Prognostic Factors in Adult Patients with Acute Promyelocytic Leukemia Receiving ATRA-Based Treatment
Authors: Jang Ji Eun , Lee Jung Yeon , Park Hyun Sung , Kim Yundeok , Kim Soo-Jeong , Kim Jin Seok , Cheong June-Won , Min Yoo Hong 
Published: October 2019

Abstract
Background: Acute promyelocytic leukemia (APL) is a distinctive subtype of acute myeloid leukemia (AML) characterized by translocation between chromosome 15 and 17, t(15;17). Addition of all-transretinoic acid (ATRA), which can induce differentiation of leukemic blasts and promyelocyte, to anthracycline-based chemotherapy brought novel concept and made major advance in treatment for APL. Although APL patients show the highest survival rate among AML patients, some fraction of patients eventually relapsed. However, prognostic factors have been unclearly defined than those in other subtypes of AML in which cytogenetic and molecular abnormalities have been emphasized. In this study, we evaluated prognostic factors in APL patients receiving ATRA-based treatments.
Patients and Methods: A total of 77 patients who newly diagnosed with APL treated at Severance Hospital from 2005 to 2014 were enrolled, and clinical data was retrospectively reviewed. All patients had treated with modified PETHEMA protocol consisting with ATRA and anthracycline-based regimen.
Results: Except 9 patients who refused the treatment or did not complete the first cycle of chemotherapy due to treatment-related mortalities, 68 patients completed at least one cycle of chemotherapy and all achieved molecular complete remission (CR). During the treatment or follow-up period, eleven (16.2%) of 68 patients experienced relapse, and median duration of the first CR of these 11 patients was 38.8 months (range 28.0 ~ 88.0 months). Clinical and laboratory parameters analyzed were listed in Table 1. Severe bleeding episodes were more correlated with initial abnormal coagulation profiles than initial platelet counts. Interestingly, delayed achievement of molecular CR was not significant risk factor for relapse. Univariate analysis for overall survival (OS) showed that older age more than 60 year-old (p=0.045), higher initial WBC counts (p=0.035), abnormal coagulation profiles (P<0.0001), initial presence of documented fever or infection (p=0.002), and higher Charlson comorbidity index (p=0.008) were significant poor prognostic factors. For disease-free survival (DFS), initial presence of documented fever or infection (p=0.007), and higher Charlson comorbidity index (p<0.0001) were significant poor prognostic factors. In multivariate analysis for OS, higher initial WBC counts (p=0.05), abnormal coagulation profiles (p=0.005), and higher Charlson comorbidity index (p<0.0001) were independent poor prognostic factors, and for DFS, initial presence of documented fever or infection (p=0.025) was single independent poor prognostic factor.
Conclusion: Because APL is already belong to cytogenetically very good or good risk group and treated by chemotherapy containing differentiating agents such as ATRA, predicting prognosis must be distinguished from that in AML. In this study, initial WBC counts, coagulation profiles, and comorbidity are independent prognostic factors for OS, and initial fever or infection is for DFS. For the next step, to figure out how initial systemic inflammation related to fever or infection influence the differentiation or apoptosis of leukemic myeloid cells by treatment will expand our understanding of APL.
Table 1. [Clinical and laboratory characteristics of APL patients] Characteristics Total No. of patients 77 Age, median (range), years 44.8(17-81) ≤60/>60 64/13 Gender, M/F 42/35 Charlson comorbidity index, median (range) 2.54(0-10) WBC x 10^9/L, median (range) 16.17(0.39-208.65) ≤10/>10/NA 54/21/2 PLT x 10^9/L, median (range) 35(7-155) ≤4/>4/NA 51/24/2 Hb, g/L, median (range) 8.82(3.4-14.8) Lymphocyte, %, median (range) 31.8(1-84) LDH, IU/L, median (range) 537(40-3418) Ferritin, ng/mL, median (range) 832(15.8-4567.6) PT/aPTT, sec, median (range) 14.6(9.8-23.8)/29.0(20.4-39.8) Albumin, g/dL, median (range) 4.0(2.3-5.9) Sanz risk category Low/Intermediate/High 14/40/21 Initial fever or infection, n (%) 12(15.6%) Abnormal coagulation profile PT prolongation only, n (%) 14(18.7%) Low ATIII level only, n (%) 10(13.3%) Both PT prolongation and low ATIII level, n (%) 4(5.4%) NA, n (%) 2(2.7%) Additional Chromosome aberration, n (%) 12(15.6%) Outcome of induction, n (%) Hematologic CR/NA 68/9 F/U period (months), median (range) 35.8(0.1-98.4) Timing of mCR achievement, n (%) After 1st/2nd/3rd/4th CTx 32/29/6/1

Disclosures
No relevant conflicts of interest to declare.