TREATMENT OUTCOMES OF PATIENTS WITH NEWLY DIAGNOSED ACUTE PROMYELOCYTIC LEUKEMIA; EXPERIENCE FROM A DEVELOPING COUNTRY

Authors

  • Hammad Javed Army Medical Corps
  • Qamar Un Nisa Chudary Armed Forces Bone Marrow Transplant center, Rawalpindi
  • Raheel Iftikhar Armed Forces Bone Marrow Transplant center, Rawalpindi
  • Nighat Shahbaz Armed Forces Bone Marrow Transplant center, Rawalpindi
  • Mehreen Ali Armed Forces Bone Marrow Transplant center, Rawalpindi
  • Saima Hamayun Armed Forces Bone Marrow Transplant center, Rawalpindi

DOI:

https://doi.org/10.55519/JAMC-04-10127

Abstract

Background: Acute promyelocytic leukaemia (APL) characterized by t (15;17) leading to formation of fusion protein PML-RARA is an acute leukaemia with highest mortality. A remarkable improvement in the outcomes has been witnessed due to evolution of highly effective targeted therapies replacing the traditional chemotherapy is most patients. However limited data is available regarding treatment outcomes of APL using various novel regimens from developing countries like Pakistan. Methods: This was a retrospective descriptive study which included APL patients treated at AFBMTC Rawalpindi from 2005 to 2020. It included a total of 51 eligible patients with a diagnosis of de novo APL confirmed by the presence of PML-RARA transcript or presence of t (15;17) by cytogenetics or FISH analysis. The protocols used for treatment included the UKAML MRC 12, the LPA-99/LPA-2005 PETHEMA, the APML4 and non-chemotherapy based ATO-ATRA protocol. Results: The study included 51 patients in which 31 (60.78%) were male and 20 (39.2%) were female. The median age at diagnosis was 30 years (range 5–70). The commonest symptom was fever seen in 43 (84.3%) patients and bruising was the commonest physical finding present in 44 (86.3%) patients. High-risk patients were 23 (46.1%), 18 (35.3%) were intermediate risk and 10 (19.6%) were low risk. The LPA99/LPA2005 was most frequently employed protocol being used in 36 (72%) patients. There were 2 deaths during induction and 44 (86.3%) achieved CR post induction. The median follow up time was 32 months (range 1 to 190 months) with an overall survival (OS) of 76.5% and a relapse free survival (RFS) of 66.7%. Conclusion: Our study shows APL is a highly curable malignancy and outcomes have improved with newer non-chemotherapy based therapies. It can also be concluded that outcomes of APL gradually improved over the past 2 decades due to improvement in supportive care, provision of blood products and use of newer protocols. The prognosis remains less favourable in high risk patients.

Author Biography

Hammad Javed, Army Medical Corps

Medical Specialist

References

Thomas X. Acute Promyelocytic Leukemia: A History over 60 Years—From the Most Malignant to the most Curable Form of Acute Leukemia. Oncol Ther 2019;7(1):33–65.

de Thé H, Pandolfi PP, Chen Z. Acute Promyelocytic Leukemia: A Paradigm for Oncoprotein-Targeted Cure. Cancer Cell 2017;32(5):552–60.

Cao M, Li T, He Z, Wang L, Yang X, Kou Y, et al. Promyelocytic extracellular chromatin exacerbates coagulation and fibrinolysis in acute promyelocytic leukemia. Blood 2017;129(13):1855–64.

Jimenez JJ, Chale RS, Abad AC, Schally AV. Acute promyelocytic leukemia (APL): a review of the literature. Oncotarget 2020;11(11):992–1003.

Osman AEG, Anderson J, Churpek JE, Christ TN, Curran E, Godley LA, et al. Treatment of Acute Promyelocytic Leukemia in Adults. J Oncol Pract 2018;14(11):649–57.

Yilmaz M, Kantarjian H, Ravandi F. Acute promyelocytic leukemia current treatment algorithms. Blood Cancer J 2021;11(6):123.

Zhang X, Liu L, Yao Y, Gong S, Wang M, Xi J, et al. Treatment of non-high-risk acute promyelocytic leukemia with realgar-indigo naturalis formula (RIF) and all-trans retinoid acid (ATRA): study protocol for a randomized controlled trial. Trials 2020;21(1):7.

Noguera NI, Pelosi E, Angelini DF, Piredda ML, Guerrera G, Piras E, et al. High-dose ascorbate and arsenic trioxide selectively kill acute myeloid leukemia and acute promyelocytic leukemia blasts in vitro. Oncotarget 2017;8(20):32550–65.

Gurnari C, De Bellis E, Divona M, Ottone T, Lavorgna S, Voso MT. When Poisons Cure: The Case of Arsenic in Acute Promyelocytic Leukemia. Chemotherapy 2019;64(5-6):238–47.

Stahl M, Tallman MS. Differentiation syndrome in acute promyelocytic leukaemia. Br J Haematol 2019;187(2):157–62.

Abedin S, Altman JK. Acute promyelocytic leukemia: preventing early complications and late toxicities. Hematology Am Soc Hematol Educ Program 2016;2016(1):10–5.

Sanz MA, Fenaux P, Tallman MS, Estey EH, Löwenberg B, Naoe T, et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood 2019;133(15):1630–43.

Karim F, Shaikh U, Adil SN, Khurshid M. Clinical characteristics, outcome and early induction deaths in patients with acute promyelocytic leukaemia: a five-year experience at a tertiary care centre. Singapore Med J 2014;55(8):443–7.

Shaikh MU, Ali N, Karim F, Raheem A, Sarwar S. Improved outcome in early induction deaths in patients with acute promyelocytic leukemia after therapeutic and supportive interventions: a follow up study of seven-years' experience at a tertiary care center. Am J Blood Res 2020;10(4):82–9.

Jillella AP, Kota VK. The global problem of early deaths in acute promyelocytic leukemia: A strategy to decrease induction mortality in the most curable leukemia. Blood Rev 2018;32(2):89–95.

Yildirim R, Gundogdu M, Ozbıcer A, Kiki I, Erdem F, Dogan H. Acute promyelocytic leukemia, centre, experience, Turkey. Transfus Apher Sci 2013;48(1):45–9.

Iland HJ, Bradstock K, Supple SG, Catalano A, Collins M, Hertzberg M, et al. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood 2012;120(8):1570–80.

Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 2013;369(2):111–21.

Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, et al. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood 2010;115(25):5137–46.

Raza S, Ullah K, Ahmed P, Khan B. Comparison of anthracycline-based combination chemotherapy with or without all-trans retinoic acid in acute promyelocytic leukemia. J Coll Physicians Surg Pak 2008;18(9):546–50.

Kayser S, Schlenk RF, Lebon D, Carre M, Götze KS, Stölzel F, et al. Characteristics and outcome of patients with low-/intermediate-risk acute promyelocytic leukemia treated with arsenic trioxide: an international collaborative study. Haematologica 2021;106(12):3100–6.

Zhang X, Zhang H, Chen L, Wang M, Xi J, Liu X, et al. Arsenic trioxide and all-trans retinoic acid (ATRA) treatment for acute promyelocytic leukemia in all risk groups: study protocol for a randomized controlled trial. Trials 2018;19(1):476.

Published

2022-09-27

Issue

Vol. 34 No. 4 (2022): JOURNAL OF AYUB MEDICAL COLLEGE ABBOTTABAD

Section

ORIGINAL ARTICLE

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