L&M conf: Prognostic factors versus Response Predictors in CLL

[Guest guest]

Greetings,

Notably, in CLL there are many cytogenetic factors that appear to predict

survival, clinical behavior, and response to specific therapies.

Below are my notes on prognostic factors in CLL.

Also posted to http://www.lymphomation.org/type-CLL.htm#prognosis

~ Karl

=Prognostic factors versus Response Predictors:

" Oncology does not need more prognostic factors, it needs

predictive factors that treatment-regimen specific. Prognostic factors

are unlikely to be used unless they are therapeutically relevant ... "

~ Simon, DSc

Prognostic factors are features of the disease that are associated with the

clinical behavior, response to treatment and survival.

=Prognostic factors:

The many interrelated factors that influence survival have not been defined

definitively at this time.

* Mutated (more favorable) versus non-mutated (less favorable)

(Immunoglobulin variable region heavy chain gene (IgVH) mutation). *

* ZAP-70 (less favorable)

* CD38 immunophenotype (has cd38 protein on cell surface).

* Stage (see Rai staging system

and Binet classification above)

* High Lymphocyte doubling time (unfavorable)

* High Beta-2-microglobulin (unfavorable)

* Telomere and mutation status:

Mutation status is correlated with Telomere

lengths, which can vary based on the cellular

derivation of B-cells (see prior post)

=Response predictors:

Questionable predictor:

CD38+, Zap 70+, Unmutated

(either alone or combined)

Stronger predictors:

* High Beta-2-microglobulin -

poor response to chemo-immunotherapy

* CLLU1 gene -

poor response to chemo-immunotherapy

* Patients achieving response have longer survival

Minimal Residual Disease (MRD) after treatment correlates

with better outcome (Progression Free Survival and Overall Survival)

* MRD-positivity - particularly increasing MRD levels, anticipates

clinical relapse (exception: after allotransplantation)

Weak predictors:

* Clinical stage, Bone marrow infiltration,

* Doubling time, Morphology (appearance)

Strong predictors:

* Genetics:

17p- resistance to Fludarabine, alkylators, Rituxan

11q- lower response rate to fudarabine (vs. FC)

early relapse from autologous Stem Cell Transplant

chromosomal translocations lower response to

CDA (Does CDA mean cladribine?)

p53 mutations and deletions

Alemtuzumab is an effective therapy for chronic

lymphocytic leukemia with See bloodjournal.hematologyli pdf

* Response to therapy: Patients achieving response have longer survival

Minimal Residual Disease (MRD) after treatment correlates

with better outcome (Progression Free Survival and Overall Survival)

MRD-positivity - particularly increasing MRD levels, anticipates

clinical relapse (exception: after allotransplantation)

Question: Does treatment timing correlate with MRD negativity?

Source: Dr. Emillio Montserrat, MD presentation L & M conference 2007