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Biomedical subjects

S Brunet

Publications and source records attributed to S Brunet.

201 records · Page 12Linked to original sources

Mutational analysis of p53 in 16 cases of acute lymphoblastic leukemia and Burkitt's lymphoma.

BACKGROUND AND OBJECTIVE: Improvements in therapy for patients with B-cell acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma (BL) depend on the identification of subsets of patients who require more intensive therapy. Abnormalities of the p53 gene are the most common molecular lesions in human cancer, and may be of prognostic significance in hematologic malignancies. In this study, we examined the p53 gene status in a group of patients with ALL/BL to determine whether some types of mutants were more frequent in this selected group of patients. METHODS: We selected a group of 16 patients with acute lymphoblastic leukemia (ALL) and Burkitt's lymphoma (BL) in order to investigate the presence of p53 mutations. DNA obtained from affected organs (bone marrow, lymph node and a renal mass) was used for the molecular studies. Single-strand conformation polymorphism (SSCP) analysis of exons 5 to 9 of the gene was used to detect p53 mutants. After detecting an abnormal migration pattern on the SSCP, mutations were determined by direct sequencing. RESULTS: Point mutations were found in eight patients; a misense mutation in seven cases and a non-sense mutation in one case. The normal allele was also identified in 7 mutated samples. The same mutation at codon 282 was identified in three different patients, in whom an identical conformer was detected after SSCP analysis. Mutation at codon 282 was present in an extramedular relapse (renal) appearing after a BMT. No such alteration was present in the bone marrow analyzed at the same time. INTERPRETATION AND CONCLUSIONS: Our findings suggest that p53 mutations are quite frequent in recognized clinical groups. The criteria chosen in this study allowed us to identify a high percentage of the samples with mutation. Different malignant phenotypes could be determined by functional heterogeneity of p53 mutants.

Adolescent↗

High incidence of chronic graft versus host disease after allogeneic peripheral blood progenitor cell transplantation. The Spanish Group of Allo-PBPCT.

BACKGROUND AND OBJECTIVE: The incidence of acute GVHD (aGVHD) in allogeneic peripheral blood progenitor cell transplantation (allo-PBPCT) seems to be similar to that seen in allogeneic bone marrow transplantation (allo-BMT). In contrast, some preliminary results suggest that the incidence of chronic GVHD (cGVHD) might be higher. The aim of the present study was to analyze the actuarial probability of developing cGVHD in allo-PBPCT, its clinical manifestations and response to treatment. METHODS: We have retrospectively analyzed clinical results from 21 allo-PBPCT recipients that had been transplanted at least 18 months before this study and that fulfilled the following criteria: HLA identical sibling donor, non T-cell depleted apheresis and more than 90 days of survival with sustained engraftment. The median follow-up was 12 months (range 4.5-22). RESULTS: Twelve out of the 21 (57%) patients presented cGVHD, 1 limited and 11 extensive. The actuarial probability of cGVHD was 72.7% (95% CI, 49-96%). The median interval from transplant to onset was 180 days (range 95-270). Nine of the 12 cases (75%) presented combined skin and liver involvement. Of the other three, the liver was involved in one case; skin, mouth, and nail cGVHD was observed in another case; and skin and mouth involvement together with an obstructive pulmonary disease was observed in the remaining case. Under therapy, a complete resolution of cGVHD manifestations was achieved in five cases, and a partial improvement was attained in three other cases. In two responsive patients, cGVHD reappeared after stopping treatment. Four patients were refractory to the treatment. INTERPRETATION AND CONCLUSIONS: It would appear from this retrospective and multicenter study that, after a median follow-up of 12 months, cGVHD after allo-PBPCT could be more frequent than after allo-BMT. A randomized trial with a large number of patients and a sufficient follow-up will be necessary to answer this question definitively.

Adolescent↗

Acute rhabdomyolysis and myonecrosis complicating aeromonas bacteremia in neutropenic patients with hematologic malignancies: report of two cases.

Infections by Aeromonas spp. are a rare cause of systemic infection in normal and immunocompromised hosts. We report the cases of two patients with acute non-lymphoblastic leukemia who developed septic shock by Aeromonas species with unusual soft-tissue complications. One patient who was undergoing consolidation chemotherapy developed septic shock by Aeromonas hydrophila with rhabdomyolysis and subsequent soft-tissue destruction consistent with myonecrosis. She recovered with combination antibiotic therapy and supportive care. The second patient developed neutropenia due to ganciclovir treatment for post-allogeneic transplant cytomegalovirus antigenemia. He developed a rapidly progressive septic shock due to Aeromonas sobria with rhabdomyolysis, multi-organ failure and bilateral lower limb myonecrosis, and died within 48 hours. The portal of entry was not identified in either case. These cases confirm the potentially aggressive nature of these bacteria in neutropenic cancer patients with an unusual tendency to produce muscular and soft-tissue destruction.

Acute Disease↗