Treatment of Primary Myelofibrosis with Elevated Blasts in Blood or Marrow: Accelerated Phase and Blast Phase (Transplant Eligible)
This protocol addresses the management of transplant-eligible patients with primary myelofibrosis who have progressed to accelerated phase or blast phase — defined by a persistent increase in blasts detected on blood smear or bone marrow examination.
Clinical scenario
Accelerated phase is defined by a persistent increase to 10–19% blasts in the blood or marrow; blast phase is defined by a persistent increase to 20% or more blasts. Both represent significant disease progression and present distinct management challenges, particularly in older patients. The patients addressed here are considered transplant eligible.
Treatment approach
Management centres on remission-induction therapy with the primary objective of reducing blast burden prior to transplant — the full regimen selection, sequencing, and algorithm depend on individual disease stage, kinetics, donor availability, and local practice, and are set out in the structured protocol below.
Key clinical goal: Reduction of blasts in blood or marrow prior to transplant, which is associated with improved outcomes and reduced relapse risk.
References
- Accelerated phase (AP; persistent increase to 10%–19% blasts in blood or marrow) and blast phase (BP; persistent increase to ≥20% blasts in blood or marrow) MF presents many challenges, particularly in the older population.
- Considered transplant eligible
- Dependent on disease stage, kinetics, donor availability and local practice, patients often receive remission induction high-dose chemotherapy or hypomethylating agent (HMA)-based regimens with a plan to reduce blasts prior to allo-HSCT; some may proceed with sequential chemo-RIC transplant-based approaches.
- Frequently induction is with standard daunorubicin and cytarabine-based (DA) regimens and there is no direct comparison to other regimens such as fludarabine, cytarabine, granulocyte colony-stimulating factor (G-CSF) and idarubicin (FLAG-Ida), FLAG-Ida-venetoclax or liposomal cytarabine/daunorubicin (Vyxeos) in this setting.
- HMAs, either azacytidine or decitabine, alone or combined with ruxolitinib are increasingly used regimens 'off-licence' as previous synergy has been demonstrated.
- Reduction of blasts prior to transplant, in general, associates with improved outcomes and less risk of relapse (Grade 1C).
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