Prevention of Early Death in Very Elderly Acute Promyelocytic Leukemia Patients Using Lower Induction Doses of All-trans Retinoic Acid
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Acute promyelocytic leukemia, induction death, ATRA, arsenic trioxide
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1. Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21.
2. Jácomo RH, Melo RA, Souto FR, de Mattos ER, de Oliveira CT, Fagundes EM, Bittencourt HN, Bittencourt RI, Bortolheiro TC, Paton EJ, Bendlin R, Ismael S, Chauffaille Mde L, Silva D, Pagnano KB, Ribeiro R, Rego EM. Clinical features and outcomes of 134 Brazilians with acute promyelocytic leukemia who received ATRA and anthracyclines. Haematologica. 2007 Oct;92(10):1431-2.
3. Lehmann S, Ravn A, Carlsson L, Antunovic P, Deneberg S, Möllgård L, Derolf AR, Stockelberg D, Tidefelt U, Wahlin A, Wennström L, Höglund M, Juliusson G. Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. Leukemia. 2011 Jul;25(7):1128-34. doi: 10.1038/leu.2011.78. Epub 2011 Apr 19.
4. Park JH, Qiao B, Panageas KS, Schymura MJ, Jurcic JG, Rosenblat TL, Altman JK, Douer D, Rowe JM, Tallman MS. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood. 2011 Aug 4;118(5):1248-54.
5. Lengfelder E, Hanfstein B, Haferlach C, Braess J, Krug U, Spiekermann K, Haferlach T, Kreuzer KA, Serve H, Horst HA, Schnittger S, Aul C, Schultheis B, Erben P, Schneider S, Müller-Tidow C, Wörmann B, Berdel WE, Sauerland C, Heinecke A, Hehlmann R, Hofmann WK, Hiddemann W, Büchner T; German Acute Myeloid Leukemia Cooperative Group (AMLCG). Outcome of elderly patients with acute promyelocytic leukemia: results of the German Acute Myeloid Leukemia Cooperative Group. Ann Hematol. 2013 Jan;92(1):41-52. Epub 2012 Oct 23.
6. Jillella AP, Arellano ML, Gaddh M, Langston AA, Heffner LT, Winton EF, McLemore ML, Zhang C, Caprara CR, Simon KS, Bolds SL, DeBragga S, Karkhanis P, Krishnamurthy SH, Tongol J, El Geneidy MM, Pati A, Gerber JM, Grunwald MR, Cortes J, Bashey A, Stuart RK, Kota VK. Comanagement Strategy Between Academic Institutions and Community Practices to Reduce Induction Mortality in Acute Promyelocytic Leukemia. JCO Oncol Pract. 2021 Apr;17(4):e497-e505. Epub 2020 Oct 30.
7. Jin B, Zhang Y, Hou W, Cao F, Lu M, Yang H, Tian X, Wang Y, Hou J, Fu J, Li H, Zhou J. Comparative analysis of causes and predictors of early death in elderly and young patients with acute promyelocytic leukemia treated with arsenic trioxide. J Cancer Res Clin Oncol. 2020 Feb;146(2):485-492. Epub 2019 Nov 4.
8. Testi AM, D'Angiò M, Locatelli F, Pession A, Lo Coco F. Acute Promyelocytic Leukemia (APL): Comparison Between Children and Adults. Mediterr J Hematol Infect Dis. 2014 Apr 15;6(1):e2014032.
9. Ortega JJ, Madero L, Martín G, Verdeguer A, García P, Parody R, Fuster J, Molines A, Novo A, Debén G, Rodríguez A, Conde E, de la Serna J, Allegue MJ, Capote FJ, González JD, Bolufer P, González M, Sanz MA; PETHEMA Group. Treatment with all-trans retinoic acid and anthracycline monochemotherapy for children with acute promyelocytic leukemia: a multicenter study by the PETHEMA Group. J Clin Oncol. 2005 Oct 20;23(30):7632-40.
10. Castaigne S, Lefebvre P, Chomienne C, Suc E, Rigal-Huguet F, Gardin C, Delmer A, Archimbaud E, Tilly H, Janvier M, et al. Effectiveness and pharmacokinetics of low-dose all-trans retinoic acid (25 mg/m2) in acute promyelocytic leukemia. Blood. 1993 Dec 15;82(12):3560-3.
11. Jillella AP, Lee SJ, Altman JK, Luger SM, Tallman MS, Foran JM, Bradshaw D, Law LY, Bryan LJ, Abou Zahr A, Begna KH, Perl AE, Vadakara JJL, Qamar R, Bergan RC, Fisch MJ, Carlos RC, Wagner LI, Kota VK, Litzow MR. Academic Community Partnership in Acute Promyelocytic Leukemia and Early Mortality: The ECOG-ACRIN EA9131 Trial. JAMA Oncol. 2025 Feb 27:e247033.
12. Jillella AP, Karkhanis P, Sharma R, Bolds S, Shrestha A, Sitchenko K, Jonnalagadda V, Gaddh M, Bernal-Mizrachi L, Heffner LT, Winton EF, McLemore ML, Langston A, Galipeau J, Bodó I, Al-Kadhimi Z, Bashey A, Stuart RK, Vidito S, Pati A, Gerber JM, Grunwald MR, Bradley KT, Tongol J, El-Geneidy M, Khoury HJ, Arellano M, Kota V. A Multi-Center Prospective Study Utilizing a Simplified Treatment Algorithm Complemented By Expert Support Decreases Induction Mortality and Improves Survival in Acute Promyelocytic Leukemia (APL). Results of the APL Trial in Georgia, South Carolina and Neighboring States. Blood 2016; 128 (22): 2793.
13. Lo-Coco F, Avvisati G, Vignetti M, Breccia M, Gallo E, Rambaldi A, Paoloni F, Fioritoni G, Ferrara F, Specchia G, Cimino G, Diverio D, Borlenghi E, Martinelli G, Di Raimondo F, Di Bona E, Fazi P, Peta A, Bosi A, Carella AM, Fabbiano F, Pogliani EM, Petti MC, Amadori S, Mandelli F; Italian GIMEMA Cooperative Group. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood. 2010 Oct 28;116(17):3171-9.
14. Montesinos P, Sanz MA. The differentiation syndrome in patients with acute promyelocytic leukemia: experience of the pethema group and review of the literature. Mediterr J Hematol Infect Dis. 2011;3(1):e2011059. Epub 2011 Dec 4.
15. Stahl M, Tallman MS. Differentiation syndrome in acute promyelocytic leukaemia. Br J Haematol. 2019 Oct;187(2):157-162.
16. Wen J, Xu F, Zhou Q, Shi L, Liu Y, Yue J, Zhang Y, Liang X. Effects of peripheral blood leukocyte count and tumor necrosis factor-alpha on early death in acute promyelocytic leukemia. BMC Cancer. 2023 Jan 7;23(1):27
2. Jácomo RH, Melo RA, Souto FR, de Mattos ER, de Oliveira CT, Fagundes EM, Bittencourt HN, Bittencourt RI, Bortolheiro TC, Paton EJ, Bendlin R, Ismael S, Chauffaille Mde L, Silva D, Pagnano KB, Ribeiro R, Rego EM. Clinical features and outcomes of 134 Brazilians with acute promyelocytic leukemia who received ATRA and anthracyclines. Haematologica. 2007 Oct;92(10):1431-2.
3. Lehmann S, Ravn A, Carlsson L, Antunovic P, Deneberg S, Möllgård L, Derolf AR, Stockelberg D, Tidefelt U, Wahlin A, Wennström L, Höglund M, Juliusson G. Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. Leukemia. 2011 Jul;25(7):1128-34. doi: 10.1038/leu.2011.78. Epub 2011 Apr 19.
4. Park JH, Qiao B, Panageas KS, Schymura MJ, Jurcic JG, Rosenblat TL, Altman JK, Douer D, Rowe JM, Tallman MS. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood. 2011 Aug 4;118(5):1248-54.
5. Lengfelder E, Hanfstein B, Haferlach C, Braess J, Krug U, Spiekermann K, Haferlach T, Kreuzer KA, Serve H, Horst HA, Schnittger S, Aul C, Schultheis B, Erben P, Schneider S, Müller-Tidow C, Wörmann B, Berdel WE, Sauerland C, Heinecke A, Hehlmann R, Hofmann WK, Hiddemann W, Büchner T; German Acute Myeloid Leukemia Cooperative Group (AMLCG). Outcome of elderly patients with acute promyelocytic leukemia: results of the German Acute Myeloid Leukemia Cooperative Group. Ann Hematol. 2013 Jan;92(1):41-52. Epub 2012 Oct 23.
6. Jillella AP, Arellano ML, Gaddh M, Langston AA, Heffner LT, Winton EF, McLemore ML, Zhang C, Caprara CR, Simon KS, Bolds SL, DeBragga S, Karkhanis P, Krishnamurthy SH, Tongol J, El Geneidy MM, Pati A, Gerber JM, Grunwald MR, Cortes J, Bashey A, Stuart RK, Kota VK. Comanagement Strategy Between Academic Institutions and Community Practices to Reduce Induction Mortality in Acute Promyelocytic Leukemia. JCO Oncol Pract. 2021 Apr;17(4):e497-e505. Epub 2020 Oct 30.
7. Jin B, Zhang Y, Hou W, Cao F, Lu M, Yang H, Tian X, Wang Y, Hou J, Fu J, Li H, Zhou J. Comparative analysis of causes and predictors of early death in elderly and young patients with acute promyelocytic leukemia treated with arsenic trioxide. J Cancer Res Clin Oncol. 2020 Feb;146(2):485-492. Epub 2019 Nov 4.
8. Testi AM, D'Angiò M, Locatelli F, Pession A, Lo Coco F. Acute Promyelocytic Leukemia (APL): Comparison Between Children and Adults. Mediterr J Hematol Infect Dis. 2014 Apr 15;6(1):e2014032.
9. Ortega JJ, Madero L, Martín G, Verdeguer A, García P, Parody R, Fuster J, Molines A, Novo A, Debén G, Rodríguez A, Conde E, de la Serna J, Allegue MJ, Capote FJ, González JD, Bolufer P, González M, Sanz MA; PETHEMA Group. Treatment with all-trans retinoic acid and anthracycline monochemotherapy for children with acute promyelocytic leukemia: a multicenter study by the PETHEMA Group. J Clin Oncol. 2005 Oct 20;23(30):7632-40.
10. Castaigne S, Lefebvre P, Chomienne C, Suc E, Rigal-Huguet F, Gardin C, Delmer A, Archimbaud E, Tilly H, Janvier M, et al. Effectiveness and pharmacokinetics of low-dose all-trans retinoic acid (25 mg/m2) in acute promyelocytic leukemia. Blood. 1993 Dec 15;82(12):3560-3.
11. Jillella AP, Lee SJ, Altman JK, Luger SM, Tallman MS, Foran JM, Bradshaw D, Law LY, Bryan LJ, Abou Zahr A, Begna KH, Perl AE, Vadakara JJL, Qamar R, Bergan RC, Fisch MJ, Carlos RC, Wagner LI, Kota VK, Litzow MR. Academic Community Partnership in Acute Promyelocytic Leukemia and Early Mortality: The ECOG-ACRIN EA9131 Trial. JAMA Oncol. 2025 Feb 27:e247033.
12. Jillella AP, Karkhanis P, Sharma R, Bolds S, Shrestha A, Sitchenko K, Jonnalagadda V, Gaddh M, Bernal-Mizrachi L, Heffner LT, Winton EF, McLemore ML, Langston A, Galipeau J, Bodó I, Al-Kadhimi Z, Bashey A, Stuart RK, Vidito S, Pati A, Gerber JM, Grunwald MR, Bradley KT, Tongol J, El-Geneidy M, Khoury HJ, Arellano M, Kota V. A Multi-Center Prospective Study Utilizing a Simplified Treatment Algorithm Complemented By Expert Support Decreases Induction Mortality and Improves Survival in Acute Promyelocytic Leukemia (APL). Results of the APL Trial in Georgia, South Carolina and Neighboring States. Blood 2016; 128 (22): 2793.
13. Lo-Coco F, Avvisati G, Vignetti M, Breccia M, Gallo E, Rambaldi A, Paoloni F, Fioritoni G, Ferrara F, Specchia G, Cimino G, Diverio D, Borlenghi E, Martinelli G, Di Raimondo F, Di Bona E, Fazi P, Peta A, Bosi A, Carella AM, Fabbiano F, Pogliani EM, Petti MC, Amadori S, Mandelli F; Italian GIMEMA Cooperative Group. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood. 2010 Oct 28;116(17):3171-9.
14. Montesinos P, Sanz MA. The differentiation syndrome in patients with acute promyelocytic leukemia: experience of the pethema group and review of the literature. Mediterr J Hematol Infect Dis. 2011;3(1):e2011059. Epub 2011 Dec 4.
15. Stahl M, Tallman MS. Differentiation syndrome in acute promyelocytic leukaemia. Br J Haematol. 2019 Oct;187(2):157-162.
16. Wen J, Xu F, Zhou Q, Shi L, Liu Y, Yue J, Zhang Y, Liang X. Effects of peripheral blood leukocyte count and tumor necrosis factor-alpha on early death in acute promyelocytic leukemia. BMC Cancer. 2023 Jan 7;23(1):27
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Published
Aug 31, 2025
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How to Cite
Dalgetty, M. (2025) “Prevention of Early Death in Very Elderly Acute Promyelocytic Leukemia Patients Using Lower Induction Doses of All-trans Retinoic Acid”, Mediterranean Journal of Hematology and Infectious Diseases, 17(1), p. e2025066. doi: 10.4084/MJHID.2025.066.
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Scientific Letters
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