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H Piguet

Publications and source records attributed to H Piguet.

At least 19 recordsLinked to original sources
PubMed1996

Ifosfamide, etoposide, cytarabine, and methotrexate as salvage chemotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma.

BACKGROUND: Patients with relapsed or resistant non-Hodgkin's lymphoma (NHL) have a poor prognosis and are rarely cured with usual salvage chemotherapy. Intensive treatment with the support of peripheral blood stem cells (PBSC) may be an effective therapy for these patients. We used a combination of ifosfamide, etoposide, cytarabine, and methotrexate (IVAM) with the intention both to reduce tumor burden and collect PBSC prior to transplantation. METHODS: Thirty-one patients (17 with relapsed NHL and 14 with refractory NHL) were treated with 2 courses of chemotherapy: IVAM regimen (ifosfamide, 1500 mg/m2 daily for 5 days plus mesna; etoposide, 150 mg/m2 daily for 3 days; cytarabine, 100 mg/m2 daily for 3 days; and methotrexate, 3 g/m2 on Day 5, with leucovorin rescue). Twenty-three patients had an intermediate grade and 8 patients had a high grade lymphoma. RESULTS: After IVAM therapy, 19 patients (61%) achieved complete response, 8 patients (26%) achieved partial response and 4 patients (13%) failed to respond. The major toxicity of IVAM was myelosuppression, but there were no toxic deaths. PBSC harvest could be performed in 29 patients (94%) with a median granulocyte-macrophage colony-forming unit count of 55 x 10(4)/kg (range, 2-391 x 10(4)/kg). Three patients could not undergo transplantation because of disease progression. One patient received a syngeneic transplant, 25 patients received PBSC transplantation, and 2 patients received a bone marrow transplant. In an intent-to-treat analysis, the overall survival rate at 4 years was 37% for the whole group (95% confidence interval: 22-55). CONCLUSIONS: We conclude that IVAM is an effective salvage chemotherapy for refractory or relapsed NHL and permits PBSC collection in most of these patients.

Adult↗
PubMed1996

p190bcr/abl rearrangement in myelodysplastic syndromes: two reports and review of the literature.

We describe two patients with myelodysplastic syndrome (MDS) and the Philadelphia chromosome (Ph). The patients were 64- and 69-year-old men who were diagnosed as having refractory anaemia with excess of blasts. During the terminal phase, the MDS evolved to myeloblastic leukaemia. Chromosome analysis showed normal karyotypes mixed with metaphases containing a classic Ph chromosome t(9;22)(q34;q11). Surprisingly, molecular studies showed breakpoint cluster region rearrangement between exons e1 and a2, compatible with a p190bcr/abl breakpoint, as observed in acute lymphoblastic leukaemia. We discuss the correlation between MDS and acquisition of the Ph chromosome, and the occurrence of p190bcr/abl in MDS.

Adult↗
PubMed1994

Residual disease in B-cell chronic lymphocytic leukemia patients and prognostic value.

Twenty-two B-cell chronic lymphocytic leukemia (CLL) patients were investigated to evaluate residual disease in clinico-hematological remission. Residual disease was determined by monotypy of surface light-chain expression and by dual-color staining with CD5 and CD19 markers. Samples were analyzed on flow cytometer. Total CD19+ cells above 25%, the CD5+CD19+/total CD19+ cells ratio above 0.25, clonal excess above 0.4 were considered positive for residual disease. According to these immunological criteria, only four cases achieved phenotypic remission. Our data confirm that dual marker analysis is more sensitive than clonal excess and may predict an early relapse. Ig gene rearrangements were studied by Southern blot analysis using IGHJ and IGKC probes in fifteen cases. All 12 cases that retained a detectable rearrangement displayed a phenotypic residual disease. Conversely, in two cases, DNA analysis failed to detect the residual disease characterized by flow cytometry. In conclusion, this study suggests that in B-CLL, dual marker analysis is sensitive in predicting an early relapse in sequential evaluations of residual disease, whereas rearranged bands are undetectable when the proportion of malignant cells is low.

Adult↗
PubMed1993

Expression of the hyaluronan-binding glycoprotein hyaluronectin in leukemias.

Hyaluronectin (HN), a hyaluronan (hyaluronic acid, HA)-binding glycoprotein is normally expressed in the nervous system, found in the desmoplasia of tumours, and is also produced in vitro by peripheral blood mononuclear cells. We have therefore investigated the expression and the production of HN by leukemic cells, with the hypothesis that HN would be expressed in leukemias of the myeloid lineage. Fresh and frozen leukemic cells were studied from 70 patients of whom 53 had acute myeloblastic leukemia (AML). HN was strongly expressed (> 80% blood cells) in two out of 13 M4 AMLs and four out of four M5B AMLs. One further M4 AML displayed 25% positive cells and two 20% cell positivity cases were seen, in one case of M4 AML and in one case of chronic myelomonocytic leukemia (CMML). The rest of the cases of AML as well as all cases of acute lymphoblastic leukemia (ALL) showed almost no positivity (< 1%). The residual positive cells appeared to be normal blood promonocytes. Taken together > or = 20% positive cells was seen in eight out of 56 (14%) examined myeloid leukemias. The HN production was significantly higher (p < 0.0001) in cell culture media of M4 and M5 AML cells than in other AML or ALL cell culture media. A significant correlation was found (p < 0.0001) between the number of HN-positive leukemic cells and the number of cells with a monocytic morphology, suggesting that HN is a marker for the promonocyte.

Acute Disease↗
PubMed1992

Translocations involving band 3q27 and Ig gene regions in non-Hodgkin's lymphoma.

We report a series of 20 non-Hodgkin's lymphomas (NHL) in which cytogenetic analysis showed a translocation involving band 3q27 and the site of one of the three Ig genes (14q32, 2p12, 22q11) in the neoplastic cells. These cases were found in a series of 319 patients with clonal chromosomal abnormalities studied over a 7-year period. Fourteen patients had diffuse lymphoma, mainly of large cell type and the remaining six were follicular lymphomas. All cases studied were of B-cell phenotype. A t(3;14)(q27;q32) was commonest, found in 15 patients (4.7%), with the two variant translocations, t(3;22)(q27;q11) and t(2;3)(p12;q27), being found in three and two patients, respectively. Additional chromosomal defects were present in most patients, but two patients had this type of translocation as the sole abnormality. These results indicate that translocations involving band 3q27 and Ig genes are not uncommon, and suggest that a novel oncogene, located at band 3q27, may be implicated in B-cell NHL.

Adult↗
PubMed1992

Immunological evaluation of harvested stem cells obtained by leukapheresis after chemotherapy.

Some patients suffering from malignancies may benefit of myeloablative chemotherapy followed by hematological reconstitution with autologous peripheral blood reinfusion. A quick evaluation of the number of hematopoietic progenitors present in leukapheresis blood samples is necessary to ensure the collection of a sufficient number of these cells. A study was performed on a series of 25 leukapheresis following initial chemotherapy. The number of granulomonocytic colony-forming unit (CFU-GM) and the number of CD34+ cells were evaluated simultaneously, in each sample. Results have shown a relatively strong linear correlation between both methods of evaluation of hematopoietic progenitors, suggesting that immunophenotyping could be a useful method to estimate the number of progenitors.

Adult↗
PubMed1992

[Production of hyaluronan-binding glycoprotein by human monocytes. Its use as marker in myeloid leukemia].

A hyaluronan-binding protein fraction was isolated by affinity chromatography of peripheral human blood mononuclear cell culture medium through immobilized hyaluronan. The presence of a hyaluronan-binding protein similar to human brain hyaluronectin was demonstrated by (i) the ELISA method on hyaluronan-coated plastic plates using anti-hyaluronectin antibodies, (ii) the lowering of the elution volume of the protein on liquid gel chromatography in the presence of hyaluronan, (iii) the extinction of the reaction to human brain hyaluronectin when antibodies were absorbed out with monocyte hyaluronectin, (iv) western blotting with polyclonal and monoclonal anti-hyaluronectin antibodies. The hyaluronectin-producing cells were adherent (10 min., 37 degrees C) to plastic, esterase (+) and CD 14 (+) cells and had the morphology of monocytes. The protein expression was investigated in leukemic cells by means of the immunocytochemical method. Hyaluronectin expression was restricted to 4/12 of M4 and M5 types of acute myeloid leukemias. Other myeloid leukemia and acute lymphoblastic leukemia cells were negative. The results indicate that hyaluronectin can be produced under free form in the absence of hyaluronan, by human peripheral blood monocytes. It supports the hypothesis that the expression of hyaluronectin in tumour stroma could be due, at least in part, to inflammatory cells of the tumour. The expression of the protein by M4 and M5 acute myeloid leukemia cells suggests that hyaluronectin could be synthesized by immature cells of the monocytic lineage as well as by mature monocytes.

Biomarkers, Tumor↗
PubMed1991

Cytogenetic studies in untreated Hodgkin's disease.

Very little data have been published on cytogenetic abnormalities in Hodgkin's disease (HD) and their correlation with clinicopathologic features are scanty. We have performed chromosomal analysis of lymph nodes from 60 previously untreated HD patients and obtained analyzable metaphases in 49 patients (82%). Chromosomal abnormalities were found in 33 patients (55%) but only 31 karyotypes could be, at least partially, described. Twenty-nine cases showed numerical abnormalities that involved all chromosomes with the exception of chromosomes 13 and Y, which were gained less frequently and lost more frequently than other chromosomes. Structural abnormalities were found in 30 cases, involving all chromosomes except Y. Chromosomal regions 12p11-13, 13p11-13, 3q26-28, 6q15-16, and 7q31-35 were rearranged in more than 20% of the analyzable cases. No correlation was found between cytogenetic findings and initial characteristics. When compared with diffuse B-cell lymphomas, defects in regions 2p25 (P less than .01), 12p11-13 (P less than .01), 13p11-13 (P less than .01), 14p11 (P less than .01), 15p11-13 (P less than .02), and 20q12-13 (P less than .05) were more frequent in HD. When compared with T-cell lymphomas, only defects in regions 12p12-13 (P less than .01) and 13p11-13 (P less than .01) were more frequent in HD. Failure to obtain analyzable metaphases was correlated with stage IV of the disease (P less than .05) and with a poor survival (P less than .01), but cytogenetic results showed no other correlation with clinical outcome. We conclude that molecular studies in HD should be focused on the short arms of chromosomes 12 and 13. Determination of the clinical significance of cytogenetic findings will require a larger number of patients and a longer follow-up period.

Adolescent↗
PubMed1991

Rearrangements of immunoglobulin light and heavy chain genes and correlation with phenotypic markers in B-cell chronic lymphocytic leukemia.

Twenty-five patients with B-cell chronic lymphocytic leukemia (B-CLL) were investigated to correlate the immunological phenotype with the description of the Ig gene rearrangements of the B-cell clone. All patients were positive for the CD19 antigen and one pan B-antigen, markers of late cells (CD20, CD37 or Y2955). Twenty-four of the 25 patients tested expressed monoclonal cell surface immunoglobulin (SIg). The CD5 antigen was present in 21 of the 25 tested patients. Immunoglobulin gene rearrangements were detected by hybridization of the BamHI, EcoRI, BgIII, and HindIII digested genomic DNAs to the IGHJ, IGKC, IGLC, and IGLJ2 probes. Twenty-four of 25 patients had two rearranged IGH loci. The IGKC rearrangements were observed in 20 patients. In four patients, the IGK loci were deleted on both chromosomes. One patient without SIg displayed a germline pattern. All six patients with lambda producing B-CLL showed a lambda gene rearranged band, although the use of IGL polymorphism to investigate IGL rearrangements must be noted. These clonal rearrangements of IGL genes, together with the detection of either the kappa or lambda light chain of SIg, confirm that patients with B-CLL meet the developmental scheme of ordered light chain gene rearrangements.

B-Lymphocytes↗
PubMed1990

Effect of chemotherapy on resting energy expenditure in patients with non-Hodgkin's lymphoma. Results of a sequential study.

This study compared the resting energy expenditure (REE) modifications observed during successive intensive identical chemotherapy courses in non-Hodgkin's lymphoma patients to assess indirectly the metabolic changes induced by the cytotoxic effect of drugs on the tumor. With this therapeutic regimen, reduction of tumor mass is mostly achieved during the first course of chemotherapy. The study included 10 non-Hodgkin's lymphoma adult patients receiving three intensive 5-day courses of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, vindesine, and bleomycin. Resting energy expenditure was evaluated by indirect calorimetry during each course, first within the first 2 days before chemotherapy and then on days 2, 3 and 5. Initial REE (day 0) on entry into the study (21.8 +/- 1.2 kcal/kg.d-1) represented 99 +/- 6.7% of theoretical REE. Resting energy expenditure on day 0 was lower during course 2 and 3 (19.1 +/- 0.7 and 18.4 +/- 1.8 kcal/kg/d) than during course 1 (21.8 +/- 1.2 kcal/kg/d). The REE profile was different among the 3 courses: course 1 induced a significant REE decrease on days 3 and 5 (P less than 0.01); during course 2, REE remained stable and was lower than during course 1; during course 3, REE increased on days 2, 3, and 5 (P less than 0.05). Energy balance was positive during the three courses and nutritional status remained stable. The REE decrease observed during course 1 may be regarded as the metabolic effect of chemotherapy on the tumor metabolism.

Adult↗
PubMed1990

Cyclosporin for treatment of life-threatening alloimmunization.

We describe a 16-year-old girl with aplastic anemia who, 1 year after initial diagnosis developed a refractory state to platelet transfusions due to alloimmunization and resulting in severe bleeding. Treatment with cyclosporin, initially prescribed as treatment of the bone marrow failure, resulted in prompt decrease in lymphocytotoxic antibodies, which paralleled a marked improvement in platelet recovery. To our knowledge, such a dramatic effect of cyclosporin on alloimmunization has not been previously reported and merits further attention.

Adolescent↗
PubMed1990

New evaluations of circulating granulocyte and macrophage stem cells in healthy adults using conditioned media and recombinant human growth factors.

Peripheral human blood contains granulo-monocyte (CFU-GM) and eosinophil (CFU-Eo) progenitors. In vitro, the number of colony forming units is thought to range from 0.1-14 per 2 x 10(5) plated cells. We show that the number of CFU-GM, Eo depends on culture methods. By modifying the usual assay method (using human umbilical cord plasma and the association of 2 stimulating conditioned media: activated lymphocyte conditioned medium and bone marrow fibroblast conditioned medium), we found different circulating CFU-GM, Eo numbers. The mean number of circulating CFU-GM, Eo in 107 healthy adults was 22.4 per 2 x 10(5) plated cells (range: 1-84). There was a slight difference between males (mean number: 23.6) and females (mean number: 20.4). The mean number of CFU-GM, Eo harvested on Percoll gradient was 123/ml of peripheral blood (range: 7-513). These results are far over those commonly reported in literature. This suggests that these latter results were probably underestimated. The use of recombinant human interleukin 3 and recombinant human GM (granulocyte-monocyte) colony-stimulating factors shows that CFU-GM, Eo numbers are found to be comparatively increased compared to that obtained with our modified method (using rhIL-3 alone), or that the size of those colonies is notably increased (using rhIL-3 + rhGM-CSF).

Adult↗
PubMed1989

[Preventive treatment of infection caused by gram-negative bacteria using anti-lipopolysaccharide antibodies. Evaluation in patients with aplasia].

The prophylaxis of severe Gram-negative infections with human antiserum to lipopolysaccharide (LPS) was evaluated in a randomised study of 60 patients with therapeutic aplasia for leukaemia. The antiserum was found to be ineffective in preventing Gram-negative infections. The levels of anti-LPS antibodies showed that passive immunization was obtained in only one half of the patients. These disappointing results warrant further investigations to evaluate the effectiveness of this prophylactic treatment.

Adult↗
PubMed1989

Peripheral blood stem cells collected before and after leukapheresis in the very early remission phase of hematopoietic malignancies.

Human peripheral blood obtained after chemotherapy-induced remission in hemopoietic malignancies has been suggested to be a potential substitute for autologous bone marrow as regards autologous hematopoietic reconstitution. The schedule and consequences of early leukapheresis are, however, still imprecise. We report a study performed in two series of, respectively, 10 and 14 patients where sequential leukapheresis (total number = 84) was evaluated with regard to colony-forming unit (CFU) potency. Our data demonstrate that adequate numbers of progenitor cells can be collected by leukapheresis and that, even when this is performed at an early stage after remission, subsequent hematopoietic reconstitution is not impaired.

Adult↗
PubMed1989

[Splenectomy in chronic idiopathic thrombopenic purpura in adults. Apropos of 49 cases].

The authors reviewed the case files of 49 adult patients undergoing splenectomy for chronic idiopathic thrombocytopenic purpura at the Centre Henri Becquerel between 1970 and 1987. Although the postoperative course was straightforward in 83.7% of cases, one reoperation for subphrenic abscess was necessary and there was one postoperative death. Remission from thrombocytopenia was obtained in 87.5% of the patients, but only transiently in 8.5% of them. No preoperative predictive factors could be demonstrated. An early postoperative rise in the platelet count to more than 500 G/litre appears to ensure a good subsequent result. Secondary infectious complications are not exceptional and can be fatal (one death in our series); they require prophylaxis by anti-pneumococcal vaccination. The place of prophylactic antibiotic therapy has yet to be defined.

Adolescent↗