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A Bosly

Publications and source records attributed to A Bosly.

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

A double-blind comparison of fluconazole and nystatin in the prevention of candidiasis in patients with leukaemia. Antifungal Prophylaxis Study Group.

In this multicentre, randomised, double-blind study, the safety and efficacy of oral fluconazole (200 micrograms/day) and nystatin suspension (6,000,000 IU/day) for the prevention of fungal infections were compared in patients with leukaemia undergoing remission induction chemotherapy. Antifungal prophylaxis was initiated at the time chemotherapy was started and continued throughout the hospital stay or the period of neutropenia to a maximum of 42 days. Prophylaxis was successful (no evidence of fungal infection or fever of unknown origin unresponsive to antibiotics) in 38 of 56 (68%) fluconazole-treated and 25 of 53 (47%) nystatin-treated patients (P = 0.03). 2 patients (4%) in the fluconazole group and 6 (11%) patients in the nystatin group developed systemic fungal infections (P = 0.15). The overall frequency of adverse events was similar among fluconazole-treated (29%) and nystatin-treated (32%); most events in both treatment groups involved the gastrointestinal tract. These results indicated fluconazole was more effective than nystatin in preventing Candida infections in patients with leukaemia; fluconazole was well tolerated.

Acute Disease↗
PubMed1999

Peripheral blood stem cell contamination in mantle cell non-Hodgkin lymphoma: the case for purging?

Intensification using peripheral blood stem cells collected after chemotherapy followed by growth factors is being increasingly investigated as an alternative to conventional chemotherapy for mantle cell non-Hodgkin lymphoma. We investigated 14 grades III-IV, t(11;14)-positive cases for contamination of PBSC collected after a polychemotherapy regimen followed by G-CSF. Patients were first treated with a polychemotherapy regimen. There were four CR, seven PR, two refractory and one early death. Seven patients have been transplanted, in whom PBSC were mobilized, using either cyclophosphamide/VP16 or Dexa-BEAM followed by G-CSF. For all patients, whether actually autografted or not, PB cells were tested at the time of regeneration on G-CSF after the first polychemotherapy or after the mobilizing regimen. PCR evaluation of contamination was performed first by a semi-quantitative approach, using serial dilutions of initial DNA, then confirmed using a limiting-dilution analysis. Two patients were not informative (one early death and one without an available molecular marker). PB cells collected at regeneration contained at least one log more lymphoma cells than steady-state blood or marrow, apart from in two cases. Moreover, where a mobilizing treatment diminished tumor burden in the patient, at the same time it increased PB contamination in most cases. We conclude that advanced mantle cell NHL appears to be largely resistant to significant in vivo purging by conventional chemotherapy. Where treatment brings benefits by reducing tumor load, it may at the same time negate it by mobilizing malignant cells into the collections used to intensify. Although the clonogenic potential of this massive infiltration is unknown (only gene marking studies could provide a definitive answer regarding the source of relapses), strategies aimed at reducing the level of contamination in the graft should be considered when designing future protocols.

Adult↗
PubMed1999

Myelodysplastic syndrome with monosomy 5 and/or 7 following therapy with 2-chloro-2'-deoxyadenosine.

A few cases of secondary neoplasms occurring after treatment with 2-chloro-2'-deoxyadenosine (2CdA) have been reported, mostly in patients previously exposed to other anti-cancer drugs including alkylating agents (AA). Here we report on the occurrence of a myelodysplastic syndrome (MDS) with monosomy 5 and/or 7 in two patients after 2CdA treatment, without or prior to other toxic exposure. In light of a literature review and given the involvement of chromosomes frequently abnormal in secondary leukaemias, we suggest that 2CdA may induce therapy-related MDS (t-MDS).

Adult↗
PubMed1998

Prognostic significance of T-cell phenotype in aggressive non-Hodgkin's lymphomas. Groupe d'Etudes des Lymphomes de l'Adulte (GELA).

Peripheral T-cell lymphomas (PTCL) have been generally reported to have a worse prognosis than B-cell lymphomas (BCL). Because of their heterogeneity and scarcity, the outcomes of the different histological subtypes have not been compared. From October 1987 to March 1993, 1,883 patients with diffuse aggressive non-Hodgkin's lymphomas (NHL) included in the LNH87 protocol could be assessed for both morphology and immunophenotyping. Among them, 288 (15%) had PTCL and 1,595 (85%) had BCL. According to the Kiel classification, most PTCL were classified as angioimmunoblastic (AIL; 23%), pleomorphic medium and large T-cell (PML; 49%), or anaplastic large cell (ALCL; 20%) lymphomas. Comparing PTCL with BCL patients, the former had more disseminated disease (78% v 58%), B symptoms (57% v 40%), bone marrow involvement (31% v 17%), skin involvement (21% v 4%), and increased beta2-microglobulin (50% v 34%), whereas BCL patients had more bulky disease (41% v 26%). According to the International Prognostic Index (IPI), PTCL and BCL scores were, respectively: 0 factors, 13% and 15%; 1 factor, 17% and 22%; 2 factors, 24% and 25%; >/=3 factors, 45% and 37% (P = .09). For BCL and PTCL, respectively, complete remission rates were 63% and 54% (P = .004); the 5-year overall survival (OS) rates were 53% and 41% (P = .0004) and event-free survival (EFS) rates were 42% and 33% (P < . 0001). Comparison of the different histological subtypes of lymphoma showed that the 5-year OS rate for T-ALCL (64%) was superior to those of other PTCL (35%) as well as diffuse large B-cell (53%) NHL. When multivariate analysis was applied using the IPI score as one factor, nonanaplastic PTCL remained an independent parameter (P = . 0004). Although the poor prognosis of non-ALCL PTCL could be due in part to the presence of adverse prognostic factors at diagnosis, this study shows that the T-cell phenotype is an independent significant factor, which should be incorporated into the definition of prognostic groups.

Adolescent↗
PubMed1997

Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin's lymphoma: updated results of the prospective study LNH87-2. Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: To update the randomized study that compared consolidative sequential treatment (ifosfamide, etoposide, asporaginase, and cytarabine) versus the high-dose regimen of cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission and to focus on high-intermediate and high-risk patients identified by the international prognostic index. PATIENTS AND METHODS: Nine hundred sixteen patients received induction treatment on the LNH84 protocol with open randomization for the anthracycline. In a subsequent randomization, 541 patients in complete remission were assigned to receive consolidation by either sequential chemotherapy (n = 273) or autotransplant (n = 268). Among the higher risk population (two or three risk factors), 236 patients in complete remission were assessable for the consolidation phase, with 111 in the sequential chemotherapy arm and 125 in the autotransplant arm. RESULTS: Among 541 randomized patients, disease-free survival and survival did not differ significantly between the two consolidative treatment arms. In the higher risk population, CBV was superior to sequential chemotherapy, with 5-year disease-free survival rates of 59% (95% confidence interval, 49% to 69%) and 39% (95% confidence interval, 28% to 50%), respectively (P = .01, relative risk = 1.19). The 5-year survival rate was superior in the CBV group at 65% (95% confidence interval, 56% to 74%) compared with 52% in the sequential chemotherapy group (95% confidence interval, 42% to 62%) (P = .06, relative risk = 1.49). CONCLUSION: This study shows a superior disease-free survival for higher risk patients in complete remission. Dose-intensive consolidation therapy should be considered for patients at higher risk who achieve complete remission after induction treatment.

Adolescent↗
PubMed1997

Placebo-controlled phase III study of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) in aggressive non-Hodgkin's lymphoma: factors influencing chemotherapy administration. Groupe d'Etude des Lymphomes de l'Adulte.

The purpose of this study was to, assess the efficacy of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) in the prevention of neutropenia and infection in patients receiving dose-intensive chemotherapy for non-Hodgkin's lymphoma (NHL). A second objective was to determine clinical predicators of delay to cytotoxic chemotherapy administration. One hundred-sixty two patients with intermediate- or high-grade NHL and at least one poor prognostic factor received a total of 4 cycles of the LNH-84-regimen every 2 weeks, with an open randomization to treatment with anthracyclines. Patients were randomized to receive subcutaneous lenograstim 5 micrograms/kg/day (n = 82) or placebo (n = 80) from day 6 to day 13 of each cycle. The incidence of severe neutropenia (absolute neutrophil count (ANC) < 0.5 x 10(9)/L) was reduced in the lenograstim group compared with placebo (52% vs 75%). A significant reduction (p < 0.001) in the median duration of ANC < 0.5 x 10(9)/L was also observed in patients treated with lenograstim during each cycle of chemotherapy (0-1 day vs 2-4 days in placebo recipients). Fever occurred in 66 patients in each treatment group. Thirty-four percent of placebo recipients had documented infections during ANC < 1.0 x 10(9)/L compared with 18.5% of lenograstim-treated patients (p < 0.05). Infections of > or = 2 severity were significantly less frequent (p = 0.001) among lenograstim recipients compared with placebo (25 vs 49). The most common adverse events among lenograstim recipients were headache, mild bone pain and injection site reactions. Although lenograstim significantly increased (p = 0.0001) relative dose intensity compared with placebo (93% vs 80%), no difference in CR rate (67% vs 71%) or 3-year survival (63% vs 55%) was observed. The results of this study suggest that patients treated with a chemotherapy regimen that induces severe neutropenia can benefit from treatment with lenograstim. Furthermore, lenograstim permits treatment to be delivered at full dose intensity at 2 week intervals, even in patients with bone marrow involvement, and may permit further dose escalation of the chemotherapeutic regimen used.

Adolescent↗
PubMed1997

Quantification of CD34+ cells mobilized into the peripheral blood predicts the yield of the leukapheresis product and can replace progenitor assays.

We reviewed 333 concomitant blood and cytapheresis samples from 101 patients with solid malignancies of various histological cell types. All samples were analyzed for CFU-GM, BFU-E and CD34+ determination. We found a good correlation between progenitor assays CFU-GM and CD34+ determination in the blood and cytapheresis (r = 0.77, p < 0.0001 and r = 0.79, p < 0.0001 respectively). The number of CD34+ cells in the peripheral blood was predictive of the CD34+ yield in the cytapheresis (r = 0.86, p < 0.0001), and we determined that a threshold of 26 CD34+/microliter of blood was sufficient to harvest 10(6) CD34+/kg in a single apheresis. Thirty breast cancer patients received injections of peripheral blood stem cells after the same high-dose chemotherapy. For these patients, we found a significant correlation between the quantity of CD34+ cells or CFU-GM collected and both granulocyte and platelet recovery. In conclusion, there is a very good correlation between CFU-GM assays and CD34+ determination and a good correlation between circulating CD34+ cells and the yield obtained by the cytapheresis. The number of CD34+ cells collected is also significantly correlated with hematological recovery. Because CD34+ quantification is an accurate, fast and inexpensive technique, this can lead to the progressive forsaking of progenitor assays in a clinical setting.

Adolescent↗
PubMed1997

[Recent data on the epidemiology of non-Hodgkin lymphoma. Groupe d'Etudes des Lymphomes de l'Adulte (GELA)].

Non-Hodgkin's lymphoma is a common condition whose incidence has increased by 75% over the last 15 years. The HIV epidemic is among the factors that have contributed to this increase: patients with AIDS have 1% annual risk of developing non-Hodgkin's lymphoma, and the increase in survival of AIDS patients has led to an increase in the frequency of AIDS-associated lymphomas. A number of other viruses are directly involved in the occurrence of lymphomas, such as the HTLV-1 and the EBV. The HSV type 8 has recently been incriminated in the occurrence of lymphomas located in the cavities of the body. The role of the hepatitis C virus in the occurrence of lymphoma is controversial. Inherited or acquired immunodeficiencies (e.g., due to treatment for an autoimmune disease or transplant) are associated with an increased incidence of lymphoma. The role of toxic chemicals, especially those used in farming, is receiving increasing attention. A number of infectious diseases promote the occurrence of lymphomas; the best illustration of this link is the association between Helicobacter pylori and primary low-grade gastric lymphomas.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Acute leukaemia in paroxysmal nocturnal haemoglobinuria. Case report and review of the literature.

Paroxysmal nocturnal haemoglobinuria (PNH) terminating in acute leukaemia (AL) is an infrequent condition. In several cases, flow cytometric analysis of glycosylphosphatidylinositol anchored membrane proteins such as DAF and CD59/MACIF has suggested the leukaemic cells to be derived from the PNH clone, thereby implicating PNH as a potential preleukaemic disease. In the present paper, we review the data for one patient treated in our hospital and 20 cases reported in the literature from 1969 to 1993. The sex ratio is 1 female/2 males, mean age at diagnosis of PNH was 46 years and the mean interval between the diagnoses of PNH and AL was 53 months. AL type was AML M6 in 8 patients, other types of AML in 12 and ALL in one, with a mean survival of 7.1 months following diagnosis of AL. In all cases analyzed, the PNH phenotype of erythrocytes disappeared with progression of AL, whereas reappearance of this phenotype with complete remission of AL was inconstant. PNH would thus appear to be a potential preleukemic disease. When this disorder terminates in AL, the type is often AML M6, although ALL is also possible. The prognosis of AL in PNH is poor as for other secondary leukaemias. Apart from marrow aplasia, leukaemic transformation is another life threatening complication of PNH which may justify allogeneic bone marrow transplantation (allo-BMT) and potential leukaemic transformation can therefore be an additional argument in favour of allo-BMT when pancytopenia develops in PNH patients.

Acute Disease↗
PubMed1996

Transient complete remission of acute lymphoblastic leukemia in relapse after allogeneic bone marrow transplantation induced by donor leukocyte transfusions.

We report the case of a young patient with refractory acute lymphoblastic leukemia relapse, after allogeneic bone marrow transplantation, who was treated by donor leukocyte infusions. We observed potent adoptive immunotherapy which produced a cytologic complete remission and total chimeric state. This was of short duration and the patient died of severe graft-versus-host disease. We present a short summary of the literature concerning acute lymphoblastic leukemia and donor leukocyte infusions.

Adolescent↗
PubMed1996

Cytogenetic and clinicobiological features of acute leukemia with stem cell phenotype: study of nine cases.

Morphologic, immunologic, cytogenetic, and clinical features were studied in 9 cases of acute undifferentiated leukemia (AUL). These patients were unclassifiable by FAB criteria, they were CD34+ and did not express myeloid- or lymphoid-associated antigens (CD13, CD33, CD14, CD15, CD61, CD19, CD10, CD22, CD7, CD2, CD5, CD3). Clonal abnormalities were seen in 8 of 9 cases. Del(5q) as the sole anomaly was observed in 3 cases; +13 was the primary change in 3 cases, and isolated trisomy 12 was found in 1 patient. A complex karyotype with trisomy 12q, in association with del 17p and trisomy 21q was detected in 1 case. One patient with 5q- relapsed with refractory anemia with excess of blasts; the presence of dysgranulopoiesis and a few blasts with possible monocytoid morphology in the remaining 2 patients point to a "myeloid nature" of these leukemias. Analysis of cytologic features in our 3 patients with +13, in combination with previously reported cases, suggests the occurrence of immature stem cell involvement with limited differentiation potential, possibly more along the myeloid than the lymphoid lineage. The significance of trisomy 12q in this subset of leukemia remains elusive; some clues of minimal differentiation towards the myeloid lineage in our cases are provided by positivity for the CD117 (c-kit) antigen and by relapse with acute myeloid leukemia without maturation (M1) in one patient. We conclude that, with presently available diagnostic techniques, AUL is a rare subset of leukemia, in which cytogenetic changes are confined to a few chromosomes, with prevalent involvement of 5q and of chromosomes 13 and 12. Chromosome findings may be of value in clinical practice, especially in those cases with "myeloid-oriented" karyotype.

Acute Disease↗
PubMed1996

Deletions of the long arm of chromosome 7 in myeloid disorders: loss of band 7q32 implies worst prognosis.

Clinical and cytogenetic data were analysed in 54 patients with acute non-lymphocytic leukaemias (ANLL) or MDS (myelodysplastic syndromes) and deletion of the long arm of chromosome 7 (7q-), in order to determine if there is a commonly deleted region in 7q and to establish possible correlations between karyotypic features, such as karyotype pattern, karyotype complexity, associated anomalies, and/or the type of deleted segments, and outcome of patients with these disorders. The median follow-up of our patients was 4 months (range 1-89), as was the median survival. In 30% of the cases there was a history of preceding MDS or previous chemotherapy. Clinical and cytogenetic remission was obtained in 7/36 patients treated with chemotherapy (CT). At the time of 7q- detection, three patients previously treated with CT for ANLL were in clinical remission. 5q- was the most recurrent associated abnormality. Complex karyotypes were observed in 68% of the cases. In univariate analysis, statistical differences in survival were observed according to diagnosis (therapy-related and secondary diseases had a worse prognosis than primary disorders), the chromosomal segments deleted (the loss of band 7q32 was of poor prognostic value), the karyotype complexity (patients with single anomalies did better than patients with complex anomalies) and the response to therapy (patients who achieved complete remission had a better survival probability). In multivariate analysis, the loss of band 7q32 was found to be significantly related to very poor prognosis. This finding suggests that band 7q32 may contain critical genes that should be explored at the molecular level.

Adolescent↗
PubMed1996

Infectious complications after 2-chlorodeoxyadenosine therapy.

Infection is a common adverse event after therapy with nucleoside analogs, including 2-chlorodeoxyadenosine (CdA). However, the incidence of CdA-related infections has been poorly documented. In this study we compare, in the same patient population, the incidence of infectious episodes during the 6-month period before CdA to their incidence during the 6 months after initiating therapy. Ninety-five patients with hematological malignancies were studied. The incidence of infectious episodes almost doubled after CdA (0.87 vs. 0.47 during the pre-CdA period). The following factors were associated with an increased risk of infection after therapy: a history of previous chemotherapy, infection during the pre-CdA period and a diagnosis of chronic lymphocytic leukemia or of non-Hodgkin's lymphoma. Age, neutrophil and lymphocyte count at onset of CdA and time interval between diagnosis and therapy with CdA did not correlate with the infectious risk. The pattern of infections was modified after therapy with an increase of herpes virus infections ( 1 vs. 8 episodes, p=0.04) and of fever of unknown origin (6 vs. 17 episodes, p=0.03). In conclusion, a population at high risk for developing infectious complications after CdA therapy can be identified. Specific measures aimed at reducing the incidence of infectious events should concentrate on this population.

Adult↗
PubMed1996

Phase II trial of fludarabine monophosphate as first-line treatment in patients with advanced follicular lymphoma: a multicenter study by the Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: Fludarabine monophosphate (FAMP) is a major drug in the treatment of chronic lymphocytic leukemia and showed efficacy in selected groups of patients with low-grade lymphomas, most of them pretreated. The aim of this trial was to assess the efficacy and the toxicity of FAMP in untreated patients with follicular lymphoma. PATIENTS AND METHODS: Fifty-four untreated patients with advanced follicular lymphoma were treated with intravenous (i.v.) fludarabine at a dose of 25 mg/m2/d during 5 days every 4 weeks, to a maximum of nine cycles. RESULTS: The toxicity of the drug was mild, mainly granulocytic. Granulocytopenia > or = 3 (World Health Organization [WHO]) was observed during 48 of 328 cycles (14.6%) and in 22 of 53 (41%) patients assessable for toxicity. Fludarabine had to be stopped prematurely because of toxicity in nine patients: marrow toxicity in five, peripheral neuropathy in two, and interstitial pneumonitis and hepatitis in one patient each. Among 49 patients assessable for response, the overall response rate was 65% and the complete response (CR) rate 37%. The median progression-free survival interval for all patients was 13.6 months. CONCLUSION: These results confirm that fludarabine is active when used as first-line treatment in patients with follicular lymphoma and has a low toxicity rate. It may be used as single treatment in elderly patients. Associations of fludarabine with other drugs active against follicular lymphoma need to be determined.

Adult↗
PubMed1996

Translocation t(8;16)(p11;p13) in acute non-lymphocytic leukemia: report on two new cases and review of the literature.

Two new cases of t(8;16)(p11;p13) in acute nonlymphocytic leukemia (ANLL) are described. These two patients in addition to the 34 previously described, showed a striking association with myelomonocytic (M4) or monocytic (M5) leukemia, extramedullary infiltration, erythrophagocytosis and disseminated intravascular coagulation. One of our patients showed a TCRbeta gene rearrangement. Alltogether 36 cases of t(8;16) ANLL have been documented until today. We here review their clinical and cytogenetic features.

Adolescent↗
PubMed1996

Limited activity of mini-dose interferon alpha-2a in the treatment of myelodysplastic syndrome.

Impairment in marrow function often characterizes the evolution of myelodysplastic syndrome. As a differentiating agent, interferon alpha 2a (INF alpha) has been shown to be active in the correction of cytopenias related to myelodysplastic syndromes (MDS). We report the clinical course of 9 patients with MDS treated with low-dose subcutaneous INF alpha (1 x 10(6), 3 times per week). A significant effect on anemia was only demonstrated in one patient (11%). In the other, eight, therapy was totally ineffective and four of them could not receive the complete treatment due to worsening cytopenias or leukemic transformation. In conclusion, in our study, INF alpha had only limited activity in the treatment of myelodysplastic syndrome.

Drug Evaluation↗
PubMed1995

TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13).

A t(5;12)(q33;p13) translocation is a recurrent chromosome abnormality in a subgroup of myeloid malignancies with features of both myeloproliferative disorders and myelodysplastic syndromes (MDSs). The molecular consequence of a t(5;12) is a fusion between the platelet-derived growth factor receptor-B gene on chromosome 5 and a novel ETS-like gene, TEL, on chromosome 12. We report on three patients with a t(5;12)(q33;p13) diagnosed as chronic myelomonocytic leukemia, and one case of a t(10;12)(q24;p13) in a progressive MDS, with eosinophilia and monocytosis. Involvement of the TEL gene in these chromosome translocations was investigated by fluorescence in situ hybridization (FISH) with cosmid probes containing selectively the 5' end or 3' end of TEL. Hybridization of these cosmids to the der(5)/der(10) or a der(12), respectively, demonstrated a rearrangement of TEL in both translocations, showing that the t(10;12) is a variant translocation of the t(5;12). Cloning of the fusion cDNA of one case of t(5;12) showed that the breakpoint occurred at the RNA level at exactly the same position as reported by Golub et al (Cell 77:307, 1994). In addition, the TEL gene on chromosome 12 could be localized between two probes previously mapped to 12p13, namely PRB1 and D12S178, leading to a better definition of the position of TEL in this chromosome region. Moreover, in the case involving chromosome 10, the breakpoint occurred between cKTN206 and cKTN312/LYT-10 at 10q24. Clinicohematological data in these studies as well as the restriction mapping of chromosomal breakpoints strongly suggest that (1) common features in MDSs involving the TEL gene are monocytosis and eosinophilia, (2) chromosomes other than no. 5 may be involved and at least a t(10;12)(q24;p13) variant chromosome translocation does exist in these MDSs, and (3) both standard and variant 12p/TEL translocations may be identified by FISH with appropriate probes.

Adult↗