Treatment and survival of patients with Non-Hodgkin Lymphoma: population based studies in the Netherlands

Djamila Elisabeth Issa

    Research output: PhD ThesisPhD-Thesis - Research and graduation internal

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    Abstract

    The main aim of this thesis was to deepen our understanding of incidence, treatment, relative survival, mortality, and quality of life of patients with non-Hodgkin lymphoma (NHL) in a population-based setting. In chapter 1, a general introduction on NHL and the three different registries employed for the studies described in this thesis is given. In chapter 2, we studied incidence, treatment, relative survival, and mortality of patients with NHL. The incidence of indolent B-cell and T- and NK-cell neoplasms increased over time, whereas the incidence of aggressive B-cell neoplasms remained stable. The 5-year RS rates rose for indolent and aggressive mature B-cell neoplasms. The 5-year RS remained stable over time for T- and NK-cell neoplasms. In chapter 3, we focused on aggressive B-cell lymphoma, describing incidence, first-line treatment and survival. Incidence remained stable for DLBCL, while for MCL and BL the incidence increased for men and remained stable for women. Between 1989-1993 and 1994-1998, 5-year RS did not improve for patients with aggressive B-cell lymphoma. However, an improvement was observed from 1999-2004 to 2005-2010. This improvement was most prominent in patients aged <65 years. The main contributors to the improvement in survival in our study appear to be rituximab therapy, autologous stem cell transplantation, and use of more intensive chemotherapy. In Chapter 4, we focused on first-line treatment in patients with DLBCL. We demonstrated that R-CHOP14 and R-CHOP21 were equally effective. Besides, we demonstrated that R-CHOP14 were associated with significantly more polyneuropathy compared to R-CHOP21. Secondly, we demonstrated that 6x and 8x R-CHOP were as well equally effective modalities. Next, we compared 6x R-CHOP21 (± two additional cycles of rituximab; ±2R) to 6x R-CHOP14 (±2R), 8x R-CHOP14 and 8x R-CHOP21 among patients aged 18-64 years. OS was similar across the four regimens. Therefore, 6xR-CHOP21 could be considered as first-line regimen. In chapter 5, we analysed the contribution of primary therapy to RS in very elderly DLBCL patients in response to an analysis of Giri et al. We showed significant improvement in RS was confined to patients age 80-84 years who were diagnosed in the period from 2008-2015. The multivariable analysis demonstrated that the application of rituximab accounted for the improvement. Despite recent improvements, the overall outcome of patients age ≥80 years remains unsatisfactory. In chapter 6, we presented results of primary therapy and RS in patients with BL. Our data are presented in response to an analysis of Evens et al. To complement and extend their observations, we assessed the results of 990 adults. The RS of BL patients aged 18-75 years improved over time. We confirmed benefit of rituximab added to chemotherapy. Outcome of patients aged >75 years remained comparatively poor over the past three decades, even in the rituximab era. In chapter 7, we analyzed outcome of 161 patients with transformed follicular lymphoma. In conclusion, long term survival can be reached in young patients with TFL. Although there was no difference in outcome with ASCT in our population based registry, our data suggest that up-front ASCT might benefit patients previously treated for FL. In chapter 8, we described 148 patients with FL. Mean HRQoL scores were worse for FL patients treated with immunochemotherapy compared to a normative population. Patients treated with immunochemotherapy reported clinically relevant higher mean fatigue scores than those who underwent radiotherapy. In chapter 9, we described 256 patients with DLBCL. Compared to patients treated with (R-) CHOP21, those who underwent (R-) CHOP14 more often reported tingling in hands and feet and fatigue and reported a lower global health status/HRQoL. Mean HRQoL was statistically and clinically relevantly lower among DLBCL patients compared to a normative population.
    Original languageEnglish
    QualificationDr.
    Awarding Institution
    • Vrije Universiteit Amsterdam
    Supervisors/Advisors
    • Zweegman, Sonja, Supervisor, -
    • Chamuleau, Martine Elisabeth Dorothé, Co-supervisor, -
    • Dinmohamed, Avinash, Co-supervisor, -
    Award date11 Feb 2022
    Place of PublicationEnschede
    Publisher
    Print ISBNs9789464194012
    Publication statusPublished - 11 Feb 2022

    Keywords

    • Incidence
    • Survival
    • Non-Hodgkin lymphoma
    • Treatment
    • Quality of Life
    • Population based

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