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Review
. 2020 May 21;12(5):1313.
doi: 10.3390/cancers12051313.

PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review

Marta Sobas  1 , Maria Carme Talarn-Forcadell  2 , David Martínez-Cuadrón  3   4 , Lourdes Escoda  2 , María J García-Pérez  5 , Jose Mariz  6 , María J Mela-Osorio  7 , Isolda Fernández  7 , Juan M Alonso-Domínguez  8 , Javier Cornago-Navascués  8 , Gabriela Rodríguez-Macias  9 , María E Amutio  10 , Carlos Rodríguez-Medina  11 , Jordi Esteve  12 , Agnieszka Sokół  13 , Thais Murciano-Carrillo  14 , María J Calasanz  15 , Manuel Barrios  16 , Eva Barragán  4   17 , Miguel A Sanz  3   4 , Pau Montesinos  3   4
Affiliations
Review

PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review

Marta Sobas et al. Cancers (Basel). .

Abstract

It has been suggested that 1-2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RARα) fusion gene, with the promyelocytic leukaemia zinc finger (PLZF)/RARα being the most frequent. Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RARα and other variant APLs. Herein, we analyze the incidence, characteristics, and outcomes of variant APLs reported to the multinational PETHEMA (Programa para el Tratamiento de Hemopatias Malignas) registry, and we perform a systematic review in order to shed light on strategies to improve management of these extremely rare diseases. Of 2895 patients with genetically confirmed APL in the PETHEMA registry, 11 had variant APL (0.4%) (9 PLZF-RARα and 2 NPM1-RARα), 9 were men, with median age of 44.6 years (3 months to 76 years), median leucocytes (WBC) 16.8 × 109/L, and frequent coagulopathy. Eight patients were treated with ATRA plus chemotherapy-based regimens, and 3 with chemotherapy-based. As compared to previous reports, complete remission and survival was slightly better in our cohort, with 73% complete remission (CR) and 73% survival despite a high relapse rate (43%). After analyzing our series and performing a comprehensive and critical review of the literature, strong recommendations on appropriate management of variant APL are not possible due to the low number and heterogeneity of patients reported so far.

Keywords: acute promyelocytic leukemia; characteristics; outcomes; systematic review; variant.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

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