Clinical Features and Outcomes of Relapsed Acute Lymphoblastic Leukemia in Children_West China Medical Journal

Authors：

 CHENXiao-xi , WUJian-rong , WANChao-min ,  GAOJu

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

GAOJu, Email: gaoju651220@126.com

Keywords：

Acute lymphoblastic leukemia; Relapse; Clinical features; Children

DOI：

10.7507/1002-0179.20150254

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Objective To explore the clinical features and outcomes of relapsed acute lymphoblastic leukemia (ALL) in children. Methods Thirty-two ALL children treated in line with the Chinese Child Leukemia Cooperative Group ALL-2008 protocol with a relapse of the disease during January 2009 to May 2013 were enrolled into this study. Their clinical features and outcomes were retrospectively analyzed and compared with those who achieved continuous complete remission (CCR). Results There were 32 relapsed cases among 319 newly diagnosed ALL cases (excluding infantile ALL) during the study period, with a relapse rate of 10%. In the relapse group, the proportions of patients with peripheral blood white blood cell count ≥50×10⁹/L at diagnosis, positive BCR/ABL fusion gene, poor prednisone response, high risk stratification, and who failed to achieve bone marrow complete remission at d15 and d33 of induction chemotherapy, were significantly higher than those in the CCR group (all P<0.05). Multivariate analysis showed that high risk stratification was an independent risk factor for relapse (OR=3.529, P=0.002). In terms of site of relapse, isolated marrow relapse, isolated central nervous system relapse, isolated testicular relapse and combined relapse accounted for 23 (72%), 6 (19%), 1 (3%) and 2 (6%), respectively. As regard to the time of relapse, 26 cases (81%), 4 cases (13%) and 2 cases (6%) were categorized as very early relapse, early relapse and late relapse respectively. Twenty-four children with relapsed ALL received re-induction chemotherapy. Among them, 16 cases (67%) achieved second complete remission. Nevertheless, 9 cases ultimately suffered second relapse. Conclusion Relapse, which occurs more commonly in high risk ALL group, still remains a great challenge in clinical practice. Relapsed ALL, especially those with very early and early marrow relapse, has poor prognosis.

Citation： CHENXiao-xi, WUJian-rong, WANChao-min, GAOJu. Clinical Features and Outcomes of Relapsed Acute Lymphoblastic Leukemia in Children. West China Medical Journal, 2015, 30(5): 885-889. doi: 10.7507/1002-0179.20150254 Copy

1.	Pui CH, Pei D, Sandlund JT, et al. Long-term results of St Jude Total Therapy Studies 11, 12, 13A, 13B, and 14 for childhood acute lymphoblastic leukemia[J]. Leukemia, 2010, 24(2):371-382.
2.	Möricke A, Zimmermann M, Reiter A, et al. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000[J]. Leukemia, 2010, 24(2):265-284.
3.	Tsuchida M, Ohara A, Manabe A, et al. Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984-1999[J]. Leukemia, 2010, 24(2):383-396.
4.	吴敏媛, 李志光, 李志刚. 儿童急性淋巴细胞性白血病治疗策略的思考[J]. 中华儿科杂志, 2010, 48(3):161-165.
5.	梅妍妍, 高超, 崔蕾, 等. 儿童E2A-PBX1融合基因阳性急性淋巴细胞白血病两种化疗方案的疗效比较[J]. 中华儿科杂志, 2013, 51(6):467-471.
6.	Eckert C, Henze G, Seeger K, et al. Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group[J]. J Clin Oncol, 2013, 31(21):2736-2742.
7.	Nguyen K, Devidas M, Cheng SC, et al. Factors influencing survival after relapse from acute lymphoblastic leukemia:a Children's Oncology Group study[J]. Leukemia, 2008, 22(12):2142-2150.
8.	Marjerrison S, Antillon F, Fu L, et al. Outcome of children treated for relapsed acute lymphoblastic leukemia in Central America[J]. Cancer, 2013, 119(6):1277-1283.
9.	贾友超, 竺晓凡. 儿童急性淋巴细胞白血病复发的治疗[J]. 国际输血及血液学杂志, 2008, 31(2):167-170.
10.	Leung AW, Vincent L, Chiang AK, et al. Prognosis and outcome of relapsed acute lymphoblastic leukemia:a Hong Kong Pediatric Hematology and Oncology Study Group report[J]. Pediatr Blood Cancer, 2012, 59(3):454-460.
11.	August KJ, Narendran A, Neville KA. Pediatric relapsed or refractory leukemia:new pharmacotherapeutic developments and future directions[J]. Drugs, 2013, 73(5):439-461.
12.	Miano M, Pistorio A, Putti MC, et al. Clofarabine, cyclophosphamide and etoposide for the treatment of relapsed or resistant acute leukemia in pediatric patients[J]. Leuk Lymphoma, 2012, 53(9):1693-1698.
13.	Bailey LC, Lange BJ, Rheingold SR, et al. Bone-marrow relapse in paediatric acute lymphoblastic leukaemia[J]. Lancet Oncol, 2008, 9(9):873-883.
14.	Barredo JC, Devidas M, Lauer SJ, et al. Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation:a pediatric oncology group study[J]. J Clin Oncol, 2006, 24(19):3142-3149.
15.	Jacobs JE, Hastings C. Isolated extramedullary relapse in childhood acute lymphocytic leukemia[J]. Curr Hematol Malig Rep, 2010, 5(4):185-191.
16.	Freeman AI, Weinberg V, Brecher ML, et al. Comparison of intermediate-dose methotrexate with cranial irradiation for the post-induction treatment of acute lymphocytic leukemia in children[J]. N Engl J Med, 1983, 308(9):477-484.
17.	Brecher ML, Weinberg V, Boyett JM, et al. Intermediate dose methotrexate in childhood acute lymphoblastic leukemia resulting in decreased incidence of testicular relapse[J]. Cancer, 1986, 58(5):1024-1028.
18.	Arima K, Hasegawa D, Ogawa C, et al. Detection of submicroscopic disease in the bone marrow and unaffected testis of a child with T-cell acute lymphoblastic leukemia who experienced "isolated" testicular relapse[J]. Int J Hematol, 2009, 90(3):370-373.
19.	Hagedorn N, Acquaviva C, Fronkova E, et al. Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia:a more precise definition of "isolated" and its possible clinical implications, a collaborative study of the Resistant Disease Committee of the International BFM study group[J]. Blood, 2007, 110(12):4022-4029.

1. Pui CH, Pei D, Sandlund JT, et al. Long-term results of St Jude Total Therapy Studies 11, 12, 13A, 13B, and 14 for childhood acute lymphoblastic leukemia[J]. Leukemia, 2010, 24(2):371-382.
2. Möricke A, Zimmermann M, Reiter A, et al. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000[J]. Leukemia, 2010, 24(2):265-284.
3. Tsuchida M, Ohara A, Manabe A, et al. Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984-1999[J]. Leukemia, 2010, 24(2):383-396.
4. 吴敏媛, 李志光, 李志刚. 儿童急性淋巴细胞性白血病治疗策略的思考[J]. 中华儿科杂志, 2010, 48(3):161-165.
5. 梅妍妍, 高超, 崔蕾, 等. 儿童E2A-PBX1融合基因阳性急性淋巴细胞白血病两种化疗方案的疗效比较[J]. 中华儿科杂志, 2013, 51(6):467-471.
6. Eckert C, Henze G, Seeger K, et al. Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group[J]. J Clin Oncol, 2013, 31(21):2736-2742.
7. Nguyen K, Devidas M, Cheng SC, et al. Factors influencing survival after relapse from acute lymphoblastic leukemia:a Children's Oncology Group study[J]. Leukemia, 2008, 22(12):2142-2150.
8. Marjerrison S, Antillon F, Fu L, et al. Outcome of children treated for relapsed acute lymphoblastic leukemia in Central America[J]. Cancer, 2013, 119(6):1277-1283.
9. 贾友超, 竺晓凡. 儿童急性淋巴细胞白血病复发的治疗[J]. 国际输血及血液学杂志, 2008, 31(2):167-170.
10. Leung AW, Vincent L, Chiang AK, et al. Prognosis and outcome of relapsed acute lymphoblastic leukemia:a Hong Kong Pediatric Hematology and Oncology Study Group report[J]. Pediatr Blood Cancer, 2012, 59(3):454-460.
11. August KJ, Narendran A, Neville KA. Pediatric relapsed or refractory leukemia:new pharmacotherapeutic developments and future directions[J]. Drugs, 2013, 73(5):439-461.
12. Miano M, Pistorio A, Putti MC, et al. Clofarabine, cyclophosphamide and etoposide for the treatment of relapsed or resistant acute leukemia in pediatric patients[J]. Leuk Lymphoma, 2012, 53(9):1693-1698.
13. Bailey LC, Lange BJ, Rheingold SR, et al. Bone-marrow relapse in paediatric acute lymphoblastic leukaemia[J]. Lancet Oncol, 2008, 9(9):873-883.
14. Barredo JC, Devidas M, Lauer SJ, et al. Isolated CNS relapse of acute lymphoblastic leukemia treated with intensive systemic chemotherapy and delayed CNS radiation:a pediatric oncology group study[J]. J Clin Oncol, 2006, 24(19):3142-3149.
15. Jacobs JE, Hastings C. Isolated extramedullary relapse in childhood acute lymphocytic leukemia[J]. Curr Hematol Malig Rep, 2010, 5(4):185-191.
16. Freeman AI, Weinberg V, Brecher ML, et al. Comparison of intermediate-dose methotrexate with cranial irradiation for the post-induction treatment of acute lymphocytic leukemia in children[J]. N Engl J Med, 1983, 308(9):477-484.
17. Brecher ML, Weinberg V, Boyett JM, et al. Intermediate dose methotrexate in childhood acute lymphoblastic leukemia resulting in decreased incidence of testicular relapse[J]. Cancer, 1986, 58(5):1024-1028.
18. Arima K, Hasegawa D, Ogawa C, et al. Detection of submicroscopic disease in the bone marrow and unaffected testis of a child with T-cell acute lymphoblastic leukemia who experienced "isolated" testicular relapse[J]. Int J Hematol, 2009, 90(3):370-373.
19. Hagedorn N, Acquaviva C, Fronkova E, et al. Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia:a more precise definition of "isolated" and its possible clinical implications, a collaborative study of the Resistant Disease Committee of the International BFM study group[J]. Blood, 2007, 110(12):4022-4029.

West China Medical Journal

Clinical Features and Outcomes of Relapsed Acute Lymphoblastic Leukemia in Children

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