Abstract
The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46–79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status ≥2. MRD < 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.
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References
Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009;27(6):911–8. doi:10.1200/jco.2008.18.6916.
Hallböök H, Simonsson B, Ahlgren T, Björkholm M, Carneskog J, Grimfors G, et al. High-dose cytarabine in upfront therapy for adult patients with acute lymphoblastic leukaemia. Br J Haematol. 2002;118(3):748–54.
Gökbuget N. How I treat older patients with ALL. Blood. 2013;122(8):1366–75. doi:10.1182/blood-2012-07-379016.
Holowiecki J, Krawczyk-Kulis M, Giebel S, Jagoda K, Stella-Holowiecka B, Piatkowska-Jakubas B, et al. Status of minimal residual disease after induction predicts outcome in both standard and high-risk Ph-negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4-2002 MRD Study. Br J Haematol. 2008;142(2):227–37. doi:10.1111/j.1365-2141.2008.07185.x.
Patel B, Rai L, Buck G, Richards SM, Mortuza Y, Mitchell W, et al. Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: Final results of the international trial UKALL XII/ECOG2993. Br J Haematol. 2010;148(1):80–9. doi:10.1111/j.1365-2141.2009.07941.x.
Gokbuget N, Kneba M, Raff T, Trautmann H, Bartram CR, Arnold R, et al. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012;120(9):1868–76. doi:10.1182/blood-2011-09-377713.
Beldjord K, Chevret S, Asnafi V, Huguet F, Boulland ML, Leguay T, et al. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia. Blood. 2014;123(24):3739–49. doi:10.1182/blood-2014-01-547695.
Fossat C, Roussel M, Arnoux I, Asnafi V, Brouzes C, Garnache-Ottou F, et al. Methodological aspects of minimal residual disease assessment by flow cytometry in acute lymphoblastic leukemia: A French multicenter study. Cytom Part B Clin Cytom. 2015;88(1):21–9. doi:10.1002/cyto.b.21195.
Bruggemann M, Schrauder A, Raff T, Pfeifer H, Dworzak M, Ottmann OG, et al. Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18–20 September 2008. Leukemia. 2010;24(3):521–35. doi:10.1038/leu.2009.268.
Ladetto M, Bruggemann M, Monitillo L, Ferrero S, Pepin F, Drandi D, et al. Next-generation sequencing and real-time quantitative PCR for minimal residual disease detection in B-cell disorders. Leukemia. 2014;28(6):1299–307. doi:10.1038/leu.2013.375.
Acknowledgments
The Swedish adult ALL group would like to thank Ann-Sofi Hörstedt and Hanna Åberg, Regionalt Cancer Centrum, Lund; Linda Fogelstrand, MD, PhD, Sahlgrenska University Hospital, Göteborg; Professor Göran Roos, Umeå University Hospital; Fredrik Ellin, MD, Kalmar County Hospital; Ylva Hammarlund, MD, Falun County Hospital; Michael Karlsson, Växjö County Hospital; Andréas Asplund, MD, Östersund County Hospital; Mattias Mattson, MD, Karlstad County Hospital; Jonas Wallwik, MD, Sundsvall County Hospital; Maria Eckerrot, MD, Västerås County Hospital; Christina Rhedin, MD, Borås County Hospital; Björn Andréasson, MD, Uddevalla County Hospital; and Nevzetta Kuric, MD, Halmstad County Hospital. The research was supported by the Lions Cancer Research Foundation, Uppsala (HH).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
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On behalf of the Swedish adult ALL Group, SVALL.
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Bergfelt, E., Kozlowski, P., Ahlberg, L. et al. Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study. Med Oncol 32, 135 (2015). https://doi.org/10.1007/s12032-015-0582-2
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DOI: https://doi.org/10.1007/s12032-015-0582-2