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CC BY-NC-ND 4.0 · South Asian J Cancer 2016; 05(04): 176-178
DOI: 10.4103/2278-330X.195336
LEUKEMIA : Original Article

Philadelphia chromosome-positive acute lymphoblastic leukemia: 8 years’ experience from a tertiary care center in India

Madhav Danthala
Department of Medical Oncology, Nizam′s Institute of Medical Sciences, Hyderabad, Telangana
,
Sadashivudu Gundeti
Department of Medical Oncology, Nizam′s Institute of Medical Sciences, Hyderabad, Telangana
,
Laxmi Srinivas Maddali
Department of Medical Oncology, Nizam′s Institute of Medical Sciences, Hyderabad, Telangana
,
Ashok Pillai
Department of Medical Oncology, Nizam′s Institute of Medical Sciences, Hyderabad, Telangana
,
Krishna Chaitanya Puligundla
Department of Medical Oncology, Nizam′s Institute of Medical Sciences, Hyderabad, Telangana
,
Raja Praveen Adusumilli
Department of Medical Oncology, Nizam′s Institute of Medical Sciences, Hyderabad, Telangana
› Author Affiliations Financial support and sponsorship: Nil.
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Abstract

Introduction: The Philadelphia chromosome (Ph) is the most common cytogenetic abnormality associated with adult acute lymphoblastic leukemia (ALL) occurring in 20% to 40% of patients. It is also detected in 2% to 5% of children with ALL. Historically, patients with Ph-positive ALL carried a dismal prognosis, with poor response to most chemotherapy combinations, short remission durations, and long-term disease-free survival rates of 10% to 20%. The advent of tyrosine kinase inhibitors (TKIs) has revolutionized therapy of Ph-positive ALL. Materials and Methods: This retrospective and descriptive single center study was carried out based on data retrieved of 508 patients treated for ALL from 2007 to 2014. Of these thirty patients were Ph-positive ALL and were available for analysis, and these patients were included in the study. Ph-positive ALL was defined as ALL carrying the t(9;22) translocation on standard karyotype and/or fluorescent in situ hybridization analysis and/or positivity for BCR-ABL fusion transcript detection by real-time quantitative polymerase chain reaction (RQ-PCR) analysis. Patients were treated with combination chemotherapy and oral TKIs and responses were classified as either CR defined by the absence of circulating blasts and <5% marrow blasts on a bone marrow examination done at the end of induction chemotherapy or failure, including persistent disease and early death. Results: There were 30 (5.9%) cases of Ph-positive ALL out of a total of 508 cases of ALL with a median age of 27.5 years (range: 7-55). The choice of first line TKI was Imatinib in 25 (83.3 %) patients and Dasatinib in 1 (3.3 %) patient. Fourteen patients (46.6 %) had a CR, 3 (10 %) had a partial response (PR), 8 (26.6 %) had persistence of disease at the end of induction chemotherapy. The overall survival in those who received sequential chemotherapy followed by TKI (n = 4) was 28.5 months (95% CI 10.78 to 46.21 months) compared with 13.98 months (95% CI 6.04 to 21.97 months) for patients who received concurrent chemotherapy and TKI (n = 20); log rank (Mantel Cox) X 2 = 8.33, P = 0.040), however limited sample precluded meaningful subgroup analysis. Conclusion: The results of our study showed that we still have a long way to go to match outcomes of western published series, even when the same treatment protocol is used, probably due to the underutilization of Allogeneic SCT as an option in first CR.

Key words

Acute lymphoblastic leukemia - chemotherapy - overall survival - Philadelphia chromosome


Publication History

Article published online:
28 December 2020

© 2016. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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  • References

  • 1 Tuszynski A, Dhut S, Young BD, Lister TA, Rohatiner AZ, Amess JA, et al. Detection and significance of BCR-ABL mRNA transcripts and fusion proteins in Philadelphia-positive adult acute lymphoblastic leukemia. Leukemia 1993;7:1504-8.
  • 2 Schlieben S, Borkhardt A, Reinisch I, Ritterbach J, Janssen JW, Ratei R, et al. Incidence and clinical outcome of children with BCR/ABL-positive acute lymphoblastic leukemia (ALL). A prospective RT-PCR study based on 673 patients enrolled in the German pediatric multicenter therapy trials ALL-BFM-90 and CoALL-05-92. Leukemia 1996;10:957-63.
  • 3 Gleissner B, Gökbuget N, Bartram CR, Janssen B, Rieder H, Janssen JW, et al. Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: A prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood 2002;99:1536-43.
  • 4 Kano Y, Akutsu M, Tsunoda S, Mano H, Sato Y, Honma Y, et al. In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents. Blood 2001;97:1999-2007.
  • 5 Thomas DA, O′Brien SM, Faderl S, Ravandi Kashani F, Wierda WG, Andreeff M, et al. Long-term outcome after hyper-CVAD and imatinib (IM) for de novo or minimally treated Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). InASCO Annual Meeting Proceedings 2010;28:6506.
  • 6 Lim SN, Joo YD, Lee KH, Kim DY, Lee JH, Lee JH, et al. Long-term follow-up of imatinib plus combination chemotherapy in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Am J Hematol 2015;90:1013-20.
  • 7 Wassmann B, Pfeifer H, Goekbuget N, Beelen DW, Beck J, Stelljes M, et al. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL). Blood 2006;108:1469-77.