Prior Treatment More Important than ZAP-70, CD38, Mutation Status in Richter's

[Guest guest]

[Males more likely to develop a second hematologic cancer as well.]

[2777] Prior Treatment Relates More Strongly to Richters

Transformation Than ZAP-70, CD38, IgVH Gene Mutation Status, and

Cytogenetic Abnormalities: Findings of an Observational Cohort Study

of 962 Patients with CLL. Session Type: Poster Session, Board #6-III

Kami Maddocks-Christianson, Clive S. Zent, Slager,

Schwager, Reinalda, G. Call, Deborah Bowen,

Hoyer, Diane F. Jelinek, Neil E. Kay, Tait D. Shanafelt Mayo Clinic

Cancer Center, Mayo Clinic, Rochester, MN, USA

BACKGROUND: Studies have suggested that patients with CLL are at a

significantly increased risk of developing other lymphoid

malignancies. Whether the risk of developing a 2nd

lymphoproliferative disorder (LPD) is more strongly related to

characteristics of the leukemia cell or to other factors such as

prior chemotherapy is unknown. This distinction is important given

increasing momentum to pursue early treatment of CLL patients based

on recently identified prognostic markers, e.g. ZAP-70, IgVH

mutation status. We used the Mayo Clinic CLL Database (DB) to

conduct an observational cohort study to evaluate the relationship

between clinical, biologic, and treatment characteristics and the

risk of secondary LPD.

METHODS: The Mayo Clinic CLL DB was established in 1999 and included

962 patients at the time of the present analysis. Clinical

information regarding date of diagnosis, prognostic parameters,

treatment history, disease-related complications, and co-morbidities

was abstracted from clinical records on all patients at the time of

study enrollment and maintained on an ongoing basis. For the present

study, cases of secondary LPD were identified by chart review and

cross referencing patient clinic numbers from the CLL DB with the

Mayo Clinic Lymphoma and Leukemia/Myelodysplasia databases.

Additionally, all clinic numbers were cross-referenced with an

electronic hematopathology database that has recorded results of all

bone marrow and lymph node biopsies of all Mayo Clinic patients

since 1992.

RESULTS: A second LPD was identified in 26 (2.7%) of the 962 CLL

patients during a median follow-up of 7.12 years (range 0.1-21.0).

The median time from diagnosis to development of secondary LPD was

4.4 years (range 0-19 years). Diffuse large B-cell lymphoma was the

most common subtype of secondary LPD (12 of 26 cases). Gender was

associated with increased risk of developing 2nd hematologic cancer

where 1% of women compared to 3.4% of men (p=0.051) developed a 2nd

LPD.

Treatment history was also related to development of a 2nd LPD. 2nd

LPD developed among 4% of previously treated CLL patients compared

to 2% of untreated patients (p=0.08). Among the 362 patients who

were treated for CLL prior to developing a second LPD, the median

time to first treatment was shorter for those who developed a 2nd

LPD (2.43 years vs. 6.22 years; p<0.001). No statistically

significant association was observed between other clinical or

biologic leukemia cell characteristics and development of 2nd LPD

including IgVH gene mutation status, ZAP-70 status, CD38 status,

cytogenetic abnormalities by FISH, B2M, stage at diagnosis, or ALC

at diagnosis.

CONCLUSIONS: In this observational cohort study, prior treatment

demonstrated a stronger correlation with the risk of developing a

2nd LPD than did leukemia cell characteristics including IgVH gene

mutation status, FISH, ZAP-70, B2M, and CD38. This finding suggests

Richters transformation may relate more to therapy than

characteristics of the leukemia cell itself. Until the results of

clinical trials evaluating the role of early treatment based on

prognostic parameters are available, this result underscores the

importance of delaying administration of chemotherapy until patients

meet established criteria for treatment.