Treatment of blast phase chronic myeloid leukaemia: A rare and challenging entity

Copland, Mhairi

doi:10.1111/bjh.18370

Cited by 18 publications

(16 citation statements)

References 102 publications

(240 reference statements)

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“…The general aim of curative therapy in adult patients is to reduce the blast population to reach a CP and to proceed with allogeneic HSCT [34,35]. Selection of the optimal patient-specific therapeutic pathway depends on the BP phenotype, the presence of BCR::ABL1 kinase domain mutations, previous therapy for secondary CML-BP, and the availability of suitable stem cell donors.…”

Section: Treatment Principles In Cml-bpmentioning

confidence: 99%

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Management of children and adolescents with chronic myeloid leukemia in blast phase: International pediatric CML expert panel recommendations

et al. 2023

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Treatment of chronic myeloid leukemia has improved significantly with the introduction of tyrosine kinase inhibitors (TKIs), and treatment guidelines based on numerous clinical trials are available for chronic phase disease. However for CML in the blast phase (CML-BP), prognosis remains poor and treatment options are much more limited. The spectrum of treatment strategies for children and adolescents with CML-BP has largely evolved empirically and includes treatment principles derived from adult CML-BP and pediatric acute leukemia. Given this heterogeneity of treatment approaches, we formed an international panel of pediatric CML experts to develop recommendations for consistent therapy in children and adolescents with this high-risk disease based on the current literature and national standards. Recommendations include detailed information on initial diagnosis and treatment monitoring, differentiation from Philadelphia-positive acute leukemia, subtype-specific selection of induction therapy, and combination with tyrosine kinase inhibitors. Given that allogeneic hematopoietic stem cell transplantation currently remains the primary curative intervention for CML-BP, we also provide recommendations for the timing of transplantation, donor and graft selection, selection of a conditioning regimen and prophylaxis for graft-versus-host disease, post-transplant TKI therapy, and management of molecular relapse. Management according to the treatment recommendations presented here is intended to provide the basis for the design of future prospective clinical trials to improve outcomes for this challenging disease.

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Section: Treatment Principles In Cml-bpmentioning

confidence: 99%

“…In adult patients, the preferred curative approach combines the use of lineage-specific induction chemotherapy with a TKI [34,35]. Therapeutic approaches with documented tolerable toxicities that can be combined with TKI therapy include hyperCVAD and Ida-FLAG [41][42][43].…”

Section: Treatment Of Cml-bp Lymphoid Phenotypementioning

confidence: 99%

Management of children and adolescents with chronic myeloid leukemia in blast phase: International pediatric CML expert panel recommendations

et al. 2023

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“…Consideration of mutation analysis and patient characteristics, including co-morbidities, should then be made to provide individualised treatment decisions. Ponatinib remains reserved for those patients where a T315I mutation is present or where there has been failure of two previous lines of therapy (Hehlmann, 2020 ; Copland, 2022 ; Copland et al, 2022 ).…”

Section: Choosing the Right Therapymentioning

confidence: 99%

“…In those progressing to BP on TKI, the approach is similar, however, ponatinib may be more attractive here. This approach has been supported in the recently published phase 1/2 MATCHPOINT trial which used either 1 or 2 cycles of fludarabine, cytarabine, granulocyte-colony stimulating factor and idarubicin (FLAG-IDA) chemotherapy in combination with ponatinib 30 mg daily before proceeding to alloHSCT with median OS of 12 months and 41% of patients being alive at 3 years (Copland, 2022 ; Copland et al, 2022 ).…”

Section: Choosing the Right Therapymentioning

confidence: 99%

Targeting BCR-ABL1-positive leukaemias: a review article

Leak

Horne

Copland

2023

Camb. prisms Precis. med.

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Leukaemia describes a mixed group of cancers affecting blood cell development. Its management has changed drastically over the past 40 years and with this we have seen significant improvements in patient outcomes. These advances have come about through continued research into the underpinning mechanisms driving leukaemia development.In addition to better treatments for leukaemia, our understanding of the genes which cause leukaemia has improved. This review focuses on the blood cancer-causing gene BCR::ABL1 which results from an abnormal join between two chromosomes, 9 and 22. The BCR::ABL1 gene most commonly leads to a blood cancer called chronic myeloid leukaemia (CML), but can also cause an acute leukaemia, more commonly Acute Lymphoblastic Leukaemia and rarely, Acute Myeloid Leukaemia.Our knowledge of how the BCR::ABL1 gene and resulting protein drive cancer cell progression and survival through complex processes within the cell which promote cell growth and switch off normal cell death pathways. At the same time, targeted treatments have been developed which directly stop BCR::ABL from affecting cell growth and survival, replacing traditional, more toxic chemotherapy drugs which have a blanket effect on all developing cells, both healthy and cancer cells. These new drugs are called tyrosine kinase inhibitors or "TKIs"; the first of which was designed nearly 25 years ago, and is now called imatinib (trade name "Gleevec" or "Glivec"). TKIs have led to much improved survival for patients, especially with CML, but also reduced toxicity and improved quality of life. Indeed patients with the most benign phase of CML, termed chronic phase, if responding to these targeted drugs, can expect normal life expectancy. This paper will discuss the advances made in BCR::ABL1-positive leukaemias, and discuss ongoing issues with their use and highlight where research must now focus to continue to improve outcomes for patients through precision medicine.

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“…Nevertheless, in contrast to major advances in chronic phase (CP) CML, outcome is still dismal for this important minority of patients [ 15 , 16 ]. BP can be of myeloid, lymphoid, mixed, or megakaryoblastic phenotype, can evolve from a previous CML, but can also be the disease presentation at diagnosis, the so-called de novo BP [ 11 , 12 ]. Treatment of BP with TKI monotherapy often leads to short-term remissions, with inevitably almost all patients experiencing a disease relapse if alloSCT is not performed [ 17 – 22 ].…”

Section: Introductionmentioning

confidence: 99%

Management and outcome of patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era – analysis of the European LeukemiaNet Blast Phase Registry

Brioli,

Lomaia,

Fabisch

et al. 2024

Leukemia

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Blast phase (BP) of chronic myeloid leukemia (CML) still represents an unmet clinical need with a dismal prognosis. Due to the rarity of the condition and the heterogeneity of the biology and clinical presentation, prospective trials and concise treatment recommendations are lacking. Here we present the analysis of the European LeukemiaNet Blast Phase Registry, an international collection of the clinical presentation, treatment and outcome of blast phases which had been diagnosed in CML patients after 2015. Data reveal the expected heterogeneity of the entity, lacking a clear treatment standard. Outcomes remain dismal, with a median overall survival of 23.8 months (median follow up 27.8 months). Allogeneic stem cell transplantation (alloSCT) increases the rate of deep molecular responses. De novo BP and BP evolving from a previous CML do show slightly different features, suggesting a different biology between the two entities. Data show that outside clinical trials and in a real-world setting treatment of blast phase is individualized according to disease- and patient-related characteristics, with the aim of blast clearance prior to allogeneic stem cell transplantation. AlloSCT should be offered to all patients eligible for this procedure.

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Treatment of blast phase chronic myeloid leukaemia: A rare and challenging entity

Cited by 18 publications

References 102 publications

Management of children and adolescents with chronic myeloid leukemia in blast phase: International pediatric CML expert panel recommendations

Management of children and adolescents with chronic myeloid leukemia in blast phase: International pediatric CML expert panel recommendations

Targeting BCR-ABL1-positive leukaemias: a review article

Management and outcome of patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era – analysis of the European LeukemiaNet Blast Phase Registry

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