Post-remission therapy for Philadelphia chromosome positive acute lymphoblastic leukemia in adults
- Richard A Larson, MD
Richard A Larson, MD
- Editor-in-Chief — Hematology
- Section Editor — Leukemia
- Professor of Medicine
- University of Chicago Pritzker School of Medicine
Acute lymphoblastic leukemia (ALL) refers to a group of hematopoietic neoplasms involving cells committed to the lymphoid lineage. Philadelphia chromosome positive ALL (Ph+ ALL) is a biologically and clinically distinct variant of ALL classified as ALL with t(9;22)(q34;q11.2);BCR-ABL1 in the WHO classification system . Ph+ ALL accounts for approximately 20 to 30 percent of ALL in adults and 2 to 3 percent of ALL in children [2,3].
When treated with chemotherapy alone, patients with Ph+ ALL have a uniformly poor prognosis with few survivors at five years after treatment. Allogeneic hematopoietic cell transplantation (allo-HCT) provides better results, curing approximately 30 to 60 percent of patients with Ph+ ALL. The incorporation of a BCR-ABL1 tyrosine kinase inhibitor (eg, imatinib, dasatinib) into the treatment regimen has resulted in superior response rates, thereby allowing more patients to proceed to allo-HCT. It is not yet known whether treatment with chemotherapy plus a tyrosine kinase inhibitor will provide durable long-term remissions and better survival than allo-HCT. The treatment of Ph+ ALL is distinct from that of other types of ALL and is comprised of several stages that, in total, may span three years of treatment (table 1):
●Remission induction – Induction therapy aims to reduce the total body leukemia cell population from approximately 1012 to below the cytologically detectable level of about 109 cells.
●Consolidation – Over 80 percent of adult patients with Ph+ ALL will attain a complete remission (CR) with induction chemotherapy that incorporates a tyrosine kinase inhibitor. However, without additional cytotoxic therapy, virtually all of these patients will relapse within a few weeks or months despite continuing a tyrosine kinase inhibitor. In contrast, patients who receive post-remission therapy may expect five-year survival rates of 40 to 60 percent. Post-remission therapy includes an early allo-HCT or the continuation of chemotherapy plus a tyrosine kinase inhibitor.
●Maintenance – Remission maintenance therapy, sometimes called continuation therapy, is a standard component of the management of non-Ph+ ALL and is generally given for two to three years after consolidation chemotherapy. Maintenance chemotherapy is not used after allo-HCT for most patients with ALL; however, a tyrosine kinase inhibitor may be offered as maintenance after allo-HCT to some patients who had Ph+ ALL.
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- POST-REMISSION THERAPY
- Overview of post-remission therapy
- Allogeneic HCT
- Autologous HCT
- TKI-based consolidation chemotherapy
- EVALUATING RESPONSE AFTER CONSOLIDATION
- MAINTENANCE THERAPY
- After transplantation
- After consolidation chemotherapy
- RELAPSED DISEASE
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS