Treatment Outcome and Prognostic Factors for Children with Advanced Non-Hodgkin's Lymphoma at a Single Institution

Joon Sup Song; Hoe Soo Youn; Ho Joon Im; Thad Ghim; Hyung Nam Moon; Jong Jin Seo

doi:10.5045/kjh.2006.41.3.157

Journal List > Korean J Hematol > v.41(3) > 1032668

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Song, Youn, Im, Ghim, Moon, and Seo: Treatment Outcome and Prognostic Factors for Children with Advanced Non-Hodgkin's Lymphoma at a Single Institution

Original Article

Korean J Hematol 2006;41(3):157-166.

Published online: 19 September 2006

DOI: https://doi.org/10.5045/kjh.2006.41.3.157

Treatment Outcome and Prognostic Factors for Children with Advanced Non-Hodgkin's Lymphoma at a Single Institution

Joon Sup Song, M.D., Hoe Soo Youn, M.D., Ho Joon Im, M.D., Thad Ghim, M.D., Hyung Nam Moon, M.D., Jong Jin Seo, M.D.

Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

∗Presently working at Pediatric Hematology-Oncology Center, Korean National Cancer Center, Goyang-si, Gyeonggi-do, Korea

Correspondence to：Jong Jin Seo, M.D. Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine 388-1, Pungnap-2 dong, Songpa-gu, Seoul 138-736, Korea Tel: +82-2-3010-3383, Fax: +82-2-473-3725 E-mail: jjseo@amc.seoul.kr

Received 20 July 2006 Revised 2 August 2006 Accepted 17 August 2006

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

Non-Hodgkin's lymphoma (NHL) accounts for over 80% of pediatric malignant lymphoma in Korea; the event free survival (EFS) of advanced stage NHL has been reported to be 60 to 70%. We accessed the outcome of advanced stage pediatric NHL at a single institution.

Methods:

Pediatric patients who were diagnosed as stage 3 or 4 with NHL from May 1991 to June 2004 at Asan Medical Center were analyzed for outcomes according to histopathology, gender, age at present, involvement of bone marrow or central nervous system (CNS), and serum level of lactate dehydrogenase (LDH).

Results:

Sixty-three patients were enrolled in this study. The head and neck were the most common primary site. The five-year EFS and overall survival (OS) were 68% and 78%, respectively. Five-year EFS for lymphoblastic, Burkitt, anaplastic large cell and diffuse large B cell lymphoma were 62%, 86%, 74% and 63%, respectively. Five-year EFS and OS for patients with LDH≤500IU/L were 85% and 100%, while those with LDH＞500IU/L were 64% and 72% (P=0.04). There was no significant difference in EFS or OS with regard to other factors. Sixteen out of the 63 patients relapsed, and the five-year OS for those who relapsed was 44%.

Conclusion:

The outcome of patients with advanced stage NHL treated at our institution was comparable with previous reports. High serum level of LDH at diagnosis proved to be a poor prognostic factor. New effective treatment regimens are needed to improve the outcome of pediatric patients with relapsed NHL.

Keywords: Non-Hodgkin's lymphoma, Advanced stage, Outcome, Prognostic factor, Children

REFERENCES

1). Fisher SG., Fisher RI. The epidemiology of non-Hodgkin's lymphoma. Oncogene. 2004. 23:6524–34.

2). Sandlund JT., Downing JR., Crist WM. Non-Hodgkin's lymphoma in childhood. N Engl J Med. 1996. 334:1238–48.

3). Lyu CJ., Kang IJ., Koo HH, et al. Epidemiology and clinical outcome in children with malignant lymphoma in Korea. Korean J Pediatr Hematol-Oncol. 2004. 11:153–63.

4). Laver JH., Kraveka JM., Hutchison RE, et al. Advanced-stage large-cell lymphoma in children and adolescents: results of a randomized trial incorporating intermediate-dose methotrexate and high-dose cytarabine in the maintenance phase of the APO Regimen: a Pediatric Oncology Group phase III trial. J Clin Oncol. 2005. 23:541–7.

5). Mora J., Filippa DA., Qin J., Wollner N. Lymphoblastic lymphoma of childhood and the LSA₂L₂ protocol: the 30-year experience at Memorial Sloan-Kettering Cancer Center. Cancer. 2003. 98:1283–91.

6). Brecher ML., Schwenn MR., Coppes MJ, et al. Fractionated cyclophosphamide and back to back high dose methotrexate and cytosine arabinoside improves outcome in patients with stage III high grade small non-cleaved cell lymphomas (SNCCL): a randomized trial of the Pediatric Oncology Group. Med Pediatr Oncol. 1997. 29:526–33.

7). Yoo KH., Kim SJ., Kim SH, et al. Clinical characteristics and treatment outcome of pediatric patients with Burkitt lymphoma. Korean J Pediatr Hematol-Oncol. 2002. 9:38–45.

8). Lim YJ., Kim YJ., Song JS, et al. Treatment outcome of childhood B-cell lymphoma and L3 acute lymphoblastic leukemia from a single institution. Korean J Pediatr Hematol-Oncol. 2005. 12:28–39.

9). Seidemann K., Tiemann M., Schrappe M, et al. Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. Blood. 2001. 97:3699–706.

10). Atra A., Imeson JD., Hobson R, et al. Improved outcome in children with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL): results of the United Kingdom Children Cancer Study Group (UKCC SG) 9002 protocol. Br J Cancer. 2000. 82:1396–402.

11). Sposto R., Meadows AT., Chilcote RR, et al. Comparison of long-term outcome of children and adolescents with disseminated non-lymphoblastic nonHodgkin lymphoma treated with COMP or daunomycin-COMP: a report from the Children's Cancer Group. Med Pediatr Oncol. 2001. 37:432–41.

12). Reiter A., Schrappe M., Tiemann M, et al. Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: a report of the Berlin-Frankfurt-Munster Group trial NHL-BFM 90. Blood. 1999. 94:3294–306.

13). Seidemann K., Tiemann M., Schrappe M, et al. Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Munster Group Trial NHL-BFM 90. Blood. 2001. 97:3699–706.

14). Williams DM., Hobson R., Imeson J, et al. Anaplastic large cell lymphoma in childhood: analysis of 72 patients treated on The United Kingdom Children's Cancer Study Group chemotherapy regimens. Br J Haematol. 2002. 117:812–20.

15). Laver JH., Mahmou H., Pick TE, et al. Results of a randomized phase III trial in children and adolescents with advanced stage diffuse large cell non-Hodgkin's lymphoma: a Pediatric Oncology Group study. Leuk Lymphoma. 2002. 43:105–9.

16). Schwenn MR., Blattner SR., Lynch E., Weinstein HJ. HiC-COM: a 2-month intensive chemotherapy regimen for children with stage III and IV Burkitt's lymphoma and B-cell acute lymphoblastic leukemia. J Clin Oncol. 1991. 9:133–8.

17). Finlay JL., Anderson JR., Cecalupo AJ, et al. Disseminated nonlymphoblastic lymphoma of childhood: a Children Cancer Group Study, CCG 552. Med Pediatr Oncol. 1994. 23:453–63.

18). Reiter A., Schrappe M., Parwaresch R, et al. Non-Hodgkin's lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage-a report of the Berlin-Frankfurt-Münster Group. J Clin Oncol. 1995. 13:359–72.

19). Patte C., Philip T., Rodary C, et al. High survival rate in advanced-stage B-cell lymphomas and leukemias without CNS involvement with a short intensive polychemotherapy: results from the French Pediatric Oncology Society of a randomized trial of 216 children. J Clin Oncol. 1991. 9:123–32.

20). Bowman WP., Shuster JJ., Cook B, et al. Improved survival for children with B-cell acute lymphoblastic leukaemia and stage IV small noncleaved-cell lymphoma: a Pediatric Oncology Group study. J Clin Oncol. 1996. 14:1252–61.

21). Anderson JR., Jenkin RD., Wilson JF, et al. Longterm follow-up of patients treated with COMP or LSA₂L₂ therapy for childhood non-Hodgkin's lymphoma: a report of CCG-551 from the Childrens Cancer Group. J Clin Oncol. 1993. 11:1024–32.

22). Patte C., Philip T., Rodary C, et al. Improved survival rate in children with stage III and IV B cell non-Hodgkin's lymphoma and leukemia using multiagent chemotherapy: results of a study of 114 children from the French Pediatric Oncology Society. J Clin Oncol. 1986. 4:1219–26.

23). Yaniv I., Fischer S., Mor C, et al. Improved outcome in childhood B-cell lymphoma with the intensified French LMB Protocol. Med Pediatr Oncol. 2000. 35:8–12.

24). Pillon M., Di Tullio MT., Garaventa A, et al. Longterm results of the first Italian Association of Pediatric Hematology and Oncology protocol for the treatment of pediatric B-cell non-Hodgkin lymphoma (AI EOP LNH92). Cancer. 2004. 101:385–94.

25). Reiter A., Schrappe M., Ludwig WD, et al. Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM group report. Blood. 2000. 95:416–21.

26). Harris NL., Jaffe ES., Stein H, et al. A Revised European-American Classification of Lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood. 1994. 84:1361–92.

27). Patte C., Auperin A., Michon J, et al. The Societe Francaise d'Oncologie Pediatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood. 2001. 97:3370–9.

28). Gururangan S., Sposto R., Cairo MS., Meadows AT., Finlay JL. Outcome of CNS disease at diagnosis in disseminated small non cleaved-cell lymphoma and B-cell leukemia: a Children's Cancer Group study. J Clin Oncol. 2000. 18:2017–25.

29). Levine JE., Harris RE., Loberiza FR Jr, et al. A comparison of allogeneic and autologous bone marrow transplantation for lymphoblastic lymphoma. Blood. 2003. 101:2476–82.

30). Ladenstein R., Pearce R., Hartmann O., Patte C., Goldstone T., Philip T. High-dose chemotherapy with autologous bone marrow rescue in children with poor-risk Burkitt's lymphoma: a report from the European Lymphoma Bone Marrow Transplantation Registry. Blood. 1997. 90:2921–30.

31). Brugieres L., Quartier P., Le Deley MC, et al. Relapse of childhood anaplastic large-cell lymphoma: treatment results in a series of 41 children-a report from the French Society of Pediatric Oncology. Ann Oncol. 2000. 11:53–8.

32). Kung FH., Harris MB., Krischer JP. Ifosfamide/carbo-platin/etoposide (ICE), an effective salvaging therapy for recurrent malignant non-Hodgkin lymphoma of childhood: a Pediatric Oncology Group phase II study. Med Pediatr Oncol. 1999. 32:225–6.

33). Sandlund JT., Bowman L., Heslop , et al. Intensive chemotherapy with hematopoietic stem-cell support for children with recurrent or refractory NHL. Cy-totherapy. 2002. 4:253–8.

Fig. 1

Five-year event free survival (EFS) and overall survival (OS) of total pediatric patients with advanced stage non-Hodgkin's lymphoma. The estimates are means±SE.

Fig. 2

Five-year event free survival (EFS) and overall survival (OS) of pediatric patients with non-Hodgkin's lymphoma according to serum lactate dehydrogenase (LDH) level. A: EFS at 5 years for pediatric patients with serum LDH≤500 IU/L, B: EFS at 5 years for pediatric patients with serum LDH＞500 IU/L: P=0.15, C: OS at 5 years for pediatric patients with serum LDH≤500 IU/L, D: OS at 5 years for pediatric patients with serum LDH＞500 IU/L: P=0.04. The estimates are means±SE.

Fig. 3

Five-year overall survival (mean±SE) of pediatric patients with relapsed non-Hodgkin's lymphoma.

Table 1.

Characteristics of pediatric patients with advanced stage non-Hodgkin's lymphoma

Variables	No. of patients with stage 3 (n=33)	No. of patients with stage 4 (n=30)	Total (n=63)
Age (years)
Median	9.1	5.7	8
Range	1.1～15.9	1.4～14.2	1.1～15.9
Gender (male:femal	e) 20:13	20:10	40:23
Initial serum LDH
≤500 IU/L	5	10	15
＞500 IU/L	22	23	45
Metastasis
BM (－)/CNS (－	) 33	7	40
BM (+)/CNS (－)	) 0	15	15
BM (－)/CNS (+)	) 0	6	6
BM (+)/CNS (+)	0	2	2
Histopathology
Lymphoblastic	12	17	29
Burkitt	7	7	14
Diffuse large B c	ell 4	4	8
Anaplastic large	cell 8	1	9
Other	2	1	3

Abbreviations: LDH, lactate dehydrogenase; BM, bone marrow; CNS, central nervous system.

Table 2.

Presenting manifestations at diagnosis in pediatric patients with advanced stage non-Hodgkin's lymphoma

Clinical manifestations	No. of patients (%)
Palpable mass	16 (26%)
Fever	14 (23%)
Lymph node enlargement	9 (14%)
Abdominal pain	7 (11%)
Abdominal distention	4 (6%)
Dyspnea	4 (6%)
Nasal obstruction	4 (6%)
Weight loss	2 (3%)
Cough	2 (3%)
Petechiae, anemia	1 (2%)

Table 3.

Primary site of pediatric patients with non-Hodgkin's lymphoma at diagnosis

Primary site	No. of patients (%)
Head and neck	24 (36)
Abdomen	14 (22)
Mediastinum	13 (21)
Peripheral lymph node	10 (16)
Other	2 (3)

Table 4.

Incidence of pediatric patients with advance stage non-Hodgkin lymphoma by histopathology

Histopathology	No. of patients (%)
Lymphoblasrtic lymphoma	29 (48)
Burkitt lymphoma	14 (24)
Anaplastic large cell lymphoma	9 (15)
Diffuse large B cell lymphoma	8 (13)
Total patients	60

Table 5.

Five-year event free survival (EFS) and overall survival (OS) of pediatric patients with non-Hodgkin's lymphoma according to factors

Factor	No. of patients	5-year EFS			5-year OS
Factor	No. of patients	%	SE (%)	P	%	SE (%)	P
Age at diagnosis				0.17			0.88
≤10-year	40	74.6	7.0		77.2	6.7
＞10-year	23	55.8	19.5		78.3	8.6
Stage				0.22			0.17
3	33	74.9	7.8		84.9	6.2
4	30	60.0	8.9		70.0	8.4
Histopathology				0.42			0.20
LL	29	61.7	9.1		75.5	8.1
BL	14	85.7	9.4		85.7	9.4
DLBL	8	62.5	17.1		62.5	17.1
ALCL	9	74.1	16.1		100	－
Serum LDH level				0.15			0.04
≤500 IU/L	14	85.1	9.7		100	－
＞500 IU/L	47	63.6	7.1		72.2	6.6
CNS/BM involvement				0.12			0.12
CNS (－)/BM (－)	40	77.1	6.7		77.1	6.7
CNS (－)/BM (+)	15	93.3	6.4		93.3	6.4
CNS (+)/BM (－)	6	50.0	20.0		50.0	20.0

Abbreviations: SE, standard error; LL, lymphoblastic lymphoma; BL, Burkitt lymphoma; DLBL, diffuse large B cell lymphoma ALCL, anaplastic large cell lymphoma; CNS, central nervous system; BM, bone marrow.

TOOLS

Similar articles