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Characteristics and predictors of early hospital deaths in newly diagnosed APL: a 13-year population-wide study.

ABSTRACT: Despite therapeutic advances, early death (ED) remains a major factor curtailing survival of acute promyelocytic leukemia (APL). Studies examining factors that cause early death (ED; within 30 days of admission) and the correlation of survival with the timing of administration of all-trans retinoic acid (ATRA) and hemostatic parameters are scarce. We performed a cohort analysis of nonselect patients with newly diagnosed APL who presented to the health care system in Hong Kong, where oral arsenic trioxide was used. From 1 January 2007 to 30 April 2020, 358 patients (median age, 47 [1-97] years) with newly diagnosed APL were identified. ED occurred in 56 patients (16%): 11 (3%) died in the first 2 days after admission (intracranial hemorrhage [ICH], n = 6; APL-differentiation syndrome [APL-DS], n = 4; infection, n = 1); 22 (6%) died within 3 to 7 days (ICH, n = 12; APL-DS, n = 8; infections, n = 2), and 23 (6%) died within 8 to 30 days (ICH, n = 7; APL-DS, n = 11; infection, n = 5). Factors significantly associated with ED by multivariate analysis included male sex (P = .01); presenting leukocyte count ≥10 × 109/L (P = .03); fibrinogen <1.5 g/L (P = .02); and ATRA administration >24 hours after hospital admission (P < .001). After a median follow-up of 47 (0-166) months, the 5- and 10-year overall survival (OS) was 68.6% and 61.2%, respectively. Excluding EDs, the 5- and 10-year post-30-day OS improved to 81.3% and 72.5%. Early administration of ATRA (<24 hours) and vigorous correction of hemostatic abnormalities, including hypofibrinogenemia, are key to reducing ED.

SUBMITTER: Gill H

PROVIDER: S-EPMC8341351 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In standard-risk acute promyelocytic leukemia, recent results have shown that all-trans retinoic acid plus arsenic trioxide combinations are at least as effective as classical all-trans retinoic acid plus anthracycline-based chemotherapy while being less myelosuppressive. However, the role of frontline arsenic trioxide is less clear in higher-risk acute promyelocytic leukemia, and access to arsenic remains limited for front-line treatment of standard-risk acute promyelocytic leukemia in many countries. In this randomized trial, we compared arsenic, all-trans retinoic acid and the "classical" cytarabine for consolidation treatment (after all-trans retinoic acid and chemotherapy induction treatment) in standard-risk acute promyelocytic leukemia, and evaluated the addition of arsenic during consolidation in higher-risk disease. Patients with newly diagnosed acute promyelocytic leukemia with a white blood cell count <10x109/L, after an induction treatment consisting of all-trans retinoic acid plus idarubicin and cytarabine, received consolidation chemotherapy with idarubicin and cytarabine, arsenic or all-trans retinoic acid. Patients with a white blood cell count >10x109/L received consolidation chemotherapy with or without arsenic. Overall, 795 patients with acute promyelocytic leukemia were enrolled in this trial. Among those with standard-risk acute promyelocytic leukemia (n=581), the 5-year event-free survival rates from randomization were 88.7%, 95.7% and 85.4% in the cytarabine, arsenic and all-trans retinoic acid consolidation groups, respectively (P=0.0067), and the 5-year cumulative incidences of relapse were was 5.5%, 0% and 8.2%. (P=0.001). Among those with higher-risk acute promyelocytic leukemia (n=214), the 5-year event-free survival rates were 85.5% and 92.1% (P=0.38) in the chemotherapy and chemotherapy plus arsenic groups, respectively, and the corresponding 5-year cumulative incidences of relapse were 4.6% and 3.5% (P=0.99). Given the prolonged myelosuppression that occurred in the chemotherapy plus arsenic arm, a protocol amendment excluded cytarabine during consolidation cycles in the chemotherapy plus arsenic group, resulting in no increase in relapse. Our results therefore advocate systematic introduction of arsenic in the first-line treatment of acute promyelocytic leukemia, but probably not concomitantly with intensive chemotherapy, a situation in which we found myelosuppression to be significant. (ClinicalTrials.gov Identifier: NCT00378365).

Project description:The aim of this study was to analyze the distribution of clusters and drug resistance of CRF01_AE among newly diagnosed, treatment-naïve HIV-infected teenagers and young adults in 3 major HIV-affected geographic regions of Guangxi Province, including the cities of Hezhou, Liuzhou, and Nanning. Samples were sequentially collected from newly diagnosed HIV-infected 16- to 25-year olds in these 3 regions from 2009 to 2013. The viral genome was extracted, and the partial pol gene was amplified and sequenced. Phylogenetic analyses were used to determine HIV-1 subtypes and CRF01_AE clusters. Transmitted drug resistance (TDR) mutations were identified using the 2009 WHO list of TDR mutations. A total of 216 sequences were obtained from CRF01_AE strains, which accounted for 83.1% of the 260 genotyped samples, of which 36 were from Hezhou, 147 from Liuzhou, and 33 in Nanning. Most (83.3%, 180/216) were from heterosexuals, followed by injection drug users (5.6%), homosexuals (4.2%), and unknown risk group (6.9%). Based on phylogenetic analyses by the maximum likelihood method, 5 distinct clusters (cluster 1-5) were identified with 213 (98.6%) sequences, whereas 3 (1.4%) sequences were ungrouped. In Hezhou, 88.9% (32/36) of CRF01_AE infections were caused by cluster 2, and 11.1% (4/36) were caused by cluster 1. In Liuzhou, 83.0% (122/147) of the CRF01_AE strains were found in cluster 1, 11.6% (17/147) from cluster 2, 1.4% (2/147) from cluster 3, 2.7% (4/147) from cluster 4, and 0.7% (1/147) from cluster 5. The distribution of CRF01_AE clusters was more even in Nanning than it was in the other 2 regions, with 18.2% (6/33) from cluster 1, 36.3% (12/33) from cluster 2, 9.1% (3/33) from cluster 3, 18.2% (6/33) from cluster 4, and 12.1% (4/33) from cluster 5. The most frequent TDR mutations were M46I (2) in the protease region and Y181C (2) from the reverse transcriptase fragment. Clusters 1 and 2 of CRF01_AE strains were prevalent in Liuzhou and Hezhou, respectively. However, multiple CRF01_AE clusters existed in Nanning. This can be partially explained by the high mobility of laborers in Nanning, the capital city of Guangxi. The prevalence of TDR was low.

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Characteristics and predictors of early hospital deaths in newly diagnosed APL: a 13-year population-wide study.

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