Difference between CML & CLL

[Guest guest]

Someone asked the diffence between ALL & CML. I found this at a LLS website on

their message board. Beth, by the way is going to be treated with Sprycel if

they can get permission. Someone in her condition and they have to wait for

permission, from whom, the national insurance, why can't the doctors make that

decision? I don't know, I am not in England, but she said she is getting

excellent care and has 3 doctors looking after her. It appears the myeloid is

fighting with the lymphoid, or is this correct and CML and can look like

either CLL or AML blasts? Either way, the treatment is the same - BMT stated

below? This is confusing. See post below for an explanation, it is very

technical.

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CML is a disease of the white blood cells, of which there are two types, myeloid

(neutrophils, etc) and lymphoid (T-Cells, etc). CML starts very high in the

blood stem cell hierarchy, so it affects both myeloid and lymphoid lines of

white blood cells. It also affects the red blood cells and platelets, but since

neither have a nucleus, they are not truly leukemic cells. So the WBCs are the

leukemic cells, predominantly myeloid, but also lymphoid under " normal "

circumstances; and so CML is mainly a myeloid WBC disease, even though lymphoid

WBCs are also leukemic to a lesser degree.

When CML accelerates and morphs into Blast Phase, it undergoes additional

genetic changes that give it survival advantages over TKI drugs, and these

changes normally occur in the myeloid line of WBCs, but can sometimes occur in

the lymphoid line of WBCs. So, is CML Blast Phase just AML? NO!!!!!!. It can

be either myeloid (AML is myeloid) or lymphoid (ALL is lymphoid).

CML is still CML, but looks like either AML or ALL in Blast Phase, depending on

which WBC line gets out of control first. So it is probably more that the CML

can look like AML or ALL in Blast Phase, rather than being AML or ALL. But that

is a technical point, since the treatment is the same (BMT). So the

" progression " to AML or ALL is open to debate among researchers, but there are

reasons why it is less of a " progression " and more of a " looks & acts like " . In

a nutshell, the issue is mainly secondary translocations. So it is truly " CML

Blast Phase (or Crisis) " .

2) What is the difference between CML and PH+ ALL? Is it really possible to

have CML and progress to ALL or is it a case of the patient had PH+ ALL all

along, but they were diagnosed with CML?

Since CML has both leukemic myeloid and leukemic lymphoid WBCs, but is

predominately leukemic myeloid, the diagnosis can rarely be more difficult. ALL

is a disease of the lymphoid WBCs, but most cases of ALL do not have the

Philadelphia Chromosome translocation, so that rules out most cases. So we are

only discussing about 20% of ALL cases where there is also the Philadelphia

Chromosome.

But proper diagnosis is still possible by a skilled Onc (but they are rare --

hence the problem). So the person can rarely (emphasize rarely) be misdiagnosed

as CML when they have Ph+ ALL. But a question is whether Ph+ ALL isn't really

just CML where the lymphoid line has already gained an advantage, but that is

not clear. Ph+ ALL is normally identified by a large percentage of the e1a2

version of the Philadelphia Chromosome. But be careful -- most cases of low

level e1a2 are NOT Ph+ ALL (Tedsey -- this is NOT your " AH-HA Moment " ). But let

me hasten to say that the treatment for CML and Ph+ ALL are the same -- TKI

drugs. But it would be better to go straight to Sprycel if Ph+ ALL is the

diagnosis. So if someone has a doubt about it, talk to your Onc about Sprycel.

3) In cases where PH+ ALL is misdiagnosed as CML, what are the underlying

reasons for the misdiagnosis? Is it a mistake by the doctor, or is it that PH+

ALL cannot be trully detected early on and it just looks like CML?

The e1a2 is an indicator, but the key lies in properly testing (flow cytometry)

to take a look at the lineages of the WBCs. In Ph+ ALL, the lymphoid lineage

will predominate over the myeloid. Also, the simple WBC can show basic levels

of myeloid vs lymphoid WBCs to provide clues. In CML, the myeloid WBC line

should predominate.

4) Is there any way for someone who has been diagnosed with " typical " CML to

determine if they are really PH+ ALL? Are there things to look for in BMB or

PCR?

If the PCR shows e1a2 at a relatively high level, then further investigation is

required since Ph+ ALL is more likely. If CBC- WBC differentials (percentages)

shows relatively high levels of lymphoid line at diagnosis (careful -- the

percentage levels can fluctuate after starting TKI drugs). BMB might show

secondary chromosome mutations. Flow cytometry (not often done at diagnosis)

provides more details and is the best indicator.

Let me emphasize that we are discussing this as an academic exercise (at least I

am). This is extremely rare. CML TKI drugs are the treatment for Ph+ ALL just

like CML, but Sprycel is preferred.

But if something changes for the Ph+ ALL patient, they should have a backup plan

in place for BMT (at least HLA testing of siblings) because the TKI drugs are

not as effective against Ph+ ALL as they are for CML. But the key is try TKI

drug therapy first. So this issue should NOT be a source of concern for 99.9%

of those with CML.

http://community.lls.org/message/77074

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FYI,

Lottie Duthu