Complete substitution of cyclophosphamide by fludarabine and ATG in a busulfan-based preparative regimen for children and adolescents with beta-thalassemia.

Children and adolescents with homozygous beta-thalassemia can be cured by transplantation of normal stem cells after eradication of the thalassemic hematopoietic system. In an attempt to achieve durable engraftment and to minimize regimen-related toxicity (RRT), we have initiated a fludarabine-based pilot protocol not containing cyclophosphamide. Between 1999 and 2004, five children with beta-thalassemia major were enrolled. Median age at transplantation was 11.5 years (range 4-14 years). Three patients received conditioning with fludarabine (30 mg/m2/day x 6), oral busulfan (3.5 mg/kg/day x 4), and ATG rabbit Fresenius (10 mg/kg/day x 4). Two children received intravenous busulfan instead of oral busulfan at a dose of 2 x 1.4 mg/kg/day x 4 days. All children were transplanted with a fresh bone marrow graft from an HLA-identical sibling. Mean cell doses given were 3.7 x 10(8) nucleated cells/kg BW (range 2.4-6.2 x 10(8)/kg). Overall, 5/5 patients achieved donor engraftment and are alive and well. No GVHD exceeding grade I was observed, and 2/5 children maintained donor chimerism at 100%. One patient maintains mixed hematopoietic donor chimerism being between 94 and 97% nearly 5 years after transplant.

[Hospital hygiene and antibiotherapy counselling: an operational dual solution against the spreading of multiresistant bacteria]. / L'hygiène hospitalière et le conseil en antibiothérapie: un duo opérationnel face au problème de la diffusion des bactéries multirésistantes aux antibiotiques.

OBJECTIVES: The authors had for aim to show that preventing the diffusion of multidrug-resistant organism (MRO) is possible thanks to the coordination of recommended preventive actions and the implementation of a sensible anti-infective prescription policy. They also wanted to highlight the role played by the nursing care staff in enforcing recommendations. METHOD: We compared the results of two health care facilities having both implemented the same strategy aimed at preventing cross-transmission and prescribing anti-infective drugs. RESULTS: Audits reported a very variable enforcement of recommendations. The results obtained from microbiological monitoring confirmed the essential impact of protocol enactment by every team, on the control of MRO diffusion. The antibiotherapy specialist has a key role in the suggested strategy, allowing a significant decrease in the number of anti-infective prescriptions and a more rational use. CONCLUSION: The collaboration of a hygiene specialist with an antibiotherapy specialist has proved operational in the fight against MRO diffusion, as long as the competences of both specialists are acknowledged and their cross-disciplinary activities accepted. For the entire staff, enacting a corporate culture is a crucial asset.

Results of a mammographic and clinical screening in a health district (USSL) of Brescia, Italy.

AIMS AND BACKGROUND: Screening by mammography has been shown to be effective in reducing breast cancer mortality. We present the results of a mammographic and clinical screening program carried out in an Italian health district. METHODS: The first screening round started in June 1987 and ended in July 1990, and 25,100 women between the age of 50 and 60 years were invited. The second screening round invited 34,332 women between the age of 50 and 64 years and was carried out from September 1990 to September 1993. Women with positive or equivocal results at palpation or mammography were referred for immediate diagnostic assessment followed by surgery, when required. RESULTS: The attendance rate was 67.3% at the first and 62.1% at the repeat screening. At the first screening, 206 biopsies were advised and 197 were performed; 129 of the 197 were found to be malignant. At repeat screening, 248 biopsies were recommended, 208 were performed, and 125 were found to be malignant. The cancer detection rate was 7.7 per thousand at the first and 5.9 per thousand at repeat screening. Of 129 cancers, 107 (83.0%) were T1 at first screening; 6.2% were in situ carcinomas. Axillary lymph nodes were histologically positive in 24% of cases. At repeat screening, 77.6% (97/125) of cancers were T1; 11.2% were in situ carcinomas. Positive axillary lymph nodes were found in 16.8% of cases. CONCLUSIONS: The attendance to screening was satisfactory. A higher frequency of small tumors (83.0%) was found at first screening than before the introduction of screening (56.6%). A marked difference in lymph node positivity (24.0% vs 40.6% in the pre-screening era) was also observed. Such a difference was even more evident at repeat screening. Quality standards of the screening in our study proved to be higher than those currently recommended. The reported results are encouraging, also considering the greater chance for conservative treatment.

[Diagnostic role of mammography and clinical examination in the framework of a screening program for breast carcinoma in Brescia]. / Ruolo diagnostico della mammografia e dell'esame clinico nell'ambito del programma di screening per il carcinoma mammario a Brescia.

Screening by mammography is at present the only way to obtain good results in terms of diagnosis of breast cancer at an early stage. In this paper we present the results of first and second rounds of a mammographic and clinical screening programme carried out in the health district of Brescia. At the first round out of 129 cancers detected, mammography was diagnostic in 124 cases; in 82 cases, the examination also allowed the identification of a suspicious nodule, while in 42 cases non palpable neoplasm was diagnosed with mammography alone. In the remaining 5 cases mammography was negative and only clinical examination led to the discovery of breast neoplasms. In the second round, in the 125 cancers detected, mammography was diagnostic in 124 cases; clinical examination allowed the identification of 59 of these tumours, while in 65 cases non palpable tumours were found with mammography alone. Only in one case mammography was negative and clinical examination led to the identification of the tumour.

[10 years transplantation of bone marrow and hematopoietic stem cells in adults at the Hannover Medical School]. / Zehn Jahre Transplantation von Knochenmark und hämatopoetischen Stammzellen bei Erwachsenen an der Medizinischen Hochschule Hannover.

PATIENTS AND METHODS: From January 1986 until August 1995 230 adult patients received an allogeneic or autologous transplantation of bone marrow or hematopoietic blood stem cells. The conditioning and myeloablative treatment regimens were chosen according to the underlying disease and type of transplant. RESULTS: The observation period comprises 1 to 115 months after transplantation. After allogeneic transplantation from HLA-identical family donors, the probabilities of disease-free survival were for acute myeloid leukemia in first complete remission (CR) (n = 35) 77%, for acute lymphoid leukemia in 1st CR (n = 7) 72% and in 2nd CR (n = 10) 40%, in first chronic phase of chronic myeloid leukemia (n = 34) 50% and in severe aplastic anemia (n = 7) 100%. Following myeloablative therapy and autologous transplantation the probabilities of disease-free survival were 47% in relapsed Hodgkin's disease (n = 22) and 42% for relapsed high-grade non-Hodgkin's lymphoma (n = 12). Eight of 10 patients with acute myeloid and 7 of 8 with acute lymphoid leukemia suffered a leukemic relapse after autologous bone marrow transplantation. Three of 8 patients with relapsed testicular cancer survived relapse-free. Treatment failures were due to more advanced acute graft versus host disease after allogeneic transplantation and caused by relapse after autologous transplantation. Current protocols evaluate the allogeneic transplantation of enriched CD34+ blood stem cells. In chronic myeloid leukemia the autologous transplantation of blood stem cells after myeloablative therapy is being studied.

Can busulfan replace fractionated total body irradiation as conditioning regimen for allogeneic bone marrow transplantation in children with acute lymphoblastic leukemia.

The results of allogenic bone marrow transplantation (allo-BMT) in 26 children with ALL treated with the same initial- and relapse-BFM-protocols, but transplanted in different centers (Poznan, Wroclaw, Hannover) after conditioning with two different regimens have been compared. Ten children (6 in Poznan, 4 in Wroclaw) were conditioned for BMT with busulfan and cyclophosphamide when fractionated TBI (FTBI) was not available there. Sixteen children obtained FTBI and etoposide (11 in Hannover, where in children with ALL exclusively chemoradioconditioning regimen has been employed, and 5 in Poznan). It has been found, that the chemoconditioning procedure was probably less effective (5-year EFS 18%) than the regimen with FTBI (7-year EFS 60%). Therefore, TBI seems to be at this point still mandatory in pediatric ALL patients, unless combinations of chemotherapeutic drugs might be able to substitute the radiation in the future.

OS058. Aldosterone deficiency adversely affects pregnancy outcome in mice.

INTRODUCTION: In pregnancy, plasma volume is expanded due to high aldosterone levels to support placental perfusion and fetal nutrition. Inadequately low aldosterone levels as present in preeclampsia, a life-threatening disease for both mother and child, are discussed to be involved in its pathogenesis or severity. OBJECTIVES: We used aldosterone synthase deficient (AS(-/-)) mice to test whether the absence of aldosterone is sufficient to impair pregnancy or even to cause preeclampsia. METHODS: AS(-/-) and AS(+/+) females were mated with AS(+/+) and AS(-/-) males, respectively, always generating AS(+/-) offspring. Blood pressure was measured by tail cuff, fetal and placental number and size as well as placental histology were assessed. Placental expression of HIF-1αand angiogenic factors was assessed by semiquantitative RT-PCR. RESULTS: With maternal aldosterone deficiency in AS(-/-) mice, systolic blood pressure was low before and further reduced during pregnancy and with no increase in proteinuria. Yet, AS(-/-) had smaller litters due to loss of fetuses as indicated by a high number of necrotic placentas with massive lymphocyte infiltrations at gestational day 18. Surviving fetuses and their placentas from AS(-/-) females were smaller. High salt diet before and during pregnancy increased systolic blood pressure only before pregnancy in both genotypes and reduced blood pressure during late pregnancy as compared to normal salt controls. Litter size from AS(-/-) was slightly improved and the differences in placental and fetal weights between AS(+/+) and AS(-/-) mothers disappeared. Overall an increased placental efficiency was observed in both groups. CONCLUSION: Our results demonstrate that aldosterone deficiency has profound adverse effects on placental function. High dietary salt intake improved placental function and lowered blood pressure in wild-type mice. In this animal model, aldosterone deficiency did not cause preeclampsia.

Effect of recombinant human erythropoietin after allogenic bone marrow transplantation.

The hematologic effects of recombinant human erythropoietin after allogeneic bone marrow transplantation (BMT) were studied. Nineteen patients received 150 U/kg/day of C127 mouse-cell-derived recombinant human erythropoietin (rHu EPO) as a daily continuous intravenous infusion until hematocrit exceeded 35%. These data were compared with a treatment-matched historical control group of 43 patients. RHu EPO-treated patients recovered erythropoiesis more rapidly and became independent from erythrocyte transfusions after a median of 17 days, which was 7 days earlier than the control patients.