Acute promyelocytic leukemia current treatment algorithms

Abstract

In 1957, Hillestad et al. defined acute promyelocytic leukemia (APL) for the first time in the literature as a distinct type of acute myeloid leukemia (AML) with a "rapid downhill course" characterized with a severe bleeding tendency. APL, accounting for 10-15% of the newly diagnosed AML cases, results from a balanced translocation, t(15;17) (q22;q12-21), which leads to the fusion of the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA) gene. The PML-RARA fusion oncoprotein induces leukemia by blocking normal myeloid differentiation. Before using anthracyclines in APL therapy in 1973, no effective treatment was available. In the mid-1980s, all-trans retinoic acid (ATRA) monotherapy was used with high response rates, but response durations were short. Later, the development of ATRA, chemotherapy, and arsenic trioxide combinations turned APL into a highly curable malignancy. In this review, we summarize the evolution of APL therapy, focusing on key milestones that led to the standard-of-care APL therapy available today and discuss treatment algorithms and management tips to minimize induction mortality.

Fig. 1. Evolution of therapy in APL.

Acute promyelocytic leukemia milestones.

Fig. 2. Approach to suspected APL and treatment algorithm.

APL acute promyelocytic leukemia, WBC white blood cell count, PB peripheral blood, BM bone marrow, MFC multicolor flow cytometry, ATRA retinoic acid, LP lumbar puncture, CVC central venous catheter, DS differentiation syndrome, Dex dexamethasone, ATO arsenic trioxide, GO gemtuzumab ozogamicin, IDA idarubicin, I/Os intake and output, CNS central nervous system, RT-PCR reverse transcription polymerase chain reaction. *Lower risk APL: ATRA + IDA or ATRA + GO **Higher risk: ATRA + IDA or ATRA + DNR + ARA-C.

Fig. 3. ATRA plus ATO treatment schedule.

ATRA retinoic acid, ATO arsenic trioxide, mg milligram, 2/day two divided doses.