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PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review.
Cancers (Basel). 2020 May 21; 12(5)C

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.

Authors+Show Affiliations

Wroclaw Medical University, Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, 50-367 Wrocław, Poland.Hospital of Tarragona "Joan XXIII", Hematology-ICO, 43-005 Tarragona, Spain.Hospital Universitari I Politècnic La Fe, Department of Hematology, 46-009 Valencia, Spain. CIBERONC Instituto de Salud Carlos III, 28-020 Madrid, Spain.Hospital of Tarragona "Joan XXIII", Hematology-ICO, 43-005 Tarragona, Spain.University Hospital Torrecardenas, Department of Hematology, 04-009 Almeria, Spain.Istituto Portugues de Oncologi IPO, Department of Hematology, 4200-072 Porto, Portugal.Fundaleu, Department of Hematology, 1114 Buenos Aires, Argentina.Fundaleu, Department of Hematology, 1114 Buenos Aires, Argentina.University Hospital Universitario Fundacion Jimenez Diaz IIS-FJD, Department of Hematology, 28-040 Madrid, Spain.University Hospital Universitario Fundacion Jimenez Diaz IIS-FJD, Department of Hematology, 28-040 Madrid, Spain.Hospital Gregorio Maranion, Deapartment of Hematology, 28-010 Madrid, Spain.Hospital de Cruces, Department of Hematology, 48-903 Barakaldo, Spain.Hospital Universitario Dr. Negrin, Department of Hematology, 35-010 Las Palmas de Gran Canaria, Spain.Hospital Clinic, Department of Hematology, 08-036 Barcelona, Spain.Wroclaw Medical University, Department of Paediatric Bone Marrow Transplantation, Oncology and Hematology, 50-367 Wrocław, Poland.Hospital Vall d'Hebron, Department of Pediatric Hematology, 08-035 Barcelona, Spain.Clinica Universitaria de Navarra, Department of Hematology, 31-008 Pamplona, Spain.Hospital Carlos Haya, Department of Hematology, 29-014 Málaga, Spain.CIBERONC Instituto de Salud Carlos III, 28-020 Madrid, Spain. Hospital Universitari I Politècnic La Fe, Department of Molecular Biology Laboratory, 46-009 Valencia, Spain.Hospital Universitari I Politècnic La Fe, Department of Hematology, 46-009 Valencia, Spain. CIBERONC Instituto de Salud Carlos III, 28-020 Madrid, Spain.Hospital Universitari I Politècnic La Fe, Department of Hematology, 46-009 Valencia, Spain. CIBERONC Instituto de Salud Carlos III, 28-020 Madrid, Spain.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32455804

Citation

Sobas, Marta, et al. "PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: the PETHEMA Registry Experience and Systematic Literature Review." Cancers, vol. 12, no. 5, 2020.
Sobas M, Talarn-Forcadell MC, Martínez-Cuadrón D, et al. PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review. Cancers (Basel). 2020;12(5).
Sobas, M., Talarn-Forcadell, M. C., Martínez-Cuadrón, D., Escoda, L., García-Pérez, M. J., Mariz, J., Mela-Osorio, M. J., Fernández, I., Alonso-Domínguez, J. M., Cornago-Navascués, J., Rodríguez-Macias, G., Amutio, M. E., Rodríguez-Medina, C., Esteve, J., Sokół, A., Murciano-Carrillo, T., Calasanz, M. J., Barrios, M., Barragán, E., ... Montesinos, P. (2020). PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review. Cancers, 12(5). https://doi.org/10.3390/cancers12051313
Sobas M, et al. PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: the PETHEMA Registry Experience and Systematic Literature Review. Cancers (Basel). 2020 May 21;12(5) PubMed PMID: 32455804.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PLZF-RARα, NPM1-RARα, and Other Acute Promyelocytic Leukemia Variants: The PETHEMA Registry Experience and Systematic Literature Review. AU - Sobas,Marta, AU - Talarn-Forcadell,Maria Carme, AU - Martínez-Cuadrón,David, AU - Escoda,Lourdes, AU - García-Pérez,María J, AU - Mariz,Jose, AU - Mela-Osorio,María J, AU - Fernández,Isolda, AU - Alonso-Domínguez,Juan M, AU - Cornago-Navascués,Javier, AU - Rodríguez-Macias,Gabriela, AU - Amutio,María E, AU - Rodríguez-Medina,Carlos, AU - Esteve,Jordi, AU - Sokół,Agnieszka, AU - Murciano-Carrillo,Thais, AU - Calasanz,María J, AU - Barrios,Manuel, AU - Barragán,Eva, AU - Sanz,Miguel A, AU - Montesinos,Pau, Y1 - 2020/05/21/ PY - 2020/04/30/received PY - 2020/05/16/revised PY - 2020/05/18/accepted PY - 2020/5/28/entrez KW - acute promyelocytic leukemia KW - characteristics KW - outcomes KW - systematic review KW - variant JF - Cancers JO - Cancers (Basel) VL - 12 IS - 5 N2 - 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. SN - 2072-6694 UR - https://www.unboundmedicine.com/medline/citation/32455804/PLZF-RARα,_NPM1-RARα,_and_Other_Acute_Promyelocytic_Leukemia_Variants:_The_PETHEMA_Registry_Experience_and_Systematic_Literature_Review L2 - https://www.mdpi.com/resolver?pii=cancers12051313 DB - PRIME DP - Unbound Medicine ER -
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