Skip to main content

Evaluation of Cytogenetic Abnormalities in Patients with Acute Lymphoblastic Leukemia

Abstract

Acute lymphoblastic leukemia (ALL) accounts for 20% of all adult leukemias and is the most common leukemia during childhood (80%). We present data on cytogenetics of ALL from a tertiary centre in India correlating it with clinical factors. Karyotyping of bone marrow samples of 204 patients with newly diagnosed ALL was performed with standard G-banding technique. Clinical data of patients was obtained from case records. Survival was estimated using Kaplan–Meir curves and compared by the log-rank test. Univariate and multivariate analysis was done for survival with age, sex, immunophenotype, hyperleukocytosis, risk type, remission status and cytogenetics. The most common karyotypes observed were normal in 39.7% (N = 81), hyperdiploidy in 12.7% (N = 26), t(9;22) in 4.4% (N = 9), t(1;19) in 3.9% (N = 8). Adults with ALL had worse survival compared with pediatric patients (HR 3.62; 2.03–6.45 95% CI, p < 0.001). Patients not in morphologic remission after induction chemotherapy fared poorly (HR 4.86; 2.67–8.84 95% CI, p < 0.001). Patients with favourable cytogenetics had better overall survival (HR 0.36; 0.12–1.05 95% CI, p < 0.05). On multivariate analysis, achievement of morphologic remission emerged as single most significant predictor of survival (p < 0.001). MLL gene rearrangement and t(12;21) were seen less commonly as compared to Western data. However, incidence rates of various cytogenetic abnormalities were similar to that reported from other centres from India. Age, morphologic remission at end of induction chemotherapy and favourable cytogenetics correlated significantly with survival.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29

    Article  Google Scholar 

  2. Swaminathan R, Rama R, Shanta V (2008) Childhood cancers in Chennai, India, 1990–2001: incidence and survival. Int J Cancer 122(11):2607–2611

    Article  CAS  Google Scholar 

  3. Terwilliger T, Abdul-Hay M (2017) Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J 7(6):e577

    Article  CAS  Google Scholar 

  4. Mrózek K, Harper DP, Aplan PD (2009) Cytogenetics and molecular genetics of acute lymphoblastic leukemia. Hematol Oncol Clin North Am 23(5):991–1010

    Article  Google Scholar 

  5. Inaba H, Greaves M, Mullighan CG (2013) Acute lymphoblastic leukaemia. Lancet 381(9881):1943–1955

    Article  Google Scholar 

  6. Faderl S, Kantarjian HM, Talpaz M, Estrov Z (1998) Clinical significance of cytogenetic abnormalities in adult acute lymphoblastic leukemia. Blood 91(11):3995–4019

    Article  CAS  Google Scholar 

  7. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Beau MML et al (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405

    Article  CAS  Google Scholar 

  8. Moorman AV, Harrison CJ, Buck GAN, Richards SM, Secker-Walker LM, Martineau M et al (2007) Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood 109(8):3189–3197

    Article  CAS  Google Scholar 

  9. Wetzler M, Dodge RK, Mrózek K, Carroll AJ, Tantravahi R, Block AW et al (1999) Prospective karyotype analysis in adult acute lymphoblastic leukemia: the cancer and leukemia group B experience. Blood 93(11):3983–3993

    PubMed  CAS  Google Scholar 

  10. Moorman AV, Ensor HM, Richards SM, Chilton L, Schwab C, Kinsey SE et al (2010) Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial. Lancet Oncol 11(5):429–438

    Article  CAS  Google Scholar 

  11. Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM et al (2005) Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood 106(12):3760–3767

    Article  CAS  Google Scholar 

  12. Jones LK, Saha V (2005) Philadelphia positive acute lymphoblastic leukaemia of childhood. Br J Haematol 130(4):489–500

    Article  Google Scholar 

  13. Shurtleff SA, Buijs A, Behm FG, Rubnitz JE, Raimondi SC, Hancock ML et al (1995) TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. Leukemia 9(12):1985–1989

    PubMed  CAS  Google Scholar 

  14. Dastugue N, Suciu S, Plat G, Speleman F, Cavé H, Girard S et al (2013) Hyperdiploidy with 58-66 chromosomes in childhood B-acute lymphoblastic leukemia is highly curable: 58951 CLG-EORTC results. Blood 121(13):2415–2423

    Article  CAS  Google Scholar 

  15. Johansson B, Mertens F, Mitelman F (2004) Clinical and biological importance of cytogenetic abnormalities in childhood and adult acute lymphoblastic leukemia. Ann Med 36(7):492–503

    Article  CAS  Google Scholar 

  16. Wan TSK (2014) Cancer cytogenetics: methodology revisited. Ann Lab Med 34(6):413–425

    Article  Google Scholar 

  17. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53(282):457

    Article  Google Scholar 

  18. Mantel N (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50(3):163–170

    PubMed  CAS  Google Scholar 

  19. Peto R, Peto J (1972) Asymptotically efficient rank invariant test procedures. J R Stat Soc Ser A (General) 135(2):185–207

    Article  Google Scholar 

  20. Griffin TC, Tomlinson GE, Raimondi SC, Sandoval C, Timmons CF, Rosenfield C et al (1992) Childhood acute lymphoblastic leukemia with both t(1;19) and t(9;22). Leukemia 6(6):535–540

    PubMed  CAS  Google Scholar 

  21. Aliano S, Cirmena G, Fugazza G, Bruzzone R, Palermo C, Sessarego M (2013) Standard and variant Philadelphia translocation in a CML patient with different sensitivity to imatinib therapy. Leuk Res Rep 2(2):75–78

    PubMed  PubMed Central  Google Scholar 

  22. Radhakrishnan V, Gupta S, Ganesan P, Rajendranath R, Ganesan TS, Rajalekshmy KR et al (2015) Acute lymphoblastic leukemia: a single center experience with Berlin, Frankfurt, and Munster-95 protocol. Indian J Med Paediatr Oncol 36(4):261–264

    Article  Google Scholar 

  23. Amare PSK, Jain H, Kabre S, Deshpande Y, Pawar P, Banavali S et al (2016) Cytogenetic profile in 7209 Indian patients with de novo acute leukemia: a single centre study from India. J Cancer Ther 07(07):530

    Article  Google Scholar 

  24. Mazloumi SHM, Madhumathi DS, Appaji L, Prasannakumari null (2012) Combined study of cytogenetics and fluorescence in situ hybridization (FISH) analysis in childhood acute lymphoblastic leukemia (ALL) in a tertiary cancer centre in South India. Asian Pac J Cancer Prev 13(8):3825–3827

    Article  Google Scholar 

  25. Chennamaneni R, Gundeti S, Konatam ML, Bala S, Kumar A, Srinivas L (2018) Impact of cytogenetics on outcomes in pediatric acute lymphoblastic leukemia. South Asian J Cancer 7(4):263

    Article  Google Scholar 

  26. Uckun FM, Sensel MG, Sather HN, Gaynon PS, Arthur DC, Lange BJ et al (1998) Clinical significance of translocation t(1;19) in childhood acute lymphoblastic leukemia in the context of contemporary therapies: a report from the Children’s Cancer Group. J Clin Oncol 16(2):527–535

    Article  CAS  Google Scholar 

  27. Pui C-H, Gaynon PS, Boyett JM, Chessells JM, Baruchel A, Kamps W et al (2002) Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region. Lancet 359(9321):1909–1915

    Article  Google Scholar 

  28. Ganesan P, Sagar TG, Kannan K, Radhakrishnan V, Dhanushkodi M, Swaminathan R et al (2018) Acute lymphoblastic leukemia in Young adults treated with intensive “pediatric” type protocol. Indian J Hematol Blood Transfus 34(3):422–429

    Article  Google Scholar 

  29. Mancini M, Vegna ML, Castoldi GL, Mecucci C, Spirito F, Elia L et al (2002) Partial deletions of long arm of chromosome 6: biologic and clinical implications in adult acute lymphoblastic leukemia. Leukemia 16(10):2055–2061

    Article  CAS  Google Scholar 

  30. Othman MAK, Rincic M, Melo JB, Carreira IM, Alhourani E, Hunstig F et al (2014) A novel cryptic three-way translocation t(2;9;18)(p23.2;p21.3;q21.33) with deletion of tumor suppressor genes in 9p21.3 and 13q14 in a T-cell acute lymphoblastic leukemia. Leuk Res Treat 2014:357123

    Google Scholar 

  31. Lee S-G, Park TS, Won SC, Song J, Lee K-A, Choi JR et al (2010) Three-way translocation involving MLL, MLLT1, and a novel third partner, NRXN1, in a patient with acute lymphoblastic leukemia and t(2;19;11) (p12;p13.3;q23). Cancer Genet Cytogenet. 197(1):32–38

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T. S. Ganesan.

Ethics declarations

Ethical Approval

This is a retrospective study. According to institutional policies ethical committee approval is not required for such studies.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reddy, P., Shankar, R., Koshy, T. et al. Evaluation of Cytogenetic Abnormalities in Patients with Acute Lymphoblastic Leukemia. Indian J Hematol Blood Transfus 35, 640–648 (2019). https://doi.org/10.1007/s12288-019-01123-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12288-019-01123-8

Keywords