Abstract Objective To explore the clinical-biological characteristics and prognosis of pediatric pro-B cell acute lymphoblastic leukemia (pro-B-ALL). Methods A total of 64 patients aged less than 18 years old with pro-BALL were enrolled. Clinical characteristics, therapeutic effect and prognostic factors were retrospectively analyzed. Results Pro-B-ALL occurred in 6.23% (64/1 028) of pediatric ALL. Among the 64 patients, 35 were male and 29 were female. The median age was 7.0 years (range 0.4-16.0 years) at diagnosis, of which 39% and 6% were ≥ 10 years old and < 1 year old respectively. The median WBC count was 25.5×109/L[range (0.4-831.9)×109/L], of which 35.9% were ≥ 50×109/L. MLL-r positivity was the most frequent genetic alteration in pro-B ALL, occurring in 34% of patients, with lower frequency of CD22 and CD13 expression and higher frequency of CD7 expression, while lower frequency of CD33 expression was found in patients with MLL-AF4 positivity. At a median follow-up of 60.0 months (range 4.9-165.3 months), the estimated 5-year overall survival (OS) and event-free survival (EFS) in the 64 patients were (85±5)% and (78±5)% respectively. Cox proportional hazards regression analysis identified MRD ≥ 0.1% at 3 months after chemotherapy as an independent adverse prognostic factor for both 5-year OS and EFS. Conclusions Pediatric pro-B ALL is a heterogeneous disease with clinical and biological diversity. Biological characteristics, such as immunological markers, genetic alterations, and MRD at 3 months after chemotherapy may be important factors for the long-term prognosis.
Gao C, Liu SG, Yue ZX, et al. Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol:a study of 121 Chinese children[J]. Cancer Cell Int, 2019, 19:293.
[2]
Bene MC, Castoldi G, Knapp W, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL)[J]. Leukemia, 1995, 9(10):1783-1786.
[3]
Chen D, Gerasimčik N, Camponeschi A, et al. CD27 expression and its association with clinical outcome in children and adults with pro-B acute lymphoblastic leukemia[J]. Blood Cancer J, 2017, 7(6):e575.
[4]
Pui CH, Rivera GK, Hancock ML, et al. Clinical significance of CD10 expression in childhood acute lymphoblastic leukemia[J]. Leukemia, 1993, 7(1):35-40.
[5]
Winters AC, Bernt KM. MLL-rearranged leukemias-an update on science and clinical approaches[J]. Front Pediatr, 2017, 5:4.
Cui L, Li ZG, Chai YH, et al. Outcome of children with newly diagnosed acute lymphoblastic leukemia treated with CCLG-ALL 2008:the first nation-wide prospective multicenter study in China[J]. Am J Hematol, 2018, 93(7):913-920.
Attarbaschi A, Mann G, König M, et al. Mixed lineage leukemia-rearranged childhood pro-B and CD10-negative pre-B acute lymphoblastic leukemia constitute a distinct clinical entity[J]. Clin Cancer Res, 2006, 12(10):2988-2994.
[11]
Dreyer ZE, Hilden JM, Jones TL, et al. Intensified chemotherapy without SCT in infant ALL:results from COG P9407(Cohort 3)[J]. Pediatr Blood Cancer, 2015, 62(3):419-426.
[12]
Meyer C, Burmeister T, Gröger D, et al. The MLL recombinome of acute leukemias in 2017[J]. Leukemia, 2018, 32(2):273-284.
[13]
Sun YN, Hu YX, Gao L, et al. The therapeutic efficacy of pediatric ALL patients with MLL gene rearrangement treated with CCLG-ALL2008 protocol[J]. Eur Rev Med Pharmacol Sci, 2018, 22(18):6020-6029.
[14]
Kato M, Hasegawa D, Koh K, et al. Allogeneic haematopoietic stem cell transplantation for infant acute lymphoblastic leukaemia with KMT2A (MLL) rearrangements:a retrospective study from the paediatric acute lymphoblastic leukaemia working group of the Japan Society for Haematopoietic Cell Transplantation[J]. Br J Haematol, 2015, 168(4):564-570.
[15]
Bai L, Cheng YF, Lu AD, et al. Prognosis of haploidentical hematopoietic stem cell transplantation in non-infant children with t(v;11q23)/MLL-rearranged B-cell acute lymphoblastic leukemia[J]. Leuk Res, 2020, 91:106333.
Jiang Z, Wu D, Lin S, et al. CD34 and CD38 are prognostic biomarkers for acute B lymphoblastic leukemia[J]. Biomark Res, 2016, 4:23.
[18]
Raponi S, De Propris MS, Intoppa S, et al. Flow cytometric study of potential target antigens (CD19, CD20, CD22, CD33) for antibody-based immunotherapy in acute lymphoblastic leukemia:analysis of 552 cases[J]. Leuk Lymphoma, 2011, 52(6):1098-1107.
[19]
Li XM, Zhang LP, Wang YZ, et al. CD38+ CD58- is an independent adverse prognostic factor in paediatric Philadelphia chromosome negative B cell acute lymphoblastic leukaemia patients[J]. Leuk Res, 2016, 43:33-38.
van Dongen JJ, van der Velden VH, Brüggemann M, et al. Minimal residual disease diagnostics in acute lymphoblastic leukemia:need for sensitive, fast, and standardized technologies[J]. Blood, 2015, 125(26):3996-4009.
[22]
Berry DA, Zhou S, Higley H, et al. Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia:a meta-analysis[J]. JAMA Oncol, 2017, 3(7):e170580.
[23]
Pui CH, Campana D. Minimal residual disease in pediatric ALL[J]. Oncotarget, 2017, 8(45):78251-78252.
[1]
LI Lei, ZHANG Zhi-Quan, ZHENG Cheng-Zhong, SHI Yuan, Pediatric Disaster Branch of Chinese Pediatric Society of Chinese Medical Association, Pediatric Branch of Chinese People's Liberation Army. Expert consensus on the prevention and treatment of drowning in children[J]. CJCP, 2021, 23(1): 12-17.
