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M Boogaerts

Publications and source records attributed to M Boogaerts.

At least 73 records · Page 4Linked to original sources

Clinical review on features and cytogenetic patterns in adult acute myeloid leukemia with lymphoid markers.

Cytogenetic patterns in correlation with cytologic, biomolecular and clinical findings were studied in 45 adult patients with AML expressing at least one of the following lymphoid associated markers (LM): CD2, CD7, CD10, CD19, CD22, TdT. Four cytogenetic groups were recognized: group I, including 8 patients with 11q23 rearrangements; group II including 5 patients with the Ph chromosome; group III, with 19 patients and aberrations of the "myeloid type" including 4 cases with aberrations of chromosome 13, 3 cases with 1q and 7q anomalies, 2 cases with trisomy 11q; group IV, including 13 patients with normal karyotype. Patients showing extensive lineage infidelity were encountered more frequently in cytogenetic groups I and II than in groups III and IV. Two of 4 cases with aberrations of chromosome 13 showed two or more lymphoid features either at immunophenotyping or at biomolecular analysis of the configuration of lg and TCR genes. Patients with 11q23 rearrangements and with the Ph chromosome were generally young, presented with high WBC count and had low complete remission rate. Survival in Ph chromosome positive patients was uniformly short. We conclude that, although there is no cytogenetic anomaly specific for AML with LM, chromosome findings may be clinically relevant in AML with LM. A morphologic, immunologic and cytogenetic classification of AML with LM may constitute a working basis for future studies aimed at a better definition of clinicopathological features and optimal treatment strategy for these leukemias.

Adolescent↗

Multicenter randomized study comparing cyclosporine-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia.

We report the results of a randomized multicenter study comparing the efficacy of antithymocyte globulin (ATG) with that of cyclosporin A (CsA) as first-line therapy for severe aplastic anemia (SAA). Patients were randomized to receive ATG and prednisone (PDN) or CsA; hematologic response and toxicity were compared. At 3-month evaluation, patients who had no or minimal response received the alternative therapy to assess the value of a sequential immunosuppressive therapy for treatment of severe aplastic anemia. One hundred nineteen patients were randomized; 25 were excluded, of whom 3 were misdiagnosed and 22 did not follow the cross-over protocol. Ninety-four patients were analyzed; 46 received CsA, and 48 received ATG-PDN. The actuarial survival was 66.7%, with a median follow-up time of 19 months. There was no significant difference in survival between the groups with, at 3 months, an actuarial survival of 88% in the CsA group and 75% in the ATG group (NS); at 12 months, it was 70% in the CsA group and 64% in the ATG group (NS). The percentage of complete and partial response was 11.6% and 16%, respectively, at 3 months, and 31.6% and 30%, respectively, at 12 months (NS). The main prognostic factor was the absolute neutrophil count (ANC) at entry: Patients with ANC less than 0.2 x 10(9)/L had a significantly lower survival as compared with patients with more than 0.2 x 10(9)/L ANC (P = .0001). At 12 months, 62 evaluable patients were alive, with a complete or partial response in 36 patients. Patients who had responded to the first treatment had a better recovery of bone marrow failure than those who had sequential immunosuppression. The main complication was infection, which was more often observed and more often lethal during ATG and PDN therapy. In this study, initial treatment of SAA with either CsA or ATG-PDN followed by cross-over therapy for nonresponders produced comparable response and survival rates.

Adolescent↗

Cytogenetic and molecular studies of the Philadelphia translocation in myelodysplastic syndromes. Report of two cases and review of the literature.

We report two patients with a myelodysplastic syndrome and the Philadelphia (Ph) chromosome. The first patient was a 73-year-old man who was diagnosed as having a chronic myelomonocytic leukemia in combination with features suggestive of a myeloproliferative syndrome. Chromosomal analysis showed a normal karyotype in the majority of cells, mixed with metaphases containing a standard Ph translocation, t(9;22)(q34;q11), as well as a translocation between chromosome 4 and 6: t(4;6)(p15;p12). Southern blot analysis showed breakpoint cluster region rearrangement as observed in classic chronic myeloid leukemia. The second patient was a 63-year-old man with a myelodysplastic syndrome, type refractory anemia. Cytogenetic study of bone marrow cells at the time of diagnosis revealed a normal karyotype: 46,XY. The initial myelodysplastic syndrome evolved to a myeloproliferative phase with progressive leukocytosis and thrombocytosis. During the terminal phase the Ph chromosome was discovered in 100% of the examined cells. We discuss the correlation between MDS and myeloproliferative diseases, the de novo acquisition of the Ph chromosome during the course of a myelodysplastic syndrome, and review the literature.

Aged↗

A multicenter randomized study comparing cyclosporin-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia. The cooperative group on the treatment of aplastic anemia.

This article reports the results of a randomized multicentric study comparing the efficacy of antithymocyte globulin (ATG) with cyclosporin-A (CsA) as first line therapy for severe aplastic anemia (SAA). Patients were randomized to receive ATG and prednisone (PDN) or CsA; hematological response and toxicity were compared. At 3 months, patients who had no or minimal response received the alternative therapy in order to assess the value of a sequential immunosuppressive therapy for treatment of severe aplastic anemia. One hundred and sixteen patients were analysed, 60 received CsA and 56 received ATG/PDN. The actuarial survival was 55% with a median follow-up time of 19 months. There was no significant difference in survival between the two groups. The main prognostic factor was the absolute neutrophil count (ANC) at entry: patients with ANC less than 0.2 x 10(9)/L had a significantly lower survival when compared with patients with an ANC greater than 0.2 x 10(9)/L (P = 0.0001). At 3 months, 16% of patients had a complete or partial response and a cross-over treatment was given to 68 patients. At 12 months, 77 patients were alive, with a complete or partial response in 47 patients. Patients who had responded to the first treatment had a better recovery of bone marrow failure than those who had a sequential immunosuppression. The main complication was infection which was more often observed and was more often lethal during ATG and PDN. This study demonstrates that CsA is comparable to ATG for primary treatment of SAA, but it is less toxic with fewer infectious deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Aplastic↗

MR imaging of intracranial aspergilloma extending from the sphenoid sinus in an immunocompromised patient with multiple myeloma.

A case of fatal intracranial aspergillosis, extending from the sphenoid sinus via the orbit into the subarachnoid space of the optochiasmatic cistern and the cistern of the middle cerebral artery is presented in an immunosuppressed patient with multiple myeloma. Adequate treatment was not instituted and the patient died because the condition was not recognised and interpreted as a soft tissue extension of an orbital localization of myeloma. MRI, especially after intravenous injection of Gadolinium, depicted very accurately the extension of the disease, as defined at autopsy.

Aspergillosis↗

Cytogenetic effects on cells derived from patients with myelodysplastic syndromes during treatment with hemopoietic growth factors.

Hemopoietic growth factors are used with increasing frequency in the treatment of patients with myelodysplastic syndromes (MDS). While a response occurs regularly, it has not been unequivocally resolved whether this effect is due to the stimulation of normal hemopoiesis or to induced maturation of the abnormal clone. To determine whether selective responses to colony-stimulating factors of normal versus abnormal clones occurred, cytogenetic analysis was performed on bone marrow cells of MDS patients before and during in vivo treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) or recombinant human erythropoietin (rhEPO). A proliferation of additional clones could be demonstrated by karyotypic analysis in one patient during GM-CSF therapy and in two patients during rhEPO treatment. Two patients, initially with completely normal cytogenetics, developed a mixture of normal and abnormal metaphases during treatment. Two patients, initially with all abnormal metaphases, developed normal metaphases during treatment with GM-CSF. A mosaic of normal and abnormal metaphases was present in six patients. The percentage of abnormal metaphases increased in three patients during GM-CSF treatment, and in one patient during rhEPO therapy. The cytogenetic anomalies in one patient persisted after clinical response to treatment, suggesting that GM-CSF enhanced maturation of the abnormal clone. These data indicate that cytokine therapy in MDS may have diverse effects on hematopoiesis.

Adult↗

Treatment with granulocyte-macrophage colony stimulating factor and the adult respiratory distress syndrome.

We report a case of a patient who developed a fatal adult respiratory distress syndrome (ARDS) during treatment with rh granulocyte-macrophage colony stimulating factor (rhGM-CSF) (250 mcg/m2/day s.c.) and low-dose cytosine-arabinoside (Ara-C) (20 mg/m2/day s.c.). Several mechanisms which might explain the lung tissue damage in this patient were explored. GM-CSF increased the expression of the glycoproteins CD11B and CD18 on the surface of his neutrophils, which may have increased the adhesiveness of neutrophils to the pulmonary endothelium. In addition, GM-CSF primed the neutrophils of the patient to an enhanced release of superoxide anions. Both findings may at least partially explain why GM-CSF exerted a deleterious action on the pulmonary endothelial integrity in this patient. Other factors, such as increased platelet-activating factor production by the neutrophils or tumor necrosis factor-mediated mechanisms, may also have played a role. ARDS as a complication of low-dose Ara-C seems less plausible.

Antigens, Differentiation↗

Chronic myelogenous leukemia after treatment with 131I for thyroid carcinoma. Report of a case and review of the literature.

A patient who developed Philadelphia chromosome-positive chronic myelogenous leukemia (CML) 5 years after successful treatment for thyroid carcinoma, is reported. The Philadelphia chromosome was the typical 9;22 translocation. Southern blot analysis showed breakpoint cluster region rearrangement as observed in classical CML. Up to now, only two cases of CML have been reported following treatment for thyroid carcinoma. This rare complication has also been described after therapy for other malignancies. At present, it is not clear whether the development of CML after thyroid carcinoma represents a therapy-induced complication, a coincidence, or an increased susceptibility to secondary malignancies due to the malignant process itself.

Adenocarcinoma↗

In vivo administration of granulocyte-macrophage colony stimulating factor enhances neutrophil function in patients with myelodysplastic syndromes.

We studied the long-term in vivo effects of recombinant granulocyte-macrophage colony stimulating factor (rhGM-CSF) on granulocyte functions in nine patients with myelodysplastic syndrome (MDS). The treatment schedule consisted of a 14 d course of rhGM-CSF (250 micrograms/m2/d s.c.) for patients with refractory anaemia (RA) and refractory anaemia with ringed sideroblasts (RARS), while patients with refractory anaemia with excess of blasts (RAEB) and refractory anaemia with excess blasts in transformation (RAEBt) received a 14 d combination course of rhGM-CSF (250 micrograms/m2 s.c.) and low dose cytosine arabinoside (20 mg/m2 s.c.). rhGM-CSF increased the mean neutrophil count from 3.9 x 10(9)/l to 44 x 10(9)/l. Significant increases of myeloperoxidase content in granulocytes occurred during treatment (P = 0.003). Phagocytosis and killing of Staph. aureus by granulocytes was markedly enhanced during treatment. Microbicidal capacity normalized in four out of six patients during GM-CSF therapy. However, chemotaxis in response to zymosan-activated serum (ZAS) and f-Met-Leu-Phe (f-MLP), was further impaired on the last day of treatment, which was associated with a marked increase in the expression of the granulocyte adhesion receptors CD11a (P = 0.01), CD11b (P = 0.002), CD11c (P = 0.00015) and CD18 (P = 0.0014). GM-CSF therapy did not cause significant changes in hexose monophosphate (HMP)-shunt activity, chemiluminescence, nor superoxide production. The present results show that in vivo administration of GM-CSF is able to repair at least in part the neutrophil anomalies in patients with myelodysplastic syndrome (MDS), which might be useful in modulating host response to infections. However, increased adherence and impaired chemotaxis may explain some toxicities observed during treatment with GM-CSF.

Adult↗

Update on the prognostic implication of morphology, histology, and karyotype in primary myelodysplastic syndromes.

The prognostic value of the FAB classification, bone marrow histology, Bournemouth score, and chromosome findings was studied in 88 patients with primary myelodysplastic syndromes. The median survival for the whole group of patients was 22 months (RA 61.7 months, RARS 31.6 months, CMML 15.7 months, RAEB 10.3 months, and RAEBt 8.2 months). Chromosomal abnormalities were found in 37 of the 70 patients investigated (52%). Only the differences in survival between patients with complex versus normal karyotype were statistically significant (p = 0.02). The presence of small blastic cells, located away from the endosteal surface (abnormal localization of immature blasts or ALIP) appears to be a major prognostic factor in predicting the duration of survival and progression to ANLL, especially in the FAB subgroups RA and RARS. Median survival for the 22 ALIP- cases with RA/RARS was 65 months, compared with 31 months for the ALIP+ cases (p = 0.0006). Nine ALIP+ patients (53%) developed ANLL in contrast to 3 (13%) of the ALIP- cases (p = 0.008). By redefining ALIP and evaluating the number and characteristics of the accompanying cells, histological subtypes were distinguished correlating largely with the FAB subgroups. Our findings demonstrate the prognostic importance of bone marrow biopsy and quantifying the complexity of bone marrow chromosome changes. It should be helpful in evaluating current attempts to find effective treatment for patients with MDS.

Adult↗

First report of chronic meningitis caused by Trichosporon beigelii.

Trichosporon beigelii (Trichosporon cutaneum) was identified as the causative agent of chronic meningitis in a 15-year-old boy with acute lymphocytic leukaemia. After a neutropenic episode following cytostatic treatment and itraconazole therapy as prophylaxis, cerebrospinal fluid (CSF) samples yielded growth of Trichosporon beigelii. Treatment with amphotericin B, flucytosine and high doses of fluconazole was followed by clinical improvement, although CSF pleocytosis remained. The cross-reactivity between Cryptococcus neoformans and Trichosporon beigelii in a cryptococcal antigen latex test was used as a means of diagnosis in CSF and serum samples.

Adolescent↗

Morphologic, immunologic and cytogenetic studies in erythroleukaemia: evidence for multilineage involvement and identification of two distinct cytogenetic-clinicopathological types.

Clinical features, as well as morphology, immunophenotype and cytogenetics were retrospectively studied in 20 patients with an original diagnosis of erythroleukaemia (EL) reclassified according to the FAB criteria. Fifteen patients had de novo EL, five patients had therapy-related EL. Myelodysplasia preceded the onset of EL in eight cases and myelodysplastic features involving multiple haemopoietic lineages were observed at leukaemia presentation in all cases. Immunologic findings confirmed multilineage involvement, showing sub-population of cells expressing platelet-associated markers in more than 50% of cases tested and the presence of a myelomonocytic component, besides glycophorin A-positive cells. Cytogenetically, major karyotype aberrations (MAKA), defined by the presence of three or more aberrant events in the same clone, were observed in 14 cases, minor karyotype aberrations (MIKA) were observed in four cases and normal karyotype in two cases. No differences in the cytological-cytogenetic picture of our patients with de novo EL, and with therapy-related EL were found suggesting that aetiological factors and/or pathogenetic mechanisms common to EL and secondary leukaemia may exist. All patients with MAKA had leftward shift of erythropoiesis with proerythroblasts and basophilic erythroblasts usually representing more than 50% of all erythroid cells. In patients with MIKA or normal karyotype, maturatio of erythroid cells, though morphologically abnormal, was quantitatively preserved and early erythroblasts never exceeded 25% of erythroid cells. Clinically, the haemoglobin level at presentation, as well as in the proportion of patients achieving complete remission after chemotherapy, appeared to be lower in the maturation arrest-MAKA group as compared to the preserved maturation-MIKA/normal karyotype group. Median survival was shorter in the former group (3.5 months) than in the latter (median 13 months). Morphologic-immunologic-cytogenetic studies thus allow for the identification of two distinct cytogenetic-clinicopathological types of EL.

Adult↗

Tc-99m HM-PAO labelled leucocyte scanning for detection of infection in orthopedic surgery.

The use of labelled granulocyte scintigraphy is recognized as a reliable method for detecting osteomyelitis and other skeletal sepsis. Tc-99m hexamethyl propyleneamine oxime (Tc-99m HM-PAO), a lipophilic chelate offers the advantages of availability, lower radiation dose and higher image resolution, compared to other labelling agents. We have scanned 36 orthopedic patients with suspected infection, using autologous granulocytes labelled with Tc-99m HM-PAO. In all cases, scans were compared with clinical, microbiological and/or surgical findings. Sensitivity was 94% and specificity was 80%. We therefore believe that Tc-99m HM-PAO leucocyte scanning provides a useful method for detecting osteomyelitis and other skeletal infections.

Adolescent↗

[Sleeping sickness in German travelers to the tropics].

A brother and sister (the latter having been resident in Ruanda for three years) fell ill with African trypanosomiasis (sleeping sickness) after a two-day safari in the Akagera National Park. Cardinal symptoms were fever, lymphadenopathy and the typical primary lesion (trypanosomal chancre). The diagnosis was confirmed by demonstrating trypanosomes in the peripheral blood. There was no CNS involvement in either case. Administration of suramin, 1 g weekly intravenously for six weeks, quickly brought about regression of the symptoms and the parasitaemia. According to the number of cases reported since 1970, the risk for German travellers to certain African areas of contracting trypanosomiasis is about 0.3 per 100,000. Since in Africa the incidence of the disease is increasing, in some parts considerably, one must reckon with an increasing risk for tourists.

Adult↗

Cytogenetic and clinical investigations in 76 cases with therapy-related leukemia and myelodysplastic syndrome.

Clinical, cytomorphologic, and cytogenetic investigations were carried out in a series of 76 secondary MDS and ANLL. Chromosome abnormalities were more frequent in patients with a history of multiple myeloma or macroglobulinemia (92%) and myeloproliferative disorders (82%) than in patients with previous breast cancer (40%). The secondary hematologic malignancies were mostly a trilineage bone marrow disorder. The most commonly found cytogenetic anomaly was monosomy 7, followed by total or partial loss of chromosome 5. In addition six other chromosomes, i.e., chromosome 3, 8, 9, 12, 17, and 21 seemed to be consistently involved in the pathogenetic mechanisms of secondary leukemia and MDS.

Adolescent↗

Characterization of deletions of chromosome 7 short arm occurring as primary karyotypic anomaly in acute myeloid leukaemia.

Three patients with an acute myeloid leukaemia (AML) showed a deletion of the short arm of chromosome 7 with loss of the deleted material. The 7p- anomaly originated from either a terminal or an interstitial deletion and it represented the only karyotypic aberration in all the three cases. According to the clinical, morphological and immunological features of this series of patients, a 7p- chromosome appears to be associated with a group of AML with myelodysplastic features in the bone marrow, including secondary disorders in patients treated for a previous malignancy.

Adult↗

In vitro and in vivo evaluation of granulocyte labeling with [99mTc]d,1-HM-PAO.

The functional integrity of white blood cells labeled with [99mTc]d,1-HM-PAO containing variable amounts of the ligand or of the 99mTc activity was evaluated by enzymatic tests and by measuring random migration, chemotaxis, phagocytosis, killing, and adhesion. The ultrastructure of labeled cells was studied by electron microscopy. The tracer dose and the HM-PAO concentration did not significantly affect phagocytosis and killing. The results of the other tests remained normal. A maximum labeling efficiency of 80% was reached by incubating the granulocytes for 20 min with 10-20 mCi of [99mTc]d,1-HM-PAO containing 50 micrograms of the ligand in 1 ml of saline. There was only a slow washout of 20% of activity from the labeled cells in 24 hr. The ultrastructure was not influenced by the labeling technique. Proven infection sites of 17 orthopedic patients were clearly visualized. After a short transient lung uptake, there was a clear spleen and moderate liver uptake with early bladder and late prominent colon visualization. Because of the lower cost, favorable radiation dose and more suitable tracer characteristics, this technique is a promising alternative for 111In labeling of white blood cells.

Bacterial Infections↗