CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA IN BLAST CRISIS
AbstractBackground: Chronic myelogenous leukaemia (CML) is a hematopoietic stem cell disease with a relatively stable clinical course. Survival has increased with addition of Tyrosine Kinase inhibitors (TKI’s). Its conversion into blast crises (BC) heralds an accelerated clinical course that is less responsive to treatment and has high mortality. Methods: Clinical records of 20 patients with CML who transformed to BC in two years between January 2012 and December 2013 were reviewed. Results: Out of total 240 patients, 20 (8.3%) transformed to blast crisis, among them 75% were males and 25% females. Mean age was 37.9 years (24–58 years) and 19 patients were positive for t (9; 22) (q34; q11) translocation at the time of transformation. The mean initial blood cell count was 204 (range: 33 to 526). Imatinib was offered in 76% of patients. The average duration between diagnosis and transformation to blast crises was 201 days (range: 24–333 days). Eight patients (40%) were transformed to acute myeloid leukaemia (AML) and 12 (60%) had acute lymphoblastic leukaemia (ALL). These patients were treated with standard AML/ALL type induction chemotherapy except one who died early. During the study period, 11 patients died. Median survival for whole group was 55 days. On bivariate and multivariate linear regression analyses mortality was not significantly associated with the duration between diagnosis and development of blast crises or the type of treatment received. Conclusion: Treatment of BC remains a challenge, particularly in under resourced areas where allogeneic hematopoietic stem cell transplantation (Allo-SCT) facility is sparse. Outcomes remain dismal in majority of these patients.Keywords: Chronic myelogenous leukaemia, Tyrosine Kinase inhibitors, Blast crises
Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973;243(5405): 290–3.
Faderl S, Talpaz M, Estrov Z, O'Brien S, Kurzrock R, Kantarjian HM, et al. The biology of chronic myeloid leukemia. N Engl J Med 1999;341(3):164–72.
Sawyers CL. Chronic myeloid leukemia. N Engl J Med 1999;340(17):1330–40.Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE, et al. Prognostic discrimination in "good-risk" chronic granulocytic leukemia. Blood 1984;63(4):789–99.
Rushing D, Goldman A, Gibbs G, Howe R, Kennedy BJ. Hydroxyurea versus busulfan in the treatment of chronic myelogenous leukemia. Am J Clin Oncol 1982;5(3):307–13.
Hughes T, Branford S, While DL, Reynolds J, Koelmeyer R, Seymour JF, et al. Impact of early dose intensity on cytogenetic and molecular responses in chronic-phase CML patients receiving 600mg/day of imatinib as initial therapy. Blood 2008;112(10):3965–73.
Kantarijan H, Hochhaus A, Saglio G, De Souza C, Flinn IW, Stenke L, et al. Superiority of nilotinib versus imatinib for the treatment of patients newly diagnosed chronich phase Ph+ chronic myeloid leukemia: 24-month minimum follow-up of the phase 3 randomized ENESTnd study. Lancet Oncol 2011;12(9):841–851.
Hochhaus A, Kantarjian HM, Baccarani M, Baccarani M, Lipton JH, Apperley JF, et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood 2007;109(6):2303–9.
Kantarjian HM, Giles FJ, Bhalla KN, Pinilla-Ibarz J, Larson RA, Gattermann N, et al. Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results. Blood 2011;117(4):1141–5.
Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E, Devergie A et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet 1998;352(9134):1087–92.
Talpaz M, Silver RT, Druker BJ, Goldman JM, Gambacorti-Passerini C, Guilhot F et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 2002;99(6):1928–37.
Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 2006;108 (1):28–37.
Hehlmann R. How I treat CML blast crisis, Blood 2012;120(4):737–47.
Saussele S, Lauseker M, Gratwohl A, Beelen DW, Bunjes D, Schwerdtfeger R, et al. Allogeneic hematopoietic stem cell transplantation (allo SCT) for chronic myeloid leukemia in the imatinib era: evaluation of its impact within a subgroup of the randomized German CML Study IV. Blood 2010;115(10):1880–5.
Barnes DJ, Schultheis B, Adedeji S, Melo JV. Dose-dependent effects of Bcr-Abl in cell line models of different stages of chronic myeloid leukemia. Oncogene 2005;24(42):6432–40.
Modi H, McDonald T, Chu S, Yee JK, Forman SJ, Bhatia R. Role of BCR/ABL gene-expression levels in determining the phenotype and imatinib sensitivity of transformed human hematopoietic cells. Blood 2007;109(12):5411–21.
Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 2006;108(1):28–37.
Saglio G, Hochhaus A, Goh YT, Masszi T, Pasquini R, Maloisel F et al. Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study: efficacy and tolerability of 140 milligrams once daily and 70 milligrams twice daily. Cancer 2010;116(16):3852–61.
Sacchi S, Kantarjian HM, O'Brien S, Cortes J, Rios MB, Giles FJ, et al. Chronic myelogenous leukemia in nonlymphoid blastic phase: analysis of the results of first salvage therapy with three different treatment approaches for 162 patients. Cancer 1999;86(12):2632–41.
Silver RT. The blast phase of chronic myeloid leukaemia. Best Pract Res Clin Haematol 2009;22(3):387–94.
Aziz Z, Iqbal J, Akram M, Saeed S. Treatment of chronic myeloid leukemia in the imatinib era: perspective from a developing country. Cancer 2007;109(6):1138–45.
Hehlmann R, Saussele S, Treatment of chronic myeloid leukemia in blast crisis. Haematologica 2008;93(12):1765–9.
Cervantes F, Villamor N, Esteve J, Montoto S, Rives S, Rozman C, et al. Lymphoid' blast crisis of chronic myeloid leukaemia is associated with distinct clinicohaematological features. Br J Haematol 1998;100(1):123–8.