TY - JOUR
T1 - Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
AU - Abou Dalle, Iman
AU - Jabbour, Elias
AU - Short, Nicholas J.
AU - Ravandi, Farhad
N1 - Funding Information:
Iman Abou Dalle declares that she has no conflict of interest. Elias Jabbour has received research funding from Takeda, Pfizer, and Amgen.
Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - With the introduction of tyrosine kinase inhibitors (TKIs) in the management of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the prognosis of patients has improved dramatically. Currently, the standard of care in the frontline setting for fit patients is TKI in combination with chemotherapy. Age-adjusted chemotherapy or corticosteroids alone have been used with TKIs in elderly patients with comorbidities with modest long-term benefit. The primary goal of treatment is the achievement of early deep molecular remission as the achievement of complete molecular remission (CMR) at 3 months has been demonstrated to be predictive of higher long-term survival. The probability of attaining this goal by a more potent TKIs like dasatinib or ponatinib is higher, thus we recommend the use of second- or third-generation TKIs over imatinib. Clinicians should be aware of possible fatal cardiovascular events mainly related to ponatinib. Allogeneic hematopoietic stem cell transplantation (alloHSCT) should still be considered in first remission, especially for younger patients treated with imatinib combination therapy. A subset of patients achieving CMR at 3 months may be able to continue consolidation and maintenance with chemotherapy and TKI without the need for alloHSCT. Because of higher risk of relapses in the central nervous system, intrathecal chemoprophylaxis is mandatory for all patients. New strategies incorporating novel agents, such as antibody-drug conjugates, bispecific monoclonal antibodies, potent TKIs, and CAR T cells are under investigation.
AB - With the introduction of tyrosine kinase inhibitors (TKIs) in the management of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), the prognosis of patients has improved dramatically. Currently, the standard of care in the frontline setting for fit patients is TKI in combination with chemotherapy. Age-adjusted chemotherapy or corticosteroids alone have been used with TKIs in elderly patients with comorbidities with modest long-term benefit. The primary goal of treatment is the achievement of early deep molecular remission as the achievement of complete molecular remission (CMR) at 3 months has been demonstrated to be predictive of higher long-term survival. The probability of attaining this goal by a more potent TKIs like dasatinib or ponatinib is higher, thus we recommend the use of second- or third-generation TKIs over imatinib. Clinicians should be aware of possible fatal cardiovascular events mainly related to ponatinib. Allogeneic hematopoietic stem cell transplantation (alloHSCT) should still be considered in first remission, especially for younger patients treated with imatinib combination therapy. A subset of patients achieving CMR at 3 months may be able to continue consolidation and maintenance with chemotherapy and TKI without the need for alloHSCT. Because of higher risk of relapses in the central nervous system, intrathecal chemoprophylaxis is mandatory for all patients. New strategies incorporating novel agents, such as antibody-drug conjugates, bispecific monoclonal antibodies, potent TKIs, and CAR T cells are under investigation.
KW - Acute lymphoblastic leukemia
KW - Allogeneic stem cell transplantation
KW - BCR-ABL
KW - Blinatumomab
KW - Inotuzumab
KW - Tyrosine kinase inhibitor
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U2 - 10.1007/s11864-019-0603-z
DO - 10.1007/s11864-019-0603-z
M3 - Review article
C2 - 30675645
AN - SCOPUS:85060375073
SN - 1527-2729
VL - 20
JO - Current treatment options in oncology
JF - Current treatment options in oncology
IS - 1
M1 - 4
ER -