High dose chemotherapy with busulfan, cyclophosphamide, and etoposide as conditioning regimen for allogeneic bone marrow transplantation for patients with acute myeloid leukemia in first complete remission.

We explored the combination of busulfan/cyclophosphamide/etoposide as conditioning regimen prior to bone marrow transplantation in 31 patients with acute myeloid leukemia (AML) in first complete remission. The preparative regimen consisted of 16 mg/kg busulfan, 30-60 mg/kg VP-16, and 120 mg/kg cyclophosphamide. With a median follow-up of 30.5 months (range, 5-60 months), 25 patients are alive in continuous complete remission. Estimated disease-free survival at 5 years is 80.5%. Death was due to transplant-related toxicity (graft-versus-host disease and cytomegalovirus infection, graft-versus-host disease and pneumonia, sepsis and mucositis, respectively). None of the patients have relapsed. As demonstrated by the results of this analysis, the conditioning regimen busulfan/cyclophosphamide/etoposide is effective and well tolerated in patients with AML in first complete remission. Main nonhematological toxicities were mucositis and hepatotoxicity. The low mortality and relapse rate appears to justify allogeneic bone marrow transplantation for patients with AML in first complete remission who have an HLA-identical donor. Whether this regimen offers a substantial improvement in disease-free and overall survival over presently used regimens warrants further investigation.

[Age-related changes in cell content (DNA) and glycosaminoglycan-degrading enzymes (beta-glucuronidase, beta-N-acetylglucosaminidase of connective tissue and parenchymal organs of the rat caused by 6-methylprednisolone (enzyme induction, adaptation, acceleration of maturation and possible modification of aging]. / Altersabhängige Veränderungen des Zellgehaltes (DNA) und der Glykosaminoglykan-abbauenden Enzyme (beta-Glucuronidase, beta-N-Acetylglucosaminidase) bindegewebiger und parenchymatöser Organe der Ratte durch 6-Methylprednisolon (Enzyminduktion, Adaptation, Reifungsbeschleunigung und mögliche Alternsbeeinflussung).

This paper is based on previous investigations, which had shown an evident acceleration of maturation and enzyme induction in several organs, not only in the lung, due to a pre- and postnatal application of prednisolone. Applying the same dosage we now investigated whether there is a similar effect of a short-term application of prednisolone in mesenchymal and parenchymal organs of young adult and presenile rats of the same strain (Chbb: THOM/SPF) analyzing the physiological cell regeneration (DNA concentration) as well as functional parameters of the glycosaminoglycan metabolism (e.g. the lysosomal enzymes beta-glucuronidase and beta-N-acetylglucosaminidase). The results show a significant age-dependent decrease of the DNA concentration (lung, spleen, skin, and rib cartilage), a significant age-dependent decrease of the total activity of the beta-glucuronidase (kidney, rib cartilage, and skin) or a significant age-dependent increase of this enzyme activity (spleen and liver) respectively as well as a significant decrease of the beta-N-acetylglucosaminidase activity (skin and rib cartilage) or a significant increase of this enzyme activity (spleen and lung). After application of prednisolone the rats showed a significant reduction of the DNA concentration only in the skin of young adult rats, but no changes in the other organs of the young adult or presenile animals compared to untreated controls. Similar to our findings after postnatal prednisolone application, we found the greatest increases or decreases respectively of the activities of these lysosomal enzymes due to 2- to 3-fold or 4- to 5-fold prednisolone application. Again similar to our previous findings, we found the phenomena of adaptation and rebound effects including the so-called over-compensation in the young adult and especially in the presenile rats but these effects were delayed and weaker in most of the older animals compared to the young adult rats.