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Biomedical subjects

F Bauters

Publications and source records attributed to F Bauters.

At least 19 recordsLinked to original sources

Prognostic factors in agnogenic myeloid metaplasia: a report on 195 cases with a new scoring system.

We studied the survival of 195 patients with agnogenic myeloid metaplasia (AMM) diagnosed between 1962 and 1992 in an attempt to stratify patients into risk groups. Median survival was 42 months. Adverse prognostic factors for survival were age > 60 years, hepatomegaly, weight loss, low hemoglobin level (Hb), low or very high leukocyte count (WBC), high percentage of circulating blasts, male sex, and low platelet count. A new scoring system based on two adverse prognostic factors, namely Hb < 10 g/dL and WBC < 4 or > 30 x 10(9)/L, was able to separate patients in three groups with low (0 factor), intermediate (1 factor), and high (2 factors) risks, associated with a median survival of 93, 26, and 13 months, respectively. An abnormal karyotype (32 cases of 94 tested patients) was associated with a short survival, especially in the low-risk group (median survival of 50 v 112 months in patients with normal karyotype). The prognostic factors for acute conversion were WBC > 30 x 10(9)/L and abnormal karyotype. Thus, hemoglobin level and leukocyte count provide a simple prognostic model for survival in AMM, and the adverse prognostic value of abnormal karyotype may be related to a higher rate of acute conversion.

Adult

Prognostic factors in myelodysplastic syndromes: critical analysis of the impact of age and gender and failure to identify a very-low-risk group using standard mortality ratio techniques.

We studied the prognostic value of age and gender by survival, and by standard mortality ratio (SMR) analyses, in 203 untreated patients with myelodysplastic syndromes (MDS); 57 refractory anaemia (RA), 23 refractory anaemia with ringed sideroblasts, 41 refractory anaemia with excess blasts (RAEB), 3 RAEB in transformation (RAEB-T) and 79 chronic myelomonocytic leukaemia (CMML), aged 23-89 years (median 69, M/F 0.5), who were all karyotyped. Median survival was 36 months. Adverse prognostic factors were: high bone-marrow blast percentage, complex karyotype, low platelet count, age > 60 years, low or high WBC count, haemoglobin < 10 g/dl, male gender. However, the standard mortality ratio (i.e. mortality compared to that of an age- and sex-adjusted population) was not different between male and female patients. Patients < 60 had a higher SMR than older patients. Therefore the prognostic values of age and gender for survival in MDS patients may reflect, at least in part, a characteristic of the population. Furthermore, even in low-risk groups defined by scoring system we were unable to define a subgroup of patients with a mortality similar to that of the normal population, especially in MDS patients aged < 60.

Adult

Low incidence of specific anti-platelet antibodies detected by the MAIPA assay in the serum of thrombocytopenic MDS patients and lack of correlation between platelet autoantibodies, platelet lifespan and response to danazol therapy.

We prospectively studied the mechanism of thrombocytopenia in 30 patients with myelodysplastic syndrome (MDS), who had a platelet count <or= 70 x 10(9)/l, and marrows blasts <or= 10% by analysis of platelet lifespan, platelet-bound IgG antibodies by platelet radioactive antiglobulin test (PRAT), and circulating and platelet-bound autoantibodies specifically directed against platelet glycoproteins by indirect and direct MAIPA test. PRAT analysis was positive in 21/30 patients (70%), but antiplatelet antibodies were found in only eight by the MAIPA test. Platelet lifespan was shortened in five cases, only one of whom had a positive MAIPA test. Patients were treated by danazol (600 mg/d), and 9/26 evaluable patients (35%) responded, including three of the five patients with shortened platelet lifespan. No correlation between platelet lifespan, results of PRAT and MAIPA tests, and response to danazol was found. In conclusion, specific antiplatelet autoantibodies, reduced platelet lifespan, and efficacy of androgen therapy on platelets were seen in 20%, 17% and 35% of MDS with thrombocytopenia, respectively, but no correlation between these findings was found in this study.

Adolescent

Improved cytogenetics in multiple myeloma: a study of 151 patients including 117 patients at diagnosis.

Between December 1990 and January 1994, bone marrow (BM) samples from 151 patients with multiple myeloma (MM), including 117 patients evaluated at diagnosis, were collected for cytogenetic analysis. A total of 129 patients had assessable metaphases (100 patients at diagnosis). Cytogenetic studies were performed on BM cells after longterm cultures (6 days) with stimulation of cultures by granulocyte-macrophage colony-stimulating factor (GM-CSF), GM-CSF plus interleukin (IL)-6, IL-3 plus IL-6, or GM-CSF plus IL-3 plus IL-6 to improve myeloma cell growth, and 91 patients had an additional unstimulated culture. Sixty-six patients (51%) had cytogenetic abnormalities, including 47 of 100 patients at diagnosis (47%) and 17 of 24 patients at relapse (71%; P = .04). The aberration rate increased with stage (P = .007), BM plasmacytosis (P = .003), beta 2 microglobulin level (P = .001), C-reactive protein (CRP) level (P = .001), and Ki-67 (P = .007). The abnormality detection rate was higher in stimulated than unstimulated cultures, and the difference was statistically significant (P < .01). Hyperdiploidy was observed in 39 patients (30% of patients with an assessable karyotype) and hypodiploidy in 19 patients (15%). Among numeric changes, gains predominantly involved chromosomes 3, 5, 7, 9, 11, 15, 19 and losses, chromosomes 8, 13, 14, and X. The most frequent loss was loss of chromosome 13, observed in 22 patients (15%), including 18 patients at diagnosis (12%). We observed frequent structural changes of chromosomes 1 (15%) and 14 (10%) but also a 5% incidence of 19q13 abnormality and two patients with translocation t(1;16)(p11;p11). By using the proportional hazard univariate model, patients with abnormal karyotypes were demonstrated to have 2.5-fold greater chance of death than patients with normal karyotypes (P < .014). Despite a multivariate approach with the same model, the respective roles of karyotype abnormality, age, stage, and beta 2 microglobulin level could not be clearly ascertained. From these results we conclude that cytogenetic analysis using stimulation of cultures by cytokine(s) may be a promising method to identify about 50% of cytogenetic abnormalities in patients with newly diagnosed MM. Cytogenetic analysis may help to define a high-risk population that would benefit from intensive therapeutic approaches.

Adult

p16 gene homozygous deletions in acute lymphoblastic leukemia.

The p16 protein is a cyclin inhibitor encoded by a gene located in 9p21, which may have antioncogenic properties, and is inactivated by homozygous p16 gene deletion or, less often, point mutation in several types of solid tumors often associated to cytogenetic evidence of 9p21 deletion. We looked for homozygous deletion and point mutation of the p16 gene in acute lymphoblastic leukemia (ALL), where 9p21 deletion or rearrangement are also nonrandom cytogenetic findings. Other hematologic malignancies including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), chronic lymphocytic leukemia (CLL), and myeloma were also studied. Homozygous deletion of the p16 gene was seen in 9 of the 63 (14%) ALL analyzed, including 6/39 precursor B-ALL, 3/12 T-ALL, and 0/12 Burkitt's ALL. Three of the 7 ALL with 9p rearrangement (including 3 of the 5 patients where this rearrangement was clearly associated to 9p21 monosomy) had homozygous deletion compared to 5 of the 55 patients with normal 9p (the last patient with homozygous deletion was not successfully karyotyped). Single stranded conformation polymorphism analysis of exons 1 and 2 of the p16 gene was performed in 88 cases of ALL, including the 63 patients analyzed by Southern blot. Twenty-six of the cases had 9p rearrangement, associated to 9p21 monosomy in at least 12 cases. A missense point mutation, at codon 49 (nucleotide 164), was seen in only 1 of the 88 patients. No homozygous deletion and no point mutation of the p16 gene was seen in AML, MDS, CLL, and myeloma. Homozygous deletion of interferon alpha genes (situated close to p16 gene in 9p21) was seen in only 3 of the 9 ALL patients with p16 gene homozygous deletion, and none of the ALL without p16 gene homozygous deletion. Our findings suggest that homozygous deletion of the p16 gene is seen in about 15% of ALL cases, is not restricted to cases with cytogenetically detectable 9p deletion, and could have a pathogenetic role in this malignancy. On the other hand, p16 point mutations are very rare in ALL, and we found no p16 homozygous deletions or mutations in the other hematologic malignancies studied.

Base Sequence

Splenic irradiation for chronic autoimmune thrombocytopenic purpura in patients with contra-indications to splenectomy.

We treated by splenic irradiation eight patients with chronic idiopathic thrombocytopenic purpura (ITP, seven cases) or secondary autoimmune thrombocytopenic purpura (one case) who had contra-indications to splenectomy. A total dose of 15 Gy was delivered to the spleen, with left kidney protection. One patient had a good durable response (> 1 year); two patients had a good transient response (of 3 months duration) but they responded again to a second course of irradiation; two patients had only partial response, but have required no other treatments for 2 years; the three remaining patients had no response. Side-effects were minor. Therefore splenic irradiation appears to be a therapeutic option in patients with chronic ITP who have contra-indications to splenectomy.

Aged

Pulsed high-dose dexamethasone in refractory chronic idiopathic thrombocytopenic purpura: a report on 10 cases.

We treated 10 patients who had chronic refractory idiopathic thrombocytopenic purpura (ITP) with high-dose dexamethasone (DXM, 40 mg/d for 4 sequential days every month). The interval from diagnosis ranged from 49 to 300 months, and patients had previously received a median of 5.5 treatments (including splenectomy in nine cases). Median platelet count was 14 x 10(9)l (range 6-26 x 10(9)/l) at the onset of DXM and eight patients had bleeding symptoms. Eight patients received at least three cycles of DXM. Five patients had a response (i.e. platelet count at least doubled and increased by > 20 x 10(9)/l), including one almost complete remission and four minor responses (MR). Of the MR, one was probably due to concurrent IVIg administration, and all four MR were transient, in spite of further cycles of DXM. In three patients DXM was a failure after three or four cycles. In two patients DXM had to be stopped after one course because of major side-effects (systemic hypertension with stroke and insulin-dependent diabetes, respectively). In our experience, high-dose DXM had a relatively limited effect in chronic refractory ITP and was associated with severe side-effects in some cases.

Adult

CD19 and immunophenotype of bone marrow plasma cells in monoclonal gammopathy of undetermined significance.

AIMS: To determine whether a particular phenotype or antigen is preferentially related to monoclonal gammopathies of undetermined significance (MGUS). METHODS: Bone marrow specimens from 56 patients with MGUS were stained immunocytochemically (ABC peroxidase) for CD38, CD56, CD9, CD10, CD19, CD20, CD22, and MB2. Specimens from patients recently diagnosed with multiple myeloma and reactive bone marrow samples were studied in parallel. RESULTS: CD38 was expressed on all plasma cells from all MGUS samples tested, while 36% were positive for CD56, CD9 and MB2 were both expressed strongly; CD20 was moderately expressed, and staining for CD10 and CD22 was uncommon. For these five B cell antigens there was no clear difference between their expression in MGUS and in multiple myeloma. A great difference was found for CD19: in MGUS this antigen was expressed on 2-91% of plasma cells (mean 35%) and 77% patients had > 10% positive plasma cells; in multiple myeloma its expression was low and only 12% patients had > 10% positive plasma cells. When these results were converted to numbers of CD19 positive plasma cells per 100 nucleated bone marrow cells, reactive bone marrow and MGUS specimens had a similar number of positive plasma cells. There was no correlation between expression of any of the antigens tested. CONCLUSIONS: Many of the so-called pre-B, B or activation antigens are present on plasma cells from MGUS specimens, and expression of CD9, CD10, CD20, CD22, MB2, and CD38 in MGUS was very similar to that in multiple myeloma. CD56 was frequently expressed in MGUS. In this series CD19 was highly expressed in MGUS but not in multiple myeloma. Plasma cells bearing this antigen could represent the non-neoplastic process and determination of its expression could be useful for the diagnosis of MGUS.

Antigens, CD

Glomerular injury in chronic myelomonocytic leukemia.

Among 825 cases of de novo myelodysplastic syndromes (MDS) diagnosed over a period of 13 years in our center, 4 had clinically significant glomerulopathy. All 4 fulfilled diagnostic criteria of chronic myelomonocytic leukemia (CMML), and could be classified in the low or intermediate risk groups according to two scoring systems. Presenting symptoms of renal involvement were edema in 3 cases and acute renal failure in the remaining patient. Three patients had the nephrotic syndrome. Renal biopsy (performed in 2 cases but considered as contraindicated in the other cases) showed AL amyloidosis on one case and extracapillary glomerulonephritis in the other case. The 4 patients were treated with V16 or hydroxyurea and two had renal improvement. Only one previous case of MDS associated with glomerulopathy has been reported before and also very probably had CMML. This, and the response of renal disease to chemotherapy in 2 of our patients suggests a possible relationship between the two disorders. More systematic investigation of glomerular function, in CMML, could possibly disclose a higher incidence of cases of glomerular injury in this type of MDS.

Aged

Expression of the multidrug resistance P glycoprotein in newly diagnosed adult acute lymphoblastic leukemia: absence of correlation with response to treatment.

We analyzed P glycoprotein (PGP) expression and its correlation with hematological parameters and outcome in 50 cases of newly diagnosed adult acute lymphoblastic leukemia (ALL). PGP expression was evaluated by flow cytometry using MRK16 monoclonal antibody (MoAb) and/or immunocytochemistry on marrow slides, using JSB1 MoAb. Thirty-two of the 50 patients (64%) were PGP positive by at least one of the two methods, which gave concordant results in 15 of the 18 cases in which they were both used. No correlation between PGP expression and clinical and hematological parameters including WBC counts, immunophenotype and karyotype was seen, although there was a trend for more frequent CD34 expression in PGP-positive cases. All patients were treated with intensive chemotherapy. We found no difference in complete remission (CR) rate, actuarial disease-free survival and survival in PGP-positive and PGP-negative cases. Our findings suggest that the clinical significance of PGP expression is less clear in ALL than in AML. Wider use of functional techniques of evaluation of mdr1 gene expression, which assess the 'pumping' activity of PGP, and their correlation with quantitative analysis of mdr1 mRNA and protein, would probably improve knowledge of the role of PGP in ALL. Analysis of other mechanisms of drug resistance, especially multidrug resistance-associated protein (MRP) expression, would also be useful.

ATP Binding Cassette Transporter, Subfamily B, Mem

Tuberculosis associated haemophagocytic syndrome: two cases with a favourable outcome.

Haemophagocytic syndrome is a heterogenous disease characterized by disordered macrophage activation associated with viral, bacterial or parasitic infection. The few reports of haemophagocytosis occurring in the presence of mycobacterial infection show a high mortality rate and we present two further cases notable for their favourable issue. Rapidity of diagnosis and immediate treatment could explain the avoidance of a fatal outcome.

Aged

[Thoracic tumors after treatment for Hodgkin disease].

Twenty-one patients were admitted to the surgical unit for management of an intra-thoracic mass following treatment of Hodgkin's disease (HD). They consisted of 14 males and 7 females, with a mean age of 34 years (range: 17-62). Seven had recurrent HD, 14 had a non-Hodgkin solid tumour. HD recurrences were treated with repeated chemotherapy with 4 prolonged survivals including 1 relapse (40 to 84 months follow-up). Non-Hodgkin tumours were 13 lung carcinomas, which were resected in 4 cases, with only 1 prolonged survival (54 months) and malignant schwannoma. HD recurrences are observed equally in both young males and females and are subsequent to a mediastinal location of the disease, after an average 3.2 years. They are located on the borders or irradiation fields. Repeated chemotherapy is effective. Carcinomas more often appear in males, at an older age, in a favorable clinical context, after an average 10.2 years. Their prognosis is very poor. Irradiation and chemotherapy contribute to their development. Long-term risks of HD treatment must be considered.

Adolescent

Interphase fluorescence in situ hybridization (FISH) as a powerful tool for the detection of aneuploidy in multiple myeloma.

Conventional cytogenetic (CC) studies performed in multiple myeloma (MM) are difficult because of the low proliferation rate of plasma cells (PC). The purpose of this study was to compare results obtained by CC and by FISH for the detection of numeric chromosomal changes in patients with MM. PC DNA content, CC and interphase FISH analysis were performed on 29 consecutive patients with MM. Fifteen patients (control group) had known Cytogenetic abnormalities identified by CC. The other 14 patients (study group) had a normal karyotype but an abnormal DNA content. Bone marrow material prepared for CC or cytospin slides were probed with classical satellite III or alpha satellite DNA sequences for chromosomes 3, 7, 8, 9, 11 and 15 (chromosomes 3, 7, 9, 11, 15 probes for hyperdiploid patients and the chromosome 8 probe for hypodiploid patients). In the control group, an unexplained discrepancy between CC and FISH occurred for only one chromosome in one patient. Also in this group, four patients had only one abnormal cell by CC and the numeric changes in these patients were always confirmed by FISH analysis. In the study group, FISH analysis showed an abnormal result in all but one patient. From these data, we conclude that FISH improves the detection of cytogenetic abnormalities in multiple myeloma. Using commercially available DNA probes for the most frequent numeric changes and slides for CC or cytospin slides, we demonstrated abnormal cytogenetics by FISH in 28/29 patients. In further studies, use of FISH could permit a more accurate description of numeric changes and their prognostic value in MM as well as an approach to clonal evolution. It would also be of interest in the study of monoclonal gammopathies of undetermined significance.

Adult

Inv(16) may be one of the only 'favorable' factors in acute myeloid leukemia: a report on 19 cases with prolonged follow-up.

We report our experience of treatment of acute myeloid leukemia (AML) with inv(16). Nineteen of 531 (3.6%) cases of newly diagnosed AML karyotyped over a 12 year period had inv(16)(p13q22) and none had t(16;16) or del 16q. Morphologically, all patients had M4eo. All patients were treated with conventional anthracycline-Ara-C chemotherapy, followed by moderate or more intensive consolidation chemotherapy. All patients received central nervous system (CNS) prophylaxis with intrathecal methotrexate and Ara-C, and cranial irradiation. Eighteen patients (95%) achieved complete remission (CR). Three had a bone marrow relapse, one had a CNS relapse and 14 patients remained in first CR, 11 of them with a follow-up greater than 44 months. Disease-free survival was 74% after 10 months, and actuarial survival 88% after 4 years, and 62% after 6 years. No other AML subgroup, in our experience, had a long-term survival approaching that of AML with inv(16) (although similar favorable outcome may be anticipated in acute promyelocytic leukemia treated by a combination of retinoic acid and chemotherapy).

Acute Disease

Image analysis in multiple myeloma at diagnosis. Correlation with cytogenetic study.

The DNA content of plasma cells (DNA Index or DI) was determined after Feulgen reaction using computed image analysis in 46 patients with multiple myeloma at diagnosis. Aneuploidy was found in 40/46 (87.0%) patients; 27 (58.7%) were hyperdiploid (DI = 1.05-1.45), 11 (24.0%) were hypodiploid (DI = 0.90-0.95), and two (4.3%) were biclonal. Cytogenetic study showed at least one abnormal mitosis in 21/46 (45.7%) cases. All patients with numeric changes had aneuploid DI, and thus confirmed DI > or = 1.05 and DI < or = 0.95 as good limits for aneuploidy with image analysis. Since abnormal karyotypes were observed mainly in stages II and III (55.6% and 54.5%, respectively) rather than in stage I (26.7%), aneuploid DI was found in most patients in all three stages, namely in all 15/15 (100%) patients in stage I. The prognostic value of aneuploidy was difficult to ascertain in our series. Hypodiploidy or DI > 1.15 was not especially associated with aggressive disease, as it was observed in 7/15 patients in stage I; however, with the same limits, patients with stages II and III were refractory to first-line chemotherapy. Image analysis is a highly sensitive method showing aneuploidy in most patients with MM at diagnosis and, in association with cytogenetic study, may help to better understand the pathogenesis of the disease. The independent prognostic value of aneuploidy was not fully established in this report.

Aneuploidy

Two cases of t(1;16)(p11;p11) in multiple myeloma: confirmation by chromosome painting.

Two patients with multiple myeloma and an unbalanced translocation, t(1;16)(p11;p11), are reported. The fluorescence in situ hybridization (FISH) technique was used in one patient to confirm the translocation. To our knowledge, t(1;16)(p36;q13) and t(1;16)(q21;p13), but not t(1;16)(p11;p11), had been reported previously in multiple myeloma. Our results suggest that FISH is useful to characterize structural abnormalities and identify marker chromosomes in multiple myeloma where analysis with conventional cytogenetics is often difficult.

Aged