Amro Mohamed Sedky El-Ghammaz

Impact of serum soluble programed death ligand 1 on end of treatment metabolic response of diffuse large B cell lymphoma patients

AbstractProgrammed death ligand-1 (PD-L1) plays an important role in the immune evasion of cancer cells and, in turn, can influence the outcome of many malignancies. The serum soluble PD-L1 (sPD-L1) levels were measured in diffuse large B cell lymphoma (DLBCL) patients at diagnosis and at end of treatment. Their impact on end of treatment metabolic response was analyzed. Serum sPD-L1 level was significantly elevated in DLBCL patients at diagnosis than in controls (P < 0.001). Also, serum sPD-L1 level at diagnosis was significantly higher than that at end of treatment (P < 0.001). Patients who achieved partial response (PR) had significantly higher serum sPD-L1 level at end of treatment than controls (P < 0.001). In contrast, all patients especially those who achieved complete response (CR) had insignificantly different serum sPD-L1 level at end of treatment than controls (P = 0.354 and P = 0.090, respectively). There was a significant difference between serum sPD-L1 level at diagnosis and that at end of treatment in patients who achieved PR and CR (P = 0.023 and P < 0.001, respectively). On univariate analysis, presence of comorbidities, Ann Arbor stage IV, high serum sPD-L1 level at diagnosis and high serum sPD-L1 level at end of treatment were significantly associated with achievement of PR (P = 0.018 and P = 0.043, P = 0.045 and P < 0.001, respectively). On multivariate analysis, serum sPD-L1 levels at diagnosis and at end of treatment were still influencing metabolic response significantly (P = 0.014 and P = 0.007, respectively). Serum sPD-L1 is a predictor for metabolic response to immunochemotherapy in DLBCL patients.

Risk Factors Influencing Outcome of Acute Leukemia Patients Who Experience Relapse After Allogeneic Hematopoietic Stem-Cell Transplantation

Background Prognosis of acute leukemia patients who experience relapse after hematopoietic stem‐cell transplantation (HSCT) remains poor. Identifying risk factors influencing outcome of these patients is essential. Patients and Methods Follow‐up of 234 acute leukemia patients who underwent allogeneic HSCT from matched related donor was performed for occurrence of posttransplantation relapse. Statuses of remission and survival were assessed at 6 months after treatment of relapse. Analysis of risk factors influencing postrelapse overall survival (prOS), complete remission (CR), and nonrelapse mortality (NRM) was carried out. Results Posttransplantation relapse occurred in 43 patients (17.9%). After treatment, 11 patients (25.6%) experienced postrelapse remission, the prOS rate was 20.9% (9 patients), and the NRM rate was 25.6% (11 patients). Older age (P = .007) and failure to experience remission after relapse treatment (P = .027) were associated with lower prOS in multivariate analysis. Female sex (P = .027), posttransplantation extramedullary relapse (P = .001), and absence of postrelapse graft‐versus‐host disease P = .025) were associated with lower CR rate. Also, presence of extramedullary relapse (P = .011) was associated with lower risk of NRM whereas treatment of posttransplantation relapse with donor lymphocyte infusion with or without chemotherapy (P = .002) and occurrence of postrelapse graft‐versus‐host disease (P = .025) were associated with higher risk of NRM. Conclusion Survival of acute leukemia patients who experience relapse after allogeneic HSCT is poor, especially in elderly patients and those who do not experience remission after relapse treatment. Micro‐Abstract In a study of 43 patients to assess the risk factors influencing relapse outcome after hematopoietic stem‐cell transplantation in acute leukemia, older age and failure to experience complete remission (CR) after treatment were associated with inferior overall survival. Female sex, extramedullary relapse, and absence of postrelapse graft‐versus‐host disease (GVHD) were associated with lower CR; and absence of extramedullary relapse, treatment with donor lymphocyte infusion, and occurrence of postrelapse GVHD were associated with higher nonrelapse mortality.

Programmed death receptor ligand-1 plasma concentration in chronic myeloid leukemia under first-line tyrosine kinase inhibitor therapy

Background Chronic myeloid leukemia (CML) cells can suppress the immune system by secreting programmed death receptor ligand-1 (PDL-1) that acts as a coinhibitory molecule for T cells leading to T-cell exhaustion and disease progression. Aim The aim of this study was to assess the plasma level of PDL-1 in patients with chronic myelogenous leukemia and its correlation with prognostic parameters and response to first-line therapy. Patients and methods This study was carried out on 40 patients with CML in chronic phase and 40 control healthy participants. Patients with CML were subdivided into three subgroups, including 11 newly diagnosed patients, 17 imatinib mesylate-responding patients, and 12 imatinib-resistant cases. All patients were subjected to laboratory investigations including complete blood count, peripheral blood smear examination, bone marrow aspiration (if indicated), quantitative real-time PCR for Philadelphia chromosome, and plasma PDL-1 measurement by enzyme-linked immune sorbent assay. Results Our results showed high plasma levels of PDL-1 in patients with CML. Plasma PDL-1 levels showed a negative correlation with total lymphocyte count in imatinib-resistant subgroup. Imatinib-resistant subgroup showed a significant decreased level of PDL-1 versus newly diagnosed subgroup of patients with CML. The suggested PDL-1 cut-off value for prediction of patients with CML was 1327.5 ng/l. Conclusion Patients with chronic-phase CML (newly diagnosed, imatinib responding, and imatinib resistant) showed a highly significant increased PDL-1 level compared with the control group. Increased plasma PDL-1 level is a predictive risk factor for CML incidence and disease progression.

Role of Hepciden in Multiple Myeloma and Lymphoma Patients

Hepcidin-25 is thought to be the central regulator of body iron metabolism. Since the clinical characteristics of the anemias of chronic inflammation are similar to anemia found in cancer, and since several tumor types are associated with increased cytokine production, especially hepcidin has been addressed as an explanation for the associated anemia in these conditions. 14 patients with non-Hodgkin lymphoman, 12 patients with Hodgkin lymphoma and 24 patients with multiple myeloma enrolled in this study. Serum hepciden was measured in all patients using ELISA. Conclusion. Hepcidin levels are significantly higher in anemic patients with MM, HL and NHL. Hepcidin levels are inversely correlated with Hb levels.

Human leukocyte antigen HLA-BR16 is associated with reduced risk for cytomegalovirus infection and disease after allogeneic hematopoietic stem cell transplantation

Purpose Cytomegalovirus (CMV) infection and its associated disease are significant complications of allogeneic hematopoietic stem cell transplantation (HSCT). Many risk factors for CMV infection have been previously identified, including different human leukocyte antigens (HLAs) of donor/recipient pairs. We aimed to investigate the relation of broad HLAs of donor/recipient pairs to the occurrence of postallogeneic HSCT CMV infection and disease. Materials and methods A total of 112 patients undergoing allogeneic HSCT from a matched sibling donor were followed up for occurrence of CMV infection and disease by performing weekly quantitative PCR-CMV-DNA and clinical examination until day 100 after transplantation. Results CMV infection occurred in 58 patients (51.8%), whereas CMV disease occurred in 22 (19.6%). On univariate analysis, acute leukemia diagnosis (P < 0.001), donor/recipient CMV serostatus (P = 0.010), methylprednisolone administration (P = 0.002), fludarabine/cyclophosphamide/antithymocyte globulin-conditioning regimen (P = 0.002), age (P = 0.041), HLA-A1 (P = 0.037), HLA-A3 (P = 0.035), HLA-B15 (P = 0.021), HLA-B16 (P = 0.003), HLA-DR6 (P = 0.002), and HLA-Cw7 (P = 0.003) influenced the occurrence of CMV infection significantly. On multivariate analysis, HLA-A3, HLA-B16, and HLA-Cw7 significantly affected the risk for CMV infection occurrence (P = 0.025, 0.004, and 0.008, respectively). Also, HLA-B16 was associated with reduced risk for CMV disease (P = 0.048). Conclusion HLA-B16 has a protective effect against both CMV infection and disease following allogeneic HSCT.

Zinc and malondialdehyde levels among Egyptian patients with acute myeloid leukemia and their relation with disease phenotype and genotype

Objectives This study was conducted to evaluate serum zinc and plasma malondialdehyde (MDA) levels in de-novo acute myeloid leukemia (AML) before and after induction chemotherapy and their relation with AML phenotype and genotype. Materials and methods Twenty-five AML patients were subjected to serum zinc evaluation using flame atomic absorption spectrophotometry and plasma MDA evaluation using colorimetric method at day 1 before induction chemotherapy and at day 21 after induction chemotherapy. Results Pretreatment MDA levels were higher in patients in comparison with controls (P = 0.03). Pretreatment zinc levels differed significantly compared with post-treatment levels (P = 0.005). The percentage of bone marrow infiltration by blasts at diagnosis correlated inversely with zinc levels (P = 0.011) and positively with MDA levels (P = 0.041). Finally, pretreatment MDA levels were higher among patients harboring adverse cytogenetics (P = 0.004). Conclusion The elevated plasma MDA status at diagnosis in AML patients correlates with a higher tumor burden in the bone marrow and adverse cytogenetic risk.

Basophil progenitor marker histamine and its relation to the treatment response in Egyptian chronic myeloid leukemia patients

Introduction Chronic myeloid leukemia (CML) is characterized by the presence of the BCR-ABL fusion gene with constitutive tyrosine kinase activity that activates many signaling pathways contributing to the abnormal growth and survival of leukemic cells. Basophilia is a strong independent prognostic variable that correlates with the phase of CML. In CML, basophils are difficult to be identified by their morphology due to their immaturity or low frequency by tyrosine kinase inhibitors (TKIs) therapy. It is important to predict responses to therapy and to monitor levels of minimal residual disease in CML patients by cytogenetics and PCR. However, these parameters are expensive and require special technologies. Thus, the aim of the current study was to clarify whether the serum level of the basophil-marker histamine correlates with hematologic, cytogenetic, and molecular responses in CML patients and with the achievement of the optimal response to TKI therapy. Patients and methods The histamine level was measured by enzyme-linked immunosorbent assay in 48 CML patients, together with cytogenetic analysis at diagnosis and after 6 months from the start of imatinib treatment. Molecular study of BCR-ABL was also performed at 6 months. Results Histamine levels were upregulated in CML patients at diagnosis compared with the healthy control group and correlated with the total leukocytic count, the absolute peripheral blood basophil count, and the percent of bone marrow basophils. After 6 months of imatinib treatment, histamine levels were significantly reduced in CML patients compared with the levels at diagnosis and were still significantly higher than in controls. Histamine levels at 6 months correlated significantly with PCR measurements for BCR-ABL. A significant difference in histamine levels was found between patients according to their hematological, cytogenetic, and molecular responses. Also, it differed significantly among TKI response groups (optimal, warning, failure). Conclusion We found that the serum histamine level may serve as a cheap early predictor of cytogenetic and molecular remission as well as the response to imatinib. However, we could not encourage measuring serum histamine as an alternative to PCR for BCR-ABL for the monitoring of minimal residual disease.