Childhood acute myeloid leukemia: outcome in a single center using chemotherapy and consolidation with busulfan/cyclophosphamide for bone marrow transplantation.

PURPOSE: To report the impact of bone marrow transplantation (BMT) with busulfan/cyclophosphamide (BuCy) as end consolidation in a cohort of consecutively diagnosed children with acute myeloid leukemia (AML). PATIENTS AND METHODS: Between May 1987 and November 1992, 43 patients were diagnosed with AML. Tissue typing at diagnosis determined whether patients would proceed to autologous or allogeneic BMT as end consolidation after six cycles of chemotherapy. Conditioning for BMT was with BuCy, followed by allogeneic or unpurged autologous marrow infusion. RESULTS: Of 37 patients who received chemotherapy, 35 achieved remission (95%) after one to six courses of treatment and 34 (92%) were transplanted. Five relapsed before BMT, four were subsequently transplanted in second complete remission (CR2) (n = 3) or untreated first relapse (n = 1), and one failed to respond to further therapy. All other patients proceeded to BMT in first complete remission (CR1). Eleven patients received allografts: one relapsed and one died of graft-versus-host disease (GvHD), for a leukemia-free survival rate of 90% at a median of 41 months after BMT (range, 3 to 60). For 23 autografts, there were two toxic deaths and eight relapses, with a leukemia-free survival rate of 61% at a median of 11 months after BMT (range, 0 to 66). The high relapse rate following autologous BMT led us to escalate the dose of Bu from 16 mg/kg to 600 mg/m2 using a single daily dose of Bu. CONCLUSION: With modern supportive therapy, most newly diagnosed children with AML will enter remission and are eligible for intensification therapy. BuCy is well tolerated in children, which allowed us to escalate the dose of Bu in recent patients. Further follow-up is needed to determine whether this has an impact on the relapse rate following autologous BMT.

Alteration of the connective tissue network of striated muscle in copper deficient rats.

The connective tissue network in striated muscle, consisting principally of collagen is arranged in a three dimensional network and is intimately associated with muscle function. Previous studies have shown that animals maintained on a copper-deficient diet undergo myocardial hypertrophy and exhibit cardiovascular lesions such as ventricular aneurysms that eventually rupture. A deficiency of copper in the diet is known to inhibit lysyl oxidase, a metalloenzyme requiring copper as a cofactor and which is also responsible for collagen and elastin crosslinking. Examination by scanning and transmission electron microscopy of skeletal and cardiac muscle from rats maintained on copper-deficient diets showed both gross and microscopic lesions to the connective tissue network. Immunohistochemical staining by light microscopy with antibodies against lysyl oxidase showed that the enzyme was equally present in both control and experimental animals. Fluorescent staining for antibodies against collagen types I and III showed similar results. From these studies we concluded that the collagen secreted during hypertrophy was not crosslinked by lysyl oxidase due to the absence of the copper cofactor. This resulted in the failure of the connective tissue network to transmit and distribute the increased force associated with myocardial hypertrophy and resulted in myocardial aneurysms.

Effects of serum concentration on some growth characteristics of cultured murine parietal yolk sac carcinoma cells.

Murine parietal yolk sac carcinoma cells were examined by scanning and transmission electron microscopy to determine the ultrastructural changes resulting from growth, in vitro, in media containing different serum concentrations. Cells grown in medium supplemented with 10% fetal bovine serum (FBS) formed spherical bodies, were gradually oval with numerous surface microvilli, well-organized microtubules, abundant free polysomes and a well-developed Golgi apparatus. By contrast, cells grown in 1% FBS failed to form multicellular spheres, were generally flattened over the growth surface and lacked the surface and intracellular features demonstrated when cells were grown in 10% serum. These differences could explain the alterations in the glycosylation of secreted glycoprotein associated with culture in the presence of low serum.