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Biomedical subjects

A Rambaldi

Publications and source records attributed to A Rambaldi.

At least 91 records · Page 5Linked to original sources
PubMed1996

Role of anthracyclines in the treatment of adult acute lymphoblastic leukemia.

In acute myelogenous leukemia, early treatment is usually attempted with the so-called 3+7 regimen, employing daunorubicin (DNR) or idarubicin (IDR) for 3 consecutive days. In acute lymphoblastic leukemia (ALL), the role of agreement regarding ANT dosage and schedule, preferable compound, and indications for remission induction and consolidation treatment phases. Here we review the role of these drugs in adult ALL. The results indicate that ANTs may offer the best survival chance when used at full dosage during induction and early consolidation treatment. IDR may be a better choice that DNR or doxorubicin, and CD10+ t(9;22)/bcr- ALL may have an excellent prognosis following an early dose-intensive ANT consolidation program.

Adult↗
PubMed1996

Age-adapted moderate-dose induction and flexible outpatient postremission therapy for elderly patients with acute lymphoblastic leukemia.

We report the results of a recent trial in elderly acute lymphoblastic leukemia (ALL) patients (> or = 60 years). Initial chemotherapy consisted of one 14-day course with single-dose idarubicin plus vincristine-prednisone-L-asparaginase. Idarubicin was preferred to other anthracyclines because of its shorter time to response. Sequential outpatient postremission therapy included single-dose idarubicin plus vincristine-cyclophosphamide-L-asparaginase pulses, cranial irradiation with intrathecal methotrexate-cytarabine, flexible weekly vincristine-cyclophosphamide alternating with cytarabine-teniposide, and two-year standard maintenance with mercaptopurine-methotrexate. Granulocyte colony-stimulating factor (G-CSF) was added to induction and early consolidation courses. Twenty-two patients mainly with high-risk features entered the study: median age was 64 years (60-73), 40% of cases were CD10- B-lineage and T-lineage ALL, 38% of CD10+ B-lineage ALL carried a BCR-ABL rearrangement, while 23% coexpressed myeloid antigen, 86% had L2 morphology, 50% had a blast count greater than 10 x 10(9)/1, 54% had hepato-splenomegaly and lymphadenopathy. The complete remission (CR) rate after induction therapy was 59%. A partial remission was obtained in two cases. There were four early deaths (18%) and three refractory ALL (14%). Median time to response was 21 days. With G-CSF, the median duration of absolute neutropenia was 10.5 days. Flexible postremission therapy was very well tolerated, causing no major toxicity. With a median follow-up of 2.6 years, 3 patients remain alive in first CR (23%), 2 of whom at 21.3 months and 39.6 months, respectively. Median survival of responders was 12 months compared to only 1.2 months for nonresponders (p < 0.001). This moderate-dose idarubicin-containing and G-CSF-supported regimen was associated with a high early remission rate in elderly ALL. Postremission therapy results were modest, though not appreciably different from the general experience in this patient population. Because further escalation of drug intensity appears unjustified, attempts to document and reverse drug resistance patterns and restore a dysregulated apoptosis must be considered.

Aged↗
PubMed1996

The natural history of monoclonal villous lymphocytosis: a chronic lymphoproliferative disorder of CD11c+ B cells.

The long-term outcome of three asymptomatic subjects with isolated persistent lymphocytosis of monoclonal villous B-cells (MVL) is reviewed. After 7.5 years, evolution to a splenic lymphoma variant (SLVL) was documented in only one patient, accompanied by a loss of interleukin-1beta autocrine production, confirming that MVL can be an early form of a malignant disorder. The clinical course was uneventful in the other two cases; a progressive lowering of lymphocyte count being noted in one. While the strict relationship of MVL to SLVL is confirmed, time to progression is unpredictable and the mechanisms by which it occurs still remain to be elucidated.

Aged↗
PubMed1996

Molecular diagnosis and clinical relevance of t(9;22), t(4;11) and t(1 ;19) chromosome abnormalities in a consecutive group of 141 adult patients with acute lymphoblastic leukemia.

Over a time period of five years leukemic blast samples from 141 consecutive patients with adult ALL were referred to our laboratory, for molecular evaluation of chromosome abnormalities. The t(9;22), t(4;11) and t(1;19) which are most commonly found in adult ALL with a B-precursor phenotype were molecularly analyzed by similar RT-PCR based protocols. BCR-ABL transcripts generated by the t(9;22) translocation were demonstrated in 36 patients (25%) and were restricted to the 109 patients with B precursor ALL (33% of this group). Of 83 patients showing a, common phenotype (CD10+), 34 were BCR-ABL positive (41%) whereas only 2 out of 26 with Null ALL (HLADr+, CD19+, CD10) were positive. Interestingly, the percent of BCR-ABL positive CD1O+ ALL increases significantly with age being 20% in patients less than 30 years old and more than 50% in older patients. None of the T-ALL (24 patients) and B-ALL (8 patients) were positive. The majority of cases (67%) showed the p190 gene subtype. The cytogenetic diagnosis of Philadelphia chromosome was always confirmed by the molecular analysis and this approach allowed for the detection of the presence of the BCR-ABL rearrangement in 26 patients when a negative result or no metaphases were obtained. The complete remission rate was similar among BCR-ABL positive and negative patients but a shorter remission duration was observed in those showing molecular evidence of t(9;22) and this finding was significantly evident in CD1O+ ALL patients. By means of comparison, in most of the same adult ALL patients, we analyzed the yet unrecognized prevalence of the t(4;11) and t(1;19) translocations by the molecular analysis of their chromosomal breakpoints. Rearrangements of the ALL-1 gene on 11q23 band and ALL- l1AF.4 fusion transcripts specific for the t(4;11) were demonstrated in 7 out of the 21 Null ALL investigated, with no additional positive cases found among the other ALL subgroups. Overall the clinical behavior of t(4; 11) positive patients was dismal with a very short CR duration. Chimeric E2A-PBX1 transcripts generated by the t(1;19) were found in only two of the 87 B-precursor ALL analyzed. The presented results provide further evidence for the utility of RT-PCR based methods for the molecular diagnosis of chromosome translocations in ALL. The identification of such abnormalities can significantly contribute to the identification of more appropriate therapeutic options for standard and high risk ALL patients

Adolescent↗
PubMed1996

The role of anthracyclines in adult acute lymphoblastic leukaemia.

The role of anthracyclines (ANT) in the treatment of adult acute lymphoblastic leukaemia (ALL) is poorly defined as regards drug dosage, schedule, preferable compound, and indications for use in specific treatment phases or disease subset. We therefore reviewed ANT treatment results in adult ALL. Altogether, an early and intensive use of ANT would improve both initial response rate and long-term disease-free survival; idarubicin (IDR) exhibits a considerable antileukaemic activity deserving further evaluation as possible reference drug; and the prognosis of CD10+ t(9;22)/BCR-ABL- ALL can be particularly good following an early dose-intensive ANT consolidation program.

Adolescent↗
PubMed1996

G-CSF-mobilized peripheral blood progenitor cells for allogeneic transplantation of resistant or relapsing acute leukemias.

Peripheral blood progenitor cells (PBPC) were mobilized by G-CSF in normal HLA identical siblings and used for allogeneic transplantation in eight patients with refractory or relapsed acute leukemias. G-CSF administration was well tolerated and no significant side-effects were registered. The number of circulating WBC peaked at day 5 after G-CSF (range: 22.6-74.6 x 10(9)/l) with a median of 65 CD34+ cells/microl (38-155). As a consequence of leukaphereses, platelets progressively decreased, reaching the nadir after the last procedure (84-205 x 10(9)/l). A mean of two aphereses (1-3) were performed between day +4 and +7 during which 10 liters of blood were processed each time by a cell separator. Conditioning regimens were: fractionated total body irradiation (FTBI) plus either HDAra-C (2 g/m2 x 2/day for 6 days) (n=5) or melphalan (110 mg/m2) (n= 1) and busulfan (4 mg/kg/day for 4 days) and melphalan (110 mg/m2) in two patients relapsed after a previous FTBI-based allogeneic or autologous BMT. At transplantation, a median of 6.9 x 10(6) CD34+ cells/kg (4.2-16.5) and 279 x 10(6) CD3+ cells/kg (161-786) were infused. Engraftment of both neutrophils (> or v=1.5 x 10(9)/l) and platelets (> or v=20 x 10(9)/l) was observed in all patients after a median time of 18 days (range: 11-20 and 10-26, respectively). The evaluation of engraftment after transplantation was accomplished by PCR analysis of four hypervariable genomic regions (VNTR) (ApoB, ApoC2, YNZ-22, and MCT 118) which allowed to demonstrate the condition of donor chimaera in all patients after transplantation. As far as the clinical outcome, two patients died of interstitial pneumonitis at day +243 and +69 and two patients died at day +62 and +152 of pulmonary aspergillosis. Four patients remain alive in remission between day +88 and +287 with grade 0-l GVHD. Allogeneic PBPC transplantation is associated with a complete hematologic recovery and despite the infusion of a large amount of mature CD3+ lymphocytes, apparently acute GVHD is not worse than expected after transplantation of bone marrow progenitors.

Adolescent↗
PubMed1996

Different susceptibility of coagulase-positive and coagulase-negative staphylococci to ciprofloxacin.

Ciprofloxacin susceptibility was evaluated in 573 clinical staphylococcal isolates (Staphylococcus aureus 230, methicillin-resistant (MR) 36%; coagulase-negative strains 343, MR 66%) collected from 1989 to 1995. Resistance to ciprofloxacin for MR Staphylococcus aureus was 25% until 1991 when ciprofloxacin was introduced into the hospital formulary, and rose progressively to 90% in 1994-1995. MR Staphylococcus haemolyticus showed a ciprofloxacin resistance of 46% until 1991 and of 73% from 1992 to 1995. In contrast MR Staphylococcus epidermidis and other coagulase-negative strains showed a constant susceptibility to this agent (80%). Ciprofloxacin has limited usefulness against MR Staphylococcus aureus but can be still used to treat Staphylococcus epidermidis infections.

Ciprofloxacin↗
PubMed1995

Constitutive expression of GATA-1, EPOR, alpha-globin, and gamma-globin genes in myeloid clonogenic cells from juvenile chronic myelocytic leukemia.

Juvenile chronic myelocytic leukemia (JCML) is a rare disorder of early childhood. Characteristic of JCML are the progressive appearance of high levels of fetal hemoglobin (HbF), reflecting a true reversion to a fetal type of erythropoiesis, and the presence of colony-forming cells able to grow in vitro spontaneously in the absence of growth factors. To better understand the relationship between the erythroid abnormalities and the leukemic process, we analyzed the expression pattern of specific genes related to erythroid differentiation--GATA-1, EPOR, alpha-globin, beta-globin, and gamma-globin genes--in JCML peripheral blood (PB) cells and in vitro-derived colonies. Northern blot analysis of PB cells from five JCML patients indicated levels of GATA-1 transcripts much higher than those usually found in other types of leukemic cells, and S1 nuclease protection assay detected significantly increased expression of gamma-globin mRNA. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of single granulocyte-macrophage colony-forming unit (CFU-GM) colonies, obtained in vitro in the absence of added growth factors from four JCML patients, detected GATA-1, EPOR, and globin (alpha and gamma) transcripts in most of the colonies tested, in contrast with control CFU-GM from normal bone marrow, which were positive only for GATA-1. Single JCML colonies were tested for the presence of two different transcripts; whereas alpha- and gamma-globin genes appeared mostly coexpressed, beta-globin mRNA was detected only in a minority of the gamma-globin-positive colonies, indicating that the leukemic pattern of hemoglobin synthesis is mainly fetal. In addition, the leukemic cells occurring during blast crisis of one of our patients displayed the typical features of a stem cell leukemia (CD34+, CD19-, CD2-, myeloperoxidase-). In this sorted CD34+ population, we detected the presence of a marker chromosome, der(12)t(3;12), previously identified in bone marrow cells at diagnosis and an expression pattern superimposable to that of the JCML colonies, consistently displaying a high gamma-globin:beta-globin mRNA ratio. The expression of erythroid markers within populations of leukemic cells, both in vivo and in vitro, supports the hypothesis that abnormal JCML erythroid cells may originate from the same mutated progenitor that sustains the growth of the leukemic cells.

Cell Differentiation↗
PubMed1995

All-trans retinoic acid and cyclic adenosine monophosphate cooperate in the expression of leukocyte alkaline phosphatase in acute promyelocytic leukemia cells.

Treatment of acute promyelocytic leukemia (APL) blasts with cyclic adenosine monophosphate (cAMP) analogs, in combination with all-trans retinoic acid (ATRA), results in the upregulation of the expression of leukocyte alkaline phosphatase (LAP), a marker for the differentiation of the granulocyte. The synergistic interaction between the cyclic nucleotide analogs and the retinoid is not unique to APL cells, as it is observed also in the peripheral granulocytes of chronic myelogenous leukemia (CML) patients. The molecular mechanisms underlying LAP induction were studied in NB4, an immortalized APL cell line. Induction of LAP enzymatic activity is dependent on the time of exposure and on the concentrations of dibutyryl-cAMP or 8-bromo-cAMP and ATRA, two factors that influence the kinetics of appearance of detectable levels of the enzyme. Augmentation of LAP levels by ATRA and cAMP is the result of both transcriptional and early posttranscriptional events and requires de novo protein synthesis. LAP induction correlates with augmentation in the levels of the type I catalytic subunit of cAMP-dependent protein kinase transcript and with granulocytic differentiation. The transcriptional component of the process leading to increased LAP gene expression was reproduced in its main features by transient transfection experiments performed in COS-7 cells using the normal retinoic acid receptor type alpha (RAR-alpha) or the APL-specific aberrant form (PML-RAR) and the upstream promoter of the liver/bone/kidney (L/B/K)-type alkaline phosphatase gene. The promoter is upregulated by treatment with ATRA, and this upregulation is further increased by cAMP analogs.

Alkaline Phosphatase↗
PubMed1995

Tyrosine kinases but not cAMP-dependent protein kinase mediate the induction of leukocyte alkaline phosphatase by granulocyte-colony-stimulating factor and retinoic acid in acute promyelocytic leukemia cells.

Leukocyte alkaline phosphatase (LAP) is synergistically induced by the combination of all-trans retinoic acid (ATRA) and granulocyte-colony-stimulating factor (G-CSF) in acute promyelocytic leukemia (APL) cells (Gianni' M. et al., Blood 83: 1909-1921, 1994). The role of cAMP and tyrosine kinases in the induction of LAP was investigated. In the APL cell line NB4, adenosine-3': 5'-monophosphothioate, cyclic, Rp isomer, a reversible inhibitor of cAMP-dependent protein kinase (PKA), has no effect on the induction of LAP enzymatic activity and mRNA triggered by ATRA+G-CSF, in conditions where this compound completely blocks the upregulation of LAP transcript caused by the combination of the PKA agonist, dibutyryl-cAMP (db-cAMP), and ATRA. Challenge of NB4 cells with G-CSF, dbcAMP and ATRA causes a much higher induction of LAP relative to that observed in the presence of ATRA+G-CSF or ATRA+dbcAMP. Treatment of NB4 with ATRA and G-CSF results in increases in the tyrosine phosphorylation of several proteins. In the presence of the cytokine and the retinoid, tyrosine kinase inhibitors decrease LAP enzymatic activity and mRNA.

Alkaline Phosphatase↗
PubMed1995

Granulocyte colony-stimulating factor following peripheral-blood progenitor-cell transplant in non-Hodgkin's lymphoma.

PURPOSE: To compare the hematologic recovery after high-dose chemotherapy and circulating peripheral-blood progenitor-cell (PBPC) transplant between patients who received recombinant human granulocyte colony-stimulating factor (G-CSF) (treated group) and those who did not (control group). PATIENTS AND METHODS: From December 1992 through June 1994, two sequential and consecutive cohorts of 20 patients each with histologically proven non-Hodgkin's lymphoma (NHL) received high-dose chemotherapy (carmustine [BCNU], cytarabine [Ara-C], etoposide and melphalan [BEAM]) followed by PBPC transplant. The first 20 patients were treated with G-CSF (5 micrograms/kg/d) after PBPC administration. Since the time of platelet and leukocyte recovery in this group was short (< 15 days), with a narrow standard deviation from the mean value, the last 20 patients were not given G-CSF. Hematologic recovery, number of febrile days, rate of documented infections, number of hospital days, duration of gastrointestinal complications, platelet and RBC transfusions, and antibiotic requirements were compared in the two groups. RESULTS: The two groups of patients were comparable according to disease status, histology, stage, bulky disease bone marrow involvement, elevated lactate dehydrogenase (LDH) level, and median number of infused CD34+ cells and colony-forming units granulocyte-macrophage (CFU-GM). The median time to reach 0.5 x 10(9)/L and 1.0 x 10(9)/L neutrophils was 2 days shorter in G-CSF group, but this difference was not statistically significant. The median times to reach 20 x 10(9)/L and 50 x 10(9)/L platelets were, respectively, 10 and 14 days in the G-CSF group and 11 and 16 days in the control group, but again this was not statistically significant. Moreover, when considering clinically relevant end points including the number of documented infections and antibiotic requirements, platelet transfusions, gastrointestinal toxicity, and days of hospitalization, no differences were demonstrated between the two groups. CONCLUSIONS: Provided an optimal dose of circulating progenitors is infused, NHL patients transplanted with PBPC do not benefit by the administration of hematopoietic growth factors.

Adult↗
PubMed1995

Resistance to aminoglycosides and other antibiotics among clinical isolates of Enterococcus spp.

We conducted a study on 81 clinical isolates of enterococci (65 Enterococcus faecalis and 16 Enterococcus faecium) collected consecutively over a one year period at our University Hospital. Of them, 10 (15%) Enterococcus faecalis and 6 (38%) Enterococcus faecium showed high level resistance to aminoglycosides, were all acquired in surgical units and in five cases they were responsible for invasive infections. Ampicillin and imipenem were active only against Enterococcus faecalis. Vancomycin and teicoplanin were bacteriostatic; however, teicoplanin MICs were lower and in 45% of cases its MBC values were within clinically achievable serum concentrations. Ciprofloxacin and cotrimoxazole were active in vitro.

Aminoglycosides↗
PubMed1995

Autologous PBSC transplant for late onset AML after mafosfamide-purged and TBI-containing autologous BMT.

The prognosis of AML patients who fail autologous BMT and lack a donor for a salvage allogeneic BMT is very poor. We administered an alternative drug treatment including autologous PBSC transplant to a child who relapsed with AML 4 years after a mafosfamide-purged and TBI-containing BMT for second remission AML. Treatment comprised induction-consolidation with 'short' ICE courses (idarubicin-Ara C-etoposide for 2 days), high-dose CY plus G-CSF with collection of CD34+ PBSC and myeloablative treatment with high-dose mitoxantrone/BEAM supported by autologous PBSC reinfusion. The outcome was complete response, lasting 24 months. The patient died in remission of drug-related cardiotoxicity. This report emphasizes the possibility of a secondary AML after mafosfamide-purge autologous BMT, and documents the feasibility of an autologous PBSC transplant in such a high risk setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Short-term treatment for adult hypergranular and microgranular acute promyelocytic leukemia.

A high hemorrhagic risk and a complete response to the differentiative agent all-trans-retinoic acid (ATRA) are the main clinical features of acute promyelocytic leukemia (APL), two distinct subtypes of which have been recognized, the common hypergranular leukopenic form (M3) and a microgranular hyperleukocytic variant (M3v). We analyzed, with emphasis on both disease- and therapy-related prognostic factors, the results from a 9-year trial in 65 adults with M3 and M3v APL, treated homogenously with a short-term therapy (STT) program excluding maintenance. STT comprised a maximum of six courses with doxorubicin, cytosine arabinoside (ara-C), and 6-thioguanine. Sixty-five APL patients formed the study group, M3v accounting for 25% of cases. In M3v, the absolute blast cell count was significantly higher (p < 0.0001) and early hemorrhagic deaths were more frequent (p = 0.05). The blast count correlated inversely with the probability of remission (p = 0.005), poor-risk patients being those with > 10 x 10(9)/l blast cells. During the study, the median survival improved from 0.1 to 2.7 years (p = < 0.005). In first place, response to chemotherapy increased from 42 to 84% (p = 0.006), by giving daily prophylactic platelet transfusions (to > 30 x 10(9)/l) and no heparin (course I), and by avoiding too toxic high-dose ara-C and deferring treatment in infected/neutropenic patients showing the atypical differentiative bone marrow pattern (course II). Secondly, the probability of first unmaintained remission differed significantly between patients given intentionally more than four total chemotherapy courses or intermediate/high-dose ara-C consolidation (0.59 at 5 years) and those treated less intensively (0.21) (p < 0.005). Intensive STT was very effective for the management of adult APL patients at standard hemorrhagic risk and receiving optimal supportive care. In high-risk patients with hyperleukocytosis and M3v, induction results could be improved by the concomitant use of ATRA. M3v in adults must be recognized promptly because of the very high early hemorrhagic risk.

Adolescent↗
PubMed1995

Prevalence of alcohol problems among adult somatic in-patients in Naples.

The aim of this cross-sectional study was to determine the prevalence of alcohol problems among adult somatic in-patients in urban hospitals of Naples. The patients were screened with a structured questionnaire regarding life style. After discharge, the patient records were examined and the hospital discharge diagnoses were registered. A patient was considered having an alcohol problem if one or more of the following criteria were fulfilled: (1) a Michigan Alcoholism Screening Test score at or above five; (2) a self-reported daily consumption for at least 2 years of at least 60 g of ethanol for males and 36 g for females; (3) an alcohol-related discharge diagnosis. The prevalence of patients with alcohol problems was significantly (P < 0.01) higher among male (43.8%, 95% confidence limits, 37.6-50.2%) than among female patients (14.8%, 95% confidence limits, 9.6-21.4%). There were no significant differences among the different types of somatic departments regarding the prevalence of alcohol problems when gender was considered. Patients with alcohol problems differed significantly from those without alcohol problems regarding a number of variables: the former drank significantly more alcohol, smoked for more years, and had a higher prevalence of alcohol problems in the family. It is concluded that alcohol problems among in-patients are as prevalent in Naples as in other industrialized countries, that it is often not registered among discharge diagnoses, and that the problems are more prevalent in males than in females, irrespective of the type of department.

Adolescent↗
PubMed1994

Determination of orally administered all-trans-retinoic acid in human plasma by high-performance liquid chromatography.

All-trans-retinoic acid (RA) is used successfully in the treatment of acute promyelocytic leukaemia (APL), although unexplained relapses occur in many of the patients. Pharmacokinetic studies may help in understanding the mechanism of resistance to RA and a simple and rapid procedure for its determination in biological samples may be advantageous. A high-performance liquid chromatographic procedure is described, involving one-step extraction of RA from plasma, isocratic elution from a reversed-phase column (LiChrosorb RP-18, 5-microns particle size) and UV detection at 340 nm. The calibration graph is linear over a wide range and the limit of detection is approximately 10 ng/ml, using 0.5 ml of human plasma. The method is selective for RA, accurate and robust and thus suitable for the routine analysis of plasma samples from patients undergoing RA therapy. Analysis of plasma in a patient on RA therapy (45 mg/m2 per day) confirmed that during continuous treatment with RA the drug plasma concentrations are markedly lower at the time of relapse than on the first day of treatment.

Administration, Oral↗