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F Bauters

Publications and source records attributed to F Bauters.

At least 91 records · Page 5Linked to original sources

Transforming growth factor-beta and megakaryocytes in the pathogenesis of idiopathic myelofibrosis.

Although the disease is well described, the pathogenesis of bone marrow fibrosis in idiopathic myelofibrosis still remains unclear. We previously reported elevated intraplatelet transforming growth factor-beta (TGF-beta) levels in patients with this myeloproliferative disorder, compared with healthy subjects. Here, in a series of 16 patients, we show that TGF-beta expression is also increased in patients' peripheral blood mononuclear cells (PBMC): (i) at the mRNA level analysed by Northern blot hybridization and/or reverse transcription-polymerase chain reaction (RT-PCR); (ii) and/or at the secreted peptide level as evaluated in conditioned media from patients' mononuclear cells by a growth inhibition assay on CC164 cells. By immunostaining with a polyclonal anti-TGF-beta 1 antibody, TGF-beta was localized in morphologically heterogenous cells; these cells were characterized as megakaryocytes by labelling with a gpIIbIIIa monoclonal antibody. Thus we provide evidence that both TGF-beta and megakaryocytes are linked in the pathogenesis of idiopathic myelofibrosis.

Aged↗

Significance of circulating plasma cells in multiple myeloma.

The number of circulating plasma cells (CPC) was determined on mononuclear cell preparations after Giemsa (morphology) and light chain staining (immunocytochemistry). Both methods gave reproducible and identical results when CPC were 1% or more. Using this limit, no CPC were observed in MGUS (0/11) and primary amyloidosis (0/2), whereas 45/98 (45.9%) multiple myeloma (MM) pts had > or = 1% CPC. 3/14 pts (21.4%) in stage I, 5/13 pts (38.5%) in stage II, 20/28 pts (71.4%) in stage III, 4/25 pts (16%) at plateau phase, and 13/18 pts (72.2%) at relapse had > or = 1% CPC (p < 0.001). Mean beta-2 microglobulin was 3.77 mg/l and 6.08 mg/l for pts without or with > or = 1% CPC, respectively p = 0.0001). Presence of CPC was also correlated with an higher percentage of bone marrow PC, but not with the number of Ki-67 positive BM-PC, and not with CRP or LDH levels. K/L and Gamma/Alpha CPC isotype ratio showed these cells as monotypic in nearly all pts. The prognostic value could not really be assessed in this study, as only the initial response to therapy was investigated, and the latter failed to give any difference between pts with and without CPC. So, presence of CPC is not an infrequent finding, but is highly related to tumor mass and active disease; in most if not all patients they are monotypic and certainly belong to the malignant clone. Their prognostic value is unclear but under current investigation; CPC are correlated with B-2M level.

Cell Count↗

Cytomegalovirus expression in minor salivary glands and chronic graft-versus-host disease.

A systematic survey of human cytomegalovirus (CMV) was performed in 29 allogeneic bone marrow transplant (BMT) recipients. At day 100 a lip biopsy was performed and histological grading according to Sale's score was compared with the immunohistochemical detection of the immediate early protein IE2 of HCMV. In 10 patients without chronic graft-versus-host disease (GVHD), 3 had lip biopsy grade 1, 7 had grade 0 Sale's score and in 19 patients with chronic GVHD, 11 had grade 2, 1 had grade 1 and 7 had grade 0. On the same lip biopsies, we found IE2 protein in 8 of the 19 patients with chronic GVHD. None of the lip biopsies from patients without chronic GVHD expressed the protein, suggesting that HCMV expression is strongly associated with chronic GVHD and Sale's grade 2. To conclude, in our group of patients with a risk for HCMV infection, detection of the protein IE2 was a good predictive criterion of chronic GVHD with a sensitivity of 61% and a specificity of 100%.

Bone Marrow Transplantation↗

[Familial thymoma and translocation t (14;20) (q24;p13)].

A familial lympho-epithelial thymoma with constitutional chromosomal translocation t (14;20) (q24;p13) is presented: the thymoma and its particular translocation are present in the mother and the two sons of her offspring. The small number of cases do not allow establishing any relation between thymoma and this particular translocation. Concerning genetic counseling, an annual thoracic radiography is necessary for all the other family members, carriers or not of the translocation.

Adult↗

Treatment with very low-dose GM-CSF in myelodysplastic syndromes with neutropenia. A report on 28 cases.

We treated 28 cases of myelodysplastic syndrome (MDS) with neutropenia by very low-dose GM-CSF (0.25 or 0.5 micrograms/kg/day). Median age was 69 years. Nine patients had RA, 18 had RAEB, and one had RARS. Eighteen patients had absolute neutrophil counts (ANC) < or = 0.5 x 10(9)/l, and ten had ANC between 0.5 and 1.0 x 10(9)/l. Ten patients had experienced > or = WHO grade II infection(s) during the preceding 3 months. Eighteen patients (64%) had a response (i.e. ANC at least doubled and > or = 1 x 10(9)/l after 1 month), including 4/8 patients treated at 0.25 mu/kg/day, and 14/20 treated at 0.5 microgram/kg/day (difference not significant). Two of the non-responders obtained a response after dose escalation to 0.5 and 1 microgram/kg/day, respectively. The only prognostic factor of response was FAB subtype (10/11 responses in patients with RA or RARS, vs. 8/17 in RAEB, p = 0.04). Patients with ANC < or = 0.5 x 10(9)/l had a 55% (10/18) response rate, which was not significantly lower than the 80% (8/10) response rate observed in patients with ANC > 0.5 x 10(9)/l. Side-effects were generally moderate, except in three patients where the drug had to be discontinued, including the only patient who progressed to AML. In responders, GM-CSF was continued during 2 to 14 months (median 6), and the response persisted in all but one case, who relapsed after 60 days of treatment. During follow-up, only one responder had > or = WHO grade II infections, as compared to five of the non-responders (of whom two had fatal infectious episodes). In conclusion, very low-dose GM-CSF can durably increase ANC in about two thirds of MDS with neutropenia. Although it remains to be shown in randomized trials that it can reduce the incidence of infections and improve survival in MDS, very low-dose GM-CSF may be an interesting approach in MDS, associated to reasonable cost.

Aged↗

Role of early splenectomy in malignant lymphomas with prominent splenic involvement (primary lymphomas of the spleen). A study of 59 cases.

The outcomes were analyzed retrospectively of 59 cases of non-Hodgkin lymphoma (NHL) that included prominent splenic involvement (LPS). Forty-three patients had low-grade NHL, and 16 had intermediate or high-grade NHL. Forty of the 59 patients underwent splenectomy. Four patients died postoperatively before any treatment, and 10 others received no chemotherapy or radiation therapy. Twenty-nine splenectomized and 16 patients whose spleens were not removed received chemotherapy or radiation therapy. One or more cytopenias were present in 45 patients (77%). Five (18%) of the 28 patients who initially were cytopenic underwent splenectomies that did not correct their blood disorders. The median actuarial survival was 108 months in splenectomized patients and 24 months in those not treated surgically (P = 0.0001). For the 40 splenectomized patients, a normal postoperative platelet count, an initial hemoglobin level of 110 g/l or more, and a postoperative hemoglobin level 110 g/l or more were associated with prolonged survival. These results suggest that cytopenias are frequent in LPS and that their reversal is observed after early splenectomy in 82% of cases. The absence of cytopenia after early splenectomy is associated with prolonged survival.

Actuarial Analysis↗

Long-term outcome of follicular low-grade lymphoma. A report of 91 patients.

We retrospectively analyzed overall survival and survival after progression in 91 patients with low-grade follicular lymphoma (LGFL). Histological subtype was B in 75 patients and C in 16 patients. Twelve patients with localized disease received involved-field radiotherapy; seven patients without bulky disease had no initial therapy. The remaining 72 patients received long-term chlorambucil (9 patients), MOPP or COPBleo (42 patients), or a CHOP-derived regimen (21 patients). Forty-two patients (46%) achieved a complete remission (CR) and 28 patients (31%) achieved a partial remission; 48 of these 70 patients relapsed or progressed. Nineteen of the other 21 patients with stable LGFL progressed. Two other patients failed to respond and rapidly died. Thirty-two of the 67 patients with progressive or relapsed LGFL have died. Median overall survival was 111 months. Age > or = 70 years, male sex, B symptoms, histological subtype follicular mixed-cell NHL, tumor size > or = 10 cm, number of extranodal sites of disease > or = 2, pleural effusion, and Ann Arbor stage III or IV were found to adversely influence overall survival. Failure-free survival < 24 months, failure to achieve a CR after the progression, initial histological subtype follicular mixed cell, initial Ann Arbor stage III or IV, and initial tumoral size > or = 10 cm were found to adversely influence survival after progression. Our results suggest that most prognostic factors for overall survival in LGFL are related to histological subtype or tumor burden. Some initial adverse prognostic factors for survival may be also associated with a poor survival after progression.

Adult↗

Is there still a role for low-dose cytosine arabinoside in de novo acute myeloid leukemia in the elderly? A report on 77 cases.

Seventy-seven elderly patients (median age 72, range 59-85) with de novo AML were treated with low-dose Ara C (10 mg/m2/12 h over 21 days, for one or two courses). Thirteen (17%) achieved complete remission (CR), 16 (21%) partial remission (PR); 28 (35%) had resistant leukemia, and 20 (26%) early death or death during hypoplasia. Most (86%) of the patients had severe pancytopenia and 58% were hospitalized. Overall median survival was 3 months. Median duration of CR was 9 months. Five CR were longer than 1 year, and two were longer than 4 years. All but one PR were < or = 9 months, and 12/16 were < or = 4 months. Karnofsky index and karyotype (the latter performed for 52 patients) were the only significant prognostic factors of response to treatment (including CR+PR) and survival: poor response rate (8%) and survival (median 0.7 months) were found in patients with Karnofsky index < 60, compared with 44% and 4 months, respectively, in patients with Karnofsky index > or = 60; likewise, patients with rearrangements of chromosome 5 and/or 7 or complex rearrangements had a response rate of 13% and median survival of 1.5 months, compared with 68% and 8 months, respectively, in patients with normal karyotype or single abnormalities (not involving chromosomes 5, 7, or 8). Patients with isolated trisomy 8 had a response rate of 37% but short median survival (2.5 months). Significantly longer survival was seen in responders. Our findings suggest that, overall, low-dose Ara C yields limited results in AML in the elderly. However, it could remain a useful option in elderly patients with AML who are not candidates for intensive chemotherapy (even with the support of growth factors), provided their general condition is not too altered and they do not have an "unfavorable" karyotype (i.e., rearrangements of chromosomes 5 or 7 or complex abnormalities).

Aged↗

De novo myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 20: a subtype of MDS with distinct hematological and prognostic features?

We report on 8 cases of de novo myelodysplastic syndromes (MDS) with deletion of the long arm of chromosome 20 (del 20q), who represented about 2% (8/392) of our cases of de novo MDS with cytogenetic analysis seen during a period of 9 yr. Median age was 69 yr, and there were 7 males and 1 female. Anemia was absent or very mild (Hb > 11 g/dl) in 5 patients. Only 1 patient had neutrophils < 0.5 x 10(9)/l, and none had platelets < 50 x 10(9)/l. Four patients had refractory anemia (RA), 2 had refractory anemia with ringed sideroblasts (RARS), and 2 had refractory anemia with excess of blasts (RAEB). Del 20q was isolated in 5 patients, and associated with other chromosomal rearrangement(s) in 3 patients. Only 1 patient progressed to ANLL and 2 showed an increase in bone marrow blasts during evolution. The 5 other patients had stable disease after 18-77 months. By comparison with de novo MDS patients with other cytogenetic findings, patients with del 20q had a tendency towards lower incidence of anemia and excess of marrow blasts, lower incidence of progression to AML and more prolonged survival, although differences were not significant. Only patients with isolated del 5q had a more prolonged survival than patients with del 20q.

Aged↗

Long-term survivors in myelodysplastic syndromes: a report on 63 cases and comparison with short and intermediate survivors.

Sixty-three of 373 patients (17%) with de novo myelodysplastic syndrome (MDS) survived more than 5 yr (long survivors). At diagnosis, they usually had no or only moderate cytopenias; 63% of them had marrow blasts < 5%; only 1 patient had circulating blasts; 60% had refractory anaemia (RA) or refractory anaemia with ringed sideroblasts (RARS); 19% of the 43 patients who were karyotyped had an abnormal clone, and only 2 patients had complex cytogenetic findings. Only 4 of the 63 patients progressed to another FAB type within 5 yr of diagnosis, from RA to refractory anaemia with excess of blasts (RAEB) or chronic myelomonocytic leukaemia (CMML). After 5 yr, 9 patients showed progression (including progression to AML in 5 patients). The other patients remained stable (43 cases) or died from cytopenias or unrelated disorders (11 cases). Except for 3 patients who achieved prolonged complete remission with intensive chemotherapy, and possibly 3 patients who responded to low dose Ara C, prolonged survival seemed to result mainly from the low natural course of the disease. Although, as expected, significant differences for age, cytopenias, circulating and bone marrow blasts, and karyotype were seen between short (< 2 yr) and long (> 5 yr) very few significant differences were seen between intermediate and long survivors. These 2 subgroups only differed by significantly lower age and higher haemoglobin level in long survivors. Multivariate scoring systems (Bournemouth, Sanz's and Lille scores) proved of relatively limited value in differentiating them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Improved cytogenetic analysis of bone marrow plasma cells after cytokine stimulation in multiple myeloma: a report on 46 patients.

Cytogenetic analysis was successfully performed in 46 consecutive myeloma patients (40 newly diagnosed and six relapsed patients). Karyotype was performed on bone marrow cells after long-term cultures (6 d) stimulated by GM-CSF, GM-CSF+IL6 or GM-CSF+IL6+IL3. Nineteen patients (41%) had cytogenetic abnormalities including 17/40 patients at diagnosis (42.5%) and 2/6 patients at relapse. Hyperdiploidy was found in 12 patients and hypodiploidy in four patients. Of the 17 newly diagnosed patients with cytogenetic abnormalities, five died from myeloma after 1-14 months and three other patients had primary drug resistance. Our results suggest that cytogenetic analysis after stimulation of cultures by cytokines detects clonal abnormalities in 40-50% of newly diagnosed myeloma patients and that these patients often have a short survival and/or primary drug resistance.

Bone Marrow↗

High incidence of lymphoid infiltration on labial salivary gland biopsy in non-Hodgkin's lymphomas: clinical implications.

Sjögren's syndrome (SS) is characterized by an increased risk of developing a non-Hodgkin's lymphoma (NHL). We performed labial salivary gland biopsy (LSGB) in 103 patients with untreated NHL, negative for human immunodeficiency virus. Median age was 58 years (range 21-79) and M/F 1.3. Using the Working Formulation, 37 patients had low-grade NHL and 66 had intermediate- or high-grade NHL. Dense lymphocytic infiltration (positive focus score 3 or 4) was found in 28 patients. 10 (35%) of these 28 patients fulfilled criteria for possible SS. 15/28 patients had an identical monotypic infiltrate on LSGB and NHL tissue (including two of the 10 patients with criteria for SS). The significance of the lymphoid infiltrate of LSGB was unknown in the five remaining patients with positive focus score. Significant correlations were found between positive focus score and presence of two or more extranodal sites of disease (P = 0.02), impaired performance status (P = 0.004), splenomegaly (P = 0.05), increased gammaglobulin level (P = 0.03), and beta 2 microglobulin (P = 0.004). Considering intermediate- or high-grade NHL, we found significant correlation between positive focus score and unfavourable prognosis according to the two Dana Farber Cancer Institute indexes (P < 0.04), to the LNH-84 index (P = 0.05), and to the international index (P = 0.003). In conclusion, systematic evaluation of LSGB in 103 patients with NHL found lymphoid infiltration in 28% of them, but possible SS could be considered in only 10%. This lymphoid infiltration, though not correlated with any particular histological subtypes, was associated with unfavourable clinical prognostic factors, especially in intermediate- or high-grade NHL.

Adult↗

Prognostic factors in Waldenström's macroglobulinemia: a report of 167 cases.

PURPOSE: A single-center retrospective analysis was conducted in 167 patients with Waldenström's macroglobulinemia (WM) to delineate prognostic factors. PATIENTS AND METHODS: One hundred sixty-seven patients diagnosed between January 1969 and December 1988, fulfilling diagnostic criteria of WM, were entered onto this study. One hundred twenty-eight patients were treated with chlorambucil (0.1 mg/kg/d): 117 at diagnosis and 11 during the disease course. Seventeen variables were analyzed in all patients and in treated patients for their prognostic value on survival using the Kaplan-Meier method and a Cox multivariate regression analysis. RESULTS: Median survival duration for all patients was 60 months. Pretreatment factors associated with shorter survival in the entire population were age > or = 60 years (P = .006), male sex (P = .0001), general symptoms (P = .01), hemoglobin less than 10 g/dL (P = .008), leukocytes less than 4 X 10(9)/L (P = .02), neutrophils less than 1.7 X 10(9)/L (P = .02), and platelets less than 150 X 10(9)/L (P = .0006). Organomegaly, signs of hyperviscosity, renal failure, monoclonal immunoglobulin M (M IgM) level, blood lymphocytosis, and percentage of marrow lymphoid cells were not significantly correlated with survival. In a Cox multivariate regression analysis, the combination of factors that gave the best prognostic value was the association of sex (P = .0002), neutrophils (P = .002), age (P = .008), and hemoglobin (P = .02). CONCLUSION: Our findings suggest that some pretreatment parameters, including older age, male sex, general symptoms, and cytopenias, carry a poor prognosis in WM. By contrast, high initial tumor burden (indicated by organomegaly, high IgM level, and high percentage of marrow lymphoid cells) does not seem to be significantly associated with short survival. Our results help define a high-risk population that could perhaps benefit from newer therapeutic approaches.

Aged↗

A multicentric randomised study of alpha 2b interferon (IFN) and hydroxyurea (HU) with or without cytosine-arabinoside (Ara-c) in previously untreated patients with Ph+ chronic myelocytic leukemia (CML): preliminary cytogenetic results.

The CML 88 study was designed to evaluate the efficacy of maintenance therapy in a multicentric randomised protocol using IFN combined with low-dose Ara-C versus IFN alone, following an induction with IFN + HU. Between April 1988 and February 1991, 237 patients from 36 French Hematology Centres were entered in the study. Preliminary cytogenetic results show a slightly higher, although not statistically significant, proportion of major chromosomal responses, including complete cytogenetic remissions, in the IFN + Ara C arm.

Adolescent↗