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Published in: Indian Journal of Hematology and Blood Transfusion 1/2018

01-01-2018 | Original Article

Comparative Study of Clinico-hematological Features, Molecular Spectrum and Response to Imatinib in Chronic Myelogenous Leukemia Patients: Pediatric and Adolescent Versus Adults

Authors: Anita Tahlan, Neelam Varma, Shano Naseem, Deepak Bansal, Jogeshwar Binota, Anil Sood, Man Updesh Singh Sachdeva, Pankaj Malhotra, Subhash Varma

Published in: Indian Journal of Hematology and Blood Transfusion | Issue 1/2018

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Abstract

Chronic myelogenous leukemia (CML) is a rare disease in children, accounting for approximately 3% of leukemias in children and adolescents, with an annual incidence of 1 case per million children in western countries. This study was conducted, at PGIMER, Chandigarh. Ninety eight patients, 48 in children and adolescents group, and 50 in adult group were included in the study. Their hematological profiles along with the bone marrow findings were analyzed. The diagnosis of CML was confirmed by cytogenetics and/or molecular analysis. The complete hematological response (CHR) was analyzed at 3 months and cytogentic response (CgR) at 12 months after starting imatinib therapy. Compared to adults, pediatric and adolescent patients were more symptomatic at presentation (93.5 vs. 75%). Among symptomatic patients, massive splenomegaly (>10 cm), higher total leucocyte and platelet counts were seen more frequently in pediatric patients. The most common transcript in both groups was e14a2. The distribution of pediatric and adolescent cases in Sokal, Hasford and EUTOS score, showed only statistically significant difference for low risk Sokal group, which had more patients in pediatric group. Compared to adults, pediatric and adolescent patients had similar CHR rate (91.3 vs. 92%), but showed lesser major CgR rate (90.9 vs. 95.5%) however, this was not statistically significant.
Literature
1.
go back to reference Millot F, Traore P, Guilhot J, Nelken B, Leblanc T, Leverger G et al (2005) Clinical and biological features at diagnosis in 40 children with chronic myeloid leukemia. Pediatrics 116:140–143CrossRefPubMed Millot F, Traore P, Guilhot J, Nelken B, Leblanc T, Leverger G et al (2005) Clinical and biological features at diagnosis in 40 children with chronic myeloid leukemia. Pediatrics 116:140–143CrossRefPubMed
2.
go back to reference Hasan SK, Sazawal S, Kumar B, Chaubey R, Mishra P, Mir R et al (2006) Childhood CML in India: b2a2 transcript is more common than b3a2. Cancer Genet Cytogenet 169:76–77CrossRefPubMed Hasan SK, Sazawal S, Kumar B, Chaubey R, Mishra P, Mir R et al (2006) Childhood CML in India: b2a2 transcript is more common than b3a2. Cancer Genet Cytogenet 169:76–77CrossRefPubMed
3.
go back to reference Pemmaraju N, Kantarjian H, Shan J, Jabbour E, Quintas-Cardama A, Verstovsek S et al (2012) Analysis of outcomes in adolescents and young adults with chronic myelogenous leukemia treated with upfront tyrosine kinase inhibitor therapy. Haematologica 97:1029–1035CrossRefPubMedPubMedCentral Pemmaraju N, Kantarjian H, Shan J, Jabbour E, Quintas-Cardama A, Verstovsek S et al (2012) Analysis of outcomes in adolescents and young adults with chronic myelogenous leukemia treated with upfront tyrosine kinase inhibitor therapy. Haematologica 97:1029–1035CrossRefPubMedPubMedCentral
5.
go back to reference Horner MJ, Ries LAG (2007) Leukemia. In: Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (eds) SEER survival monograph: cancer survival among adults: U.S. SEER program, 1988–2001, patient and tumor characteristics. National Cancer Institute, SEER program, NIH, 07-6215 Horner MJ, Ries LAG (2007) Leukemia. In: Ries LAG, Young JL, Keel GE, Eisner MP, Lin YD, Horner M-J (eds) SEER survival monograph: cancer survival among adults: U.S. SEER program, 1988–2001, patient and tumor characteristics. National Cancer Institute, SEER program, NIH, 07-6215
6.
go back to reference Vardiman JW, Melo JV, Baccarani M, Thiele J (2008) Chronic myelogeneous leukemia, BCR-ABL1 positive. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al (eds) World Health Organization classification of tumours of haemopoietic and lymphoid tissues. IARC Press, Lyon, pp 32–37 Vardiman JW, Melo JV, Baccarani M, Thiele J (2008) Chronic myelogeneous leukemia, BCR-ABL1 positive. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al (eds) World Health Organization classification of tumours of haemopoietic and lymphoid tissues. IARC Press, Lyon, pp 32–37
7.
go back to reference Anand MS, Varma N, Varma S, Rana KS, Malhotra P (2012) Cytogenetic & molecular analyses in adult chronic myelogenous leukaemia patients in north India. Indian J Med Res 135:42–48CrossRefPubMedPubMedCentral Anand MS, Varma N, Varma S, Rana KS, Malhotra P (2012) Cytogenetic & molecular analyses in adult chronic myelogenous leukaemia patients in north India. Indian J Med Res 135:42–48CrossRefPubMedPubMedCentral
8.
go back to reference Sokal JE (1987) Prognosis in chronic myeloid leukaemia: biology of the disease versus treatment. Baillieres Clin Haematol 1:907–929CrossRefPubMed Sokal JE (1987) Prognosis in chronic myeloid leukaemia: biology of the disease versus treatment. Baillieres Clin Haematol 1:907–929CrossRefPubMed
9.
go back to reference Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC et al (1998) A new prognostic score for the survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst 90:850–858CrossRefPubMed Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC et al (1998) A new prognostic score for the survival of patients with chronic myeloid leukemia treated with interferon alfa. J Natl Cancer Inst 90:850–858CrossRefPubMed
10.
go back to reference Hasford J, Baccarani M, Hoffman V, Guilhot J, Saussele S, Rosti G et al (2011) Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood 118:686–692CrossRefPubMed Hasford J, Baccarani M, Hoffman V, Guilhot J, Saussele S, Rosti G et al (2011) Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood 118:686–692CrossRefPubMed
11.
go back to reference National Comprehensive Cancer Network (2012). NCCN clinical practice guidelines in oncology: chronic myelogenous leukemia. Version 3. 2013. http://www.nccn.org National Comprehensive Cancer Network (2012). NCCN clinical practice guidelines in oncology: chronic myelogenous leukemia. Version 3. 2013. http://​www.​nccn.​org
12.
go back to reference Hehlman R, Hochhaus S, Baccarani M (2007) European Leukemia Net. Chronic myeloid leukemia. Lancet 370:342–350CrossRef Hehlman R, Hochhaus S, Baccarani M (2007) European Leukemia Net. Chronic myeloid leukemia. Lancet 370:342–350CrossRef
13.
go back to reference Paz-J-Miño C, Burgos R, Morillo SA, Santos JC, Fiallo BF, Leone PE (2002) BCR-ABL rearrangement frequencies in chronic myeloid leukemia and acute lymphoblastic leukemia in Ecuador, South America. Cancer Genet Cytogenet 132:65–67CrossRef Paz-J-Miño C, Burgos R, Morillo SA, Santos JC, Fiallo BF, Leone PE (2002) BCR-ABL rearrangement frequencies in chronic myeloid leukemia and acute lymphoblastic leukemia in Ecuador, South America. Cancer Genet Cytogenet 132:65–67CrossRef
14.
go back to reference de Lemos JA, de Oliveira CM, Scerni AC, Bentes AQ, Beltrão AC, Bentes IR et al (2005) Differential molecular response of the transcripts B2A2 and B3A2 to imatinib mesylate in chronic myeloid leukemia. Genet Mol Res 4:803–811PubMed de Lemos JA, de Oliveira CM, Scerni AC, Bentes AQ, Beltrão AC, Bentes IR et al (2005) Differential molecular response of the transcripts B2A2 and B3A2 to imatinib mesylate in chronic myeloid leukemia. Genet Mol Res 4:803–811PubMed
15.
go back to reference Suryanarayan K, Hunger SP, Kohler S et al (1991) Consistent involvement of bcr gene by 9;22 breakpoints in pediatric acute leukemias. Blood 77:324–330PubMed Suryanarayan K, Hunger SP, Kohler S et al (1991) Consistent involvement of bcr gene by 9;22 breakpoints in pediatric acute leukemias. Blood 77:324–330PubMed
16.
go back to reference Mondal BC, Bandyopadhyay A, Majumdar S, Mukhopadhyay A, Chandra S, Chaudhuri U et al (2006) Molecular profiling of chronic myeloid leukemia in eastern India. Am J Hematol 81:845–849CrossRefPubMed Mondal BC, Bandyopadhyay A, Majumdar S, Mukhopadhyay A, Chandra S, Chaudhuri U et al (2006) Molecular profiling of chronic myeloid leukemia in eastern India. Am J Hematol 81:845–849CrossRefPubMed
18.
go back to reference Suttorp M, Millot F (2010) Treatment of pediatric chronic myeloid leukemia in the year 2010: use of tyrosine kinase inhibitors and stem-cell transplantation. Hematol Am Soc Hematol Educ Program 2010:368–376 Suttorp M, Millot F (2010) Treatment of pediatric chronic myeloid leukemia in the year 2010: use of tyrosine kinase inhibitors and stem-cell transplantation. Hematol Am Soc Hematol Educ Program 2010:368–376
19.
go back to reference Lakshmaiah KC, Bhise R, Purohit S, Abraham LJ, Lokanatha D, Suresh TM et al (2012) Chronic myeloid leukemia in children and adolescents: results of treatment with imatinib mesylate. Leuk Lymphoma 53:2430–2433CrossRefPubMed Lakshmaiah KC, Bhise R, Purohit S, Abraham LJ, Lokanatha D, Suresh TM et al (2012) Chronic myeloid leukemia in children and adolescents: results of treatment with imatinib mesylate. Leuk Lymphoma 53:2430–2433CrossRefPubMed
20.
go back to reference Kantarjian H, O’Brien S, Jabbour E (2012) Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single institution historical experience. Blood 119:1981–1987CrossRefPubMedPubMedCentral Kantarjian H, O’Brien S, Jabbour E (2012) Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single institution historical experience. Blood 119:1981–1987CrossRefPubMedPubMedCentral
21.
go back to reference Suttorp M, Glauche I, Salas DG, Tauer JT, Nowasz C, Thiede C (2013) Scoring systems for predicting outcome of chronic myeloid leukemia in adults are poorly informative in pediatric patients treated with imatinib. 55th ASH, New Orleans, Dec 7–10, 2013: abstract no. 2725 Suttorp M, Glauche I, Salas DG, Tauer JT, Nowasz C, Thiede C (2013) Scoring systems for predicting outcome of chronic myeloid leukemia in adults are poorly informative in pediatric patients treated with imatinib. 55th ASH, New Orleans, Dec 7–10, 2013: abstract no. 2725
22.
go back to reference Bansal D, Shava U, Varma N, Trehan A, Marwaha RK (2012) Imatinib has adverse effect on growth in children with chronic myeloid leukemia. Pediatr Blood Cancer 59:481–484CrossRefPubMed Bansal D, Shava U, Varma N, Trehan A, Marwaha RK (2012) Imatinib has adverse effect on growth in children with chronic myeloid leukemia. Pediatr Blood Cancer 59:481–484CrossRefPubMed
23.
go back to reference Mahon FX, Rea D, Guilhot F et al (2009) Discontinuation of imatinib therapy after achieving a molecular response in chronic myeloid leukemia patients. Blood 114:859 (ASH Annual Meeting Abstract) Mahon FX, Rea D, Guilhot F et al (2009) Discontinuation of imatinib therapy after achieving a molecular response in chronic myeloid leukemia patients. Blood 114:859 (ASH Annual Meeting Abstract)
Metadata
Title
Comparative Study of Clinico-hematological Features, Molecular Spectrum and Response to Imatinib in Chronic Myelogenous Leukemia Patients: Pediatric and Adolescent Versus Adults
Authors
Anita Tahlan
Neelam Varma
Shano Naseem
Deepak Bansal
Jogeshwar Binota
Anil Sood
Man Updesh Singh Sachdeva
Pankaj Malhotra
Subhash Varma
Publication date
01-01-2018
Publisher
Springer India
Published in
Indian Journal of Hematology and Blood Transfusion / Issue 1/2018
Print ISSN: 0971-4502
Electronic ISSN: 0974-0449
DOI
https://doi.org/10.1007/s12288-017-0827-7

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