cmlphase

                           CML DISEASE PHASES

CML can be biphasic or triphasic. 90% of patients will be diagnosed in the chronic phase
(CP). If left untreated, the disease progresses over time to the accelerated phase (AP) and the
terminal stage, blast phase.(BP) AP and BP can be hard to treat so the goal of today’s CML
drug treatment is to arrest the disease in the chronic phase and prolong it over time.

The table below gives the criteria for accelerated phase, these differ from sources- MDACC or
MD Anderson Cancer Center, International Bone Marrow Transplant Registry and World
Health Organization. Cytogenetic clonal evolution (CE) is when there are abnormalities in
chromosomes other than chromosomes 9 and 22, like other translocations, additions and
deletions of chromosomes. In recent times, it has been shown from studies, that with Gleevec
therapy, patients diagnosed with CE and with no other accelerated phase features can be
classified as low-risk chronic phase. Fibrosis is when the marrow forms scar tissue.
Chloromas are tumors outside the marrow, in organs and on the skin, the spine, etc.

                   Classification of accelerated phase according to 3 institutions



Most doctors and institutions classify blast phase as having more than 30% blasts in the
blood or marrow or extramedullary blast crisis.(when blasts appear outside the marrow in
organs and tissues)

On therapy, if chromosomal abnormalities appear, the WBC goes out of control, there is a
sudden fall in platelet counts accompanied by fever, night sweats, weight loss, tests must be
done to see if the disease is transforming. Blast crisis can be of lymphoid or myeloid,
depending on the type of blast cells. The lymphoid blast crisis can mimic acute
lymphoblastic leukemia (ALL) and myeloid blast crisis can mimic acute myeloid leukemia
(AML).

Gleevec has shown excellent results in patients diagnosed in chronic phase and prevented
93% of patients from progressing to advanced phase in a 5 year follow-up by controlling the
disease. Unfortunately, 70% of AP patients have relapsed on Gleevec and 93% of BP
patients have relapsed on Gleevec.

The new kinase inhibitors, Sprycel and Tasigna, have also shown some relapses in advanced
phase disease. Stem cell transplant still remains an option to treat accelerated and blast
phase CML with 40-60% of AP patients and 10-20% of BP patients surviving transplant and
having long-term disease-free survival.

	MDACC	IBMTR	WHO
Blasts	>15%	>10%	10-19%
Blasts + Promyelocytes	>30%	>20%	NA
Basophils	>20%	>20%	>20%
Platelets (10 X e9/L)	<100	Unresponsive increase or persistent decrease	<100 or >1000 unresponsive to treatment
Clonal evolution	Present	Present	CE not at diagnosis
White blood cell count	NA	Difficult to control or doubling in <5days	NA
Anemia	NA	Unresponsive	NA
Enlarged spleen	NA	Increasing in size	NA
Other	NA	Chloromas, fibrosis	fibrosis