Cancer Research and Treatment

Original Articles

Pediatric cancer

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

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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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Genome-Wide Association Study for the Identification of Novel Genetic Variants Associated with the Risk of Neuroblastoma in Korean Children: Joon Seol Bae, Ji Won Lee, Jung Eun Yoo, Je-Gun Joung, Keon Hee Yoo, Hong Hoe Koo, Yun-Mi Song, Ki Woong Sung; Cancer Res Treat. 2020;52(4):1251-1261. Published online June 30, 2020; DOI: https://doi.org/10.4143/crt.2020.140

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Purpose
Neuroblastoma (NB) is the most common extracranial solid tumor found in children. To identify significant genetic factors for the risk of NB, several genetic studies was conducted mainly for Caucasians and Europeans. However, considering racial differences, there is a possibility that genetic predispositions that contribute to the development of NB are different, and GWAS study has not yet been conducted on Korean NB patients.
Materials and Methods
To identify the genetic variations associated with the risk of pediatric NB in Korean children, we performed a genome-wide association analysis with 296 NB patients and 1000 unaffected controls (total n = 1,296) after data cleaning and filtering as well as imputation of non-genotyped SNPs using IMPUTE v2.3.2.
Results
After adjusting for multiple comparisons, we found 21 statistically significant SNPs associated with the risk of NB (P^corr < 0.05) within 12 genes (RPTN, MRPS18B, LRRC45, KANSL1L, ARHGEF40, IL15RA, L1TD1, ANO7, LAMA5, OR7G2, SALL4, and NEUROG2). Interestingly, out of these, 12 markers were nonsynonymous SNPs. The SNP rs76015112 was most significantly associated with the risk of NB (p = 8.1E-23, P^corr = 2.3E-17) and was located in the RPTN gene. In addition, significant nonsynonymous SNPs in ADGRE1 were found in patients with MYCN amplification (rs7256147, p = 2.6E-05). In high-risk group, rs7256147 was observed as a significant SNP (p = 5.9E-06).
Conclusion
Our findings might facilitate improved understanding of the mechanism of pediatric NB pathogenesis. However, functional evaluation and replication of these results in other populations are still needed.

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Expression of anoctamin 7 (ANO7) is associated with poor prognosis and mucin 2 (MUC2) in colon adenocarcinoma: a study based on TCGA data
Chen Chen, Siripat Aluksanasuwan, Keerakarn Somsuan
Genomics & Informatics.2023; 21(4): e46. CrossRef
An Overview of Long Non-Coding (lnc)RNAs in Neuroblastoma
Francesca Baldini, Matilde Calderoni, Laura Vergani, Paola Modesto, Tullio Florio, Aldo Pagano
International Journal of Molecular Sciences.2021; 22(8): 4234. CrossRef

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ALK Protein Expression Is Related to Neuroblastoma Aggressiveness But Is Not Independent Prognostic Factor: Ji Won Lee, Sung Hye Park, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn; Cancer Res Treat. 2018;50(2):495-505. Published online May 22, 2017; DOI: https://doi.org/10.4143/crt.2016.577

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Purpose
In this study, anaplastic lymphoma kinase (ALK) mutation and amplification, ALK protein expression, loss of the nuclear alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein, and telomerase reverse transcriptase (TERT) protein expressionwere studied to investigate potential correlations between these molecular characteristics and clinical features or outcomes in neuroblastoma.
Materials and Methods
Seventy-two patients were enrolled in this study. Polymerase chain reaction amplification and direct sequencing were used for mutation analysis. ALK and MYCN amplifications were detected by fluorescence in situ hybridization. Protein expressionwas evaluated by immunohistochemical (IHC) staining.
Results
ALK mutation was found in only two patients (4.1%); ALK amplification was not detected. ALK positivity, loss of nuclear ATRX protein, TERT positivity by IHC were detected in 40 (55.6%), nine (13.0%), and 42 (59.2%) patients, respectively. The incidence of ALK expression increased in accordance with increasing tumor stage (p=0.001) and risk group (p < 0.001). The relapse rate was significantly higher in ALK⁺ patients compared to that of other patients (47.5% vs. 11.3%, p=0.007). However, there was no significant difference in relapse rate when the survival analysis was confined to the high-risk patients.
Conclusion
Although ALK mutation was rare and no amplification was observed, ALK protein expression was found in a significant number of patients and was correlated with advanced stage and high-risk neuroblastoma. ALK protein expression could be considered as a marker related to the aggressive neuroblastoma, but it was not the independent prognostic factor for the outcome.

Citations

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Emerging Molecularly Defined Bone and Soft Tissue Diagnoses: When Do They Matter?
Jessica L. Davis, Azadeh Samiei
Modern Pathology.2026; 39(4): 100981. CrossRef
The Role of ATRX and TERT Expressions in Determining Aggressiveness of Neuroblastoma
Murat Tuncel, Selen Kum Özşengezer, Gamze Sanlav, Deniz Kızmazoğlu, Safiye Aktaş, Zekiye Altun, Tekincan Çağrı Aktaş, Erdener Özer, Nur Olgun
Journal of Dr Behcet Uz Children s Hospital.2026; 16(1): 1. CrossRef
Immunohistochemical expression of anaplastic lymphoma kinase in neuroblastoma and its relations with some clinical and histopathological features
Thu Dang Anh Phan, Thao Quyen Nguyen, Nhi Thuy To, Thien Ly Thanh, Dat Quoc Ngo
Journal of Pathology and Translational Medicine.2024; 58(1): 29. CrossRef
Multi-omics revealed that ELAVL3 regulates MYCN in neuroblastoma via immunogenic cell death: Risk stratification and experimental research
Peng Hong, Zaihong Hu, Jie Lin, Kongkong Cui, Zhiqiang Gao, Xiaomao Tian, Qinlin Shi, Tao Lin, Guanghui Wei
International Journal of Biological Macromolecules.2024; 282: 137045. CrossRef
Prominent Staining of MYCN Immunohistochemistry Predicts a Poor Prognosis in MYCN Non-Amplified Neuroblastoma
Manli Zhao, Weizhong Gu, Fei Liu, Lihua Yu, Yan Shu, Lei Liu, Jiahui Hu, Yang Liu, Hongfeng Tang, Jianhua Mao
Pediatric and Developmental Pathology.2023; 26(2): 124. CrossRef
ALKGene Mutation and ALK Protein Expression in Advanced Neuroblastoma and the Potential Value in Risk Stratification in Fine-Needle Aspiration Biopsy Samples
Neha Bhardwaj, Manish Rohilla, Upasana Gautam, Amita Trehan, Deepak Bansal, Nandita Kakkar, Radhika Srinivasan
American Journal of Clinical Pathology.2023;[Epub] CrossRef
Rapid detection of telomerase expression of neuroblastoma in paraffin-embedded tissue: combination of in situ hybridisation and quantitative PCR
Manli Zhao, Zhonghai Guan, Liang Gong, Fei Liu, Weizhong Gu, Lei Liu, Kewen Jiang, Jiabin Cai, Chunyue Feng, Chik Hong Kuick, Kenneth Tou En Chang, Jinhu Wang, Hongfeng Tang, Minzhi Yin, Jianhua Mao
Pathology.2023; 55(7): 958. CrossRef
Interactions of Butyrylcholinesterase with Neuroblastoma-associated Oncoproteins
Janina Baranowska-Kortylewicz, Zbigniew P. Kortylewicz, Erin M. McIntyre, John G. Sharp, Don W. Coulter
Current Enzyme Inhibition.2023; 19(2): 109. CrossRef
Combined Detection of Copy Number Variations of MYCN and ALK using Droplet Digital Polymerase Chain Reaction to Identify High-Risk Patients with Neuroblastoma
Trupti Trivedi, Kinjal Panchal, Neha Bhalala, Priti Trivedi, Harsha Panchal
World Neurosurgery.2022; 159: e48. CrossRef
ALK expression, prognostic significance, and its association with MYCN expression in MYCN non-amplified neuroblastoma
Dinesh Babu Somasundaram, Sheeja Aravindan, Nandita Gupta, Zhongxin Yu, Ashley Baker, Natarajan Aravindan
World Journal of Pediatrics.2022; 18(4): 285. CrossRef
Multifarious Functions of Butyrylcholinesterase in Neuroblastoma: Impact of BCHE Deletion on the Neuroblastoma Growth In Vitro and In Vivo
Janina Baranowska-Kortylewicz, Zbigniew P. Kortylewicz, Erin M. McIntyre, John G. Sharp, Don W. Coulter
Journal of Pediatric Hematology/Oncology.2022; 44(6): 293. CrossRef
Differential Impact of ALK Mutations in Neuroblastoma
Tara O'Donohue, Nitya Gulati, Audrey Mauguen, Brian H. Kushner, Neerav Shukla, M. I. Rodriguez-Sanchez, Nancy Bouvier, Stephen Roberts, Ellen Basu, Nai-Kong Cheung, Shakeel Modak
JCO Precision Oncology.2021; (5): 492. CrossRef
The challenge of defining “ultra‐high‐risk” neuroblastoma
Daniel A. Morgenstern, Rochelle Bagatell, Susan L. Cohn, Michael D. Hogarty, John M. Maris, Lucas Moreno, Julie R. Park, Andrew D. Pearson, Gudrun Schleiermacher, Dominique Valteau‐Couanet, Wendy B. London, Meredith S. Irwin
Pediatric Blood & Cancer.2019;[Epub] CrossRef
ALK in Neuroblastoma: Biological and Therapeutic Implications
Ricky Trigg, Suzanne Turner
Cancers.2018; 10(4): 113. CrossRef

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Topotecan-Vincristine-Doxorubicin in Stage 4 High-Risk Neuroblastoma Patients Failing to Achieve a Complete Metastatic Response to Rapid COJEC: A SIOPEN Study: Loredana Amoroso, Giovanni Erminio, Guy Makin, Andrew D. J. Pearson, Penelope Brock, Dominique Valteau-Couanet, Victoria Castel, Marlène Pasquet, Genevieve Laureys, Caroline Thomas, Roberto Luksch, Ruth Ladenstein, Riccardo Haupt, Alberto Garaventa, SIOPEN Group; Cancer Res Treat. 2018;50(1):148-155. Published online March 21, 2017; DOI: https://doi.org/10.4143/crt.2016.511

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Purpose
Metastatic response to induction therapy for high-risk neuroblastoma is a prognostic factor. In the International Society of Paediatric Oncology Europe Neuroblastoma (SIOPEN) HR-NBL-1 protocol, only patients with metastatic complete response (CR) or partial response (PR) with ≤ three abnormal skeletal areas on iodine 123-metaiodobenzylguanidine ([¹²³I]mIBG) scintigraphy and no bone marrow disease proceed to high dose therapy (HDT). In this study, topotecan-vincristine-doxorubicin (TVD) was evaluated in patients failing to achieve these criteria, with the aim of improving the metastatic response rate.
Materials and Methods
Patients with metastatic high-risk neuroblastoma who had not achieved the SIOPEN criteria for HDT after induction received two courses of topotecan 1.5 mg/m²/day for 5 days, followed by a 48-hour infusion of vincristine, 2 mg/m², and doxorubicin, 45 mg/m².
Results
Sixty-three patients were eligible and evaluable. Following two courses of TVD, four (6.4%) patients had an overall CR, while 28 (44.4%) had a PR with a combined response rate of 50.8% (95% confidence interval [CI], 37.9 to 63.6). Of these, 23 patients achieved a metastatic CR or a PR with ≤ 3 mIBG skeletal areas and no bone marrow disease (36.5%; 95% CI, 24.7 to 49.6) and were eligible to receive HDT. Toxicity was mostly haematological, affecting 106 of the 126 courses (84.1%; 95% CI, 76.5 to 90.0), and dose reduction was necessary in six patients. Stomatitis was the second most common nonhematological toxicity, occurring in 20 patients (31.7%).
Conclusion
TVD was effective in improving the response rate of high-risk neuroblastoma patients after induction with COJEC enabling them to proceed to HDT. However, the long-term benefits of TVD needs to be determined in randomized clinical trials.

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Clinical Significance of Tyrosine Hydroxylase mRNA Transcripts in Peripheral Blood at Diagnosis in Patients with Neuroblastoma: Na Hee Lee, Meong Hi Son, Young Bae Choi, Eunsang Yi, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo; Cancer Res Treat. 2016;48(4):1399-1407. Published online March 24, 2016; DOI: https://doi.org/10.4143/crt.2015.481

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to investigate the clinical significance of tyrosine hydroxylase (TH) expression in peripheral blood (PB) at diagnosis in patients with neuroblastoma.
Materials and Methods
TH mRNA expression in PB was measured by reverse transcription quantitative real-time polymerase chain reaction in 210 patients who were newly diagnosed with neuroblastoma from July 2005 to June 2015 and the clinical significance of TH expression in PB at diagnosis was evaluated.
Results
TH expression was positive in 60 patients (28.6%). Fifty of 60 TH-positive patients had metastatic tumors and the remaining 10 had localized tumors. TH expression was associated with high-risk features (i.e., advanced stage, older age, unfavorable pathology, and MYCN amplification) at diagnosis. Among TH-positive patients, higher TH expression level was observed in high-risk patients than in low- or intermediate-risk patients (p=0.035). The probability of 5-year progression-free survival (PFS) was lower in TH-positive patients than in TH-negative patients (63.8±6.9% vs. 94.7±2.1%, p < 0.001). In analysis confined to high-risk patients, the 5-year probability of PFS remained lower in TH-positive patients (55.7±8.2% vs. 89.6±5.8%, p < 0.001). Among TH-positive patients, a higher expression level of TH was associated with a worse outcome. In multivariate analyses, positive TH expression in PB at diagnosis was an independent poor prognostic factor for PFS.
Conclusion
The treatment intensity should be tailored according to TH expression in PB at diagnosis.

Citations

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Effect on Cell Cycle Progression by N-Myc Knockdown in SK-N-BE(2) Neuroblastoma Cell Line and Cytotoxicity with STI-571 Compound: Un-Young Yu, Je-Eun Cha, Sun-Young Ju, Kyung-Ah Cho, Eun-Sun Yoo, Kyung-Ha Ryu, So-Youn Woo; Cancer Res Treat. 2008;40(1):27-32. Published online March 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.1.27

Abstract PDF PubReader ePub

Purpose

Neuroblastoma is a common tumor in childhood, and generally exhibits heterogeneity and a malignant progression. MYCN expression and amplification profiles frequently correlate with therapeutic prognosis. Although it has been reported that MYCN silencing causes differentiation and apoptosis in human neuroblastoma cells, MYCN expression influences the cytotoxic potential of chemotherapeutic drugs via the deregulation of the cell cycle. STI-571 may constitute a promising therapeutic agent against neuroblastoma, particularly in cases in which c-Kit is expressed preferentially in MYCN-amplified neuroblastoma.

Materials and Methods

To determine whether STI-571 exerts a synergistic effect on cytotoxicity with MYCN expression, we assessed apoptotic cell death and cell cycle distribution after 72 h of exposure to STI-571 with or with out treatment of SK-N-BE(2) neuroblastoma cells with MYCN siRNA.

Results

MYCN siRNA-treated SK-N-BE(2) cells did not affect apoptosis and cells were arrested in G0/G1 phase after STI-571 treatment.

Conclusions

siRNA therapy targeted to MYCN may not be effective when administered in combination with STI-571 treatment in cases of neuroblastoma. Therefore, chemotherapeutic drugs that target S or G2-M phase may prove ineffective when applied to cells arrested in the G0/1 phase as the result of MYCN knockdown and STI-571 treatment.

Citations

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Journal of Translational Medicine.2026;[Epub] CrossRef
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Timofey Lebedev, Anton Buzdin, Elmira Khabusheva, Pavel Spirin, Maria Suntsova, Maxim Sorokin, Vladimir Popenko, Petr Rubtsov, Vladimir Prassolov
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Long Gu, Peiguo Chu, Robert Lingeman, Heather McDaniel, Steven Kechichian, Robert J. Hickey, Zheng Liu, Yate-Ching Yuan, John A. Sandoval, Gregg B. Fields, Linda H. Malkas
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A PCNA-Derived Cell Permeable Peptide Selectively Inhibits Neuroblastoma Cell Growth
Long Gu, Shanna Smith, Caroline Li, Robert J. Hickey, Jeremy M. Stark, Gregg B. Fields, Walter H. Lang, John A. Sandoval, Linda H. Malkas, Anja-Katrin Bielinsky
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SUMOylation of Myc-Family Proteins
Arianna Sabò, Mirko Doni, Bruno Amati, Ramin Massoumi
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Conditional expression of retrovirally delivered anti-MYCN shRNA as an in vitro model system to study neuronal differentiation in MYCN-amplified neuroblastoma
Jørn R Henriksen, Bjørn Helge Haug, Jochen Buechner, Ellen Tømte, Cecilie Løkke, Trond Flaegstad, Christer Einvik
BMC Developmental Biology.2011;[Epub] CrossRef

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Effect of Retinoic Acid on the Growth of Subcutaneously Injected C1300 Neuroblastoma and on the Survival of the Host A / J Mice: Hee Boong Park, Byeong Jun, Seung Hoon Choi; J Korean Cancer Assoc. 1994;26(1):113-119.

Abstract PDF: Deficiency of vitamin A and/or its precursors has been associated with increased cancer risk in animals and humans. Therapeutic trials of vitamin A and related compounds(retinoids) have demonstrated activities in several cancerous and precancerous conditions. We measured the effects of a retinoic acid on the growth of subcutaneously injected C1300 neuroblastoma and on the survival of the host A/J mice. The fifty A/J mice were inoculated with 10' of C- 1300 neuroblastoma cell in the right back. They were divided into five groups. One group received saline as a control. Two groups recieved 2 mg/kg and 5 mg/kg of retinoic acid. The other two groups recieved low dose(50 mg/kg and 100 mg/kg) cysclophosphamide. Tumor volume and survival were assessed. The survivals were significantly increased(p<0.05) in three groups, mice recieved 5 mg/kg of retinoic acid, 50 mg/kg and 100 mg/kg of cyclophosphamide. Tumor volumes of the mice treated with 5 mg/kg of retinoic acid were significantly lower than the control group(p<0.05). Retinoic acid suppressed the growth of neuroblastoma, it increased the survival of the treated mice if adequate doses were used.

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Effects of natural Killer Cell Manupulation on the Metastatic Cancer and Host Immune Response: Seung Hoon Choi; J Korean Cancer Assoc. 1996;28(2):368-375.

Abstract PDF: The purpose of this study was to determine the susceptibility of murine Cl300 neuroblstoma to in vivo natural killer(NK) cell mediated cytolysis and to determine if NK cells influence metastasis of this tumor. The role of NK cells in controlling the metastasis af C1300 neuroblastama to the lung was examined in A/J mice. Treatment with Interleukin-2 on days 1 through 5 after C1300 inoculation significantly decreased the tumor growth, inhibited pulmonary metastasis, and enhanced in vitro NK killing of YAC-l.Treatment with gamma Interferon on days 1 through 5 after tumuor inoculation significantly inhibited pulmonary metastasis. Antitumor effects of Interleukin-2 was stronger than that of gamma Interferon. In vivo depletion of NK cells with anti-asialo GMl significantly enhanced tumor growth and decreased host antitumor activity. These results demonstrated that in vivo elinimation of anti-asialo GM1 positive cells increased pulmonary metastasis, and in such mice, there were significant differences in metastatic potential between control and Interleukin-2, gamma Interferon treated groups.

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CD34+ Selected Peripheral Blood Stem Cell Transplantation: Hoon Kook, Hyeoung Joon Kim, Jin Soo Hwang, Keun Mo Kim, Keun Mo Kim, Ik Joo Chung, Tai Ju Hwang; J Korean Cancer Assoc. 1996;28(5):910-921.

Abstract PDF: The CD34 antigen is a 115 kDa glycoprotein that marks 1%-4% of human bone marrow cells, including virtually all committed progenitor cells and long-term reconstituting stem cells. The selection of CD34+ cells may be useful in several areas of clinical stem cell transplantation, including purging of tumor cells, T cell depletion, stem cell expansion and gene therapy. Using immunomagnetic beads method (Isolex-50TM), we report hereby the first two Korean experiences of CD34+ selected peripheral blood stem cell (PBSC) transplantations. As a mean of tumor cell purging, CD34+ cells were positively selected from mobilized PBPCs and infused to a 5-year-old girl with a relapsed stage IV neuroblastoma with resultant early short-term trilineage hematopoietic recovery. In the second patient with chronic myelogenous leukemia who showed poor graft function after having underwent an initial partially-matched bone marrow transplant, CD34+ selected allogeneic PBSC transplantation was attempted to reduce the likelihood of inducing graft-versus-host disease. Augmentation of marrow function was noted with infused PBSCs which were depleted of T cells to the degree of log3.65. As CD34+ selected PBSCs are capable of restoring hematopoietic recovery after high dose therapy, further development of selection technique to ensure high purging efficiency without significant loss of stem cells and further identification of best mobilizing and conditioning regimens are required in this new field of clinical transplantation.

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Complete Response to Treatment in a Patient with Patient with Grossly Unresectable Neuroblastoma: Won Hoe Kuh, Dong Yi Kim, Sang Young Chung, Shin Kon Kim; J Korean Cancer Assoc. 1994;26(6):1013-1020.

Abstract PDF: Neuroblastoma occurs as a derivative of neurel crest cells and occasionally can be matured from a malignant neuroblastoma into a benign ganglioneuroma. Neuroblastoma ie responsible for 10 percent of all pediatric neoplasms and seen most often in the newborn period. and the median age at diagnosis is 2 years. It has the highest rate of spontaneoue regression of any pediatric tumor. But this tumor presents with metastaaes in 70% of cases, and despite aggressive multimodal therapy, has not significantly increased the proportion of patients with advanced disease who are cured. Recently, combined treatment, including aggressive chemotherapy, radiation therapy, and surgery, has induced complete regression and prolongation of disease free survival in some patients. This article presents a case of complete regression of neuroblastoma with brief review of the literature.

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Histologically Transformed Non - Hodgkin's Lymphoma in Pregnancy: Seock Ah Im, Ki Nam Shim, Soon Nam Lee, Soo Yeon Cho, Hae Soo Koo, Kyung Ja Lee; J Korean Cancer Assoc. 1994;26(6):1020-1028.

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