Entwicklung eines neuen prognostischen Index für Patienten mit fortgeschrittenem Mantelzell-Lymphom

Background: Mantle cell lymphoma (MCL) shows a particularly bad
prognosis with a median survival of less than 5 years. There is no
generally established prognostic classification system for patients
with MCL as the International Prognostic Index (IPI) and the
Follicular Lymphoma International Prognostic Index (FLIPI) have
been developed based on data of patients with diffuse large B-cell
and follicular lymphoma, respectively. The data of 455 patients
with advanced stage MCL treated within three randomized trials of
German Low-Grade Lymphoma Study Group (GLSG) and European MCL
Network were used to clarify the prognostic relevance of IPI, FLIPI
and potential prognostic factors and, if needed, to develop a new
prognostic index. Methods: The outcome parameter was overall
survival, the time from trial registration to death from any cause.
Potential prognostic factors were the clinical parameters
documented after primary diagnosis before start of treatment. The
prognostic relevance of IPI and FLIPI was evaluated with
Kaplan-Meier estimates and the log rank test. Candidate prognostic
factors were analyzed using univariate Cox regression. In multiple
Cox regression, independent prognostic factors were identified with
backward elimination and the prognostic score was determined.
Prognostic groups were defined with optimal cutpoints for the
prognostic score maximizing the log rank statistic. Internal
validation was performed using the bootstrap method. Results:
According to the IPI more than two thirds of patients were
classified into the low intermediate or high intermediate risk
groups whose survival curves were not clearly separated. According
to the FLIPI, 6% of patients were classified into the low risk
group, survival curves of low risk and intermediate risk patients
were not separated, and the high risk group of almost two thirds of
patients showed a relatively good survival. Of the candidate
prognostic factors, age, ECOG performance status, B-symptoms,
spleen involvement, tumor size, serum LDH activity, leukocyte,
lymphocyte, granulocyte and monocyte count, hemoglobin, and
beta2-microglobulin showed univariate prognostic relevance. In
contrast, sex, Ann Arbor stage III vs. IV, bone marrow involvement,
number of extranodal sites, number of involved nodal areas,
platelet count, and albumin showed no prognostic relevance.
Multiple Cox regression identified age, performance status, LDH and
leukocyte count as independent prognostic factors. Using these four
parameters, a new prognostic index, the mantle cell lymphoma
international prognostic index (MIPI) defined three prognostic
groups with significantly different overall survival. Bootstrap
validation confirmed the separation of the prognostic groups and
indicated superiority over IPI and FLIPI. Conclusions: In this work
a new prognostic index for patients with advanced stage MCL was
defined based on four easily available clinical prognostic factors.
The modest prognostic relevance of IPI and FLIPI underlines the
inappropriateness of transferring results from one lymphoma entity
to another. The results of this work may be applied in clinical
research for stratified randomization, risk-adjusted analyses, and
as a reference to establish new biologic or molecular prognostic
factors. Furthermore, the new prognostic index may facilitate
risk-adapted treatment strategies to improve the prognosis of this
severe disease.