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Critical Reviews in Oncology/hematology Jul 2015Erdheim-Chester disease (ECD) is a rare form of non-Langerhans-cell histiocytosis, associated in more than 50% of cases to BRAF(V600E) mutations in early multipotent... (Review)
Review
Erdheim-Chester disease (ECD) is a rare form of non-Langerhans-cell histiocytosis, associated in more than 50% of cases to BRAF(V600E) mutations in early multipotent myelomonocytic precursors or in tissue-resident histiocytes. It encompasses a spectrum of disorders ranging from asymptomatic bone lesions to multisystemic, life-threatening variants. We reviewed all published reports of histologically-confirmed ECD and explored clinical, radiological, prognostic and therapeutic characteristics in a population of 448 patients, including a unique patient from our Department. To find a clinically relevant signature defining differentiated prognostic profiles, the patients' disease features were compared in relation to their CNS involvement that occurred in 56% of the entire population. Diabetes insipidus, visual disturbances, pyramidal and extra-pyramidal syndromes were the most recurrent neurological signs, whereas concomitant pituitary involvement, retro-orbital masses and axial lesions in the presence of symmetric bilateral osteosclerosis of long bones depicted the typical ECD clinical picture. Patients with CNS infiltration showed a lower occurrence of heart involvement and a higher incidence of bone, skin, retro-peritoneal, lung, aortic and renal infiltration. No difference in the therapeutic algorithm was found after stratification for CNS involvement. A better understanding of the disease pathogenesis, including BRAF deregulation, in keeping with improved prognostic criteria, will provide novel suggestions for the management of ECD.
Topics: Adrenal Cortex Hormones; Adult; Bone and Bones; Central Nervous System; Erdheim-Chester Disease; Humans; Kidney; Male; Myocardium; Point Mutation; Prognosis; Proto-Oncogene Proteins B-raf
PubMed: 25744785
DOI: 10.1016/j.critrevonc.2015.02.004 -
The Journal of Pathology. Clinical... Mar 2021Immune cell infiltration has been identified as a prognostic biomarker in several cancers. However, no immune based biomarker has yet been validated for use in... (Meta-Analysis)
Meta-Analysis
Immune cell infiltration has been identified as a prognostic biomarker in several cancers. However, no immune based biomarker has yet been validated for use in pancreatic ductal adenocarcinoma (PDAC). We undertook a systematic review and meta-analysis of immune cell infiltration, measured by immunohistochemistry (IHC), as a prognostic biomarker in PDAC. All other IHC prognostic biomarkers in PDAC were also summarised. MEDLINE, EMBASE and Web of Science were searched between 1998 and 2018. Studies investigating IHC biomarkers and prognosis in PDAC were included. REMARK score and Newcastle-Ottawa scale were used for qualitative analysis. Random-effects meta-analyses were used to pool results, where possible. Twenty-six articles studied immune cell infiltration IHC biomarkers and PDAC prognosis. Meta-analysis found high infiltration with CD4 (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.51-0.83.) and CD8 (HR = 0.68, 95% CI = 0.55-0.84.) T-lymphocytes associated with better disease-free survival. Reduced overall survival was associated with high CD163 (HR = 1.62, 95% CI = 1.03-2.56). Infiltration of CD3, CD20, FoxP3 and CD68 cells, and PD-L1 expression was not prognostic. In total, 708 prognostic biomarkers were identified in 1101 studies. In summary, high CD4 and CD8 infiltration are associated with better disease-free survival in PDAC. Increased CD163 is adversely prognostic. Despite the publication of 708 IHC prognostic biomarkers in PDAC, none has been validated for clinical use. Further research should focus on reproducibility of prognostic biomarkers in PDAC in order to achieve this.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; B7-H1 Antigen; Biomarkers; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Carcinoma, Pancreatic Ductal; Disease-Free Survival; Humans; Immunohistochemistry; Pancreatic Neoplasms; Prognosis; Receptors, Cell Surface; Reproducibility of Results
PubMed: 33481339
DOI: 10.1002/cjp2.192 -
Hematology (Amsterdam, Netherlands) Dec 2019The addition of lenalidomide (LEN) to azacitidine (AZA) may further improve the outcomes of acute myeloid leukemia (AML) patients as well as patients with high-risk... (Meta-Analysis)
Meta-Analysis
A systematic review and metaanalysis of the efficacy and adverse events of azacitidinepluslenalidomide treatment for patients with acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia .
OBJECTIVES
The addition of lenalidomide (LEN) to azacitidine (AZA) may further improve the outcomes of acute myeloid leukemia (AML) patients as well as patients with high-risk myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients although the evidence for this combination treatment is still relatively limited. This meta-analysis aimed to evaluate efficacy and adverse effects of AZA plus LEN for the treatment of patients with high-risk MDS, AML or CMML.
METHODS
The current study systematically identified all cohort studies of patients with AML and/or MDS and/or CMML who received AZA in combination with LEN that reported the overall complete remission (CR) rate and/or overall response rate (ORR). A DerSimonian-d random-effects model with double arcsine transformation was used for the pooled rates and 95% confidence interval (CI) of the all outcomes.
RESULTS
A total of 10 studies with 406 patients were identified and included into the meta-analysis. The pooled CR rate after the treatment with AZA-plus-LEN regimen was 33.0% (95% CI, 27.7%-38.7%, I = 18%) while the pooled ORR was 49.9% (95% CI, 38.4%-61.5%, I = 72%). Nonetheless, adverse events including grade 3-4 neutrophil toxicity events, platelet toxicity events and febrile neutropenia were common with AZA-plus-LEN regimen.
CONCLUSIONS
The current study may serve as a preliminary data to suggest that the addition of LEN may offer incremental benefit to patients with high-risk MDS, AML and CMML. However, randomized-controlled studies that directly compare the efficacy and adverse events of AZA-plus-LEN regimen versus AZA monotherapy are still needed.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Cohort Studies; Female; Hematologic Diseases; Humans; Lenalidomide; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Male; Middle Aged; Myelodysplastic Syndromes; Treatment Outcome
PubMed: 31221030
DOI: 10.1080/16078454.2019.1631425 -
Cytometry. Part B, Clinical Cytometry May 2021
Topics: Aged, 80 and over; CD4 Antigens; CD56 Antigen; Dendritic Cells; Flow Cytometry; Humans; Leukemia, Myelomonocytic, Chronic; Male; Myeloproliferative Disorders; Skin Neoplasms
PubMed: 32830878
DOI: 10.1002/cyto.b.21932 -
Clinical Lymphoma, Myeloma & Leukemia Apr 2018High-dose chemotherapy with allogeneic hematopoietic stem cell transplantation (allo-HSCT) can produce long-term remission in patients with higher-risk myelodysplastic...
High-dose chemotherapy with allogeneic hematopoietic stem cell transplantation (allo-HSCT) can produce long-term remission in patients with higher-risk myelodysplastic syndromes (HR-MDS) and chronic myelomonocytic leukemia (CMML). However, this treatment regimen is not appropriate for elderly and/or comorbid patients; in these cases, azacitidine is a standard treatment. This systematic review was conducted to evaluate real-world evidence of treatment options for patients with HR-MDS/CMML. Medline and Embase (January 2006 to May 2016) were searched, in addition to conference proceedings and treatment guideline reviews. Studies on clinical effectiveness/efficacy outcomes with a sample size ≥50 patients were included. From 1061 unique citations identified, 87 full-text articles were reviewed, of which 24 articles reported at least 1 outcome of interest. Studies showed that HR-MDS/CMML patients treated with a conventional chemotherapy regimen (CCR) have poorer overall survival (OS). Key findings from individual HR-MDS studies showed improved survival with azacitidine over CCRs and higher overall response rates with clofarabine relative to low-dose cytosine arabinoside (but no significant difference in 2-year OS favoring clofarabine). OS was highest for patients treated with allo-HSCT. Findings indicate limited real-world data on treatment strategies available for HR-MDS/CMML patients. Most studies address the effect of chemotherapy or allo-HSCT on clinical outcomes, so are not applicable to elderly/comorbid patients who are too frail for those treatments. In particular, our analysis revealed limited evidence on viable options after failure of treatment with azacitidine, identifying a significant unmet need in this patient population.
Topics: Aged; Antineoplastic Agents; Combined Modality Therapy; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myelomonocytic, Chronic; Male; Middle Aged; Myelodysplastic Syndromes
PubMed: 29475821
DOI: 10.1016/j.clml.2018.02.001 -
Scandinavian Journal of Immunology Jan 2020Tumour-associated macrophages (TAMs) play an important role in the tumour environment and were reported to be associated with poor prognosis in several tumours. However,... (Meta-Analysis)
Meta-Analysis
Tumour-associated macrophages (TAMs) play an important role in the tumour environment and were reported to be associated with poor prognosis in several tumours. However, the prognostic significance of TAMs in Non-Hodgkin's Lymphoma (NHL) remains controversial. Consequently, we aimed to evaluate the relationship between subpopulations of TAMs and clinical outcomes in NHL patients. We did a comprehensive search of the PubMed, elsevier ScienceDirect, and Cochrane databases and extracted hazard ratio (HR) and their corresponding 95% confidence intervals (95% CIs) from eligible studies. Pooling total effect value by the stata statistical software and analysing correlation of TAMs with overall survival (OS) and progression-free survival (PFS). Furthermore, subgroup analysis and sensitivity analysis were also conducted. We deemed eleven studies, including 1211 NHL patients. Our study demonstrated that high-density CD68 TAMs are associated with poor OS (HR: 1.17; 95% CI, 0.81-1.54; P = .000) and poor PFS (HR: 1.15; 95% CI, 0.63-1.67; P = .000) compared with low-density CD68 TAMs in the tumour microenvironment. Similarly, high-density CD163 TAMs can also predict poor OS (HR: 1.52; 95% CI, 1.11-1.92; P = .000) and shorter PFS (HR: 1.52; 95% CI, 0.73-2.30; P = .000). In addition, the high CD163 /CD68 TAMs ratio is significantly correlated with poor OS (HR: 3.59; 95% CI, 0.77-6.40; P = .013). However, in our subgroup analysis, high-density CD68 TAMs in the tumour microenvironment is associated with better OS (HR: 0.75; 95% CI, 0.41-1.09; P = .000) in NHL patients treated with rituximab chemotherapy. Our results suggest that TAMs are a robust predictor of outcomes in NHL.
Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Cell Count; Humans; Immunophenotyping; Lymphoma, Non-Hodgkin; Macrophages; Prognosis; Publication Bias; Receptors, Cell Surface; Tumor Microenvironment
PubMed: 31419843
DOI: 10.1111/sji.12814 -
Hematology (Amsterdam, Netherlands) Dec 2021The present meta-analysis was performed to evaluate the efficacy, toxicities of both hypomethylating agents (decitabine and azaciticine) in the treatment of CMML... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The present meta-analysis was performed to evaluate the efficacy, toxicities of both hypomethylating agents (decitabine and azaciticine) in the treatment of CMML patients.
METHODS
All available cohort studies of patients with CMML treated with decitabine and azacitidine were identified. The primary endpoints of this meta-analysis were response to hypomethylating agents. Pooled estimates of treatment response and drug-related adverse events were calculated using fixed or random effect models.
RESULTS
Fourteen studies with 600 CMML patients (decitabine: n=196; azacitidine: n=404) were identified and included for meta-analysis. HMAs yielded a pooled ORR estimate of 43% (95% CI: 36%-50%) in patients with CMML. Patients received either azacitidine or decitabine exhibited comparable incidence of ORR (43% vs. 45%, P=0.810), while significantly higher incidence of mCR was observed in patients treated with decitabine (23% vs. 10%, P=0.000). Decitabine treatment was also associated with higher incidence of transfusion independence (42% vs. 20%, P=0.044). Both HMAs led to objective hematologic or non-hematologic AEs (27%-43%), while dosage modification/delay were more frequent in patients treated with azacitidine (81% vs. 67%, P=0.021).
CONCLUSION
This current study may provide preliminary data in evaluating the efficacy and safety of HMAs in patients with CMML. Decitabine and azacitidine are comparable effective and safe in treating CMML. However, it is necessary to point out that any comparison of decitabine and azacitidine with respect to clinical outcomes can only be done in the context of a randomized controlled trial.
Topics: Antimetabolites, Antineoplastic; Azacitidine; Decitabine; Humans; Leukemia, Myelomonocytic, Chronic; Treatment Outcome
PubMed: 33706667
DOI: 10.1080/16078454.2021.1875600 -
International Journal of Dermatology Oct 2023Myeloid neoplasms may metastasize to the skin, presenting a wide range of clinical-pathological features that often lead to a reduction in patients' survival. The... (Review)
Review
Cutaneous involvement in Ph-negative myeloproliferative neoplasms: from extramedullary hematopoiesis to myeloid metastasis with histiocytic differentiation. A systematic review of the literature.
Myeloid neoplasms may metastasize to the skin, presenting a wide range of clinical-pathological features that often lead to a reduction in patients' survival. The presentation varies depending on the category of myeloid neoplasm and its prognostic significance. The literature has specifically focused on the features of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myelomonocytic leukemia (CMML). In this article, we aimed to uncover the peculiarities of clonal skin proliferations in the course of Ph-negative myeloproliferative neoplasms (MPNs). We conducted a systematic review and statistical analysis of the literature data. MPN patients mainly exhibited cutaneous extramedullary hematopoiesis, while a minority displayed cutaneous histiocytic lesions. Furthermore, these patients showed lower survival rates compared to the median survival of MPN patients, especially when calculating survival from the appearance of cutaneous lesions. Our work highlights, for the first time, the prognostic relevance and histological heterogeneity of cutaneous lesions in MPN. Moreover, it emphasizes the importance of dermatological and histological examinations when cutaneous lesions are present.
Topics: Humans; Hematopoiesis, Extramedullary; Hematologic Diseases; Leukemia, Myelomonocytic, Chronic; Physical Examination; Skin
PubMed: 37649236
DOI: 10.1111/ijd.16809 -
Annals of Hematology Mar 2018t(12;22)(p13;q12) is a rare but recurrent chromosomal abnormality involving the ETS transcription factor ETV6 and meningioma 1 (MN1) genes. In this study, we analyzed... (Review)
Review
t(12;22)(p13;q12) is a rare but recurrent chromosomal abnormality involving the ETS transcription factor ETV6 and meningioma 1 (MN1) genes. In this study, we analyzed the clinical, cytogenetic, and molecular features of five new patients with the t(12;22)/MN1-EVT6 who presented with acute myeloid leukemia or chronic myelomonocytic leukemia. We subsequently reviewed the literature and identified seven additional cases reported with t(12;22)/MN1-EVT6. Our data suggest that neoplasms carrying the t(12;22)/MN1-ETV6, although rare, can commonly present as myeloid neoplasms at the initial diagnosis, including acute myeloid leukemia (n = 8), myelodysplastic syndrome (n = 2), and myelodysplastic/myeloproliferative neoplasms (n = 2). There were five men and seven women with a median age of 43 years (range, 15-63 years) at initial diagnosis. Cytogenetics revealed t(12;22) as the sole abnormality in five patients, with the remaining seven patients harboring additional chromosomal aberrations. Of the five patients who received known therapy regimens, all of them had poor response to the idarubicin/mitoxantrone + cytarabine regimen. Of the seven patients with follow-up information, six patients died with a median overall survival time of only 5 months (range, 1-12 months) after the emergence of t(12;22). In summary, patients with t(12;22) are frequently associated with myeloid neoplasms, poor response to chemotherapy, and inferior outcome.
Topics: Adolescent; Adult; Bone Marrow Neoplasms; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 13; Female; Humans; Male; Middle Aged; Oncogene Proteins, Fusion; Proto-Oncogene Proteins c-ets; Repressor Proteins; Retrospective Studies; Trans-Activators; Translocation, Genetic; Tumor Suppressor Proteins; Young Adult; ETS Translocation Variant 6 Protein
PubMed: 29273914
DOI: 10.1007/s00277-017-3208-2 -
Journal of the American Academy of... Jun 2024
Review
PubMed: 38906261
DOI: 10.1016/j.jaad.2024.05.086