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:
●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.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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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