Clinical features of childhood refractory cytopenia
AN Wen-Bin1, ZHANG Pei-Hong2, REN Yuan-Yuan1, GUO Ye1, WANG Shu-Chun1, CHEN Xiao-Juan1, YANG Wen-Yu1, CHANG Li-Xian1, ZHU Xiao-Fan1
Pediatric Blood Diseases Centre, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
Abstract Objective To study the clinical features of patients with refractory cytopenia of childhood (RCC). Methods The clinical data of 1 420 children (0-14 years old) with an initial diagnosis of non-severe aplastic anemia between January 1990 and June 2013 were retrospectively analyzed. Bone marrow cell morphology and histopathology were re-evaluated, and the patients were re-classified using the criteria proposed in the 2008 edition of the World Health Organization classification of RCC in hematopoietic and lymphoid tumor tissues. The clinical outcomes were followed up every 3-6 months. Results Among all the 1 420 cases, 152 (10.7%) were reassessed as RCC. Patients with RCC had a lower level of hemoglobin and a higher percentage of fetal hemoglobin than those with non-severe aplastic anemia. Of the patients with RCC, 21.5% showed abnormal karyotypes at diagnosis. The median follow-up period for all patients was 36 months (ranging from 1 to 283 months). The rates of complete response, partial response, and no response to cyclosporine and androgen treatment in RCC patients were 19.0%, 26.7%, and 54.3%, respectively. The 5- and 10-year prospective overall survival rates of RCC patients were 87.9% and 72.4%, respectively. The 5- and 10-year prospective clonal evolution rates were 15.3% and 20.0%, respectively. The 2-year prospective incidence of newly diagnosed karyotype abnormality after the initial diagnosis was 3.6%. The 5- and 10-year prospective leukemia transformation rates were 10.0% and 20.0%, respectively. Conclusions RCC shows clinical features similar to adult myelodysplastic syndrome. Children with RCC have a poor prognosis, an increased risk of transformation to leukemia, and a low response rate to cyclosporine treatment.
Baumann I, Niemeyer CM, Bennett JM, et al. WHO classification of tumors of haematopoietic and lymphoid tissues[M]//Swerdlow SH, Campo E, Harris Nl, et al. Childhood Myelodysplastic Syndrome, 2008: 104-107.
[2]
Niemeyer CM, Baumann I. Myelodysplastic syndrome in children and adolescents[J]. Semin Hematol, 2008, 45(1): 60-70.
[3]
Hasle H, Niemeyer CM, Chessells JM, et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases[J]. Leukemia, 2003, 17(2): 277-282.
[4]
Kardos G, Baumann I, Passmore SJ, et al. Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7[J]. Blood, 2003, 102(6): 1997-2003.
[5]
Incidence of aplastic anemia: the relevance of diagnostic criteria. By the International Agranulocytosis and Aplastic Anemia Study[J]. Blood, 1987, 70(6): 1718-1721.
Yang W, Zhang P, Hama A, et al. Diagnosis of acquired bone marrow failure syndrome during childhood using the 2008 World Health Organization classification system[J]. Int J Hematol, 2012, 96(1): 34-38.
[8]
Baumann I, Führer M, Behrendt S, et al. Morphological differentiation of severe aplastic anaemia from hypocellular refractory cytopenia of childhood: reproducibility of histopathological diagnostic criteria[J]. Histopathology, 2012, 61(1): 10-17.
[9]
Niemeyer CM, Baumann I. Classification of childhood aplastic anemia and myelodysplastic syndrome[J]. Hematology Am Soc Hematol Educ Program, 2011, 2011: 84-89.
Bennett JM, Orazi A. Diagnostic criteria to distinguish hypocellular acute myeloid leukemia from hypocellular myelodysplastic syndromes and aplastic anemia: recommendations for a standardized approach[J]. Haematologica, 2009, 94(2): 264-268.
[12]
Cantù Rajnoldi A, Fenu S, Kerndrup G, et al. Evaluation of dysplastic features in myelodysplastic syndromes: experience from the morphology group of the European Working Group of MDS in Childhood (EWOG-MDS)[J]. Ann Hematol, 2005, 84(7): 429-433.
[13]
Thiele J, Kvasnicka HM, Facchetti F, et al. European consensus on grading bone marrow fibrosis and assessment of cellularity[J]. Haematologica, 2005, 90(8): 1128-1132.
[14]
Shaffer LG, Slovak ML, Campbell LJ. An International System for Human Cytogenetic Nomenclature. Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature[M]. Basel, Switzerland: S. Karger AG, 2009.
[15]
Chun K, Hagemeijer A, Iqbal A, et al. Implementation of standardized international karyotype scoring practices is needed to provide uniform and systematic evaluation for patients with myelodysplastic syndrome using IPSS criteria: An International Working Group on MDS Cytogenetics Study[J]. Leuk Res, 2010, 34(2): 160-165.
[16]
Maciejewski JP, Sloand EM, Nunez O, et al. Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia[J]. Blood, 2003, 102(10): 3584-3586.
Hama A, Muramatsu H, Ito M, et al. Risk factors for clonal evolution of acquired bone marrow failure after immunosuppressive therapy in children[J/OL]. Blood (ASH Annual Meeting Abstracts), 2013, 122(21): 2473.
[19]
Narita A, Muramatsu H, Yoshida K, et al. Whole exome sequencing shows a paucity of somatic gene mutations in pediatric idiopathic bone marrow failure syndrome[J/OL]. Blood (ASH Annual Meeting Abstracts), 2013, 122(21): 3708.
[20]
Yoshimi A, Niemeyer C, Baumann I, et al. High incidence of Fanconi anaemia in patients with a morphological picture consistent with refractory cytopenia of childhood[J]. Br J Haematol, 2013, 160(1): 109-111.
[21]
Karow A, Flotho C, Schneider M, et al. Mutations of the Shwachman-Bodian-Diamond syndrome gene in patients presenting with refractory cytopenia-do we have to screen[J]. Haematologica, 2010, 95(4): 689-690.
[22]
DeZern AE, Pu J, McDevitt MA, et al. Burst-forming uniterythroid assays to distinguish cellular bone marrow failure disorders[J]. Exp Hematol, 2013, 41(9): 808-816.
[23]
Maciejewski JP, Rivera C, Kook H, et al. Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones[J]. Br J Haematol, 2001, 115(4): 1015-1022.
[24]
Wang H, Chuhjo T, Yasue S, et al. Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone marrow failure syndrome[J]. Blood, 2002, 100(12): 3897-3902.
[25]
Dunn DE, Tanawattanacharoen P, Boccuni P, et al. Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes[J]. Ann Intern Med, 1999, 131(6): 401-408.
[26]
Sugimori C, Chuhjo T, Feng X, et al. Minor population of CD55-CD59-blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia[J]. Blood, 2006, 107(4): 1308-1314.
[27]
Hata T, Tsushima H, Baba M, et al. Long-term outcome of immunosuppressive therapy for Japanese patients with lowerrisk myelodysplastic syndromes[J]. Int J Hematol, 2013, 98(6): 687-693.
[28]
Yoshimi A, van den Heuvel-Eibrink MM, Baumann I, et al. Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood[J]. Haematologica, 2014, 99(4): 656-663.
[29]
Yoshida N, Yagasaki H, Hama A, et al. Predicting response to immuno-suppressive therapy in childhood aplastic anemia[J]. Haematologica, 2011, 96(5): 771-774.
[30]
Hama S, Muramatsu H, Ito M, et al. Comparison of clinical outcome between children with aplastic anemia and refractory cytopenia of childhood who received immunosuppressive therapy with anti-thymocyte globulin and cyclosporine[J/OL]. Blood (ASH Annual Meeting Abstracts), 2011, 118: 53.
