Time-dependent effect of non-Hodgkin's lymphoma grade on disease-free survival of relapsed/refractory patients treated with high-dose chemotherapy plus autotransplantation

Abstract Evaluation of time to event outcomes usually is examined by the Kaplan–Meier method and Cox proportional hazards models. We developed a modified statistical model based on histologic grade and other variables to describe the time-dependent outcome for autologous stem cell transplant (autotr...

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Bibliographic Details
Published in:Contemporary clinical trials 2008-03, Vol.29 (2), p.157-164
Main Authors: Fu, P, van Heeckeren, W.J, Wadhwa, P.D, Bajor, D.J, Creger, R.J, Xu, Z, Cooper, B.W, Laughlin, M.J, Gerson, S.L, Koç, O.N, Lazarus, H.M
Format: Article
Language:English
Subjects:
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Autologous stem cell transplantation
Biological and medical sciences
Cardiovascular
Carmustine - administration & dosage
Cisplatin - administration & dosage
Disease-Free Survival
Etoposide - administration & dosage
Female
Hematologic and hematopoietic diseases
Hematology, Oncology and Palliative Medicine
Humans
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Lymphoma, Non-Hodgkin - mortality
Lymphoma, Non-Hodgkin - pathology
Lymphoma, Non-Hodgkin - therapy
Male
Medical sciences
Middle Aged
Models, Statistical
Non-Hodgkin's lymphoma
Proportional Hazards Models
Stem Cell Transplantation
Survival analysis
Time
Time-dependent effect
Transplantation, Autologous
Treatment Outcome
Tumor grade
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Summary:Abstract Evaluation of time to event outcomes usually is examined by the Kaplan–Meier method and Cox proportional hazards models. We developed a modified statistical model based on histologic grade and other variables to describe the time-dependent outcome for autologous stem cell transplant (autotransplant) performed for non-Hodgkin's lymphoma (NHL) based on histologic grade and other variables. One hundred and fourteen relapsed or refractory NHL patients were treated using BCNU 600 mg/m2 , etoposide 2400 mg/m2 , and cisplatin 200 mg/m2 IV followed by autotransplant. Median age was 53.5 (range: 25–70) years, 78 patients had aggressive NHL and 36 indolent NHL. Seventy-five patients received involved-field radiotherapy just prior to transplant. At a median follow-up of 33 (range: 3 to 118) months, the estimated 5-year Kaplan–Meier probabilities of overall survival and disease-free survival were 61% and 51%, respectively. Cox proportional hazards model analysis showed that proportionality did not hold for lymphoma grade, indicating that the relationship between the grade and disease-free survival differed over time. By piece-wise Cox model, the relative risk for experiencing relapse or death after 1 year in patients with indolent compared with patients with aggressive NHL was 2.81 ( p = 0.019) with 95% confidence interval (1.19, 6.65). The time-dependent effect of lymphoma grade on disease-free survival suggests the need for early (within first year) incorporation of novel therapeutic approaches in management of patients with indolent NHL undergoing autotransplant.
ISSN:1551-7144
1559-2030
DOI:10.1016/j.cct.2007.07.005