Thromboembolic events in patients with paroxysmal nocturnal hemoglobinuria (PNH): Real world data of a Greek nationwide multicenter retrospective study.

Thrombosis is the most common and a life-threatening complication in patients with Paroxysmal Nocturnal Hemoglobinuria. One-third of patients with PNH experience at least one thromboembolic event during the course of the disease, with thrombosis being the most common cause of death in these patients. The mechanism of thrombosis in PNH is complex and continues to be of great research interest. Since the introduction of C5 complement inhibitors in the treatment of PNH, the incidence of thromboembolic events has decreased substantially. We retrospectively analyzed data concerning the thrombotic episodes of 41 patients with PNH from 14 different national hematology centers in Greece. Sixteen patients (39%) experienced at least one episode of thrombosis, including, seven (43.8%) at diagnosis, seven (43.8%) during the course of the disease and two (12.5%) patients prior to PNH diagnosis. Nearly half of these individuals (n=7, 43.8%) had multiple episodes of thrombosis during the course of their disease. The most common sites of thrombosis were intra-abdominal veins. Three out of 26 patients developed thrombosis while on eculizumab. In none of the 16 patients, the thrombotic event was fatal. Our findings, despite the small number of patients, confirmed that thrombosis continues to be a significant complication of PNH affecting more than one third of the patients.

Arsenic trioxide-based therapy of relapsed acute promyelocytic leukemia: registry results from the European LeukemiaNet.

In 2008, a European registry of relapsed acute promyelocytic leukemia was established by the European LeukemiaNet. Outcome data were available for 155 patients treated with arsenic trioxide in first relapse. In hematological relapse (n=104), 91% of the patients entered complete hematological remission (CR), 7% had induction death and 2% resistance, 27% developed differentiation syndrome and 39% leukocytosis, whereas no death or side effects occurred in patients treated in molecular relapse (n=40). The rate of molecular (m)CR was 74% in hematological and 62% in molecular relapse (P=0.3). All patients with extramedullary relapse (n=11) entered clinical and mCR. After 3.2 years median follow-up, the 3-year overall survival (OS) and cumulative incidence of second relapse were 68% and 41% in hematological relapse, 66% and 48% in molecular relapse and 90 and 11% in extramedullary relapse, respectively. After allogeneic or autologous transplantation in second CR (n=93), the 3-year OS was 80% compared with 59% without transplantation (n=55) (P=0.03). Multivariable analysis demonstrated the favorable prognostic impact of first remission duration ⩾1.5 years, achievement of mCR and allogeneic or autologous transplantation on OS of patients alive after induction (P=0.03, P=0.01, P=0.01) and on leukemia-free survival (P=0.006, P<0.0001, P=0.003), respectively.

A prospective, cohort, multicentre study of candidaemia in hospitalized adult patients with haematological malignancies.

Invasive candidiasis is a life-threatening infection in patients with haematological malignancies. The objective of our study was to determine the incidence, microbiological characteristics and clinical outcome of candidaemia among hospitalized adult patients with haematological malignancies. This is a population-based, prospective, multicentre study of patients ≥ 18 years admitted to haematology and/or haematopoietic stem cell transplantation units of nine tertiary care Greek hospitals from January 2009 through to February 2012. Within this cohort, we conducted a nested case-control study to determine the risk factors for candidaemia. Stepwise logistic regression was used to identify independent predictors of 28-day mortality. Candidaemia was detected in 40 of 27,864 patients with haematological malignancies vs. 967 of 1,158,018 non-haematology patients for an incidence of 1.4 cases/1000 admissions vs. 0.83/1000 respectively (p <0.001). Candidaemia was caused predominantly (35/40, 87.5%) by non-Candida albicans species, particularly Candida parapsilosis (20/40, 50%). In vitro resistance to at least one antifungal agent was observed in 27% of Candida isolates. Twenty-one patients (53%) developed breakthrough candidaemia while receiving antifungal agents. Central venous catheters, hypogammaglobulinaemia and a high APACHE II score were independent risk factors for the development of candidaemia. Crude mortality at day 28 was greater in those with candidaemia than in control cases (18/40 (45%) vs. 9/80 (11%); p <0.0001). In conclusion, despite antifungal prophylaxis, candidaemia is a relatively frequent infection associated with high mortality caused by non-C. albicans spp., especially C. parapsilosis. Central venous catheters and hypogammaglobulinaemia are independent risk factors for candidaemia that provide potential targets for improving the outcome.

Comparative molecular analysis of therapy-related and de novo acute promyelocytic leukemia.

Therapy-related acute promyelocytic leukemia (t-APL) has been reported as a late complication of exposure to radiotherapy and/or chemotherapeutic agents targeting DNA topoisomerase II. We have analyzed in t-APL novel gene mutations recently associated with myeloid disorders. Unlike previous reports in acute myeloid leukemia (AML), our results showed neither IDHs nor TET2 mutations in t-APL. However we found an R882H mutation in the DNMT3A gene in a patient with t-APL suggesting a possible role of this alteration in the pathogenesis of t-APL.

Laparoscopic adrenalectomy for large adrenal metastasis from contralateral renal cell carcinoma.

We present herein the case of a patient with solitary metachronous contralateral adrenal metastasis from renal cell cancer. The patient had undergone left radical nephrectomy and adrenalectomy for localized renal cancer 7 years previously. Laparoscopic transperitoneal right adrenalectomy was performed. The postoperative period was uneventful. Histology showed right adrenal metastasis from renal cancer. At 6-month follow-up, there was no evidence of recurrence.

Laparoscopic resection of large adrenal ganglioneuroma.

We report on a 23-year-old woman with a right adrenal tumor 13 cm in diameter who was treated by laparoscopy. The patient was asymptomatic, and the tumor was incidentally diagnosed on abdominal ultrasonography. A subsequent computed tomography (CT) of the abdomen confirmed a 12 x 7 x 8-cm homogenous mass of the right adrenal. Magnetic resonance imaging (MRI) showed a solid mass measuring 13 x 7 x 7.5 cm arising from the right adrenal. Laparoscopic complete excision of the mass was accomplished through a transabdominal lateral approach. The postoperative period was uneventful, and the patient was discharged on the second postoperative day. Histology was consistent with an adrenal ganglioneuroma. Two years later, there is no evidence of recurrence on abdominal CT scan.

Addition of cyclosporin-A to chemotherapy in secondary (post-MDS) AML in the elderly. A multicenter randomized trial of the Leukemia Working Group of the Hellenic Society of Hematology.

In elderly patients with secondary leukemia, poor therapeutic response and low overall survival have been attributed mainly to age and to the primary resistance of leukemic cells to chemotherapy. Modulation of resistance has been attempted in different studies, but the results have been contradictory. We conducted an open, randomized multicenter clinical trial involving patients more than 60 years old with secondary leukemia preceded by a myelodysplastic syndrome. The induction chemotherapy regimen included idarubicin, cytarabine, and etoposide (group A); randomization involved simultaneous administration of cyclosporin-A per os (group B). Fifty-five patients were evaluated, 26 in group A and 29 in group B. Overall complete remission was achieved in 40% of the patients, 27% vs 52% in groups A and B, respectively (p=0.01). Leukemia-free survival was more favorable in patients who received cyclosporin-A, 12 vs 7 months for groups B and A, respectively (p=0.03). In a follow up period of 30 months, 7 out of 55 patients (13%) were alive, 4 of whom were in complete remission. Five out of the 7 alive patients were randomized in group B and had received cyclosporin-A. Treatment failure was higher in group A [19 of 26 patients (73%)] than in group B with CsA [14 of 29 patients (48%)] (p<0.0001). Treatment-related toxicity/mortality was 13%. Modulation of drug resistance by CsA in elderly people suffering from secondary acute leukemia may improve the outcome of chemotherapy without increasing drug toxicity and treatment-related mortality.

Treatment of early clinically staged Hodgkin's disease with a combination of ABVD chemotherapy plus limited field radiotherapy.

The current management of early stage Hodgkin's disease (HD) is usually based on clinical staging, combined modality therapy and the use of less toxic chemotherapy regimens. This approach entails high cure rates, while ensures less long term toxicity with avoidance of laparotomy. The aim of this study was to assess the efficacy of a brief course of Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by limited field radiotherapy (RT) in favorable clinical stage (CS) I and IIA HD. Forty patients, aged 17-68 (median 34) years, with favorable CS I and IIA HD, without bulky mediastinal disease, have been treated with 4-6 (median 4) cycles of ABVD plus limited field RT. Twenty seven (67%) patients received 4 cycles of chemotherapy, while 13 received 5-6 cycles. Thirty five (87%) patients received limited field RT with dose 24-36 Gy and five (13%) received extended field with 36-46 Gy. All patients responded completely to chemotherapy. One patient experienced a relapse two months after the end of therapy. All patients are alive; 39 in continuous complete remission. With a median follow-up period of 44 months (range 18-101) the actuarial overall and progress free survival was 100 and 97% at 5 years. We did not observe any case of secondary leukemia or solid tumor. Pulmonary toxicity was mild in cases of mediastinal irradiation. Considering the short follow-up time and the small number of patients, the combination of a brief course of ABVD plus regional RT is a very efficacious treatment of favorable CS I and IIA HD with mild toxicity. However, long term survival data are needed, which could give confident answers regarding the risk of late therapy related complications, particularly second malignancies.