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Diagnosing Acute Lymphoblastic Leukemia


As soon as the diagnosis is made, treatment is initiated.

Prognostic factors

High-risk for acute B-lymphoblastic leukemia:

  • Philadelphia chromosome/bcr-abl/t(9;22)(q34;q11)
  • t(4;11)(q21;q23) and other 11q23 anomalies
  • massively hypodiploid karyotype
  • complex karyotype, that is > 5 discrepancy
  • leukocytes in blood > 30 x 109/l
  • ≥ 5 % blasts in bone marrow smear 4 weeks after starting treatment
  • positive MRD-status 12 months after time of diagnosis

High-risk for T-cell illness:

  • ≥ 5 % blasts in bone marrow smear 4 weeks after starting treatment
  • pro T-ALL
  • mature T-ALL
  • positive MRD status 12 months after time of diagnosis

All others are considered standard risk.

Minimal residual disease (MRD)

In younger patients (< 60), it is recommended to try to define the leukemia-specific marker with immunophenotyping or molecular genetic method at the time of diagnosis and follow the MRD level during treatment when the clone-specific marker can be defined. If, as in the case of high-risk leukemia, a decision to use allogeneic stem cell transplant as primary consolidation treatment has been made, or this is clearly inappropriate (age > 60), the MRD determination has no practical consequences and can be left out.

It is recommended that the MRD is determined in the bone marrow aspirate at the concluded consolidation treatment (before starting maintenance treatment) and 12 months after the time of diagnosis, if clone-specific markers are successfully defined at the time of the diagnosis. Examinations should be avoided in the aplasia phase since the chance for an unsuccessful test is the greatest.

In order for the MRD analysis to be emphasized, the sensitivity of the analysis must be at least 10-4. Ideally, the analysis should be carried out on two clone-specific markers. If the results are difficult to interpret, the analysis should be repeated.

  • With positive MRD-status (> 10–4) after concluded induction (about week 16) an allogeneic stem cell transplantation should be considered. Alternatively, the MRD level is followed with a new test after 1 month. Increasing MRD (1 log unit or more) indicates a high risk for recurrence.
  • With positive MRD-status (> 10–4) after 12 months, an allogeneic stem cell transplantation is considered. For transition from previous negative to positive status which is not due to variation in test sensitivity, supplementary reinduction treatment is considered. Contact the Section for Blood Diseases for planning further treatment.

It is currently recommended that all patients complete full maintenance treatment even if MRD is negative in week 16 and 12 months. Rapid decline of MRD (negative in week 2 and week 16) indicates good prognosis.

Knowledge of the use of MRD is under rapid development.

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