Prognostic factors of remission in patients with acute lymphoblastic leukemia after a first relapse
Keywords:
Precursor Cell Lymphoblastic Leukaemia- Lymphoma, Risk Factors, Remission Induction, Survival, Anti-neoplastic Combined Chemotherapy ProtocolsAbstract
Aims: To identify those factors that affect therapeutic response to achieve a second remission (2 RC) in patients with acute lymphoblastic leukaemia (ALL) in relapse.
Methods: Observational, descriptive and analytical study nested in a retrospective cohort of adults (> 18 years-old) ALL carriers treated during the period from 2008 to 2014 that disrupted the HGMLAL07 protocol when relapse was detected and began another therapeutic scheme.
Results: The study included 69 patients, of whom 62.3% (n = 43) were males, and the mean age was 29 years-old. The therapeutic regimens used were: high intensity (55.1%) [Hyper-CVAD (n = 34), IDA-Flag (n = 1), mitoxantrone-DARAC (n = 3)], moderate intensity (4.3%) [Re-induction schemes (n = 3)], and palliative treatment of low intensity with transfusion support (40.6%, n = 28).Only 19 patients (27.5%) achieved a 2 RC. The median overall survival was 120 (2- 575) days, 29% of patients were alive at one year. Using a high or moderate intensity regime as the rescue scheme gave no advantage over the conservative one (log-rank test, P = .812). None of the variables showed prognostic value of survival at one year. The duration of the first RC (OR 6.78, P = .005, 95% CI; 1.75 - 26.28) and receiving high intensity treatment (OR 0.22, P = 018, 95% CI: 0.06 - 0.78) were predictors of treatment failure to achieve 2 RC.
Conclusions: To achieve a first RC < 1 year was an important risk factor for not achieving a 2 RC. No prognostic factors for survival were identified. None of the schemes used for rescue showed superiority.
Author Biographies
Christian Omar Ramos-Peñafiel, Hospital General de México ‘‘Dr. Eduardo Liceaga’’
Servicio de Hematología, Hospital General de México ‘‘Dr. Eduardo Liceaga’’, Ciudad de México, México
Irma Olarte-Carrillo, Hospital General de México ‘‘Dr. Eduardo Liceaga’’
Laboratorio de Biología Molecular, Servicio de Hematología, Hospital General de México ‘‘Dr. Eduardo Liceaga’’, Ciudad de México, México
Adrián Santoyo-Sánchez, Universidad Nacional Autónoma de México
Unidad de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México
Humberto Castellanos-Sinco, Hospital General de México ‘‘Dr. Eduardo Liceaga’’
Servicio de Hematología, Hospital General de México ‘‘Dr. Eduardo Liceaga’’,Servicio de Hematología, Hospital General de Zona con UMAA No. 48 ‘‘San Pedro Xalpa’’, Instituto Mexicano del Seguro Social, Ciudad de México, México
Efreen Montano-Figueroa, Hospital General de México ‘‘Dr. Eduardo Liceaga’’
Servicio de Hematología, Hospital General de México ‘‘Dr. Eduardo Liceaga’’, Ciudad de México, México
Guadalupe León-González, Hospital General de México ‘‘Dr. Eduardo Liceaga’’
Servicio de Hematología, Hospital General de México ‘‘Dr. Eduardo Liceaga’’, Ciudad de México, México
Silvia Cabrera-Ozuna, Hospital General de México ‘‘Dr. Eduardo Liceaga’’
Servicio de Hematología, Hospital General de México ‘‘Dr. Eduardo Liceaga’’, Ciudad de México, México
Juan Collazo-Jaloma, Hospital General de México ‘‘Dr. Eduardo Liceaga’’
Servicio de Hematología, Hospital General de México ‘‘Dr. Eduardo Liceaga’’, Ciudad de México, México
Adolfo Martínez-Tovar, Hospital General de México ‘‘Dr. Eduardo Liceaga’’
Laboratorio de Biología Molecular, Servicio de Hematología, Hospital General de México ‘‘Dr. Eduardo Liceaga’’, Ciudad de México, México
References
Jabbour EJ, Faderl S, Kantarjian HM. Adult acute lymphoblastic leukemia. Mayo Clin Proc. 2005;80:1517-27,
http://dx.doi.org/10.4065/80.11.1517.
Larson S, StockW. Progress in the treatment of adults with acute lymphoblastic leukemia. Curr Opin Hematol. 2008;15:400-7,
http://dx.doi.org/10.1097/MOH.0b013e3283034697.
Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, et al. 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. 2005;106:3760-7,
http://dx.doi.org/10.1182/blood-2005-04-1623.
Gökbuget N, Hoelzer D. Treatment of adult acute lymphoblastic leukemia. Semin Hematol. 2009;46:64-75,
http://dx.doi.org/10.1053/j.seminhematol.2008.09.003.
Portell CA, Advani AS. Antibody therapy for acute lymphoblastic leukemia. Curr Hematol Malig Rep. 2012;7:153-9,
http://dx.doi.org/10.1007/s11899-012-0120-7.
Ai J, Advani A. Current status of antibody therapy in ALL. Br J Haematol. 2015;168:471-80,
http://dx.doi.org/10.1111/bjh.13205.
Hoelzer D, Thiel E, Löffler H, Ganser A, Heimpel H, Büchner T, et al. Risk groups in adult acute lymphoblastic leukemia. Haematol Blood Transfus. 1987;30:104-10.
https://doi.org/10.1007/978-3-642-71213-5_17
Wang H, Chen XQ, Geng QR, Liu PP, Lin GN, Xia ZJ, et al. Induction therapy using the MRC UKALLXII/ECOG E2993 protocol in Chinese adults with acute lymphoblastic leukemia. Int J Hematol. 2011;94:163-8,
http://dx.doi.org/10.1007/s12185-011-0891-y.
Larson RA, Dodge RK, Burns CP, Lee EJ, Stone RM, Schulman P, et al. A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood. 1995;85:2025-37.
https://doi.org/10.1182/blood.V85.8.2025.bloodjournal8582025
Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G, et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2007;109:944-50, http://dx.doi.org/10.1182/blood-2006-05-018192.
Ramos-Peñafiel CO, Martínez-Tovar A, Olarte-Carrillo I, Castellanos-Sinco H, Martínez-Murillo C, León-González G, et al. Experiencia del tratamiento de la leucemia linfoide aguda en recaída en el Hospital General de México. Rev Med Hosp Gen Mex. 2010;73:263-7.
Enciso LJ, Carreño JA, Suárez ML, Bermúdez CD, Arango M, Samudio I, et al. Tratamiento de rescate de leucemia aguda refractaria o en recaída con el régimen IDA-FLAG: experiencia en la rutina de los servicios. Rev Colomb Cancerol. 2014;18:53-61,
http://dx.doi.org/10.1016/j.rccan.2014.04.001.
Ramos-Peñafiel CO, Cabrera-García A, Rozen-Fuller E, González-León G, Balderas C, Kassack-Ipi˜na JJ, et al. [Comparison of the Hyper-CVAD with an institutional regimen for the treatment of acute lymphoblastic leukemia in adults in a hospital of Mexico]. Rev Perú Med Exp Salud Publica. 2014;31:525-9.
https://doi.org/10.17843/rpmesp.2014.313.91
Annino L, Vegna ML, Camera A, Specchia G, Visani G, Fioritoni G, et al. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood. 2002;99:863-71.
https://doi.org/10.1182/blood.V99.3.863
Koller CA, Kantarjian HM, Thomas D, O'Brien S, Rios MB, Kornblau S, et al. The hyper-CVAD regimen improves outcome in relapsed acute lymphoblastic leukemia. Leukemia. 1997;11:2039-44.
https://doi.org/10.1038/sj.leu.2400861
Fleischhack G, Hasan C, Graf N, Mann G, Bode U. IDAFLAG (idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poor-prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial. Br J Haematol. 1998;102:647-55.
https://doi.org/10.1046/j.1365-2141.1998.00836.x
Reece DE, Barnett MJ, Shepherd JD, Hogge DE, Klasa RJ, Nantel SH, et al. High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV + /- P) and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy. Blood. 1995;86:451-6.
https://doi.org/10.1182/blood.V86.2.451.bloodjournal862451
Guía de Práctica Clínica: Diagnóstico y Tratamiento de Leucemia Linfoblástica Aguda. 2009.
Rowe JM. Reasons for optimism in the therapy of acute leukemia. Best Pract Res Clin Haematol. 2015;28(2-3):69-72,
http://dx.doi.org/10.1016/j.beha.2015.10.002.
Forman SJ, Rowe JM. The myth of the second remission of acute leukemia in the adult. Blood. 2013;121:1077-82,
http://dx.doi.org/10.1182/blood-2012-08-234492.
Tavernier E, Boiron JM, Huguet F, Bradstock K, Vey N, Kovacsovics T, et al. Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial. Leukemia. 2007;21:1907-14,
http://dx.doi.org/10.1038/sj.leu.2404824.
Oriol A, Vives S, Hernández-Rivas J-M, Tormo M, Heras I, Rivas C, et al. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group. Haematologica. 2010;95:589-96,
http://dx.doi.org/10.3324/haematol.2009.014274.
Paydas S, Yavuz S, Disel U. Feasibility of FLAG-IDA regimen in cases with relapsed/refractory acute leukemia cases.Ann Hematol. 2006;85:63,
http://dx.doi.org/10.1007/s00277-005-0015-y.
Specchia G, Pastore D, Carluccio P, Liso A, Mestice A, Rizzi R, et al. FLAG-IDA in the treatment of refractory/ relapsed adult acute lymphoblastic leukemia. Ann Hematol. 2005;84:792-5,
http://dx.doi.org/10.1007/s00277-005-1090-9.
Batlevi CL, Matsuki E, Brentjens RJ, Younes A. Novel immunotherapies in lymphoid malignancies. Nat Rev Clin Oncol. 2015;13:25-40,
http://dx.doi.org/10.1038/nrclinonc.2015.187.
Jabbour E, O’Brien S, Ravandi F, Kantarjian H. Monoclonal antibodies in acute lymphoblastic leukemia. Blood. 2015;125:4010-6,
http://dx.doi.org/10.1182/blood-2014-08-596403.
Buie LW, Pecoraro JJ, Horvat TZ, Daley RJ. Blinatumomab: A First-in-Class Bispecific T-Cell Engager for Precursor B-Cell Acute Lymphoblastic Leukemia. Ann Pharmacother. 2015;49:1057-67,
http://dx.doi.org/10.1177/1060028015588555.
Magee MS, Snook AE. Challenges to chimeric antigen receptor (CAR)-T cell therapy for cancer. Discov Med. 2014;18:265-71.
Dahl J, Mace M, Kantarjian H, Jabbour E. Blinatumomab for the treatment of adult acute lymphoblastic leukemia. Drugs Today (Barc). 2015;51:231-41,
http://dx.doi.org/10.1358/dot.2015.51.4.2291051.
Topp MS, Gökbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S, et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014;32:4134-40,
http://dx.doi.org/10.1200/JCO.2014.56.3247.
Daver N, Boumber Y, Kantarjian H, Ravandi F, Cortes J, Rytting ME, et al. A Phase I/II Study of the mTOR Inhibitor Everolimus in Combination with HyperCVAD Chemotherapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia. Clin Cancer Res. 2015;21:2704-14,
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