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Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Risk-based Treatment Assignment

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The following subgroups of patients are sometimes considered candidates for allogeneic SCT in first complete remission (CR1): [9,158,159,160]

  • Infants with MLL translocations.
  • Patients with hypodiploidy.
  • Patients with initial induction failure.
  • Other subsets of patients who have a less than 50% chance of long-term remission with current therapies.

However, because of small numbers, possible patient selection bias, and center preference, studies to definitively show whether transplantation in CR1 is superior to intensive chemotherapy for these very high-risk patients have not been feasible. The use of allogeneic SCT in CR1 for patients with Ph+ ALL is less clear in the era of tyrosine kinase inhibitors.[112]

Berlin-Frankfurt-Münster (BFM) risk groups

Since 2000, risk stratification on BFM protocols has been based almost solely on treatment response criteria. In addition to prednisone prophase response, treatment response is assessed via MRD measurements at two time points, end induction (week 5) and end consolidation (week 12).

The BFM risk groups include the following:[140]

  • Standard risk: Patients who are MRD-negative at both time points are classified as standard risk.
  • Intermediate risk: Patients who have positive MRD at week 5 and low MRD (<10-3) at week 12 are considered intermediate risk.
  • High risk: Patients with high MRD (≥10-3) at week 12 are high risk. Patients with a poor response to the prednisone prophase are also considered high risk, regardless of subsequent MRD.

Phenotype, leukemic cell mass estimate, also known as BFM risk factor, and CNS status at diagnosis do not factor into the current risk classification schema. However, patients with either the t(9;22) or the t(4;11) are considered high risk, regardless of early response measures.

Prognostic (risk) groups under clinical evaluation

COG AALL08B1(Classification of Newly Diagnosed ALL): COG protocol AALL08B1 stratifies four risk groups for patients with B-precursor ALL (low risk, average risk, high risk, and very-high risk) based on the following criteria:

  • Age and presenting leukocyte count (using NCI risk-group criteria).[1]
  • Initial CNS status.
  • Genetic abnormalities.
  • Day 8 peripheral blood MRD.
  • Day 29 bone marrow morphologic response and MRD.

Morphologic assessment of early response in the bone marrow is no longer performed on days 8 and 15 of induction as part of risk stratification. Patients with T-cell phenotype are treated on a separate study and are not risk classified in this way.

For patients with B-precursor ALL:

  • Favorable genetics are defined as the presence of either hyperdiploidy with trisomies of chromosomes 4 and 10 (double trisomy) or the ETV6-RUNX1 fusion.
  • Unfavorable characteristics are defined as CNS3 status at diagnosis, induction failure (M3 marrow at day 29), older than 13 years, and the following unfavorable genetic abnormalities: hypodiploidy (<44 chromosomes), MLL rearrangement, and iAMP21. The presence of any of these unfavorable characteristics is sufficient to classify a patient as very high risk, regardless of other presenting features. Patients with BCR-ABL (Ph+ ALL) are treated on a separate clinical trial.
  • MRD is assessed by flow cytometry. At day 29, a level of less than 0.01% is considered low risk.

The four risk groups for B-precursor ALL are defined in Table 1.

1|2|3|4|5|6|7|8|9|10|11

WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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