How I treat newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia
| Diagnostics/evaluation | Patient: Age, fitness/frailty, cardiovascular risk factors, support Disease: Genetic risk: cytogenetic, molecular (IKZF1; IKZF1 plus) MRD monitoring: RT-PCR p190 vs p210; NGS or PCR for clonal tracking |
| When possible, (a) enroll on clinical trial, (b) follow published regimen | |
| Phase: Induction Goal: Complete remission (CR) | TKI: DAS or PON or clinical trial PLUS: Low intensity (steroids, steroids + vincristine, steroids + blinatumomab) |
| Phase: Consolidation Goal: Prolong CR (indefinitely) | TKI: DAS or PON or clinical trial -If DAS, consider change to PON if inadequate response -If PON, dose reduce to 15 mg after achievement of CMR PLUS: 1. TKI alone (if alloHCT planned or palliative goal) 2. Chemotherapy (age adjusted) 3. Blinatumomab (within 3 months) 4. AlloHCT |
| AlloHCT, in CR1 | Favoring yes 1. High-risk genetic features (chromosomes: complex, “double” Ph; IKZF1 plus) 2. No achievement of CMR by 3 months (with TKI+/- chemotherapy) 3. Fit, appropriate donor 4. No blinatumomab available or not tolerated Favoring no 1. No high-risk genetic features 2. Achievement of CMR by 3 months (with TKI+/- chemotherapy) 3. Blinatumomab Unknown 1. Poor response to TKI+/- chemo but CMR with blinatumomab 2. High-risk genetics but optimal MRD response |
| CNS prophylaxis | IT chemotherapy (12-15) High-dose methotrexate and/or cytarabine |
| Monitoring | BCR::ABL1 RT-PCR NGS, to establish presence of CML-like biology, and if present to supplement BCR::ABL1 transcript monitoring |
| Diagnostics/evaluation | Patient: Age, fitness/frailty, cardiovascular risk factors, support Disease: Genetic risk: cytogenetic, molecular (IKZF1; IKZF1 plus) MRD monitoring: RT-PCR p190 vs p210; NGS or PCR for clonal tracking |
| When possible, (a) enroll on clinical trial, (b) follow published regimen | |
| Phase: Induction Goal: Complete remission (CR) | TKI: DAS or PON or clinical trial PLUS: Low intensity (steroids, steroids + vincristine, steroids + blinatumomab) |
| Phase: Consolidation Goal: Prolong CR (indefinitely) | TKI: DAS or PON or clinical trial -If DAS, consider change to PON if inadequate response -If PON, dose reduce to 15 mg after achievement of CMR PLUS: 1. TKI alone (if alloHCT planned or palliative goal) 2. Chemotherapy (age adjusted) 3. Blinatumomab (within 3 months) 4. AlloHCT |
| AlloHCT, in CR1 | Favoring yes 1. High-risk genetic features (chromosomes: complex, “double” Ph; IKZF1 plus) 2. No achievement of CMR by 3 months (with TKI+/- chemotherapy) 3. Fit, appropriate donor 4. No blinatumomab available or not tolerated Favoring no 1. No high-risk genetic features 2. Achievement of CMR by 3 months (with TKI+/- chemotherapy) 3. Blinatumomab Unknown 1. Poor response to TKI+/- chemo but CMR with blinatumomab 2. High-risk genetics but optimal MRD response |
| CNS prophylaxis | IT chemotherapy (12-15) High-dose methotrexate and/or cytarabine |
| Monitoring | BCR::ABL1 RT-PCR NGS, to establish presence of CML-like biology, and if present to supplement BCR::ABL1 transcript monitoring |