Understanding your results

This section outlines your treatment milestones and how your treatment response will be monitored. It also describes the different levels of treatment response that you and your healthcare team will monitor. One of the main sources for this article is La Leucemia Mieloide Cronica – authored by Elisabetta Abruzzese, Michele Baccarani, Felice Bombaci, Massimo Breccia, Fausto Castagnetti, Gabriele Gugliotta, Luigiana Luciano, Gianantonio Rosti, Fabio Stagno e Mario Tiribelli.

Here we answer some FAQs:

What are haematological, cytogenetic and molecular responses?

A haematological response is the first response doctors look for, using a blood test.1 When you are first diagnosed with CML, your white blood cell count is high.1 A haematological response means your full blood count has gone back to normal. Your spleen will also have returned to its normal size if it was enlarged. This is the first sign that the treatment is working.

A cytogenetic response refers to the proportion of cells that have the Philadelphia chromosome in your bone marrow.1 This is measured by testing the level of Philadelphia chromosome positive metaphases.2 Metaphase is a phase when cells divide where duplicated chromosomes align in the middle of the cell.2 After this the cell divides into two giving an equal number of chromosomes in each cell.2 As the treatment continues to work, the number of Philadelphia chromosome-positive metaphases in your bone marrow will decline.

A molecular response refers to the level of BCR-ABL1 protein transcripts in your blood, after you have reached a complete cytogenetic response.2 The presence of BCR-ABL1 transcripts means that there are a small number of cells with the Ph+ chromosome left in your body.2 These can only be detected by PCR.2

The list below shows the different levels of response and how they are defined.1,2

Level of haematological response definition

Complete haematological response (CHR):

  • White blood cell count <10x109/L
  • No immature granulocytes
  • Basophils less than 5%
  • Platelet count less than 450x109/L
  • Spleen can’t be felt by physical examination
Level of cytogenetic response (CyR) definition

Complete CyR

  • Philadelphia chromosome isn’t detected or less than 1% BCR–ABL transcripts detectable by analysing the chromosomes metaphases

Partial CyR

  • 1%–35% positive Philadelphia chromosome metaphases

Minor CyR

  • 36%–65% positive Philadelphia chromosome metaphases

Minimal CyR

  • 66%–95% positive Philadelphia chromosome metaphases

No CyR

  • More than 95% positive Philadelphia chromosome metaphases
Level of molecular response (MR) definition

Major MR (MMR)

  • BCR–ABL transcript level at 0.1% or less on the International Scale using PCR

Deep MR: MR4

  • BCR–ABL transcript level 0.01% or less on the International Scale using PCR

Deep MR: MR4,5

  • BCR–ABL transcript level 0.0032% or less on the International Scale using PCR

What are the treatment milestones for TKIs?

There are three main objectives of treatment:1

  • To prevent progression of the CML to accelerated or blast crisis and ensure normal life expectancy3
  • To eliminate or reduce CML cells to such small levels that TKI treatment may be stopped (called treatment-free remission, learn more about what is required here)3
  • To ensure good quality of life3

The list below describes the treatment milestones: failure, warning and optimal response.1 Optimal response means treatment should continue, warning means your response will be monitored more closely, and failure means your treatment needs to change.1

Within 3 months

Optimal response

  • 35% or less white blood cells have Ph+
  • There are less than 10% BCR-ABL transcripts

Warning

  • Levels of blood cells are normal (CHR has been reached)
  • 36% to 95% of white blood cells have Ph+
  • There are over 10% BCR-ABL transcripts

Failure

  • Levels of blood cells are not normal (CHR hasn’t been reached)
  • More than 95% of white blood cells have the Philadelphia chromosome (Ph+)
Within 6 months 

Optimal response

  • 0% white blood cells have Ph+
  • There are less than 1% BCR-ABL transcripts

Warning

  • 1% to 65% of white blood cells have Ph+
  • There are between 1% and 10% BCR-ABL transcripts

Failure

  • More than 35% of white blood cells has Ph+
  • There are more than 10% BCR-ABL transcripts
Within 12 months

Optimal response

  • There are less than 0.1% BCR-ABL transcripts (MMR)

Warning

  • There are no detectable white blood cells with Ph+
  • There are between 0.1% and 1% BCR-ABL transcripts

Failure

  • 1% or more of white blood cells have Ph+
  • There are more than 1% BCR-ABL transcripts
Long-term (over 18 months)

Optimal response

  • There are less than 0.01% BCR-ABL transcripts (Deep MR)

Warning

  • There are between 0.1% and 1% BCR-ABL transcripts

Failure

  • n/a
At anytime

Optimal response

  • n/a

Warning

  • n/a

Failure

  • Relapse or loss of MMR

What tests are used to monitor CML? 

Blood counts

After diagnosis, blood tests to check the numbers of each type of blood cell, called blood counts, will be done every 15 days (or more often) until a complete haematological response (CHR) has been reached.1 Once CHR has been reached, blood counts are done every 3 months.1

Bone marrow tests

Bone marrow tests to monitor the level of Philadelphia chromosome metaphases should be done at 3 and 6 months after diagnosis, and then every 6 months until a complete cytogenetic response (CCyR) has been reached.1 This is done by doing bone marrow biopsies and/or aspirations. These are procedures where a small sample of bone and/or bone marrow are removed, usually from the hip bone.2 This is normally done using a special wide needle and under local anaesthetic.2 

Polymerase chain reaction (PCR)

The PCR test used for treatment monitoring is called “quantitative reverse transcriptase polymerase chain reaction” (qRT-PCR, or PCR in short).1 This test is used to monitor the level of BCR–ABL transcripts in the blood. It is recommended that PCR is done every 3 months.1 However, for people who are in treatment free remission (TFR) a PCR should be done every 4 to 6 weeks for the first year after treatment has been stopped.1

Interphase fluorescent in-situ hybridisation (iFISH)

iFISH is a technique used to identify changes in genes and chromosomes in the blood.2 iFISH is only used if Philadelphia chromosome metaphases in the bone marrow cannot be analysed, or if they are found to be normal and molecular response cannot be assessed.1

  1. Hochhaus, A., Saussele, S., Rosti, G., Mahon, F.-X., Janssen, J. J. W. M., Hjorth-Hansen, H. et al on behalf of the ESMO Guidelines Committee. (2017). Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 28(suppl_4), iv41–iv51. https://doi.org/10.1093/annonc/mdx219.
  2. ESMO patient guide [CML: a guide for patients - Information based on ESMO Clinical Practice Guidelines - v.2013.1]
  3. LMConline. La terapia della LMC. Accessed and translated May 2018.