low-expression group and compared the baseline characteristics of the two groups. Second, we used multivariate analysis to predict the dependent variable for age, pathology, ECOG score, lactate dehydrogenase (LDH) ratio, and NR3C1 expression level. Finally, we analyzed the progression-free survival (PFS) and overall survival rate (OS) of DLBCL patients with high or low NR3C1 expression. Results: DLBCL patients with high NR3C1 expression had a better prognosis than those with low NR3C1 expression (OS, P < 0.0001). In DLBCL patients of CHOP therapy, high NR3C1 expression was associated with a good survival prognosis in OS (OS, P = 0.028). Conclusion: In multivariate analysis, NR3C1 high expression was an independent prognostic factor that predicted a longer OS of DLBCL (OS, P = 0.0003). NR3C1 is considered an independent predictor of DLBCL patients and can be used as a biomarker for the prognosis of DLBCL.
... Although prior exposure to radiotherapy or chemotherapy has always been considered a prerequisite for t-MN development, the list of "trigger drugs" and the latency between exposition to each treatment and disease manifestation have been periodically updated. 8,9,2 This evolution reflects not only the constant improvement in the understating of the mutagenic mechanisms of chemotherapy but also the need to include novel agents in the debate. ...
Therapy-related myeloid neoplasms (t-MNs) encompass a specific sub-group of myeloid malignancies arising after exposure to radio/cytotoxic agents for the treatment of unrelated diseases.
Such malignancies present unique features, including advanced age, high comorbidities burden, and unfavorable genetic profiles. All these features justify the need for a specific diagnostic work-up and dedicated treatment algorithms. However, as new classification systems recognize the unique clinical characteristics exhibited by t-MNs patients, how to assess fitness status in this clinical setting is largely unexplored. Optimizing fitness assessment would be crucial in the management of t-MNs patients, considering that factors usually contributing to a worse or better outcome (like age, comorbidities, and treatment history) are patient-specific.
In the absence of specific tools for fitness assessment in this peculiar category of AML, the aim of this review is to describe all those factors related to patient, treatment and disease that allow planning treatments with an optimal risk/benefit ratio.
