# Current and emerging maintenance strategies after stem cell transplantation in children and adolescents with acute leukemias

**Authors:** Alexander W. Rankin, Amy K. Keating, Rolla F. Abu-Arja, Monica S. Thakar, Hemalatha G. Rangarajan

PMC · DOI: 10.1016/j.omton.2026.201141 · Molecular Therapy Oncology · 2026-01-29

## TL;DR

This paper reviews strategies to prevent leukemia relapse after stem cell transplants in children and adolescents, focusing on emerging targeted and immunotherapies.

## Contribution

The paper provides a comprehensive review of post-HSCT maintenance strategies specifically for pediatric and adolescent patients with acute leukemias.

## Key findings

- Post-HSCT relapse remains a significant challenge in pediatric acute leukemias.
- Targeted and immunotherapeutic agents show promise in improving post-HSCT outcomes.
- Early prophylactic intervention can improve survival in high-risk patients.

## Abstract

Hematopoietic stem cell transplantation (HSCT) can promote durable long-term remissions for children and adolescents with high-risk acute leukemias. While many patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) can achieve a cure, post-HSCT relapse remains a possibility for many. Recent therapeutic advances, particularly in the realm of targeted therapeutics, have revolutionized both first-line and relapsed/refractory management strategies, opening the door to more personalized and potentially less toxic approaches to treatment. Many of these agents have also either been proposed or have been actively investigated as having a role in the post-HSCT setting. Post-HSCT relapse often carries a dismal prognosis, and early prophylactic intervention has in many cases been shown to improve outcomes. Herein, we comprehensively review maintenance strategies for prevention of post-HSCT relapse of ALL and AML, with a specific focus on pediatric and adolescent populations. While drawing on experience in adult patients, we highlight data specific to pediatrics where available and draw attention to areas where further research in children and adolescents is needed. Future efforts aimed at determining who will benefit from, when to initiate and discontinue, and what agent(s) to employ as maintenance will be crucial to optimizing post-HSCT outcomes.

Strategies to prolong leukemia remission after allogeneic hematopoietic stem cell transplantation (HSCT) in children and adolescents are increasingly utilized. When employed post-HSCT, many targeted and immunotherapeutic approaches hold potential to improve outcomes both through direct antileukemic effects and synergistic immunomodulatory properties. Rankin and colleagues provide a comprehensive review of the available literature.

## Linked entities

- **Diseases:** acute lymphoblastic leukemia (MONDO:0004967), acute myeloid leukemia (MONDO:0015667)

## Full-text entities

- **Genes:** TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, FOSL1 (FOS like 1, AP-1 transcription factor subunit) [NCBI Gene 8061] {aka FRA, FRA1, fra-1}, CLEC12A (C-type lectin domain family 12 member A) [NCBI Gene 160364] {aka CD371, CLL-1, CLL1, DCAL-2, MICL, hKLRL1}, FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322] {aka CD135, FLK-2, FLK2, STK1}, IL15 (interleukin 15) [NCBI Gene 3600] {aka IL-15}, BCR (BCR activator of RhoGEF and GTPase) [NCBI Gene 613] {aka ALL, BCR1, CML, D22S11, D22S662, PHL}, GLIS2 (GLIS family zinc finger 2) [NCBI Gene 84662] {aka NKL, NPHP7}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}, CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, FCGR1A (Fc gamma receptor Ia) [NCBI Gene 2209] {aka CD64, CD64A, FCG1, FCGR1, FCRI, FcgammaRI}, KIR3DL2 (killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 2) [NCBI Gene 3812] {aka 3DL2, CD158K, KIR-3DL2, NKAT-4, NKAT4, NKAT4B}, WT1 (WT1 transcription factor) [NCBI Gene 7490] {aka AWT1, GUD, NPHS4, WAGR, WIT-2, WT-1}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, DNMT1 (DNA methyltransferase 1) [NCBI Gene 1786] {aka ADCADN, AIM, CXXC9, DNMT, HSN1E, MCMT}, IL3RA (interleukin 3 receptor subunit alpha) [NCBI Gene 3563] {aka CD123, IL-3R-alpha, IL3R, IL3RAY, IL3RX, IL3RY}, CD33 (CD33 molecule) [NCBI Gene 945] {aka CD33rSiglec, SIGLEC-3, SIGLEC3, p67}, ARHGAP45 (Rho GTPase activating protein 45) [NCBI Gene 23526] {aka HA-1, HLA-HA1, HMHA1}, CD47 (CD47 molecule) [NCBI Gene 961] {aka IAP, MER6, OA3}, CD22 (CD22 molecule) [NCBI Gene 933] {aka SIGLEC-2, SIGLEC2}, PRAME (PRAME nuclear receptor transcriptional regulator) [NCBI Gene 23532] {aka CT130, MAPE, OIP-4, OIP4}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}, KIR2DL4 (killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 4) [NCBI Gene 3805] {aka CD158D, G9P, KIR-103AS, KIR-2DL4, KIR103, KIR103AS}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) [NCBI Gene 25] {aka ABL, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL}, CD7 (CD7 molecule) [NCBI Gene 924] {aka GP40, LEU-9, TP41, Tp40}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, KLRK1 (killer cell lectin like receptor K1) [NCBI Gene 22914] {aka CD314, D12S2489E, KLR, NKG2-D, NKG2D}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, CTAG1A (cancer/testis antigen 1A) [NCBI Gene 246100] {aka CT6.1, ESO1, LAGE-2, LAGE2A, NY-ESO-1}, KMT2A (lysine methyltransferase 2A) [NCBI Gene 4297] {aka ALL-1, ALL1, CXXC7, GAS7, HRX, HTRX}
- **Diseases:** SOS (MESH:D006504), Hematological Malignancies (MESH:D019337), MDS (MESH:D009190), AML (MESH:D015470), T cell leukemia and lymphoma (MESH:D015459), GvHD (MESH:D006086), chronic myeloid leukemia (MESH:D015464), T cell lymphopenia (MESH:D008231), Cancer (MESH:D009369), calculus (MESH:D002137), Ph (MESH:D010677), CR (MESH:D012075), ADCC (MESH:C565972), DLI (MESH:D000075662), Lymphoma (MESH:D008223), FLT3-ITD (MESH:C566928), B cell ALL (MESH:D015456), cytotoxicity (MESH:D064420), ALL (MESH:D054198), ICANS (MESH:C000722498), T cell ALL (MESH:D054218), infections (MESH:D007239), leukemia (MESH:D007938), cytopenias (MESH:D006402), WIS (MESH:D013375), T cell deficient (MESH:D016399)
- **Chemicals:** cyclophosphamide (MESH:D003520), ivosidenib (MESH:C000627630), Decitabine (MESH:D000077209), sorafenib (MESH:D000077157), ipilimumab (MESH:D000074324), Bortezomib (MESH:D000069286), glasdegib (MESH:C000592580), imatinib (MESH:D000068877), GO (MESH:D000079982), panobinostat (MESH:D000077767), zoledronic acid (MESH:D000077211), Magrolimab (MESH:C000629291), gilteritinib (MESH:C000609080), Venetoclax (MESH:C579720), Blinatumomab (MESH:C510808), AZA (MESH:D001379), DAS (MESH:C025953), enasidenib (MESH:C000605269), ponatinib (MESH:C545373), azacitidine (MESH:D001374), inotuzumab ozogamicin (MESH:D000080045), nivolumab (MESH:D000077594), daratumumab (MESH:C556306), pembrolizumab (MESH:C582435), Nelarabine (MESH:C104457), dasatinib (MESH:D000069439), vorinostat (MESH:D000077337), DEC (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** 2 DELPHINUS, T315I
- **Cell lines:** CIK — Rattus norvegicus (Rat), Rat large granular lymphocyte leukemia, Cancer cell line (CVCL_F856)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12915188/full.md

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12915188/full.md

## References

259 references — full list in the complete paper: https://tomesphere.com/paper/PMC12915188/full.md

---
Source: https://tomesphere.com/paper/PMC12915188