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John Hansen

Publications and source records attributed to John Hansen.

20 records · Page 2Linked to original sources

Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome after conditioning with busulfan and fractionated total body irradiation is associated with low relapse rate but considerable nonrelapse mortality.

The objectives of this study were to develop transplantation regimens for patients with advanced myelodysplastic syndrome (MDS) that would be associated with low transplantation-related mortality and improved relapse-free survival. Sixty patients with advanced MDS or acute myeloid leukemia evolving from MDS (sAML), 12 to 62 years old (median, 40 years), were conditioned with busulfan (7 mg/kg) and TBI (6 x 200 cGy) (BU/TBI) and received transplants from related (n = 20) or unrelated donors (n = 40). By French-American-British (FAB) criteria, 21 patients had refractory anemia with excess blasts (RAEB), 16 had RAEB in transformation (RAEB-T), 15 had sAML, and 8 had chronic myelomonocytic leukemia (CMML). By International Prognostic Scoring System (IPSS) criteria, 1 patient had low, 10 had intermediate-1, 13 had intermediate-2, and 31 had high-risk MDS (5 patients had proliferative CMML). All evaluable patients achieved sustained engraftment. The cumulative incidence (CI) of acute GVHD grades II to IV was 83% with unrelated donors and 85% with related donors. The CI of relapse was 25% at 3 years. The incidence of nonrelapse mortality (NRM) at 100 days was 38%. The Kaplan-Meier estimate of survival was 26% at 3 years. Major causes of death were relapse, organ failure, GVHD, and infection. In multivariate analysis, improved relapse-free survival was associated with good cytogenetic risk (P = .002) and shorter disease duration (P = .004). NRM was increased with longer disease duration (P = .0002), positive cytomegalovirus serology (P = .02), and male sex (P = .02). Relapse was associated with poor cytogenetic risk (P = .0004). Thus, BU/TBI conditioning as used in this trial was associated with relapse rates comparable to those observed with a previously used more intensive regimen combining BU/TBI with cyclophosphamide. However, despite the omission of cyclophosphamide, transplantation-related morbidity and mortality were considerable, particularly with transplants from unrelated donors. Future trials should explore the efficacy and tolerability of reduced-intensity conditioning regimens.

Adolescent↗

Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia.

OBJECTIVE: To determine the effectiveness of the Wyeth heptavalent pneumococcal conjugate vaccine against clinical and radiograph-confirmed pneumonia in children. METHODS: The heptavalent CRM(197) pneumococcal conjugate vaccine (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a randomized, double blind trial. Children were randomized to receive either the CRM(197) PCV (vaccine group) or the meningococcal type C CRM(197) conjugate vaccine (control group). The primary outcome of this trial was invasive pneumococcal disease. In addition children with the clinical diagnosis of pneumonia in the study population were identified through review of automated inpatient, emergency and outpatient databases. The subset of the cohort of these children who had chest radiographs obtained at the time of diagnosis was identified, and the original reading of their radiographs by the radiologist was obtained from automated databases. Rates of clinically diagnosed pneumonia, of pneumonia with a radiograph obtained regardless of result, of pneumonia with positive radiograph (consolidation, empyema or parenchymal infiltrate) and of pneumonia with only perihilar infiltrates were compared between vaccinated and nonvaccinated groups. In addition risk of disease pneumonia was evaluated by race and ethnicity. RESULTS: The incidence of a first pneumonia episode in the control group was 55.9 per 1000 person-years. A radiograph was obtained in 61% of episodes, a positive radiograph in 21% and perihilar findings in an additional 5%. In per protocol follow-up of children given PCV, first episodes of all clinically diagnosed pneumonia were reduced by 4.3% [95% confidence interval (CI), -3.5, 11.5%, = 0.27], episodes with a radiograph were reduced by 9.8% (CI 0.1, 18.5%, < 0.05) and episodes with a positive radiograph were reduced by 20.5% (CI 4.4, 34.0, = 0.02). In the intent to treat analysis including all episodes after randomization, episodes with a positive radiograph were reduced by 17.7%, =.01). The greatest impact was in the first year of life with a 32.2% reduction and a 23.4% reduction in the first 2 years, but only a 9.1% reduction in children >2 years of age. Asians, blacks and Hispanics were at higher risk of pneumonia than were whites, but there was no evidence of ethnic variation in PCV effectiveness. Ten of the 11 cases of pneumococcal pneumonia with a positive blood culture were in the control group. CONCLUSION: The pneumococcal conjugate vaccine tested was effective in reducing the risk of pneumonia in young children.

Age Factors↗