Early assessment of endocan level as a predictor of remission status in acute leukemia patients

Background STAB-1 (common lymphatic endothelial and vascular endothelial receptor) was found to be expressed on tumor lymphatic vessels in different malignancies and it is a bad prognostic marker. This study will assess the role of serum stabilin1 (STAB1) as a prognostic marker in adult patients with newly diagnosed acute leukemia and correlate it with the other well established prognostic markers. Acute lymphoblastic leukemia (ALL) is a hematologic malignancy arising from precursors of the lymphoid lineage. Conventional cytotoxic chemotherapies have resulted in high cure rates of up to 90% in pediatric ALL, but the outcomes for adult patients remain suboptimal with 5-year survival rates of only 30%-40%. Aim of the Work To measure STAB1 expression in patients with AML and patients with ALL and assess its role as a prognostic factor with correlating it with other prognostic factors. Patients and Methods A case control study in Ain Shams University Hospitals, Clinical Haematology and Oncolgy division of Internal Medicine Department for one year on total 75 subjects divided into: 25 patients with newly diagnosed acute myeloid leukemia (AML), 25 patients with newly diagnosed acute lymphoblastic leukemia (ALL) and 25 age and sex matched healthy control subjects. The study population was recruited from Ain Shams University Hospitals, Clinical Haematology and Oncolgy division of Internal Medicine Department. Results There was no significant difference between cases of acute leukemia pts and control group as there was no statistically significant difference between control and patients group regarding sex, age, spleen size, liver size, LDH, CRP, uric acid and ESR of the studied subjects. Our study shows that as regard CBC; there was significant difference between the studied groups as regard leucocytic count, BUT Platelets, and hemoglobin was insignificant, which was also described in the study. Our study showed that there was high statistically significant difference between the acute leukemia patients and the healthy control group as regard sabilin1. Our study shows that the mean serum level of stabilin1 in the patients who didn’t respond to chemotherapy was higher than that of the patients that responded to chemotherapy. Conclusion There was high statistically significant difference between the studied groups as stabilin1. There was significant correlation between stabilin2 and chemotherapy response. Stabilin1 expression levels also identified a new subgroup at a higher risk for relapse and with a poor prognosis in acute leukemia patients. Stabilin 1 can be used as a prognostic factor in patients with acute leukemia.

Background Interleukin 15 (IL-15), a proinflammatory cytokine, regulates the functions of the immune system and controls the differentiation of hematopoietic cells. However, it may also promote the development of leukemia through its role in enhancing the survival, proliferation and differentiation of leukemic precursors. Aim of the work To assess expression of IL-15 level in adult Egyptian acute leukemia patients, its correlation with disease free survival, overall survival and relapse rate, as well as its possible correlation with other prognostic parameters. Patients and methods Serum IL-15 level was measured using enzyme-linked immunosorbent assay in 30 newly diagnosed acute lymphoblastic leukemia (ALL) patients, 30 newly diagnosed acute myeloid leukemia (AML) patients and 30 age and sex-matched healthy control subjects. The patients were recruited from clinical hematology department at Ain shams university hospital over the period from April 2017 to October 2018. Results In ALL patients: The serum IL-15 level was higher in ALL patients compared to control subjects (P = 0.015). Patients with ALL with high serum IL 15 level had shorter survival compared to those with low or average serum IL 15 level (P = 0.005). In AML patients: The serum IL-15 level was higher in AML patients compared to control subjects (P = 0.010). Patients with AML with high serum IL 15 level had shorter survival compared to those with low or average serum IL 15 level (P < 0.001). Serum IL15 level has negative correlation with the date of death in patients with AML (P = 0.001). Conclusion Interleukin 15 (IL-15) is a useful poor prognostic marker in patients with newly diagnosed acute leukemia, also it can be used as a predictor for survival. Abbreviations AML (acute myeloid leukemia), ALL (acute lymphoblastic leukemia), IL-15 (Interleukin 15).

Vitamin D deficiency(<20 ng/mL) is a common condition, associated with an inferior prognosis in some cancers. However, the prognostic significance of vitamin D deficiency in acute leukemia is largely unknown. The present study aimed to assess the baseline status of vitamin D [25-(OH) D3] and find its association with induction remission rate and mortality using standard chemotherapy in patients with acute leukemia. In this prospective observational study, blood samples were collected from 73 newly diagnosed patients before starting induction chemotherapy to measure serum vitamin D [25(OH)D] levels along with routine investigations.44/73 (60.3%) patients were acute lymphoblastic leukemia (ALL), and 29/77 (39.7%) were acute myeloid leukemia (AML) patients. Descriptive statistics and frequency distribution were used in SPSS software, and Pearson’s chi-squared test compared the categorical variables. Post-induction remission status (complete and incomplete remission) and induction-related mortality were correlated with vitamin D levels. 44/73 patients (60.3%) included in this study were males, and the remaining were females. The mean age of the participants was 30.32 ± 14.95 years. The mean serum vitamin D level in the cohort was 15.74 ± 28.14 ng/mL. Vitamin D deficiency was observed in 59/73 (80.8%) patients, whereas 14/73 (19.2%) had normal levels (≥20ng/mL) of the vitamin. Vitamin D deficiency is common among acute leukemia patients. Herein, we observed that low vitamin D level is associated with higher rates of incomplete remission in acute leukemia patients (P = 0.016). Vitamin D deficiency is common among acute leukemia patients and is associated with poor short-term outcomes.

Invasive fungal disease (IFD) is a major cause of morbidity and mortality in acute leukemia (AL) patients. The impact of primary antifungal prophylaxis (PAP) on AL patients with different risk factors is unclear. We analyzed 2015 Chinese AL patients who received a total of 2274 chemotherapy courses, including 1410 courses in acute myeloid leukemia (AML) patients and 864 courses in acute lymphocytic leukemia (ALL) patients. The IFD incidence was significantly higher among AML than ALL patients (11.8 vs. 7.1%, P < 0.001) and in patients receiving induction chemotherapy than in those receiving consolidation chemotherapy (21.6 vs. 3.7%, P < 0.001). Induction chemotherapy, decreased serum albumin, indwelling central venous catheters, parenteral nutrition, and male gender were independent risk factors for IFD in AL patients, whereas PAP independently protected against IFD development. For patients on induction chemotherapy, PAP significantly reduced IFD incidence (P < 0.001). For patients on consolidation chemotherapy, however, PAP did not significantly alter IFD incidence, although PAP did lower IFD incidence in patients with certain risk factors. PAP is highly recommended for patients on induction therapy; for those on consolidation chemotherapy, PAP should be considered for patients who present with severe neutropenia, decreased albumin, and/or an indwelling central venous catheter.

Invasive fungal disease (IFD) is a major cause of morbidity and mortality in acute leukemia (AL) patients. The impact of primary antifungal prophylaxis (PAP) on AL patients with different risk factors is unclear. We analyzed 2015 Chinese AL patients who received a total of 2274 chemotherapy courses, including 1410 courses in acute myeloid leukemia (AML) patients and 864 courses in acute lymphocytic leukemia (ALL) patients. The IFD incidence was significantly higher among AML than ALL patients (11.8 vs. 7.1%, P<0.001) and in patients receiving induction chemotherapy than in those receiving consolidation chemotherapy (21.6 vs. 3.7%, P<0.001). Induction chemotherapy, decreased serum albumin, indwelling central venous catheters, parenteral nutrition, and male gender were independent risk factors for IFD in AL patients, whereas PAP independently protected against IFD development. For patients on induction chemotherapy, PAP significantly reduced IFD incidence (P<0.001). For patients on consolidation chemotherapy, however, PAP did not significantly alter IFD incidence, although PAP did lower IFD incidence in patients with certain risk factors. PAP is highly recommended for patients on induction therapy; for those on consolidation chemotherapy, PAP should be considered for patients who present with severe neutropenia, decreased albumin, and/or an indwelling central venous catheter.

To investigate the auxiliary diagnostic value of serum adenosine deaminase (ADA) in acute leukemia (AL) at clinical test. 123 AL patients hospitalized in Zhejiang hospital from November 2018 to March 2020 were enrolled as the observation group, and 98 healthy people in the same period were randomly enrolled as the control group. AL patients were divided into two groups: 77 acute myeloid leukemia (AML) patients for AML group and 46 acute lymphoblastic leukemia (ALL) patients for ALL group. The levels of adenosine deaminase (ADA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) and homocysteine (Hcy) in serum of the patients were detected, and the correlation of ADA with these items was analyzed. Receiver operating characteristic curve (ROC) was used to analyze the clinical diagnostic value of ADA, Yoden index was used to confirm the best cut-off point. The serum ADA level in AL patients was significant higher than that in control group (P < 0.05). The results of Pearson correlation analysis showed that there was a significant positive correlation of ADA with Hcy, ALT, AST, GGT, LDH in AML group (r = 0.47, r = 0.28, r = 0.37, r = 0.22, r = 0.55); and also there was a significant positive correlation of ADA with GGT in ALL group (r = 0.54). In AML group, the maximum area under ROC curve was 0.761 (P = 0.00), 95% confidence interval was 0.682-0.841, sensitivity was 54.50%, specificity was 98.90%, and the best cut-off point was 17.1 U/L. In ALL group, the maximum area under ROC curve was 0.785, 95% confidence interval was 0.694-0.877, sensitivity was 65.90%, specificity was 84.00%, and the best cut-off point was 13.45 U/L. The detection of ADA in serum can be used as an auxiliary examination in patients with AL, which can provide a certain value for the diagnosis of the disease.

Clinical studies have shown that NST has better therapeutic results with chronic myelogenous leukemia (CML) than acute leukemia (AL), but whether the generation of graft-versus-leukemia (GVL) effects is different between AL and CML patients early after NST has not yet been studied, so we used a pentamer-staining technique in combination with ICCS to detect WT1(+)CD8(+)CTL/WT1(+)Tc1 and WT1(+)Th1 cells in these two groups of patients. Results showed that the emergence time of WT1(+)CD(8) (+)CTL/WT1(+)Tc1 cells after NST in AL patients was similar to that in CML patients (P = 0.58), while the emergence time of WT1(+)Th1 cells after NST in AL patients was shorter than in CML patients (P = 0.047). Furthermore, the peak proportions of WT1(+)CD(8) (+)CTL/WT1(+)Tc1 (P > 0.05) and WT1(+)Th1 (P > 0.05) cells were similar between AL and CML patients, and the increased rates (P > 0.05) and elevated levels (P > 0.05) of WT1-specific T cells were not statistically different between the groups after G-CSF mobilized donor mononuclear cell infusion. In addition, the reconstruction of lymphocyte subsets (P > 0.05) and CD4/8 ratios (P > 0.05) in AL patients were not statistically different from those in CML patients within 180 days after NST. These results suggested that WT1 maybe induces similar GVL effects in both AL and CML patients early after NST.

Background Interleukin 15 (IL-15), proinflammatory cytokine, regulates immune system functions and controls hematopoietic cell differentiation. It promotes leukemia development through enhancing survival, proliferation, and differentiation of leukemic precursors. Aim The aim was to assess the expression of IL-15 level in adult Egyptian acute leukemia patients, its correlation with disease-free survival, overall survival and relapse rate, and its possible correlation with other prognostic parameters. Patients and methods Serum IL-15 was measured using ELISA in 30 newly diagnosed acute lymphoblastic leukemia (ALL) patients, 30 newly diagnosed acute myeloid leukemia (AML) patients, and 30 healthy controls recruited from Ain Shams University Hospital from 2017 to 2018. Results In ALL patients IL-15 was higher in patients compared with the control. IL-15 was higher in patients with non-high-risk cytogenetics compared with those with high-risk cytogenetics. Patients with high IL-15 who achieved first complete response (CR) were less than those with low/average IL-15. Patients with high IL-15 who achieved minimal residual disease (MRD) negativity were less than those with low/average IL-15. Patients with high IL-15 had shorter survival compared with those with low/average IL-15 level. Optimal cutoff value for IL-15 in predicting patient survival in ALL patients was 200 ng/l. In AML patients: IL-15 was higher in patients compared with the control. IL-15 was higher in patients with high-risk features compared with those without. Patients with high IL-15 achieved first CR less than those with average IL-15. Patients with high IL-15 achieved MRD negativity less than those with average IL-15. Patients with high IL-15 had shorter survival compared with those with low/average IL-15. Optimal cutoff value for IL-15 in predicting patient survival in AML patients was 190 ng/l. IL-15 has negative correlation with death date in AML patients. Conclusion IL-15 is a useful poor prognostic marker in newly diagnosed acute leukemia patients’ also it can be used as a predictor for CR, MRD, and survival.

Objectives To evaluate the count of endothelial progenitor cells (EPCs) in peripheral blood (PB) and bone marrow (BM) of acute leukemia (AL) patients and explore its clinical significance. Methods EPCs were detected by flow cytometry procedures in 43 AL patients and in 10 benign hematologic patients as control group. Results The absolute counts of EPCs in AL patients before the treatment [(119.46±72.23)/μl in BM and (13.69±8.26)/μl in PB] were significantly higher than those in control group [(23.21 ±12.59)/μl in BM and (1.86±1.18)/μl in PB] (P 0.05). After the treatment, the absolute counts of EPCs both in BM and in BP of CR group [(26.32±17.44)/μl and (2.54±2.12)/μl, respectively] were significantly lower than those before treatment [(113.18±69.22)/μl and (14.45±10.76)/μl, respectively] (P 0.05). The absolute counts of EPCs whether in PB or in BM were no significant difference between acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) (P > 0.05). The absolute counts of EPCs in PB of AL had a positive correlation with β2-MG and LDH (P < 0.05). Conclusions EPC levels are significantly increased in BM and BP of AL patients and may correlate with disease status , response to treatment and prognosis. Key words: Acute leukemia; Endothelial progenitor cells; Flow cytometry

The antitumor effect of natural killer T cells has been reported in several studies analyzing the expression of CD1d on antigen-presenting cells (APCs). Therefore, the present study questioned whether APCs may be abnormal in the peripheral blood (PB) of acute leukemia (AL) patients, particularly the levels of CD1d. To improve the understanding of the role of CD1d on APCs, the levels of CD1d on monocytes were analyzed in healthy controls, AL patients and AL patients with complete remission (CR). In addition, the correlation between the number of CD3+CD56+ T lymphocytes and levels of CD1d on monocytes was analyzed. Flow cytometry was used to determine the levels of CD1d on monocytes and lymphocytes. A significant decrease was observed in the levels of CD1d on monocytes in the PB of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients compared with the healthy controls. Simultaneously, significantly different levels of CD1d on monocytes were identified between the CR-AML and the CR-ALL patients; the levels of CD1d on monocytes remained low in the CR-AML patients, while the levels of CD1d on monocytes recovered in the CR-ALL patients. A significantly negative correlation was observed between the number of CD3+CD56+ T lymphocytes and the levels of CD1d on monocytes in AL patients. However, a significantly positive correlation was identified between the cytotoxicity of the CD3+CD56+ T lymphocytes and the levels of CD1d on monocytes. These results suggested that the significantly low levels of CD1d on monocytes may contribute to AML and ALL progression. In addition, a significant correlation was observed between the levels of CD1d on monocytes and the number/cytotoxicity of CD3+CD56+ T lymphocytes in AML and ALL patients.

Endocan is a soluble dermatan sulfate proteoglycan expressed by endothelial cells and detected in serum/plasma. Its expression is increased in tumors/tumor vessels in several human malignancies, and high expression (high serum/plasma levels or tumor levels) has an adverse prognostic impact in several malignancies. The p14 endocan degradation product can also be detected in serum/plasma, but previous clinical studies as well as previously unpublished results presented in this review suggest that endocan and p14 endocan fragment levels reflect different biological characteristics, and the endocan levels seem to reflect the disease heterogeneity in acute leukemia better than the p14 fragment levels. Furthermore, decreased systemic endocan levels in previously immunocompetent sepsis patients are associated with later severe respiratory complications, but it is not known whether this is true also for immunocompromised acute leukemia patients. Finally, endocan is associated with increased early nonrelapse mortality in (acute leukemia) patients receiving allogeneic stem cell transplantation, and this adverse prognostic impact seems to be independent of the adverse impact of excessive fluid overload. Systemic endocan levels may also become important to predict cytokine release syndrome after immunotherapy/haploidentical transplantation, and in the long-term follow-up of acute leukemia survivors with regard to cardiovascular risk. Therapeutic targeting of endocan is now possible, and the possible role of endocan in acute leukemia should be further investigated to clarify whether the therapeutic strategy should also be considered.

Biphenotypic acute leukemia is a rare disorder that is difficult to diagnose. It displays features of both myeloid and lymphoid lineage. There is still a lack of studies in biphenotypic acute leukemia in a Chinese population. We present here a comprehensive investigation of the clinical and biological characteristics, and outcome of biphenotypic acute leukemia in our hospital in over a seven year period. We retrospectively analyzed 452 adult acute leukemia patients diagnosed according to French-American-British (FAB) classification and biphenotypic acute leukemia diagnosed according to European Group for the Immunological Characterization of Leukemias (EGIL) classification, respectively. Biological characteristics, response to treatment, and outcome were examined in biphenotypic acute leukemia patients and compared with that in acute myeloid leukemia and acute lymphoblastic leukemia patients with complete follow-up profiles diagnosed in the same period. Of 452 acute leukemia patients, 21 cases (4.6%) were diagnosed as biphenotypic acute leukemia. Among them, 14 (66.7%) were B lymphoid and myeloid, 5 (23.8%) were T lymphoid and myeloid, one (4.8%) was T/B lymphoid and one (4.8%) was trilineage differentiation. When compared with acute myeloid leukemia and acute lymphoblastic leukemia, patients with biphenotypic acute leukemia showed significantly higher incidence of CD34 antigen expression, unfavorable karyotypes, and extramedullary infiltration (p<0.05). In this cohort of patients with biphenotypic acute leukemia, t(9;22) was the most common abnormality in chromosome structure. The median disease-free survival and overall survival in biphenotypic acute leukemia patients was five months and ten months, respectively, significantly shorter than those in acute myeloid leukemia and acute lymphoblastic leukemia patients (p<0.05). The prognosis of biphenotypic acute leukemia patients is poor when compared with de novo acute myeloid leukemia or acute lymphoblastic leukemia. Biphenotypic acute leukemia patients showed a much higher incidence of CD34 antigen expression, complex abnormal karyotype, extramedullary infiltration, relapse, and resistance to therapy after relapse.

Differences in Experiences Reported By Patients with Acute and Chronic Leukemia: A Global Survey

Background: Cancer stem cells are the cancer cells that have abilities to self-renew, differentiate into defined progenies, and initiate and maintain tumor growth. Among the reported makers of the cancer stem cells, CD133 is the most well-known marker for isolating and studying cancer stem cells in different types of cancer. The CD133high population of cancer cells are not only capable of self-renewal, proliferation, but also highly metastatic and resistant to therapy. Aim and Objectives: To know about PROM-1 (CD 133) overexpression in adult acute lymphoblastic leukemia Egyptian patients and relation to outcome. Subjects and Methods:This is a Prospective study, was conducted at Ain Shams university hospitals. Internal medicine department, Clinical hematology and stem cell transplantation unit, on 47 adult patients with Acute Lymphocytic Leukemia, over aperiod of Six months. Result: according to outcome there were 22 (68.75%) with Complete remission, 8 (25%) with Resistant and 2 (6.25%) died. There were 26 (81.2%) with fever, 10 (31.2%) with Bleeding tendency, 26 (81.2%) with Lymph node, 17 (53.1%) with Hepatosplenomegaly, 9 (28.1%) with Mediastinal mass and 17 (53.1%) with Bone pain. Conclusion: Prominin 1 positive expression is a helpful prognostic marker in patients with ALL. Prominin 1 should be routinely assessed at diagnosis in ALL patients for better prognostic assessment and should be taken in consideration in designing future therapeutic strategies based on patient specific risk factors.

Objective To evaluate the quality of life of patients with pediatric acute leukemia post hematopoietic stem cell transplantation (HSCT) and to analyze the influential factors for patients' quality of life. Methods Sixty of acute leukemia patients from 2 to 18 years old received HSCT and attained more than 4 months survival were recruited from 2 hematology centers in Beijing.PedsQL™ Cancer Module 3.0 Chinese mandarin version was completed by both parents and 8-18 years old patients.Clinical data were extracted from medical records.The quality of life of patients was evaluated and analyzed. Results Forty-nine parents and 32 patients consented to participate and completed the questionnaires, with 34 boys (69.4%) and 15 girls (30.6%). The age of them was (9.94±4.24)years old. The sample included 28 acute lymphoblastic leukemia patients (57.1%), 19 acute myeloid leukemia patients (38.8%) and 2 acute mixed leukemia patients (4.1%); 16 second complete remission patients (32.7%) and 33 first remission patients (67.3%). The mean scores of overall quality of life after HSCT were 68-75 (out of 100), which was above the average.The disease status before transplantation (OR=0.197, P=0.021) and the education level of patient's mother (OR=3.932, P=0.043) were the influential factors for children's quality of life post HSCT: second complete remission status and the lower education level of mother resulted in worse quality of life.Neither gender, diagnosis, donor sources, slight graft versus host disease, parents' job, education level of father, nor home area influenced the quality of life significantly. Conclusions The overall quality of life of HSCT patients is above the average.The influential factors for patients' quality of life include the disease status before transplantation and the educational level of patients' mother. Key words: Hematopoietic stem cell transplantation; Quality of life; Influence factor; Acute leukemia; Child