ETD

Digital archive of theses discussed at the University of Pisa

 

Thesis etd-10222023-190043


Thesis type
Tesi di specializzazione (4 anni)
Author
MAVILIA, FABRIZIO
URN
etd-10222023-190043
Thesis title
Investigating clinical heterogeneity and its implications on disease outcome in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
Department
MEDICINA CLINICA E SPERIMENTALE
Course of study
EMATOLOGIA
Supervisors
relatore Prof.ssa Galimberti, Sara
Keywords
  • SLL
  • CLL
  • chronic lymphocytic leukemia
  • small lymphocytic lymphoma
Graduation session start date
06/11/2023
Availability
Withheld
Release date
06/11/2093
Summary
Chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) are regarded as a single diagnostic entity characterised by the accumulation of clonal mature CD5+ B lymphocytes in the blood, bone marrow, and lymphoid tissues. The hematologic community has debated the significance of the clinical presentation of CLL. However, the answer in the existing literature remains inadequate.
In this study, a retrospective observational analysis was conducted on 401 patients well characterized in terms of demographic information, genetic data, manifestations of the disease at the time of diagnosis, the history of treatment, and the latest follow-up status (for untreated patients) or at the time of staging for those who required first-line treatment. This study aims to investigate the clinical significance of the phenotypic heterogeneity of CLL/SLL and to identify potential associations between various clinical manifestations and the clinical fate of both treated and untreated patients.
In accordance with the iwCLL guidelines, we identified two categories of patients based on the primary treatment criterion, comparing patients treated for bulky lymphadenopathy (approximately 25% of all patients treated) with patients treated for hyporegenerative cytopenia (approximately 50% of all patients treated). The analyses revealed significant differences in the majority of clinical characteristics of these patients, including lymphocytosis, haemoglobin, platelet count, and splenic and lymph node dimensions, both at the time of the first therapy and at diagnosis. In the absence of significant biases associated with the prognostic factors IGHV, FISH, and TP53/del(17p), a significant difference was found in the median time to first treatment (21 months for lymphadenopathy versus 66.7 months for cytopenia, p value < 0.01). For patients treated in the first line, the comparison between the median time to next treatment was also significant, and the sub-analyses guided by the therapies performed (post-2016, only target therapies) showed interesting findings.
In conclusion, the work focuses to the clinical presentation as a critical factor in determining the clinical fate and prognosis of CLL patients. This aspect merits more in-depth molecular and genetic analyses in order to completely comprehend the biological bases of the different aggressiveness of these two forms of the disease, which may in the future necessitate different clinical management and treatment strategies.
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