Early post-BMT liver function in children conditioned for bone marrow transplantation with busulfan-containing and with hyperfractionated TBI-containing preparative regimens

Liver toxicity following preparatory regimen (prep-reg) for bone marrow transplantation (BMT) creates one of the major problems in the early post-BMT period, especially in patients (pts.) with pretransplant HCV and/or HBV infections, and liver dysfunction. This gave rise to the search for prep-reg, that would be less hepatotoxic, but would still have sufficient antileukemic effect. Therefore, we compared liver function in children prepared for allo-BMT with busulfan-containing and with hyperfractionated TBI-containing regimens.Patients and methodsSeventeen pts. have been conditioned with busulfan-containing prep-reg (10 with BuVpCy, 7 with BuCy) (Bu-group). Diagnosis consisted of ALL (6) and AML (11). All pts. fram Bu-group have been transplanted with bone marrow from HLA-identical, MLC non-reactive siblings. Pretransplant screening showed positive HBsAg in one patient, and HCV antibody in 6 pts. For GvHD prevention CsA+MTX have been given in 12 pts., CsA+MTX+PRED in 3 pts., and CsA alone in 2 pts. Acute GvHD II- IVO occured in 4 pts. Hyperfractionated TBI (hFTBI) (2 × 1,5 Gy on 4 consecutive days) was employed in 10 pts. (hFTBI+Cy in 6 pts., hFTBI+Vp in 4 pts.) (hFTBI-group). Nine pts. were transplanted for ALL, and one child for AML. Nine pts. from hFTBI-graup have been transplanted with bone marraw fram HLA-identical, MLC non-reactive siblings, and one child from a syngeneic twin. For GvHD prevention 5 pts. have been treated with CsA+MTX, 2 with CsA+PRED, and 2 with CsA alone (recipient of syngeneic bone marrow received no GvHD prophylaxis). Acute GvHD IIO was observed in one child. For HVOD prevention in all children from both groups continuous infusion of alprostadil and/or low-dose heparin (100 units/kg/day) has been administered. Total bilirubine concentration, alanine aminotransferase (AIAt) and aspartate aminotransferase (AspAt) activity were measured in serum on day −10, −1, +7, +14, +21, +28 and +35 by automated chemical analysis using standard reagents.ResultsOne child (AML, pos. HCV antibody, BuCy, CsA alone for GvHD prevention) from Bu-group developed on day +18 day recurrent form of severe HVOD leading to the death on day +102.ConclusionsAccording to liver function parameters observed till day +35 post-BMT, ie. during the period, when the risk of HVOD is highest, hFTBI seems to be less hepatotoxic than busulfan-containing prep-reg. Therefore BM-recipients with liver dysfunction observed prior to BMT should rather be prepared for transplantation with hFTBI

47. Allogeneic bone marrow transplantation in children with acute lymphoblastic leukemia in first and second complete remission conditioned with fractionated total body irradiation and etoposide or cyclophosphamide

Patients and methodsFrom 1993 to 2001 thirty two children underwent bone marrow transplantation (BMT) for ALL (12 in I CR and 20 in II CR after early BM or BM/organ relapse). Except 2 syngeneic all other were HLA-identical siblings transplants. All patients (pts) were conditioned with FTBI 2×1,5 Gy for 4 days (total dose 12 Gy) with lung shielding (9 Gy) and CY 60 mg/kg i.v for 2 days (total dose 120 mg/kg) (n=1 in I CR and n = 11 in II CR) or VP 60 mg/kg i.v (n = 11 in I CR and n = 9 in II CR), Pts in I CR have been given 1,1–4,9×108 MNC/kg (med. 2,7×108/kg), while pts in II CR 1,9–4,0×108 MNC/kg (med. 2,7×108/kg). For GvHD prevention CsA 3 mg/kg/d i.v was administered alone in 22 pts (n = 9 in I CR and n = 13 in II CR) or in combination with “short” MTX +/− PRED in 8 pts (n = 3 in I CR and n = 5 in II CR). Two pts transplanted with syngeneic BM received no GvHD prevention. Regimen related toxicity (RRT) was graded according to the system developed by Bearman et al. (1988).ResultsOnly mild or moderate expression of RRT was observed (GI toxicity, I°− 80%, II° −4%; stomatitis I° −40%, II° −20%; hepatic toxicity I°− 28%; renal, bladder and cardiac toxicity I°− 4%) and no transplant related deaths occured (TRM=0%). Among 12 pts transplanted in I CR only one child relapsed 4 months from BMT, while remaining 11 pts are alive in CCR with a median follow-up of 33months (range 6 to 66 months) and 92% probability of 5-year EFS. Of 20 children transplanted in II CR 6 relapsed 1–14 months from BMT (median 6,5 months). Fourteen of them remain in CCR with a median follow-up 19,5 months (range 1 to 96 months) and 66% probability of 8-year EFS.Conclusions1.In children with ALL the FTBI-12 Gy-containing regimen is well tolerated without the life-threatening toxic complications.2.FTBI-12 Gy-containing regimen demonstrates very good antileukemic efficacy for HR-ALL in I CR, but only limited for ALL in II CA.3.3. In context of good tolerance of FTBI in a total dose of 12 Gy and its limited antileukemic efficacy in children with ALL in II CR the escalation of FTBI total dose from 12 Gy to 13,2 Gy appears to be justified in those children. Supported by grant KBN 4 PO5E 108 18

Application of the yeasts Yarrowia lipolytica for in-situ gioremediation of soil contaminated with creosote oil - A case study

Podano wyniki analiz mikrobiologicznych i chemicznych próbek gruntu zanieczyszczonego olejem kreozotowym na terenie zakładu przetwórstwa drewna. Wybrany teren zakładu o powierzchni ok. 0,12 ha poddano bioremediacji metodą in situ z wykorzystaniem autochtonicznych drożdży Yarrowia lipolytica do bioaugmentacji gruntu. Zastosowano trzy preparaty drożdży - komórki immobilizowane w alginianie sodu i skrobi oraz zawiesiny komórek. Do badanego gruntu wprowadzono około 2*10[do potęgi 12] komórek drożdży (238 g). Na pod-stawie uzyskanych wyników jednoznacznie wykazano poprawę struktury gruntu i zmniejszenie zawartości występujących na tym terenie zanieczyszczeń. Sumaryczna zawartość wielo-pierścieniowych węglowodorów aromatycznych zmniejszyła się 3-krotnie podczas 9 miesięcy bioremediacji. Znacząco wzrosła jedynie zawartość antracenu. Zanieczyszczenie olejem kreozotowym, mierzone jako suma węglowodorów ropopochodnych (TPH), zmniejszyło się o prawie 70% na terenie, gdzie wprowadzono drożdże unieruchomione (immobilizowane) w alginianie sodu oraz o ponad 33% na całym badanym obszarze. Wprowadzenie unieruchomionej biomasy drożdży Y. lipolytica wzbogaciło eukariotyczną mikroflorę gleby, poprawiając stosunek liczby bakterii do liczby drożdży i pleśni. Z gruntu poddanego procesowi oczyszczania, obok szczepów gatunku Y. lipolytica, wyizolowano i zidentyfikowano także drożdże Rhodotorula glutinis oraz Cryptococcus albidus.Creosote-contaminated soil samples collected within the premises of a timber processing plant were made the subject to microbiological and chemical analysis. An area of approximately 0.12 ha was chosen for in-situ bioremediation involving an autochthonous Yarrowia lipolytica yeast species. Use was made of three yeast preparations: cells immo-bilized in sodium alginate or starch, and yeast suspensions. The number of yeast cells introduced into the soil approached 2*10 12 (238 g). The results obtained have revealed substantial improvement in the soil structure and noticeable reduction in the concentrations of the particular contaminants detected in this area. During nine months of bioremediation, the total content of polycyclic aromatic hydrocarbons decreased threefold, but a significant increase was observed in the concentration of anthracene. Contamination with creosote oil, expressed as the level of total petroleum hydrocarbons, was reduced by about 70% in the area treated with sodium-alginate-immobilized yeasts, and by more than 33% over the entire area examined. The introduction of immobilized Y. lipolytica biomass enriched the eukariotic microflora of the soil, improving the proportion of bacterial counts to the counts of yeasts and those of mould. Apart from the strains of Y. lipolytica, another two yeast species were isolated from and identified in the soil being bioremediated - Rhodotorula glutinis and Cryptococcus albidus