CML response criteria

2013 European LeukemiaNet Recommendations for Management of Chronic Myeloid Leukemia

Response Criteria

ResponseCriteria
Complete Hemat­ologic Response (CHR)Platelets < 450 x109/L, AND
White cells < 10 x109/L, AND
No circulating immature myeloid cells, AND
< 5% basophils on differential, AND
No palpable splenomegaly
Partial Cyto­genetic Response (PCyR)1 - 35% Ph+ cells*
Complete Cyto­genetic Response (CCyR)No Ph+ cells*; fewer than 1 out of 200 nuclei BCR-ABL1–positive by FISH
Major Mol­ecular Response (MMR)BCR-ABLIS ≤ 0.10%
MR4.0BCR-ABLIS < 0.01%
MR4.5BCR-ABLIS < 0.0032%
Mol­ecular­ly un­detect­able leukemiaBCR-ABL tran­scripts non-quant­ifiable and non-detect­able
* At least 20 metaphases analysed on conventional cytogenetics of bone marrow aspirate

Response Expectations for FIRST-LINE therapy (or second-line after intolerance)

Time (m)Optimal responseTreat­ment failure
3BCR-ABLIS ≤ 10% and/or PCyRNo CHR or Ph+ cells > 95% by karyotyping
6BCR-ABLIS < 1% and/or CCyRBCR-ABLIS > 10% or Ph+ cells > 35% by karyotyping
12BCR-ABLIS ≤ 0.1% (MMR)BCR-ABLIS > 1% or CCyR not achieved
At any timeBCR-ABLIS ≤ 0.1% (MMR)Loss of CHR, loss of CCyR, confirmed loss of MMR*, BCR-ABL1 mutation, additional cytogenetic abnormality in Ph+ cells
* Confirmed loss of MMR requires two consecutive results showing BCR-ABL1 > 0.1%, of which one is ≥ 1%

Response Expectations for SECOND-LINE therapy

Time (m)Optimal responseTreat­ment failure
3BCR-ABLIS ≤ 10% and/or Ph+ cells < 65% by karyotyping No CHR or Ph+ cells > 95% by karyotyping or new mutations
6BCR-ABLIS ≤ 10% and/or PCyRBCR-ABLIS > 10% or Ph+ cells > 65% by karyotyping or new mutations
12BCR-ABLIS < 1% and/or CCyRBCR-ABLIS > 10% or PCyR not achieved
At any timeMMRLoss of CHR, loss of CCyR, confirmed loss of MMR*, BCR-ABL1 mutation, additional cytogenetic abnormality in Ph+ cells
* Confirmed loss of MMR requires two consecutive results showing BCR-ABL1 > 0.1%, of which one is ≥ 1%

These updated chronic myeloid leukemia (CML) response assessment guidelines, for chronic phase patients treated with tyrosine kinase inhibitors (TKIs), were produced by the European Leukemia Network (LeukemiaNet), and published in 2013.1

The panel recommended that treatment be continued in patients with optimal responses, and changed in those with treatment failure. Results fall between optimal response and treatment failure are considered to constitute ‘warning’ results, and close monitoring is suggested. The guidelines also make recommendations for specific TKIs, and for treatment of accelerated and blast phase CML.

A PDF pocket card summarising European LeukemiaNet recommendations is available at this link.

BCR-ABL fusion gene juxtaposing BCR (breakpoint cluster region) and ABL1 (Abelson) genes
CCyR complete cytogenetic response
CHR complete hematologic response
CML chronic myeloid leukemia
IS international standard
MMR major molecular response
MR molecular response
PCyR partial cytogenetic response
TKI tyrosine kinase inhibitor