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I Lorand-Metze

Publications and source records attributed to I Lorand-Metze.

At least 19 recordsLinked to original sources
PubMed2006

Frontline therapy with early intensification and autologous stem cell transplantation versus conventional chemotherapy in unselected high-risk, aggressive non-Hodgkin's lymphoma patients: a prospective randomized GEMOH report.

This prospective multicenter randomized trial compares conventional with early intensification with high-dose sequential chemotherapy (HDS) and autologous stem cell transplantation (ASCT) as frontline therapy in high-risk non-Hodgkin lymphomas (NHL). Newly diagnosed patients with aggressive high-risk [intermediate-high (HI) and high-risk (HR)] NHL according to the international prognosis index (IPI) were randomized to receive 12-week VACOP-B (arm A, 27 patients) or 6-week VACOP-B followed by HDS and ASCT (arm B, 29 patients). Complete remission rate was 52% in arm A and 55% in B. Nine patients (16%) died early due to progression. According to intention-to-treat, with a median follow-up of 23 months, the 5-year actuarial overall survival, progression-free survival and disease-free survival in arms A and B were 47 and 40% (p = nonsignificant), 47 and 30% (p = nonsignificant), and 97 and 47% (p = 0.02), respectively. Abbreviated chemotherapy followed by intensification with HDS-ASCT does not seem to be superior to conventional chemotherapy in HI/HR aggressive NHL.

Adolescent↗
PubMed2006

Phenotypic quantitative features of patients with acute myeloid leukemia.

The recent WHO classification for acute myeloid leukemias (AML) separates entities by recurrent cytogenetic abnormalities and immunophenotypic features presenting prognostic impact. We have examined the expression of several lineage and maturation linked antigens used in routine immunophenotyping of patients with de novo AML, using a 3-color two-step panel. Cases were diagnosed by peripheral blood counts, bone marrow cytology, cytochemistry, cytogenetics and immunophenotyping (CD2, CD3, CD7, CD19, CD13, CD33, myeloperoxydase -- MPO, CD14, CD15, HLA-DR, CD34, CD56 and CD45). Antigen expression was measured by mean fluorescence intensity (MFI) by flow cytometry (Paint-a-gate software). Thirty five patients were analyzed. Median age: 51 years (15-79). Predominant FAB types were M2 and M4. In 6 cases more than one phenotypically distinct blast subpopulation could be detected. Although our set was small, we tried to analyze the impact of MFI of the examined antigens on the overall survival of the patients. In Cox univariate analysis, age, peripheral leukocytes (WBC) at diagnosis, MFI of CD45, and MPO were significant for worse a survival. In the multivariate analysis only MFI of CD45 and WBC remained in the model (p=0.018 and p=0.014 respectively). After bootstrap resampling, MFI of CD45 entered the model in 69%, WBCin 60%, age in 42% and MFI of MPO in 35% of the sets. Analysis of antigen expression by MFI permitted to detect cases presenting phenotypically distinct blast subpopulations. This may represent a pitfall in studies of minimal residual disease by flow cytometry, as chemotherapy may select one of these subsets.

Acute Disease↗
PubMed2005

Optimization of CD34+ collection for autologous transplantation using the evolution of peripheral blood cell counts after mobilization with chemotherapy and G-CSF.

BACKGROUND: Peripheral blood progenitor cells (PBPC) collection after high dose chemotherapy can be influenced by several factors. We searched for parameters that may predict the best day to start harvesting of PBPC in order to collect most CD34+ cells with the least number of aphereses. METHODS: We studied patients who underwent mobilization chemotherapy for autologous transplantation. The influence of age, sex, diagnosis, number of previous chemotherapy cycles, peripheral blood (PB) counts at day of mobilization (D0), day of neutrophils <1.0 x 10(9) l(-1) and day of nadir and interval between both (delta) on harvesting was investigated. Multivariate linear correlation models were built to predict the best harvesting with principles of parsimony. In patients where sequential CD34+ cell count was performed, the theoretical day of peak was calculated by interpolation in polynomial regression. RESULTS: One hundred and thirty four patients entered the analysis: 36 Hodgkin's lymphoma (HL), 65 B-large cell lymphoma (NHL) and 33 multiple myeloma (MM). Day of harvesting correlated with nr CHT, hemoglobin on D0, day of granulocytes <1.0 x 10(9) l(-1), delta and dosis of mobilization therapy. The day of CD34+ peak could be calculated by the formula = (-0.41) x Hemoglobin D0 + (day peripheral CD34+ cells = 10 x 10(6) microl(-1)) x 0.99 + 7.8. This model could explain 81% of the variance of the peak day and was stable by bootstrap resampling. Day of peripheral CD34+ cells = 10 x 10(6) microl(-1) preceded the calculated peak by 3-9 days. CONCLUSIONS: Although the day of best collection can be predicted using only sequential PB counts after mobilization chemotherapy, a model of prediction using peripheral CD34+ cell count is important especially for optimizing collection in poor mobilizing patients.

Adolescent↗
PubMed2005

Bone marrow features in children with HIV infection and peripheral blood cytopenias.

HIV infection is associated with numerous abnormalities affecting both the myeloid and lymphoid lineages. We studied the features associated with peripheral cytopenias as the first sign of HIV infection in children. Peripheral blood (PB) counts, PB and bone marrow (BM) lymphocyte subsets, as well as viral load and serum levels of ferritin, vitamin B12, and folic acid were determined. Five children were naive of treatment (Group 1) and three were under HAART (Group 2). In Group 1 all patients had anemia of chronic disease. One had a bone marrow culture positive for Mycobacterium avium intracellulare and pancytopenia. Besides this, neutropenia and thrombocytopenia were seen in one patient each. In Group 2 anemia was found in all, neutropenia in one, and thrombocytopenia in two patients. Peripheral blood cytopenias were due to HAART toxicity in one patient. In the other two they were due to iron or folate deficiency. Bone marrow cytology showed cell abnormalities mainly in granulocytic precursors and megakaryocytes. All except two (taking HAART) patients had a high viral load. There was a straight correlation between viral load in PB and bone marrow. Viral load was correlated with peripheral CD4 but not with CD8 lymphocytes. A decrease in bone marrow B lymphocytes was seen in all patients. The introduction of HAART improved peripheral cytopenias. Bone marrow examination was useful for determining the etiology of the cytopenias and for detection of opportunistic infection. Hemopoietic cell abnormalities were similar to those seen in adults and indicative of HIV infection.

Anemia, Aplastic↗
PubMed2004

Cutaneous adverse reaction to 2-chlorodeoxyadenosine with histological flame figures in patients with chronic lymphocytic leukaemia.

INTRODUCTION: 2-Chlorodeoxyadenosine (cladribine or 2-CdA) is a purine analogue that has been used successfully in hairy cell leukaemia (HCL). Moreover, it has been increasingly used to treat chronic lymphoproliferative syndromes and paediatric acute myeloid leukaemia. Cutaneous side-effects associated with this drug have seldom been described in cases of HCL. PATIENTS AND METHODS: We describe three patients with chronic lymphocytic leukaemia that presented generalized skin eruptions after treatment with 2-CdA. RESULTS: All patients had advanced disease, receiving 2-CdA as a second or third line chemotherapy. Skin lesions were severe and chemotherapy had to be discontinued. Histological examination of skin biopsies showed an eosinophil-rich infiltrate with flame figures, similar to what is observed in Wells' syndrome (eosinophilic cellulitis). Corticosteroids were effective to control the eruptions. CONCLUSIONS: Cutaneous adverse reactions associated with 2-CdA have seldom been observed in the treatment of HCL. However, as this purine analogue has been used in more advanced cases these may be more frequent and severe. The pathophysiology of these lesions is unclear, but it is probably related to drug-induced change in T-cell imbalance in severely immunosuppressed patients.

Aged↗
PubMed2003

A possible role of the P53 gene deletion as a prognostic factor in multiple myeloma.

The role of P53 gene abnormalities in the pathogenesis of multiple myeloma (MM) and their potential use as prognostic indicators remain uncertain. To further define this question, we studied genomic DNA from 50 MM and one plasma cell leukemia patients by polymerase chain reaction single-strand conformation polymorphism and sequencing, and fluorescence in situ hybridization in order to detect P53 mutation and deletion, respectively. Kaplan-Meier survival curves and the log-rank test were used to analyze the survival data. No P53 mutation was detected in our patients. In contrast, P53 deletion, predominantly monoallelic, was detected in 8 of 51 (15.7%) patients. Similar frequencies of P53 deletion were observed in patients stratified by age ( P=0.71), gender ( P=0.44), status, and stage of the disease ( P=0.70 and P=0.23, respectively). However, patients with P53 deletion had significantly shorter median overall survival compared with those without a deletion (7.4 vs 139.0 months, P<0.0001). On univariate regression analysis, P53 deletion was a parameter for predicting shortened survival ( P=0.02). We concluded that P53 mutation may be seen as a prognostic indicator of limited value in MM. In contrast, P53 deletion may be seen as a prognostic indicator of poor outcome. However, as the cohort of patients is rather limited for a prognostic analysis, these results should be confirmed by further studies with larger sized samples.

Adult↗
PubMed2003

Acute leukemias in Piauí: comparison with features observed in other regions of Brazil.

Differences in age and sex distribution as well as FAB (French-American-British classification) types have been reported for acute leukemias in several countries. We studied the demographics and response to treatment of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) between 1989 and 2000 in Teresina, Piau , and compared these results with reports from Brazil and other countries. Complete data concerning 345 patients (230 ALL, 115 AML) were reviewed. AML occurred predominantly in adults (77%), with a median age of 34 years, similar to that found in the southeast of Brazil but lower than the median age in the United States and Europe (52 years). FAB distribution was similar in children and adults and FAB-M2 was the most common type, as also found in Japan. The high frequency of FAB-M3 described in most Brazilian studies and for Hispanics in the United States was not observed. Overall survival for adults was 40%, similar to other studies in Brazil. A high mortality rate was observed during induction. No clinical or hematological parameter influenced survival in the Cox model. ALL presented the characteristic peak of incidence between 2-8 years. Most of the cases were CD10+ pre-B ALL. In 25%, abnormal expression of myeloid antigens was observed. Only 10% of the patients were older than 30 years. Overall survival was better for children. Age and leukocyte count were independent prognostic factors. These data demonstrate that, although there are regional peculiarities, the application of standardized treatments and good supportive care make it possible to achieve results observed in other countries for the same chemotherapy protocols.

Adolescent↗
PubMed2002

Characteristics of nasal T/NK-cell lymphoma among Brazilians.

Nasal T/NK-cell lymphomas are highly associated with Epstein-Barr virus (EBV). They are more frequent in Asia than in Western countries. In Central and South America there are few studies about nasal T/NK-cell lymphoma and they have shown a strong predominance of this phenotype in Native American descents, supporting the hypothesis of a racial predisposition for the disease. We studied the lymphomas involving midline facial region at a Brazilian institution. T/NK cell lymphomas (16/25) were more frequently found compared to B lymphomas (9 cases, all B large cell). T/NK cell lymphomas involved predominantly the nasal region. Histologically they showed angioinvasion and necrosis. All of them were positive for CD3 and CD56 and showed numerous tumor cells labeled by EBER-1. Although disease was localized in 61% at diagnosis, there was no tendency to cure. The racial distribution of patients with T/NK-cell phenotype was similar to that found in B-cell lymphomas. EBV was more frequently found in adenoids than in palatine tonsils. In inflammatory lesions of the nasal and palatal regions EBV was not found. In the present study the relative frequency of T/NK versus B cell sinonasal lymphomas was high and similar to that observed in other Latin American countries. However, there was not any racial association with T/NK-cell phenotype and the tumor showed an agressive behavior similar to that reported in Asia. The high frequency of EBV-positive lymphocytes in nasopharyngeal lymphoid tissue (adenoids) suggests that they could serve as a reservoir for the virus.

Adult↗
PubMed2001

Spontaneous apoptosis in chronic lymphocytic leukemia and its relationship to clinical and cell kinetic parameters.

Chronic lymphocytic leukemia (CLL) presents considerable variability in clinical presentation as well as in its evolution. In contrast to the inhibition of apoptosis in vivo, spontaneous apoptosis after short-term culture occurs. We studied the degree of this apoptosis in vitro, and its interactions with several clinical and laboratory parameters. Apoptosis was measured by the annexin V technique. Proliferation rate was evaluated by the AgNOR (nucleolar organizer regions) technique. There were inverse correlations between the percentage of annexin V-positive cells and peripheral lymphocyte count (r = - 0.49), Rai stage (r = - 0.40), Binet stage (r = - 0.50), TTM (total tumor mass score; r = - 0.51), and percentage of cells with one AgNOR cluster (r = - 0.45). Direct correlations were found with hemoglobin values ( r = 0.34) and platelet counts (r = 0.52). The number of CD8-positive cells showed a correlation with peripheral lymphocyte count (r = 0.49). When this variable was held constant, a correlation was detected between CD8-positive cells and staging (r = -0.47), TTM (r = - 0.42), and platelet count (r = 0.67). CD4-positive lymphocytes presented a correlation only with CD8-positive lymphocytes. In a cluster analysis, it was possible to create three groups of patients with different apoptosis rates using the TTM and AgNOR values. We conclude that, with the progression of the disease, together with the increase of tumor mass and proliferation rate, there is a decrease in the susceptibility to apoptosis.

Aged↗
PubMed2001

p53, Mdm2, and c-Myc overexpression is associated with a poor prognosis in aggressive non-Hodgkin's lymphomas.

The expression of p53, p21/WAF-1, Mdm2, c-Myc, and proliferating cell nuclear antigen (PCNA) proteins was examined by the immunohistochemistry of paraffin-embedded tissues of 62 patients with aggressive non-Hodgkin's lymphomas (NHL) and correlated to clinical data. Expression of p53, p21/WAF-1, Mdm2, and c-Myc protein was observed in 17 out of 62 cases (30%), 25 out of 60 (42%), 13 out of 44 (30%), and 39 out of 51 (76.5%), respectively. The p53+/p21WAF-1 phenotype, which is more frequently found in p53 mutations, was associated with a worse overall survival (P = 0.04) and with a lower rate of complete response (CR) (PF = 0.01). p53 and c-Myc negative expression was related to a better response to chemotherapy (PF = 0.005 and 0.035, respectively). The expression of p53, c-Myc, and Mdm2 was related to a shortened overall survival (P < 0.001, 0.05, and 0.037, respectively), suggesting that the expression of these proteins could be associated with a poor outcome in these patients.

Actuarial Analysis↗
PubMed2001

Increased risk for acute myeloid leukaemia in individuals with glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) gene defects.

OBJECTIVES: Glutathione S-transferases (GST) modulate the effects of exposure to various cytotoxic and genotoxic agents, including those associated with increased risks of the myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) and aplastic anemia (AA). Both the GST mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. In this study, we tested whether null genotypes for the GSTM1 and GSTT1 genes altered the risks for MDS, AML and AA. METHODS: Genomic DNA from 49 MDS, 38 AML and 37 AA patients and 276 controls was analysed using the polymerase chain reaction (PCR). RESULTS: The frequencies of GSTM1 (73.6%) and GSTT1 (34.2%) null genotypes were significantly higher in AML patients than in the controls (36.9 and 18.1%, respectively). A higher frequency of the combined null genotype for both genes was also observed in patients with AML (26.3% compared with 5.0% in the controls). In contrast, no differences in the frequencies of the null genotypes were found among MDS patients, AA patients and the controls. CONCLUSION: Our observation of a 4.7-fold (95% CI: 2.1-11.0) and 2.3-fold (95% CI: 1.0-5.2) increased risk associated with the GSTM1 and GSTT1 null genotypes, respectively, and a 6.6-fold (95% CI: 2.4-7.9) increased risk associated with the combined null genotype presents preliminary evidence that the inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.

Acute Disease↗
PubMed2001

Nitric oxide regulates human eosinophil adhesion mechanisms in vitro by changing integrin expression and activity on the eosinophil cell surface.

1. The nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), inhibits both rat and human eosinophil chemotaxis in vitro. Here, the role of nitric oxide (NO) in human eosinophil cell surface integrin expression and function was investigated. 2. Human peripheral blood eosinophils were treated with L-NAME (0.01 - 1.0 mM) and their adhesion to human fibronectin and serum observed. Adhesion of cells to fibronectin and serum increased by 24.0+/-4.6 and 43.8+/-4.7%, respectively, when eosinophils were treated with 1.0 mM L-NAME. Increased adhesion by L-NAME could be abolished when cells were co-incubated with VLA-4- and Mac-1-specific monoclonal antibodies (mAbs). 3. The NO donor, sodium nitroprusside (2.5 mM), significantly inhibited eosinophil adhesion to fibronectin and serum by 34.3+/-4.5 and 45.2+/-5.6%, respectively. This inhibition was accompanied by a 4 fold increase in the levels of intracellular cyclic GMP. 4. Flow cytometrical analysis demonstrated that L-NAME induced an increased expression of CD11b (Mac-1) on the eosinophil cell surface of 36.3+/-7.4%. L-NAME had no effect upon CD49d (VLA-4) expression. 5. Treatment of human eosinophils, in vitro, with H-[1,2,4] oxadiazolo quinoxalin-1-one (ODQ) (0.1 mM), an inhibitor of soluble guanylate cyclase, also significantly increased eosinophil adhesion to fibronectin and serum by 73.5+/-17.9 and 91.7+/-12.9%, respectively. This increase in adhesion could also be inhibited by co-incubation with the Mac-1 and VLA-4-specific mAbs. 6. In conclusion, results indicate that NO, via a cyclic GMP-dependent mechanism, inhibits the adhesion of human eosinophils to the extracellular matrix (ECM). This inhibition is accompanied by a decrease in the expression and function of the eosinophil's adhesion molecules, in particular, the expression of the Mac-1 integrin and the function of the VLA-4 integrin.

Cell Adhesion↗
PubMed2001

Analysis of Vgamma/Jbeta trans-rearrangements in paediatric patients undergoing chemotherapy.

The frequency of the hybrid Vgamma/Jbeta trans-rearrangement in peripheral blood lymphocytes (PBLs) was analysed in a transversal study of paediatric patients (n = 210) with acute lymphoblastic leukaemia (ALL) and solid tumours (ST). Different amounts of DNA were used as the template for a nested polymerase chain reaction to evaluate the frequency of hybrid Vgamma/Jbeta genes, using silver-stained gels. The frequency of the rearrangement was evaluated in groups before, during and after therapy. A greatly increased frequency of Vgamma/Jbeta trans-rearrangement was found in PBLs of both groups of patients during exposure to chemotherapeutic agents compared with patients before chemotherapy. In patients who had finished treatment, the frequency of the rearrangement fell promptly to the baseline levels in ST but showed a slow decrease in ALL in those in whom increased levels could be found until 4 years after the end of treatment. We hypothesize that the chemotherapeutic agents are able to induce the Vgamma/Jbeta trans-rearrangement, but this is transient in most cases. The exact relationship between the persistence of the rearrangement and the occurrence of secondary leukaemia remains to be determined.

Anthracyclines↗
PubMed2001

Magnetic resonance imaging of femoral marrow cellularity in hypocellular haemopoietic disorders.

AIM: Magnetic resonance imaging (MRI) of the femora was used to investigate the marrow cellularity during the evolution of non-transplanted aplastic anaemia (AA) and hypocellular myelodysplastic syndrome (h-MDS) in order to investigate the relationship between this cellularity and disease progression. METHODS: Magnetic resonance imaging was performed in adult patients with pancytopaenia and hypocellular bone marrow. Coronal T1 weighted and STIR images were obtained, and analysed semiquantitatively. These data were compared with diagnosis, peripheral blood counts and bone marrow histology at diagnosis and at the time of the MRI examination. RESULTS: Patients were examined 2-84 months after diagnosis (median, 16 months). In AA, 11/13 patients showed a fatty, faint or nodular pattern. In h-MDS, the majority of the patients (10/14) had a scattered or uniform signal pattern. In AA, a significant correlation was found between the degree of femoral cellularity and disease duration. Only three cases had diffuse high signal on STIR: among them, one had paroxysmal nocturnal haemoglobinuria and the other developed acute leukaemia 3 months after MRI examination. Four patients have died: three with h-MDS presenting a scattered (two cases) or a uniform (one case) MRI signal and one with AA (with a nodular pattern) CONCLUSION: In AA, femoral haemopoiesis is usually not pronounced, and if present, does not contribute to the improvement of blood counts. In h-MDS, patients with discrete femoral haemopoiesis had an improvement in their blood counts with disease duration, similar to that found in AA. Conversely, in patients with pronounced femoral cellularity, blood counts remained stable or had deteriorated since diagnosis. This favours the hypothesis that, as is observed in MDS with a hypercellular marrow, scattered or uniform marrow patterns in femoral MRI are signs of more aggressive disease.

Adolescent↗
PubMed2000

Conventional chemotherapy for acute myeloid leukemia: a Brazilian experience.

CONTEXT: Young patients affected by acute myeloid leukemia (AML) achieve complete remission (CR) using conventional chemotherapy in about 55-85%. However, 30% of patients fail to achieve CR and the remission duration is often only about 12 months. More intensive treatment after CR seems to be necessary in order to maintain CR and obtain a definitive cure. In Brazil, few reports have been published on this important subject. OBJECTIVE: The aim of this study was to describe a Brazilian experience in the treatment of "de novo" acute myeloid leukemia (AML) in younger adult patients (age < 60 years). DESIGN: Retrospective analysis. SETTING: University Hospital, Hematology and Hemotherapy Center, State University of Campinas, Brazil. PARTICIPANTS: Newly diagnosed cases of "de novo" AML in the period from January 1994 to December 1998 were evaluated retrospectively, in relation to response to treatment, overall survival (OS) and disease free survival (DFS). Cases with acute promyelocytic leukemia (APL) were also included in this analysis. RESULTS: On the basis of an intention to treat, 78 cases of AML, including 17 cases of APL, were evaluated. The overall median follow-up was 272 days. The complete remission (CR) rate was 63.6% in the AML group (excluding APL) and 78% in the APL group. The 5-year estimated disease-free survival (DFS) was 80% for the APL group and 34% for the AML group (P = 0.02). The 5-year estimated overall survival (OS) was 52% for the APL group and 20.5% for the AML group, respectively (P = NS). Relapse was observed in 12/39 (30.7%) patients with AML and 1/11 (9%) with APL. CONCLUSIONS: These results are similar to those reported in the literature. However, relapse and mortality rates remain high, and a search for more aggressive strategies in order to prevent relapse is recommended.

Acute Disease↗
PubMed2000

Nucleolus organizer regions (AgNORs) and total tumor mass are independent prognostic parameters for treatment-free period in chronic lymphocytic leukemia.

The aim of our study was to evaluate whether the nucleolus organizer regions (AgNOR) of circulating lymphocytes in chronic lymphocytic leukemia (CLL) could predict the duration of the stable phase (treatment-free period) of this disease. Age, sex, peripheral lymphoctes, hemoglobin, platelet count, Binet's stage, total tumor mass (TTM) and AgNOR pattern at diagnosis were assessed in 57 patients and compared with the time from diagnosis until patients fulfilled the criteria to start chemotherapy. In univariate Cox regression, Binet's stage, hemoglobin, number of peripheral lymphocytes, TTM and the percentage of lymphocytes containing one AgNOR cluster (circulating proliferative fraction) had predictive value. In the multivariate Cox model, only TTM and the percentage of cells with one AgNOR cluster were independent factors predicting the duration of the stable phase. Repetition of these analyses in 500 data sets created by bootstrap resampling confirmed the results. Summing up the percentage of lymphocytes with an AgNOR cluster and the TTM value, a simple prognostic index could be created to give information about the duration of the stable phase in CLL.

Cell Division↗
PubMed2000

Vanishing bile duct syndrome in Hodgkin's disease: case report.

CONTEXT: Liver damage is relatively common in patients affected by Hodgkin's disease. A smaller proportion of cases develops jaundice. Recently, the vanishing bile duct syndrome was described in Hodgkin's disease. The mechanisms of this severe complication have been poorly understood until now. OBJECTIVE: To describe a rare case of intra-hepatic cholestasis due to vanishing bile duct syndrome. DESIGN: Case report. CASE REPORT: A 38-year-old male patient affected by Hodgkin's disease. Liver biopsy showed no detectable Hodgkin's disease. Intra-hepatic cholestasis was found and none of the six portal tracts analyzed contained normal bile ducts. The treatment was based on conventional and high-dose escalation chemotherapy. The patient died from an irreversible liver failure while in complete remission from Hodgkin's disease.

Adult↗