Eleni Kapsali

Administration of a modified chemotherapeutic regimen containing vincristine, liposomal doxorubicin and dexamethasone to multiple myeloma patients: preliminary data.

Abstract: For elderly patients with multiple myeloma (MM), conventional melphalan and prednisone (MP) therapy has been the treatment of choice; the vincristine, doxorubicin and dexamethasone (VAD) regimen is preferred for younger patients who also receive high‐dose melphalan in combination with autologous or allogeneic bone marrow transplantation (BMT). Although survival time is similar in both the MP and VAD regimens, the continuous infusion of doxorubicin which the latter treatment entails constitutes a disadvantage along with the 4‐day hospitalization required. Doxorubicin also induces cardiotoxicity, particularly in the elderly. A modified form of VAD therapy includes liposomal doxorubicin (Caelyx®) (40 mg/kg for 1 d), oncovin (2 mg for 1 d) and dexamethasone 40 mg for 4 d per os. Doxorubicin encapsulated with liposomes has less cardiotoxicity, is more efficient and has fewer side effects than conventional doxorubicin, and it can be administered on an outpatient basis: dexamethasone can be given orally and vincristine in bolus infusion. In order to estimate its efficacy and tolerability, we administered this regimen to 12 patients (first‐line treatment in 6 patients, salvage therapy in 6 patients). All patients exhibited good tolerance to liposomal doxorubicin with no severe side effects. Eight patients achieved complete hematological remission and three partial response. One patient died before completing the treatment.

Brucellosis-Induced Autoimmune Hemolytic Anemia Treated with Rituximab

Objective: To present a case of brucellosis-induced severe autoimmune hemolytic anemia (AIHA) that was refractory to traditional corticosteroid treatment and eventually treated with rituximab apart from antibiotic therapy and to discuss the potential role of rituximab in similar cases of AIHA triggered by an underlying reversible cause. Case Summary: A 79-year-old woman was diagnosed with severe AIHA (reticulocyte count 21.5%, hemoglobin 6 g/dL). Initial treatment with prednisone in a regional hospital was not efficacious. Brucellosis was diagnosed by serology; the disease was further complicated by hepatic and splenic granulomatous involvement and sacral bone localization. Due to the severity of AIHA as demonstrated by reticulocyte count and hemoglobin levels, the initial unresponsiveness to corticosteroid therapy, the potential of the underlying infectious cause to relapse along with AIHA, and the localization of the pathogen in a focal site (bone involvement) that could act as a constant AIHA trigger, the patient was treated aggressively with rituximab, apart from the typical antimicrobial therapy. Discussion: Brucellosis can induce autoimmunity and mimic primary hematologic diseases. We reviewed reports on the unique forms of Brucella-induced hemolysis available in the literature. Massive hemolysis, though, is rare, and in the case of a pathogen such as brucellosis, one cannot ignore the potential for infection relapse accompanied by hemolysis relapse. Cases refractory to corticosteroids are typically treated with invasive amputative procedures such as splenectomy. However, in cases where an underlying therapeutically reversible cause of infection can be identified, the proven short-term efficacy and safety profile of rituximab can be of significance. Conclusions: Novel therapeutic approaches with molecular agents such as rituximab may assist in treatment of considerably severe infectious pathogen-induced autoimmune hemolytic anemia that is refractory to first-line therapy.

Serum beta‐2‐microglobulin, TNF‐α and interleukins in myeloproliferative disorders

Whereas beta‐2‐microglobulin (β2M) has mainly been used as a prognostic factor in patients with lymphoproliferative disorders, some studies have reported the value of β2M in myeloproliferative disorders (MPD). In order to investigate a potential role in the pathogenesis of MPD and to find a possible value as indicators in monitoring the course of the disease, we measured β2M, TNF‐α, IL‐1α, IL‐1β, IL‐2, sIL‐2R, IL‐6 and IL‐10 in 55 patients with MPD, at diagnosis and during the course of the disease. In progressive disease and particularly when transformation to acute leukemia occurred, high levels of β2M, IL‐2 and sIL‐2R were found in all patients; the elevation was progressive, which suggests a potential prognostic usefulness in the individual patient.

Recombinant human erythropoietin for the treatment of refractory anemia in lymphoproliferative disorders: preliminary results

To the Editor: A number of malignant hematological disorders are characterized by refractory anemia; these include hematopoietic stem cell disorders (aplastic anemia, myelodysplastic and myeloproliferative disorders and leukemias), malignant lymphomas and monoclonal gammopathies (1). Various mechanisms including low production and impaired use of erythropoietin (EPO) are responsible for anemia in these conditions (2,3). Anemia in cancer patients, including those with lymphoproliferative disorders, is usually due to a shortened erythrocyte lifespan and the failure of the bone marrow to increase red cell production (1, 4). Reduced iron stores, inadequate erythropoietin production and inhibiting erythropoiesis by cytokine overproduction constitute the most important factors which diminish red cell production (4). On the other hand, advanced chronic lymphoproliferative disorders usually develop progressive marrow infiltration and anemia, although often the degree of anemia is not necessarily related to the degree of marrow involvement by lymphocytes (5 ) . Excessive release of cytokines such as IL-1 and TNF may blunt the normal production of EPO (6). Patients with cancer and lymphoproliferative disorders have been found to have low levels of EPO for the degree of anemia (4, 7-9). Recombinant human erythropoietin (rHuEpo) has been shown to be safe, well tolerated and effective in correcting anemia in cancer patients, even if they undergo chemotherapy (4,9). In this study we tested the efficacy and safety of rHuEpo administration to patients with anemia associated with CLL, HCL and Waldenstrom’s macroglobulinemia.

Rivaroxaban Use in Patients with Hemoglobinopathies

Abstract The use of rivaroxaban in patients with hemoglobinopathies and thrombotic events has not been studied extensively. Here we present eight cases of such patients, five receiving rivaroxaban for stroke and systemic embolism prevention due to non-valvular atrial fibrillation and three for deep vein thrombosis treatment. The follow-up period ranged from 6 to 34 months. During this period none of the patients experienced any thrombotic or bleeding event.There were no other adverse events reported. Further studies with larger numbers of patients with hemoglobinopathies are needed to determine the use of rivaroxaban and ensure its safety in this patient setting.

Electrocardiographic abnormalities and arrhythmic risk markers in adult patients with beta thalassemia major

BACKGROUND There seems to be a significant arrhythmia burden in β-thalassemia major (TM) patients without overt cardiomyopathy. Apart from conventional electrocardiographic (ECG) and arrhythmic risk markers we studied novel markers of ventricular repolarization and autonomic imbalance both at rest and after exercise testing. METHODS We studied 47 adult TM patients without systolic heart failure and 47 age and sex-matched healthy control subjects. The median age of the studied population was 36 [32-43] years, 57% men. Baseline demographic and clinical characteristics were recorded while 12-lead electrocardiograms, 24-hour ECG Holter recordings, and treadmill exercise stress tests were analyzed. RESULTS TM patients exhibited increased QTc intervals in both 12-lead ECG recordings and in 24-hour Holter recordings. In addition, they had increased indexes of ventricular repolarization heterogeneity such as QT dispersion, and T peak-to-end/QT ratios. Furthermore, TM patients had decreased indexes of heart rate variability while the heart rate recovery after exercise was significantly attenuated compared to controls. Also, they had increased P wave and QRS duration while the QRS fragmentation was very prevalent. Finally, premature atrial extrasystoles and paroxysmal atrial fibrillation episodes were more frequent in TM patients. CONCLUSIONS TM patients with preserved left ventricular systolic function have several ECG abnormalities including alterations in ventricular depolarization and repolarization. Also, cardiac autonomic dysfunction is evident in 24-hour ECG monitoring as well as in the recovery phase after exercise testing. The prognostic value of specific arrhythmic risk indexes in this setting remains to be elucidated.

Plasmablastic Lymphoma with Coexistence of Chronic Lymphocytic Leukemia in an Immunocompetent Patient: A Case Report and Mini-Review

Background Plasmablastic lymphoma (PBL) is a rare, aggressive B-cell lymphoma with poor prognosis usually found in the oral cavity of HIV-positive patients. Chronic lymphocytic leukemia (CLL) is an indolent B-cell lymphoma with a variable clinical course. Transformation of CLL to PBL as Richters syndrome is rare while coexistence of CLL and PBL at diagnosis is even rarer. Case Report We describe a case of a male immunocompetent patient with an ileum-cecum valve mass and a soft tissue mass at the left humerus with histologic evidence of PBL with coexistence of CLL in the bone marrow and peripheral blood. Amputation of the patients left arm was inevitable, and the patient was started on bortezomib and dexamethasone. However, prolonged hospitalization was complicated by aspiration pneumonia, and the patient passed away. Conclusions No standard of care exists for patients with PBL, and prognosis remains dismal. Concomitant presentation of hematological malignancies becomes increasingly recognized, and further insight is needed in order to delineate whether they originate from the same clone or from different ones.

Safety and efficacy of prolonged hydroxycarbamide administration in patients with sickle cell disease in Northwestern Greece.

Hydroxycarbamide (HC) is a ribonucleotide reductase inhibitor which promotes fetal hemoglobin (HbF) induction and has proven efficacy in sickle cell disease (SCD) patients. Given its mechanism of action and pr ior reports of genotoxicity in animal models, concern exists regarding long - term safety in relation to its cytotoxic effects. The purpose of this study was to retrospectively analyze the long - term (range 3 - 20 years, median 11) HC - derived clinical and biological effects, in 30 SCD patients (age range 20 - 68 years) from one referral center. HC treatment resulted in significant reduction of painful crises and transfusions, increase of HbF and hemoglobin as well as drop of white blood cell count and lactate dehydrogenase values. During the long term follow up time the following disea se complications were observed: pulmonary hypertension (2 patients), leg ulcers (1 patient) and renal impairment (1 patient). Seven patients discontinued HC therapy because of sc heduled pregnancy (3), severe neutropenia (2) and non - compliance (2). One poor HC compliant

The Role of Plerixafor in the Management of Non-Hodgkin’s Lymphoma and Hematopoietic Stem Cell Transplantation

Autologous hematopoietic stem cell transplantation (HSCT) is an established treatment for relapsed chemotherapy sensitive non-Hodgkin’s lymphoma (NHL) and an important component of anti-myeloma therapy. Recovery of bone marrow function after autologous HSCT is dependant on the dose of infused hematopoietic stem cells (HSCs) after bone marrow ablation. Despite the use of chemotherapy and granulocyte colony-stimulating factor (G-CSF) based mobilization regimens, some patients are unable to mobilize adequate numbers of CD34+ HSCs and cannot undergo potentially lifesaving autologous HSCT. Plerixafor (AMD3100 or Mozobil) is a newly licensed drug which is used with G-CSF to mobilize CD34+ HSCs for autologous HSCT, reducing apheresis requirements, and the rate of primary mobilization failure. Plerixafor and G-CSF “rescue” protocols allow the successful mobilization of HSCs in patients that have failed standard G-CSF based mobilization protocols. Hematopoietic stem cell biology and the use of Plerixafor in the management of NHL are reviewed.