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Biomedical subjects

E Morra

Publications and source records attributed to E Morra.

At least 55 records · Page 3Linked to original sources
PubMed2000

Rituximab (IDEC-C2B8): validation of a sensitive enzyme-linked immunoassay applied to a clinical pharmacokinetic study.

Rituximab is a chimeric monoclonal antibody (MAb) directed against the B-cell CD20 antigen that has been approved for therapy of relapsed and resistant follicular non-Hodgkin's lymphoma (NHL). This study describes the development and validation of a highly sensitive, rapid, accurate, precise enzyme-linked immunosorbent assay (ELISA) to measure Rituximab serum concentrations. This study also describes the application of the ELISA method to a pharmacokinetic study in a homogeneous group of patients with follicular lymphoma who received 4 weekly doses of MAb at the standard dose of 375 mg/m2 as consolidation of chemotherapy. In the patients in this study, the median Rituximab serum concentrations increased during therapy, and showed a slow decline during the posttreatment period. The Rituximab elimination half-life of approximately 20 days accounts for the demonstrated accumulation of MAb in serum samples. Because previous pharmacokinetic studies showed a correlation between Rituximab serum levels and tumor response, the ELISA method used in this study, which allows a precise control of serum concentrations, could be useful for predicting the final response to the MAb and for selecting patients able to benefit from higher dosage or repeated drug administration.

Antibodies, Monoclonal↗
PubMed2000

Mucormycosis in hematologic malignancies: an emerging fungal infection.

BACKGROUND AND OBJECTIVES: In recent years pulmonary mucormycosis has been reported in patients with leukemia and lymphoma and bone marrow transplant recipients. It carries an extremely poor prognosis. We report our experience of clinical findings, diagnostic procedures, treatment and outcome of mucormycosis diagnosed in neutropenic patients affected by hematologic neoplasms admitted to our Department. DESIGN AND METHODS: From November 1987 to July 1999 we observed 13 cases of Mucor. Their median age was 61 years (range 20-75), and they were predominantly in the aplastic post-chemotherapy period (12/13), affected by acute myeloid leukemia (11 cases ) or non-Hodgkin's lymphoma (2 cases). Six patients (all with leukemia) were receiving inductionEth consolidation therapy, 7 had progressive hematologic disease. At the onset of infection all patients were neutropenic (N < 0.5x10(9)/L). No patients had diabetes mellitus. Two patients had been receiving steroid therapy for 5 and 7 days. RESULTS: The lung was involved in all cases (13/13); disseminated disease was present in 8/13 patients. All cultures (blood, sputum, nasal swabs and bronchoalveolar lavage) were negative. In 3 patients a histologic diagnosis was made in vivo: in 1 patient by percutaneous pulmonary biopsy, in 1 patient by pulmonary lobectomy, and in the last patient by percutaneous pulmonary biopsy confirmed by excision of a cerebellar abscess. In the remaining 10 cases diagnosis was made post-mortem. Five patients were not treated, 2 because of poor clinical condition and 3 because fungal infection was not suspected. Amphotericin B (1 mg/kg/day) was given empirically to 6 patients and 2 responded to treatment. The remaining 2 patients with neurologic symptoms at the onset of infection were treated with liposomal amphotericin, Ambisome, one with 3 and one with 5 mg/kg/day; of these two patients the first died in 4 days; the second, with both pulmonary and cerebellar localizations, was treated successfully with 5 mg/kg/day for 4 weeks and then with 3 mg/kg/day, and excision of a brain abscess at neutrophil recovery (total dose of Ambisome: 12,000 mg). The 3 surviving leukemic patients were able to complete subsequent consolidation therapy using amphotericin B or liposomal amphotericin as secondary prophylaxis during aplasia. INTERPRETATION AND CONCLUSIONS: In neutropenic hematologic patients Mucor is rarely suspected. In our patients infection was often characterized by disseminated disease and a rapidly fatal course; only early aggressive amphotericin B (or Ambisome) treatment together with neutrophil recovery appeared to improve the outcome. Diagnosis is very important for programming antifungal therapy and secondary prophylaxis with amphotericin B, because Mucor is usually resistant to itraconazole.

Adult↗
PubMed1999

Fludarabine, cytarabine, and granulocyte-colony stimulating factor for the treatment of high risk myelodysplastic syndromes.

BACKGROUND: The prognosis of patients with high risk myelodysplastic syndromes (MDS) (i.e., refractory anemia with excess of blasts [RAEB] and refractory anemia with excess of blasts in transformation [RAEB-t]) usually is poor. The combination of fludarabine, cytarabine, and granulocyte-colony stimulating factor (G-CSF) (FLAG regimen) has been reported to be effective in patients with these diseases. METHODS: Forty-two patients (32 with RAEB-t and 10 with RAEB) were treated with the FLAG regimen. The median age was 61 years (range, 27-74 years). Forty patients were diagnosed with primary MDS and 2 patients had treatment-related MDS. Induction therapy was comprised of the FLAG regimen, whereas consolidation therapy included idarubicin and cytarabine. Patients with a compatible donor and who were age < 50 years were scheduled to undergo an allogeneic bone marrow transplantation (BMT), whereas for those patients without a donor and who were age < 60 years autologous BMT with peripheral blood stem cells mobilized by the consolidation regimen plus G-CSF was planned. RESULTS: Complete remission (CR) was achieved in 31 of 42 patients (74%; 95% confidence interval, 60-87%). Death during induction therapy occurred in 4 patients (9%) whereas 7 patients (17%) were resistant to the FLAG regimen. Toxicity from the consolidation regimen was negligible. All patients age < 50 years and achieving CR were eligible for allogeneic BMT procedures, with early recurrence being the only reason for exclusion. The median overall survival and disease free survival were 13 months and 18 months, respectively. Patients with favorable cytogenetics had a significantly better outcome compared with those patients with an adverse karyotype. CONCLUSIONS: The FLAG regimen is effective in patients with high risk MDS as well as in patients age > 60 years. The toxicity of the regimen is low and the majority of patients are eligible to undergo allogeneic BMT procedures after induction/consolidation therapy.

Aged↗
PubMed1999

Hepato-splenic gammadelta T-cell lymphoma: a rare entity mimicking the hemophagocytic syndrome.

Hepatosplenic gammadelta T-cell lymphoma is a rare histologic type of the peripheral T-cell lymphomas, clinically characterized by predominant involvement of liver and spleen, no or little adenopathy, and an often aggressive course; it affects mainly adolescents and young adults, with a male predominance. Postthymic T-cell malignancies are heterogeneous in their clinical and laboratory features. Among the gammadelta postthymic T-cell lymphomas, two distinct entities (cutaneous and hepatosplenic, respectively) are reported in the literature. The former shows predominant multiple involvement of the skin and subcutaneous tissue; it occurs mostly in older patients and the phenotype is CD3-, CD4-, CD8-. Because of the small number of reports, the course of the disease was unknown. The latter shows a clinical picture characterized by hepatosplenomegaly, no or little adenopathy, and sometimes systemic symptoms (fever, cytopenias likely due to hypersplenism); it presents a peculiar sinusoidal involvement of liver and spleen. The bone marrow histologic feature often reveals a little infiltration, especially sinusoidal and easily underestimated phenotype: CD2+, CD3+, CD7+, CD5-, CD4-, CD8-, CD44+. Few cases of this lymphoma associated by hemophagocytic syndrome are described (Sun, 1990; Kadin, 1981; Jaffe, 1983). We report a case of a young man with a rapid and fatal course in which the more important clinical feature was hemophagocytosis. The diagnosis of lymphoma was very difficult because of paucity of histologic involvement, and only the rearrangement of TCR gamma chain gene by polymerase chain reaction on paraffin sections confirmed a clonal T-cell proliferation.

Adult↗
PubMed1999

Infectious complications in chronic lymphocytic leukaemia.

Infections are the major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). Predisposition to infection in CLL is mediated through various abnormalities including both the immune defects inherent in the primary disease (impairment in humoral and cellular immunity) and in the further immunosuppression related to the management of CLL. Hypogammaglobulinemia is probably the most important immune defect in terms of risk of severe bacterial infections, its frequency and severity progressing with the duration of the disease. Newer antineoplastic agents such as purine analogues, especially when used in previously treated patients, may be associated with a new spectrum of pathogens (Listeria monocytogenes, Pneumocystis carinii, cytomegalovirus, herpes simplex virus, and mycobacteria) involving T-cell dysfunction. In this review we focus on the clinical characteristics of infections in CLL and on the risk factors involved in the pathogenesis of this complication. Furthermore, we describe the evolving patterns of infections associated with purine analogues and discuss the currently accepted approaches to prophylaxis and treatment.

Animals↗
PubMed1999

Mediastinal B-cell lymphoma: a study of its histomorphologic spectrum based on 109 cases.

Mediastinal B-cell lymphoma (MBL) is a distinct variant of aggressive non-Hodgkin's lymphoma with characteristic clinical and biological features but less well-defined histomorphology. We reevaluated 124 biopsy specimens from 109 MBL patients of an Italian/French/German retrospective clinical study. MBL was primarily diagnosed on clinical and histological grounds in conjunction with the detection of CD20 expression by immunohistology. Cytologically, MBL features limited intralesional but considerable interindividual cytological diversity, ranging from medium-sized to very large, atypical cells. Sclerosis and necrosis are restricted to extrathymic and extranodal sites of involvement, predominantly the lung, as is angioinvasion, which predominantly affects larger vessels. The medium-sized and the large cell variants resemble marginal zone lymphoma variants, whereas the very large cell variant of MBL has not so far been found to have any extramediastinal counterpart. We conclude that MBL displays a broad morphological spectrum covering more than is implied by the term "diffuse large cell lymphoma." Because statistical analysis of cytological and histological criteria failed to correlate with prognosis in this comprehensive group of patients, we think it inadvisable further to subclassify MBL.

Humans↗
PubMed1999

Centre effect on treatment outcome for patients with untreated acute myelogenous leukaemia? An analysis of the AML 8A Study of the Leukemia Cooperative Group of the EORTC and GIMEMA. European Organization for Research and Treatment of Cancer (EORTC) Leukemia Cooperative Group and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA).

In the AML 8A study patients were treated with remission-induction therapy followed by one consolidation course. Patients in complete remission (CR) were randomised between autologous bone marrow transplantation (ABMT) and a second intensive consolidation course, except for those with a histocompatible sibling donor, who received allogeneic bone marrow transplantation (alloBMT). This analysis was performed to determine whether centres which only performed induction and consolidation therapy, achieved similar results as centres who also performed transplantation. 542/676 (80%) from transplantation centres and 150/194 (77%) from referring centres achieved CR, with an early death rate of 5% and 11%, respectively (P = 0.01). 66% of patients with a donor from transplantation centres received alloBMT in first CR compared with 57% from referring centres (P = 0.2). Transplantation centres randomised 64% of patients without a donor, referring centres 47% (P = 0.04). The full protocol treatment was completed by 275/542 (51%) and 61/150 (41%) patients, respectively (P = 0.04). The overall survival rate at 6 years from diagnosis was 34% and 36%, respectively (P = 0.9). In conclusion, the type of centre did not appear to have an influence on overall survival. The feasibility of the study was acceptable for both types of centres. The referring centres applied more selection for transplantation. Despite a more intensive second-line treatment at transplantation centres, the overall outcome remained similar to that of referring centres.

Acute Disease↗
PubMed1999

Fludarabine, cyclophosphamide, and dexamethasone (FluCyD) combination is effective in pretreated low-grade non-Hodgkin's lymphoma.

PURPOSE: Fludarabine phosphate is effective as a single agent in low-grade non-Hodgkin's lymphoma (NHL). Combined with other antineoplastic agents it enhances the antitumor effect. Our aim was to define the therapeutic efficacy and toxicity of a combination of fludarabine, cyclophosphamide and dexamethasone (FluCyD) in patients with advanced low-grade lymphoma. PATIENTS AND METHODS: Twenty-five adults with pretreated advanced-stage low-grade NHL were treated with three-day courses of fludarabine 25 mg/m2/day, cyclophosphamide 350 mg/m2/day, and dexamethasone 20 mg/day, every four weeks for a maximum of six courses. RESULTS: Of the 25 patients, 18 (72%) responded, 8 (32%) achieving CR and 10 (40%) PR. Seven were failures. The median follow-up was 21 months (5-26). Eight CR patients remain in CR after 5-21 months. Of 10 PR patients, 3 are in continuous PR without further treatment after 12, 17 and 18 months. Myelosuppression was the most prevalent toxic effect. Although severe granulocytopenia (granulocyte count nadir < 500/microliter) and thrombocytopenia (platelet count nadir < 50,000/microliter) occurred in only 10% and 16% of courses, respectively, slow granulocyte or platelet count recovery caused delay of 40% of the courses. Nine patients (36%) required discontinuation of therapy because of persistent granulocytopenia and/or thrombocytopenia: three after one course, three after 2-4 courses, and three after five courses. Thirteen infectious episodes in 11 patients complicated 11% of courses. Two of 10 patients monitored for the circulating EBV load showed increased viral load. One of these developed aggressive lymphoma. CD4+ lymphocytes declined from a pre-therapy median value of 425/microliter to 141/microliter post-treatment (P = 0.001). Non-hematologic toxicities were rare and mild. CONCLUSIONS: The combination of fludarabine with cyclophosphamide and dexamethasone is effective in pretreated advanced-stage low-grade NHL. It may broaden the range of therapeutic options in the salvage treatment of these patients. The main toxicity of this combination is prolonged myelosuppression that may cause treatment delay or withdrawal. The benefit of adding granulocyte colony-stimulating factor, particularly in patients with poor marrow reserve, needs to be investigated.

Adult↗
PubMed1999

Retrospective study of candidemia in patients with hematological malignancies. Clinical features, risk factors and outcome of 76 episodes.

A retrospective study of 76 episodes of candidemia in 73 patients with underlying hematological malignancy, from 1988 until 1997, has been conducted to evaluate the clinical characteristics and to ascertain the variables related to the onset and the outcome of candidemia. The most frequent malignancy was acute myeloid leukemia (29 episodes). Candidemia developed mainly during aplasia in patients refractory to chemotherapy (42%). In 65 episodes (86%) the patients were neutropenic (ANC <1 x 10(9)/l) before the candidemia diagnosis for a median time of 13 d, and in 53 episodes (70%) at microbiological diagnosis of candidemia ANC was <1 x 10(9)/l. Candida albicans was the most frequently isolated etiologic agent (31 episodes), but C. non-albicans species sustained the majority of candidemia. Seventeen candidemias developed during azoles prophylaxis. One month after the diagnosis of candidemia, 26 patients died. In 19 cases, death was attributable to candidemia. The case-control study demonstrated, at univariate analysis, that the colonization with Candida. spp. (p=0.004), antimycotic prophylaxis (p=0.01), presence of central venous catheter (p=0.01), neutropenia (p=0.002), and the use of glycopeptide (p=0.0001) increased the risk of candidemia. Using multivariate regression analysis only colonization with Candida spp. and the previous therapy with glycopeptide were associated with a significantly increased risk. Acute mortality, expressed by a cumulative probability of survival at 30 d from diagnosis of candidemia, was 0.67 (95% C.I. 0.55-0.77) and was significantly reduced in patients with neutrophils <1 x 10(9)/l when compared to those with neutrophils >1 x 10(9)/l (p at Mantel-Cox=0.029). Overall cumulative probability of survival at 1 yr was 0.38 (95% C.I. 0.27-0.49) and only the treatment with Amfotericin B significantly reduced the risk of death.

Adolescent↗
PubMed1998

Serum CA 125 is of clinical value in the staging and follow-up of patients with non-Hodgkin's lymphoma: correlation with tumor parameters and disease activity.

BACKGROUND: CA 125 is a glycoprotein produced by epithelial ovarian tumors and by mesothelial cells; its levels also have been shown to be elevated in patients with non-Hodgkin's lymphoma (NHL). METHODS: The authors evaluated serum CA 125 levels in patients with NHL to elucidate the frequency of this finding, its relationship with other presenting features, and its potential role as tumor marker. One hundred and fifty-seven patients underwent the first CA 125 assessment at onset, 54 at disease recurrence or progression, and 62 during complete remission (CR). RESULTS: Of the 157 patients evaluated at diagnosis (median CA 125: 26 U/mL; range, 2-1400 U/mL), 63 (40%) had increased CA 125 values. Higher CA 125 levels were associated with advanced disease, aggressive histology, mediastinal and/or abdominal involvement, bulky tumor, high tumor burden, effusions, contiguous extranodal extension, high serum lactate dehydrogenase (LDH) activity, and elevated beta2-microglobulin (beta2-M) levels. Parameters identified by multivariate analysis to be independently associated with high CA 125 were: aggressive histology, mediastinal and/or abdominal disease, bulky tumor, high serum LDH activity and beta2-M serum levels, and the presence of effusion (P = 0.0000; explained variation = 0.64). Of the patients presenting with abnormal CA 125 levels, all those who achieved a CR (35) and 3 of the 6 who achieved a partial response had normalization of CA 125 values by the end of treatment. Conversely, CA 125 remained above normal values in 18 nonresponders. All 62 patients evaluated during CR showed normal CA 125 levels. Among patients first evaluated at disease recurrence or progression, 22 of 54 (41%) showed increased CA 125 levels, which were associated with the same parameters of disease found in patients examined at diagnosis. CONCLUSIONS: High serum CA 125 levels were found to correlate with mediastinal and/or abdominal involvement, high tumor mass, and effusions, reflecting the reaction of mesothelial cells to the tumor. Serum CA 125 is a reliable biologic marker for the staging and restaging of patients with lymphoma. Serial measurements are useful, in conjunction with other markers, for monitoring response to treatment.

Adolescent↗
PubMed1998

In vivo differentiation of mast cells from acute myeloid leukemia blasts carrying a novel activating ligand-independent C-kit mutation.

The primary role of protooncogene c-kit in mast cell differentiation is supported by the development of mast cells from CD34+/CD117+(c-kit) myeloid precursors. Growth factor independence, neoplastic transformation and differentiation of mast cells were found in association with c-kit activating mutations in both murine and human mastocytoma and mast cell diseases. We have identified a novel c-kit mutation (D816Y) in peripheral blood mononuclear cells from a patient with AML (M2), massive presence of mast cells in bone marrow and rapid progression of the disease. The mutation, a G-->T transversion at nt 2467 of the c-kit gene resulting in Asp816-->Tyr substitution, corresponds to the D814Y and D817Y mutations identified and characterized in the murine P815 mastocytoma and the rat RBL-2H3 mast cell leukemia cell lines. The absence of SCF transcripts that we found by RTPCR in the patient's blasts indicates that, also in humans, this activating mutation leads to SCF independent growth. The expression of the mutant allele on Kit signaling may be further enhanced by trisomy of chromosome 4 (carrying the c-kit gene) in the patient's blasts. From these findings it is concluded that mast cells could be generated from a leukemic CD34/CD117-positive clone, that combines the antigenic expression of mast cell precursor to the growth and differentiation factor-independence which was derived by the c-kit D816Y mutation.

Alleles↗
PubMed1998

[MALT lymphoma of the left lacrimal and mammary glands, liver cirrhosis caused by HCV and type II cryoglobulinemia].

We describe a case of MALT (mucosa-associated lymphoid tissue) lymphoma associated to post-hepatitis C liver cirrhosis, type II cryoglobulinaemia, gastrointestinal bleedings and thromboses. HCV infection justified the association between the first three pathologies, while gastrointestinal bleedings and thromboses were respectively attributed to portal hypertension secondary to liver cirrhosis and to some thrombophilic conditions. Among the latter there was also an antithrombin III deficiency. The singularity of the case and some difficulties met in its treatment, justify the report.

Aged↗
PubMed1997

Primary mediastinal B-cell lymphoma: update of its clinicopathologic features.

The peculiar clinical, histomorphological and biological characteristics of PMBCL are reviewed. Special emphasis is given to the frequent aggressive clinical behaviour of this lymphoma in which conventional prognostic factors seem inadequate to identify high risk cases. The need for new clinical and/or biological prognostic markers is stressed.

Biomarkers, Tumor↗
PubMed1997

Non-Hodgkin's lymphoma with rheumatism-like presentation and multiple cystic and nodular lesions in the liver.

We report the case of a non-Hodgkin's lymphoma in an isolated and not previously diagnosed "adult polycystic liver disease". In this case, a rheumatism-like presentation was associated with the discovery of multiple nodular and cystic lesions in the liver. Of these, the former were related to lymphoma involvement, the latter to pre-existent liver disease. The singularity of the case, not previously reported, and some difficulties met in diagnosing the two pathologies, justify the report.

Biopsy↗
PubMed1996

Anaplastic large cell (CD30/Ki-1+) lymphoma in HIV+ patients: clinical and pathological findings in a group of ten patients.

We compared the clinical and pathological features of 10 HIV+ CD30+ anaplastic large cell lymphoma (ALCL) patients with 28 HIV+ CD30- non-Hodgkin's lymphoma (NHL) patients. The incidence of ALCL among 38 HIV+ systemic NHL patients was 26%. Clinical features were similar in all the HIV-related NHL cases, but ALCL patients seemed to differ from HIV+ CD30- systemic NHL only in the greater frequency of lung tumours (40% v 21%) without concomitant mediastinal mass, bone marrow (75% v 18%) and gastroenteric involvement (40% v 25%). Among the HIV+ ALCL patients, histologic subtypes did not differ in frequency from ALCL in the general population. The B phenotype was predominant (50%) as in other HIV-related NHL. EBV genoma, studied in all HIV+ ALCL patients, was present in 3/10 by in situ hybridization (ISH) and in 5/10 cases using PCR. The clinical course of lymphomas was similar in CD30 positive and negative NHL patients. Overall survival also was short in our series, particularly in HIV+ ALCL (84 v 188 d), probably because of profound immunodepression of the ALCL patients. Our findings suggest that severe immunodepression due to HIV infection determines-more than any other factor-the clinical features of HIV+ ALCL, making them very similar to those of other high-grade systemic HIV+ NHL.

Adult↗
PubMed1996

Intravenous gamma globulin in refractory thrombotic thrombocytopenic purpura.

We report the case of a young woman with refractory thrombotic thrombocytopenic purpura (TTP), treated with different therapies (standard therapy with plasma exchange, prostacyclin infusion, vincristine sulfate) and responding to these for brief periods. High-dose immunoglobulin (400 mg/kg/day for 5 days), on the other hand, yielded a complete response which has lasted for 14 months up to the time of this report.

Adult↗