Increased risk of subsequent neoplasm after hematopoietic stem cell transplantation in 5-year survivors of childhood acute lymphoblastic leukemia

Sep 21, 2026

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Acute lymphoblastic leukemia (ALL) survivors face elevated long-term risk of subsequent neoplasms, yet long-term risk patterns and associated factors for both subsequent malignant and non-malignant neoplasms remain insufficiently characterized. This study analyzed 3291 Dutch Childhood Cancer Survivor Study-LATER 5-year survivors and estimated standardized incidence ratios, cumulative incidences, and risk factors using multivariable Cox models. Overall, 97 SMNs and 266 SNMNs occurred, with 30-year cumulative incidences of 4.1% for SMNs and 10.4% for SNMNs. HSCT—particularly with total body irradiation—and cranial radiotherapy increased SMN risk, including HSCT without TBI, supporting careful follow-up.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Study aim and rationale

Methods and outcomes

Cohort and statistical approach

Incidence and risk factors

Conclusion and implications

Blood Cancer [Journal](Journal www.nature.com/bcj)[ www.nature.com/bcj](Journal www.nature.com/bcj) ARTICLE OPEN Increased risk of subsequent neoplasm after hematopoietic stem cell transplantation in 5-year survivors of childhood acute lymphoblastic leukemia Aimée S. R. Westerveld 1,8 ✉ , Pien Roesthuis1,8, Helena J. H. van der Pal 1, Dorine Bresters1, Marc Bierings 1, Jacqueline Loonen2, Andrica C. H. de Vries1,3, Marloes Louwerens4, Maria M. W. Koopman 1, Marry M. van den Heuvel-Eibrink1, Margriet van der Heiden-van der Loo1, Peter Hoogerbrugge 1, Geert O. Janssens 1,5, Ronald R. de Krijger 1,5, Cecile M. Ronckers 1,6 , Rob Pieters 1, Leontien C. M. Kremer1,7 and Jop C. Teepen1 © The Author(s) 2024 | | Acute lymphoblastic leukemia (ALL) survivors are at risk for developing subsequent neoplasms, but there is limited information on long-term risks and risk factors for both subsequent malignant neoplasms (SMNs) and subsequent non-malignant neoplasms (SNMNs) . We analyzed long-term risk and risk factors for SMNs and SNMNs among 3291 5-year ALL survivors from the Dutch Childhood Cancer Survivor Study-LATER cohort (1963–2014) . We calculated standardized incidence ratios (SIRs) and cumulative incidences and used multivariable Cox proportional hazard regression analyses for analyzing risk factors. A total of 97 survivors developed SMNs and 266 SNMNs. The 30-year cumulative incidence was 4.1%(95%CI: 3.5–5.3) for SMNs and 10.4%(95%CI: 8.9–12.1) for SNMNs. Risk of SMNs was elevated compared to the general population (SIR: 2.6, 95%CI: 2.1–3.1) . Survivors treated with hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI) (HR:4.2, 95%CI: 2.3–7.9), and without TBI (HR:4.0,95%CI: 1.2–13.7) showed increased SMN risk versus non-transplanted survivors. Cranial radiotherapy (CRT) was also a risk factor for SMNs (HR:2 . 1, 95%CI: 1 .4–4. 0) . In conclusion, childhood ALL survivors have an increased SMN risk, especially after HSCT and CRT. A key ﬁnding is that even HSCT-treated survivors without TBI treatment showed an increased SMN risk, possibly due to accompanied chemotherapy treatment. This emphasizes the need for careful follow-up of HSCT | | | --- | --- | --- | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | and/or CRT-treated survivors. | | | | | Blood Cancer Journal (2024)14:150; [https://doi.org/10.1038/s41408-024-01](https://doi.org/10.1038/s41408-024-01)122-7 | | | | | | INTRODUCTION Acute lymphoblastic leukemia (ALL) is the most common typeof childhood cancer [1–3], with a 5-year survival rate currently exceeding 90%[4] . However, ALL survivors are at risk for longterm adverse health outcomes including the development of subsequent neoplasms [5, 6] . Compared to the general population, childhood ALL survivors have a 2.6 to 13.5 times higher risk of developing subsequent malignant neoplasms (SMNs) [5–8] . The most frequently observed SMNs in ALL survivors are central nervous system (CNS) tumors [6, 9] . In addition to SMNs, some types of subsequent non-malignant neoplasms (SNMNs) can also cause serious morbidity, such as subsequent meningiomas [5, 10] . Treatment protocols for ALL patients have changed overtime. Major adjustments in the Netherlands were 1) the substitution of cranial radiotherapy (CRT) by CNS prophylaxis with intrathecal high-dose methotrexate since to the DCOGALL VI protocol in December 1984 [11, 12] and 2) trials with replacing TBI with a chemotherapy conditioning regimen for HSCT between 2011 and 2021 [13, 14] Several studies examined treatment-related risk factors for subsequent neoplasms in ALL survivors [5, 15–17] . Although many studies were limited by short follow-up times [15–17] or the limited availability of speciﬁc treatment data [5, 15–17], several risk factors have been suggested. The risk of developing a subsequent neoplasm was found to be higher in patients

FAQs

What was the main aim of the study in childhood ALL 5-year survivors?

To quantify long-term risk and identify associated risk factors for subsequent malignant neoplasms (SMNs) and subsequent non-malignant neoplasms (SNMNs).

How many SMN and SNMN cases were observed, and what were the 30-year cumulative incidences?

A total of 97 survivors developed SMNs and 266 developed SNMNs. The 30-year cumulative incidence was 4.1% for SMNs and 10.4% for SNMNs.

Which treatments were linked to increased SMN risk compared with non-transplanted survivors?

Hematopoietic stem cell transplantation (HSCT) increased SMN risk versus non-transplanted survivors, with higher hazard ratios when combined with total body irradiation (TBI), and cranial radiotherapy (CRT) was also a risk factor.

Sep 21, 2026

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