Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

lymphoid blast crisis

1st line – tyrosine kinase inhibitor (TKI)

Back
ACUTE
|
lymphoid blast crisis
1st line – 

tyrosine kinase inhibitor (TKI)

A TKI combined with high-dose acute lymphoblastic leukaemia (ALL)-type induction chemotherapy is preferred for patients with lymphoid blast crisis preparing for allogeneic haematopoietic stem cell transplantation (HSCT).[2][40][47]​​​[48]​​​​​​​[49]

If chemotherapy is not suitable, a TKI plus a corticosteroid is recommended for patients with lymphoid blast crisis.[2]

The goal of initial treatment is to achieve a response sufficient to proceed to consolidation with allogeneic HSCT (e.g., return to chronic phase); transplantation in frank blast phase is not recommended.

TKIs target the BCR::ABL fusion protein associated with the Philadelphia chromosome.

Choice of TKI for patients who have progressed on TKI therapy should be based on prior therapy and mutation profile.[2]

Previously untried second- or third-generation TKIs are preferred (e.g., dasatinib, bosutinib, nilotinib, ponatinib).[2][54][55][56][57]

Ponatinib should be considered for patients who have the T315I mutation. It may be an option for those without the T315I mutation who have resistance or intolerance to at least two prior TKIs.[58][59]

Ponatinib is associated with a significant risk of serious vascular events, heart failure, pancreatitis, and hepatotoxicity.[60]​ Caution is required for patients with cardiovascular risk factors. Post-marketing cases of reversible posterior leukoencephalopathy syndrome (RPLS) have been reported.[61]

Patients with de novo blast crisis are usually treated with a second- or third-generation TKI.[2][6]​ Imatinib may be considered for patients with contraindications to second- and third-generation TKIs; it may be less potent, but it is well-tolerated.[2]

Central nervous system (CNS) involvement has been reported in some patients with lymphoid and biphenotypic blast crisis. If CNS involvement is confirmed, dasatinib, a second-generation TKI, may be considered.[2][3]​​​ There is some evidence that dasatinib may penetrate the blood-brain barrier.[2][3][53]

See local specialist protocol for dosing guidelines.

Primary options

dasatinib

OR

nilotinib

OR

bosutinib

OR

ponatinib

Secondary options

imatinib

Consider – ALL induction chemotherapy or corticosteroid

Back
ACUTE
|
lymphoid blast crisis
Consider – 

ALL induction chemotherapy or corticosteroid

Additional treatment recommended for SOME patients in selected patient group

A tyrosine kinase inhibitor (TKI) combined with high-dose acute lymphoblastic leukaemia (ALL)-type induction chemotherapy (e.g., hyper-CVAD [hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with cytarabine and methotrexate]) is preferred for patients with lymphoid blast crisis preparing for allogeneic stem cell transplantation.[2][40][47]​​​[48]​​​​[49]

Hyper-CVAD plus dasatinib may be an option, especially for younger patients. One retrospective analysis of patients with chronic myeloid leukaemia (CML)-lymphoid blast phase receiving hyper-CVAD plus dasatinib found that 70% (14/20) achieved major molecular response, and 55% (11/20) complete molecular response (5-year progression-free survival 46%; 5-year overall survival 59%).[50]

Less intensive regimens, such as a TKI plus vincristine, may be considered for older or less fit patients.[51]

If chemotherapy is not suitable, a TKI plus a corticosteroid is recommended for patients with lymphoid blast crisis.[2]

See local specialist protocol for dosing guidelines.

Primary options

Hyper-CVAD

cyclophosphamide

and

vincristine

and

doxorubicin

and

dexamethasone

and

cytarabine

and

methotrexate

Secondary options

vincristine

OR

prednisolone

Plus – supportive care

Back
ACUTE
|
lymphoid blast crisis
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be provided throughout the course of treatment.

Granulocyte colony-stimulating factors may be used adjunctively if anaemia, thrombocytopenia, or neutropenia occurs during any phase of treatment. Therapy causing thrombocytopenia or neutropenia may be withheld if the platelet count is <50 × 10⁹/L (<50,000/microlitre) or absolute neutrophil count is <1 × 10⁹/L (<1000/microlitre).

Hydroxycarbamide to reduce very high white blood cell counts (i.e., >100 × 10⁹/L [>100,000/microlitre]), in tandem with prophylaxis for tumour lysis syndrome (e.g., with allopurinol and hydration), is given prior to tyrosine kinase inhibitor therapy or chemotherapy in patients with a high disease burden.

Other components of supportive care include blood transfusions and palliative care to manage symptoms.

myeloid blast crisis

1st line – tyrosine kinase inhibitor (TKI)

Back
ACUTE
|
myeloid blast crisis
1st line – 

tyrosine kinase inhibitor (TKI)

A TKI combined with an acute myeloid leukaemia (AML)-type induction chemotherapy regimen (e.g., cytarabine plus daunorubicin) is preferred for patients with myeloid blast crisis preparing for allogeneic haematopoietic stem cell transplantation (HSCT).[2][40][41]

If chemotherapy is not suitable, a TKI alone may be an alternative option.[2]

The goal of initial treatment is to achieve a response sufficient to proceed to consolidation with allogeneic HSCT (e.g., return to chronic phase); transplantation in frank blast phase is not recommended.

TKIs target the BCR::ABL fusion protein associated with the Philadelphia chromosome.

Choice of TKI for patients who have progressed on TKI therapy should be based on prior therapy and mutation profile.[2]

Previously untried second- or third-generation TKIs are preferred (e.g., dasatinib, bosutinib, nilotinib, ponatinib).[2][54][55][56][57]

Ponatinib should be considered for patients who have the T315I mutation. It may be an option for those without the T315I mutation who have resistance or intolerance to at least two prior TKIs.[58][59]

Ponatinib is associated with a significant risk of serious vascular events, heart failure, pancreatitis, and hepatotoxicity.[60]​ Caution is required for patients with cardiovascular risk factors. Post-marketing cases of reversible posterior leukoencephalopathy syndrome (RPLS) have been reported.[61]

Patients with de novo blast crisis are usually treated with a second- or third-generation TKI.[2][6]​ Imatinib may be considered for patients with contraindications to second- and third-generation TKIs. Imatinib may be less potent than second- and third-generation TKIs, but it is well-tolerated.[2]

​Central nervous system (CNS) involvement has been reported in some patients with myeloid blast crisis. Myeloid blasts are, however, less likely to infiltrate the CNS than lymphoid blasts.[52]​ If CNS involvement is confirmed, dasatinib, a second-generation TKI, may be considered.[2][3]​​​​ There is some evidence that dasatinib may penetrate the blood-brain barrier.[2][3][53]

See local specialist protocol for dosing guidelines.

Primary options

dasatinib

OR

nilotinib

OR

bosutinib

OR

ponatinib

Secondary options

imatinib

Consider – AML induction chemotherapy

Back
ACUTE
|
myeloid blast crisis
Consider – 

AML induction chemotherapy

Additional treatment recommended for SOME patients in selected patient group

A tyrosine kinase inhibitor (TKI) combined with an acute myeloid leukaemia (AML)-type induction chemotherapy regimen (e.g., cytarabine plus daunorubicin) is preferred for patients with myeloid blast crisis preparing for allogeneic stem cell transplantation.[2][40][41]

Ponatinib with the induction chemotherapy regimen FLAG-IDA (fludarabine, cytarabine, idarubicin, and the granulocyte colony-stimulating factor filgrastim) may be an option, especially for younger patients.[40][42][43]​​ In one phase 1/2 dose-finding trial, 11 (69%) of 16 evaluable patients with blast-phase chronic myeloid leukaemia (CML; including myeloid, lymphoid, and mixed phenotypes) achieved haematological or cytogenetic response after a single cycle of ponatinib-FLAG-IDA.[42]​ Four patients had dose-limiting toxicity.[42]

​Less intensive regimens, such as a TKI plus a hypomethylating agent (e.g., decitabine or azacitidine), may be considered for older or less fit patients.[44][45][46]

See local specialist protocol for dosing guidelines.

Primary options

FLAG-IDA

fludarabine

and

cytarabine

and

idarubicin

and

filgrastim

OR

cytarabine

and

daunorubicin

Secondary options

decitabine

OR

azacitidine

Plus – supportive care

Back
ACUTE
|
myeloid blast crisis
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be provided throughout the course of treatment.

Granulocyte colony-stimulating factors may be used adjunctively if anaemia, thrombocytopenia, or neutropenia occurs during any phase of treatment. Therapy causing thrombocytopenia or neutropenia may be withheld if platelet count is <50 × 10⁹/L (<50,000/microlitre) or absolute neutrophil count is <1 × 10⁹/L (<1000/microlitre).

Hydroxycarbamide to reduce very high white blood cell counts (i.e., >100 × 10⁹/L [>100,000/microlitre]), in tandem with prophylaxis for tumour lysis syndrome (e.g., with allopurinol and hydration), is given prior to tyrosine kinase inhibitor therapy or chemotherapy in patients with a high disease burden.

Other components of supportive care include blood transfusions and palliative care to manage symptoms.

biphenotypic blast crisis

1st line – tyrosine kinase inhibitor (TKI)

Back
ACUTE
|
biphenotypic blast crisis
1st line – 

tyrosine kinase inhibitor (TKI)

Patients with biphenotypic blast crisis are treated similarly to those with lymphoid and myeloid blast crisis; an acute lymphoblastic leukaemia (ALL)- or acute myeloid leukaemia (AML)-type induction chemotherapy regimen can be considered alongside TKI therapy.

The goal of initial treatment is to achieve a response sufficient to proceed to consolidation with allogeneic haematopoietic stem cell transplantation (HSCT); transplantation in frank blast phase is not recommended.

TKIs target the BCR::ABL fusion protein associated with the Philadelphia chromosome.

Choice of TKI for patients who have progressed on TKI therapy should be based on prior therapy and mutation profile.[2]

Previously untried second- or third-generation TKIs are preferred (e.g., dasatinib, bosutinib, nilotinib, ponatinib).[54][55][56][57]

Ponatinib should be considered for patients who have the T315I mutation. It may be an option for those without the T315I mutation who have resistance or intolerance to at least two prior TKIs.[2][58]​​[59]

Ponatinib is associated with a significant risk of serious vascular events, heart failure, pancreatitis, and hepatotoxicity.[60]​ Caution is required for patients with cardiovascular risk factors. Post-marketing cases of reversible posterior leukoencephalopathy syndrome (RPLS) have been reported.[61]

Patients with de novo blast crisis are usually treated with a second- or third-generation TKI.[2][6]​ Imatinib may be considered for patients with contraindications to second- and third-generation TKIs. Imatinib may be less potent than second- and third-generation TKIs, but it is well-tolerated.[2]

​Central nervous system (CNS) involvement has been reported in some patients with lymphoid and biphenotypic blast crisis. If CNS involvement is confirmed, dasatinib, a second-generation TKI, may be considered.[2][3]​​​​​ There is some evidence that dasatinib may penetrate the blood-brain barrier.[2][3][53]

See local specialist protocol for dosing guidelines.

Primary options

dasatinib

OR

nilotinib

OR

bosutinib

OR

ponatinib

Secondary options

imatinib

Consider – ALL or AML induction chemotherapy

Back
ACUTE
|
biphenotypic blast crisis
Consider – 

ALL or AML induction chemotherapy

Additional treatment recommended for SOME patients in selected patient group

Patients with biphenotypic blast crisis who require chemotherapy to achieve a haematological response can be considered for treatment with an induction chemotherapy regimen.

An acute lymphoblastic leukaemia (ALL) regimen (e.g., hyper-CVAD [hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with cytarabine and methotrexate]), or an acute myeloid leukaemia (AML) regimen (e.g., cytarabine plus daunorubicin; FLAG-IDA [fludarabine, cytarabine, idarubicin, and the granulocyte colony-stimulating factor filgrastim]; or a hypomethylating agent [e.g., decitabine or azacitidine]) can be considered alongside tyrosine kinase inhibitor therapy.

See local specialist protocol for dosing guidelines.

Primary options

ALL induction regimen - hyper-CVAD

cyclophosphamide

and

vincristine

and

doxorubicin

and

dexamethasone

and

cytarabine

and

methotrexate

OR

AML induction regimen - FLAG-IDA

fludarabine

and

cytarabine

and

idarubicin

and

filgrastim

OR

AML induction regimen

cytarabine

and

daunorubicin

OR

AML induction regimen

decitabine

OR

AML induction regimen

azacitidine

Plus – supportive care

Back
ACUTE
|
biphenotypic blast crisis
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be available throughout the course of treatment.

Granulocyte colony-stimulating factors may be used adjunctively if anaemia, thrombocytopenia, or neutropenia occurs during any phase of treatment. Therapy causing thrombocytopenia or neutropenia may be withheld if the platelet count is <50 × 10⁹/L (<50,000/microlitre) or absolute neutrophil count is <1 × 10⁹/L (<1000/microlitre).

Hydroxycarbamide to reduce very high white blood cell counts (i.e., >100 × 10⁹/L [>100,000/microlitre]), in tandem with prophylaxis for tumour lysis syndrome (e.g., with allopurinol and hydration), is given prior to tyrosine kinase inhibitor therapy or chemotherapy in patients with a high disease burden.

Other components of supportive care include blood transfusions and palliative care to manage symptoms.

ONGOING

suboptimal response to initial treatment

1st line – alternative tyrosine kinase inhibitor (TKI) and chemotherapy

Back
ONGOING
|
suboptimal response to initial treatment
1st line – 

alternative tyrosine kinase inhibitor (TKI) and chemotherapy

In the absence of at least a partial response to initial treatment, an alternative TKI and chemotherapy regimen should be considered.[40]

Early referral for allogeneic haematopoietic stem cell transplantation (HSCT) is critical to improve outcomes.

Plus – supportive care

Back
ONGOING
|
suboptimal response to initial treatment
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be available throughout the course of treatment.

Granulocyte colony-stimulating factors may be used adjunctively if anaemia, thrombocytopenia, or neutropenia occurs during any phase of treatment. Therapy causing thrombocytopenia or neutropenia may be withheld if the platelet count is <50 × 10⁹/L (<50,000/microlitre) or absolute neutrophil count is <1 × 10⁹/L (<1000/microlitre).

Hydroxycarbamide to reduce very high white blood cell counts (i.e., >100 × 10⁹/L [>100,000/microlitre]), in tandem with prophylaxis for tumour lysis syndrome (e.g., with allopurinol and hydration), is given prior to tyrosine kinase inhibitor therapy or chemotherapy in patients with a high disease burden.

Other components of supportive care include blood transfusions and palliative care to manage symptoms.

partial haematological response or second chronic phase

1st line – allogeneic stem cell transplantation plus tyrosine kinase inhibitor (TKI) maintenance therapy

Back
ONGOING
|
partial haematological response or second chronic phase
1st line – 

allogeneic stem cell transplantation plus tyrosine kinase inhibitor (TKI) maintenance therapy

Allogeneic haematopoieticstem cell transplantation (HSCT) should be considered promptly if at least a partial haematological response or second chronic phase is achieved with initial drug therapy and a suitable donor is found.[2][32][40]

Long-term remission is rare in blast crisis, but allogeneic HSCT provides the best chance of cure.

The goal of initial treatment is to achieve a response sufficient to proceed to consolidation with allogeneic HSCT (e.g., return to chronic phase); transplantation in frank blast phase is not recommended. It is important to find a suitable transplant donor early, as the response to drug treatment is not often durable.[2][32]

Careful monitoring is essential during drug treatment to ensure optimal timing of HSCT​; survival outcomes for allogeneic HSCT are vastly improved in patients who respond to drug treatment and have a lower disease burden.[62][63][64]

Following allogeneic HSCT, consideration of TKI maintenance therapy is recommended for at least 1 year to help reduce the risk of relapse.[65][66][67]​​ See local specialist protocol for choice of appropriate TKI maintenance therapy regimen and dosing guidelines.

Monitoring post-transplant for early detection of BCR::ABL1 transcripts is important to identify patients who require further treatment before relapse occurs.[2]

Plus – supportive care

Back
ONGOING
|
partial haematological response or second chronic phase
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be available throughout the course of treatment.

Granulocyte colony-stimulating factors may be used adjunctively if anaemia, thrombocytopenia, or neutropenia occurs during any phase of treatment. Therapy causing thrombocytopenia or neutropenia may be withheld if the platelet count is <50 × 10⁹/L (<50,000/microlitre) or absolute neutrophil count is <1 × 10⁹/L (<1000/microlitre).

Other components of supportive care include blood transfusions and palliative care to manage symptoms.

transplant failure or recurrence post-transplant

1st line – tyrosine kinase inhibitor (TKI) with or without donor lymphocyte infusion or clinical trial

Back
ONGOING
|
transplant failure or recurrence post-transplant
1st line – 

tyrosine kinase inhibitor (TKI) with or without donor lymphocyte infusion or clinical trial

Options for further treatment in patients with allogeneic stem cell transplant (SCT) failure or recurrence post-transplant should be discussed with the transplant team.

A TKI, with or without donor lymphocyte infusion (DLI), may be considered.[2] One study found that imatinib combined with DLI was more effective than either treatment alone.[68]​​​ Potential complications of DLI include graft-versus-host disease and opportunistic infection due to immunosuppression.[2]

Post-transplant choice of TKI depends on prior therapy, BCR::ABL1 mutation profile, and post-transplant morbidities. Ponatinib may be an option if no other TKIs are indicated. Dasatinib may be an option for extramedullary relapse.[2][3]

Enrollment in a clinical trial with best supportive care may be an option for patients with transplant failure or recurrence post-transplant, depending on the clinical context.[2]

Evidence for different treatment strategies is limited.

Plus – supportive care

Back
ONGOING
|
transplant failure or recurrence post-transplant
Plus – 

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care should be provided throughout the course of treatment.

Granulocyte colony-stimulating factors may be used adjunctively if anaemia, thrombocytopenia, or neutropenia occurs during any phase of treatment. Therapy causing thrombocytopenia or neutropenia may be withheld if the platelet count is <50 × 10⁹/L (<50,000/microlitre) or absolute neutrophil count is <1 × 10⁹/L (<1000/microlitre).

Other components of supportive care include blood transfusions and palliative care to manage symptoms.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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