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Biomedical subjects

B Rio

Publications and source records attributed to B Rio.

At least 19 recordsLinked to original sources
PubMed2006

HLA-identical sibling allogeneic peripheral blood stem cell transplantation with reduced intensity conditioning compared to autologous peripheral blood stem cell transplantation for elderly patients with de novo acute myeloid leukemia.

We conducted a retrospective registry-based analysis to compare the outcome of 361 allogeneic human leukocyte antigen (HLA)-identical peripheral blood stem cell transplants (PBSCT) with reduced intensity conditioning (RIC) to that of 1369 autologous (auto) PBSCT in patients aged 50 years or older with de novo acute myeloid leukemia (AML), performed from 1997 until 2003 and reported to the European Group for Blood and Marrow Transplantation. Median age was 58 and 57 years in the RIC and auto groups, respectively. RIC patients had more advanced disease at the time of transplant. At a median follow-up of 24 months for RIC and 16 months for auto, multivariate analysis showed a lower risk for relapse (RR 0.77, P=0.013) without increased non-relapse mortality (NRM) in RIC patients (RR 1.26, P=0.28). Moreover, leukemia-free survival (RR 1.22, P=0.02) and overall survival (OS) (RR 1.32, P=0.005) were superior in the RIC group. In patients in 1st (CR), fewer relapses were counterbalanced by significantly increased NRM. Therefore, there was no survival advantage in this subgroup. In patients in 2nd or subsequent CR, LFS and OS were superior in the RIC group. RIC transplants show encouraging results in this older patient population with de novo AML.

Aged↗
PubMed2006

A phase I dose-finding and pharmacokinetic study of subcutaneous semisynthetic homoharringtonine (ssHHT) in patients with advanced acute myeloid leukaemia.

To determine the maximum-tolerated dose (MTD), dose-limiting toxicities and pharmacokinetic of semisynthetic homoharringtonine (ssHHT), given as a twice daily subcutaneous (s.c.) injections for 9 days, in patients with advanced acute leukaemia, 18 patients with advanced acute myeloid leukaemia were included in this sequential Bayesian phase I dose-finding trial. A starting dose of 0.5 mg m(-2) day(-1) was explored with subsequent dose escalations of 1, 3, 5 and 6 mg m(-2) day(-1). Myelosuppression was constant. The MTD was estimated as the dose level of 5 mg m(-2) day(-1) for 9 consecutive days by s.c. route. Dose-limiting toxicities were hyperglycaemia with hyperosmolar coma at 3 mg m(-2), and (i) one anasarque and haematemesis, (ii) one life-threatening pulmonary aspergillosis, (iii) one skin rash and (iv) one scalp pain at dose level of 5 mg m(-2) day(-1). The mean half-life of ssHHT was 11.01+/-3.4 h, the volume of distribution at steady state was 2+/-1.4 l kg(-1) and the plasma clearance was 11.6+/-10.4 l h(-1). Eleven of the 12 patients with circulating leukaemic cells had blood blast clearance, two achieved complete remission and one with blast crisis of CMML returned in chronic phase. The recommended daily dose of ssHHT on the 9-day schedule is 5 mg m(-2) day(-1).

Acute Disease↗
PubMed2005

Thalidomide salvage therapy following allogeneic stem cell transplantation for multiple myeloma: a retrospective study from the Intergroupe Francophone du Myélome (IFM) and the Société Française de Greffe de Moelle et Thérapie Cellulaire (SFGM-TC).

Thalidomide is effective in multiple myeloma (MM), even in patients who have relapsed after high-dose therapy. A potent graft-versus-myeloma (GVM) effect can be induced against MM after allogeneic stem cell transplantation (allo-SCT). In all, 31 MM patients received thalidomide as a salvage therapy after progression following allo-SCT. The median maximum daily dose of thalidomide was 200 mg (range, 50-600). Thalidomide had to be discontinued in six patients (19%) because of toxicity. In all, nine patients (29%; 95% CI, 13-45) achieved an objective response with thalidomide therapy (six partial and three very good partial responses, VGPR). Five patients developed graft-versus-host disease (GVHD) after thalidomide therapy, including the three patients achieving a VGPR. These data demonstrate that thalidomide is potentially effective in MM patients failing allo-SCT.

Adult↗
PubMed2004

Reassessing autotransplantation for acute myeloid leukaemia in first remission - a matched pair analysis of autologous marrow vs peripheral blood stem cells.

The role of autologous stem cell transplantation in adult patients with acute myeloid leukaemia (AML) in first remission is unclear, yet it has become standard treatment for myeloma and this paper explores whether the source of transplanted stem cells may explain this paradox. In total, 57 patients from the Royal Marsden Hospital who received an unpurged bone marrow transplant (ABMT) were matched with 114 patients from the EBMT registry who had undergone peripheral blood stem cell transplantation (PBSCT). Patients were matched for karyotype, FAB type, remission-autograft interval and age. In the PBSCT group, haematopoietic recovery was significantly faster and nonrelapse mortality at 4 years was significantly lower (13 vs 1%, P=0.04). The relapse rate and overall survival at 4 years (20 vs 31% and 77 vs 63%) were also better with PBSCT, although the differences were not statistically significant. Autografting should be reassessed in a randomised trial for first remission AML patients using peripheral blood as a source of stem cells rather than bone marrow.

Acute Disease↗
PubMed2003

Risk assessment in adult acute lymphoblastic leukaemia before early haemopoietic stem cell transplantation with a geno-identical donor: an easy clinical prognostic score to identify patients who benefit most from allogeneic haemopoietic stem cell transplantation.

In 1402 patients allografted in Europe during the period 1990-2000 with an HLA-identical sibling in first remission (CR1), the median interval from CR1 to allotransplant (96 days) was a major prognostic factor, patients transplanted earlier having a worse outcome. We studied in depth the 414 fully evaluable patients transplanted less than 96 days after achieving CR1; in these patients, only three factors predicted for the outcome by multivariate analysis: patient age, CR1 achievement with one or more induction courses and the recipient/donor sex combination. These three factors overcame the information from cytogenetics and source of stem cells. Three prognostic groups could be identified in relation to the outcome, using a prognostic score affecting 1 to each poor risk factor (total from 0 to 3): Group 1 (good prognosis) includes patients <35 years old, achieving CR1 with one induction course and to be transplanted with any other sex combination than female to male (score 0); group 2 (intermediate) with one adverse factor (score 1); and group 3 (bad prognosis) with two or three adverse criteria (scores 2 and 3). In these three groups, the 3-year leukaemia-free survival was 56+/-5%, 48+/-4% and 29+/-4% and the overall survival was 65+/-5, 53+/-4 and 29+/-5%, respectively. Therefore, adult patients with ALL and a score of 0 or 1 are good candidates for an early transplant if they have an identical sibling donor. Patient age, response to induction and the sex of the HLA-identical family donor (if existing) are the strongest easy predictors of the outcome for an early transplant in an adult patient with ALL. No additional information is mandatory.

Adolescent↗
PubMed2001

Pregnancy outcomes after peripheral blood or bone marrow transplantation: a retrospective survey.

BACKGROUND: Some patients treated by transplantation of haemopoietic stem cells (peripheral blood or bone marrow) become permanently infertile, but others retain or recover fertility. We assessed the outcome of conception in women, and partners of men previously treated by autologous or allogeneic stem cell transplantation (SCT). METHODS: We sent questionnaires to 229 centres of the European Group for Blood and Marrow Transplantation. We sought details about the original disease, transplant procedure, and outcome of conception for both male and female patients. FINDINGS: 199 centres gave information relating to 19412 allogeneic and 17950 autologous transplant patients. 232 (0.6%) patients conceived after SCT. Crude annual birth rate for 4-month survivors of SCT was lower than the national average for England and Wales at 1.7 per 1000 patients. 312 conceptions were reported in 113 patients (74 allograft) and partners of 119 patients (93 allograft). Most pregnancies were uncomplicated and resulted in 271 livebirths. 28 (42%) of 67 allograft recipients had caesarean section compared with 16% in the normal population (difference =26% [95% CI 15-38]), 12 (20%) of 59 had preterm delivery compared with a normal rate of 6% (14% [4-24]), and 12 (23%) of 52 had low birthweight singleton offspring compared with a normal rate of 6% (17% [6-29]). INTERPRETATION: Pregnancy after SCT is likely to have a successful outcome. Pregnancies in allograft patients who have received total body irradiation should be treated as high risk for maternal and fetal complications.

Adolescent↗
PubMed2001

In vitro effect of lead acetate on human erythropoietic progenitors.

Lead is known to induce hematological disturbances resulting from abnormalities in cell differentiation and hemoglobin synthesis during hematopoiesis. The aim of the present work was to study human erythropoiesis in vitro in the presence of lead. Human erythroblastic progenitors, burst-forming units-erythroid (BFU-E), were exposed to lead acetate at increasing concentrations during 14 days of culture. Hematotoxicity was evaluated in vitro according to proliferation and differentiation of cell colonies arising from BFU-E development. The ability of cells to synthesize proteins, porphyrins, and hemoglobin was measured by spectrophotometric tests and by high-pressure liquid chromatography (HPLC). Results showed that in the presence of 10(-3) mol/L lead acetate, no hemoglobinized cells were observed in culture and no fluorescent porphyrins were detected in cells. Up to 10(-3) mol/L, lead acetate is not cytotoxic, i.e., it does not induce cell destruction. The present work demonstrates that lead acetate interferes with the porphyrin synthesis of human erythroblastic progenitors in vitro. The decrease of porphyrin content with 10(-5) mol/L lead acetate suggest that delta-aminolevulinic acid dehydratase can be inhibited by lead acetate during in vitro erythropoiesis. In vivo erythropoiesis occurs in the bone marrow. As about 95% of the body burden of lead in adults is located in the bones with a biological half-life of some years, the concentration of lead acetate found to block porphyrin synthesis in vitro has to be compared with in situ bone marrow lead concentrations.

Cell Division↗
PubMed2001

Acute myeloid leukaemia in human immunodeficiency virus-infected adults: epidemiology, treatment feasibility and outcome.

The epidemiology and clinical outcome of acute myeloid leukaemia in human immunodeficiency virus (HIV)-infected adults is poorly documented. We retrospectively surveyed all French haematology centres for adult acute myeloid leukaemia (AML) cases diagnosed between January 1990 and July 1996 who were found to be HIV-seropositive before or at the time of AML diagnosis. Medical charts were reviewed to determine the stage of HIV infection, the characteristics of AML and the response of AML to chemotherapy. Sixteen cases of AML (13 men, three women) were reported by 12 haematology units. Based on assumptions on the size, age and sex distribution of the HIV-infected population in France, the estimated risk of AML in 1990 to 1996 among HIV-infected adults was twice that of the general population (standardized incidence ratio = 2.05; 95% confidence interval, 1.17-3.34). Two other cases occurring before 1990 were spontaneously notified to the authors and were included in the clinical analysis. At AML diagnosis, the median CD4+ cell count was 275 x 106/l and nine patients had acquired immune deficiency syndrome (AIDS). Fifteen patients were scheduled for remission-induction therapy of AML. No deaths were related to AML treatment. Complete remission was obtained in 11 out of 15 patients. Three patients were long-term survivors: two remain alive in complete remission at 8 years and 9 years, respectively, and the third died of AIDS at 8 years. A CD4+ cell count above 200 x 106/l at AML diagnosis was predictive of longer survival (log-rank test: P = 0.004). Like many other malignancies, the incidence of AML appears to be increased in HIV-infected patients. Our results show a twofold higher incidence, although this needs to be confirmed in a specifically designed prospective epidemiological study. Such patients, especially those with CD4+ cell counts above 200 x 106/l at AML diagnosis, should receive remission-induction therapy, which can confer long-term survival.

Acute Disease↗
PubMed2000

Molecular epidemiology of human herpesvirus 8 in africa: both B and A5 K1 genotypes, as well as the M and P genotypes of K14.1/K15 loci, are frequent and widespread.

We have studied 52 new HHV8 strains by sequencing the complete hypervariable K1 gene and genotyping the K14.1/K15 loci located at both sides, respectively, of the viral genome. The samples originated from 49 patients with Kaposi's sarcoma (KS; 32 patients), multicentric Castleman's disease (MCD; 12 patients), or primary effusion lymphoma (PEL; 5 patients). Among these patients, 32 were of African origin (West and Central African countries and Creoles from French Guiana) and the 17 others were mostly French homosexuals. Comprehensive phylogenetic studies allowed the identification of distinct groups within the three already known main subtypes. Interestingly, two new sequences that did not cluster within a known subtype or group could be considered as prototypes of early/ancient variants of the C subtype and A/C set, respectively. Among the 32 African strains, the majority were either of the B subtype (13 cases) or of the A5 group (11 cases), indicating that this latter genotype is frequent and widespread in Africa. In contrast, a subtype C strain infected most of the 17 other patients. PCR-based genotyping of the K14.1/K15 loci revealed an overall predominance of P subtype, except in the A5 and B K1 groups, in which the P and M alleles were equally represented. The implications of these data on the evolution and spread of HHV8 among human African populations are discussed.

Adult↗
PubMed2000

Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Société Française de Greffe de Moelle (SFGM).

To assess the place of allogeneic hematopoietic stem cell transplantation (HSCT) in the advanced stage of acute myeloid leukemia (AML), we retrospectively analyzed 379 consecutive patients who underwent allogeneic HSCT for advanced AML. The median follow-up of the entire cohort was 7.5 years. Sixty-nine patients (18%) were transplanted with primary resistant disease. Three hundred and ten (82%) were relapsed patients, 94 (30%) of whom were in untreated relapse, 67 (22%) in refractory relapse and 149 (48%) in 2nd or 3rd complete remission at time of transplantation. The 5-year probabilities of overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) were 22 +/- 4%, 20 +/- 4%, 45 +/- 6%, respectively. In multivariate analysis, we demonstrated the favorable impact on OS, DFS and TRM of two factors over which we have no control (age <15 years, complete remission achievement) and three factors over which we have some control (female donor, acute and chronic graft-versus-host disease). The results of this study suggest that the graft-versus-leukemia effect is important in advanced AML and that new HSCT modalities are needed for some patients with this indication.

Acute Disease↗
PubMed2000

Feasibility and recent improvement of autologous stem cell transplantation for acute myelocytic leukaemia in patients over 60 years of age: importance of the source of stem cells.

A total of 193 patients with acute myelocytic leukaemia (AML) [147 in first complete remission (CR1)], ranging from 60 years to 75 years of age (median 63 years), were autografted between January 1984 and December 1998. The source of stem cells was peripheral blood (PB) in 128 patients, bone marrow in 51 patients and a combination of both in 14 patients. Total body irradiation (TBI) was used in 34 cases. Ninety-seven per cent of patients had successful engraftment of neutrophils on day 15 (range days 7-71) and of platelets on day 30 (range days 9-894). In patients autografted in CR1, the transplant-related mortality (TRM) was 15 +/- 4%, the relapse incidence (RI) was 58 +/- 5%, the leukaemia-free survival (LFS) was 36 +/- 5% and the overall survival was 47 +/- 5% at 3 years. The source and dose of stem cells were studied in particular; in patients transplanted in CR1, the RI was 44 +/- 11% in those receiving marrow compared with 63 +/- 6% in those receiving PB (P = 0.04). Patients autografted in CR1 who received higher granulocyte-macrophage colony-forming units (CFU-GM) doses (above the median) had a lower RI (47 +/- 11% vs. 79 +/- 9%, P = 0.009). There was a significant improvement in patients transplanted after March 1996; for those in CR1, the RI was 41 +/- 8% vs. 65 +/- 6% (P = 0.01), the LFS was 53 +/- 8% vs. 28 +/- 5% (P = 0.01) and the overall survival was 72 +/- 7% vs. 36 +/- 6% (P = 0.02). By multivariate analyses, significant factors for the outcome were the date of transplant with recent improvement and the source of stem cells, with a lower RI for marrow. Autologous stem cell transplantation (ASCT) is a potential therapeutic approach in patients with AML over 60 years of age; results have improved recently.

Aged↗
PubMed2000

Intravascular large B-cell lymphoma with bone marrow involvement at presentation and haemophagocytic syndrome: two Western cases in favour of a specific variant.

AIMS: To report two cases of an unusual form of intravascular lymphoma, characterized by bone marrow involvement at presentation with haemophagocytic syndrome. METHODS AND RESULTS: We describe the clinicopathological features of two patients with intravascular lymphoma primarily involving bone marrow. Both patients complained only of fever with pancytopenia and reactive haemophagocytic syndrome. Diagnosis was made on bone marrow examination, which showed large tumour cells of B-cell lineage confined within the lumen of sinuses. CONCLUSION: These two cases and five previous reports could represent a variant of intravascular lymphoma, characterized by early involvement of bone marrow without dissemination to other organs. This form of intravascular lymphoma, called IVL-HS, seems to be an 'Asian' variant with a high prevalence in Asian people and a very low prevalence in Western countries. At a practical level, bone marrow biopsy may be useful in the diagnosis of intravascular lymphoma when the clinical presentation is restricted to fever of unknown origin with a reactive haemophagocytic syndrome.

Aged↗
PubMed1999

Piperacillin/tazobactam plus tobramycin versus ceftazidime plus tobramycin as empiric therapy for fever in severely neutropenic patients.

The objective of this trial was to evaluate the potential advantages of the combination of piperacillin and tazobactam in the control of fever in neutropenic patients. In this single-center study, patients who experienced a total of 247 febrile episodes were prospectively randomized to receive either our standard regimen, ceftazidime 3 g/day (1 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.), or piperacillin 12 g/day plus tazobactam 1.5 g/day (4 g+0.5 g t.i.d.) plus tobramycin 3 mg/kg per day (1.5 mg/kg b.i.d.). Vancomycin was added in all cases of persistent fever in the ceftazidime arm, but only when there was microbiologically documented resistance in the piperacillin/tazobactam arm. All 247 episodes were evaluable by "intent-to-treat" analysis. The two populations were well matched in terms of age, gender, underlying disease, chemotherapy received, oral decontamination, clinical and bacterial documentation, and severity and duration of neutropenia. Initial antibacterial therapy was successful (apyrexia at 72 h, without antibiotic change) more frequently (P = 0.008) with the regimen containing piperacillin/tazobactam (54.4%) than with the one including ceftazidime (37.6%). Fewer (P = 0.02) major infectious events (infectious death or delay in treatment of underlying disease due to infection) were observed during piperacillin/ tazobactam treatment (2.6%) than with the ceftazidime regimen (11.3%), despite a lower frequency of glycopeptide addition when piperacillin/tazobactam was used (54.4% versus 77.4%) according to the rules adopted. This trial confirmed the efficacy of the piperacillin/tazobactam combination for empirical treatment of febrile neutropenic patients. This antibiotic combination permitted a dramatic decrease in empiric glycopeptide antibiotic administration in such patients.

Adult↗