Klein Schaarsberg, L.B. (Lianne) (2014) Outcome of adult acute lymphoblastic leukemia patients treated according to the Groningen regimen. thesis, Medicine.
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Abstract
Background Acute lymphoblastic leukemia (ALL) is characterized by malignant proliferation of lymphoid precursor cells in the bone marrow. Outcome in adults remains poor with overall survival (OS) rates of 35-40%. Promising results have been obtained with the Groningen regimen which introduces a pre-induction course with standard dose cytarabine, etoposide and methotrexate (MTX) before regular induction, consolidation and maintenance courses. Previous reports, however, had limited numbers of patients and could not evaluate changes of the pre-induction course over time. Additionally, the prognostic value of minimal residual disease (MRD) in this regimen is unknown. To describe the outcome of patients treated according to the Groningen regimen, to evaluate the effect of the pre-induction course with/without MTX, and to determine the prognostic value of MRD, I conducted a retrospective cohort study. Methods All patients with newly diagnosed ALL aged 15-70 years and treated at the UMCG according to the Groningen regimen between July 1985 and December 2013 were included. Patients with Burkitt-type ALL, treated with palliative intentions, or treated with an alternative regimen were excluded. Until July 1996, only patients with a white blood cell count ≥30 x 109/l received pre-induction, thereafter the pre-induction course was given to all patients and extended with MTX. To evaluate MRD of patients in complete remission (CR), multiparametric flow cytometry data of bone marrow samples taken after induction and consolidation courses after January 1997, was re-evaluated. The detection limit was 0.1-0.05%. Disease-free survival (DFS) and OS were estimated by Kaplan-Meier, survival curves were compared by log rank, and prognostic factors were evaluated with univarate and multivariate Cox regression analysis. Results Of 197 patients, 141 were eligible. Median follow-up time of surviving patients was 111 months. CR was attained by 124 patients (88%), 9 died early (6%), and 48 relapsed in CR (39%). Five-year DFS and OS were 53% and 52%. No statistically significant benefit of pre-induction with/without MTX could be found. MRD was evaluable in 135 samples of 60 patients. MRD was present in 28% of patients after induction course 1 (15/54), 26% after induction course 2 (11/43) and 13% after consolidation (5/38). MRD was most predictive of DFS and OS after consolidation (p ≤ 0.001). In multivariate analysis, DFS was associated with MRD (p = 0.002) and central nervous system (CNS) involvement (p = 0.010); OS was related to MRD (p = 0.016), age >35 years (p = 0.026), LDH level (p = 0.036) and CNS involvement (p = 0.020). Conclusions Outcome of adult ALL patients treated according to the Groningen regimen compares favorably with results in literature, but no statistically significant beneficial effect of the pre-induction course with/without MTX could be demonstrated. MRD was the most important prognostic factor.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Daenen, Dr. S.M.G.J. and Bellido, Dr. M. |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:06 |
| Last Modified: | 25 Jun 2020 11:06 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2566 |
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