# Risk factors associated with early death, disease relapse and second primary malignancies in patients with newly diagnosed acute promyelocytic leukemia

**Authors:** Dong-Ming Zhou, Jie He, Min Zhou, Qian Zhang, Lan-Xin Chen, Cui-Ying Yuan, Hui Zeng, Bing Chen

PMC · DOI: 10.3389/fmed.2026.1671705 · Frontiers in Medicine · 2026-02-19

## TL;DR

This study identifies risk factors for early death, relapse, and new cancers in patients with newly diagnosed acute promyelocytic leukemia to improve treatment strategies.

## Contribution

The study provides insights into risk factors for adverse outcomes in APL patients and supports a risk-adapted treatment approach.

## Key findings

- Early death was linked to severe hemorrhagic and thrombotic complications during induction therapy.
- Relapse was associated with subsequent adverse outcomes, including second malignancies and death.
- The study supports prompt initiation of ATRA and intensified supportive care for high-risk patients.

## Abstract

Early death (ED), relapse, and second primary malignancies (SPMs) remain major barriers to both early and long-term outcomes in acute promyelocytic leukemia (APL). The prospective identification of key risk factors is essential to mitigate these adverse outcomes.

We retrospectively analyzed 174 consecutive patients with newly diagnosed APL treated at a single center, with a median follow-up of 59 months. We evaluated clinical, laboratory, and treatment-related factors associated with these outcomes, including comparisons across treatment eras and regimen categories, and we summarized institutional practice regarding central nervous system (CNS) prophylaxis and management.

Within the cohort, ED occurred in 9 patients, relapse in 7 patients, and SPMs in 7 patients. ED clustered with severe hemorrhagic and thrombotic complications during induction. Relapse was associated with subsequent adverse outcomes, including SPMs and death. Given the low number of events, multivariable modeling was restricted and interpreted cautiously with penalized approaches used as sensitivity analyses where applicable.

Our findings support the risk-adapted approach emphasizing prompt initiation of ATRA and intensified supportive care in patients with high-risk baseline features, alongside vigilant molecular and long-term surveillance to facilitate early detection and timely management of relapse and SPMs.

## Linked entities

- **Chemicals:** ATRA (PubChem CID 444795)
- **Diseases:** acute promyelocytic leukemia (MONDO:0012883)

## Full-text entities

- **Genes:** ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, CD5 (CD5 molecule) [NCBI Gene 921] {aka LEU1, T1}, FUT4 (fucosyltransferase 4) [NCBI Gene 2526] {aka CD15, ELFT, FCT3A, FUC-TIV, FUTIV, LeX}, PML (PML nuclear body scaffold) [NCBI Gene 5371] {aka MYL, PP8675, RNF71, TRIM19}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, RARA (retinoic acid receptor alpha) [NCBI Gene 5914] {aka NR1B1, RAR, RARalpha}, BCRP1 (BCR pseudogene 1) [NCBI Gene 644079] {aka BCR-1}, KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}, CD7 (CD7 molecule) [NCBI Gene 924] {aka GP40, LEU-9, TP41, Tp40}, BCRP2 (BCR pseudogene 2) [NCBI Gene 400892] {aka BCR-2, BCR2, BCRL2}, BCRP3 (BCR pseudogene 3) [NCBI Gene 644165] {aka BCR3, BCRL3, BCRL6}, CD34 (CD34 molecule) [NCBI Gene 947], FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322] {aka CD135, FLK-2, FLK2, STK1}, CD2 (CD2 molecule) [NCBI Gene 914] {aka LFA-2, SRBC, T11}, FCGR1A (Fc gamma receptor Ia) [NCBI Gene 2209] {aka CD64, CD64A, FCG1, FCGR1, FCRI, FcgammaRI}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}
- **Diseases:** DS (MESH:D012734), hepatic vein embolism (MESH:D004617), APL (MESH:D015473), retinoic acid syndrome (MESH:D011015), DIC (MESH:D004211), nasopharyngeal carcinoma (MESH:D000077274), primary malignancies (MESH:D001932), mCR (MESH:D012075), QT interval prolongation (MESH:D008133), carcinogenic (MESH:D011230), ED (MESH:D003643), leukemic (MESH:D007938), Thrombosis and (MESH:D013927), endothelial injury (MESH:D057772), leukocytosis (MESH:D007964), APL coagulopathy (MESH:D001778), infection (MESH:D007239), SPMs (MESH:D016609), papillary thyroid carcinoma (MESH:D000077273), acute renal failure (MESH:D058186), weight gain (MESH:D015430), intracranial hemorrhage (MESH:D020300), Hemorrhagic (MESH:D006470), gastric cancer (MESH:D013274), hypofibrinogenemia (MESH:D000347), brainstem infarction (MESH:D020526), AML (MESH:D015470), cardiotoxicity (MESH:D066126), hypotension (MESH:D007022), hematologic malignancies (MESH:D019337), unexplained fever (MESH:D005334), myelodysplastic syndromes (MESH:D009190), cervical cancer (MESH:D002583), hemostatic dysregulation (MESH:D020141), inflammatory (MESH:D007249), electrolyte abnormalities (MESH:D014883), edema (MESH:D004487), CNSL (MESH:D002493), lung cancer (MESH:D008175), dyspnea (MESH:D004417), Cancer (MESH:D009369), SPM (MESH:C567481)
- **Chemicals:** Ara-C (MESH:D003561), hydroxycarbamide (MESH:D006918), ATRA (MESH:D014212), Dexamethasone (MESH:D003907), daunorubicin (MESH:D003630), methotrexate (MESH:D008727), cholesterol (MESH:D002784), anthracycline (MESH:D018943), idarubicin (MESH:D015255), triglycerides (MESH:D014280), ATO (MESH:D000077237)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960103/full.md

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Source: https://tomesphere.com/paper/PMC12960103