Laura Marbello

Outcome of hyperleukocytic adult acute myeloid leukaemia: A single-center retrospective study and review of literature

Hyperleukocytic acute myeloid leukaemia is considered to have a poor prognosis due to high early death rate secondary to leukostasis. Supportive treatments do not seem to have reduced early exitus in this subset of patients. Prognostic impact of hyperleukocytosis on outcome has been the object of few studies. Clinical characteristics and outcome of 45 consecutive adult patients with newly diagnosed acute myeloid leukaemia presenting to our institution with a white cell count (WBC) above 100 x 10(9)L(-1) were reviewed. The outcome of this subset of patients was compared with 200 patients with a leukocyte count lower than 100 x 10(9)L(-1) similarly treated in the same period. Eight hyperleukocytic patients (17%) died of intracranial haemorrhage or pulmonary failure due to leukostasis within the first 7 days of treatment. A significant association was found between complete response (CR) and absence of hyperleukocytosis, but if early deaths were removed from analysis the difference was no longer significant. Hyperleukocytosis also significantly reduces the overall survival (OS) but does not significantly influence the disease-free survival (DFS). We reviewed in literature studies in which the outcome of series of at least 10 patients with hyperleukocytosis were compared with that of patients with a leukocyte count lower than 100 x 10(9)L(-1). Our data were consistent with those of the literature regarding the rate of early mortality and causes of death. In most of the reviewed series hyperleukocytosis does not seem to influence the outcome of patients. Avoiding early death seems to be an important step in this subset of patients. New data about pathophysiology of leukostasis are needed.

Advanced mast cell disease: an Italian Hematological Multicenter experience

The aim of the study is to evaluate clinical features, treatments and outcome of patients with systemic mast cell disease (MCD) who arrived to the attention of hematologists. A retrospective study was conducted over 1995–2006 in patients admitted in 18 Italian hematological divisions. Twenty-four cases of advanced MCD were collected: 12 aggressive SM (50%), 8 mast cell leukemia (33%), 4 SM with associated clonal non-mast cell-lineage hematologic disease (17%). Spleen and liver were the principal extramedullary organ involved. The c-kit point mutation D816V was found in 13/18 patients in which molecular biology studies were performed (72%). Treatments were very heterogeneous: on the whole Imatinib was administered in 17 patients, α-Interferon in 8, 2-CdA in 3; 2 patients underwent allogeneic hematopoietic stem cell transplantation. The overall response rate to Imatinib, the most frequently employed drugs, was of 29%, registering one complete remission and four partial remission; all responsive patients did not present D816V c-kit mutation. Overall three patients (12%) died for progression of disease. We conclude that MCD is characterized by severe mediator-related symptoms but with a moderate mortality rate. D816V c-kit mutation is frequent and associated with resistance against Imatinib. Because of the rarity of these forms, an effective standard of care is lacking. More data are needed to find new and successful therapeutic strategies.

Mast cell leukemia: A report of ten cases.

Dear Editor, Systemic mastocytosis (SM) comprises a heterogeneous group of disorders characterized by proliferation and accumulation of mast cells (MC) in one or more organs. Mast cell leukemia (MCL) is an extremely rare subtype of SM defined by leukemic infiltration of bone marrow and other organs by atypical neoplastic MC, morphologically characterized by cytoplasmic extensions, eccentric oval nucleoli and hypogranulated cytoplasm, which could exhibit a more immature blast-like morphology with no signs of maturation, prominent nucleoli and fine nuclear chromatin. Flow cytometric analysis of neoplastic MC reveals detection of CD2 and/or CD25 antigen, CD117/kit, CD68 [1, 2]. This infiltration may lead to bone marrow myelofibrosis with hemopoietic insufficiency, organ disfunction, bleeding and death after a median survival time of 6–7 months [2, 3]. Diagnostic criteria for MCL correspond to that used for diagnosis of SM, but also include a high percentage of bone marrow (≥20% of all nucleated cells) and circulating (≥10% of leukocytes) MC. According to the WHO consensus classification, cases of MCL with less than 10% circulating MC should be termed aleukemic variant [4]. The prognosis of disease is severe: Most patients (pts) survive less than 1 year and respond poorly to cytoreductive drugs or chemotherapy. A curative therapy is currently not available. Over the years 1995–2006, in collaboration with 17 Italian hematological divisions, 36 cases of SM were observed: 13 aggressive SM, ten MCL, seven indolent SM and six SM with associated hematopoietic non-mast cell lineage disease, particularly one acute myeloid leukemia, three myeloproliferative disorders (one idiopathic myelofibrosis, one polycythemia vera and one essential thrombocytemia) and two low-grade B-cell lymphoma; however, we focused the attention only on the ten cases of MCL. All centres were asked to report data about epidemiological, clinical features, treatments and outcome of their cases of MCL. Diagnostic features included hematological parameters with morphological examination of peripheral blood smears, bone marrow aspirate and bone marrow biopsy with an evaluation of MC infiltrate and immunophenotypic examinations of MC by flow cytometry. Furthermore, information about cytogenetic analysis, molecular biology analysis for the presence of the c-kit point Ann Hematol (2008) 87:505–508 DOI 10.1007/s00277-007-0430-3

Bone marrow hypoplasia complicating tacrolimus (FK506) therapy

Tacrolimus (FK506)-induced hematological toxicity, which has rarely been reported in transplant recipients, may result in anemia episodes, reported mainly in kidney and heart transplant recipients, sporadic cases of thrombotic thrombocy-topenic purpura/hemolytic uremic syndrome, red cell aplasia (4 reported cases), and generalized bone marrow suppression (only 1 reported case). We describe a case of a liver transplant recipient with pancytopenia that appeared during immunosuppressive therapy with tacrolimus. This patient suffered from progressive anemia, leukopenia with severe neu-tropenia, and mild thrombocytopenia; bone marrow biopsy showed hypoplasia (20% of cellularity) without dysplasia. Bone marrow recovery was made possible by suspending tacrolimus and changing to immunosuppression with cyclo-sporine A, despite the two drugs being very similar in their mechanism of immunosuppression. Contrary to previously reported cases (pure red cell aplasia and bone marrow hypoplasia), the recovery of hemoglobin and neutrophil values was slow after tacrolimus suspension, even though in the first month transfusions were no longer necessary.

Prospective monocentric study of non-tunnelled central venous catheter-related complications in hematological patients

Indwelling central venous catheters (CVCs) are used in the management of hematologic patients. However, insertion and maintenance of CVCs are susceptible to complications. Study design and methods data concerning 388 consecutive catheterisations, performed in oncohematologic patients between April 2003 and December 2004, were prospectively collected. At insertion thrombocytopenia was present in 109 cases (28.1%) and neutropenia in 67 (17.3%). Hemorrhage after CVC insertion occurred in five thrombocytopenic patients (1.3%). The median duration of catheterisation was 18.8 days (range 1–89), longer in the 7-French CVCs utilised in leukemic patients (24.3 days) and shorter in 12-French CVCs (11 days), used for PBSC harvesting. Deep venous thrombosis was diagnosed in 13 cases (3.3%). Ninety-two catheterisations (12.6/1000 days-catheter) were complicated by infections: 19 local infections (4.8%) and 73 (18.8%) bacteraemias of which 45 (11.6%) were catheter-related, mainly due to Gram positive germs (32/45, 71.1%). The frequency of catheter-related bacteraemia was 7.2 events/1000 days-catheter. Thirteen CVCs were removed due to thrombosis, 15 due to infections, 20 due to malfunction, the remaining 333 at patients discharge. At univariate analysis high-dose chemotherapy (p = 0.013), 7-Fr lumen (p = 0.023), acute myeloid leukemia (AML) (p = 0.001), duration of neutropenia >10 days and length of catheterisation were significantly correlated to infection. Multivariate analysis confirmed the duration of catheterisation, AML and high-dose chemotherapy as risk factors. Even though hematological in-patients are at increased risk for bleeding and infections, non-tunnelled CVCs offer a safe venous access also in patients affected by severe thrombocytopenia and prolonged neutropenia.

Invasive fungal infections in lymphoproliferative disorders: a monocentric retrospective experience

Abstract Invasive fungal infections (IFIs) seem to be a relevant cause of morbidity and mortality in patients with chronic lymphoproliferative disorders. We studied retrospectively the epidemiology, clinical manifestations and outcome of invasive fungal infections in 42 patients with lymphoproliferative diseases, treated between January 2004 and February 2012 for probable or proven IFI. In our entire population (1355 patients) of chronic lymphoproliferative malignancies, the incidence of probable/proven IFI was 3% (molds 2.3%, yeasts 0.5%, mixed infections 0.2%). Eight patients developed a yeast infection documented by blood cultures in seven cases and by the microscopic observation of Candida spp. in the vitreum after vitrectomy in one case. Among molds we diagnosed three proven infections by histologic evidence of Aspergillus spp. (n = 2) and Mucor (n = 1) in the lung and 28 probable mycoses. Three mixed infections from both molds and yeasts were also observed. Twenty-two cases showed positivity of galactomannan antigen in the serum (n = 16), in bronchoalveolar lavage (BAL) fluid (n = 4) or in both (n = 2). Cultures were positive in 11 cases. The overall rate of response to therapy was 64%. Fungal-attributable mortality rate was 17%, with a significant difference between molds and yeasts (16% vs. 25%, p = 0.03). At univariate analysis, the only risk factors related to mortality were severe and prolonged neutropenia (p = 0.003) and age (p = 0.03). Among molds, the rapid start of antifungals was probably partially responsible, together with new drugs, for the reduction of mortality, despite the severe immunosuppression of these patients.

Clinical management of peripherally inserted central catheters compared to conventional central venous catheters in patients with hematological malignancies: A large multicenter study of the REL GROUP (Rete Ematologica Lombarda - Lombardy Hematologic Network, Italy)

Tao Cai , Xiang Chen, Jinchen Li, Bingwu Xiang, Liu Yang, Yidian Liu, Qiuli Chen, Zhouwen He, Kevin Sun, P. Paul Liu Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland Physical Medicine and Rehabilitation Center, Second Affiliated Hospital of Wenzhou Medical University and Yuying Children’s Hospital, Wenzhou, Zhejiang, China Genetic Metabolic CentraLand of Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China Department of Neurology, First Affiliated Hospital of Nanhua University, Hengyang, Hunan, China Oncogenesis and Development Section, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, Maryland