Ebru Koca

Spontaneous tumor lysis syndrome in a patient with diffuse large B cell lymphoma and Richter syndrome

A 77-year-old man with a past medical history of hypertension, coronary heart disease, a cerebrovascular accident, and squamous cell lung cancer cured only by surgery 5 years ago, was admitted to our emergency department with complaints of dyspnea, fatigue, lethargy, and vague abdominal pain. When the patient was hospitalized for a cerebrovascular accident about 1 month before, he was diagnosed as having stage 1 chronic lymphocytic leukemia by lymphocytosis and enlarged peripheral lymph nodes with a greatest size of 3×2 cm, and was taken to a watch and wait program. Upon the current admission, physical examination revealed arterial blood pressure of 140/60 mmHg, heart rate of 100 bpm, respiration of 26 bpm, body temperature of 36.2°C, cervical multiple lymphadenopathies that were slightly smaller than those revealed 1 month before, marked splenomegaly, and marked peripheral edema. Fine crackles were also heard from the lung bases. Laboratory findings on the patient in due course are been depicted in Table 1. Abdominal ultrasound disclosed a 175mm splenomegaly. Many uric acid crystals were observed upon urine analysis. Since the findings were consistent with hypervolemia and acute renal failure accompanied with many electrolite disturbances, emergent hemodialysis was employed. Peripheral flow cytometric analysis revealed cluster of differentiation 3 (CD3) 1%, CD5 95%, CD19 74%, CD20 98%, CD23 15%, kappa 17%, lambda 17%, CD38 5%, FMC-7 negative, and human leukocyte antigen-DR (HLA-DR) 63%, indicating a monoclonal B cell population bearing lambda weakly on their surfaces. Cervical lymph node biopsy exhibited diffuse large B cell lymphoma. On the patient’s second day of admission, hemodialysis was repeated for anuria. On his third day of hospitalization, he developed upper gastrointestinal bleeding and hypotension. Esophagogastroduodenoscopy revealed gastroesophageal junctional erosive ulcers that were not actively bleeding. Despite the proper management, he died due to ventricular fibrillation and shock. Consent for an autopsy was refused.

Renin-angiotensin system expression in the K562 human erythroleukaemic cell line:

Local renin-angiotensin system (RAS) may affect leukaemic cell production within the bone marrow microenvironment.Angiotensin-converting enzyme (ACE), renin, and angiotensin could influence leukaemogenesis. In this study, mRNA expressions of the major RAS components (ACE, renin, and angiotensinogen) in K562 human erythroleukaemia cell line have been searched by Real Time quantitative polymerase chain reaction. K562 blasts are multipotential, haematopoietic malignant cells that spontaneously differentiate into recognisable progenitors of the erythrocyte, granulocyte and monocytic series.We observed significant expressions of ACE, renin, and angiotensinogen in K562 leukaemic blast cells.Therefore, K562 human erythroleukaemia cell line may serve as an in vitro model to elucidate the role of RAS in leukaemia and to test the effects of RAS-affecting drugs on leukaemic cellular proliferation.

Effects of Imatinib Mesylate on Renin-Angiotensin System (RAS) Activity During the Clinical Course of Chronic Myeloid Leukaemia

The renin–angiotensin system (RAS) is involved in cell growth, proliferation and differentiation in bone marrow in an autocrine–paracrine manner, and it modulates normal and neoplastic haematopoietic cell proliferation. This study aimed to assess expressions of the RAS components, renin, angiotensinogen and angiotensin-converting enzyme (ACE), during imatinib mesylate treatment of patients with chronic myeloid leukaemia (CML). Expressions of RAS components were studied in patients with CML at the time of diagnosis (n = 83) and at 3, 6 and 12 months after diagnosis (n = 35) by quantitative real-time polymerase chain reaction. De novo CML patients had increased ACE, angiotensinogen and renin mRNA levels and these expression levels decreased following administration of imatinib. The RAS activities were significantly different among Sokal risk groups of CML, highlighting the altered biological activity of RAS in neoplastic disorders. The results of this study confirm that haematopoietic RAS affects neoplastic cell production, which may be altered via administration of tyrosine kinase inhibitors such as imatinib mesylate.

Predicting Chronic Leukaemias from Assessment of Complete Peripheral Blood Counts

The chronic leukaemias include two distinct chronic neoplastic disease states, namely chronic myelogenous leukaemia (CML) and chronic lymphocytic leukaemia (CLL). The aim of this study was to assess the utility of leucocyte count, neutrophil percentage and absolute lymphocyte count from differential complete blood count analyses as indicators of the possible presence of CML and CLL. Blood counts from 102 patients with histopathologically confirmed CML and CLL were compared with counts for 858 cancer-free control subjects. Optimal cut-off values were identified by selecting values with the highest sensitivity–specificity combination for each blood count parameter for the two diseases. The results indicated that any individual with mature-appearing lymphocytes at a level > 6.65 × 109/l in the peripheral blood should be examined further for CLL, and that any individual with a leucocyte count > 18.0 × 109/l or a neutrophil proportion > 72.6% should be investigated for CML.

Unusual extramedullary recurrences and breast relapse despite hepatic GVHD after allografting in Ph+-ALL

Abstract Extramedullary recurrences with or without bone marrow involvement are reported in up to a half of leukemic relapses after BMT. Our report describes a case of an extramedullary recurrence and breast relapse after second-allografting in a female patient with Ph+-acute lymphoblastic leukemia (ALL), occurring when there was active hepatic GHVD. This case illustrates the complex relationship between graft-versus-host disease (GVHD) and graft-versus-leukemia since she had no evidence of leukemia in her marrow demonstrating 100% full-donor chimerism while she had ALL relapse in her breast.

Changing clinical manifestations of a T-peripheral lymphoma: From hypereosinophilic syndrome to questionable Kimura's disease resulting in parotid mass

The diagnosis of low-grade lymphoproliferative disorders during a long clinical course sometimes represents a great clinical challenge. The idiopathic hypereosinophilic syndrome (HES) represents a pre-malignant state in some patients and close follow-up is necessary to detect early signs of malignant transformation. Kimuras disease (KD) mimicking HES is an immune mediated inflammatory disorder that usually involves the head and neck region, primarily affecting the salivary glands, adjacent muscle and regional lymph nodes. Clinically, it is very difficult to differentiate KD from salivary gland lymphoid malignancies. Lymphomas may uncommonly present as a parotid mass. One, herein, would like to present a 35-year-old patient with changing clinical presentation patterns over a period of more than 6 years of follow-up. The first clinical presentation of the patient was HES. The ‘diagnosis’ of KD was reached after 4 years of management with HES. The final manifestation was parotid gland, preauricular and cutaneous manifestations of a peripheral T-cell lymphoma. This unique clinical presentation pattern of the patient may represent the distinct pathobiological progression of a clonal neoplastic lymphoproliferative disorder.

Endogenous thrombopoietin levels during the clinical management of acute myeloid leukaemia

Thrombocytopenia represents a major problem in the management of acute myeloid leukaemia (AML). The data regarding the alterations of endogenous thrombopoietin (TPO) regulation during the clinical course of AML are limited. The aim of this study was to investigate endogenous TPO dynamics in association with platelets during the clinical course of AML. We serially measured both TPO and platelets concurrently over the entire treatment period of newly diagnosed patients receiving both remission induction and consolidation chemotherapies. The median concentration of TPO in AML patients at the initial diagnosis was 469.71u2009pg/ml and increased significantly during the aplastic period due to remission induction chemotherapy (median: 1085.33u2009pg/ml) but then decreased to a level (median: 45.26u2009pg/ml) encountered in the healthy control subjects (median: 56.90u2009pg/ml). In the cytopenic period due to consolidation treatment, TPO level again increased significantly to a high level (median: 891.38u2009pg/ml) during the platelet nadir, but decreased toward normal (median: 100.75u2009pg/ml) after the thrombocytopenic period had elapsed. In conclusion, endogenous TPO levels exhibit an inverse fluctuation in relation to platelet counts during the clinical course of AML. Pharmacological stimulation of thrombopoiesis in AML with novel molecules, including the recombinant thrombopoietins and the small peptide agonists, should be based on a critical administration strategy that must consider the endogenous levels of TPO. TPO levels in distinct AML disease states may explain the unsuccessful recombinant TPO trials and could help to design better strategies for ‘pharmacological stimulation of thrombopoiesis’ in AML.

Soluble Platelet Glycoprotein V in Distinct Disease States of Pathological Thrombopoiesis

Quantitative platelet disorders (i.e., thrombocytosis or thrombocytopenia) may also be associated with qualitative platelet alterations. Clonal thrombocythemia (CT), reactive thrombocytosis (RT), immune thrombocytopenic purpura (ITP), and thrombocytopenia of aplastic pancytopenia (AA) or infiltrative bone marrow disorders represent the major classes of pathological thrombopoiesis. Glycoprotein V may serve as an in vivo marker of platelet activation in thrombotic and hemorrhagic states. The aim of this study was to assess circulating plasma soluble platelet glycoprotein V (sGPV) concentrations in distinct disease states of pathological thrombopoiesis. The whole study group comprised 20 patients with thrombocytopenia, 32 patients with thrombocytosis and 14 healthy adults as the control group. sGPV was significantly increased in the group of thrombocytosis patients in comparison to the thrombocytopenic group and the healthy control groups. When sGPV levels were corrected according to platelet number (sGPV/tr), this ratio was very high in patients with thrombocytopenia compared to patients with thrombocytosis and the control group. Our results suggest that there is an ongoing platelet activation associated with thrombocytosis regardless of its origin is either CT or RT. Therefore, glycoprotein V system may serve to activate residual platelets in thrombocytopenia regardless of its origin is either ITP or AA.

Unchanged global fibrinolytic capacity during the course of hematopoietic stem cell transplantation.

Hemostatic changes due to vascular endothelial damage are seen during the course of hematopoietic stem cell transplantation (HSCT). The fibrinolytic response to ongoing hemostatic activation in HSCT remains to be elucidated. Global fibrinolytic capacity (GFC) is a novel method, which reflects the amount of generated D-dimer when fibrinolysis of a freeze-dried fibrin clot is stopped by introducing aprotinin. GFC is sensitive to all the factors involved in the process of fibrinolysis. The aim of this study was to serially assess GFC at certain critical time points (days −1, +7, +14, +21 prior to and following stem cell infusion) during the course of HSCT. The study group comprised 16 patients with hematological malignancies (11 women, five men; median age 32 ± 9 years) in whom HSCT had been performed. Thirty healthy adults (21 women, nine men; median age 31 ± 7 years) served as controls. In this study, global fibrinolytic response, as reflected by GFC, was unchanged despite ongoing hemostatic activation, as indicated by D-dimer, moreover GFC remained stable, despite the development of thrombocytopenia associated with HSCT prior to platelet engraftment. Our results indicate that a global fibrinolytic response was impaired as a compensatory response to endothelial activation and to other hemostatic changes seen in HSCT. Further studies in larger HSCT populations are warranted to better understand the implications of these findings.