Acute promyelocytic leukemia
ICD-10 C92.4 · ICD-11 2A60.0&XH1A50
Next-Line Protocol

Low/Intermediate-Risk APL (WBC ≤10,000/ml): What to Do When Salvage Therapy Fails to Restore Molecular Remission

This protocol applies to patients with acute promyelocytic leukemia in the low or intermediate risk category — defined by a white blood cell count at or below 10,000/ml — who have undergone salvage therapy for relapsed or refractory disease but have not achieved the required molecular response.

Clinical Scenario

APL risk is stratified by white blood cell count. The low/intermediate-risk category applies when WBC is at or below 10,000/ml. Most clinicians currently classify APL into two categories: high risk (WBC >10,000/ml) and low/intermediate risk.

Prior Treatment — Failure Condition

Escalation trigger

Salvage therapy for relapsed or refractory disease — which may include arsenic trioxide (ATO) combined with idarubicin or gemtuzumab ozogamicin, ATRA combined with ATO, single-agent gemtuzumab ozogamicin, or tamibarotene combined with ATO — did not achieve the required goal: regaining of molecular complete remission (PML-RARA negative).

This protocol represents the next step taken when that molecular remission endpoint was not reached.

Consolidation Approach

Consolidation of second remission involves stem cell transplantation. The specific transplant pathway is determined by the patient's molecular response status.

The full protocol specifies the criteria that guide the selection between transplant approaches and the conditions under which each applies.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.3389/fonc.2022.1062524

  1. In the era of ATRA, APL has been stratified into three categories of risk with regards to relapse-free survival (RFS): WBC >10,000/ml (high-risk), WBC ≤10,000 ml with platelet count ≤40,000/ml (intermediate-risk), and WBC ≤10,000/ml with platelet count >40,000/ml (low-risk).
  2. Today, most clinicians will categorize APL within two categories, high risk (>10,000/ml) and low/intermediate risk.
  3. In summary, ATO-based induction with consolidation either with autologous or allogeneic SCT for patients with MRD negativity or positivity, respectively, remains the recommended treatment for patients in first relapse, with extended ATO consolidation and GO as a single or combination agent remaining a reasonable option for patients who cannot or prefer not to undergo SCT.
  4. PCR-positivity for PML-RARa at the time of autologous SCT appears to be a strong predictor of post-transplant relapse; allogeneic SCT is therefore a reasonable consideration in those patients unable to reach a complete molecular response ahead of planned transplantation.
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