Chronic Myelogenous Leukemia

The staging of CML is a little more difficult than most other hematologic cancers. There isn't universal agreement about how to stage.

Accelerated phase has:

11-20% blasts in blood or BM
>20% basophils in blood or bone marrow
Platelets < 100 unrelated to therapy
Platelets > 1000 despite therapy
Development of ACA (additional chromosomal abnormalities)
Increasing metabolic symptoms or splenomegali despite treatment

Blast crisis has:

>20% blasts in blood or BM
Chloromas
Large clusters of blasts in the BM

Prognosis based on the SOKAL score, which is a weighted calculation based on age, blasts in peripheral blood, spleen size and platelet count. The formula reads like this:

e (0.0116({age in years}-43.4)+0.0345({spleen size in cm below coastal margin}-7.51)+0.188(({platelet/ 700x10 9 /l }) 2 -0.563)+0.0877({blast %}-2.1)

but can be calculated here

The Sokal score dates back to 1984 (PROGNOSTIC DISCRIMINATION IN “GOOD RISK”. CHRONIC GRANULOCYTIC LEUKEMIA. J.E. SOKAL, E.B. COX, M. BACCARANI, S. TURA,. G.A. GOMEZ et al, BLOOD 1984). The Hasford score from 1998 is somtimes used and includes number of platelets and eosinophils. A nice review of these scoring systems can be found here.

The scoring systems were devised before TKIs (and the Sokal score before interferon therapy) but continue to hold prognostic validity. There is no newer scoring system.

When discussing prognosis with patients, physicians often quote the IRIS study, as this is the largest and oldest cohort of CML patients treated with any TKI. 553 patients were randomized to what would later be called Gleevec or interferon. Most of the interferon group later got Gleevec, so there are no survival data. There is an 8-year update, which was presented at ASH in 2009. Overall, 92-93% of patients have stayed clear of their disease and the survival curve has flattened out. Only one person succumbed to CML in the 8th year of the study.

This does not mean that it was "smooth sailing" on Gleevec for the whole cohort. In fact, little less than half the patients had to go off study for AEs or disease progression. Some were able to regain their response on a higher dose of Gleevec, and - later - some got second generation TKIs, which induced responses.


Treatment

The big question now is whether someone should get a seond generation TKI up front, and this is already being done in some places. Both Nilotinib (Tasigna) and Dasatinib (Sprycel) have data showing decreased time to cytogenetic and molecular responses. The ENESTnd trail comparing Gleevec to two different doses of Tasigna also showed a trend toward improved survival. The DASISION study is similar for Sprycel.
Links