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Biomedical subjects

S Brunet

Publications and source records attributed to S Brunet.

At least 145 records · Page 8Linked to original sources

High-dose busulfan and melphalan before bone marrow transplantation for acute nonlymphoblastic leukemia.

Fourteen patients with acute nonlymphoblastic leukemia (ANLL) (n = 13) or juvenile chronic myelomonocytic leukemia (n = 1) were transplanted after conditioning with high-dose busulfan (4 mg/kg daily on days -7 to -4) and melphalan (180 mg/m2 on day -2). This protocol was designed for patients considered unable to receive standard conditioning regimens with cyclophosphamide and/or TBI. Five patients (4 children and 1 adult) received a second allogeneic BMT in untreated early marrow relapse after a first BMT. There were 3 procedure-related deaths (PRD), 2 during aplasia and 1 from acute GVHD. Two patients survived the procedure; 1 relapsed at 6 months and 1 is alive at 43+ months. Nine subjects (8 children and 1 adult) received an autologous BMT, 7 in first and 2 in second complete remission (CR). Of the 7 patients grafted in first CR, there was 1 PRD, 2 relapses at 3 and 15 months, and four are alive at 38 to 82+ months. One patient grafted in second CR relapsed at 7 months and 1 is alive at 67+ months. Toxicities were mild or moderate in autologous BMT recipients, mainly affecting the gastrointestinal tract. In the allogeneic BMT group, there were more moderate to severe toxicities, including 3 cases of moderate-severe renal toxicity; no cases of such toxicity were seen in ABMT recipients. Two cases of HVOD occurred, 1 in each group. These results are encouraging, although the small patient group does not allow any firm conclusions.

Adult↗

Various patterns of chimerism after allogeneic bone marrow transplantation for advanced chronic lymphocytic leukemia.

Chimerism studies after allogeneic BMT are performed to determine the donor and/or recipient origin of peripheral blood and marrow lymphoid and hematopoietic cells. These studies have been performed mostly in leukemias and aplastic anemia. We report DNA-based chimerism studies in three patients transplanted for advanced CLL from a histocompatible sibling. Following conditioning with chlorambucil, cyclophosphamide and TBI all three successfully engrafted. One has remained in continuous complete remission (CR) with a complete donor chimerism (CDC) for 110 months post-BMT. Another was in mixed chimerism (MC) with minimal residual disease (MRD) at 3 months post-BMT but was in CR and in CDC at 6 months, suggesting that the persistent CLL cells has disappeared between these two studies. The third patient has been in persistent MC since BMT (24 months follow-up), although he is in CR with no evidence of persistent CLL. We postulate that this patient's MC status is due to normal residual recipient lymphohematopoietic cells that survived the conditioning regimen. In conclusion, various patterns of chimerism can be observed in CLL patients after BMT while remaining in CR and with no evidence of residual CLL.

Adult↗

Malondialdehyde-modified high-density lipoprotein cholesterol: plasma removal, tissue distribution and biliary sterol secretion in rats.

Evidence has been accumulating for the putative role of chemically or oxidatively altered lipoproteins in accelerating events in the atherogenic process. In this study, the movement of free cholesterol from native high density lipoprotein (HDL) and malondialdehyde (MDA)-modified HDL to the liver for biliary cholesterol secretion and bile acid transformation was examined in vivo. To this end, HDL from normal donor rats was isolated, conjugated with MDA, labelled with [14C]cholesterol and injected i.v. into rats with bile diversion. While the 6 h collection revealed no substantial differences in bile flow, less 14C excretion was recovered in the fresh bile of animals receiving MDA-modified HDL. Bile analysis indicated that a significant decline in labelled bile acid secretion characterized these rats. Compared with controls, MDA-modified HDL also caused an enhanced accumulation of [14C]cholesterol in the liver and the kidneys, with reduced delivery to the sites of steroidogenesis, i.e., the adrenals and testes. No plasma removal differences were noted in the HDL of both groups of rats. Thus, modification of HDL by MDA seems to impair the tissue distribution of its cholesterol moiety, particularly in the liver, where it accumulates at the expense of bile acid transformation.

Animals↗

Spontaneous splenic rupture as the initial manifestation of acute lymphoblastic leukaemia: immunophenotype and cytogenetics.

Spontaneous splenic rupture is a rare, though life-threatening complication of some hematological malignancies and is even more infrequent as the initial symptom of acute lymphoblastic leukemia. We describe the fourth case, to our knowledge, of acute lymphoblastic leukemia presenting as splenic rupture, and for the first time the immunophenotype and cytogenetic pattern observed.

Adult↗

Acute rhabdomyolysis complicating viridans streptococcal shock syndrome.

A 20-year-old male underwent an allogeneic bone marrow transplantation for acute myelogenous leukemia after conditioning with cyclophosphamide and total body irradiation. On day +6 of the procedure, he developed fever, chills and myalgias. Empiric treatment with ceftazidime and amikacin was begun, and blood cultures grew viridans streptococci. Biochemical changes suggestive of acute rhabdomyolysis were evident. Within 24 h, adult respiratory distress syndrome with multiorgan failure appeared, and he died 7 days later. At autopsy, the presence of rhabdomyolysis was confirmed.

Acute Disease↗

Prognostic factors in autologous stem cell transplantation for multiple myeloma: an EBMT Registry Study. European Group for Bone Marrow Transplantation.

Autologous bone marrow- and blood progenitor cell transplantation was performed in 130 patients with multiple myeloma in 16 European centers between 1986 and 1993. At the time of follow-up, 77 patients were alive and 53 were dead. Complete remission after transplantation was obtained in 47% of all patients. The actuarial survival at 65 months was 28%. The median duration of relapse-free survival among patients who were in complete remission after transplantation was 29 months. The following factors were predictive for longer survival and freedom of progression in a univariate analysis: Male sex, age less than 45 years, a low serum-beta-2-microglobulin value at diagnosis, prior administration of only one treatment regimen, response on conventional chemotherapy immediately pretransplant and the use of a preparative regimen including melphalan. The last factor, in addition to stage I disease at diagnosis, male sex and responsive disease immediately pretransplant, were also demonstrated as independent predictive variables for longer survival in a multivariate analysis. Progression-free survival was significantly better for patients who were in complete remission after transplantation, as compared to those with persisting signs of disease. We conclude that high-dose chemo-radiotherapy with autologous stem cell transplantation can induce long-term responses, primarily in younger, male patients with chemotherapy-responsive early disease. High-dose melphalan, as single drug or in combination, appeared to be superior to other regimens. The chance of being persistently disease-free seemed to be greatest for patients being in complete remission already before the transplantation.

Adult↗

Second bone marrow transplantation for leukemia in untreated relapse.

Seven patients with relapsed acute leukemia (4 ANLL, 3 ALL) and one with juvenile chronic myelomonocytic leukemia (JCMML) received a second BMT (BMT2). Patients were conditioned with CY/TBI (n = 7) or BU/CY (n = 1) for the first BMT (BMT1), with adequate recovery in all and without the appearance of acute GVHD (n = 3) or with mild forms (grade I, n = 2; grade II, n = 3). Relapse after BMT1 occurred in < 6 months (n = 2), between 6 and 12 months (n = 5) and > 12 months (n = 1), and the interval from BMT1 to BMT2 was < 6 months (n = 1), from 6 to 12 months (n = 5) or > 12 months (n = 2). Conditioning for BMT2 was done in untreated relapse and included combinations of BU/CY (n = 2), CY/TBI (n = 1) or BU 1 mg/kg at intervals of 6 h by mouth on days -7 to -4 and melphalan 180 mg/m2 i.v. on day -2, with the addition of VP-16 in the patient with JCMML. Two patients died on day +11 with no evidence of residual leukemia at autopsy. Six patients engrafted, one of whom had an uneventful BMT2, but he relapsed 6 months later. The other five developed severe acute GVHD (grades III-IV), with a fatal outcome in three cases, while two responded to treatment and are currently alive in continuous CR at 12 and 36 months. All patients had received conventional prophylaxis against acute GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Acute tumor lysis syndrome complicating conditioning therapy for bone marrow transplantation in a patient with chronic lymphocytic leukemia.

We report a case of acute tumor lysis syndrome appearing during chemoradiotherapeutic conditioning for allogeneic bone marrow transplantation (BMT) in a patient with chronic lymphocytic leukemia. This complication appeared in spite of prophylactic therapy and although the outcome was satisfactory, the patient required temporary hemodialysis and strict supportive care. This case emphasizes the importance of recognizing that the acute tumor lysis syndrome is not confined to high-grade malignancies.

Acute Disease↗