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E Matutes

Publications and source records attributed to E Matutes.

At least 73 records · Page 4Linked to original sources
PubMed1999

The incidence of trisomy 3 in splenic lymphoma with villous lymphocytes: a study by FISH.

Splenic lymphoma with villous lymphocytes (SLVL) is a low-grade B-cell lymphoproliferative disorder characterized by splenomegaly and circulating villous lymphocytes. The relationship between SLVL and splenic marginal zone lymphoma (SMZL), a disorder with identical splenic histology to SLVL, is not clear. Previous studies have failed to show a consistent karyotypic abnormality in SLVL whereas trisomy 3 has been reported in patients with SMZL. The presence of trisomy 3 in SMZL and its absence in SLVL has been viewed as evidence that these are different diseases. However, it is possible that the frequency of trisomy 3 in SLVL has been underestimated because previous studies have relied on conventional cytogenetics. We have therefore used interphase fluorescence in situ hybridization (FISH) to re-assess the frequency of trisomy 3 in SLVL. We studied 70 patients, who were stratified into four groups according to the percentage of circulating villous lymphocytes. Trisomy 3 was found overall in 17% of patients. In particular, trisomy 3 was detected in 13% of cases with >50% of villous lymphocytes and which were considered typical of SLVL. In conclusion, we have demonstrated that some patients with SLVL have circulating cells with trisomy 3, which does not support the view that SLVL and SMZL are different diseases on the basis of the incidence of trisomy 3.

Aged↗
PubMed1999

Long-term follow-up of patients with hairy cell leukaemia after treatment with pentostatin or cladribine.

We report the long-term follow-up results on two groups of patients with hairy cell leukaemia (HCL) treated with either pentostatin (deoxycoformycin) or cladribine (2-chlorodeoxyadenosine). 165 HCL patients received treatment with pentostatin (between 1986 and 1994), and 45 were treated with cladribine (between 1992 and 1997). Age and sex characteristics were similar in the two groups. 38 patients in the pentostatin group and 12 in the cladribine group were previously untreated. 22 patients in the cladribine group had received prior treatment with pentostatin; four were resistant, 17 had relapsed following partial (four) or complete (13) responses, and one was not evaluable for response. The response rates were the same in the two groups: 82% complete response (CR), 15% partial response (PR) for pentostatin and 84% CR, 16% PR for cladribine. Relapse rates were 24% for pentostatin and 29% for cladribine after median follow-up of 71 and 45 months respectively. At 45 months, however, the relapse rate for pentostatin was only 9.7%. We found a statistically significant difference in the disease-free interval (DFI) between the two groups suggesting that patients may relapse more quickly after cladribine. The majority of relapsed patients achieved second remissions following further therapy with either pentostatin or cladribine, with no evidence of cross resistance between the two agents. The 5-year survival for all patients was 97% and treatment- related toxicity was low. We conclude that both pentostatin and cladribine induce durable remissions in the majority of HCL patients. Longer follow-up is required to establish whether some patients are cured as there is no plateau in DFI, and which of these two agents may be the treatment of choice.

Adult↗
PubMed1999

HTLV-I induced intestinal lymphoma.

We document an unusual case of HTLV-I positive adult T-cell leukaemia lymphoma (ATLL) in a 25 year old Chilean patient who presented with primary small intestinal involvement and during evolution developed a leukaemic phase. Duodenal biopsy showed infiltration by pleomorphic lymphoid cells with a CD45RO+ CD20- phenotype. Circulating lymphocytes had a convoluted nucleus and displayed a mature T-cell phenotype: CD2+, CD3+, CD4+, CD8-, CD25+, HLA-Dr+. HTLV-I serology was positive and HTLV-I retroviral sequences were demonstrated by PCR in the tissue. The patient was treated with chlorambucil and is well, disease free five years from diagnosis. Intestinal lymphoma as initial manifestation of ATLL is extremely uncommon, but when a T-cell lymphoma is detected in this localisation, in patients from a HTLV-I endemic area, retroviral studies are recommended in order to exclude an association with this retrovirus.

Adult↗
PubMed1999

Effect of lamivudine on human T-cell leukemia virus type 1 (HTLV-1) DNA copy number, T-cell phenotype, and anti-tax cytotoxic T-cell frequency in patients with HTLV-1-associated myelopathy.

Patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) typically have a high HTLV-1 proviral load in peripheral blood mononuclear cells and abundant, activated HTLV-1-specific cytotoxic T lymphocytes (CTLs). No effective treatment for HAM/TSP has been described so far. We report a 10-fold reduction in viral DNA for five patients with HAM/TSP during treatment with the reverse transcriptase inhibitor lamivudine. In one patient with recent-onset HAM/TSP, the reduction in viral DNA was associated with a fall in the frequency of CTLs specific to two peptides in the immunodominant viral antigen Tax. The half-life of peripheral blood mononuclear cell populations was estimated from changes in viral DNA copy number, CTL frequency, reduction in CD25 expression, and the loss of dicentric chromosomes following radiation-induced damage. Each of these four different techniques indicated a cellular half-life of approximately 3 days consistent with continuous lymphocyte replication and destruction. These results indicate that viral replication through reverse transcription significantly contributes to the maintenance of HTLV-1 viral DNA load. The relative contribution of proliferation versus replication may vary between infected people.

Adult↗
PubMed1999

High dose methyl prednisolone in refractory chronic lymphocytic leukaemia.

We treated 14 patients with advanced, resistant chronic lymphocytic leukaemia (CLL) including three with >10% prolymphocytes (CLL/PL) with high dose methyl prednisolone (HDMP). All patients had stage C CLL or bulky stage B disease. There were 11 males and 3 females with a median age of 58.5 years (range: 49-69). Six out of eleven CLL patients had a partial response as defined by the NCI guidelines, no patient had a complete remission. The mean duration of PR was 19.6 months with a median of 8 months (range 6-78). Seven patients have died including the 5 non-responders. None of the 3 patients with CLL/PL had a measurable response. Previous treatments included chlorambucil, fludarabine, deoxycoformycin, anthracycline containing regimens such as CHOP and Campath-1H. HDMP was given at a dose of 1 g/m2 for five days, at monthly intervals for one to seven courses depending on the response. H2 antagonists and antimicrobial prophylaxis were given concurrently. Acyclovir prophylaxis was given if there was a recent history of herpes infection. HDMP was generally well tolerated. Side effects included fluid retention, hyperglycaemia, bradycardia (1 patient), herpes simplex (1), and pneumonia (1) in a patient with a previous history of recurrent chest infection and pneumonia. These results suggest that HDMP may be beneficial in the treatment of refractory CLL but is of no value in CLL/PL.

Aged↗
PubMed1999

Acute erythroid leukemia (M6): outcome of bone marrow transplantation.

Erythroid leukemia is an uncommon form of acute myeloid leukemia (AML) which has previously been associated with a poor prognosis. We present the outcome of 27 patients with AML-M6 (19 de novo and 8 secondary) treated with intensive regimens including bone marrow transplantation (BMT). In the de novo group, median age was 30 years (2-72); 5 cases were under 15 years. Remission rate after induction chemotherapy was 95%. Consolidation in those achieving remission with BMT was 82%. Transplant related mortality was 36%. Median survival for de novo M6 was 2.9 years which was not significantly different to matched controls with AML (non M6). Overall relapse rate was 35%. In contrast, patients with secondary disease had a poor prognosis with lower remission rates (57%) and higher relapse rates (75% of those achieving remission after induction chemotherapy). In our series, the prognosis of patients with AML-M6 was most closely related to age and disease status at presentation (de novo or secondary). The disease is sensitive to AML induction regimens and long-term survival can be achieved with BMT in first complete remission.

Adolescent↗
PubMed1999

Splenic lymphoma with circulating villous lymphocytes/splenic marginal-zone lymphoma.

Splenic lymphoma with villous lymphocytes (SLVL) represents a low-grade B-cell non-Hodgkin's lymphoma (NHL) that histologically is indistinguishable from splenic marginal-zone lymphoma (SMZL). Characteristic features of SLVL are splenomegaly, moderate lymphocytosis, nodular and intrasinusoidal pattern of bone marrow infiltration, serum monoclonal band, slow benign course, and response to splenectomy. The diagnosis is made by the morphology of the circulating villous cells and their immunophenotype, which is distinct from that of chronic lymphocytic leukemia (CLL) and hairy-cell leukemia (HCL), diseases with which SLVL may be confused. When treatment is indicated, splenectomy is the treatment of choice, but some patients may require additional chemotherapy to control progression. In those circumstances, fludarabine may be the agent of choice. Despite its unique features, which, compounded, suggest that SLVL is a clinicopathologic entity, there are no specific chromosome abnormalities and problems of differential diagnosis with other B-cell NHLs, chiefly mantle-cell lymphoma (MCL), remain in a minority of patients.

Humans↗
PubMed1999

Quantitative analysis of CD79b, CD5 and CD19 in mature B-cell lymphoproliferative disorders.

BACKGROUND AND OBJECTIVE: Distinction between B-cell chronic leukemias can be difficult due to overlap in cell morphology and immunologic features. We investigated, by quantitative flow cytometry, the expression of CD79b, CD5 and CD19 in cells from a variety of B-cell disorders to see whether this analysis adds further information useful to the diagnosis and characterization of these diseases. DESIGN AND METHODS: Peripheral blood cells from 6 normal individuals were used as reference controls. The diseases of the 63 patients investigated comprised: 29 chronic lymphocytic leukemia (CLL), six of them with atypical morphology, 6 B-cell prolymphocytic leukemia (PLL), 12 splenic lymphoma with villous lymphocytes (SLVL) and 16 mantle-cell (Mc) lymphoma in leukemic phase. The study was carried out by triple immunostaining with directly conjugated monoclonal antibodies (MoAb) against CD79b, CD5 and CD19 and quantitative estimation of the antigens per cell assessed with standard microbeads (Quantum Simply Cellular). RESULTS: Compared to normal B-cells, the number of CD19 molecules was significantly lower in cells from all of the B-cell disorders except PLL. The intensity of CD5 in leukemic B-cells was significantly higher in CLL cells, including atypical cases, and Mc lymphoma than in normal B-cells, whilst PLL and SLVL had values similar to those of normal B-lymphocytes. CD79b was expressed at lower levels in all types of leukemic cells compared to normal B-lymphocytes but differences were statistically significant in CLL, Mc lymphoma and SLVL. The number of CD79b molecules per cell was significantly lower in typical CLL than in the remaining B-cell diseases whilst the comparison of CD5 and CD19 intensity between CLL and non-CLL samples failed to show any statistically significant difference. INTERPRETATION AND CONCLUSIONS: Distinct antigen density patterns for the various conditions emerged from this analysis: Typical CLL was characterized by moderate CD5 and weak or negative CD79b expression. Mc lymphoma showed an homogeneous pattern, characterized by similar expression of CD5 than CLL but significantly stronger expression of CD79b whilst PLL and SLVL had weak CD5 and moderate CD79b expression. Atypical CLL had an intermediate pattern of CD79b antigen expression ranging from weak to moderate with bright CD5. Unlike CD5 and CD79b, CD19 did not discriminate the various B-cell disorders but only between normal and leukemic cells.

Antigens, CD↗
PubMed1999

Outcome of biphenotypic acute leukemia.

BACKGROUND AND OBJECTIVE: Although biphenotypic leukemia is now a defined entity, outcome of this rare form of acute leukemia has not been well documented. We present the first comprehensive study analyzing induction and consolidation therapy of biphenotypic leukemia and correlate outcome to prognostic factors. DESIGN AND METHODS: In this retrospective study, the incidence of biphenotypic leukemia was found to be 3.6% from 693 adult and pediatric acute leukemias referred to our center for treatment over the last 8 years. Of these, 15 were B-lymphoid/myeloid, 8 were T-lymphoid/myeloid, one was T/B lymphoid and one had trilineage differentiation. RESULTS: Induction of remission in de novo cases was achieved in 70% of patients and relapse of disease occurred in 15%. The use of combined lymphoid and myeloid drugs for induction resulted in a high incidence of early deaths (25%). The overall probability of survival at 2 years was 39.4%. Patients with secondary disease had a uniformly poor outcome with low remission rates and high relapse rates. INTERPRETATION AND CONCLUSIONS: Prognosis was most strongly related to the presence of the Philadelphia chromosome (p=0.03) and age under 15 years (p=0.01). We conclude that patients with biphenotypic leukemia should have risk stratification with treatment tailored to their prognostic factors.

Acute Disease↗
PubMed1999

Impact of immunophenotyping on management of acute leukemias.

BACKGROUND AND OBJECTIVE: The diagnosis of acute leukemias (AL) requires a multiparametric approach in order to apply risk-adapted therapeutic protocols and appreciate the potential outcome of any given patient. Blast cells immunophenotyping is a key test in this issue, yet the information provided by immunophenotyping has become staggering, and it may be difficult to identify relevant characteristics clearly. This manuscript provides a critical review of the literature regarding the importance of immunophenotyping in acute leukemia diagnosis and management. DATA SOURCES AND METHODS The information given here is based on the experience of the authors, on their literature files and on additional material retrieved through articles and reviews covered by the Institute for Scientific Information (ISI) and the Medline database. Studies with proper definition of the patients and sufficient information regarding follow-up were considered. RESULTS: Immunophenotyping allows an early confirmation of AL diagnosis and establishes lineage assignment. Adequate and comprehensive panels of monoclonal antibodies also allow detection of aberrant immunophenotypic profiles of prognostic value or of use in detecting minimal residual disease. A number of unusual immunophenotypic features are also associated with prognosis. The development of new antibodies, new insights in the functional properties of differentiation antigens, and the quantimetric approach of immunophenotyping will keep this field changing. Moreover, as therapeutic protocols evolve, some earlier results need to be reconsidered. INTERPRETATION AND CONCLUSIONS: Immunophenotyping, together with cytologic, karyotypic and molecular approaches, retains a crucial place in the diagnosis and management of acute leukemias. It remains a rather specialized approach and should be interpreted in a multidisciplinary perspective, considering for each patient the idiosyncrasies possibly relevant to prognosis.

Acute Disease↗
PubMed1999

[Adult T cell leukemia lymphoma in Chile. A clinical pathologic and molecular study of 26 patients].

BACKGROUND: Adult T cell leukemia lymphoma is a lymphoproliferative syndrome etiologically associated to human T cell lymphotropic virus type I. AIM: To describe the clinical and laboratory features of 26 Caucasian Chilean patients, with HTLV-I positive adult T-cell leukemia lymphoma (ATLL). MATERIAL AND METHODS: Diagnostic criteria included clinical features, cell morphology, immunophenotype, HTLV-I serology and/or DNA analysis by Southern blot or PCR. RESULTS: According to the clinical presentation, 12 cases had the acute ATLL form, 6 had a lymphoma, 4 the chronic form and 4 had smoldering ATLL. The median presentation age was 50 years, younger than the Japanese patients, but significantly older than patients from other South American countries (e.g. Brasil, Jamaica, Colombia). The main clinical features: lymphadenopathy, skin lesions and hepatosplenomegaly, were similar in frequency to those of patients from other countries, except for the high incidence of associated neurological disease. Tropical Spastic Paraparesis (TSP) in our series of ATLL, was seen in one third of the patients (8/26). A T-cell immunophenotype was shown in all 26 cases and HTLV-I serology was positive in 25/26 patients. Molecular analysis on the seronegative patient showed clonal integration of proviral HTLV-I DNA into the lymphocytes DNA, and thus he may have been a poor responder to the retroviral infection. Proviral DNA integration was also demonstrated in 15/16 patients being clonal in 10, polyclonal in 3 (all smoldering cases) and oligoclonal in one. CONCLUSIONS: ATLL in Chile has similar clinical and laboratory features than the disease in other parts of the world, except for a younger age than Japanese patients but older than those from other Latin American countries and a high incidence of patients with associated TSP. Detailed morphological and immunophenotypic analysis of the abnormal circulating lymphocytes, together with the documentation of HTLV-I by serology and/or DNA analysis are key tests for the identification of this disease.

Acute Disease↗
PubMed1998

The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL).

We document findings on c-kit (CD117) expression in 1,937 pediatric and adult de novo acute leukemia cases, diagnosed in five single European centers. All cases were well characterized as to the morphologic, cytochemical, and immunologic features, according to the European Group for the Immunological Classification of Leukemias (EGIL). The cases included 1,103 acute myeloid leukemia (AML), 819 acute lymphoblastic leukemia (ALL), 11 biphenotypic acute leukemia (BAL), and 4 undifferentiated (AUL). c-kit was expressed in 741 (67%) AML cases, regardless of the French-American-British (FAB) subtype, one third of BAL, all four AUL, but only in 34 (4%) of ALL cases. The minority of c-kit+ ALL cases were classified as: T-cell lineage (two thirds), mainly pro-T-ALL or T-I, and B lineage (one third); cells from 62% of these ALL cases coexpressed other myeloid markers (CD13, CD33, or both). There were no differences in the frequency of c-kit+ AML or ALL cases according to age being similar in the adult and pediatric groups. Our findings demonstrate that c-kit is a reliable and specific marker to detect leukemia cells committed to the myeloid lineage, and therefore should be included in a routine basis for the diagnosis of acute leukemias to demonstrate myeloid commitment of the blasts. c-kit expression should score higher, at least one point, in the system currently applied to the diagnosis of BAL, as its myeloid specificity is greater than CD13 and CD33. Findings in ALL and AUL suggest that c-kit identifies a subgroup of cases, which may correspond to leukemias either arising from early prothymocytes and/or early hematopoietic cells, both able to differentiate to the lymphoid and myeloid pathways.

Acute Disease↗
PubMed1998

Molecular cytogenetic analysis in splenic lymphoma with villous lymphocytes: frequent allelic imbalance of the RB1 gene but not the D13S25 locus on chromosome 13q14.

Structural abnormalities of chromosome 13q are one of the most frequent genetic aberrations in human tumors. 13q rearrangements are, however, infrequent in splenic lymphoma with villous lymphocytes (SLVL) by karyotype analysis. We have investigated the incidence of 13q14 deletions in a series of 74 SLVL cases by interphase fluorescence in situ hybridization using unique sequence probes for the RB1 and the D13S25 loci, which are frequently deleted in chronic lymphocytic leukemia. Chromosome 12 was also evaluated by fluorescence in situ hybridization using a pericentromeric DNA probe. 13q14 deletion was detected in 37 of 74 (50%) tumors. Thirty-five cases (47%) exhibited monoallelic loss of RB1, and 9 (12%) showed hemizygous D13S25 deletion. Seven cases displayed coexistence of RB1 and D13S25 deletion. Trisomy 12 was detected in 2 of 74 (3%) tumors. G-banding analysis in 40 tumors showed no interstitial deletion of 13q14 in any case. In contrast with the molecular findings observed in chronic lymphocytic leukemia, our results indicate that trisomy 12 is an uncommon chromosomal aberration in SLVLs, and microdeletion of 13q14 at the RB1 locus but not D13S25 is a frequent and specific genetic event in this disease, suggesting that allelic loss of the RB1 gene may play a role in the pathogenesis of SLVL.

Aged↗
PubMed1998

Establishing a KSHV+ cell line (BCP-1) from peripheral blood and characterizing its growth in Nod/SCID mice.

Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) sequences are present in primary effusion lymphomas (PEL). KSHV+ cell lines have been established from such lymphomas. Here we report the first description of the establishment of a KSHV+, EBV- cell line (BCP-1) from the peripheral blood of a patient with PEL. Using this cell line and a KSHV+, EBV+ PEL cell line (HBL-6) previously established from ascitic fluid, we investigated whether in nonobese diabetic/severe combined immunodeficiency disease (Nod/SCID) mice tumors representing PEL can be established. When injected intravenously (IV) into Nod/SCID mice, BCP-1 and HBL-6 infiltrated organs, with only occasional macroscopic tumor formation. Intraperitoneal injections (ip) led to the development of ascites and diffuse infiltration of organs, without obviously solid lymphoma formation, resembling the diffuse nature of human PEL. To investigate a possible mechanism for the peculiar phenotype of PEL, we examine the presence of adhesion molecules and homing markers on PEL cells before and after growing in mice. Both BCP-1 and HBL-6 cells lack expression of important cytoadhesion molecules including CD11a and CD18 (LFA1 alpha and beta chains), CD29, CD31, CD44, CD54 (ICAM-1), and CD62L and E (L and E selectins).

Animals↗
PubMed1998

ATM is usually rearranged in T-cell prolymphocytic leukaemia.

T-prolymphocytic leukaemia (T-PLL) is a rare, sporadic leukaemia similar to a mature T-cell leukaemia seen in some patients with Ataxia Telangiectasia (A-T), a recessive multisystem disorder caused by mutations of the ATM gene at chromosome 11q23. ATM sequence mutations have been reported in 46% of T-PLL cases, but some cases also have karyotypic abnormalities at 11q, including 11q23. This led us to investigate the structure of the ATM locus in a panel of eight cases, two of which had 11q23 abnormalities. As expected, nucleotide changes were detected in some samples. Two remission samples were wild type. To test for structural lesions, DNA fibres were hybridized with a contig of four labelled cosmids spanning the ATM locus. In all samples there were structural lesions and in four samples both alleles were affected. This provides strong evidence for our suggestion that ATM acts as a tumour suppressor during T-PLL tumorigenesis. Some additional role for ATM during T-PLL tumorigenesis is possible since nucleotide changes were present in addition to structural lesions disrupting both alleles. The mechanism of inactivation appeared to be unusual because multiple structural lesions on one allele were often observed.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1998

Levels of expression of CD52 in normal and leukemic B and T cells: correlation with in vivo therapeutic responses to Campath-1H.

The CD52 antigen is expressed on most normal and neoplastic lymphoid cells. The reshaped humanized IgG1 anti-CD52 monoclonal antibody (Campath-1H) has been used in the treatment of hemopoietic and non-hemopoietic diseases for its ability to induce lymphocyte depletion both in vitro and in vivo. Good activity has been shown in patients with chronic T and B cell leukemias, in particular T-prolymphocytic leukemia (T-PLL). However, the response to treatment is not uniform and this variability may depend on differences in the level of antigen expression on the leukemic cells. To test this hypothesis, we used quantitative flow cytometry to investigate the intensity of the expression of CD52 in 45 cases of lymphoid leukemia, 24 with B-cell chronic lymphocytic leukemia (CLL), 21 with T-PLL and 12 normal controls. Normal T lymphocytes expressed higher CD52 antigen than B lymphocytes (p < 0.005) and the antigen was also significantly higher in T-PLL compared to CLL (p < 0.001). Moreover, the differences in CD52 expression were somewhat higher in Campath-1H treated patients who responded than in non responders. Although other factors may play a role in the response to Campath-1H in vivo, the quantitative estimation of CD52 expression may provide a rationale for the greater response in T-PLL and help select those patients with a higher probability of responding to this therapy.

Alemtuzumab↗