Clinical features and prognosis of children with acute lymphoblastic leukemia and different platelet levels
ZHANG Ao-Li1,2, CHEN Xiao-Juan1, ZOU Yao1, YANG Wen-Yu1, GUO Ye1, WANG Shu-Chun1, ZHANG Li1, LIU Xiao-Ming1, RUAN Min1, LIU Tian-Feng1, QI Ben-Quan1, ZHU Xiao-Fan1
Department of Pediatric Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China
Abstract：Objective To study the association of platelet level at diagnosis with prognosis in children with acute lymphoblastic leukemia (ALL). Methods A total of 892 children with ALL who underwent chemotherapy with the CCLG-ALL 2008 regimen were enrolled. According to the platelet count at diagnosis, these children were divided into normal platelet count group (platelet count ≥ 100×109/L; n=263) and thrombocytopenia group (platelet count < 100×109/L; n=629). The thrombocytopenia group was further divided into (50- < 100)×109/L (n=243), (20- < 50)×109/L (n=263), and < 20×109/L (n=123) subgroups. The association of clinical features (sex, age, immunophenotype, and molecular biology) with event-free survival (EFS) and overall survival (OS) was analyzed. Results Compared with the thrombocytopenia group, the normal platelet count group had significantly lower positive rate of MLL gene rearrangement and recurrence rate (P < 0.05), as well as a significantly higher 10-year EFS rate (P < 0.05). There was no significant difference in 10-year OS between the two groups (P > 0.05). The normal platelet count group still had a significantly higher 10-year EFS rate than the thrombocytopenia group after the children with MLL gene rearrangement were excluded (P < 0.05), and there was still no significant difference in 10-year OS between the two groups (P > 0.05). The < 20×109/L subgroup had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50- < 100)×109/L subgroup, and the (20- < 50)×109/L subgroup (P < 0.05). After the children with MLL gene rearrangement were excluded, the < 20×109/L subgroup still had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50- < 100)×109/L subgroup, and the (20- < 50)×109/L subgroup (P < 0.05). Conclusions ALL children with MLL gene rearrangement often have the clinical manifestation of thrombocytopenia. Platelet level at diagnosis is associated with the prognosis of ALL children. The children with normal platelet count have a low recurrence rate and good prognosis, and those with a platelet count of < 20×109/L have the worst prognosis.
ZHANG Ao-Li,CHEN Xiao-Juan,ZOU Yao et al. Clinical features and prognosis of children with acute lymphoblastic leukemia and different platelet levels[J]. CJCP, 2019, 21(8): 766-771.
Hunger SP, Lu X, Devidas M, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005:a report from the children's oncology group[J]. J Clin Oncol, 2012, 30(14):1663-1669.
[5]
Pieters R, de Groot-Kruseman H, Van der Velden V, et al. Successful therapy reduction and intensification for childhood acute lymphoblastic leukemia based on minimal residual disease monitoring:study ALL10 from the Dutch Childhood Oncology Group[J]. J Clin Oncol, 2016, 34(22):2591-2601.
[6]
Stary J, Zimmermann M, Campbell M, et al. Intensive chemotherapy for childhood acute lymphoblastic leukemia:results of the randomized intercontinental trial ALL IC-BFM 2002[J]. J Clin Oncol, 2014, 32(3):174-184.
[7]
Faderl S, Thall PF, Kantarjian HM, et al. Time to platelet recovery predicts outcome of patients with de novo acute lymphoblastic leukaemia who have achieved a complete remission[J]. Br J Haematol, 2002, 117(4):869-874.
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.
[11]
Yokoyama A. Transcriptional activation by MLL fusion proteins in leukemogenesis[J]. Exp Hematol, 2017, 46:21-30.
[12]
Behm FG, Raimondi SC, Frestedt JL, et al. Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age[J]. Blood, 1996, 87(7):2870-2877.
[13]
Marschalek R. MLL leukemia and future treatment strategies[J]. Arch Pharm (Weinheim), 2015, 348(4):221-228.
[14]
Tabe Y, Konopleva M. Advances in understanding the leukaemia microenvironment[J]. Br J Haematol, 2014, 164(6):767-778.
[15]
Ruscetti FW, Akel S, Bartelmez SH. Autocrine transforming growth factor-β regulation of hematopoiesis:many outcomes that depend on the context[J]. Oncogene, 2005, 24(37):5751-5763.
[16]
Villmow T, Kemkes-Matthes B, Matzdorff AC. Markers of platelet activation and platelet-leukocyte interaction in patients with myeloproliferative syndromes[J]. Thromb Res, 2002, 108(2-3):139-145.
[17]
Verheul HM, Pinedo HM. Tumor growth:a putative role for platelets?[J]. Oncologist, 1998, 3(2):Ⅱ.
[18]
Ostman A. PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma[J]. Cytokine Growth Factor Rev, 2004, 15(4):275-286.
[19]
Gupta GP, Massagué J. Platelets and metastasis revisited:a novel fatty link[J]. J Clin Invest, 2004, 114(12):1691-1693.
[20]
Stanger BZ, Kahn ML. Platelets and tumor cells:a new form of border control[J]. Cancer Cell, 2013, 24(1):9-11.
[21]
Qian X, Wen-jun L. Platelet changes in acute leukemia[J]. Cell Biochem Biophys, 2013, 67(3):1473-1479.
