Chronic Lymphocytic Leukemia
 

Prognostic features in chronic lymphocytic leukemia


Good prognostic features

1.Low Rai or Binet clinical stage

2.Interstitial or nodular pattern of lymphocyte infiltration in marrow

3.Lymphocyte doubling time >12 months

4.CD 38 negativity

5.Mutated immunoglobulin Vh genes

6.ZAP-70 negativity (low levels)

7.Chromosome 13q14


Poor prognostic features

1.High Rai or Binet stages

2.Diffuse pattern of lymphocyte marrow infiltration

3.Lymphocyte doubling time <12 months

4.CD 38 positivity

5.Unmutated immunoglobulin Vh genes

6.ZAP-70 positivity (high levels)

7.Del 11q23

8.17p-/p 53 abnormalities

9.p 53 dysfunction or increased expression

10.Increased levels of TNF-alpha, beta-2 microglobulin, IL-6, IL-8, IL-10, LDH, VEGFR-2, CD20, and CD52

Survival of patients with chronic lymphocytic leukemia stratified by beta-2 microglobulin levels
























Data from Fayad, L, et al. Blood 2001; 97:256.

CLL and SLL guidelines are contained in the NCCN section of NHL

Modified Rai clinical staging system for chronic lymphocytic leukemia



Low Risk

Stage 0

Lymphocytosis in blood or bone marrow



Intermediate Risk

Stage I

Lymphocytosis + enlarged lymph nodes

Stage II

Lymphocytosis + enlarged liver or spleen with or without lymphadenopathy



High Risk

Stage III

Lymphocytosis + anemia (Hgb <11 g/dL) with or without enlarged liver, spleen, or lymph lnodes

Stage IV

Lymphocytosis + thrombocytopenia (platelet count <100,000/µL) with or without anemia or enlarged liver, spleen, or lymph nodes

CLL/SLL (Practice Guidelines in Oncology from NCCN – v.3.2009)


Supportive Care for Patients with CLL


I.Recurrent Infections (requiring IV antibiotics or hospitalization)

Antibiotic Prophylaxis


· Antimicrobials as appropriate · Evaluate serum IgG, if < 500 mg/dl b begin monthly IVIG 0.3-0.5 g/kg, adjust dose/interval to maintain nadir level > 500-700 mg/dl

· Consider for patients during treatment and thereafter, if tolerated:

Frontline treatment: Herpes virus (acyclovir or equivalent)

Retreatment: Herpes virus (acyclovir or equivalent)

For PCP (bactrim or equivalent)


· Alemtuzumab: CMV monitoring of antigen during treatment every 1-2 wks or valganciclovir during and for 2 mo after


II. Autoimmune Cytopenias


· Auto-immume hemolytic anemia (AIHA) diagnosis with reticulocyte count, haptoglobin, DAT:

AIHA that develops in setting of treatment with fludarabine, stop, treat, and avoid

subsequent fludarabine

· Immune thrombocytopenia purpura (ITP): Evaluate bone marrow for cause of low PLT · Pure red blood cell aplasia (PRCA): Evaluate for parvo B19

· Treatment: Corticosteroids, rituximab, IVIG, cyclosporin A, splenectomy, eltrombopag (ITP)


III. Vaccination


· Annual Influenza vaccinea · Pneumococcal vaccine every 5 yrs

· Avoid all live vaccines, including Zoster


IV. Blood Product Support


· Transfuse according to institutional or published standards

· Irradiate all blood products

Nomogram for time to first treatment. Nomogram used by totaling points identified at top scale for each of four independent variables. Point score for lactate dehydrogenase (LDH) identified based on IGHV mutation status. This summed point score then identified on total point scale to identify 2- and 4-year treatment-free probability (prob) and estimate treatment-free survival. Fluorescent in situ hybridization (FISH) was categorized by Dohner hierarchic categorization. LN, lymph node.

Time to first treatment by fluorescent in situ hybridization (FISH; n = 835). Previously untreated patients with chronic lymphocytic leukemia had bone marrow aspirate samples evaluated for chromosome abnormalities by FISH at initial presentation to MD Anderson Cancer Center. Patients were observed for time to first treatment. Kaplan-Meier estimates of treatment-free survival are shown

Time to first treatment by IGHV mutation status and ZAP-70 expression. Previously untreated patients with chronic lymphocytic leukemia had leukemia cells evaluated for IGHV mutation status and ZAP-70 expression by flow cytometry or immunohistochemistry at initial presentation to MD Anderson Cancer Center. Patients were observed for time to first treatment. Kaplan-Meier estimates of treatment-free survival are shown