Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia [see comments]

The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).     

An undifferentiated variant derived from the human acute myelogenous leukemia cell line (KG-1)

A variant subline (KG-1a) of the human acute myelogenous leukemia (AML) cell line (KG-1) has been isolated. The cells retain the same constitutive markers as the parent line, including HLA antigens, isoenzymes, and karyotype. The cells from the subline are morphologically and histochemically undifferentiated blast cells, while the parent cells and several of its clones are at the myeloblast and promyelocyte stages of development. The variant cells do not respond to colony-stimulating factor (CSF), and they do not express the human la antigen, nor a recently characterized AML antigen. The parent KG-1 cells are stimulated to proliferate in the presence of CSF and the cells express the la and AML antigen. Variant AML cell lines, such as KG-1a, will be useful in vitro models for investigating cellular response to CSF and for studying antigen expression in leukemic cells.     

Persistence, reproducibility, and cost-effectiveness of an intervention to improve the quality of osteoporosis care after a fracture of the wrist: results of a controlled trial

INTRODUCTION: Older patients with fragility fractures are not commonly tested or treated for osteoporosis. Compared to usual care, a previously reported intervention led to 30% absolute increases in osteoporosis treatment within 6 months of wrist fracture. Our objective was to examine longer-term outcomes, reproducibility, and cost-effectiveness of this intervention. METHODS: We conducted an extended analysis of a non-randomized controlled trial with blinded ascertainment of outcomes that compared a multifaceted intervention to usual care controls. Patients >50 years with a wrist fracture treated in two Emergency Departments in the province of Alberta, Canada were included; those already treated for osteoporosis were excluded. Overall, 102 patients participated in this study (55 intervention and 47 controls; median age: 66 years; 78% were women). The interventions consisted of faxed physician reminders that contained osteoporosis treatment guidelines endorsed by opinion leaders and patient counseling. Controls received usual care; at 6-months post-fracture, when the original trial was completed, all controls were crossed-over to intervention. The main outcomes were rates of osteoporosis testing and treatment within 6 months (original study) and 1 year (delayed intervention) of fracture, and 1-year persistence with treatments started. From the perspective of the healthcare payer, the cost-effectiveness (using a Markov decision-analytic model) of the intervention was compared with usual care over a lifetime horizon. RESULTS: Overall, 40% of the intervention patients (vs. 10% of the controls) started treatment within 6 months post-fracture, and 82% (95%CI: 67-96%) had persisted with it at 1-year post-fracture. Delaying the intervention to controls for 6 months still led to equivalent rates of bone mineral density (BMD) testing (64 vs. 60% in the original study; p = 0.72) and osteoporosis treatment (43 vs. 40%; p = 0.77) as previously reported. Compared with usual care, the intervention strategy was dominant - per patient, it led to a $13 Canadian (U.S. $9) cost savings and a gain of 0.012 quality-adjusted life years. Base-case results were most sensitive to assumptions about treatment cost; for example, a 50% increase in the price of osteoporosis medication led to an incremental cost-effectiveness ratio of $24,250 Canadian (U.S. $17,218) per quality-adjusted life year gained. CONCLUSIONS: A pragmatic intervention directed at patients and physicians led to substantial improvements in osteoporosis treatment, even when delivered 6-months post-fracture. From the healthcare payer's perspective, the intervention appears to have led to both cost-savings and gains in life expectancy.     

Adherence of L1210 murine leukemia cells to sephacryl- aminopropylcobalamin beads treated with transcobalamin-II

Sephacryl beads containing an immobilized aminopropylcobalamin- transcobalamin-II complex serve as foci for the adherence of L1210 murine leukemia cells. Bead-cell interaction does not occur when (A) nonderivatized beads are used; (B) transcobalamin-II is omitted or presaturated with cyanocobalamin in the preparation of the bead complex; (C) intrinsic factor replaces transcobalamin-II; and (D) the complex is removed from beads by photolysis. These observations suggest that adherence results from the ability of transcobalamin-II to form a bridge between immobilized cobalamin on the bead and receptors in the plasma membrane of the cell.