ABSTRACT
BACKGROUND AND OBJECTIVE: Allogeneic transplantation can not be offered to many patients due to potential side-effects of conventional conditioning. Dose-reduced conditioning approaches improve tolerability, however, treatment efficacy may be reduced as well. We have, therefore, developed a dose intense but toxicity reduced conditioning regimen based on treosulfan and fludarabine and report first results. PATIENTS AND METHODS: 65 patients with a median age of 50 years were transplanted from related (n = 21) or unrelated donors (n = 44) after conditioning with treosulfan (3 x 10, 3 x 12 or 3 x 14 g/m(2) i. v.) and fludarabine (5 x 30 mg/m(2) i. v.). 21 patients were in complete remission (CR) and 44 patients had not reached a CR at the time of transplantation. 59 of 65 patients were considered unfit for a conventional conditioning regimen. RESULTS: The actuarial overall survival after 3 years is 59.2 %, the event-free survival 40.1 %. Patients with a related donor or transplantation in CR had a better overall (85.4 resp. 74.2 %) and event-free survival (52.2 % resp. 61.9 %). The cumulative incidence of relapse at 3 years was 26.2 %. Non-relapse mortality at day 100 is 17.4 % (cumulative incidence). In stepwise Cox regression analyses for overall survival, event-free survival and non-relapse mortality the covariables transplantation in CR vs. not in CR and the donor status were shown to be influential. CONCLUSIONS: These results with a conditioning therapy of treosulfan and fludarabine indicate that patients despite higher age, concomitant disease or after intensive pretreatment can be successfully transplanted without increased treatment-related mortality.
Subject(s)
Antineoplastic Agents/therapeutic use , Busulfan/analogs & derivatives , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Vidarabine/analogs & derivatives , Adult , Antineoplastic Agents/administration & dosage , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/therapeutic use , Busulfan/administration & dosage , Busulfan/therapeutic use , Disease-Free Survival , Dose-Response Relationship, Drug , Female , Graft vs Host Disease/epidemiology , Hematologic Neoplasms/mortality , Hematopoietic Stem Cell Transplantation/mortality , Hematopoietic Stem Cell Transplantation/standards , Humans , Incidence , Male , Middle Aged , Recurrence , Regression Analysis , Remission Induction , Risk Factors , Survival Analysis , Transplantation Conditioning/mortality , Transplantation Conditioning/standards , Transplantation, Homologous , Vidarabine/administration & dosage , Vidarabine/therapeutic useABSTRACT
The German Multicentre acute lymphoblastic leukaemia (ALL) study group (GMALL) performed a pilot study using pegylated asparaginase (PEG-ASP) in combination with high-dose methotrexate as consolidation therapy in the 05/93 protocol. The aim of the study was an intra-individual comparison of two different doses of PEG-ASP in 26 patients, with regard to the depletion of asparagine in serum and toxicity. 'Pharmacokinetic' monitoring was performed to evaluate the effect of an intra-individual dose escalation of PEG-ASP from 500 to 1000 U/m2 intravenously in successive doses. Serum asparaginase activity was targeted at > or =100 U/l for 1 week and > or =50 U/l for 10 d. The second course of PEG-ASP was administered to 23 patients. Due to hypersensitivity reactions in five patients, only 18 patients were evaluable for pharmacokinetic monitoring. With respect to the PEG-ASP activity, an effective depletion of asparagine could be postulated in the majority of patients during 10 d after the first administration. The effect of an intraindividual dose escalation form 500 to 1000 U/m2 was evaluable in 17 of 22 patients. An increment in peak PEG-ASP activity >70% was observed in 65% of the patients. PEG-ASP was well tolerated. Despite the long half-life of PEG-ASP, neither pancreatic nor central nervous toxicities occurred among the 26 adult patients treated in this pilot study.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Asparaginase/administration & dosage , Asparaginase/adverse effects , Asparagine/blood , Blood Coagulation/drug effects , Drug Administration Schedule , Female , Humans , Liver/drug effects , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Pilot Projects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Remission InductionABSTRACT
The 1-pool-model of sodium kinetics during hemodialysis is based upon the assumption of an immediate compensation of osmotic shifts. This assumption is not supported by measurements of plasma sodium, total protein concentration and colloid osmotic pressure kinetics. When a high dialysate sodium concentration is applied, an inflow of sodium into the plasma space occurs, which results in an osmotic suction and thus a plasma dilution. These conditions can be represented by a 2-pool-model taking into consideration capillary filtration. The results indicate that following the first treatment period the sodium kinetics are sufficiently explained by a 1-pool-model with the total body water as distribution volume. Both the plasma sodium concentration and the eliminated sodium at the end of a hemodialysis treatment can be described to an acceptable level by the 1-pool-model. The input of the measured in-vivo sodium dialysance value (or alternatively the urea clearance) is necessary.
Subject(s)
Kidney Failure, Chronic/blood , Renal Dialysis , Sodium/blood , Water-Electrolyte Balance/physiology , Blood Proteins/metabolism , Humans , Kidney Failure, Chronic/therapy , Models, Theoretical , Osmotic PressureABSTRACT
Considering the plasma colloid osmotic pressure (COP) as a possible parameter for the monitoring of dialysis treatment compatibility, a characteristic time course was found. The COP and the total protein concentration very often do not increase significantly during the first treatment hour in spite of ultrafiltration. An increase in the plasma sodium concentration, which was higher than expected, was found to be the reason for a plasma dilution effect. This can be explained by a transcapillary sodium transfer coefficient which is not infinitely high as assumed in single-pool sodium modelling. From a 2-pool model considering the plasma volume as a separate pool and including capillary filtration time courses for plasma sodium, total protein concentration and COP could be calculated, which was very similar to the measured curves.