ATRA plus chemotherapy, followed by ATO-based consolidation therapy for high-risk disease

The AIDA-2000 study (NCT00180128) combined oral ATRA until CR or for a maximum of 45 days and four doses of intravenous idarubicin (12 mg/m2) on days 2, 4, 6, and 8. Consolidation was then risk stratified so low- to intermediate-risk patients received additional cycles of anthracycline and ATRA, and high-risk patients also received cytarabine, etoposide, 6-thioguanine, and CHT chemotherapy (6-mercaptopurine plus methotrexate) as consolidation.[6]

The AIDA-2000 study (NCT00180128) combined oral ATRA until CR or for a maximum of 45 days and four doses of intravenous idarubicin (12 mg/m2) on days 2, 4, 6, and 8. Consolidation was then risk stratified so low- to intermediate-risk patients received additional cycles of anthracycline and ATRA, and high-risk patients also received cytarabine, etoposide, 6-thioguanine, and CHT chemotherapy (6-mercaptopurine plus methotrexate) as consolidation.[6]

After induction, 420 of 445 patients (94.4%) treated on the AIDA-2000 protocol were in CR. The 6-year OS rate was 87.4% and the cumulative incidence of relapse rate was 10.7%.[6][Level of evidence B4]

In the phase II APML4 study, ATO was added to the ATRA-and-idarubicin remission−induction backbone.[7] An ATO-based regimen, which includes gemtuzumab ozogamicin as the only cytotoxic drug, has been developed.

In the phase II APML4 study, ATO was added to the ATRA-and-idarubicin remission−induction backbone.[7] An ATO-based regimen, which includes gemtuzumab ozogamicin as the only cytotoxic drug, has been developed.

Of the 124 patients who could be evaluated, there were 4 (3.2%) early deaths and 118 (95%) hematologic CRs.

In the phase II APML4 study, ATO was added to the ATRA-and-idarubicin remission−induction backbone.[7] An ATO-based regimen, which includes gemtuzumab ozogamicin as the only cytotoxic drug, has been developed.

The 2-year freedom-from-relapse rate was 97.5% (95% CI, 90.4%−99.4%), the failure-free survival rate was 88.1% (95% CI, 80.7%−92.8%), and the OS rate was 93.2% (95% CI, 85.8%−96.8%).[7][Level of evidence B4]

In a single-institution study, patients received ATRA plus ATO induction. They also received a dose of gemtuzumab ozogamicin (or idarubicin) if the WBC was greater than 10 × 109/L on presentation or rose to more than 30 × 109/L during induction.[8] Patients in remission received ATO and ATRA in alternating months for a total of seven cycles as consolidation; gemtuzumab ozogamicin was substituted if either ATO or ATRA were discontinued because of toxicity. Long-term follow up from this study has been published.[9]

In a single-institution study, patients received ATRA plus ATO induction. They also received a dose of gemtuzumab ozogamicin (or idarubicin) if the WBC was greater than 10 × 109/L on presentation or rose to more than 30 × 109/L during induction.[8] Patients in remission received ATO and ATRA in alternating months for a total of seven cycles as consolidation; gemtuzumab ozogamicin was substituted if either ATO or ATRA were discontinued because of toxicity. Long-term follow up from this study has been published.[9]

Of the 54 patients with high-risk disease treated on the protocol, one patient received both gemtuzumab ozogamicin and idarubicin (12 mg/m2 daily for 3 days) because of persistent leukocytosis despite receiving gemtuzumab ozogamicin.

In a single-institution study, patients received ATRA plus ATO induction. They also received a dose of gemtuzumab ozogamicin (or idarubicin) if the WBC was greater than 10 × 109/L on presentation or rose to more than 30 × 109/L during induction.[8] Patients in remission received ATO and ATRA in alternating months for a total of seven cycles as consolidation; gemtuzumab ozogamicin was substituted if either ATO or ATRA were discontinued because of toxicity. Long-term follow up from this study has been published.[9]

The CR rate was 96%, and five (9%) patients relapsed.

In a single-institution study, patients received ATRA plus ATO induction. They also received a dose of gemtuzumab ozogamicin (or idarubicin) if the WBC was greater than 10 × 109/L on presentation or rose to more than 30 × 109/L during induction.[8] Patients in remission received ATO and ATRA in alternating months for a total of seven cycles as consolidation; gemtuzumab ozogamicin was substituted if either ATO or ATRA were discontinued because of toxicity. Long-term follow up from this study has been published.[9]

The 5-year rates were 81% for EFS, 89% for disease-free survival (DFS), and 86% for OS, indicating that the responses are durable.

In a single-institution study, patients received ATRA plus ATO induction. They also received a dose of gemtuzumab ozogamicin (or idarubicin) if the WBC was greater than 10 × 109/L on presentation or rose to more than 30 × 109/L during induction.[8] Patients in remission received ATO and ATRA in alternating months for a total of seven cycles as consolidation; gemtuzumab ozogamicin was substituted if either ATO or ATRA were discontinued because of toxicity. Long-term follow up from this study has been published.[9]

Across the entire study population, the 5-year OS rate was similar among the 45 high-risk patients who received gemtuzumab ozogamicin (84%) compared with the seven patients who received a dose of idarubicin (100%, P = .453).[8][Level of evidence B4]