Biomedical subjects

D Simon

Publications and source records attributed to D Simon.

At least 109 records · Page 6Linked to original sources

PubMed2000

Associations of tibial lead levels with BsmI polymorphisms in the vitamin D receptor in former organolead manufacturing workers.

We evaluated associations of tibial lead levels with polymorphisms in the vitamin D receptor (VDR) in 504 former organolead manufacturing workers with past exposure to lead. In this cross-sectional study, we measured tibial lead by (109)Cd K-shell X-ray fluorescence. Tibial lead was evaluated in subjects with different VDR genotypes defined using the BsmI restriction enzyme, adjusting for confounding variables. Study participants had a mean age +/- SD of 57.4 +/- 7.6 years. A total of 169 (33.5%) subjects were homozygous for the BsmI restriction site (designated bb), 251 (49.8%) were heterozygous (Bb), and 84 (16.7%) were homozygous for the absence of the restriction site (BB). Among all of the study subjects, tibial lead concentrations were low, with a mean +/- SD of 14.4 +/- 9.3 microg Pb/g bone mineral. There were only small differences in tibial lead concentrations by VDR genotype, with mean +/- SD tibial lead concentrations of 13.9 +/- 7.9, 14.3 +/- 9.5, and 15.5 +/- 11.1 in subjects with bb, Bb, and BB, respectively. In a multiple linear regression model of tibial lead concentrations, the VDR genotype modified the relation between age and tibial lead concentrations; subjects with the B allele had larger increases in tibial lead concentrations with increasing age (0.37, 0.48, and 0.67 microg/g per year of age in subjects with bb, Bb, and BB, respectively; the adjusted p-value for trend in slopes = 0.04). The VDR genotype also modified the relation between years since last exposure to lead and tibial lead concentrations. Subjects with bb evidenced an average decline in tibial lead concentrations of 0.10 microg/g per year since their last exposure to lead, whereas subjects with Bb and BB evidenced average increases of 0.03 and 0.11 microg/g per year, respectively (the adjusted p-value for trend in slopes = 0.01). Polymorphisms in the vitamin D receptor modified the relations of age and years since the last exposure to lead with tibial lead concentrations. Although controversy remains on the influence of the VDR genotype on bone mineral density, the data suggest that variant VDR alleles modify lead concentrations in bone, either by influencing lead content or calcium content or both.

Adult↗

PubMed2000

Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and [delta]-aminolevulinic acid dehydratase genes.

A cross-sectional study was performed to evaluate the influence of polymorphisms in the [delta]-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead levels in 798 lead workers and 135 controls without occupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by (109)Cd-induced K-shell X-ray fluorescence, and DMSA-chelatable lead was estimated as 4-hr urinary lead excretion after oral administration of 10 mg/kg DMSA. The primary goals of the analysis were to examine blood lead, tibia lead, and DMSA-chelatable lead levels by ALAD and VDR genotypes, controlling for covariates; and to evaluate whether ALAD and VDR genotype modified relations among the different lead biomarkers. There was a wide range of blood lead (4-86 microg/dL), tibia lead (-7-338 microg Pb/g bone mineral), and DMSA-chelatable lead (4.8-2,103 microg) levels among lead workers. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele and there were no homozygotes. For VDR, 10.7% (n = 85) had the Bb genotype, and 0.5% (n = 4) had the BB genotype. Although the ALAD and VDR genes are located on different chromosomes, lead workers homozygous for the ALAD(1) allele were much less likely to have the VDR bb genotype (crude odds ratio = 0.29, 95% exact confidence interval = 0.06-0.91). In adjusted analyses, subjects with the ALAD(2) allele had higher blood lead levels (on average, 2.9 microg/dL, p = 0.07) but no difference in tibia lead levels compared with subjects without the allele. In adjusted analyses, lead workers with the VDR B allele had significantly (p < 0.05) higher blood lead levels (on average, 4.2 microg/dL), chelatable lead levels (on average, 37.3 microg), and tibia lead levels (on average, 6.4 microg/g) than did workers with the VDR bb genotype. The current data confirm past observations that the ALAD gene modifies the toxicokinetics of lead and also provides new evidence that the VDR gene does so as well.

Adolescent↗

PubMed2000

Management of diabetic patients by general practitioners in France 1997: an epidemiological study.

To describe the characteristics of diabetic patients, the associated risk factors, the complications of the disease and its management by general practitioners (GPs) in France, a randomised sample of French GPs was asked to record data on all consecutive diabetic patients attending a regular visit within 3 months. Data were obtained by interview, clinical examination and usual follow-up complementary examinations of the patients. Patients were classified into 3 groups:, patients treated with insulin and considered to have type 1 diabetes, [2i], insulin-treated patients expected to have type 2 diabetes, [2d], patients with type 2 diabetes and not treated with insulin. Data from 7540 diabetic out-patients were recorded by 3084 GPs: 657 patients (8.7%) belonged to group 1, 1383 patients (18.3%) to group 2i and 5351 (71.0%) to group 2d. Patients, including 53.7%, [2i] 54.1%, and [2d] 56.5% of men, were (mean +/- SE) 58.8 +/- 0.7, [2i] 63.4 +/- 0.3, and [2d] 63.9 +/- 0.2 years old, respectively. Duration of diabetes was 15.9 +/- 0.4, [2i] 11.4 +/- 0.2, and [2d] 10.1 +/- 0.1 yr. The last fasting blood glucose level (laboratory assay) was 1.61 +/- 0.02, [2i] 1.68 +/- 0.01, and [2d] 1.61 +/- 0.01 g/L, and the last HbA1c 8.5 +/- 0.1, [2i] 8.1 +/- 0.1, and [2d] 7.8 +/- 0.1%, respectively. Tobacco smoking was observed in 19.2%, [2i] 13.1%, and [2d] 12.6% of the patients, hypertension in 39.6%, [2i] 55.9%, and [2d] 58.6%, micro- or macro-albuminuria in 18.6%, [2i] 11. 2%, and [2d] 9.5%, retinopathy in 31.1%, [2i] 12.9%, and [2d] 8.6%, and history of coronary artery disease in 16.3%, [2i] 15.0%, and [2d] 12.8%. Self-monitoring of blood glucose was performed by 93.2%, [2i] 37.9%, and [2d] 16.9% of the patients. During the previous 12 months, a visit had been performed with a diabetologist in 54.0%, [2i] 20.7%, and [2d] 12.9% of the patients, with an ophthalmologist in 62.9%, [2i] 51.5%, and [2d] 49.4%. These results underline the specific characteristics of French diabetic patients. A high prevalence of uncontrolled risk factors, mainly hypertension, contrasts with a relatively low frequency of micro- and macro-angiopathy, maybe underestimated by non-systematic routine follow-up. Closer collaboration between GPs and specialists should be developed to improve the management and care of diabetic patients in France.

Alcohol Drinking↗

PubMed2000

Mapping of a minimal deleted region in human hepatocellular carcinoma to 1p36.13-p36.23 and mutational analysis of the RIZ (PRDM2) gene localized to the region.

Human chromosome band 1p36 commonly undergoes loss of heterozygosity (LOH) in hepatocellular carcinoma (HCC) but the minimal deleted region remains to be mapped. This chromosomal region contains a candidate HCC suppressor gene, RIZ (PRDM2), that is a member of the PR (PRDI-BF1-RIZ homology)-domain-containing zinc finger gene family. One characteristic of this family is the unusual yin-yang involvement in human cancers. The PR-domain-containing RIZ1 product of the RIZ locus, in contrast to the PR-domain-minus product RIZ2, is commonly lost or underexpressed in HCC. Furthermore, RIZ1 can induce cell cycle arrest, apoptosis, or both and suppress HCC tumorigenicity in nude mice. To help identify the putative HCC locus on 1p36 and to evaluate a genetic role of RIZ in HCC, we studied 97 HCC cases and mapped a minimal deleted region in HCC to 1p36.13-p36. 23 between markers D1S434 and D1S436. Notably, RIZ mapped within this region and was found to undergo LOH in 37% (25/67) of HCC cases. Single-strand conformation polymorphism (SSCP) analysis, however, did not show mutations in the PR-domain region of RIZ1 in 49 cases of HCC examined. Our data suggest that the RIZ locus is a target of frequent deletion in HCC, but that the more common way of RIZ inactivation in HCC may not involve mutations that alter peptide sequences. Genes Chromosomes Cancer 28:269-275, 2000.

Alleles↗

PubMed2000

[Description of type 2 diabetes mellitus in residents of Ile-de-France aged at most 70 years].

Our study of patients with type 2 diabetes mellitus residing in the Paris area (Ile-de-France) aged 70 years or younger included 1 591 patients examined by national health insurance expert physicians who also filled out a self-administrated questionnaire. Their primary care physicians also answered a questionnaire (79% participation, indicating their personal implication). We found that diabetes was most often discovered during regular check-ups. Single-drug regimens were the most widely used. Sulfamides were prescribed for 77% of the patients. Among the 912 patients who were overweight (BMI > 28 Kg/m2), 34.3% were taking sulfamides alone despite the fact that metformin is recommended as the first intention drug for these patients. Blood pressure control was not satisfactory in 30% of the patients who were treated or not for high blood pressure. This proportion rose to about 50% among treated patients alone. The patients appeared to be knowledgeable about the risk of complications, particularly ocular complications. They were aware of a certain number of messages but the results would suggest difficulty in application.

Adult↗

PubMed2000

Von Willebrand factor gene polymorphisms in three Brazilian ethnic groups.

Von Willebrand factor gene polymorphisms were studied in three Brazilian ethnic groups: Euro-Brazilians, Afro-Brazilians, and Amerindians. Six polymorphic sites were analyzed: RsaI (exon 18), NlaIV (exon 20), HphI, KpnI, D1472H, and V1565L (all four in exon 28). The allele frequencies were significantly different between Euro- and Afro-Brazilians for RsaI, HphI, D1472H, and V1565L, while in Amerindians NlaIV and HphI showed significant differences among tribes. This is the first report of these allele frequencies in Amerindians. Eighteen haplotypes were observed, and they showed significant differences between Euro- and Afro-Brazilians, among Amerindian tribes, and among the three ethnic groups. These results furnish important background data for evolutionary and anthropological investigations; in addition, they will be useful for establishing the origin and molecular characterization of the different forms of von Willebrand disease, as well as for detecting carriers and offering genetic counseling to those with this condition.

Brazil↗

PubMed1999

Decreased RIZ1 expression but not RIZ2 in hepatoma and suppression of hepatoma tumorigenicity by RIZ1.

The distal short arm of human chromosome 1 (1p36) is commonly altered in primary hepatoma tumors and cell lines. This region includes the RIZ gene, a member of the PR (PRDI-BF1/BLIMP1 and RIZ homology) domain family of transcription factors. An unusual feature of this family is the yin-yang involvement in human cancers. Two products are normally produced from a PR family member which differ by the presence or absence of the PR domain; the PR-plus product is disrupted or underexpressed whereas the PR-minus product is present or overexpressed in cancer cells. The PR-plus product RIZ1 is a candidate tumor suppressor because it can induce G(2)/M arrest and/or apoptosis and is commonly underexpressed in breast cancer. Here, we have investigated the role of RIZ in hepatoma. RIZ1 transcript was undetectable in 80% of hepatoma cell lines (8 of 10 lines examined). RIZ1 expression was also decreased in hepatoma tumor specimens. In contrast, RIZ2 transcript was uniformly present in all samples examined. Adenovirus-mediated RIZ1 expression in hepatoma cell lines caused cell cycle arrest in G(2)/M and/or programmed cell death. RIZ1 expression also suppressed tumorigenicity of hepatoma cells in nude mice. Our observations reinforce the yin-yang notion of RIZ gene products in human cancer and suggest a RIZ1 tumor suppressor role in hepatoma.

Animals↗

PubMed1999

A solid-phase immobilized epitope immunoassay (SPIE-IA) permitting very sensitive and specific measurement of angiotensin II in plasma.

We have developed a new enzyme immunometric assay for angiotensin II (AII) based on SPIE-IA technology (solid-phase immobilized epitope-immunoassay). A monoclonal antibody with optimal properties (mAb3 131) was selected from a series of 19 anti-AII mAbs. The mAb had to be purified from ascitic fluid in a specific manner in order to remove endogenous AII from the antibody-binding sites. We established a sensitive (minimum detectable concentration 0.5 pg/ml) and precise (CV below 15% in the 2-100 pg/ml range) SPIE-IA. Using different AII-related peptides, we observed that this new assay has a specificity profile that compares favourably with the corresponding competitive immunoassay. We have used the assay to measure AII in 42 plasma samples, and demonstrated a good correlation with values obtained using a commercial radioimmunoassay. Assay specificity was supported by HPLC fractionation experiments, confirming the absence of interference induced by endogenous AII-related products.

Acetylcholinesterase↗

PubMed1999

Neurobehavioral function and tibial and chelatable lead levels in 543 former organolead workers.

OBJECTIVE: To evaluate the associations between tibial lead, dimercaptosuccinic acid (DMSA)-chelatable lead, and neurobehavioral function in former organolead manufacturing workers with past exposure to organic and inorganic lead. METHODS: Data were collected from 543 subjects with a mean age of 58 years and an average of 17.8 years since last lead exposure. Years since last exposure to lead was used to estimate tibial lead levels in the year of last occupational lead exposure, termed "peak tibial lead." Current tibial lead levels, measured by x-ray fluorescence, were extrapolated back using a clearance half-time of lead in tibia of 27 years, assuming first-order clearance from tibia. RESULTS: Peak tibial lead levels ranged from -2.2 to 105.9 microg Pb/g bone mineral, and DMSA-chelatable lead levels were between 1.2 and 136 microg. After adjustment for confounding variables, peak tibial lead was a significant negative predictor of performance on the Wechsler Adult Intelligence Scale-Revised vocabulary subtest (p = 0.02), serial digit learning test (p = 0.04), Rey Auditory-Verbal Learning Test (immediate recall and recognition, p = 0.03 for each), Trail Making Test B (p = 0.03), finger tapping (dominant hand [p = 0.02] and nondominant hand [p < 0.01]), Purdue pegboard (dominant hand, nondominant hand, both hands, and assembly, p < 0.01 for each), and Stroop Test (p < 0.01). Moreover, with one exception, average neurobehavioral test scores were poorer at higher peak tibial lead levels. DMSA-chelatable lead was only significantly associated with choice reaction time (p = 0.01). CONCLUSION: Peak tibial lead was consistently associated with poorer neurobehavioral test scores, particularly in the domains of manual dexterity, executive ability, verbal intelligence, and verbal memory.

Adult↗

PubMed1999

Multiple genetic alterations, 4q28, a new suppressor region, and potential gender differences in human hepatocellular carcinoma.

Primary hepatocellular carcinomas (HCCs) of different etiologies were studied to determine the rate of alteration of several genetic regions previously associated with the HCC phenotype. The focus of our study was to identify the frequency of genetic alterations within individual HCCs and their distribution among male and female cases. Genetic differences were evaluated between DNA isolated from tumor (T) and corresponding non-tumor (N) tissue using short tandem repeat (STR)-microsatellites and restriction fragment length polymorphism (RFLP) analyses. Twenty-eight HCC cases were studied with polymorphic markers from different parts of the genome. Three or more loci were identified with genetic alterations from 28 loci tested in 63% of HCC cases. The highest frequency of alteration occurred in the chromosome regions 1p36, 13q14, 17p13, and the 4q28 region identified in HCCs for the first time. High loss of heterozygosity (LOH) in 1p36, 4q28, 13q14, and 17p13 regions indicates important HCC suppressors within the regions. The study documents no association between cause and specific genetic change or their frequency in HCCs analyzed. The data document a significant gender distortion for genetic alteration in chromosome 13q14 and 17p13 regions and a concordant gender alteration rate in the 1p36 and 4q28 regions. An overall higher frequency of genetic alterations was identified in male cases. Future study with an extended number of HCC cases should substantiate the frequency of alteration between genders and identify tentative suppressors in the 1p36 and 4q28 regions.

Adult↗

PubMed1999

[Cytokine-producing lymphoma T cells in the skin and peripheral blood associated with atopy and hypereosinophilia].

A 47 year old female with a history of hay fever and a family history of atopic eczema developed localized pruritic eczematous lesions over a three year period. The lesions became generalized within just three months. Episodes of recurrent erythroderma followed and became resistant towards any therapy. Many immediate and some delayed hypersensitivity reactions were diagnosed. In the peripheral blood, leukocytosis and hypereosinophilia were observed. In addition, levels of total IgE were highly increased in serum. Immunophenotyping of the peripheral blood T cells revealed evidence for a clonal expansion of highly activated CD4(+) T cells with reduced CD2 and CD5 surface expression. After a three-year course of severe disease, the diagnosis of a pleomorphic T cell lymphoma of the small-cell variant was established by histological examination and a polymerase-chain reaction technique to determine the rearrangements of the gamma chain of the T cell receptor. Moreover, analysis of cytokine gene expression suggested that the high IgE concentrations and eosinophil numbers observed in this patient were likely due to an increased IL-5 and IL-13 production by lymphoma T cells.

CD4-Positive T-Lymphocytes↗

PubMed1999

Studies of oncogenes and tumor-suppressor genes in human thyroid carcinomas, and their clinical implications.

INTRODUCTION AND DISCUSSION: Molecular genetic investigations relating to thyroid cancer have started to gain clinical importance, with discovery of the tumor-specific oncogenes PTC 1-3 in papillary thyroid cancer and the syndrome-specific mutations of the RET protooncogene in MEN-2a, MEN-2b and familial MTC patients. Furthermore, the thyroid-specific sodium-iodine symporter, causing iodine accumulation in thyroid tissue, has been cloned and now offers studies to enhance iodine and radioiodine uptake in thyroid cancer, which could soon prove to be clinically applicable.

Carcinogens↗

PubMed1999

MEN I gene mutations in sporadic adrenal adenomas.

Loss of heterozygosity (LOH) on chromosome 11q13 occurs in about 20% of sporadic adrenal neoplasms. Adrenal lesions, mostly benign, occur in up to 40% of patients from MEN I kindreds. The MEN I gene, positioned on 11q13, has been considered a primary candidate gene in these lesions. We studied a group of 15 patients with sporadic adrenal adenoma, and 1 patient with multinodular hyperplasia. Of the 16 patients, 4 had incidentally discovered masses, 5 had Conn's syndrome, 6 suffered from Cushing's syndrome, and 9 had high sex hormone production. Studies with the markers D11S480, PYGM, D11S449, and D11S987 in 13 patients (12 of whom were from our group of 16) revealed 4 losses of heterozygosity on D11 S480 on 11q13, but the deletion did not affect the MEN I gene in any case. We present complete direct DNA sequencing data of the menin gene in 14 sporadic adrenal adenomas and one with adrenal hyperplasia. We identified one heterozygous missense mutation, T552S, in a hormonally inactive adrenal adenoma. One base exchange was identified close to the intron-exon boundary in intron 9 of a nodular adrenal hyperplasia. mRNA expression studies found that MEN I was transcribed in all 13 samples analyzed. In summary, our study identified the second patient with sporadic benign adrenal tumor presenting a menin gene mutation. Our complete direct sequencing approach adds evidence that menin gene mutations may account only for a minority of benign adrenal tumors if at all. Another tumor-suppressor gene inactivated in sporadic adrenal neoplasms may be located on chromosome 11q13.

Adenoma↗

PubMed1999

Post graft development of short children treated with growth hormone before kidney graft.

Sixteen prepubertal patients with chronic renal failure (CRF) were given daily recombinant human growth hormone (rhGH) treatment (1.2 IU/kg per week) for 2.6+/-1.6 years until kidney transplant. Therapy was then discontinued and the patients followed for a further 3. 5+/-1.4 years. During treatment, mean height increased from -3.0+/-0. 9 standard deviation score (SDS) to -1.9+/-1.4 SDS (P<0.001) at the time of transplantation, corresponding to a mean height gain of +1. 2+/-0.9 SDS. After discontinuation of rhGH therapy, prepubertal children continued a partial catch-up growth with a height gain of +0.5+/-0.8 SDS for the follow-up period. Conversely, negative changes of height were observed in pubertal transplanted children: -0.5+/-0.4 SDS in patients grafted at early stages of puberty (P2-P3) and -0.15+/-0.9 SDS in patients grafted at late stages of puberty (P4-P5). These data confirmed the benefit of rhGH therapy in CRF patients. Nevertheless, only early initiation of rhGH treatment led some of these patients to their target height at transplantation, thus preserving their potential growth. Reinitiation of rhGH therapy after transplantation should be considered in order to complete catch-up growth to target height in prepubertal children.

Age Factors↗

PubMed1999

Involvement of soluble CD95 in Churg-Strauss syndrome.

Deficiency of CD95 (Apo-1/Fas)-mediated apoptosis has recently been found in some autoimmune lymphoproliferative disorders due to inherited mutations of the CD95 gene. In this study, impairment of CD95 ligand-mediated killing of lymphocytes and eosinophils in Churg-Strauss Syndrome (CSS), which was a result of variation of CD95 receptor isoform expression, is demonstrated. Compared to those from healthy individuals, peripheral blood lymphocytes from eight CSS patients exhibit a switch from the membrane-bound CD95 receptor expression to its soluble splice variant, which protects from CD95L-mediated apoptosis. In five out of seven CSS patients recurrent oligoclonal T cell expansions were found, all using a Vbeta-gene from the Vbeta21 family associated with similar CDR3 motifs, indicating the predominance of T cell clones of a similar specificity in the CSS patients. In two of them, the effect of immunosuppressive therapy was studied. In both cases aberrant overexpression of the soluble CD95 receptor isoform and deviations from normal TCR Vbeta-gene usage normalized in parallel with the clinical improvement. Furthermore, soluble CD95 was identified as a survival factor for eosinophils rescuing eosinophils from apoptosis in the absence of growth factors in vitro. Given the role of eosinophils as effector cells in CSS, these findings suggest that soluble CD95 may be mechanistically involved in the disease.

Adult↗

PubMed1999

Validity of an illness severity measure for headache in a population sample of migraine sufferers.

The headache impact questionnaire (HImQ) is used to measure pain and activity limitations from headache over a 3-month recall period. In a prior study, the test-retest reliability of the eight-item HImQ score was found to be relatively high (0.86). In the current study, we examined the validity of the eight-item HImQ by comparing the overall score and individual items to equivalent measures from a 90-day diary. Pain and activity limitations due to headache were assessed in a population-based sample of 132 migraine headache sufferers enrolled in a 90-day daily diary study who completed the HImQ at the end of the study. The HImQ score was derived from four frequency-based questions (i.e. number of headaches, missed days of work, missed days of chores, or missed days of non-work activity) and four summary measures of average experience across headaches (i.e. average pain intensity, and average reduced effectiveness when having a headache at work, during household chores, and in non-work activity). Diary based measures were used as the gold standard in evaluating the HImQ score. Mean and median values of frequency-based HImQ items (e.g. number of headaches) were similar to equivalent diary measures, indicating no systematic bias. In contrast, HImQ measures of average experience across attacks (e.g. average pain intensity) overestimated equivalent diary measures and, in general, better approximated diary measures for migraine headaches, rather than all headaches. The highest correlations between HImQ and diary items were observed for headache frequency and average pain intensity, the two general headache measures, followed by measures of reduced effectiveness. Among frequency-based measures, the strength of the correlation was directly related to the magnitude of the mean. The higher the mean value, the higher the correlation. The correlation between the HImQ score and diary based score was 0.49. The HImQ score is moderately valid. Frequency-based items (e.g. number of missed work days) were found to be unbiased and the highest correlation coefficients were observed for frequency-based items with relatively high mean counts (number of headaches, number of missed non-work days). These findings have implications for measuring severity of chronic episodic conditions like headache, asthma, back pain, arthritis, epilepsy, and panic disorder, which can cause limitations to activities. The validity of illness severity measures may be improved by using frequency-based questions to assess both missed activity days and days with significantly reduced effectiveness or productivity (e.g. by 50% or more). By combining the count for both missed days and days where productivity is substantially reduced, the mean of the frequency-based measure will be increased, a factor which may improve the overall validity of the item. A severity measure can be derived from such items by simple addition and provides a scale with intuitively meaningful units.

Adolescent↗

PubMed1999

Feasibility of tandem autologous stem-cell transplantation (ASCT) in induction failure or very unfavorable (UF) relapse from Hodgkin's disease (HD). SFGM/GELA Study Group.

BACKGROUND: Despite high-dose therapy and ASCT some patients with aggressive HD fail to achieve long-term survival. PATIENTS AND METHODS: Forty-three patients with induction failure (n = 19) or very unfavorable (UF) relapse (n = 24) from HD were included in a multicentric study of tandem ASCT. They planned to receive two course of IVA75 with GCSF and blood stem cell collection. ASCT1 was conditioned with CBV + mitoxantrone (30 mg/m2) and ASCT2 (cytarabine 6 g/m2 melphalan 140 mg/m2 and total body irradiation at 12 Gy or busulfan 16 (n = 4) than 12 mg/kg). After salvage therapy, response > 50% was observed in 63% of the patients (six patients were included for refractory relapse). Four patients had no ASCT for disease progression; seven patients had only ASCT1 (disease progression, n = 3) and thirty-two patients (74%) received the two ASCT. RESULTS: Hematologic recovery was normal after ASCT1 but delayed platelet recovery was observed after ASCT2 with busulfan in the conditioning regimen. Two VOD with one fatal occurred with busulfan at 16 mg/kg and one hemorrhagic cystic, no further grade 4 toxicity was observed with the reduced doses of busulfan (12 mg/kg). After ASCT2, 83% of these UF patients were in remission and 20% relapsed within the first year. On an intent-to-treat analysis, 22 of 43 patients are in continuous CR (including 8 patients with induction failure). For the whole population (n = 43) and for patients receiving the two ASCT (n = 32), the two-year survival from the date of progression were respectively at 65% and at 74%. CONCLUSION: Double ASCT is feasible in very UF relapse from HD and may lead to some prolonged remission.

Adult↗

PubMed1999

Tandem transplant of peripheral blood stem cells for patients with poor-prognosis Hodgkins's disease or non-Hodgkin's lymphoma.

To improve the results of high-dose therapy with autologous stem cell transplantation, new conditioning regimens with acceptable toxicity must be developed. The aim of this study was to evaluate the feasibility and toxicity of two myeloablative regimens performed at a 2-month interval. After salvage chemotherapy and collection of peripheral stem cell progenitors (median CD34+ cells/kg: 11 x 106/kg), (n = 15) patients with aggressive non-Hodgkin's lymphoma with poor prognostic factors or refractory Hodgkin's disease (n= 9) received intensified regimens. The first conditioning regimen, consisting of BCNU-cyclophosphamide-VP16-mitoxantrone was followed by transplantation of a median number of 4 x 10(6) CD34+ cells/kg; then, after a median interval of 56 days, a second preparative regimen, combining busulfan-aracytine-melphalan or TBI + aracytine-melphalan, was followed by transplantation of a median of 4 x 10(6) CD34+ cells/kg. After regimens 1 and 2, respectively: median time to neutrophil recovery >500/microl was 11 days (both times); median time to platelet counts >50,000/microl was 14 and 36 days, but values > 20,000/microl were reached by days 13 and 16 (P = 0.9); mucositis grade III-IV was observed in 11 and 15 cases. The median number of days with fever >38 degrees C was significantly higher (7.8 days) after the second transplant (P <0.05). Three cases of veno-occlusive disease (VOD) were observed after the second transplant. At a median follow-up of 18 months, 14/24 (58%) patients remained in CR, seven patients had died (two of VOD and five after relapse) and two were alive in relapse. These results indicate that tandem transplants performed at a 2-month interval in poor risk lymphoma can be used with acceptable hematotoxicity. VOD remains the major drawback and hepatotoxic drugs, such as busulfan, should be used with caution. Longer term follow-up of a larger cohort of patients is needed to ascertain the overall efficacy.

Adolescent↗