bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Term Follow up of Chinese Children with Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Detection
Authors: Tang Yongmin , Xu Xiaojun , Shen Hongqiang , Song Hua , Shi Shuwen , Yang Shilong , Wei Jian , Xu Weiqun 
Published: April 2020

Abstract
Introduction and objective: Recent studies from resource-rich countries have showed that minimal residual diseases (MRD) were the most important independent prognostic factor for children with acute lymphoblastic leukemia (ALL). However, experience from Chinese children with this disease has not been reported in the English literature. In this study, we reported our experience in small series of children with ALL based on multi-parameter flow cytometric detection of MRD to study the relationship between MRD levels and the long term survivals in Chinese children with ALL.
Methods: Using multi-parameter flow cytometry and at least one patient specific leukemia associated immunophenotype (LAIP) to determine the MRD levels in 71 Chinese children with ALL expressing leukemia associated immunophenotype (LAIP) from January 2002 to December 2003. Bone marrow aspirates were collected on day 15 and the 1st, 3rd, 6th, 12th, 18th, 24th, 30th month after chemotherapy. Leukemia associated Immunophenotype for each patient was identified according to the patients’ initial immunophenotypes determined by multi-parameter flow cytometry using a panel of more than 30 antibodies.
Results: The one, two and three year disease free survival (DFS) for patients with a MRD level less than 10−2 on day 15 were (88.3±6.4) %, (84.3±7.2) % and (76.3±8.5) %, respectively, whereas those for patients with MRD levels ≥10−2 on day 15 were 100%, 0% and 0%, respectively (log rank test, P=0.004). The 5-year DFS for patients with MRD levels &lt;10−2 and ≥10−2 on day 15 were (83.8±6.1) % and 0%, respectively (P&lt;0.01). The 5-year DFS were significantly different between patients with MRD levels &lt;10−4 and those ≥10−4 on the 6th or 12th month. Out of 71 patients, the 5-year DFS for patients with MRD levels &lt;10−3 was 100%, however, the 1-year, 3-year and 5-year DFS for patients with MRD levels ≥10−3 were (87.3±5.3) %, (71.4±7.3) % and (68.0±7.7) %, respectively (log rank test, P=0.004). And the 1-year, 3-year and 5-year relapse rates for the latter group were 10.5%, 13.5% and 15.8%, which showed a tendency of difference in terms of relapse rate when compared to patients with MRD levels &lt;10−3 (5-year relapse rate: 15.8% vs. 0%, P=0.08).
Conclusions: MRD detected by multi-parameter flow cytometry is also an independent prognostic factor in Chinese children with ALL.
Short Time Latency in Infant Leukemia with ETV6/RUNX1 fusion Gene
Authors: Emerenciano Mariana , Bungaro Silvia , Cazzaniga Giovanni , Dorea Maria Dolores Fonseca , Coser Virginia Maria , Magalhaes Isis Quezado , Biondi Andrea , Pombo-de-Oliveira Maria S. 
Published: April 2020

Abstract
Acute lymphoblastic leukemia (ALL) in infants is characterized by a high frequency of MLL gene rearrangements. By contrast, the ETV6/RUNX1 (TEL/AML1) fusion gene is usually detected in children older than 2 years. In a series of Brazilian infant leukemia cases collected in an epidemiological study, a screening was performed to identify fusion genes found in ALL, we have identified four cases harboring ETV6/RUNX1 in blast cells of infants with 2, 3, 5 and 7 months-old, and common-ALL. To underlie additional genomic hits required to accelerate the emergence of a frank leukemia in these c-ALL cases, we applied the SNP-based genomic copy number analysis, comparing t(12;21) infants with other children with c-ALL in older age-range groups. The presence of ETV6/RUNX1 fusion gene was demonstrated by reverse transcription polymerase chain reaction (RT-PCR) and confirmed by fluorescence in situ hybridization (FISH). All cases were negative for MLL rearrangements, as assessed both by RT-PCR and FISH analyses. As control group (non-leukemic children), we selected 5 samples from children younger than 2 years-old already included in a previous epidemiological study. Infant cases described here present high WBC count (on average 131 × 109/L), and adverse prognosis: two of them relapsed, and one patient only (relapsed) is still alive four years after diagnosis. Recurrent deletions, including 9p21.3 (CDKN2A/2B and MTAP), 11p13 (CD44), 12p13.2 (ETV6) and regions affected by copy number neutral loss of heterozigosity (LOH) were observed. The frequency of genomic deletions and amplifications detected by 100K SNP arrays varied significantly between age-related c-ALL subgroups. The infant leukemia group showed the lower number of chromosome imbalances, whereas the mean number of deletions was similar in the &lt;2 years and 2–10 years age groups, consistent with the observation that the number of gains was largely increasing in older children. It has been postulated that infant leukemia might be caused by transplacental exposures during pregnancy. Then, with these unusual results we have reviewed the data of their mothers’ interviews. Mothers of infants were effectively exposed to a non-steroidal anti-inflammatory drug, and other chemical substances. It may be hypothesize that the pre-leukemic phase in these age-related subgroups of ETV6/RUNX1 positive patients may be evolved with different latencies due to the occurrence of a combination of genetic and environmental factors.
Identification of New Markers Discriminating Between Myeloid and Lymphoid Acute Leukemia
Authors: Haouas Houda , Haouas Samira , Uzan Georges , Hafsia Aicha 
Published: April 2020

Abstract
The heterogeneity of acute myeloid leukemia (AML) with respect to biology and clinical course resides in the fact that patients belonging to the same group show marked differences in their response to chemotherapy, which would necessitate a refinement of AML classification. In order to contribute to define molecular markers for AML we realized microarray assays on two M5 AMLs and selected four differentially expressed genes to validate their expression by RQ-PCR. We have shown that two down-regulated genes in AML, Guanine nucleotide binding protein (G protein) gamma 11 (GNG11) and Amphiregulin are also down-regulated in B-ALL and T-ALL patients. We have found a gene, Ceruloplasmin, which is up-regulated in AML but not in B-ALL and T-ALL. The level of expression of these genes varies from one patient to another. Since the group of patients studied is limited, further studies must carry on with a larger series of patients to be able to make subdivision according to the expression of GNG11, Amphiregulin and Ceruloplasmin. Our study is the first to analyze these genes in AML, B-ALL, T-ALL and CL patients by quantitative real time PCR. This rapid and sensitive method could be used to screen these genes in different types of leukemia.
Acute Lymphoblastic Leukemia with Mature Appearing Lymphocytes: First Chinese Case Report and Literature Review
Authors: Zhang QiGuo , Ouyang Jian , Li Jianyong 
Published: April 2020

Abstract
Objective: To increase the knowledge and understanding of acute lymphoblastic leukemia with maturation(ALLm).
Method: One ALLm case with clinical manifestation, bone marrow morphology, immunophenotype and cytogenetic results were presented and related literatures were reviewed.
Result: The patient was a fifty-five year old women, the haematological feature was Pancytopenia. There were 12% lymphoblasts and 82.5% mature appearing lymphocytes in the bone marrow smear. The mature appearing leukemic cells could not be separated clearly by gating. However, the immunophenotypes of mature-appearing leukemic cells(Low FSC and Low CD45) and lymphoblasts were the same. Both results were CD33+CD34+CD19+CD22+HLA−DR+CD5−CD7−CD10−CD13−CD14−CD15−CD20−CD25−CD45−CD71−CD11b−CD103−CD117−. Bone marrow biopsy showed hypercellularity with diffuse infiltration of lymphocytes, The results were CD34++,TdT++,Pax-5+++,CD43++,CD3+(scatter),CD5+(scatter),CD20−,CD10+,CyclinD1−, lymphoblasts Ki67+, mature-appearing leukemic cells ki-67-. FISH analysis of the bone marrow revealed about 1% cells with a signal pattern suggesting loss of one copy of chromosome 8. After VDP, MA, AAG and HAG regimens Complete remission was not achieved.
Conclusion: ALLm is a special morphological variant of acute lymphoblastic leukemia, most mature appearing cells are in resting G0 phase and this could be the reason why ALLm has a poor response to chemotherapy.
Long-Term Increases in Lymphocytes and Platelets in Human T-Lymphotropic Virus Type II Infection
Authors: Bartman Melissa T , Kaidarova Zhanna , Hirschkorn Dale , Sacher Ronald A. , Fridey Joy , Garratty George , Gibble Joan , Smith James W , Newman Bruce , Yeo Anthony E , Murphy Edward L 
Published: April 2020

Abstract
Human T-lymphotropic viruses types I and II (HTLV-I and HTLV-II) cause chronic infections of T-lymphocytes, leading to adult T-cell lymphoma (HTLV-I) and myelopathy (both types) in a minority of infected humans. However, their long-term effects on blood counts and hematopoiesis are not fully understood. We followed 151 HTLV-I and 387 HTLV-II seropositive former blood donors, and 799 HTLV seronegative donors from five US blood centers prospectively for a median of 14.0 years. Complete blood counts were performed every 2 years on fresh anticoagulated blood at licensed clinical laboratories near each center. Multivariable repeated measures analyses were conducted to evaluate the independent effect of HTLV infection and potential confounders on 9 hematologic measurements. HTLV-II subjects had significant (p&lt;0.05) increases in their adjusted lymphocyte counts (+126 cells/mm3; approx +7%), hemoglobin (+0.2 gm/dL) and mean corpuscular volume (MCV; 1.0 fL) compared to seronegative subjects. Both HTLV-I and -II subjects had higher adjusted platelet counts (+16,544 and +21,657 cells/mm3; p&lt;0.05) than seronegatives. Among all subjects, time led to decreases in platelet count (−6,750 to −6,600 cells) and lymphocyte counts (−67 to −66 cells), and to increases in MCV (+0.4 fL) and monocytes (+19 to +20 cells per uL; all per two-year interval). Women had lower hemoglobin but higher platelet and white blood cell (WBC) counts than men. Blacks had lower hemoglobin, MCV and neutrophil counts, but higher platelet and lymphocyte counts than whites. Heavy drinking was associated with higher MCV but lower WBC counts, whereas cigarette smoking was associated with higher WBC counts of all lineages. These results suggest that HTLV-I and -II infection can produce significant, independent and long term changes in lymphocytes, platelets and red blood cells. The finding of increased lymphocytes in HTLV-II infection is novel and may be related to viral transactivation or immune response. HTLV-I and –II associations with higher platelet counts suggest viral effects on hematopoietic growth factors or cytokines.
Relationship Between Galectin-10 Expression and Severity of Celiac Disease Abolished in the Presence of Gammadelta-Positive T-Cell Clonal Expansion
Authors: Simula Maria Paola , De Re Valli , De Zorzi Mariangela , Canzonieri Vincenzo , Spina Michele , Cannizzaro Renato 
Published: April 2020

Abstract
Celiac disease (CD) patients are prone to develop T-cell lymphoma throughout a progressive accumulation of aberrant, clonal gd+ T-cells. It is supposed that high production of pro-inflammatory cytokines, and chronic antigenic stimulation, due to gluten ingestion, plays a key role in inducing inflammation, resistance to apoptosis and the emergence of these T-clones. Regulatory T-cells maintain immunological self-tolerance by active suppression of auto aggressive T-cells. Among them, Tr1 subset plays a role in the suppression of naïve and memory T-cells. The role of Tr1 in human diseases is not well understood, even because there are no specific markers able to identify these cells, however recently, Galectin-10 has been proposed as a marker for functional Tr1. To better understand pathogenetic mechanisms associated with CD and clonal T-cell proliferations we investigated galectin-10 expression from gut epithelium by 2D-DIGE approaches. Patients were selected and grouped for histological inflammatory degree and for gd+T pattern defined by g-TCR genescan analysis. Groups consisted of 7 individuals with Marsh-0 (4/7 oligoclonal), 3 with a Marsh-1 or -2 (3/3 polyclonal) and 5 with Marsh-3 (2/5 clonal gd+T). Control consisted of 4 individuals with excluded CD. We found, a parallel increase in galectin-10 levels and Marsh index in individuals with polyclonal gd+T cells (p=0.0092), while reduced levels were evidenced from patients with clonal gd+T cells and Marsh-3 (p=0.017). We assume that galectin-10 up-expression is induce to an attempt to extinguish inflammation. If these clones are those more susceptible to malignant progression reserve further exploration.
CD3-Zeta Gene Expression in Workers Benzene-Exposed and Benzene- Poisoned Workers
Authors: Li Bo , Li Yangqiu , Chen Shaohua , Yang Lijian , Yu Wei , Liu Weiwei , Chen Jiayu 
Published: April 2020

Abstract
Benzene is an industrial chemical and component of cigarette smoke, gasoline, and automobile emissions. Benzene’s toxic effects on the blood and bone marrow can induce aplastic anemia and leukemia. Benzene is known to be highly toxic to a variety of cell types including lymphocytes. Our previous study showed that skewed distribution and clonal expansion of TCR Vα subfamily T cells had been found in benzene-exposed workers, indicating that the disorder of T cell immune function might relate to benzene-exposed. The TCR expressed on the surface of T cells is associated with an invariant structure-CD3 and composed the TCR/CD3 complex. The CD3ζ chain plays an important role in the complex which involved in signal transduction. Little is known about the feature of CD3 ζ chain expression in benzene-exposed workers. To further identify the expression level of CD3 ζ gene in benzene-exposed workers, real-time PCR with SYBR Green±technique was used for detecting CD3 ζ gene expression level in peripheral blood mononuclear cells from 29 benzene-exposed workers, 42 benzene-poisoned workers and 20 normal individuals. β2- microglobulin gene (β2M) was used as an endogenous reference. Relative changes in CD3 ζ gene expression level was used by the 2−ΔCt×100% method (ΔCt=Ct(ζ) −Ct(β2M) ). CD3ζ gene could be detected in all of normal individuals, however, only 21 out of 29 benzeneexposed workers could be detected the CD3ζ gene with a mean expression level of 15.0 ±24.9, and in 33 of all 45 benzene-poisoned workers with mean value of 19.8 ±29.7. The detectable CD3 ζ gene expression level in both benzene-exposed and benzene-poisoned groups increased significantly compared with that in normal individuals (3.00±2.11, P&lt; 0.05). This is, to our knowledge, the first description of the effect of benzene-exposed on the expression of the CD3 ζ gene. The abnormality expression of CD3 ζ gene might lead to immune dysfunction in benzene-exposed and benzene-poisoned workers. In addition, CD3ζ gene could not be detected in a part of samples, whether the absence of CD3ζ gene might related to dysfunction of T cells in workers with benzene-exposed and benzenepoisoned, it remains an open question.
A Prospective, Observational Study on the Incidence of Chemotherapy-Induced Neutropenia in Lymphoma Patients
Authors: Salar Antonio , López Andrés , Torres Juan Pío , López María Dolores , Prieto Elena , Caballero Dolores , Giraldo Pilar , Batlle Montserrat , Benedit Patricia , Garrido Teresa 
Published: April 2020

Abstract
Background. Neutropenia is a common toxicity in patients (pts) with lymphoma (lymph) who receive myeloablative chemotherapy (CT). It frequently leads to CT delays and dose reductions, potentially compromising the clinical outcome. Granulocyte colonystimulating factors (G-CSFs) represented a major development in the prevention of this disorder. Current European and US guidelines (2006) recommend primary prophylaxis with G-CSF for patients at overall ≥20% risk of febrile neutropenia (FN) due to CT and patient-related factors.
Methods. A multicentre, prospective, observational study, in adult pts with lymph initiating a new CT regimen with at least 4 planned cycles, assessing the incidence of grade 3–4 neutropenia (G3–4N) [defined as absolute neutrophil count &lt;1.0 × 109/L] over the first four cycles of CT regimens with high or intermediate FN risk (FN risk ≥20% or 10–20%, respectively).
Results. This interim analysis contains data from 270 consecutive lymph pts (300 pts per protocol) from 31 Spanish centres from November 2005 to November 2007. Pts were 53.3% male, median age 57.5 years (range: 19–85), 87.0% ECOG 0-1 and 60.9% III–IV stage (43.6% IV stage). 71.8% of lymph pts were treated with CHOP-based CT (83.0% R-CHOP). G-CSF was used in 83.9% of pts (76.8% primary prophylaxis (PP), 23.2% secondary prophylaxis (SP)). The G-CSF received was 49.1% filgrastim and 50.9% pegfilgrastim. Global incidence of G3-4N over the first four cycles was 39.9%. The G3-4N incidence was 39.6% in pts treated with pegfilgrastim while it was 52.3% in pts treated with filgrastim. Pts treated with PP had an FN incidence of 15.4% while the incidence was 22.0% in those receiving SP. Full dose on schedule (FDOS) [defined as ≤ 15% dose reduction and ≤ 3 days dose delay] was achieved in 65.1% of pts treated as PP and 60.8% of pts treated as SP.
Conclusion. This study of clinical practice suggests that current guideline recommendations on the use of G-CSF PP with CT are becoming widely adopted in Spain. In patients receiving CT with intermediate/high FN risk, G-CSF PP and pegfilgrastim prophylaxis seemed to reduce neutropenia events compared with SP and Filgrastim. PP also improved the delivery of CT at full dose on schedule.
Intrapleural Rituximab (R) Is Effective in Refractory Pleural Effusion Due to Non- Hodgkin’s Lymphoma
Authors: Rivas-Vera Silvia , Cadena-Eumaña Carlos , Chalapud-Revelo Juan , Aguilar-Navarro Adriana , Sobrevilla-Calvo Pedro , Lievano-Torres Cristina 
Published: April 2020

Abstract
We report the case of a 65 years old woman with a NHL, CD20 +, BCL-2 negative, Grade III, CS: IVBX, FLIPI High Risk, diagnosed on September 2005. The patient was treated with several chemotherapy regimens (CHOP, chlorambucil/prednisone, cyclophosphamide/prednisone), while on treatment a large pleural effusion was found on a chest X-ray. On pleural fluid cytology we observed numerous abnormal lymphocytes. We did repeated thoracocentesis without success, finally a pleural tube was inserted and intrapleural bleomycin instilled, again with no success (Table 1). Six weeks later, after signing informed consent, we administered 50 mg of intrapleural R (50 mg in 50 cc of SS 0.9%) without immediate or delayed adverse events. On day +4 a new chest X-ray showed marked improvement. We planned to repeat the dose every week × 4, unfortunately the patient could not afford it. After seven months the patient is asymptomatic and without recurrence of the pleural effusion.
Table 1
Date (2007) Fluid drained (ml) Action September 12 Dyspnea September 21 1,500 October 4 1,500 October 6 570 October 8 400 October 12 20 Bleomycin 10 U November 6 Dyspnea/1,300 November 9 40 November 16 400 November 17 200 November 20 100 Rituximab 50 mg
Discussion Although the pharmacology of IV R is welll known, there is scarce information about dosage, penetration into the tissues and efficacy of intracavitary R. It is likely that the intrapleural instillation of R was effective in the control of this complication in a definitive way, without adverse effects, Our case supports the results reported by Schmidt et al (Table 2). The mechanism of action at the local site is not known, but it could be the same as described with the systemic use. Pleural effusion secondary to refractory lymphoma is a rare complication, we propose the integration of an international registry of this cases to study the pharmacokinetics, pharmacodynamics, efficacy and safety of intrapleural rituximab.
Table 2
Features Our patient Schmidt Patient Age age 65 years 57 years Diagnosis Follicular NHL, Grado II Lymphoplasmacytic NHL No. Previous Therapy 3 1 Effusion therapy Thoracocentesis and drainage by pleurostomy Thoracocentesis Rituximab Dose 50mg, single dose 50mg day 1 200mg day 2 400mg day 3 Time to Response 4 days 3 days
Increased ABCG2 Expression Could Be Responsible for Resistance to Imatinib Mesylate in Patients with Chronic Myeloid Leukemia Who Do Not Have Mutations in BCR-ABL Kinase Domain
Authors: Balasubramanian Poonkuzhali , Markose Preetha , Chendamarai Ezhilarasi , Mathews Vikram , Srivastava Vivi , Velayudhan Shaji R , Lakshmi Kavitha M , Viswabandhya Auro , George Biju , Srivastava Alok , Chandy Mammen 
Published: April 2020

Abstract
Mutation in the Bcr-Abl kinase domain is one of the most common mechanism of resistance to imatinib mesylate (IM), seen in 30– 90% of patients with chronic myeloid leukemia (CML). A total of 57 patients with CML, 41 in chronic phase, 10 in accelerated phase and 6 in blast crisis, were analyzed for bcr-abl kinase domain (KD) mutations using reverse transcriptase polymerase chain reaction (RT-PCR) amplification of the bcr-abl KD followed by direct sequencing. Twelve different mutations including three novel mutations were identified in the bcr-abl KD in 18 patients. Resistance to IM was considered if the patient had rising white blood cell counts or did not achieve hematological remission at 6 months; or had rising bcr-abl levels (as determined by fluorescence in situ hybridization or real-time quantitative PCR) after the start of IM treatment. In order to evaluate other potential mechanisms of resistance in patients without mutations in the bcr-abl kinase domain, we tested the expression levels of transporter genes known to be involved in IM influx and efflux. mRNA expression levels of efflux transporters, ABCG2 and ABCB1, and influx transporter, hOCT1 were measured by real time quantitative PCR using ABL to normalize the expression levels of the same. Serially diluted cDNA made from HepG2 RNA was used to make the standard curve and amplification efficiencies of the target and the house keeping genes were similar. Each sample was analyzed in duplicate and the experiment was repeated twice. In the patients without mutations in the bcr-abl KD, significantly higher ABCG2 mRNA levels were observed compared to patients with mutations (Table). Transcript levels of ABCB1, hOCT1 or bcr-abl were not significantly different between the two groups. This study suggests that over expression of ABCG2 may be one of the mechanisms of resistance to imatinib in patients without mutations in bcr-abl. Future studies should not only compare the expression of these transporters at diagnosis (before the start of IM treatment) but also at the time of clinical resistance. This will help understand the influence of expression levels of these transporters in achieving haematological or molecular response to increased IM doses.
Bcr-abl mutation positive (n=18) Bcr-abl mutation negative (n=39) p value ABCG2: median (range) 0.0126 (0.0004–0.45) 0.051 (0.0041–0.51) 0.034 ABCB1: median (range) 0.1842 (0.00349–0.51) 0.1819 (0.0463–0.68) NS hOCT1: median (range) 488 (3.4–3394) 486 (62–3059) NS BCR-ABL: median (range) 53.96 (5.73–179.1) 51.3 (2.36–129) NS