Question
A 69-year-old woman is assessed after noticing a gradually enlarging, painless swelling in her left axilla over the past several weeks. She otherwise feels well and denies fever, drenching night sweats, unintentional weight loss, or marked fatigue.
Blood tests show:
- Hb: 114 g/L
- Platelets: 155 × 10⁹/L
- WBC: 69 × 10⁹/L
- Neutrophils: 4.8 × 10⁹/L
- Lymphocytes: 63 × 10⁹/L
- Peripheral blood film: numerous fragile lymphocytes with smudge cells
Which finding would be associated with an unfavourable prognosis?
A. Isolated deletion of chromosome 13q
B. Lymphocyte doubling time greater than 2 years
C. Negative CD38 expression
D. Del 17p
E. Age below 65 years
Answer
D. Del 17p
Explanation
This presentation is typical of chronic lymphocytic leukaemia (CLL):
- Older patient
- Painless lymphadenopathy
- Marked absolute lymphocytosis
- Smudge cells on peripheral blood film
- Often no B symptoms at presentation
Why is del 17p important?
Deletion 17p involves loss of the region containing the TP53 tumour-suppressor gene.
TP53 normally helps damaged cells undergo cell-cycle arrest or apoptosis. Loss or dysfunction of TP53 therefore allows abnormal lymphocytes to survive despite DNA damage.
For MRCP purposes:
CLL + del 17p / TP53 abnormality = poor prognosis.
It is particularly important because TP53-abnormal CLL responds poorly to traditional chemoimmunotherapy.
Important CLL prognostic factors
Poor prognostic features include:
- Del 17p / TP53 abnormality
- TP53 mutation
- Older age
- Male sex
- Very high lymphocyte count
- Rapid lymphocyte doubling time
- Increased LDH
- Increased β2-microglobulin
- CD38 positivity
- Increased proportion of prolymphocytes
A particularly useful chromosome comparison is:
Del 13q → relatively favourable prognosis
Del 17p → poor prognosis
Other classic chromosome association
Do not confuse del 17p with the Philadelphia chromosome:
t(9;22) → BCR-ABL1
This is classically associated with CML and is also found in a subgroup of ALL; it is not the characteristic poor-prognostic cytogenetic abnormality being tested in CLL.
Summary for quick exam revision
Chronic lymphocytic leukaemia typically affects older adults and may present incidentally or with painless lymphadenopathy. The blood count characteristically shows a marked absolute lymphocytosis. Peripheral blood films often contain smudge cells, produced because the abnormal lymphocytes are fragile and rupture during slide preparation. Many patients have no constitutional symptoms at diagnosis, although fever, night sweats and weight loss may occur with more advanced disease. Splenomegaly and hepatomegaly can also occur. Prognosis in CLL depends partly on clinical stage, lymphocyte kinetics and molecular abnormalities. Deletion 17p is one of the most important adverse prognostic findings. The deleted region contains TP53, and TP53 mutation or deletion is associated with biologically aggressive disease and poor response to conventional chemoimmunotherapy. Remember the high-yield contrast: del 13q alone generally indicates a favourable prognosis, whereas del 17p indicates a poor prognosis. A rapidly rising lymphocyte count and a short lymphocyte-doubling time are also adverse features. Raised LDH, raised β2-microglobulin and CD38 positivity are associated with less favourable disease. Older age and male sex are traditionally associated with poorer outcomes. A low β2-microglobulin level is therefore not an adverse feature. The Philadelphia chromosome, t(9;22) producing BCR-ABL1, is principally associated with CML and some cases of ALL rather than being the classic prognostic abnormality in CLL. For an MRCP question asking for the classic poor-prognosis genetic abnormality in CLL, think del 17p / TP53 abnormality.