CLL / SLL

SLL – morphology and immuno of CLL but is non-leukaemic

Associated with AIHA, pure red blood cell aplasia and hypogammaglobulinaemia

Small M-component may be found

Clinical features

§   40% Asymptomatic at diagnosis

§   Lymphadenopathy

§   Systemic symptoms

§   Complications

1.      Immunosuppression

§        Cell mediated immunity – imbalance of CD4/8

§        Viral infection / reactivation

2.      Autoimmune disease

§        AIHA

§        ITP

§        Neutropenia / pure red cell aplasia less common

3.      Large cell transformation / Richter’s syndrome

§        Systemic symptoms

§        Unexpalined unilateral lymph node enlargement

§        Often associated with monoclonal protein in serum or urine

§        May be associated with EBV

Diagnosis

Lymph node histology

§        Effacement of architecture

§        Pseudofollicular pattern

§        Small lymphocytes

§        Mitotic activity low

Blood/ Bone marrow

§        Increased prolymphocytes associated with more aggressive clinical course, p53 abnormalities, trisomy 12

§        BCLL/PL = variant with 10-55% prolymphocytes

§        BM involvement may be nodular, interstitial, diffuse or all 3

§        Paratrabecular aggregates NOT typical

Immuno

CLL score

CD23 and cyclin D1 are useful to distinguish between CLL and MCL

Cytogenetics

§        Poor prognosis

§        11q23 (20%)

§        Trisomy 12 (20%)

§        17p21 (P53) (10%)

§        Good prognosis

§        Del(13q) (40%)

ZAP70 / CD38

§        50% Pre-greminal centre phenotype (ZAP70+/CD38+) – worse prognosis

§        50% Post-germinal centre phenotype (ZAP70-/CD38-) – better prognosis

§        ZAP 70 surrogate marker for unmutated CLL cells (ie for cells that haven’t undergone somatic hypermutation)

§        Tyrosine kinase

§        Assoc with worse prognosis

§        Some CLL cells undergo somatic hypermutation and are more mature than previously thought

§        Can do DNA sequencing IgVH mutations but not practical, CD38 is also a surrogate marker

Other prognostic markers

§        Age / male sex

§        Lymphocyte count

§        Doubling of count in 6-12 months

§        Response to treatment

§        Serum markers

§        B2-microglobulin / albumin 

§        LDH

§        Soluble CD23

§        Thymidin kinase

§        Stage

Indications for Treatment

• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia

• Massive (i.e., at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.

• Massive nodes (i.e., at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.

• Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of
  <6 months. In patients with initial blood lymphocyte counts
  <30 9 109/l, LDT should not be used as a single parameter to define a treatment indication.

• Autoimmune anaemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy.

• Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs

• Unintentional weight loss of 10% or more within the previous 6 months;

• Significant fatigue (i.e., Eastern Cooperative Oncology Group Performance Score 2 or worse; inability to work or perform usual activities);

• Fever higher than 380°C for two or more weeks without other evidence of infection; or

• Night sweats for more than 1 month without evidence of infection.

• Pre treatment check Hep B/C and TP53 status

Treatment

• FCR 1st line in fit TP53 negative patients

• Stable after 2 cycles = high risk disease

• If relapse >2 yrs use FCR again

• Unfit TP53 negative – 1st line = R bendamustine or R chlorambucil

• High risk disease – Campath/ Methylprednisolone

• Consider clinical trials

• Consider Allogeneic transplant in all eligible patients

• SLL managed same as CLL

• No role for autograft – if poor risk disease consider allograft

• Immune cytopenias treated as normally, consider treating underlying CLL if immune suppression treatment fails.

• Immunoglobulin prophylaxis if low IgG with major or recurrent minor bacterial infection despite antibacterial prophylaxis.

• Give strep pneumonia and Hib vaccine, annual flu vaccine. Avoid live vaccines.