1. National Resource Center for Late Effects after Cancer Treatment
Long-term survival after high dose chemotherapy with autologous stem cell support (HDT) for lymphomas in adults – a national multi-center study
K Smeland 1, H Holte 2, Stein Kvaløy 2, GF Lauritzen 2, A Fosså 2, B Østenstad 2, A Kolstad 2, UM Fagerli 3, Ø Fluge 4, M Maisenhølder 5, JH Loge 1, SD Fosså 1, C Kiserud 1
1 National Resource Center for Late Effects after Cancer Treatment, Department of Oncology, Oslo University Hospital. 2 Department of Oncology, Oslo University Hospital.
3 Department of Oncology, St. Olav's Hospital. 4 Department of Oncology, Haukeland University Hospital. 5 Department of Oncology, University Hospital of North Norway 1
Background
High dose chemotherapy with autologous stem cell support (HDT) is a highly intensive, and potentially curative treatment for lymphoma, that has been used in Norway for the last 25 years. The purpose of this study is to investigate long-term survival after HDT compared to age- and gender matched controls, and compare survival between the different groups of lymphomas and conditioning regimens.
Results
- Controls (n = 3553)
- Cases (n = 711)
Methods
This project is part of a national multi-center study exploring several late effects after HDT for lymphomas. Inclusion criteria identify all lymphoma-patients aged ≥18 years at time of HDT and treated in the period at five Norwegian university hospitals (N=711, in total).
Data were obtained from The Cancer Registry of Norway, and linked with clinical data from each hospital. The patients were grouped based on histopathological diagnosis:
Hodgkin lymphoma (HL)
Very aggressive/aggressive lymphomas (large B-cell, mantle cell, Burkitt’s, lymphoblastic and T-cell lymphoma) and
Indolent lymphomas (follicular lymphoma and other).
Observation time was estimated from date of HDT to death or cut-off on December Crude cumulative probabilities for survival were calculated by the Kaplan-Meier method and the groups compared with log-rank tests. Five age and gender matched controls were drawn from the general Norwegian population, and compared using the Cox proportional Hazard method.
Fig. 1: 10-year overall survival for lymphoma patients treated with HDT i Norway was 55% (95 % CI: 51 % - 58 %). Age- and gender matched controls from the general Norwegian population are shown in comparison (5 per case). HR 15 (95% CI: 13-19), p<0.001.
- Females (n = 250)
- Males (n = 461)
Fig. 2: Survival by gender: 10-year overall survival for females and males was 62 % (95 % CI: 55 % - 68 %) and 52 % (95 % CI: 47 % - 57 %), p = 0.04.
Patient Characteristics (n = 711)
Age at HDT
Median (range) 48
(18-69)
Number %
Gender
Male
461 65
Female
250 35
Diagnosis group
Hodgkin
147 21
Aggressive/very aggressive
467 67
Indolent 84 12
High dose regimen
TBI* + cyclophosphamide
102 14
BEAM**
609 86
- Hodgkin lymphoma (n = 147)
- Indolent lymphomas (n = 84)
- Aggressive/very aggressive
lymphomas (n = 467)
Fig. 3: Survival by group of lymphoma: 10-year overall survival for Hodgkin lymphoma, indolent lymphomas and aggressive/very aggressive lymphomas was 65% (95 % CI: 57 % - 73 %), 57 % (95 % CI: 45 % - 69 %) and 52 % (95 % CI: 47 % - 57 %) respectively, p = 0.02.
- TBI + Cyclophosphamide
(n = 102)
*TBI = Total body irradiation, **BEAM = Carmustine, Etoposide, cytarabin and melphalan
- BEAM (n = 609)
Summary of results
Lymphoma patients treated with HDT have 15-times increased mortality compared to controls.
More than half of lymphoma patients are alive ten years after HDT
Hodgkin lymphoma is the most favourable group
Females have better survival than males.
There is no significant difference in survival between the high-dose regimens
Cause of death will be included in final analysis
Fig. 4: Survival by high dose regimen: 10-year overall survival for total body irradiation (TBI) with high dose cyclophosphamide and BEAM (Carmustine, Etoposide, cytarabin and melphalan) was 55 % (95 % CI: 45 % - 65 %) and 55 % (95 % CI: 51 % - 60 %), p = 0.77.
Conclusion
Survivors after HDT are heavily treated, and are likely to carry a large burden of late effects. As a subsequent part of this project, all survivors (n = 411) will be invited to answer a questionnaire and to attend an examination at the out-patient clinic at the hospital they received their HDT, including assessment of a wide range of physical, psycho-social and cognitive late effect.
National Resource Center for Late Effects after Cancer Treatment
Contact: Knut H. B. Smeland, mail: