Smoking places the patient at risk for increased time to union and complications. Previous smoking history also appears to increase the risk of osteomyelitis and increased time to union. The results highlight the need for orthopaedic surgeons to encourage their patients to enter a smoking cessation programs.

Seventy-one allograft recipients receiving voriconazole, in whom complete clinical, microbiologic and pharmacokinetic data were available, were studied to determine the efficacy of voriconazole in preventing fungal infections. The length of voriconazole therapy was 6-956 days (median 133). The total number of patient-days on voriconazole was 13 805 (B38 years). A total of 10 fungal infections were seen in patients on voriconazole (18% actuarial probability at 1 year): Candida glabrataand Mucor (n ¼ 1). Two of the four zygomycosis cases were preceded by short durations of voriconazole therapy, but prolonged itraconazole prophylaxis. The plasma steady-state trough voriconazole levels around the time the infection occurred were o0.2, o0.2, 0.33, 0.55, 0.63 and 1.78 lg/ml in the six candidiasis cases. Excluding the four zygomycosis cases, all the six candidiasis cases were seen among the 43 patients with voriconazole levels of p2 lg/ml and none among the 24 with levels of 42 lg/ml (P ¼ 0.061). We conclude that voriconazole is effective at preventing aspergillosis. However, breakthrough zygomycosis is seen in a small proportion of patients. The role of therapeutic voriconazole monitoring with dose adjustment to avoid breakthrough infections with fungi that are otherwise susceptible to the drug needs to be explored prospectively.

BACKGROUND. Low voriconazole levels have been associated with a higher failure rate in patients with confirmed fungal infections. METHODS. Steady‐state plasma trough voriconazole levels were measured after at least 5 days of therapy in 87 patients with hematologic malignancies on 201 separate occasions (1–5 levels per patient; median, 2). Most patients (90%) had undergone allogeneic hematopoietic stem cell transplantation. The daily voriconazole dose, administered in 2 divided doses, was 200 mg (n = 4), 400 mg (n = 151), 500 mg (n = 20), 600 mg (n = 18), and 800 mg (n = 8); corresponding to 2.0–16.3 (median, 5.4) mg/kg. Plasma voriconazole levels were 0–12.5 μg/mL (median, 1.2). Voriconazole was undetectable (<0.2 μg/mL) in 15%. RESULTS. The correlation between dose and levels was weak (r = 0.14; P = .045). The median absolute daily drug dose (400 mg) was identical in groups of patients with levels of 0, 0.2 to 0.5, >0.5 to 2.0, >2.0 to 5.0, and >5.0. Whereas the daily drug dose in mg/kg was significantly higher when the levels were >5.0 μg/mL, there was no consistent relation between dose and level below that threshold. In adult patients getting standard doses of voriconazole orally, the drug levels are highly variable. Based on limited available data, between a quarter and two‐thirds of these levels could potentially be associated with a lower likelihood of response or a higher likelihood of failure. CONCLUSIONS. Future voriconazole studies should incorporate prospective therapeutic drug monitoring and consideration should be given to checking levels in patients receiving the drug for confirmed, life‐threatening fungal infections. Cancer 2007. © 2007 American Cancer Society.

Although numerous reports indicate that patients receiving autotransplants for lymphoma are at increased risk for myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), the separate contributions of pretransplantation-and transplantation-related therapy are not well characterized. We conducted a case-control study of 56 patients with MDS/AML and 168 matched controls within a cohort of 2 739 patients receiving autotransplants for Hodgkin disease or non-Hodgkin lymphoma at 12 institutions (1989-1995). Detailed abstraction of medical records was undertaken to determine all pre-and posttransplantation therapy, and transplantation-related procedures. In multivariate analyses, risks of MDS/AML significantly increased with the intensity of pretransplantation chemotherapy with mechlorethamine (relative risks [RRs] ‫؍‬ 2.0 and 4.3 for cumulative doses < 50 mg/m 2 and > 50 mg/m, 2 respectively; trend over dose categories, P ‫؍‬ .04) or chlorambucil (RRs ‫؍‬ 3.8 and 8.4 for duration < 10 months or > 10 months, respectively; trend, P ‫؍‬ .009), compared with cyclophosphamide-based therapy. Transplantation-conditioning regimens including total-body irradiation (TBI) at doses 12 Gy or less did not appear to elevate leukemia risk (RR ‫؍‬ 1.3; P ‫؍‬ .48) compared with non-TBI regimens; however, a statistically significant increased risk was found for TBI doses of 13.2 Gy (RR ‫؍‬ 4.6; P ‫؍‬ .03). Peripheral blood stem cells were associated with a nonsignificant increased risk of MDS/AML (RR ‫؍‬ 1.8; P ‫؍‬ .12) compared with bone marrow grafts. Our data show that type and intensity of pretransplantation chemotherapy with alkylating agents are important risk factors of MDS/AML following autotransplantation. Transplantationrelated factors may also modulate this risk; however, the apparent contribution of highdose TBI requires confirmation. (Blood.

We identified 5,350 oncology APPs and conclude that number may be as high as 7,000. Survey results suggest that practices that incorporate APPs routinely rely on them for patient care. Given the increasing number of patients with and survivors of cancer, APPs are important to ensure access to quality cancer care now and in the future.

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A B S T R A C T PurposeTo determine the maximum-tolerated radiation-absorbed dose (RAD) to critical organs delivered by yttrium-90 ( 90 Y) ibritumomab tiuxetan in combination with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy with autologous transplantation. Patients and MethodsEligible patients had relapsed or refractory CD20ϩ non-Hodgkin's lymphoma (NHL). Individualized 90 Y activities were based on dosimetry and were calculated to deliver cohort-defined RAD (1 to 17 Gy) to critical organs with three to six patients per cohort. The therapeutic dose of 90 Y ibritumomab tiuxetan was followed by high-dose BEAM and autologous transplantation. ResultsForty-four patients were treated. Thirty percent of patients had achieved less than a partial remission to their most recent therapy and would not have been eligible for autologous transplantation at most centers. The toxicity profile was similar to that associated with high-dose BEAM chemotherapy. Two dose-limiting toxicities occurred at the 17 Gy dose level, which made 15 Gy the recommended maximum-tolerated RAD. Although eight patients received at least twice the conventional dose of 0.4 mCi/kg, a weight-based strategy at 0.8 mCi/kg would have resulted in a wide range of RAD; nearly 25% of patient cases would have received 17 Gy or more, and many would have received less than 10 Gy. With a median follow-up of 33 months for all patients, the estimated 3-year progression-free and overall survivals were 43% and 60%, respectively. Conclusion Dose-escalated90 Y ibritumomab tiuxetan may be safely combined with high-dose BEAM with autologous transplantation and has the potential to be more effective than standard-dose radioimmunotherapy. Careful dosimetry is required to avoid toxicity and undertreatment.