Plzf-rarα, npm1-rarα, and other acute promyelocytic leukemia variants: The pethema registry experience and systematic literature review

June 21, 2020

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Publicated to: Cancers. 12 (5): 1313- - 2020-05-01 12(5), DOI: 10.3390/cancers12051313

Authors: Sobas M; Talarn-forcadell MC; Martínez-cuadrón D; Escoda L; García-pérez MJ; Mariz J; Mela-osorio MJ; Fernández I; Alonso-domínguez JM; Cornago-navascués J; Rodríguez-macias G; Amutio ME; Rodríguez-medina C; Esteve J; Sokół A; Murciano-carrillo T; Calasanz MJ; Barrios M; Barragán E; Sanz MA; Montesinos P

Affiliations

CIBERONC Inst Salud Carlos III, Madrid 28020, Spain - Author

Clin Univ Navarra, Dept Hematol, Pamplona 31008, Spain - Author

Clínica Universitaria de Navarra - Author

Complejo Hospitalario Torrecardenas de Almeria - Author

Fundacion para Combatir La Leucemia - Author

Fundaleu, Dept Hematol, RA-1114 Buenos Aires, DF, Argentina - Author

Hosp Carlos Haya, Dept Hematol, Malaga 29014, Spain - Author

Hosp Clin Barcelona, Dept Hematol, Barcelona 08036, Spain - Author

Hosp Cruces, Dept Hematol, Baracaldo 48903, Spain - Author

Hosp Gregorio Maran, Deapartment Hematol, Madrid 28010, Spain - Author

Hosp Tarragona Joan XXIII, Hematol ICO, Tarragona 43005, Spain - Author

Hosp Univ Dr Negrin, Dept Hematol, Las Palmas Gran Canaria 35010, Spain - Author

Hosp Univ I Politecn La Fe, Dept Hematol, Valencia 46009, Spain - Author

Hosp Univ I Politecn La Fe, Dept Mol Biol Lab, Valencia 46009, Spain - Author

Hosp Valle De Hebron, Dept Pediat Hematol, Barcelona 08035, Spain - Author

Hospital Clinic Barcelona - Author

Hospital de Gran Canaria Dr. Negrin - Author

Hospital Gregorio Maranion - Author

Hospital Regional Universitario Carlos Haya - Author

Hospital Universitari de Tarragona Joan XXIII - Author

Hospital Universitari I Politècnic la Fe - Author

Hospital Universitari Vall d'Hebron - Author

Hospital Universitario Fundacion Jimenez Diaz - Author

Instituto de Salud Carlos III - Author

Instituto Portugues de Oncologia de Francisco Gentil Porto - Author

Ist Portugues Oncol IPO, Dept Hematol, P-4200072 Porto, Portugal - Author

Osakidetza, Cruces University Hospital - Author

Univ Hosp Torrecardenas, Dept Hematol, Almeria 04009, Spain - Author

Univ Hosp Univ Fdn Jimenez Diaz IIS FJD, Dept Hematol, Madrid 28040, Spain - Author

Wroclaw Med Univ, Dept Hematol, Blood Neoplasms & Bone Marrow Transplantat, PL-50367 Wroclaw, Poland - Author

Wroclaw Med Univ, Dept Paediat Bone Marrow Transplantat Oncol & Hem, PL-50367 Wroclaw, Poland - Author

Wroclaw Medical University - Author

Abstract

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. 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 leukemiacharacteristicsoutcomessystematic reviewAcute promyelocytic leukemiaAplArsenic trioxideCharacteristicsCytogenetic characterizationFusion geneMolecular characterizationOutcomesPlzf-rar-alphaReceptor-alphaRisk-adapted treatmentSystematic reviewTrans-retinoic acidTranslocationVariant

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Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cancers due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position 51/242, thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-12-15:

WoS: 14
Scopus: 3
Europe PMC: 9

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This work has been carried out with international collaboration, specifically with researchers from: Argentina; Poland; Portugal.

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