Cancer Research and Treatment

The Effect of Hematopoietic Stem Cell Transplantation on Treatment Outcome in Children with Acute Lymphoblastic Leukemia: Hee Young Ju, Na Hee Lee, Eun Sang Yi, Young Bae Choi, So Jin Kim, Ju Kyung Hyun, Hee Won Cho, Jae Kyung Lee, Ji Won Lee, Ki Woong Sung, Hong Hoe Koo, Keon Hee Yoo; Received February 14, 2024 Accepted July 4, 2024 Published online July 5, 2024; DOI: https://doi.org/10.4143/crt.2024.155 [Epub ahead of print]

Abstract PDF PubReader ePub: Purpose
Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups.
Materials and Methods
A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients’ disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease.
Results
Among the 549 screened patients, a total of 418 patients were included in the study; B-cell ALL (n=379) and T-cell ALL (T-ALL) (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher-risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.002). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.002) and OS (p=0.022) when HSCT was done as upfront treatment.
Conclusion
HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

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Pediatric cancer

Tandem High-Dose Chemotherapy Increases the Risk of Secondary Malignant Neoplasm in Pediatric Solid Tumors: Hana Lim, Minji Im, Eun Seop Seo, Hee Won Cho, Hee Young Ju, Keon Hee Yoo, Sung Yoon Cho, Jong-Won Kim, Do Hoon Lim, Ki Woong Sung, Ji Won Lee; Cancer Res Treat. 2024;56(2):642-651. Published online November 24, 2023; DOI: https://doi.org/10.4143/crt.2023.999

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to investigate the incidence and risk factors for secondary malignant neoplasms (SMN) in pediatric solid tumors, focusing on the effects of tandem high-dose chemotherapy (HDCT).
Materials and Methods
Patients (aged < 19 years) diagnosed with or treated for pediatric solid tumors between 1994 and 2014 were retrospectively analyzed. The cumulative incidence of SMN was estimated using competing risk methods by considering death as a competing risk.
Results
A total of 1,435 patients (413 with brain tumors and 1,022 with extracranial solid tumors) were enrolled. Seventy-one patients developed 74 SMNs, with a 10-year and 20-year cumulative incidence of 2.680±0.002% and 10.193±0.024%, respectively. The types of SMN included carcinoma in 28 (37.8%), sarcoma in 24 (32.4%), and hematologic malignancy in 15 (20.3%) cases. Osteosarcoma and thyroid carcinoma were the most frequently diagnosed tumors. Multivariate analysis showed that radiotherapy (RT) > 2, 340 cGy, and tandem HDCT were significant risk factors for SMN development. The SMN types varied according to the primary tumor type; carcinoma was the most frequent SMN in brain tumors and neuroblastoma, whereas hematologic malignancy and sarcomas developed more frequently in patients with sarcoma and retinoblastoma, respectively.
Conclusion
The cumulative incidence of SMN in pediatric patients with solid tumors was considerably high, especially in patients who underwent tandem HDCT or in those who received RT > 2,340 cGy. Therefore, the treatment intensity should be optimized based on individual risk assessment and the long-term follow-up of pediatric cancer survivors.

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Rising Prevalence of Low-Frequency PPM1D Gene Mutations after Second HDCT in Multiple Myeloma
Katja Seipel, Nuria Z. Veglio, Henning Nilius, Barbara Jeker, Ulrike Bacher, Thomas Pabst
Current Issues in Molecular Biology.2024; 46(8): 8197. CrossRef

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Absolute Neutrophil Count after the First Chemotherapy Cycle as a Surrogate Marker for Treatment Outcomes in Patients with Neuroblastoma: Ji Won Lee, Joon Seol Bae, Jin Ho Kim, Hee Won Cho, Hee Young Ju, Keon Hee Yoo, Hong Hoe Koo, Sook-young Woo, Seonwoo Kim, Ki Woong Sung; Cancer Res Treat. 2022;54(1):259-268. Published online April 12, 2021; DOI: https://doi.org/10.4143/crt.2021.010

Abstract PDF Supplementary Material PubReader ePub

Purpose
We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma.
Materials and Methods
The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed.
Results
An ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC.
Conclusion
In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.

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Impact of 10% Dose Reductions and Duration of Treatment Delays in the Management of Chemotherapy‐Induced Neutropenia in Dogs Treated With Common Chemotherapy Protocols: A Single‐Centre Experience
Suzanne Busser, Laura Blackwood, Constanza Pereira, Margo Chase‐Topping, Spela Bavcar, Quentin Fournier
Veterinary and Comparative Oncology.2024; 22(4): 542. CrossRef
Targeting the myeloid microenvironment in neuroblastoma
Marjolein C. Stip, Loes Teeuwen, Miranda P. Dierselhuis, Jeanette H. W. Leusen, Daniëlle Krijgsman
Journal of Experimental & Clinical Cancer Research.2023;[Epub] CrossRef

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