Biomedical subjects
Publications and source records attributed to L Pagano.
We report a patient with acute myeloid leukemia and Blastoschizomyces capitatus sepsis who developed multiple abscesses when neutrophils recovered. The patient did not respond to antifungal therapy and her clinical condition showed an improvement only after rhGM-CSF was added to the treatment.
We retrospectively studied a consecutive series of 100 patients with acute leukemia and aspergillosis to evaluate the clinical findings and risk factors for colonization of the central nervous system (CNS) by Aspergillus species. The diagnosis of CNS aspergillosis was made in 14 patients on the basis of the following criteria: neurological signs of CNS involvement (13 of 14 patients); cerebral CT scan findings (9 of 12); microbiological findings (6 of 12); and histological findings at autopsy (11 of 11). The majority of patients had severe neurological complications (i.e., hemiparesis or seizures), due mainly to brain abscesses or mycetomas. Autopsies were performed on 11 of 14 patients and provided evidence that CNS localization was secondary to invasive aspergillosis; in each case, the most likely primary focus of infection was the lung. Although all patients had received oral antimycotic prophylaxis and had received timely empirical antifungal treatment, they all died within a median time of 5 days from the onset of neurological symptoms. Analysis of the characteristics of patients with invasive aspergillosis did not reveal any difference between those with CNS localization and those without CNS localization.
We studied serum lipid and lipoprotein changes before and after induction treatment in 25 acute nonlymphocytic leukemia (ANLL) and in 18 acute lymphocytic leukemia (ALL) patients in order to investigate their relationship with disease activity and their prognostic relevance. ANLL at diagnosis is associated with significantly low levels of all lipid parameters, the same applies to ALL patients apart from plasma triglycerides and very-low-density-lipoprotein cholesterol (VLDL-C) which are significantly higher than in the normal population. In ANLL responders, after effective chemotherapy, a significant increase of total cholesterol, low-density-lipoprotein cholesterol (LDL-C) and apolipoprotein B levels, without changes of high-density-lipoprotein cholesterol (HDL-C) values, is observed. A further decrease of total cholesterol and LDL-C was found in nonresponders and in ANLL responders treated with granulocyte-macrophage colony-stimulating factor (GM-CSF), known for its cholesterol-lowering action; in fact after the completion of GM-CSF therapy, these parameters returned progressively toward normal values. In ALL responders an increase of total cholesterol, HDL-C and apolipoprotein A1 with a simultaneous decrease of triglycerides and VLDL-C is evident; no variation was found in the nonresponder group. These results suggest a close correlation between serum lipids and acute leukemia: total cholesterol and LDL-C in ANLL, and HDL-C and VLDL-C in ALL may be considered reliable markers of complete remission and may be useful in the follow-up of leukemic patients.
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BACKGROUND: Despite advances in the treatment of acute lymphoblastic leukemia (ALL), overt meningeal leukemia remains a dire condition. The role of intraventricular chemotherapy (IVC) in its treatment is still a matter for debate. Data suggesting benefit from it have been countered by statements of concern regarding the potential complications associated with its use. This report details our results from using IVC. PATIENTS AND METHODS: We compared two groups of adult patients with ALL at their first meningeal involvement. Twelve of them were submitted to ILC and 9 to IVC. RESULTS: Our data showed that IVC yielded a higher rate of complete response (88% vs. 33%) and a lower incidence of second CNS relapse than did ILC (none vs. 50%). Even though there were more long-term disease-free survivors (33% vs. 8%) among the IVC patients, the difference in median event-free survival was not significant (120 vs. 80 weeks; p = 0.66). IVC was associated with a longer overall survival (p = 0.005) and CNS remission time (p = 0.046). Two cases refractory to ILC were later fully responsive to IVC. There were 22% device-related and 11% drug-related complications. CONCLUSIONS: The results are promising, but the small series does not allow for any definite conclusion. In our opinion, the hazards inherent in the placement and operation of the device do not outweight the benefits of IVC for the treatment of overt meningeal leukemia and should not preclude its use. Accurate neurosurgical technique, meticulous care in drug administration and experience with this form of therapy can all contribute to minimizing complications so that full advantage can be taken of IVC's potential.
A retrospective study on a consecutive series of 116 patients affected by acute leukaemia with documented pulmonary filamentous mycosis (FM) admitted between 1987 and 1992 to 14 tertiary-care hospitals in Italy was made in order to evaluate the characteristics of those patients who developed fatal massive haemoptysis. In 59/116 cases of pulmonary FM the infection was the principal cause of death and in 12 of these patients a massive haemoptysis was responsible for death. The diagnosis of FM infection was made ante-mortem in only four out of these 12 patients. The autopsy was performed in 11/12 patients and documented a FM infection. The mycetes isolated were: Hyphomycetes spp. (three patients), Mucorales spp. (two patients), Aspergillus spp. (seven patients). At the time of the massive haemoptysis the mean neutrophil count was 7.2 x 10(9)/l, and no patient had relevant thrombocytopenia (mean 184 x 10(9)/l, range 28-350) or coagulative abnormalities. The mean time which elapsed between resolution of chemotherapy-induced neutropenia (WBC < 10(9)/l) and occurrence of haemoptysis was 7 d. No signs or symptoms predictive of this fatal complication were identified. Massive haemoptysis can be the cause of death in patients with acute leukaemia and pulmonary FM which in the majority of patients was not diagnosed in vivo. This complication occurs most frequently shortly after the recovery from chemotherapy-induced aplasia. The mechanism of lesion is unknown, but it may involve the vascular tropism of FM and the release of leucocyte enzymes. Better preventive and therapeutic antifungal treatments are needed to avoid this serious, albeit rare, complication.
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We describe a white Italian kindred in which hereditary elliptocytosis (HE) is associated with abnormal level of alpha I/78 peptide in spectrin digest. Clinical phenotype varied among the family members ranging from asymptomatic to mild haemolytic HE. The original mutation responsible is a G-C substitution of the spectrin alpha-gene: alpha 45 Arg-->Thr (AGG-->ACG). The corresponding spectrin is designated spectrin Anastasia. Utilizing a secondary structure predictive method we suggest that this mutation has a poor capability to induce conformational changes of the tetramerization site and thus shows a moderate elliptocytogenic potential.
In a patient affected by acute lymphoblastic leukemia (ALL) and subjected to therapy with Erwinia L-asparaginase, acute parotitis was observed. Microbiological studies excluded any infectious etiology. Regression of parotitis was spontaneous. This complication has not been previously reported and could be due to the same mechanism of pancreatic injury. The occurrence of acute parotitis needs to be promptly recognized in order to avoid the continuation of L-asparaginase.
We studied the hormonal pattern of nine patients with acute lymphoblastic leukemia. The patients were treated with standard therapeutic regimens. They were overweight by a mean of 52% at the end of the consolidation treatment, and this persisted after a follow-up of 2 years. The only endocrine alteration observed was a moderate decrease in serum testosterone levels in male patients. The other parameters studied were in the normal range. We conclude that prolonged treatment with high doses of corticosteroids, which have a depressive effect on metabolism, was responsible for the obesity.
Current studies suggest a derangement of the cholesterol homeostasis in certain types of leukaemia. The low serum cholesterol levels observed in patients with AML have been related to the tumoral mass and to the disease activity. Only a few studies have taken into consideration a possible change of the serum lipids in ALL. The aim of this study was to evaluate a possible prognostic significance of serum levels of total cholesterol (TC), triglycerides, HDL-C, LDL-C, VLDL-C, apolipoproteins A1 and B and lipoprotein (a), investigated in 10 newly diagnosed ALL patients before and after induction treatment. At diagnosis all these parameters were not significantly different in our patients vs control group except cholesterol and HDL-C levels, which were significantly lower. After the induction treatment, we found a significant increase of HDL-C and Apo A1 values only in those patients that achieved a complete remission. These results support the idea that some serum lipids, such as HDL-C and Apo A1, may have a role as early and reliable markers of the effectiveness of chemotherapy.
We detected Hb D-Los Angeles [beta 121(GH4)Glu-->Gln], the most common hemoglobin variant after Hb S and Hb Lepore-Boston, in six unrelated families in Southern Italy. Ten patients were studied; eight patients were heterozygotes and two were compound heterozygotes for the hemoglobin variant and the beta-thalassemia codon 39 (C-->T) nonsense mutation. The beta-globin gene sequence was characterized by polymerase chain reaction direct sequencing; restriction fragment length polymorphisms were defined by Southern blot analysis. The gene variant, due to the GAA-->CAA substitution at codon 121, was found in association with the 5' subhaplotype [+ - - - -] and the beta-globin gene framework 1; in addition, it was found to be associated with the absence of Ava II/phi beta and Xmn I/5'G gamma, and with the presence of Hpa I/3' beta. This restriction fragment length polymorphism haplotype is common in the Mediterranean area as well as in other populations. The findings are equally compatible with an independent origin in the Mediterranean area or with origin in Asia and subsequent spread to Italy.
Hb O-Arab [beta 121(GH4)Glu-->Lys] was detected in two Mediterranean families, one from Southern Italy and the other from Albania. The GAA-->AAA mutation at codon 121 was characterized by DNA sequencing. The mutant genes were associated with the same beta-globin gene framework variant and with the rare Hpa I/3' beta polymorphic restriction site generating a 7.0 kb fragment. However, at 5' the gene of the Italian family was associated with the restriction fragment length polymorphism subhaplotype [+ - - - +] and the Taq I/3'G gamma polymorphic site, while that of the Albanian family was associated with subhaplotype [- - - - +] but not with the Taq I/3'G gamma site. The particular features of these polymorphisms support the hypothesis of an African origin for the Hb O-Arab gene and a subsequent recombination event leading to the haplotype found in the Italian family.
Two patients with granuloblastic masses of the breast, onsetting at diagnosis and as first relapse site of acute myeloid leukemia are reported. The first case had been diagnosed initially as a carcinoma, and the patient underwent bilateral mastectomy. Acute leukemia was only revealed by histology of the surgical specimen. In the second case a second neoplasia, occurring during acute leukemia, was suspected: a fine needle aspirate of the breast mass showed a leukemic infiltrate. Involvement of breast during acute myeloid leukemia is a rare event and, in our experience, of bad prognostic significance. Mammary glands may be a sanctuary for leukemic cells, contributing to unresponsiveness to chemotherapeutic agents.
Ninety-seven patients with refractory or relapsed acute myelogenous leukemia (AML), median age 37 years, received as salvage therapy a single course of idarubicin 6 mg/m2 as an intravenous (i.v.) bolus daily for 5 days, cytarabine (Ara-C) 600 mg/m2 i.v. for a period of 2 hours daily for 5 days and etoposide (VP-16) 150 mg/m2 for a period of 2 hours daily for 3 days (ICE protocol). Thirty-six patients were primarily resistant to standard inductive therapy with daunorubicin and Ara-C; 50 patients were in first relapse, three patients in second or third relapse, and eight patients in relapse after transplants. Forty-two (43%) out of 97 patients achieved complete remission, 11 patients died of infection or hemorrhage during induction, and 44 patients (45%) had resistant disease. Of the various variables examined, only disease status (i.e. refractory versus relapsed AML) was predictive for a significantly lower response rate. The median remission duration was 16 weeks; the overall median survival was 10 weeks. Nausea, vomiting, and oral mucositis were common but were rarely severe. No patient experienced treatment-related cardiac toxicity. In conclusion, the ICE protocol is a tolerable regimen providing effective antileukemic activity in patients with advanced AML. The evolution of this protocol in previously untreated patients with AML appears indicated.
We describe a patient who, at the onset of acute myelomonocytic leukemia, presented with marked polyuria, polydipsia and laboratory findings consistent with diabetes insipidus (DI). He was treated with vasopressin (DDAVP) with a good response and concurrently induced with daunorubicin and conventional doses of cytosine arabinoside. CR was achieved. The vasopressin requirement decreased progressively, but the patient remained DDAVP-dependent after consolidation treatment. He underwent allogeneic BMT, conditioned with busulfan and cyclophosphamide. By day 15 after BMT vasopressin was no longer required and at a follow-up of 9 months the patient has no evidence of DI. In the absence of specific findings, we think it possible that he had leukemic microinfiltration of the hypothalamic-pituitary area. The drugs used for conditioning may have eradicated CNS disease.
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