Diagnostic workup and supportive care
| Recommendation . | Level of evidence . | Grade of recommendation . |
|---|---|---|
| 1.1. Once a diagnosis of APL is suspected, the disease should be managed as a medical emergency. | IV | C |
| 1.2. Diagnosis should be confirmed by molecular detection of PML-RARA fusion (or rare molecular variants). | IIa | B |
| 1.3. In addition to conventional karyotyping, FISH, and RT-PCR, immunostaining with anti-PML antibody can be used for rapid diagnosis of APL. | IIa | B |
| Management of coagulopathy | ||
| 1.4. Treatment with ATRA should be started immediately that a diagnosis of APL is suspected. | Ib | A |
| 1.5. Liberally transfuse with fresh frozen plasma, fibrinogen, and/or cryoprecipitate and platelet transfusions to maintain the fibrinogen concentration and platelet count above 100-150 mg/dL and 30-50 × 109/L, respectively. | IIb | B |
| 1.6. The benefit of heparin, tranexamic acid, or other anticoagulant or antifibrinolytic therapy remains questionable and should not be used routinely outside the context of clinical trials. | IV | C |
| Management of hyperleukocytosis (WBC >10 × 109/L) | ||
| 1.7. Chemotherapy should be started without delay, even if the molecular results are still pending. | IV | C |
| 1.8. Leukopheresis should be avoided due to risk of precipitating fatal hemorrhage. | III | B |
| 1.9. Prophylactic steroids can be given, which may reduce the risk of APL differentiation syndrome. | IV | C |
| Management of APL differentiation syndrome | ||
| 1.10. Steroids (10 mg dexamethasone intravenously bd) should be started immediately at the earliest clinical suspicion of incipient APL differentiation syndrome. Once the syndrome has resolved, steroids can be discontinued and ATO/ATRA recommenced. | IIa | B |
| 1.11. Temporary discontinuation of differentiation therapy (ATRA or ATO) is indicated only in case of severe APL differentiation syndrome. | IIa | B |
| Management of treatment with ATO | ||
| 1.12. Treatment with ATO should be restricted to cases confirmed to be PML/RARA-positive. | IIb | B |
| 1.13. Treatment with ATO requires careful monitoring to maintain electrolytes in the normal range, keeping the serum potassium above 4.0 mEq/L and serum magnesium above 1.8 mg/dL. | IV | C |
| 1.14. Treatment with ATO requires careful monitoring of the QT/QTc interval.* | IV | C |
| Recommendation . | Level of evidence . | Grade of recommendation . |
|---|---|---|
| 1.1. Once a diagnosis of APL is suspected, the disease should be managed as a medical emergency. | IV | C |
| 1.2. Diagnosis should be confirmed by molecular detection of PML-RARA fusion (or rare molecular variants). | IIa | B |
| 1.3. In addition to conventional karyotyping, FISH, and RT-PCR, immunostaining with anti-PML antibody can be used for rapid diagnosis of APL. | IIa | B |
| Management of coagulopathy | ||
| 1.4. Treatment with ATRA should be started immediately that a diagnosis of APL is suspected. | Ib | A |
| 1.5. Liberally transfuse with fresh frozen plasma, fibrinogen, and/or cryoprecipitate and platelet transfusions to maintain the fibrinogen concentration and platelet count above 100-150 mg/dL and 30-50 × 109/L, respectively. | IIb | B |
| 1.6. The benefit of heparin, tranexamic acid, or other anticoagulant or antifibrinolytic therapy remains questionable and should not be used routinely outside the context of clinical trials. | IV | C |
| Management of hyperleukocytosis (WBC >10 × 109/L) | ||
| 1.7. Chemotherapy should be started without delay, even if the molecular results are still pending. | IV | C |
| 1.8. Leukopheresis should be avoided due to risk of precipitating fatal hemorrhage. | III | B |
| 1.9. Prophylactic steroids can be given, which may reduce the risk of APL differentiation syndrome. | IV | C |
| Management of APL differentiation syndrome | ||
| 1.10. Steroids (10 mg dexamethasone intravenously bd) should be started immediately at the earliest clinical suspicion of incipient APL differentiation syndrome. Once the syndrome has resolved, steroids can be discontinued and ATO/ATRA recommenced. | IIa | B |
| 1.11. Temporary discontinuation of differentiation therapy (ATRA or ATO) is indicated only in case of severe APL differentiation syndrome. | IIa | B |
| Management of treatment with ATO | ||
| 1.12. Treatment with ATO should be restricted to cases confirmed to be PML/RARA-positive. | IIb | B |
| 1.13. Treatment with ATO requires careful monitoring to maintain electrolytes in the normal range, keeping the serum potassium above 4.0 mEq/L and serum magnesium above 1.8 mg/dL. | IV | C |
| 1.14. Treatment with ATO requires careful monitoring of the QT/QTc interval.* | IV | C |
If the QT (or QTc for patients with heart rate > 60 beats per minute) interval is prolonged longer than 500 msec, ATO should be withheld, the electrolytes (potassium and magnesium) repleted, and other medications that may cause prolonged QTc interval searched for and, ideally, discontinued. Once the QT/QTc returns to approximately 460 msec and the electrolytes are repleted, ATO may be resumed.