bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Efficacy of Pegylated Liposomal Doxorubicin, Vincristine and Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma
Authors: Wu Wen , Gao Xiaodong , Xu Lan , Yan Hua , Shen Zhixiang , Hu Jiong 
Published: April 2020

Abstract
Object: To investigate the short-term and long-term efficacy and toxicity of pegylated liposomal doxorubicin, vincristine and dexamethasone (DVD) in patients with newly diagnosed multiple myeloma (MM).
Methods: Twenty-five patients (13 males, 12 females, median age 55 years) with newly diagnosed multiple myeloma were treated with pegylated liposomal doxorubicin 40 mg/m2 and vincristine 2 mg intravenously on day 1 plus dexamethasone 40 mg intravenously or orally on days 1–4 (DVD) for median 4.5 (2–8) cycles. Treatment was repeated every 4 weeks. Response was evaluated according to the International Uniform Response Criteria for Multiple Myeloma (2006) before initiation of each course. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0.
Results: After 4.5 (2–8) courses of the median cycles, clinical response was observed in 20 patients (80%), including complete response in 4 (16%), very good partial response in 3 (12%), partial response in 10 (40%), minimal response in 3 (12%) and stable disease in 2 (8%). The median time to initial response was 1.2 months and the median time to best response was 4 months. After 25 (2–50) months of median follow-up, the median progression-free survival was 20 months, while the median overall survival has not yet been reached. The overall survival rate was 72% (18/25). The most common adverse events were gastrointestinal symptoms (nausea and vomiting in 10, constipation in 9 patients), neutropenia (7 patients), anemia (6 patients) and thrombocytopenia (4 patients). DVD was associated with more hand-foot syndrome (4 patients) and mucitis (2 patients).
Conclusions: DVD scheme is an effective therapy with a high response rate and manageable toxicities for patients with newly diagnosed multiple myeloma.
Modulation of Soluble Interleukin 2 Receptor (sIL-2R) Levels in Patients with HIVWaldenstrom Macroglobulinemia (HIV-WM) Treated with Biaxin-Pentoxifylline-Dexamethasone Followed by Prednisolone (BPD-Pred)
Authors: McPherson Eugene , Tassy P. 
Published: April 2020

Abstract
Serum levels of sIL-2R represents the total amount of activated T-lymphocytes in tumor infiltrating lymphocytes of cancer tissues and metastatic organ sites. Most malignant diseases overexpress sIL-2R in comparison to non-malignant controls. Immunomodulatory effect of IL-2 therapy on interferon (IFN), tumor necrosis factor alpha (TNF-a) production, nuclear factor kappa–b (NFkb) in vivo and in vitro and on the expression of sIL-2R in Human Immunodeficiency Virus – Waldenstrom Macroglobulinemia (HIV-WM) patients with IgM is not well defined. We present a 42 year old female with HIV, CD4-343/cu mm, viral load (VL) of &gt;100K (persistently elevated VL), hypercoagulable state, serum viscosity &gt;3 centpoises, IgM level of &gt;1 gram with serum free light chain kappa/lambda ratio elevated as well as IgG and IgA on immunofixation studies. She was treated initially with BPD (Biaxin, Pentoxifylline, Dexamethasone) with partial response and with poor paraprotein parameter response. Her HAART regimen consisted of ritonavir base therapy. When dexamethasone was weaned off and prednisolone therapy started, greater than 50% reduction of paraprotein (IgM) occurred over 4–6 weeks. We measued serum sIL-2R, C-reactive protein (CRP), throughout treatment over 12 weeks. The serum sIL-2R level significantly decreased from 21,513.274 pg/ml to 5,424.779 pg/ml (normal 3,592.9 – 9,734.5 pg/ml). The C-reactive protein normalized and IgM was now 0.211 gram and within normal limits as well as serum viscosity.
CONCLUSIONS: The suppression and modulation therapy of CRP gene transcription with manipulation of NFkb/IKKb with ritonavir based HAART and BPD-Pred with normalization of sIL-2R, CRP, and IgM paraprotein in HIV-WM patients may have an independent effect on prognosis and maintenance therapy. Serum sIL-2R levels may serve as a useful marker in evaluating HIV-WM disease, stage for stage and monitoring disease progression.
BAALC and WT1 Transcript Amount Discriminates Secondary or Reactive Eosinophilia from Idiopathic Hypereosinophilic Syndrome or Chronic Eosinophilic Leukemia
Authors: Cen Jiannong , Chen Zixing , Qi Xiaofei , Yao Li , He Jun , Qiu Qiaocheng , Qiu Huiyin 
Published: April 2020

Abstract
Idiopathic hypereosinophilic syndromes (HES) or chronic eosinophilic leukemia (CEL) comprise a spectrum of indolent to aggressive diseases characterized by persistent hypereosinophilia. Hypereosinophilia can result from the presence of a defect in the hematopoietic stem cell giving rise to eosinophilia, it can present in many myeloproliferative disorders or alternatively it may be a reactive form, secondary to many clinical conditions. The fusion gene FIP1L1-PDGFR alpha was identified in a subset of patients presenting with HES/CEL. In spite of this, the majority of HES/CEL patients do not present detectable molecular lesions and for many of them the diagnosis is based on exclusion criteria and sometimes it remains doubt. CD34-positive progenitor cells from bone marrow (BM) express BAALC and WT1. Overexpression of BAALC and WT1 were seen in patients with AML and ALL. In a subset of AML it marked poor prognosis, suggesting a role for BAALC or WT1 overexpression in acute leukemia. To explored the possibility to distinguish between HES/CEL and reactive hypereosinophilia based on the measurement of BAALC and WT1 transcript amount. Twenty-two patients with hypereosinophilia were characterized at the molecular level and analyzed for BAALC and WT1 expression. The transcription of FIP1L1-PDGFRalpha fusion gene was detected by nested RT-PCR. The relative transcript amount of BAALC and WT1 were determined by real time PCR analyses. The FIP1L1-PDGFRalpha fusion gene expressed has been identified in bone marrow mononuclear cells of 4 cases. The relative expression level of BAALC and WT1 in these 4 cases with positive FIP1L1-PDGFRalpha fusion gene expression were 2.27(0.27–6.8) and 0.39(0.002–0.90), respectively. Whereas the relative amount of transcripts of BAALC and WT1 in 18 patients with negative FIP1L1-PDGFRalpha fusion gene were 0.069(0.015–0.11) and 0.054(0–0.34) respectively. The relative amount of transcripts of BAALC and WT1 in patients with HES/CEL were 32 times and 7 times than that in those with negative FIP1L1-PDGFRalpha fusion gene, respectively. These results clearly demonstrates that BAALC and WT1 quantitative assessment allows to discriminate between HES/CEL and reactive eosinophilia and represents a useful tool for disease monitoring especially in the patients lacking a marker of clonality.
Frequent Reduction or Absence of Detection of the JAK2-Mutated Clone in JAK2V617F-Positive Patients within the First Years of Hydroxyurea Therapy
Authors: Girodon François , Schaeffer C.éline , Cleyrat C.édric , Mounier Morgane , Lafon Ingrid , Santos FréD.éric Dos , Duval Aurélie , Maynadie Marc , Hermouet Sylvie 
Published: April 2020

Abstract
Objective: To analyse the effect of hydroxyurea (HU) on the JAK2-V617F allelic ratio (%JAK2-V617F) of patients with Polycythaemia Vera (PV) and Essential Thrombocythaemia (ET).
Methods: Thirty-six patients were examined sequentially prior to and after on-set of (HU) therapy (8 PV, 17 ET), or while remaining untreated (2 PV, 9 ET). For all patients, the %JAK2-V617F was determined in purified blood granulocytes using sensitive allele-specific, quantitative PCRs. In a second study, two distinct groups of patients were examined at a single time point at the time of diagnosis (99 PV, 178 ET) or while receiving HU (36 PV, 98 ET).
Results: HU therapy (median duration: 15 months) reduced the %JAK2V617F by &gt;30% in 13/25 patients (4 PV, 9 ET). For 3 patients, JAK2V617F remained undetectable for 3–27 months. There was no significant change in %JAK2-V617F for the 11 patients who received no treatment. In the single time point study of two large cohorts, the mean %JAK2-V617F was lower for patients with HU therapy (median duration: 32 months) than for patients at diagnosis (24% vs. 33%, p&lt;0.01). However, when analysed by gender, the decrease in %JAK2-V617F was significant only in female patients; this was true for both PV (39% vs. 52%, p=0.0249) and ET (12% vs. 17%, p=0.0364).
Conclusion: Reduction and even the disappearance of the JAK2-V617F-mutated clone can be obtained with HU therapy in PV and ET patients, most likely within the first two years of treatment.
A Retrospective Literature Review of Erythromelalgia and Myelorpoliferative Disorders
Authors: Milani Cannon , Pascual Sheila , Colvin Gerald A. 
Published: April 2020

Abstract
Cutaneous manifestations of myeloproliferative disorders (MPD) herald an uncommon diagnostic clue preceding a diagnosis of Essential Thrombocytosis (ET) and Polycythemia Vera (PV). If left untreated, they may progress towards acrocyanosis and even peripheral gangrene. This clincal entity can present months to years prior to an official diagnosis of a MPD. These atypical skin finding in ET and PV are referred to as Erythromelalgia, characterized by red, congested distal extremities secondary to microvascular complications. The pathophysiology of this skin abnormality involves spontaneous activation and aggregation of hypersensitive thrombocythaemic platelets in the end-arterial microvasculature, involving the peripheral, cerebral, and coronary circulation of thrombocythemia patients. The microvascular disturbances are frequently preceded or followed by atypical transient neurologic, ocular or coronary ischemic events. Thus these atypical skin findings can signal potential limb ischemia and necrosis.
We performed an extensive retrospective case review of the entire Engish language medical literature. The first reported case of Erythromelalgia was in 1872 by Weir-Mitchell. By 1938, Smith and Allen advocated the use of acteylsalicyclic acid as they reported pronounced pain relief from the use of 0.65 grams, up to five times daily. In our search, the number of cases reporting signs and symptoms of Erythromelalgia specifically preceding ET or PV, number less than twenty. We wanted to determine from review of the literatue if treatment with aspirin at the time of diagnosis of Erythomelalgia led to improved outcome.
The overriding conclusion of our review was that aspirin induced prompt relief of painful symptoms and seemed to prevent thrombotic sequelae in this patient cohort. Clinicians need to consider the underlying presence of a myeloproliferative disorder in patients manifesting vasculopathy associated skin findings, as it may be the harbinger of potentially fatal ischemic events. Earlier diagnosis and treatment may lead to improved outcome.
ALK Activates a Non-Canonical Beta-catenin Pathway in Anaplastic Large Cell Lymphoma
Authors: Ysebaert Loic , Lamant Laurence , Espinos Estelle , Giuriato Sylvie , Delsol Georges , Laurent Guy 
Published: April 2020

Abstract
Molecular profiling of Anaplastic Lymphoma Kinase (ALK)-positive versus negative cell lines and patients’ samples has unravelled critical roles for transcriptional factors (TF) (C/EBPbeta, Bcl-6) in Anaplastic Large Cell Lymphomas (ALCL), suggesting that targeting these TF with ALK tyrosine kinase inhibitors should yield better results (Lamant L et al., Blood 2008). In this latter work of our group, beta-catenin and its transcriptional partner T Cell Factor 4 (TCF4) were also found upregulated at a transcriptional level in ALK+ vs ALK− patients’ samples and cell lines. We sought to determine the relevance of such a finding. At the protein level, ALK+ cell lines (SU-DHL-1, Karpas299 and COST) and ALK− cell line (FEPD) express detectable beta-catenin. TCF-4 is also expressed at similar levels among cell lines, whatever ALK status. Since beta-catenin is mainly regulated through post-transcriptional mechanism, we assessed its phosphorylation status. ALK+ (SU-DHL-1 and Karpas299), but not ALK− cell lines displayed increased tyrosine phosphorylation at both Tyr142 and Tyr654 residues, as well as association between beta-catenin and ALK (in immuno-precipitation assays). Moreover, both total beta-catenin and phosphoTyr-beta-catenin were found associated with TCF4, and therefore transcriptionally active. Using the tetracycline system to allow conditional expression of NPM-ALK in MEF cell line (murine embryonic fibroblasts), we found that beta-catenin phosphorylation became barely detectable upon loss of NPM-ALK expression. Based on these findings, we investigated the functional consequences of the disruption of beta-catenin/TCF4 complexes using small molecules such as PKF115–584 and CGP049090 (a generous gift from Novartis). Interestingly, both compounds induced dissociation of beta-catenin/TCF4 complexes at 0.5μM for 24h, and also induced apoptosis in SU-DHL-1 cells. But, since compounds could not dissociate beta-catenin/ALK complexes, they should be combined to ALK inhibitors to fully exert their anti-lymphoma effects. Moreover, the pool of beta-catenin linked to Glycogene Synthase Kinase 3beta (regulated by external Wnt-dependant signals) is neither affected by small compounds, indicating a specific beta-catenin/TCF4 disruption with these drugs. To conclude, this study shows that, in ALCL, ALK activates a Wnt-independent pathway, which appears to be critical for cell survival. This study offers a rationale for investigating the potential of molecules designed to interfere with beta-catenin/TCF/LEF proteins and currently evaluated in colon carcinomas, alone or in combination with ALK tyrosine kinase inhibitors.
Clinical Implications of Immunophenotyping in Staging Diffuse Large B-Cell Lymphoma
Authors: Talaulikar Dipti , Dahlstrom Jane E , Shadbolt Bruce , McDonald Anne 
Published: April 2020

Abstract
Diffuse Large B-cell Lymphoma (DLBCL) is the commonest subtype of Non-Hodgkin Lymphoma (NHL). Staging bone marrow (BM) biopsies in NHL are conventionally examined using histology alone, although the use of immunophenotyping to aid diagnosis is increasing. This study addresses the clinical impact of routine use of flow cytometry (FL) and immunohistochemistry (IHC) in 156 histologically proven DLBCL cases at initial diagnosis. The median age of the patient cohort was 62 years (range 20–86 years) and the gender ratio was 1.53 in favor of males. Nine patients were treated with palliative intent and were excluded from all survival analyses. The rest were treated with anthracycline based chemotherapy regimens; 36 patients received concomitant Rituximab. Median overall survival (OS) was 6.1 years (95% CI: 3.8, 8.4). Histological involvement was noted in 30 cases (19.2 %) using standardized Cheson criteria [Cheson BD, Horning SJ, Coiffier B et al. J Clin Oncol1999; 17:1244]. FL and IHC (using T-cell, B-cell, and light chain markers) detected an additional 17 cases (10.9%) each with 4 cases detected by both methods. Thirty (19.2 %) patients were upstaged to stage IV with the use of these investigations (stage I: 6, stage II: 12, stage III: 12). Kaplan Meier curves demonstrated that positivity on FL, IHC and both (FL + IHC) resulted in a significantly worse OS and progression free survival (PFS) compared to negative cases. Cox proportional hazards models were used to determine the additional benefit of FL and IHC in predicting OS over histological involvement, after adjusting for age, performance status and use of Rituximab. The first analysis compared FL with histology and showed that FL added significant independent prognostic value [Histology: HR = 2.1, 95% CI 1.0, 4.3, p=0.05; FL: HR = 2.0, 95% CI 1.0, 3.8, p=0.04]. The second analysis compared histology with IHC and showed that the two had co linearity in their prediction of survival with IHC adding significantly more than histology alone [Histology: HR = 1.3, 95% CI 0.5, 3.0, p=0.6; IHC: HR = 2.3, 95% CI 1.1, 5.0, p = 0.03]. In the final model, we examined the interactive effect of FL and IHC over and above histological diagnosis and found the interaction to be the stronger predictor of OS [Histology: HR = 1.8, 95% CI 0.8, 3.7, p =0.1; FL/IHC: HR = 2.7, 95% CI 1.2, 6.2, p=0.02]. In conclusion, our results show that FL and IHC performed routinely can improve detection of BM involvement in DLBCL and upstage ~20 % patients to stage IV disease. We found that FL added significant independent prognostic value while IHC showed greater co linearity with routine histological diagnosis. The interactive effect of FL/IHC had additional benefit over routine histology in predicting survival. These results suggest that staging BM in DLBCL should have FL and IHC performed routinely at initial diagnosis.
Non-Hodgkin Lymphoma and Smoking: A Meta-Analysis of Case-Control Studies
Authors: Milani Cannon , Pascual Sheila , Mitri Joanna , Castillo Jorge 
Published: April 2020

Abstract
Background: The incidence of non-Hodgkins lymphoma (NHL) has followed a sustained increasing pattern for the last few decades. Potential factors implicated in developing an increased risk for NHL include immunosuppression, bacterial, and viral infections. The pathological heterogeneity of NHL suggests multifactorial etiologies. Several reports around the world have linked lifestyle habits to the development of NHL, but thus far, the relationship between smoking and NHL has been largely inconclusive.
Objective: To perform a meta-analysis of published case-control studies to clarify the potential relationship between smoking and the development of NHL.
Methods: An English literature search was conducted using Pubmed of case-control studies investigating the relationship between smoking and development of NHL. Prospective studies, case reports, editorials and letters were not included. Data were gathered including the following variables: country of origin, source of cases and controls, number of female/male cases and controls, adjusted odds ratio (OR) with 95% confidence intervals (CI) for former and current smokers, divided by male/female when available, and adjustments. Effect measures were obtained trough fixed and random-effects models to assess for heterogeneity.
Results: Eighteen case-control studies were included in the meta-analysis. A total of 22,226 cases and 30,792 controls were finally analyzed. Based on our meta-analysis, former smokers had an OR of 1.02 (95% CI, 0.92 – 1.12) when compared to never smokers; heterogeneity between studies was evident (p &lt; 0.001; I2 = 75.3%). Current smokers, on the other hand, had an OR of 1.06 (95% CI, 1.00 – 1.14); some degree of heterogeneity was observed (p = 0.04; I2 = 41.1%).
Conclusions: Despite the limitations of this meta-analysis, current smokers seem to have small but statistically significant increase in the risk of developing NHL. Clinically speaking, smoking may be a non-negligible risk factor for developing NHL. Although a causal relationship will be hard to prove, further research is needed to clarify the potential role of smoking in lymphomagenesis.
Clinical Outcome of 119 Children with Non-Hodgkin Lymphoma Treated in a Single Center in China
Authors: Zhang Yonghong , Jin Ling , Yang Jing , Duan Yanlong , Zhou Chunjv , Gao Zifen 
Published: April 2020

Abstract
One hundred and nineteen children with non-Hodgkin lymphoma were treated between February 2003 and December 2006 in Beijing Children’s Hospital on BCH-2003-NHL protocol. The diagnosis was made by histopathology of the biopsied tissue and/or bone marrow, and disease was classified according to WHO-2001 pathologic classification. We applied modified LMB89 protocol to cases with B-cell lymphoma; modified BFM90-ALL protocol for lymphoblastic lymphoma and cutaneous T-cell/NK cell lymphoma; and modified BFM90-ALCL protocol for anaplastic large-cell lymphoma (ALCL). There were 50 cases (42%) of B cell lymphoma including 32 cases of Burkitt¡’s lymphoma, 10 cases of Burkitt-like lymphoma and 8 cases of diffuse large B cell lymphoma; 44 cases (37%) of lymphoblastic lymphoma; 19 cases (16%) of ALCL; and 6 cases (5%) of cutaneous T-cell/NK cell lymphoma. The 85 boys and 34 girls (ratio, 2.5:1) ranged in age from 2 to 15 years (median, 7.8 years) at diagnosis. B cell lymphoma typically presented as abdomen mass and acute abdomen; nasopharynx and tonsil were also common sites of involvement. Lymphoblastic lymphoma generally presented with mediastinal mass and bone marrow involvement. There was no typical presentation for ALCL. According to the St. Jude staging system, 19 cases had stage I–II, and 94 cases stage III–VI diseases (exclude 6 cases of cutaneous T-cell/NK cell lymphoma). Seven cases had CNS involvement and 25 cases involved bone marrow. The treatment duration was 2 to 8 months for B-cell lymphoma, 2.5 to 3 years for lymphoblastic lymphoma and 1 to 1.5 years for ALCL. The follow-up rate was 100% and median observation period was 23 months. The overall survival (OS) at 3 years was 90.7% and the 3-year event-free survival (EFS) estimate was 82.3%. For B-cell lymphoma, 3-year OS was 88.68% and 3-year EFS was 81.8%. For lymphoblastoma lymphoma, the rates were 89.3% and 69.4%, respectively. All cases of ALCL are alive with on undergoing treatment for relapse. Patients with ALCL achieved the best 3-year OS (100%) and had 3-year EFS of 94.2%. Grade 3 or 4 bone marrow suppression occurred in 97.5% of patients with B-cell lymphoma, 100% of those with lymphoblastic lymphoma and 89.5% of cases with ALCL. As of to date, 11 patients have died, the causes of death include infection (n=4), abandonment of therapy (n=6) and relapse (n=1). Univarate analysis showed that stage IV disease, failure to achieve complete remission after 3 months of treatment, and bulky mass are were associated with poor prognosis £all P values &lt;0.05£©. In summary, we have achieved excellent treatment results using modified international protocols. Infection and financial problem remained the main reasons of treatment failure.