What is the diagnosis and treatment for blast crisis (a phase of accelerated disease progression in Chronic Myeloid Leukemia (CML) or other myeloproliferative disorders)?

From the Guidelines

Blast crisis in Chronic Myeloid Leukemia (CML) should be treated with a tyrosine kinase inhibitor (TKI) such as imatinib, dasatinib, or nilotinib, often combined with acute leukemia-type chemotherapy regimens, and allogeneic stem cell transplantation should be considered for eligible patients as it offers the best chance for long-term survival. The diagnosis of blast crisis is characterized by the presence of more than 20% blasts in the blood or bone marrow, indicating a transformation of CML from its chronic phase to an acute leukemia-like state [ 1 ]. The European LeukemiaNet 2020 recommendations suggest that the choice of TKI should be based on prior therapy and BCR-ABL1 KD-mutational status, and that allogeneic stem cell transplantation should be considered for patients with primary blast phase or those who have failed second-generation TKIs [ 1 ].

Treatment Approach

The treatment approach for blast crisis involves:

• Initiation of a TKI such as imatinib, dasatinib, or nilotinib, often combined with acute leukemia-type chemotherapy regimens [ 1 ]
• Consideration of allogeneic stem cell transplantation for eligible patients as it offers the best chance for long-term survival [ 1 ]
• Supportive care with blood product transfusions, infection prophylaxis, and treatment of complications
• Monitoring of response to treatment and adjustment of therapy as needed

Management Strategy

The management strategy for blast crisis involves:

• Assessment of the patient's risk status and BCR-ABL1 KD-mutational status to guide the choice of TKI [ 1 ]
• Consideration of intensification of treatment with a second-generation TKI or ponatinib for patients with high-risk disease [ 1 ]
• Evaluation for allogeneic stem cell transplantation for patients with primary blast phase or those who have failed second-generation TKIs [ 1 ]

Prognosis

The prognosis for blast crisis is generally poor, with a median survival of 3-6 months without effective treatment [ 1 ]. However, with prompt and aggressive treatment, including TKIs and allogeneic stem cell transplantation, some patients may achieve long-term survival and remission [ 1 ].

From the FDA Drug Label

1.2 Ph+ CML in Blast Crisis (BC), Accelerated Phase (AP) or Chronic Phase (CP) After Interferon-alpha (IFN) Therapy 2.2 Adult Patients With Ph+ CML CP, AP, or BC

The diagnosis of blast crisis in Chronic Myeloid Leukemia (CML) is not explicitly stated in the label, but it is mentioned as an indication for the use of imatinib. The treatment for blast crisis (BC) is imatinib, as it is indicated for Ph+ CML in Blast Crisis (BC) 2.

• Key points:
  • Imatinib is used to treat Ph+ CML in blast crisis.
  • The label does not provide information on the diagnosis of blast crisis.

From the Research

Diagnosis of Blast Crisis

• Blast crisis (BC) is a phase of accelerated disease progression in Chronic Myeloid Leukemia (CML) or other myeloproliferative disorders, characterized by the rapid expansion of blasts in the bone marrow or blood 3, 4.
• The diagnosis of blast crisis is often made based on the presence of blasts in the peripheral blood or bone marrow, and is typically confirmed by cytogenetic and molecular analysis 5.
• The clinical presentation of blast crisis can vary, but often includes symptoms such as fever, fatigue, and bleeding, as well as signs of leukostasis, such as respiratory distress and neurological symptoms 5.

Treatment of Blast Crisis

• The primary objective of initial treatment in blast crisis is to achieve a second chronic phase (CP) and to proceed to an allogeneic stem cell transplantation (SCT) in eligible patients 3.
• Tyrosine kinase inhibitors (TKIs) are often used as initial therapy for blast crisis, although the response to these agents is often short-lived and may not be sufficient to achieve a durable remission 4, 6.
• Allogeneic stem cell transplantation (SCT) is considered the only potentially curative treatment for blast crisis, although it is associated with significant risks and is not suitable for all patients 3, 4.
• The management of blast crisis remains challenging, and there is a need for novel therapies to improve outcomes for patients with this condition 3, 4.

Monitoring and Prevention of Blast Crisis

• Patients with CML who are in treatment-free remission (TFR) are at risk of developing blast crisis, and should be closely monitored for signs of disease progression 7.
• The use of whole-exon sequencing and other genetic tests may help to identify patients who are at high risk of developing blast crisis, and to guide treatment decisions 7.
• A long-term monitoring strategy is necessary to detect blast crisis early, and to prevent the development of this condition in patients with CML 7.