No abstract

Salvage of patients with relapsed and refractory Hodgkin disease (HD) with highdose chemoradiotherapy (HDT) and autologous stem cell transplantation (ASCT) results in event-free survival (EFS) rates from 30% to 50%. Unfortunately, the reduction in toxicity associated with modern supportive care has improved EFS by only 5% to 10% and has not reduced the relapse rate. Results of a comprehensive 2-step protocol encompassing dosedense and dose-intense second-line chemotherapy, followed by HDT and ASCT, are reported. Sixty-five consecutive patients, 22 with primary refractory HD and 43 with relapsed HD, were treated with 2 biweekly cycles of ifosfamide, carboplatin, and etoposide (ICE). Peripheral blood progenitor cells from responding patients were collected, and the patients were given accelerated fractionation involved field radiotherapy (IFRT) followed by cyclophosphamide-etoposide and either intensive accelerated fractionation total lymphoid irradiation or carmustine and ASCT. The EFS rate at a median follow-up of 43 months, as analyzed by intent to treat, was 58%. The response rate to ICE was 88%, and the EFS rate for patients who underwent transplantation was 68%. Cox regression analysis identified 3 factors before the initiation of ICE that predicted for outcome: B symptoms, extranodal disease, and complete remission duration of less than 1 year. EFS rates were 83% for patients with 0 to 1 adverse factors, 27% for patients with 2 factors, and 10% for patients with 3 factors (P < .

Recurrent event data are frequently encountered in longitudinal follow-up studies. In statistical literature, noninformative censoring is typically assumed when statistical methods and theory are developed for analyzing recurrent event data. In many applications, however, the observation of recurrent events could be terminated by informative dropouts or failure events, and it is unrealistic to assume that the censoring mechanism is independent of the recurrent event process. In this article we consider recurrent events of the same type and allow the censoring mechanism to be possibly informative. The occurrence of recurrent events is modeled by a subject-specific nonstationary Poisson process via a latent variable. A multiplicative intensity model is used as the underlying model for nonparametric estimation of the cumulative rate function. The multiplicative intensity model is also extended to a regression model by taking the covariate information into account. Statistical methods and theory are developed for estimation of the cumulative rate function and regression parameters. As a major feature of this article, we treat the distributions of both the censoring and latent variables as nuisance parameters. We avoid modeling and estimating the nuisance parameters by proper procedures. An analysis of the AIDS Link to Intravenous Experiences cohort data is presented to illustrate the proposed methods.