Vol 9, No 1 (2018)
Case report
Published online: 2018-05-23

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Effective rescue treatment with tyrosine kinase inhibitors of a patient with B-cell acute lymphoblastic leukemia Philadelpha-positive

Ilona Seferyńska1, Anna Ejduk1, Iwona Solarska2, Krzysztof Warzocha1
Hematologia 2018;9(1):73-78.

Abstract

Philadelphia chromosome (Ph) is present in 25% adult patients suffering due to acute lymphoblastic leukemia (ALL). Before the era of tyrosine kinase inhibitors (TKI) ALL-Ph(+) was regarded as a high-risk form of leukemia. Introduction of combined treatment of TKI and chemotherapy improved patient prognosis. We present a case report of a ALL-Ph(+) patient diagnosed in March 2008, who was treated with chemotherapy and imatinib. The real-time quantitative polymerase chain reaction method, was used to assess treatment outcomes and the loss of molecular response was the reason of testing for the BCR-ABL1 mutation. After induction and consolidation treatment, complete remission (CR) with a major molecular response was achieved, whilst during maintenance therapy a deep molecular response was obtained. Shortly after the maintenance therapy ended there was a loss of molecular response noted due to the appearance of a G250E mutation. Imatinib was stopped and dazatinib was introduced and a deep molecular response was again achieved. Treatment with dazatinib was complicated with recurrent pleural effusion but after short breaks the treatment was then recommenced. After six years of taking dazatinib, fully symptomatic ALL recurred, what was linked with the appearance of the F317L mutation of BCR-ABL1. Following chemotherapy and ponatinib, CR and a deep molecular response was again achieved. After almost ten years the patient is alive in good health and in remission from the leukemia.

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References

  1. Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N Engl J Med. 2004; 350(15): 1535–1548.
  2. Aricò M, Schrappe M, Hunger SP, et al. Clinical outcome of children with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia treated between 1995 and 2005. J Clin Oncol. 2010; 28(31): 4755–4761.
  3. Schultz KR, Bowman WP, Aledo A, et al. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study. J Clin Oncol. 2009; 27(31): 5175–5181.
  4. Thomas DA, O'Brien SM, Faderl S, 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). J Clin Oncol. 2010; 28(15_suppl): 6506–6506.
  5. Alam A, Qawasmeh K, Kanbar J. Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL), Tawam experience. Blood. 2015; 126: 4867.
  6. Liu-Dumlao T, Kantarjian H, Thomas DA, et al. Philadelphia-positive acute lymphoblastic leukemia: current treatment options. Curr Oncol Rep. 2012; 14(5): 387–394.
  7. Kim DY, Joo YD, Lim SN, et al. Adult Acute Lymphoblastic Leukemia Working Party of the Korean Society of Hematology. Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Blood. 2015; 126(6): 746–756.
  8. Chiaretti S, Foà R. Management of adult Ph-positive acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2015; 2015: 406–413.
  9. Short NJ, Jabbour E. Should treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia be intensive? Intensive treatment is the best treatment for these patients. Clin Adv Hematol Oncol. 2016; 14(11): 892–894.
  10. Ravandi F, Kebriaei P. Philadelphia chromosome-positive acute lymphoblastic leukemia. Hematol Oncol Clin North Am. 2009; 23(5): 1043–63, vi.
  11. Ribera JM, García O, Montesinos P, et al. Treatment of young patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia using increased dose of imatinib and deintensified chemotherapy before allogeneic stem cell transplantation. Br J Haematol. 2012; 159(1): 78–81.
  12. Pfeifer H, Wassmann B, Bethge W, et al. GMALL Study Group. Randomized comparison of prophylactic and minimal residual disease-triggered imatinib after allogeneic stem cell transplantation for BCR-ABL1-positive acute lymphoblastic leukemia. Leukemia. 2013; 27(6): 1254–1262.
  13. Chalandon Y, Thomas X, Hayette S, et al. Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood. 2015; 125(24): 3711–3719.
  14. Foà R, Vitale A, Vignetti M, et al. GIMEMA Acute Leukemia Working Party. Dasatinib as first-line treatment for adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2011; 118(25): 6521–6528.
  15. Soverini S, Hochhaus A, Nicolini FE, et al. BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet. Blood. 2011; 118(5): 1208–1215.
  16. O'Hare T, Eide CA, Deininger MWN. Bcr-Abl kinase domain mutations, drug resistance, and the road to a cure for chronic myeloid leukemia. Blood. 2007; 110(7): 2242–2249.
  17. Kolenova A, Maloney KW, Hunger SP. Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia or Chronic Myeloid Leukemia in Lymphoid Blast Crisis. J Pediatr Hematol Oncol. 2016; 38(6): e193–e195.
  18. Ravandi F, O'Brien S, Thomas D, et al. First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. Blood. 2010; 116(12): 2070–2077.
  19. Sora F, Chiusolo P, Laurenti L. Ponatinib before and after allogeneic stem cell transplantation for Ph+ acute lymphoblastic leukemia or lymphoid blast crisis of chronic myelogenous leukemia: a single center experience. J Bone Marrow Res. 2016; 4(2).
  20. Jabbour EJ, Cortes JE, Kantarjian HM. Resistance to tyrosine kinase inhibition therapy for chronic myelogenous leukemia: a clinical perspective and emerging treatment options. Clin Lymphoma Myeloma Leuk. 2013; 13(5): 515–529.
  21. Suh KJ, Lee JiY, Shin DY, et al. Analysis of adverse events associated with dasatinib and nilotinib treatments in chronic-phase chronic myeloid leukemia patients outside clinical trials. Int J Hematol. 2017; 106(2): 229–239.
  22. Jabbour E, Deininger M, Hochhaus A. Management of adverse events associated with tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Leukemia. 2011; 25(2): 201–210.
  23. Cortes JE, Jimenez CA, Mauro MJ, et al. Pleural effusion in dasatinib-treated patients with chronic myeloid leukemia in chronic phase: identification and management. Clin Lymphoma Myeloma Leuk. 2017; 17(2): 78–82.
  24. Eskazan AE, Soysal T, Erbilgin Y, et al. Chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation are resistant to dasatinib: is that true for all the patients? Leuk Res. 2011; 35(9): e145–e146.
  25. Jabbour E, Kantarjian HM, Jones D, et al. Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after therapy with tyrosine kinase inhibitors. Blood. 2008; 112(13): 4839–4842.
  26. Eden T. Acute lymphoblastic leukaemia. Medicine Online, Oxford 2010, doi: 10.1093/med/9780199204854.003.220303.
  27. NCCN clinical practice guidelines in oncology (NCCN Guidelines) acute lymphoblastic leukemia. NCCN guidelines version 4.2017.
  28. Sacha T. Ponatynib w leczeniu przewlekłej białaczki szpikowej i ostrej białaczki limfoblastycznej z chromosomem Filadelfia. Acta Haematol Pol. 2016; 47(2): 128–138.



Hematology in Clinical Practice