Acute lymphoblastic leukaemia

National Comprehensive Cancer Network (NCCN): cytogenetic and molecular risk stratification groups[57]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: acute lymphoblastic leukemia [internet publication]. https://www.nccn.org/guidelines/category_1

Standard-risk group (B-ALL):

• Hyperdiploidy (51-65 chromosomes); trisomy of chromosomes 4, 10, and 17 appear to have the most favorable outcome

• t(12;21)(p13;q22): ETV6::RUNX1

• t(1;19)(q23;p13.3): TCF3::PBX1

• DUX4 rearranged

• PAX5 P80R

• t(9;22)(q34;q11.2): BCR::ABL1 without “IKZF1 plus” (IKZF1 deletion with co-occurring deletions in CDKN2A, CDKN2B, PAX5, or PAR1, in the absence of ERG deletion) and without antecedent chronic myeloid leukaemia (CML)

Poor-risk group (B-ALL):

• Hypodiploidy (<44 chromosomes)

• TP53 mutation

• KMT2A rearranged (t[4;11] or others)

• IgH rearranged (includes IGH::IL3 rearrangement)

• HLF rearranged

• ZNF384 rearranged

• MEF2D rearranged

• MYC rearranged

• BCR::ABL1-like (Philadelphia chromosome [Ph]-like) ALL

• PAX5 alteration

• t(9;22)(q34;q11.2): BCR::ABL1 with "IKZF1 plus" (particularly with concomitant 22q11.22 deletions) and/or with antecedent CML

• Intrachromosomal amplification of chromosome 21 (iAMP21)

• IKZF1 alterations

• Complex karyotype (5 or more chromosomal abnormalities)

Standard-risk group (T-ALL):

• NOTCH1/FBXW7 mutation

Poor-risk group (T-ALL):

• RAS/PTEN mutation

• NOTCH1/FBXW7 wild type

The Children’s Oncology Group (COG) classification system for central nervous system (CNS) disease at diagnosis[68]Winick N, Devidas M, Chen S, et al. Impact of initial CSF findings on outcome among patients with National Cancer Institute standard- and high-risk B-cell acute lymphoblastic leukemia: a report from the children's oncology group. J Clin Oncol. 2017 Aug 1;35(22):2527-34. https://ascopubs.org/doi/10.1200/JCO.2016.71.4774 http://www.ncbi.nlm.nih.gov/pubmed/28535084?tool=bestpractice.com

CNS1: no blasts in the cerebrospinal fluid (CSF) regardless of white blood cell (WBC) and red blood cell (RBC) count

CNS2

• a: WBC <5/microlitre in CSF plus blasts plus RBC <10/microlitre

• b: WBC <5/microlitre in CSF plus blasts plus RBC ≥10/microlitre (trauma lumbar puncture [TLP] plus)

• c: WBC ≥5/microlitre in CSF plus blasts plus RBC ≥10/microlitre (TLP plus); CSF WBC <2 times blood WBC

CNS3

• a: WBC ≥5/microlitre in CSF plus blasts plus RBC <10/microlitre

• b: WBC ≥5/microlitre in CSF plus blasts plus RBC ≥10/microlitre; CSF WBC >2 times blood WBC

• c: clinical signs of CNS leukaemia

National Comprehensive Cancer Network (NCCN): treatment response criteria for blood and bone marrow[57]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: acute lymphoblastic leukemia [internet publication]. https://www.nccn.org/guidelines/category_1

Complete remission (CR):

• No circulating lymphoblasts or extramedullary disease

• No lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass, CNS involvement

• Trilineage haematopoiesis and blasts <5%

• Absolute neutrophil count (ANC) ≥1000/microlitre

• Platelets ≥100,000/microlitre

CR with partial haematologic recovery (CRh):

• Meets all criteria for CR except with partial recovery of peripheral blood counts (platelets ≥50,000/microlitre and ANC ≥500/microlitre)

CR with incomplete haematologic recovery (CRi):

• Meets all criteria for CR except without recovery of platelet count or without recovery of ANC (platelets <100,000/microlitre and ANC ≥1000/microlitre or platelets ≥100,000/microlitre and ANC <1000/microlitre)

Morphological leukaemia-free state (MLFS):

• Blasts <5% and no measurable extramedullary leukaemia

• ANC <500/microlitre and platelets <50/microlitre

• The marrow shows ≥10% cellularity, with ≥200 cells enumerated from an aspirate that contains spicules

Aplastic marrow:

• All criteria for MLFS are met, but with <10% cellularity and/or an aspicular aspirate with <200 cells that can be enumerated

Refractory disease:

• CR not achieved at the end of induction

Progressive disease (PD):

• Appearance of circulating leukaemic blasts or an increase of ≥25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease

Relapsed disease:

• Reappearance of blasts in the blood or bone marrow (>5%) or in any extramedullary site after a CR

European Society for Medical Oncology (ESMO): treatment response criteria (according to measurable residual disease [MRD])[59]Hoelzer D, Bassan R, Dombret H, et al. Acute lymphoblastic leukaemia in adult patients: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016 Sep;27(suppl 5):v69-82. https://www.annalsofoncology.org/article/S0923-7534(19)31639-4/fulltext http://www.ncbi.nlm.nih.gov/pubmed/27056999?tool=bestpractice.com

Complete haematological remission (CR):

• Leukaemic cells not detectable by light microscopy in bone marrow/peripheral blood/cerebrospinal fluid (bone marrow <5% blasts)

Complete molecular remission/MRD negativity (molCR):

• Patient in CR

• MRD not detectable by sensitive molecular probe(s) (sensitivity ≥10-₄)

Molecular/MRD response, less than molCR (molR):

• Patient in CR, not in molCR

• Low-level non-quantifiable MRD (<10-₄/0.01%; i.e., <1 leukaemic cell in 10,000)

• Assessable by multi-parameter flow cytometry (MFC; lower detection limit, between 10-₃ and 10-₄, higher sensitivity with 8-12 colour techniques)

Molecular failure/MRD positivity (molFail):

• Patient in CR, not in molCR/molR

• Quantifiable MRD (≥10-₄/0.01%)

• Assessable by MFC (lower detection limit, between 10-₃ and 10-₄)

Molecular/MRD relapse (molRel):

• Patient still in CR, prior molCR/molR

• Loss of molCR/molR status (≥10-₄/0.01%)

• Assessable by MFC (lower detection limit, between 10-₃ and 10-₄)

Relapse:

• Loss of CR status

• Haematologic relapse (bone marrow ALL blasts >5%)

• Extramedullary relapse (e.g., CNS)