Biomedical subjects

E Matutes

Publications and source records attributed to E Matutes.

At least 163 records · Page 9Linked to original sources

PubMed1994

The histopathology of splenic lymphoma with villous lymphocytes.

Whereas the hematologic, immunophenotypic, and molecular characteristics of splenic lymphoma with villous lymphocytes (SLVL) have been well documented, the histologic features of the spleen and lymph nodes remain uncharacterized. We have reviewed the histopathology of the spleen in 37 cases of SLVL and of involved splenic hilar lymph nodes in 6 cases. Tissue immunophenotyping was performed in 24 cases, 6 of which had frozen tissue available, and the results were compared with the membrane immunophenotype of the circulating villous lymphocytes and cells extracted from spleen and lymph nodes. In the spleen, SLVL is characterized by involvement of the white pulp follicles, which may be surrounded or replaced by the lymphoma cells. In the red pulp, the cells form small nodules and infiltrate diffusely with sinusoidal invasion. The cytologic appearance of the neoplastic cells varies from a resemblance to small mantle-zone--like lymphocytes to that of marginal-zone cells and there are scattered blast forms. In involved lymph nodes, the infiltrate again centers on the follicles that are usually replaced, but occasionally show preservation of follicle centers; sinuses are often preserved. The tissue immunophenotype is similar to that of marginal-zone B cells. Membrane immunophenotyping may give different results in some cases and may vary depending on the compartment from which the cells are obtained. SLVL in the peripheral blood is a histologically homogeneous entity identical to the condition previously characterised by histopathologists as splenic marginal-zone lymphoma.

Adult↗

PubMed1994

Adult T-cell leukemia/lymphoma: a working point-score classification for epidemiological studies.

Adult T-cell leukemia/lymphoma (ATL) is a malignancy that occurs most frequently in south-western Japan and the Caribbean basin. The primary etiologic agent for this disease, human T-lymphotropic virus type I (HTLV-I), is endemic in these areas. Only a small percentage of individuals infected with HTLV-I develop ATL. The factors that determine the development of malignant disease as an outcome of HTLV-I infection in an individual are unknown. ATL is histopathologically heterogeneous and firm diagnosis is made on the contribution of clinical, laboratory and histopathologic features. The wide variety of laboratory assays available to geographically diverse populations has led to a need to standardize the criteria for determining the diagnosis of this disease for epidemiologic studies. This report summarizes current information regarding ATL and proposes a classification facilitating comparison of case series in geographically and ethnically different populations.

Adult↗

PubMed1994

Splenic lymphoma with villous lymphocytes: analysis of BCL-1 rearrangements and expression of the cyclin D1 gene.

The translocation t(11;14)(q13;q32) occurs in about 15% of patients with splenic lymphoma with villous lymphocytes (SLVL) or the closely related disorder lymphoplasmacytic lymphoma (LPL). To characterize the nature and frequency of rearrangements of the BCL-1 locus in SLVL/LPL and to document the effect of these genetic alterations on the expression of the cyclin D1 gene, we analyzed 22 cases of SLVL/LPL with defined cytogenetic abnormalities by both conventional electrophoresis (CE) and pulse-field gel electrophoresis (PFGE) and by Northern blotting. Four SLVL/LPL cases showed rearrangement of the BCL-1 locus. In two cases with t(11;14)(q13;q32), different breakpoints were identified; one mapped adjacent to the major translocation cluster (MTC) and the other within a 28-kb region telomeric of it. In a third case of SLVL with no cytogenetic abnormality of 11q13, a novel breakpoint approximately 100 kb centromeric of MTC was detected by PFGE. The fourth case, which had a normal karyotype, demonstrated rearrangement with a BCL-1 probe immediately telomeric of MTC. This case may have had a small deletion of 0.5 kb from within the BCL-1 locus. No rearrangement of the BCL-1 locus or within the cyclin D1 gene was detected by CE or PFGE in any of the remaining 18 SLVL/LPL samples. Northern blot analysis showed expression of a normal-sized cyclin D1 transcript in the two SLVL/LPL cases with t(11;14)(q13;q32). In cases that lacked a cytogenetically demonstrable t(11;14) translocation, no cyclin D1 transcript was detected. Analysis of the BCL-1 locus was also performed in three other cases of B-cell disorders with t(11;14)(q13;q32) detected cytogenetically. Two cases were analyzed by Southern blot and showed rearrangement of the BCL-1 locus. Expression of high-level normal-sized and/or truncated cyclin D1 transcript was also detected in these cases. These data show the importance of PFGE in the detection of rearrangements in the BCL-1 locus and show further the complexity of rearrangements in this locus.

Chromosomes, Human, Pair 11↗

PubMed1994

BCL2 translocations in leukemias of mature B cells.

Although translocations of the BCL2 gene are frequent in B-cell non-Hodgkin's lymphomas (B-NHL) the incidence, nature, and prognostic significance of similar translocations in the phenotypically related chronic leukemias of mature B cells are unknown. Therefore, we examined 170 cases of B-cell chronic lymphocytic leukemia (B-CLL), 7 cases of B-cell prolymphocytic leukemia (B-PLL), 25 cases of hairy cell leukemia (HCL) and 22 cases of splenic lymphoma with villous lymphocytes (SLVL) with defined cytogenetic abnormalities by DNA blot using both 5' and 3' BCL2 probes to search for rearrangement of the BCL2 locus. Translocation t(14;18) (q32.3;q21.3) was detected cytogenetically in 3 cases of B-CLL. All had breakpoints in the 3' region of BCL2, mapping between the major breakpoint region (MBR) and the minor cluster region (mcr), the breakpoint clusters commonly detected in B-NHL. In 2 of the 3 cases, the breakpoint within BCL2 was mapped to a 1.0-kb EcoRI-HindIII fragment indicating a clustering of breakpoints. Two cases of B-CLL had cytogenetically detectable t(2;18)(p11;q21.3) or t(18;22)(q21.3;q11). Both had rearranged the 5' region of the BCL2 gene to the corresponding lg light-chain gene. Molecular cloning of the t(18;22)(q21.3;q11) showed that the translocation disrupted the BCL2 promoter region and the first untranslated BCL2 exon. Nevertheless, high levels of BCL2 protein were seen in this case. Only 2 other cases in whom cytogenetic analysis was not successful showed rearrangement of the 5' region of BCL2, an overall incidence of 2.3%. No cases of B-PLL, HCL, or SLVL showed either 5' or 3' BCL2 rearrangement. These data confirm the cytogenetic observations that translocations involving the BCL2 locus in all forms of leukemia of mature B cells are rare, and limited to a minor subset of B-CLL. BCL2 translocations in B-CLL involve hot spots of recombination of both the 5' and 3' regions of the BCL2 gene, which are distinct from those commonly seen in B-NHL, suggesting distinct pathogenic mechanisms.

Aged↗

PubMed1994

The immunophenotype of splenic lymphoma with villous lymphocytes and its relevance to the differential diagnosis with other B-cell disorders.

Splenic lymphoma with villous lymphocytes (SLVL) is a low-grade disorder that regularly presents with peripheral blood involvement. We describe the immunophenotype of the circulating cells from 100 SLVL patients whose disease has been characterized on clinical, morphologic, and histologic grounds. Cells from all cases expressed B-cell antigens (CD19 and CD37) and/or HLA-Dr and showed light chain restriction (kappa/lambda: 1.5/1) with moderate to strong intensity of membrane Ig staining. Cells from most cases (> 80%) were CD24+, FMC7+, and expressed strongly membrane CD22. The monoclonal antibodies CD10, CD23, and CD38 were positive in one-third of the cases; CD11c in 47%; and CD25 in 25% of cases. A minority of cases (< 20%) were positive with HC2, B-ly-7, and CD5. However, none of the 19 CD5+ cases had the phenotype characteristic of chronic lymphocytic leukemia (CD5+, CD23+, FMC7-, weak surface Ig and membrane CD22). None of the 17 CD25+ cases had the immunophenotype typical of hairy cell leukemia (CD25+, CD11c+, HC2+, B-ly-7+). HC2 and B-ly-7 were the most useful reagents to distinguish SLVL from hairy cell leukemia. Our findings demonstrate that SLVL has a distinct immunologic profile and that monoclonal antibodies are important for the differential diagnosis between this disease and other B-lymphoproliferative disorders with which SLVL can be confused.

Adult↗

PubMed1994

Chromosome abnormalities in hairy cell leukaemia variant.

We describe chromosome abnormalities in 6 patients with hairy cell leukaemia (HCL) variant, a rare B-cell disorder with clinical and laboratory features intermediate between HCL and B-prolymphocytic leukaemia (B-PLL). All but one had marked splenomegaly and a raised white blood cell count (median 40 x 10(9)/l) with over 80% nucleolated hairy cells. These cells had a B-cell immunophenotype distinct from that of typical HCL. All patients but one are alive with stable disease with a median follow-up of 60 months. Numerical chromosome changes included loss of chromosomes 2, 3, 4, 6, 10, 19, 21, and X. three cases had translocations involving the immunoglobulin gene regions: t(14;17)(q32;q11), t(14;22)(q32;q11), and t(2;8)(p11.12;q24). Immunocytochemistry demonstrated the presence of the MYC protein in cells from the case with t(2;8) but not in two others. Other structural abnormalities included t(3;10)(q27;q22) and t(3;12)(q27;q13) in the same patient, der(17)t(7;10;17)(p11;q27;q22), t(1;3)(q25;p21), t(8;21)(p12;q11), t(17;21)(p11;p11), del(6)(q15), del(7)(q34), and del(14)(q24).

Aged↗

PubMed1994

Acute myelomonocytic leukemia with t(10;11)(p13;q23): heterogeneity of breakpoints at 11q23 and association with recombinase activation.

The human trithorax homolog gene (MLL) is directly involved in over 90% of cases of acute leukemia with abnormalities of 11q23. However, involvement of other genes at 11q23 both centromeric and telomeric of MLL has been identified in different subtypes of leukemia and lymphoma. We describe a case of acute myelomonocytic leukemia (AMML; FAB type M4) with t(10;11)(p13;q23) in which the breakpoint at 11q23 was centromeric to the MLL gene and distinct from the breakpoint seen in promyelocytic leukemias with t(11;17)(q23;q22), thus providing further evidence of heterogeneity of breakpoints in 11q23 in acute leukemia. Rearrangements of immunoglobulin (IG) and T-cell receptor (TCR) genes were also observed, with no immunophenotypic evidence for commitment to the lymphoid lineages, indicating that inappropriate activation of the recombinases may be a feature of this particular variant translocation.

Adult↗

PubMed1994

Persistent polyclonal B-cell lymphocytosis.

We document a case of persistent lymphocytosis in which the characteristic binucleated circulating lymphocytes were shown immunologically to be polyclonal B-cells. Cytogenetic and molecular studies failed to show a clonal population. A review of the literature on this rare condition, persistent polyclonal B-cell lymphocytosis, highlights an association with the female sex, HLA-DR7 antigen, smoking and raised levels of IgM, all of which were present in our patient.

B-Lymphocytes↗

PubMed1994

Trisomy 12 in B-cell chronic lymphocytic leukaemia: assessment of lineage restriction by simultaneous analysis of immunophenotype and genotype in interphase cells by fluorescence in situ hybridization.

We have studied the lineage restriction of trisomy 12 in six patients with B-cell chronic lymphocytic leukaemia (CLL) by simultaneous analysis of immunophenotype and fluorescence in situ hybridization (FISH) signals in single interphase cells. Fresh uncultured cells from each patient were immunophenotyped by the alkaline phosphatase anti-alkaline phosphatase method (APAAP) using monoclonal or polyclonal antibodies and hybridized with a chromosome 12 specific alpha-satellite DNA probe. In all cases trisomy 12 was restricted to the clonal B-cells, kappa positive or lambda positive, whereas T-cells (CD3 positive) and non clonal B-cells had only two chromosome 12 signals. Within the clonal B-cell population a large proportion of cells were disomic for chromosome 12, whilst trisomic cells ranged from 21% to 37%. The absence of trisomy 12 in T-cells and the mosaicism demonstrated in the clonal B-cells suggests that this abnormality is a secondary event during the leukaemic transformation of CLL and develops in an already established neoplastic B-cell population.

Aged↗

PubMed1994

First report of fludarabine in gamma-heavy chain disease.

We describe a case of gamma-heavy chain disease presenting with lymphadenopathy, splenomegaly, lytic lesions and bone marrow infiltration. Chemotherapy with epirubicin, chlorambucil and prednisolone produced a partial remission which lasted 5 months. The patient was then treated with fludarabine. After six courses of fludarabine a good partial remission was achieved which converted to complete remission with disappearance of the monoclonal IgG3 in the ensuing 12 months without further therapy. This response has, so far, been sustained for 2 1/2 years after stopping treatment.

Aged↗

PubMed1994

Demonstration of cytoplasmic and nuclear antigens in acute leukaemia using flow cytometry.

AIMS: To detect cytoplasmic and nuclear antigens using flow cytometry in acute leukaemia and to use this technique for double marker combinations. METHODS: Cytoplasmic staining was carried out in samples from 40 cases of acute leukaemia with monoclonal antibodies against the myeloid antigen CD13, the lymphoid antigens CD3, CD22, mu chain and the enzymes terminal deoxynucleotidyl transferase (TdT) and myeloperoxidase (MPO). The cells were fixed with paraformaldehyde and permeabilised with Tween 20 and Becton Dickinson's FACS lysing solution. Flow cytometry results were compared in the same cases with immunocytochemistry results using the alkaline phosphatase anti-alkaline phosphatase method. RESULTS: The gentle permeabilisation induced by this method permitted preservation of the membrane antigens and the size and morphology of the cells. The results using flow cytometry were comparable with those obtained using immunocytochemistry, with nearly complete concordance in most cases. CONCLUSIONS: This technique is simple, rapid, sensitive and reproducible and it is suitable for double staining procedures, such as nuclear and cytoplasmic, nuclear and membrane, or cytoplasmic and membrane. It therefore provides a powerful tool for extending the use of immunophenotyping for the diagnosis and follow up of acute leukaemia. It could also be used for the investigation of minimal residual disease.

Acute Disease↗

PubMed1994

The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype.

PURPOSE: To assess the results of treatment with the purine analog 2'deoxycoformycin (pentostatin [DCF]) in patients with postthymic T-cell malignancies. PATIENTS AND METHODS: One hundred forty-five patients with postthymic T-cell malignancies were given DCF intravenously at 4 mg/m2/wk for the first 4 weeks and then every 2 weeks until maximal response; the last 30 patients received weekly injections until maximal response. RESULTS: The overall response rate was 32% (complete responses [CRs] plus partial responses [PRs]), with marked variation according to diagnosis. The best responses occurred in patients with Sézary syndrome (62%) and T-prolymphocytic leukemia (T-PLL) (45%), with CRs in three of 16 Sézary syndrome and five of 55 T-PLL patients. In contrast, no responses (NRs) were documented in 13 patients with other types of cutaneous T-cell lymphoma, including five mycosis fungoides. Two of five patients with large granular lymphocyte (LGL) leukemia had a CR and two of four with Sézary cell leukaemia had a PR. A low response rate was observed in 27 patients with peripheral T-non-Hodgkin's lymphoma (T-NHL) (19%) and in 25 with adult T-cell leukemia/lymphoma (ATLL) (12%). The latter included two CRs and one PR. Toxicity was low and DCF was generally well tolerated. No significant differences were observed when results were analyzed according to previous treatment. Disease subtype was the most important factor to influence results. CONCLUSION: We conclude that DCF is effective as a single agent in T-PLL, Sézary syndrome, and LGL leukemia, but has low activity in other T-cell disorders.

Adult↗

PubMed1994

The value of scoring systems for the diagnosis of biphenotypic leukemia and mature B-cell disorders.

We describe the value of three scoring systems for the characterisation of haemopoietic malignancies. One of the scorings was devised to disclose unusual cases of biphenotypic/mixed lineage acute leukemias and proved to be useful to distinguish such cases from those ALL or AML with aberrant expression of one or two markers of another lineage. The other two scorings aimed respectively: 1) to discriminate between B-CLL from all other B-cell disorders which evolve with leukemia and 2) distinguish between hairy cell leukaemia (HCL), HCL-variant and splenic lymphoma with villous lymphocytes, a group of B-cell diseases with circulating "hairy" lymphocytes. Findings derived from the application of the latter two scoring systems in a large number of cases demonstrated that both provide objective criteria to differentiate between the B-cell conditions studied and that no single marker considered in isolation allows the distinction between the various B-lymphoproliferative disorders.

Acute Disease↗

PubMed1994

Fludarabine in lymphoproliferative disorders: the Royal Marsden Hospital experience.

Fludarabine 25 mg/m2 was given on five consecutive days every four weeks to 85 patients with B- and T-cell malignancies. The median number of courses given was five. All patients except one had received previous chemotherapy. The overall response rate in non-Hodgkin's lymphoma (NHL) was 50% (five complete responses (CR) and 19 partial responses (PR)). The response rate in chronic lymphocytic leukemia (CLL) was 43% (four CR and 12 PR). Responses were seen in all groups of B-cell malignancies, but no T-cell malignancies (n = 4) responded. The median duration of CR has not been reached and the median duration of PR was 14 months for NHL and 16 months for CLL. The median survival from starting fludarabine for patients who achieved a CR or PR in NHL has not been reached and the median duration of PR in CLL was 23 months. The median duration of survival in non-responders was five months. Fludarabine was well tolerated and the main toxicity was myelosuppression. Our results suggest that even in patients who have never responded to any chemotherapy, regardless of the number of treatment regimens previously given, there is a 36% chance of response. In addition, this is the first report of fludarabine activity in Franklin's disease.

Adult↗

PubMed1994

Morphological and immunophenotypical characterization of Japanese B-cell lymphocytic leukemia.

We have analyzed the clinical and laboratory features of 42 patients with B-cell leukemia. Based on the FAB criteria, the cases were classified in 3 groups: I) typical CLL 15, II) atypical CLL 9 which included 6 cases with large cells, and III) B-cell lymphoma in leukemic phase 18. Cases diagnosed as typical CLL (group I) had similar features to those seen in CLL patients from Western countries. The morphology and markers in cases from group III corresponded to B-cell lymphoma in leukemic phase. On the other hand, group II included 3 cases classified as atypical CLL according to FAB criteria. 1 CLL/PL and 2 mixed CLL and 6 cases with rather distinct features, namely: 1) lymphocytosis (42 +/- 41 x 10(9)/l in average) with large mature-looking lymphocytes with abundant cytoplasm: 2) an immunological profile consistent with CLL but, in addition with the consistent expression of CD38; 3) absence of a monoclonal band in the serum and 4) a clinical course and prognosis similar to CLL. Our findings suggest the existence of a B-cell disorder in Japan very close to CLL but distinct from typical and atypical CLL as seen in Western countries. Further studies would clarify whether such an entity is exclusively confined to Japan having a distinct natural history.

Adult↗

PubMed1994

The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL.

We have investigated the role of immunophenotyping in distinguishing between leukemic B-cell lymphoproliferative disorders. Circulating cells from 666 cases were analyzed with a panel of markers by flow cytometry. The diseases included: chronic lymphocytic leukemia (CLL), 400; prolymphocytic leukemia, 22; hairy cell leukemia (HCL), 40; HCL variant, 15; splenic lymphoma with villous lymphocytes, 100; follicular lymphoma, 26; lymphoplasmacytic lymphoma, 25; mantle-cell lymphoma, 20; and large cell lymphoma, 18. On the basis of the most common marker profile in CLL, CD5+, CD23+, FMC7- and weak expression (+/-) of surface immunoglobulin (SmIg) and CD22, we devised a scoring system that gives for each of these five markers a value of 1 or 0 according to whether it is typical or atypical for CLL. Scores range from 5 (typical of CLL) to 0 (atypical for CLL). Application of the scoring system to all the cases showed that 87% of CLL scored 5 and 4 and only 0.4% scored 0 or 1, whereas 89% of other B-cell leukemias and 72% of lymphomas scored 0 or 1; only one case (0.3%) scored 4 and none scored 5 (p < 0.0001). There were no differences between CLL with high and low scores but higher scores were found in cases with more typical morphology (p < 0.0015). Considering each individual marker, there was no single one that distinguished CLL from other diseases, although the most reliable were SmIg intensity and FMC7. The proposed score will facilitate the diagnosis of B-lymphoproliferative disorders and improve their classification.

Antigens, CD↗

PubMed1994

Differential expression of c-myc protein in B and T lymphocytes.

Overexpression of c-myc may play a role in the multistep pathogenesis of B- and T-cell malignancies. To determine whether this expression is inappropriate requires information on the normal cellular counterparts. There is no agreement in the literature on the levels of expression of c-myc mRNA and protein in normal peripheral blood lymphocytes and there are no reports on the differential expression in different lymphocyte populations. The aim of this study was to assess the state of c-myc expression in normal peripheral blood lymphocytes at the single cell level by immunocytochemistry and flow cytometry. Two monoclonal antibodies against c-myc and specific peptide inhibition controls were tested in mononuclear cells from nine healthy volunteers and the HL60 cell line. The expression of c-myc in B- and T-lymphocyte subsets was studied by two-colour immunocytochemistry and flow cytometry. Using calibrated reference standards, we quantified the c-myc protein and results were referred as molecules of equivalent soluble fluorochrome. Almost all lymphocytes express c-myc by both techniques. Two patterns of nuclear staining (weak and strong) were found by immunocytochemistry and this was confirmed by two peaks of fluorescence intensity by flow cytometry. Double immunostaining showed that the stronger pattern of c-myc staining corresponds to B lymphocytes and the weak one to T cells. Quantification confirmed these results which demonstrated a statistically significant difference in the expression of c-myc in these two lymphocyte populations (p < 0.005). Our results demonstrate for the first time that normal circulating B cells express higher levels of c-myc protein than T lymphocytes.

Antibodies, Monoclonal↗

PubMed1994

Long term results with 2'deoxycoformycin in hairy cell leukemia.

We have treated 159 patients with hairy cell leukemia (HCL) with 2'deoxycoformycin (DCF) in a phase II study that started in 1986. 151 patients had typical HCL and 8 HCL-variant. Ages ranged from 30 to 81 years. Most patients had previously received interferon-alpha, splenectomy or both and 23 had DCF as first line; all had active disease. In the first 40 patients DCF was given at 4 mg/m2 weekly for 4 weeks and every 2 weeks thereafter and in the remainder every 2 weeks until maximal response. Three patients died early on and were non-evaluable for response. The response rates in 148 patients with typical HCL were: CR 74.3%, PR 22.3% and NR 3.4%. None of the HCL-variants achieved CR; 4 had PR and 4 NR. The median number of DCF injections to CR was 9. Lymphopenia and neutropenia were seen in 52% and 34%, respectively, but 72% of patients started treatment with low leucocyte counts. 27% had infectious complications of which 6% were life threatening. The disease free interval of the first 105 remitters (CR + PR) was 84% at 4 years with no significant difference between CR (86%) and PR (77%). There have been 12 relapses at a median time of 22 months (range 6-60 months) since stopping DCF, of these, 5 had massive abdominal lymphadenopathy, a features seen also in 4 of the 5 primary non-responders. There were 13 deaths but 7 were unrelated to HCL. The 5-year survival from starting DCF in 110 patients with typical HCL was 88% and 97% if we exclude non-HCL deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Follow-Up Studies↗