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Background and Objectives: To evaluate the characteristics of patients affected by hematologic malignancies who developed a chronic disseminated candidiasis (CDC), and to ascertain the factors that influenced the outcome, in a retrospective study conducted between January 1990 and December 2000, in 4 Hematology Divisions., Design and Methods: CDC was diagnosed by clinical features combined with radiological and/or histologic and/or microbiological data., Results: Twenty-eight patients (male/female 14/14; average age 42 years, range 12-67) developed a CDC. Twenty had acute myeloid leukemia, 5 had acute lymphocytic leukemia and 3 had non-Hodgkin's lymphoma. All patients received chemotherapy, including cytarabine for 21 of them (75%). Before the infection, 22 patients (79%) were neutropenic (absolute neutrophil count < 0.5 x 10(9)/L) for an average of 20 days (8-36), but at CDC diagnosis only 3 patients (11%) were neutropenic. Twenty-two patients (75%) received antifungal prophylaxis for an average of 15 days (10-60). Before diagnosis of CDC, 9 patients (32%) had a candidemia. The sites compromised by CDC were: liver in 27 patients (96%) and/or spleen in 11 patients (38%). Ten patients had other organs involved: lung in 6 patients (21%), kidney in 4 patients (14%), other sites 2 patients (7%). Abdominal ultrasonography was positive in 96% of patients (27/28), and abdominal computed tomography-scan was positive in 100% of cases in which it was performed (21/21). Liver biopsy was positive in 10/15 patients (67%). The main signs and symptoms were: fever 86%, abdominal pain 54%, diarrhea 32%, tenderness 25%, vomiting 25%, jaundice 29%, dysphagia 7%. Among chemical analyses, the most sensitive test was alkaline phosphatase, with a 3-5-fold increase in 24 patients (86%); an increase of liver transaminases and g-glutamyl transferase was observed in less than 50% of patients. By 30 days after diagnosis 4 patients had died, 1 from infection, and 3 progression of the hematologic malignancy without signs of active CDC. Within 3 months from diagnosis 14 out of the remaining 24 patients (58%) received further chemotherapy: in particular, 2 patients underwent transplantation procedures., Interpretation and Conclusions: In our experience CDC is not a fatal complication of patients with hematologic malignancy, on the contrary to that observed for other fungal infections (i.e. aspergillosis, candidemia), characterized by a higher mortality rate. The major problem of this fungal complication is correlated to the delay in the following treatment for the hematologic malignancy with a high risk of progression of malignancy.

In this paper we describe a case of a 65-year old man with a lymphoid blastic crisis of a chronic granulocytic leukemia occurring seven years after a palatine tonsillar non-Hodgkin's lymphoma treated with chemotherapy and radiation therapy. Bone marrow cytogenetic study demonstrated the presence of the typical t(9;22)(q34;q11) and the molecular biology study showed the p210 rearrangement (b2a2). The patient died within a few months, unresponsive to any treatment. This is the first case, described in literature, of a secondary chronic granulocytic leukemia onset with a lymphoid blastic crisis. The authors report the case and a literature review.

Background and Objective: The term secondary leukemia is usually employed to indicate both forms of acute myeloid leukemia (AML) evolving from previous myelodysplasia and forms of acute leukemia developing after exposure to environmental or therapeutic toxins or radiation (therapy related). Secondary leukemias account for 10-30% of all AML. The majority of secondary leukemias resulting from the use of cytotoxic drugs can be divided into two well defined groups depending on whether the patient has received 1) alkylating agents or 2) drugs binding to the enzyme DNA-topoisomerase II. Alkylating agents related leukemias are very similar to post MDS leukemias being characterized frequently by a preleukemic phase, tri-lineage dysplasia, frequent cytogenetic abnormalities involving chromosomes 5 and 7 and a poor prognosis. Secondary leukemias related to therapy with topoisomerase II inhibitors are not preceded by a preleukemic phase and show frequently balanced translocations involving chromosome 11q23. Among therapy-related leukemias, AML is generally a second neoplasm, thus a predisposition to malignancy, independently from previous chemotherapy, cannot be excluded. This review article examines the incidence of all secondary AMLs and the risk of therapy-related leukemia in relation to the different primary malignancies and treatments., Information Sources: The authors have been working in this field, both experimentally and at clinical level, contributing original papers for many years. In addition, the material examined in this review includes articles published in journals covered by MedLine, reviews in journals with high impact factor and recent reports presented at the Secondary Leukemia. An Update Symposium held in Rome in November 1998., State of the Art and Perspectives: The incidence of secondary leukemias is increasing because of aging of the population (MDS is more frequent in elderly people) and widespread and successful use of chemoradiotherapy in cancer patients. In the GIMEMA archive of adult acute leukemia (2,964 AML pts from June 1992 to June 1996) an antecedent hematologic disorder (AHD) and/or MDS was found in 8% of all patients (10% of 2,118 patients aged more than 45 years and in 4% of 848 patients aged less than 45). In this series of patients, 6% of all myeloid leukemias were therapy-related leukemia. Therapy-related leukemias are a major problem in patients treated for Hodgkin's disease, non-Hodgkin's lymphoma, myeloma, polycythemia, breast cancer, ovarian carcinoma, or testicular carcinoma. In the GIMEMA archive more than 50% of patients with secondary AML have breast cancer, NHL, and HD. Alkylating agents, nitrosureas and procarbazine appear to have the highest leukemogenic potential. Furthermore aggressive chemotherapy and radiotherapy followed or not by hematopoietic stem cell infusion will produce a more and more prolonged survival but also a greater incidence of secondary AML. Assessment of the risk of secondary leukemia should become part of any therapeutic plan for cancer patients. Avoidance of drugs with more leukemogenic potential will produce a marked reduction of secondary AML.

The authors describe the cases of three patients affected by acute myeloid leukemia, in complete remission, who rapidly developed neurologic symptoms leading to death. Neither clinical characteristics, nor radiological or microbiological procedures, allowed an etiological diagnosis of the neurologic syndrome. Post-mortem examination of the brain showed both macroscopic and microscopic findings compatible with acute hemorrhagic leukoencephalitis. The difficulty in distinguishing this entity from other CNS disease-related complications (e.g. leukemia infiltration, drug toxicity, hemorrhages) should not lead to an underestimation of the true incidence of this complication. We believe that with more attention to the possibility of this complication there would probably be both a greater possibility of collecting clinical informations about the real impact of this dramatic disease and a stronger hope of finding the right treatment for it.