JCHOR
Journal of Current Hematology & Oncology Research

The Journal of Current Hematology & Oncology Research regularly publishes internationally qualified research in hematology and oncology within the current scholarly knowledge.

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Original Article
Adults philadelphia-positive B–acute lymphoblastic leukemia in a moderate health access and quality index Country
Abstract
Aims: to describe clinical and demographic characteristics, as well as to evaluate response and survival outcomes in Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) Ecuadorian adults.
Methods: A retrospective, multicenter cohort study in patients aged >15 years diagnosed with Ph+ B-cell ALL was carried out. Diagnosis of B-ALL was established based on 2016 WHO classification and Ph+ mutation was confirmed in all cases.
Results: 61 (12.4%) were identified with Ph+ chromosome. 56 were included in the analysis, 33 (58.9%) were male, and median age was 40.5 years [interquartile range (IQR): 25–51; range: 16–85]. 46 (82.1%) subjects were treated with Imatinib. CR was achieved in 30 (53.6%) patients. MRD was reported in 13/41 (31.7%). Only 5/29 eligible patients underwent HSCT. 9 (16.1) died in induction phase, all deaths were attributed to bacterial infections. Relapse was recorded in 7 (12.5%). Median OS for total cohort was 11 months (95% CI 8.1–13.9), with a 5-year OS of 26.8%. Imatinib therapy [HR 0.44 (95% CI 0.19 – 0.98); p=0.046]; Imatinib 800mg dose [HR 0.30 (95% CI 0.11 – 0.83); p=0.020]; Hyper-CVAD protocol [HR 0.44 (95% CI 0.21 – 0.93); p=0.031] were associated to better OS.
Conclusion: Response and survival outcomes in Ecuadorian population are poorer compared to high income countries caused by high rate of induction death, low availability of MRD monitoring, lack of standardization of treatment protocols, restricted access to HSCT, and delayed initiation to TKIs therapy.

Keywords : Philadelphia positive, Acute Lymphoblastic Leukemia, Overall Survival, Poor outcomes, Ecuador, Middle-Low income countries

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1. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7(6): e577-e577. doi:10.1038/bcj.2017.53
2. Paul S, Kantarjian H, Jabbour EJ. Adult acute lymphoblastic leukemia. Mayo Clin Proc. 2016;91(11):1645-1666. doi:10.1016/j.mayocp.2016.09.010
3. Liu-Dumlao T, Kantarjian H, Thomas DA, O’Brien S, Ravandi F. Philadelphia-positive acute lymphoblastic leukemia: current treatment options. Curr Oncol Rep. 2012;14(5):387-394. doi:10.1007/s11912-012-0247-7
4. Leoni V, Biondi A. Tyrosine kinase inhibitors in BCR-ABL positive acute lymphoblastic leukemia. Haematologica. 2015;100(3):295-299. doi:10.3324/haematol.2015.124016
5. Ribera JM, Oriol A, González M, et al. Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial. Haematologica. 2010;95(1):87-95. doi:10.3324/haematol.2009.011221
6. Wassmann B, Pfeifer H, Goekbuget N, 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(5):1469-1477. doi:10.1182/blood-2005-11- 4386
7. Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004;103(12):4396-4407. doi:10.1182/blood-2003-08-2958
8. Bassan R, Rossi G, Pogliani EM, et al. Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group Protocol 09/00. J Clin Oncol. 2010;28(22):3644-3652. doi:10.1200/JCO.2010.28.1287
9. Tanguy-Schmidt A, Rousselot P, Chalandon Y, et al. Long-term follow-up of the imatinib GRAAPH-2003 study in newly diagnosed patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: a GRAALL study. Biol Blood Marrow Transplant. 2013;19(1): 150-155. doi:10.1016/j.bbmt.2012.08.021
10. Ravandi F. Managing Philadelphia chromosome-positive acute lymphoblastic leukemia: role of tyrosine kinase inhibitors. Clin Lymphoma Myeloma Leuk. 2011;11(2):198-203. doi:10.1016/j.clml.2011. 03.002
11. Ravandi F, O’Brien SM, Cortes JE, et al. Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2015;121(23):4158-4164. doi:10.1002/cncr.29646
12. Kim DY, Joo YD, Lim SN, et al. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015;126(6):746-756. doi:10.1182/blood-2015-03-636548
13. Jabbour E, Kantarjian HM, Aldoss I, et al. Ponatinib vs imatinib in frontline Philadelphia chromosome-positive acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2024;331(21):1814-1823. doi:10.1001/jama.2024.4783
14. Ribera JM, García-Calduch O, Ribera J, et al. Ponatinib, chemotherapy, and transplant in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood Adv. 2022;6(18):5395-5402. doi:10.1182/bloodadvances.2022007764
15. Crespo-Solis E, Espinosa-Bautista K, Alvarado-Ibarra M, et al. Survival analysis of adult patients with ALL in Mexico City: first report from the acute leukemia workgroup (ALWG) (GTLA). Cancer Med. 2018;7(6): 2423-2433. doi:10.1002/cam4.1513
16. Tasian SK, Loh ML, Hunger SP. Philadelphia chromosome-like acute lymphoblastic leukemia. Blood. 2017;130(19):2064-2072. doi:10.1182/blood-2017-06-743252
17. Jain N, Roberts KG, Jabbour E, et al. Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults. Blood. 2017;129(5):572-581. doi: 10.1182/blood-2016-07-726588
18. Silva WF, Silverio A, Duarte BKL, et al. Philadelphia-positive B-lymphoblastic leukemia in a middle-income country-a real-world multicenter cohort. Leuk Res. 2021;110:106666. doi:10.1016/j.leukres. 2021.106666
19. Colunga-Pedraza PR, Colunga-Pedraza JE, Peña-Lozano SP, Gómez-De León A, Ruiz-Delgado GJ, Ribeiro RC. Diagnosis and treatment of acute lymphoblastic leukemia in Latin America. Hematology. 2022;27(1):971-976. doi:10.1080/16078454.2022.2117119
20. Benavente R, Cid F, Puga B, et al. Quimioterapia intensiva asociada a imatinib en leucemia linfoblástica aguda del adulto, Philadelphia positivo. Experiencia en un hospital público. Rev Médica Chile. 2021; 149(9):12491257. doi:10.4067/S0034-98872021000901249
21. Duffield AS, Mullighan CG, Borowitz MJ. International consensus classification of acute lymphoblastic leukemia/lymphoma. Virchows Arch Int J Pathol. 2023;482(1):11-26. doi:10.1007/s00428-022-03448-8
22. Moorman AV, Harrison CJ, Buck GAN, et al. 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. 2006;109(8):3189-3197. doi:10.1182/blood-2006-10-051912
23. Barr RD, Ries LAG, Trama A, et al. A system for classifying cancers diagnosed in adolescents and young adults. Cancer. 2020;126(21):4634-4659. doi:10.1002/cncr.33041
24. Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for Diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21(24): 4642-4649. doi:10.1200/JCO.2003.04.036
25. Kruse A, Abdel-Azim N, Kim HN, et al. Minimal residual disease detection in acute lymphoblastic leukemia. Int J Mol Sci. 2020;21(3): 1054. doi:10.3390/ijms21031054
26. Gökbuget N, Bassan R, Dombret H, et al. Recommendations of the European Working Group for adult ALL. UNI-MED Verlag AG. 2011. doi:10.1182/blood.2023023568
27. Unal I. Defining an optimal cut-point value in ROC analysis: an alternative approach. Comput Math Methods Med. 2017;2017(1):3762651. doi:10.1155/2017/3762651
28. Cavanaugh JE, Neath AA. The Akaike information criterion: background, derivation, properties, application, interpretation, and refinements. WIREs Comput Stat. 2019;11(3):e1460. doi:10.1002/wics.1460
29. Bumbea H, Vladareanu A, Cisleanu D, Barsan L, Onisai M, Voican I. Chronic myeloid leukemia therapy in the era of tyrosine kinase inhibitors. The first molecular targeted treatment. J Med Life. 2010;3(2): 162-166. doi:10.1002/wics.1460
30. Radhakrishnan VS, Agrawal N, Bagal B, Patel I. Systematic review of the burden and treatment patterns of adult and adolescent acute lymphoblastic leukemia in India: comprehending the challenges in an emerging economy. Clin Lymphoma Myeloma Leuk. 2021;21(1):e85-98. doi:10.1016/j.clml.2020.08.023
31. Lennmyr E, Karlsson K, Ahlberg L, et al. Survival in adult acute lymphoblastic leukaemia (ALL): a report from the Swedish ALL registry. Eur J Haematol. 2019;103(2):88-98. doi:10.1111/ejh.13247
32. Shanmuganathan N, Grigg A. A critical review of management of allogeneic transplant-eligible adults with Ph+ acute lymphoblastic leukaemia. Br J Haematol. doi:10.1111/bjh.19682
33. Ahmed U, Ahmed D, Awan MN, et al. Outcomes of Philadelphia positive acute lymphoblastic leukemia in adolescent and young adults. Cureus. 2022;14(12):e32467. doi:10.7759/cureus.32467
34. Dombret H, Gabert J, Boiron JM, et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia—results of the prospective multicenter LALA-94 trial. Blood. 2002;100(7):2357-2366. doi:10.1182/blood-2002-03-0704
35. Gleißner B, Gökbuget N, Bartram CR, 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(5):1536-1543. doi:10.1182/blood.V99.5.1536
36. Ribera J, Morgades M, Zamora L, et al. Prognostic significance of copy number alterations in adolescent and adult patients with precursor B acute lymphoblastic leukemia enrolled in PETHEMA protocols. Cancer. 2015;121(21):3809-3817. doi:10.1002/cncr.29579
37. Lee HJ, Thompson JE, Wang ES, Wetzler M. Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2011;117(8):1583-1594. doi:10.1002/cncr.25690
38. Walsh KM, de Smith AJ, Chokkalingam AP, et al. GATA3 risk alleles are associated with ancestral components in Hispanic children with ALL. Blood. 2013;122(19):3385-3387. doi:10.1182/blood-2013-08-524124
39. Hatta Y, Mizuta S, Matsuo K, et al. Final analysis of the JALSG Ph+ALL202 study: tyrosine kinase inhibitor-combined chemotherapy for Ph+ALL. Ann Hematol. 2018;97(9):1535-1545. doi:10.1007/s00277-018-3323-8
40. de Labarthe A, Rousselot P, Huguet-Rigal F, et al. Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood. 2006;109(4):1408-1413. doi: 10.1182/blood-2006-03-011908
41. Fielding AK, Rowe JM, Buck G, et al. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014;123(6):843-850. doi:10.1182/blood-2013-09-529008
42. Chalandon Y, Thomas X, Hayette S, et al. Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood. 2015;125(24):3711-3719. doi:10.1182/blood-2015-02-627935
43. Vignetti M, Fazi P, Cimino G, et al. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive patients with acute lymphoblastic leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie Ematologiche dell’Adulto (GIMEMA) LAL0201-B protocol. Blood. 2007;109(9):3676-3678. doi:10.1182/blood-2006-10-052746
44. Wu C, Zeng M, Chen Y, Wu Y. Tyrosine kinase inhibitors and reduced-dose chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Hematology. 2022;27(1):1032-1040. doi:10.1080/ 16078454.2022.2119344
45. Raman HS, Kim SE, DeAngelo DJ, et al. Intensity of induction regimen and outcomes among adults with Ph+ALL undergoing allogeneic hematopoietic stem cell transplantation. Leuk Res. 2023;125:107004. doi:10.1016/j.leukres.2022.107004
46. Lee JM, Kim DY, Cho HJ, et al. Reduced-intensity chemotherapy with tyrosine kinase inhibitor followed by allogeneic transplantation is effective in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Korean J Intern Med. 2025;40(1):124-134. doi: 10.3904/kjim.2024.227
Article available in :
Volume 3, Issue 4, 2025
Page : 82-89
https://doi.org/10.51271/JCHOR-0068
Article Information
Received : 07 May 2025
Accepted : 26 Eyl 2025
Published : 13 Kas 2025
Corresponding Author :

Brenner Sabando: Centro de Especialidades Médicas IRHED

[email protected]
Citation : Sabando B, Quinonez J, Orquera A, et al. Adults philadelphia-positive B–acute lymphoblastic leukemia in a moderate Health Access and Quality Index country. J Curr Hematol Oncol Res. 2025;3(4):82-89.

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