Escalating dose of mitoxantrone with high-dose cyclophosphamide, carmustine, and etoposide in refractory lymphoma patients undergoing autologous bone marrow transplantation.
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Adult↗
Biomedical subjects
J Pris
Publications and source records attributed to J Pris.
Potential strategies for circumventing myeloperoxidase-catalyzed degradation of vinca alkaloids.
Myeloperoxidase (MPO) has recently been shown in an in vitro, cell-free system to catalyze the peroxidative degradation of vincristine (VCR). Oxidation of VCR involves a ring fission between positions 20' and 21', and is thought to be facilitated by the presence of an hydroxyl (-OH) group at position 20'. We report here two different approaches, both with potential clinical application, to decrease MPO-catalyzed vinca degradation. Firstly, we tested the hypothesis that -OH substitution at position 20' increases vinca susceptibility to peroxidation by comparing the relative extent of degradation of vinorelbine (Navelbine or NVB), which lacks a 20' hydroxyl substitution, with that of VCR. As anticipated, NVB was significantly less susceptible to MPO-catalyzed peroxidation than was VCR (p < 0.01). Secondly, we screened an array of compounds that are in current clinical use for their ability to inhibit MPO. Acetaminophen, N-acetylcysteine, propylthiouracil, D-penicillamine, mefenamic acid, dapsone, and methimazole all inhibited MPO at clinically achievable concentrations. Insofar as increased MPO activity has been observed in patients with acute myeloid leukemia, these findings suggest potential strategies for improving the activity of vinca alkaloids in this disease.
Antineoplastic Agents↗
B-cell lymphoma following polycythemia vera: evidence for the involvement of two different clones.
We report here two patients with polycythemia vera (PV) who developed secondary non-Hodgkin's lymphoma (NHL). Both cases were high grade B-cell NHL. Cytogenetic analysis of bone marrow and lymph node was performed in each case and showed numerous chromosomal abnormalities. Of interest, chromosomal abnormalities of the PV and of the NHL clones were different, suggesting the possible involvement of two different clones. A 11q23 breakpoint was common between the two cases and the putative role of this breakpoint in the pathogenesis of the NHLs is discussed.
Aged↗
Prevention of regimen-related toxicities after bone marrow transplantation by pentoxifylline: a prospective, randomized trial.
Elevated levels of tumor necrosis factor alpha (TNF-alpha) have been reported to correlate with the development of transplant-related complications after bone marrow transplantation (BMT). In a recent phase I-II trial, oral administration of pentoxifylline (PTX), a xanthine derivative capable of downregulating TNF-alpha production in vitro, was reported to reduce morbidity and mortality in patients undergoing BMT. We conducted a prospective randomized trial of PTX therapy among 140 patients undergoing either allogeneic (n = 51) or autologous BMT (n = 89). Patients were randomized to receive (n = 70) or not receive (n = 70) oral PTX, 1,600 mg/d in four divided doses from day -8 until day + 100 post-BMT. The incidence of mucositis requiring morphine sulfate (MSO4) was similar in both groups (42.9%), with the mean number of days with MSO4 being 7.8 (SD = 3.4) in the PTX group versus 8.2 (SD = 3.4) in the control group (NS). The incidence of renal insufficiency was not affected by PTX administration (15.7% in the PTX group v 21.4% in the control group [NS]) and the highest serum creatinine value during the first 100 days post-BMT was 119 mumol/L (SD = 82.4) in the PTX group versus 103.9 mumol/L (SD = 57) in the control group (NS). The incidence of grade > or = 2 graft-versus-host disease was similar in each group (11/25 [44%] in the PTX group v 12/26 [46%] in the control group). No significant difference was observed in hematologic toxicity, transfusion requirements, duration of fever, and hepatic toxicity between the treatment groups. In conclusion, our study failed to show a prophylactic effect of PTX in transplant-related toxicities after BMT. On the basis of these findings, we cannot recommend that PTX be part of early mortality and morbidity prevention programs after BMT.
Adult↗
Leuconostoc, a potential pathogen in bone marrow transplantation.
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Adult↗
De novo acute leukemia with a sole 5q-: morphological, immunological, and clinical correlations.
The 5 q deletion is frequently found in myelodysplastic syndromes and acute non lymphoid leukemia, but this anomaly is usually found in secondary diseases and associated with many other chromosomal aberrations. This report describes four cases of "de novo" acute leukemia with a sole 5q- anomaly. They had no cytological, genetic or clinical characteristics of secondary disorders. It is important to note that of the four patients studied, three had proliferation of immature blast cells. One case was classified as a MO AML and two as "undifferentiated" acute leukemia. Furthermore, these four cases of acute leukemia showed a deletion of the same portion of the long arm of chromosome 5: q22q33. On the same part of this chromosome many hematopoietic growth factor genes have been located, like IL3 and GM-CSF which have early undifferentiated hematopoietic stem cells as a their target.
Acute Disease↗
[Alveolar opacities and busulfan pneumonia].
A case of toxic pneumonia due to busulfan is reported in a man aged 65 treated for three years with busulfan for chronic myeloid leukaemia. He was admitted to hospital for dyspnoea, cough, fever and presented with crepitations, dense alveolar opacities, and a restrictive ventilatory defect. Trans-bronchial biopsy showed a filling of the alveoli by fibroblastic tissue, as well as voluminous dystrophic pneumocytes. Four months later in spite of steroid therapy the clinical state and respiratory function were worse. The alveolar opacities have regressed but some diffuse interstitial opacities had appeared. This new case is a reminder that the appearance of alveolar opacities in a patient treated with busulfan should raise the possibility of a toxic pneumonitis to busulfan in the differential diagnosis. This observation also underlines the role of the initial endo-alveolar fibrosis in the ultimate development of interstitial fibrosis.
Aged↗
[Portal thrombosis, hereditary protein C deficiency and Vaquez disease].
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Aged↗
t(9;11)(p22;q23) translocation in blastic phase of chronic myeloid leukemia.
A patient with chronic myeloid leukemia showed clonal karyotypic evolution, with the appearance of an i(17q) and t(9;11)(p22;q23). This case sheds light upon leukemogenic events related to t(9;11)(p22;q23). The presence of t(9;22) and t(9;11) in the same clone showed that t(9;11) may affect a pluripotent stem cell, thus accounting for t(9;11) in both lymphoid and monocytic leukemias. In this patient, t(9;11) could not be related to a prior cytotoxic exposure and was instead the result of natural evolution of chronic myeloid leukemia. Furthermore, this led us to assume that the phenotype of blast cells may be determined by a chromosome abnormality. A phenotypic conversion from myeloblastic to undifferentiated morphologic aspect was observed when t(9;11) was detected, suggesting that t(9;11) may have induced a loss in differentiation of blast cells affected by this change. This assumption is in agreement with the putative presence of genes activated in pluripotent progenitors by 11q23 rearrangements.
Blast Crisis↗
Intensive combined therapy for previously untreated aggressive myeloma.
A trial was initiated to determine the feasibility and efficacy of a three-phase treatment including: (1) induction chemotherapy (IC); (2) high-dose melphalan with total body irradiation supported by unpurged autologous bone marrow transplantation (ABMT); and (3) interferon (IFN) alpha maintenance treatment, in previously untreated aggressive myeloma. Thirty-five consecutive patients, ages under 65 years, were enrolled. Initial induction therapy was randomized between the VAD regimen (vincristine, doxorubicin, dexamethasone) or the VMCP regimen (vincristine, melphalan, cyclophosphamide, prednisone) that were found to give similar results as IC. Thirty-one of 35 (89%) patients, with good performance status and normal renal function after IC, received ABMT. IFN alpha was started soon after ABMT and was well tolerated. Fifteen of 35 (43%) patients achieved complete response (CR) and 14 of 35 (40%) achieved partial response (PR). Low pretreatment beta 2 microglobulin was the only predictive factor for accomplishing CR. The duration of response was significantly affected by the magnitude of response. The 33-month, post-ABMT probability of progression-free survival was 85% for patients in CR versus 24% for patients in PR. The 42-month, post-diagnosis probability of survival was 81%. This overall strategy may represent an advance in the management of multiple myeloma. Furthermore, the high rate and long duration of CR that we observed in patients with low beta 2 microglobulin suggest that such patients may preferentially benefit from this strategy.
Aged↗
Hydroxyurea versus interferon alfa-2b in chronic myelogenous leukaemia: preliminary results of an open French multicentre randomized study.
In order to compare the effects of interferon versus hydroxyurea for the treatment of chronic myelogenous leukaemia (CML), 58 CML patients, having received no previous treatment, were randomized into two treatment groups (hydroxyurea or interferon) for an open multicentre study from 1 May 1987 until 1 July 1990. Fifty patients were evaluable: 24 in the interferon group and 26 in the hydroxyurea group. Haematological response was obtained in 16/24 interferon-treated patients and 23/26 hydroxyurea patients. Failure to obtain haematological remissions occurred in eight of 24 interferon-treated patients and in three of 26 hydroxyurea patients. Four interferon-treated patient failures and one hydroxyurea-treated failure were due to drug intolerance. Progression occurred in one interferon-treated patient and in three patients given hydroxyurea. Fourteen of 16 patients in the interferon group and 17/23 in the hydroxyurea group continue on study and show no progression.
Adult↗
Prevention of gram-positive infections after bone marrow transplantation by systemic vancomycin: a prospective, randomized trial.
Gram-positive bacteria are the most commonly isolated organisms after bone marrow transplantation (BMT) and severe streptococcus septicemia has been reported. In order to evaluate the benefit of a gram-positive prophylaxis after BMT, we conducted a prospective, randomized trial of systemic vancomycin among 60 patients undergoing BMT for hematologic malignancies. Patients were randomized to receive (n = 30) or not receive (n = 30) prophylactic vancomycin 15 mg/kg every 12 hours from day -2 until resolution of neutropenia or until the first episode of fever. All patients were treated in laminar air-flow rooms, received sterile diet, total gut decontamination, and had central venous catheters placed surgically. Vancomycin was found to be highly effective in preventing gram-positive infections that occurred in 11 of 30 patients in the control group versus zero of 30 in the vancomycin group (P less than .002). All gram-positive infections occurring in the control group were symptomatic (nine septicemia and two local infections), and one patient with Streptococcus septicemia died with pneumonia. Thus, gram-positive prophylaxis was found to decrease infection morbidity after BMT. Moreover, the number of days with fever (P less than .001), and empiric antibiotic therapy (P less than .01) was reduced without added toxicity or cost. This study confirmed the high prevalence of gram-positive infections after BMT and emphasized the clinical benefits of an adapted prophylaxis.
Adolescent↗
[Magnetic resonance imaging in the bone sites of malignant non-Hodgkin's lymphoma. Apropos of 16 cases].
The primordial role of MRI in the staging of primary or secondary bone tumors has been clearly established. The authors report a study of 16 patients with NHL with suspected bone involvement, investigated by conventional radiography, bone scan, CT, bone marrow biopsy and MRI. The authors believe that, in the future, MRI will have an important role in the staging and follow-up of treatment of bone lymphomas. Better than any other techniques, MRI provides a precise assessment of tumor extension. It also represents a valuable method for monitoring patients during treatment by visualising the course of the disease.
Adult↗
Maintenance treatment with recombinant alpha interferon after autologous bone marrow transplantation for aggressive myeloma in first remission after conventional induction chemotherapy.
Twenty patients (median age 57 years) with high tumor mass myeloma in first remission after conventional chemotherapy received a two-phase treatment: autologous bone marrow transplantation (ABMT) using a preparative regimen of high dose melphalan plus total body irradiation followed by maintenance treatment with recombinant alpha interferon. Before ABMT all patients were in partial remission, while after ABMT 10 (50%) achieved complete remission, and 10 remained in partial remission (with a 90% decrease in measurable paraprotein in 7/10). With a median follow-up of 19.8 months (12.2-33.5) after diagnosis and 13 months (4-25) after ABMT, the Kaplan-Meier 2-year post-ABMT probability of progression-free survival was 85% (95% CI = 58.7-95.8%). None of the 10 patients in complete remission has relapsed. No toxic death occurred. Alpha interferon was introduced early after ABMT (2.7 months) and was well tolerated. This strategy may represent an advance in the management of aggressive myeloma.
Adult↗
Consequences of moderate hypoxia on red cell glycolytic metabolism in polycythemia rubra vera.
Red blood cell metabolism was studied in male patients with polycythemia rubra vera (Vaquez disease) and compared to a reference sample of 74 healthy adults. A total of seventeen enzyme activities and seventeen metabolite concentrations were determined. In addition to the modifications of the hematological parameters among the polycytemic patients significant variations were detected: a decreased content of hemoglobin in the cells; significantly decreased levels of ATP, ADP and AMP associated to an accelerated turn over of these metabolites; an acceleration of the glycolytic pathway associated with an increase of the energetic charge and levels of 2-3BPG and G1-6BP. In polycythemia rubra vera patients, the modifications of the hematological and biochemical parameters were compared to previous results obtained in high altitude residents (adaptative hypoxia) and in red cells belonging to new borns.
Adult↗
[Moschcowitz syndrome associated with Waldenström's disease].
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Humans↗
Translocation t(3;21)(q26;q22) in acute myeloblastic leukemia secondary to polycythemia vera.
A case of acute myeloblastic leukemia secondary to polycythemia vera suggests that the t(3;21) translocation is not restricted to blastic phases of chronic myelocytic leukemia (CML) but can be associated with blastic phases occurring after other myeloproliferative syndromes. All published cases were in myeloid crises. Furthermore, this translocation may have been induced by mutagenic effects of either 32P or various chemotherapies administered in this case. In the nine cases reported (including ours), hydroxyurea and busulfan were most frequently used (each drug was used separately in six cases and in association in three cases). Even if the t(3;21) translocation is partly therapy induced, this chromosomal abnormality appears to characterize myeloid crises of myeloproliferative syndromes (often CML, seldom polycythemia vera).
Chromosome Banding↗
Pharmacokinetics of idarubicin after oral administration in elderly leukemic patients.
We have studied the plasma pharmacokinetics of idarubicin (4-demethoxy daunorubicin) in 11 elderly patients suffering from acute myeloblastic leukemia receiving orally 30 mg/m2 per day for 3 consecutive days. Idarubicin culminated in plasma 4 hr after administration and followed three similar time courses after the three administrations. Idarubicinol (13-dihydro-4-demethoxy daunorubicin) was the only fluorescent metabolite in plasma and no aglycone could be detected; idarubicinol concentration was always higher than that of unchanged idarubicin. Due to its protracted half-life (64 hr in this study), this metabolite progressively accumulated and the ratio of the areas under the curve (0-24) idarubicinol/idarubicin increased from day to day. By comparison to results obtained after i.v. administration of the drug in another study, the bioavailability of idarubicin alone can be estimated to about 21%, whereas the bioavailability of the sum idarubicin + idarubicinol is about 41%.
Administration, Oral↗