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Biomedical subjects

R Zittoun

Publications and source records attributed to R Zittoun.

At least 37 records · Page 2Linked to original sources
PubMed1999

Incidence of haematological malignancies in French Polynesia between 1990 and 1995.

To determine the incidence of haematological malignancies in French Polynesia from 1990 to 1995, we collected cases from the local cancer registry, sanitary evacuation files and all the histopathology and clinical biology laboratories. All leukaemias, non Hodgkin's lymphomas, and multiple myelomas incidence was slightly lower among French Polynesians than among Maoris from New-Zealand and Hawaiians of Hawaii. Standardised Incidence Ratio (SIR) for Hodgkin's disease among females was 0.08 when comparing to Hawaiians and 0.33 when comparing to Maoris. Other salient features were a high proportion of high grade and Burkitt's lymphoma, the absence of Hodgkin's disease after 40 years of age, a low incidence of chronic lymphoid leukaemia, and a high non lymphoblastic/lymphoblastic acute leukaemia ratio in childhood. This study stresses the peculiar incidence of some haematological malignancies in this south pacific area.

Adolescent↗
PubMed1999

Pentostatin in T-cell malignancies--a phase II trial of the EORTC. Leukemia Cooperative Group.

PURPOSE: Within this phase II EORTC trial, we have investigated the safety and efficacy of pentostatin in lymphoid malignancies. We have previously reported the results in T- and B-cell prolymphocytic leukemia, B-cell chronic lymphocytic leukemia (B-CLL) and hairy cell leukemia. This report focuses on the outcome in T-cell malignancies: T-CLL, Sézary syndrome (Sézary), mycosis fungoides (MF) and T-zone lymphoma (TZL). PATIENTS AND METHODS: Of the 92 patients with these diagnoses enrolled, 76 were evaluable for response and toxicity, i.e., 25 of 28 with T-CLL, 21 of 26 with Sézary, 22 of 26 with MF, and 8 of 12 with TZL. All patients had progressive and advanced disease. Pentostatin was administered at a dosage of 4 mg/m2 every week for the first 3 weeks, then 4 mg/m2 every 14 days for another 6 weeks, followed by maintenance therapy of 4 mg/m2 monthly for a maximum of 6 months. RESULTS: Response rates (complete and partial responses) in patients with Sézary (n = 22) or MF (n = 21) were 33% and 23%, respectively, and in patients with T-CLL (n = 21) or TZL (n = 8) 8% and 25%, respectively. Sixteen (21%) patients died during the first ten weeks of treatment: twelve of progressive disease, two of infectious complications with progressive disease, one of myocard infarction and one of renal failure related to administration of i.v. contrast. Major toxicity (grade 3-4) included infection in 11% of patients, nausea/vomiting in 4%, diarrhea in 3%. Hematologic toxicity was mild to non-existent. CONCLUSIONS: We conclude that pentostatin is active in Sézary and MF but showed marginal activity in T-CLL or TZL. Toxicities are mild to moderate at the dose schedule administered. Due to its relatively specific lympholytic effect and its favorable toxicity spectrum, pentostatin might be especially useful for the palliative treatment of T-cell malignancies.

Adult↗
PubMed1999

Role of MRP1 in multidrug resistance in acute myeloid leukemia.

The best characterized resistance mechanism in adult acute myeloid leukemia (AML) is the one mediated by the MDR1 gene which has been shown to be associated with poor outcome. However, alternative proteins such as the more recently recognized multidrug-associated protein (MRP1), may also contribute to the resistance to anthracyclines and etoposide in AML. Recently, the role of this protein was discussed and was unclear in AML. However, recent data concerning the functionality and the modulation of the activity of MRP1 may elucidate its role in comparison with other mechanisms of resistance. In this paper, we will review these recent data concerning the role of MRP1 in adult AML.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

Cyclin D1 overexpression allows identification of an aggressive subset of leukemic lymphoproliferative disorder.

The conjunction of clinical features, cell morphology and immunological characteristics allows an accurate diagnosis in most cases of B cell chronic lymphoproliferative disorders (CLD). However, the diagnosis remains uncertain in a small percentage of cases, often referred as to unclassified B cell proliferation or atypical chronic lymphocytic leukemia (CLL). We have studied retrospectively the 192 cases of leukemic CLD seen in our institution over a 3-year period, for which both clinical and routine biological data at presentation were available. Forty cases (20%) did not fit into any of the well-identified categories according to the FAB criteria and remained unclassified. We assessed cyclin D1 expression in all of these cases and found that 10 of them expressed a high level of cyclin D1 protein. We compared the characteristics of these 10 cases with those of the 30 cyclin D1 negative CLD. Despite non-distinctive cytological and phenotypic features, the 10 cyclin D1 positive patients exhibited a strikingly uniform clinical presentation with elevated leukocytosis, massive spleen enlargement and no superficial lymphadenopathy. Their outcome was very poor with a median survival of 10 months, contrasting with the prolonged survival of the cyclin D1 negative patients. The cytological features of tumor cells from these 10 patients with cyclin D1 positive unclassified leukemic CLD were similar to those of the circulating lymphoid cells from 15 patients with histologically proven mantle cell lymphoma (MCL) and primary or secondary blood involvement. Therefore, cyclin D1 expression allowed identification among the unclassified CLD, a subset of aggressive disorders which represent a leukemic counterpart of MCL (mantle cell leukemia). We suggest that determination of cyclin D1 expression by any technique available should be systematically included when investigating atypical CLL.

Adult↗
PubMed1999

Has the prognosis of adult patients with acute myeloid leukemia improved over years? A single institution experience of 784 consecutive patients over a 16-year period.

We reviewed the reports of 784 consecutive patients admitted to our department for newly diagnosed acute myeloid leukemia (AML) over a 16-year period. Median, 5-year and 10-year overall survivals were 9. 5 months, 17.3% and 11.7% respectively. Induction treatment (698 patients) resulted in 50% complete remissions (CR) (from 26.5% in secondary AML to 81.2% in patients <60 years with de novo AML). Period of diagnosis (1980-84/85-89/90-95) demonstrated a major significance for CR achievement and OS in multivariate analysis. In patients >/=60 years (372), CR rate increased (25% to 36.8%, P = 0. 03), and 5-year OS (3.7% to 10.6%, P = 0.022) improved, probably due to an increase in the proportion of patients administered conventional combined chemotherapy (54.5% to 83.8%, P < 0.0001). In younger patients CR rate continuously increased (61.5% to 74.8%, P = 0.028) with an associated improvement of 5-year OS (19.2% to 35.4%). No significant change in DFS and CR durations was observed. This large single center study on a large cohort of unselected AML patients reflects the improvement achieved in the management of AML patients, likely due to improvement of supportive care practices, administration of conventional induction to more elderly patients, and intensification of induction and post-remission treatments in patients <60 years.

Acute Disease↗
PubMed1999

Efficacy of prevention by high-efficiency particulate air filtration or laminar airflow against Aspergillus airborne contamination during hospital renovation.

OBJECTIVE: To evaluate efficacy of laminar airflow facilities plus high-efficiency particulate air (HEPA) filtration and HEPA filtration alone in preventing environmental Aspergillus contamination during hospital renovation. To show the usefulness of environmental surveillance to facilitate protection of patients at risk for invasive pulmonary aspergillosis. DESIGN: Prospective sampling of air and surfaces for Aspergillus conidia during 2-year period. SETTING: A hematological department adjacent to building renovation at a university hospital. RESULTS: 1,047 air samples and 1,178 surface samples were collected from January 1996 to December 1997. Significantly more air samples were positive for Aspergillus species during the period of building renovation than during the periods before and after renovation in a unit without a protected air supply adjacent to the building work area (51.5% vs 31.7%; odds ratio [OR], 2.3; 95% confidence interval [CI95], 1.4-3.7; P<.001). A major increase in the frequency of positive air samples was also found in another adjacent unit that was protected with HEPA filtration alone (from 1.8% to 47.5%; OR, 48.9; CI95, 12-229; P<10(-7)). In addition, in this unit, the mean count of Aspergillus conidia in positive air samples increased significantly during construction (4 colony-forming units [CFU]/m3 to 24.7 CFU/m3; P=.04) and the proportion of positive surface samples showed a significant increase during renovation (from 0.4% to 9.7%; OR, 28.3; CI95, 3.4-623; P=10(-4)). However, none of 142 air samples collected during renovation in the area protected with laminar airflow plus HEPA filtration showed Aspergillus conidia. In a unit distant from the building renovation site, the results of air and surface samples were not affected by renovation. CONCLUSION: This study showed a strong association between building renovation and an increase in environmental Aspergillus contamination. Results confirmed the high efficacy of laminar airflow plus HEPA filtration and a high air-change rate. Although filtration with HEPA was effective during normal conditions, it alone was unable to prevent the rise of Aspergillus contamination related to building renovation. This study emphasized the necessity of an environmental survey of airborne contamination related to construction, to facilitate prevention of nosocomial aspergillosis outbreaks. A standardized protocol for aerobiological surveillance is needed.

Air Microbiology↗
PubMed1999

Fatigue in cancer patients.

The interest in fatigue seems to be growing. A Medline search combining the key words fatigue and cancer yielded 248 entries compared with 72 entries 10 years previously. The studies published are mainly descriptive, augmenting the knowledge about the extent of fatigue associated with cancer, as well as during and after the various treatments used to fight it. New measurement instruments integrating the multidimensional concept of fatigue are being proposed. In 1998, the first study describing fatigue in children and adolescents with cancer was published. The knowledge of the causes of fatigue related to cancer remains extremely limited. In only a few studies are interventions and treatment possibilities for fatigue discussed. Hopefully, the refined knowledge about the characteristics of fatigue and its epidemiology will provide new etiologic understanding, resulting in effective treatment. This article provides a survey on the literature published in 1998.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1999

Smoldering acute myelogenous leukemia in the elderly.

Out of 75 consecutive elderly AML patients who did not receive anti-leukemic treatment (52 pts) or failed to respond to differentiating agent (23 pts), 6 patients had survivals of 13.2 to 98 months with treatment restricted to supportive care. This cut-point is far longer than the median survival of the 235 elderly patients (3.5 mo.), either untreated (med. survival: 1 mo.) or treated (with treatment ranging from conventional induction to palliative chemotherapy) (4 mo.), admitted to our department within the same period of time. These cases of smoldering AML (4 women, 2 men) were all of AML2 FAB subtype (4 de novo, 2 post MDS) and presented with a significantly better performance status, lower WBC and circulating blast counts, higher platelet counts and with lower bone marrow infiltration than AML cases with more rapid progression. Cytogenetical analysis when available (3 pts) showed normal karyotypes and clonogenic assay performed in 3 of these patients showed a lack of (2 pts) or reduced in vitro leukemic cell growth (1 pt). The identification of specific characteristics of smoldering leukemia in the elderly might be an important development in the understanding of the physiopathology of acute leukemia and a tool for helping decision-making when selecting the time and intensity of cytotoxic treatment in these older patients.

Aged↗
PubMed1999

[Orbital lymphoma and AIDS. Apropos of a case].

We report the case of a 33-year-old HIV-seropositive male who had a large cell Epstein-Barr virus-associated non-Hodgkin's orbital lymphoma. A thorough medical examination enabled us to find on thoracic CT-scan a mediastinal lymph node involvement as large as 18 cm in diameter. The regression of the tumor was dramatic under chemotherapy with complete disappearance of the tumor and no recurrence was found after more than 21 months follow-up. We discuss the differential diagnosis with orbital infection.

Adult↗
PubMed1999

Modern clinical testing strategies in cobalamin and folate deficiency.

Folate or cobalamin deficiencies are usually detected by hematologic abnormalities, such as a macrocytic megaloblastic anemia, or often milder signs, such as hypersegmented neutrophils. In fact, these vitamin deficiencies may be associated with clinical conditions in which anemia and/or macrocytosis are absent, such as neuropsychiatric disorders and inborn errors of folate or cobalamin metabolism. A battery of sensitive tests, including blood vitamin levels, serum methylmaIonic acid and homocysteine assays, and the deoxyuridine suppression test in the bone marrow, allows for early detection of vitamin deficiency. Additional tests may be included to identify the causes of deficiency, such as the Schilling test using crystalline cyanocobalamin, or a modified Schilling test for showing food cobalamin malabsorption. Strategies for diagnosing a vitamin deficiency differ according to the hematologic and clinical presentations. The deleterious effects (aside from anemia) that arise from cobalamin or folate deficiency and include neurological complications, increased risk of vascular disease due to hyperhomocysteinemia, and increased risk of some types of cancer related to folate deficiency, underscore the importance of making an early diagnosis and instituting treatment with the appropriate vitamin in preventing permanent damage.

Deoxyuridine↗
PubMed1998

Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. The European APL Group.

All trans-retinoic acid (ATRA) syndrome is a life-threatening complication of uncertain pathogenesis that can occur during the treatment of acute promyelocytic leukemia (APL) by ATRA. Since its initial description, however, no large series of ATRA syndrome has been reported in detail. We analyzed cases of ATRA syndrome observed in an ongoing European trial of treatment of newly diagnosed APL. In this trial, patients 65 years of age or less with an initial white blood cell count (WBC) less than 5,000/microL were initially randomized between ATRA followed by chemotherapy (CT) (ATRA-->CT group) or ATRA with CT started on day 3; patients with WBC greater than 5,000/microL received ATRA and CT from day 1; patients aged 66 to 75 received ATRA-->CT. In patients with initial WBC less than 5, 000/microL and allocated to ATRA-->CT, CT was rapidly added if WBC was greater than 6,000, 10,000, 15,000/microL by days 5, 10, and 15 of ATRA treatment. A total of 64 (15%) of the 413 patients included in this trial experienced ATRA syndrome during induction treatment. Clinical signs developed after a median of 7 days (range, 0 to 35 days). In two of them, they were in fact present before the onset of ATRA. In 11 patients, they occurred upon recovery from the phase of aplasia due to the addition of CT. Respiratory distress (89% of the patients), fever (81%), pulmonary infiltrates (81%), weight gain (50%), pleural effusion (47%), renal failure (39%), pericardial effusion (19%), cardiac failure (17%), and hypotension (12%) were the main clinical signs, and 63 of the 64 patients had at least three of them. Thirteen patients required mechanical ventilation and two dialysis. A total of 60 patients received CT in addition to ATRA as per protocol or based on increasing WBC; 58 also received high dose dexamethasone (DXM); ATRA was stopped when clinical signs developed in 30 patients. A total of 55 patients (86%) who experienced ATRA syndrome achieved complete remission (CR), as compared with 94% of patients who had no ATRA syndrome (P = .07) and nine (14%) died of ATRA syndrome (5 cases), sepsis (2 cases), leukemic resistance (1 patient), and central nervous system (CNS) bleeding (1 patient). None of the patients who achieved CR and received ATRA for maintenance had ATRA syndrome recurrence. No significant predictive factors of ATRA syndrome, including pretreatment WBC, could be found. Kaplan Meier estimates of relapse, event-free survival (EFS), and survival at 2 years were 32% +/- 10%, 63% +/- 8%, and 68% +/- 7% in patients who had ATRA syndrome as compared with 15% +/- 3%, 77% +/- 2%, and 80% +/- 2% in patients who had no ATRA syndrome (P = .05, P = .003, and P = .03), respectively. In a stepwise Cox model that also included pretreatment prognostic variables, ATRA syndrome remained predictive for EFS and survival. In conclusion, in this multicenter trial where CT was rapidly added to ATRA in case of high or increasing WBC counts and DXM generally also used at the earliest clinical sign, the incidence of ATRA syndrome was 15%, but ATRA syndrome was responsible for death in only 1.2% of the total number of patients treated. However, occurrence of ATRA syndrome was associated with lower EFS and survival.

Acute Kidney Injury↗
PubMed1998

Pgp and MRP activities using calcein-AM are prognostic factors in adult acute myeloid leukemia patients.

Thirteen cell lines with different levels of Pgp and MRP expression were used to assess the ability of calcein acetoxymethyl ester (calcein-AM) uptake and calcein efflux to measure Pgp and MRP functions, respectively. There was a good correlation between MRP expression and the modulatory effect of probenecid (a specific modulator of MRP) on the calcein efflux (r = .91, P = .0003) and between Pgp expression and the modulatory effect of CsA on calcein-AM uptake (r = .96, P < .0001). In light of the high correlations for both proteins, we tested calcein-AM uptake and efflux in fresh myeloid leukemic cells. In 53 acute myeloid leukemia (AML) patients, there was also a good correlation between MRP expression (measured by reverse transcription-polymerase chain reaction and by MRPm6 expression by flow cytometry) and the modulatory effect of probenecid on the calcein fluorescence (r = .92, P < .0001) and between Pgp expression as measured by UIC2 antibody binding on flow cytometry and the modulatory effect of cyclosporin A on calcein-AM uptake (r = .83, P < .0001). Pgp activity was higher in CD34+ leukemia than in CD34- leukemia (2.26 +/- 1.50 v 1.46 +/- 1.21, respectively; P = .003), and MRP activity was higher in CD34- leukemia than in CD34+ leukemia (1.77 +/- 0.40 v 1.4 +/- 0. 29, respectively; P = .004). Pgp expression and activity (P = .004 and P = .01, respectively) and MRP activity (P = .03) but not MRP expression were prognostic factors for achievement of complete remission. These results suggest that functional testing (with calcein-AM +/- modulators) for the presence of both MRP and Pgp activities is of prognostic value and that MRP contributes to drug resistance in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Prognostic significance of the cell cycle inhibitor p27Kip1 in chronic B-cell lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of resting lymphocytes. The identification of p27(kip1), a cyclin-dependent kinase inhibitor that contributes to cell cycle arrest and represents a link between extracellular signals and cell cycle, prompted us to study p27 protein in the lymphocytes from 88 patients with B-CLL and 32 patients with other chronic B-lymphoproliferative disorders. The expression of p27 protein was higher in B-CLL samples with variations among them. In B-CLL, p27 levels were independent of absolute number of circulating lymphocytes, but strongly correlated with both lymphocyte and total tumor mass (TTM) doubling time. High p27 expression was associated with a poorer overall prognosis. In vitro, there was an increased spontaneous survival of B-CLL cells expressing high p27 levels. Interleukin-4 (IL-4) upregulated p27 levels in B-CLL cells, while fludarabine decreased p27 levels. Thus, our results indicate that p27 may be a valuable kinetic marker in B-CLL by providing instantaneous estimation of the disease doubling time. In addition, these results suggest that there is a link between p27 expression and the ability of CLL cells to undergo apoptosis.

Apoptosis↗
PubMed1998

Fournier's gangrene during induction treatment of acute promyelocytic leukemia, a case report.

Fournier's gangrene is described as a fulminant necrotizing fasciitis of the scrotum and penis. Few cases have been reported in the context of acute leukemia. We describe a case, complicating the induction treatment of an acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy. The evolution was favorable, following surgical excision and broad-spectrum antibiotic therapy. The respective roles of all-trans-retinoic acid and granulocytopenia are discussed. This devastating and life-threatening infection must be kept in mind for early clinical, bacteriological, and radiological diagnosis and surgical management.

Adult↗
PubMed1998

Acquired hemophilia due to factor VIII inhibitors in 34 patients.

BACKGROUND: Acquired hemophilia is a rare disease caused by the development of auto-antibodies against factor VIII. SUBJECTS AND METHODS: We studied the characteristics and outcomes of 34 patients (19 women and 15 men) with acquired hemophilia from 1980 to 1997. RESULTS: The mean age of the patients was 61 years (range, 22-93 years). An underlying disease was observed in 18 (53%) patients: 5 patients had cancer, 4 an autoimmune disorder, 2 a dermatologic disorder, 3 asthma, 3 were postpartum, and 1 had an adverse reaction to ampicillin. Factor VIII level was <5% in 30 (90%) patients; factor VIII antibodies were elevated (>10 Bethesda units) in 23 (69%) patients. Bleeding requiring transfusions was reported in 25 (75%) patients. Human factor VIII was given to 14 patients and porcine factor VIII to 5. Six patients received prothrombin complex concentrates and one desmopressin. Several immunosuppressive treatments were used, mainly corticosteroids, cyclophosphamide, and intravenous immunoglobulin. Bleeding stopped in all but one patient within 2 weeks. Most patients achieved complete remission, although two relapses were observed subsequently. CONCLUSION: This large study helps to clarify the presentation and clinical course of acquired hemophilia. Prospective studies are needed to determine the efficacy of treatment.

Adult↗
PubMed1998

Pentasomy 13q in a case of acute myelogenous leukemia (Mo).

A case of acute myelogenous leukemia Mo FAB subtype with a pentasomy 13q (associated with a trisomy 19 in a subclone) in the initial bone marrow metaphase cells is reported. The pentasomy 13q is the result of the presence of double isochromosome 13q and one normal chromosome 13. In our case, this abnormality had a poor prognosis.

Acute Disease↗