ACUTE PROMYELOCYTIC LEUKEMIA IN CHILDREN: A SINGLE CENTRE EXPERIENCE FROM TURKEY

Tekin Aksu
  • Tekin Aksu
    University of Health Sciences, Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital, Turkey | tekinaksu@gmail.com

Abstract

Background and objectives: Acute promyelocytic leukemia (APL), characterized by tendency to hemorrhage and excellent response to all-trans retinoic acid (ATRA), is a distinct subtype of acute myeloid leukemia (AML). In this retrospective study, we aimed to determine the incidence, clinical symptoms, toxicities and outcome of children with APL in our center. Methods: We retrospectively reviewed the medical records of children (age < 18 years) diagnosed with APL at our pediatric hematology department between January 2006-December 2016.

Results: Pediatric APL represents 20.5% of AML cases in this cohort. Most of the cases presented as classical M3, albeit hypogranular variant was described in 12% of the cohort. Patients with hypogranular variant APL were differed from classical APL by co-expression of CD2 and CD34. About ¾ of APL patients had hemorrhagic findings at admission or at initial phase of the treatment. Severe bleeding manifested as intracranial hemorrhage was present in three patients and intracranial arterial thrombosis was present in one. Five patients showed side effects of ATRA such as pseudotumor cerebri, dilated cardiomyopathy, and pulmonary infiltrates. Six year overall survival (OS) and early death rate was found to be 82.5% and 12% respectively.

Conclusions: A high frequency (20.5%) of APL was noted among children with AML in this single center study. The overall mortality rate was 17.5%. Since the induction death rate was 12% and life threatening bleeding was the major problem, awareness and urgent treatment are critical factors to reduce early losses.  

Keywords

Acute promyelocytic leukemia; Hypogranular variant APL; ATRA toxicity

Full Text:

PDF
HTML
Submitted: 2018-01-20 17:31:15
Published: 2018-07-01 00:00:00
Search for citations in Google Scholar
Related articles: Google Scholar

References

Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med. 1985 ;103:620-5

Zhang L, Samad A, Pombo-de-Oliveira MS, Scelo G, Smith MT, Feusner J, Wiemels JL, Metayer C. Global characteristics of childhood acute promyelocytic leukemia. Blood Rev. 2015;29:101-25

Kömür M, Erbey F, Bayram I, Tanyeli A. Incidence and prognostic importance of molecular genetic defects in children with acute myeloblastic leukemia. Asian Pac J Cancer Prev. 2010;11:1393-5

Longo L, Pandolfi PP, Biondi A, Rambaldi A, Mencarelli A, Lo Coco F, Diverio D, Pegoraro L, Avanzi G, Tabilio A, Zangrilli D, Alcalay M, Donti E, Grignani F, Pelicci PG. Rearrangements and aberrant expression of the retinoic acid receptor alpha gene in acute promyelocytic leukemias. J Exp Med. 1990;172:1571-5

Lo-Coco F, Ammatuna E, Montesinos P, Sanz MA. Acute promyelocytic leukemia: recent advances in diagnosis and management. Semin Oncol. 2008;35:401-9

Yan W, Zhang G. Molecular Characteristics and Clinical Significance of 12 Fusion Genes in Acute Promyelocytic Leukemia: A Systematic Review. Acta Haematol. 2016;136:1-15

Calleja EM, Warrell RP Jr. Differentiating agents in pediatric malignancies: all-trans-retinoic acid and arsenic in acute promyelocytic leukemia. Curr Oncol Rep. 2000 ;2(6):519-23

Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wanq ZY. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988;72:567-72

Abla O, Ribeiro RC. How I treat children and adolescents with acute promyelocytic leukaemia. Br J Haematol. 2014;164:24-38

Mathews V, George B, Lakshmi KM, Viswabandya A, Bajel A, Balasubramanian P, Shaji RV, Srivastava VM, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006;107:2627-32

Kelaidi C, Chevret S, De Botton S, Raffoux E, Guerci A, Thomas X, Pigneux A, Lamy T, Rigal-Huguet F, Meyer-Monard S, Chevallier P, Maloisel F, Deconinck E, Ferrant A, Fegueux N, Ifrah N, Sanz M, Dombret H, Fenaux P, Adès L. Improved outcome of acute promyelocytic leukemia with high WBC counts over the last 15 years: the European APL Group experience. J Clin Oncol. 2009;27:2668-76

Testi AM, Biondi A, Lo Coco F, Moleti ML, Giona F, Vignetti M, Menna G, Locatelli F, Pession A, Barisone E, De Rossi G, Diverio D, Micalizzi C, Aricò M, Basso G, Foa R, Mandelli F. GIMEMA-AIEOPAIDA protocol for the treatment of newly diagnosed acute promyelocytic leukemia (APL) in children. Blood. 2005;106:447-53

Creutzig U, Zimmermann M, Bourquin JP, Dworzak MN, Fleischhack G, Graf N, Klingebiel T, Kremens B, Lehrnbecher T, von Neuhoff C, Ritter J, Sander A, Schrauder A, von Stackelberg A, Starý J, Reinhardt D. Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004. Blood. 2013;122:37-43

Cheson BD, Cassileth PA, Head DR, Schiffer CA, Bennett JM, Bloomfield CD, Brunning R, Gale RP, Grever MR, Keating MJ. Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol. 1990;8:813-9

Frankel SR, Eardley A, Lauwers G, Weiss M, Warrell RP Jr. The "retinoic acid syndrome" in acute promyelocytic leukemia. Ann Intern Med. 1992;117:292-6

Sainty D, Liso V, Cantù-Rajnoldi A, Head D, Mozziconacci MJ, Arnoulet C, Benattar L, Fenu S, Mancini M, Duchayne E, Mahon FX, Gutierrez N, Birg F, Biondi A, Grimwade D, Lafage-Pochitaloff M, Hagemeijer A, Flandrin G; Groupe Français d'Hématologie Cellulaire; Groupe Français de Cytogénétique Hématologique; UK Cancer Cytogenetics Group; BIOMED 1 European Community-Concerted Action "Molecular Cytogenetic Diagnosis in Haematological Malignancies". A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements. Blood. 2000;96:1287-96

Gorczyca W. Acute promyelocytic leukemia: four distinct patterns by flow cytometry immunophenotyping. Pol J Pathol. 2012;63:8-17

Albano F, Mestice A, Pannunzio A, Lanza F, Martino B, Pastore D, Ferrara F, Carluccio P, Nobile F, Castoldi G, Liso V, Specchia G. The biological characteristics of CD34+ CD2+ adult acute promyelocytic leukemia and the CD34 CD2 hypergranular (M3) and microgranular (M3v) phenotypes. Haematologica. 2006;91:311-6

Cicconi L, Lo-Coco F. Current management of newly diagnosed acute promyelocytic leukemia. Ann Oncol. 2016;27:1474-81

Stein EM, Tallman MS. Acute promyelocytic leukemia in children and adolescents. Acta Haematol. 2014;132:307-12

Takahashi H, Watanabe T, Kinoshita A, Yuza Y, Moritake H, Terui K, Iwamoto S, Nakayama H, Shimada A, Kudo K, Taki T, Yabe M, Matsushita H, Yamashita Y, Koike K, Ogawa A, Kosaka Y, Tomizawa D, Taga T, Saito AM, Horibe K, Nakahata T, Miyachi H, Tawa A, Adachi S. High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group. Br J Haematol. 2016;174:437-43

Abla O, Ribeiro RC, Testi AM, Montesinos P, Creutzig U, Sung L, Di Giuseppe G, Stephens D, Feusner JH, Powell BL, Hasle H, Kaspers GJL, Dalla-Pozza L, Lassaletta A, Tallman MS, Locatelli F, Reinhardt D, Lo-Coco F, Hitzler J, Sanz MA. Predictors of thrombohemorrhagic early death in children and adolescents with t(15;17)-positive acute promyelocytic leukemia treated with ATRA and chemotherapy. Ann Hematol. 2017;96(9):1449-1456

Mantha S, Goldman DA, Devlin SM, Lee JW, Zannino D, Collins M, Douer D, Iland HJ, Litzow MR, Stein EM, Appelbaum FR, Larson RA, Stone R, Powell BL, Geyer S, Laumann K, Rowe JM, Erba H, Coutre S, Othus M, Park JH, Wiernik PH, Tallman MS. Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era. Blood. 2017;129:1763-1767

Zhou J, Zhang Y, Li J, Li X, Hou J, Zhao Y, Liu X, Han X, Hu L, Wang S, Zhao Y, Zhang Y, Fan S, Lv C, Li L, Zhu L. Single-agent arsenic trioxide in the treatment of children with newly diagnosed acute promyelocytic leukemia. Blood. 2010;115:1697-702

Coombs CC, DeAngelis LM, Feusner JH, Rowe JM, Tallman MS. Pseudotumor Cerebri in Acute Promyelocytic Leukemia Patients on Intergroup Protocol 0129: Clinical Description and Recommendations for New Diagnostic Criteria. Clin Lymphoma Myeloma Leuk. 2016;16:146-51

de Botton S, Coiteux V, Chevret S, Rayon C, Vilmer E, Sanz M, de La Serna J, Philippe N, Baruchel A, Leverger G, Robert A, San Miguel J, Conde E, Sotto JJ, Bordessoule D, Fegueux N, Fey M, Parry A, Chomienne C, Degos L, Fenaux P. Outcome of childhood acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy. J Clin Oncol. 2004;22:1404-12

Abstract views:
184

Views:
PDF
10
HTML
18

Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM


Copyright (c) 2018 Mediterranean Journal of Hematology and Infectious Diseases

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
 
© PAGEPress 2008-2018     -     PAGEPress is a registered trademark property of PAGEPress srl, Italy.     -     VAT: IT02125780185     •     Privacy