Risk adjusted therapy in chronic lymphocytic leukemia: a phase II cancer trials Ireland (CTRIAL-IE [ICORG 07-01]) study of fludarabine, cyclophosphamide, and rituximab therapy evaluating response adapted, abbreviated frontline therapy with FCR in non-del(17p) CLL

References

• Li J, Smith A, Crouch S, et al. Estimating the prevalence of hematological malignancies and precursor conditions using data from Haematological Malignancy Research Network (HMRN). Cancer Causes Control. 2016;27:1019–1026.
   PubMed Web of Science ®Google Scholar
• Keating MJ, O'Brien S, Albitar M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. JCO. 2005;23:4079–4088.
   PubMed Web of Science ®Google Scholar
• Tam CS, O'Brien S, Wierda W, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood. 2008;112:975–980.
   PubMed Web of Science ®Google Scholar
• Thompson PA, Tam CS, O'Brien SM, et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood. 2016;127:303–309.
   PubMed Web of Science ®Google Scholar
• Strati P, Keating MJ, O'Brien SM, et al. Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL. Blood. 2014;123:3727–3732.
   PubMed Web of Science ®Google Scholar
• Bottcher S, Ritgen M, Fischer K, et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 Trial. JCO. 2012;30:980–988.
   PubMed Web of Science ®Google Scholar
• Fischer K, Bahlo J, Fink AM, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016;127:208–215.
   PubMed Web of Science ®Google Scholar
• Eichhorst B, Hallek M, Dreyling M, et al. Chronic lymphocytic leukemia: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2008;19 Suppl 2:ii60–ii62.
   PubMedGoogle Scholar
• Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111:5446–5456.
   PubMed Web of Science ®Google Scholar
• Oscier D, Haematol BCS. Guidelines on the diagnosis, investigation and management of chronic lymphocytic leukaemia (vol 159, pg 541, 2012). Br J Haematol. 2013;160:868–868.
   Web of Science ®Google Scholar
• Eichhorst B, Fink AM, Bahlo J, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016;17:928–942.
   PubMed Web of Science ®Google Scholar
• Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376:1164–1174.
   PubMed Web of Science ®Google Scholar
• O'Brien SM, Lamanna N, Kipps TJ, et al. A phase 2 study of idelalisib plus rituximab in treatment-naive older patients with chronic lymphocytic leukemia. Blood. 2015;126:2686–2694.
   PubMed Web of Science ®Google Scholar
• Herishanu Y, Goldschmidt N, Bairey O, et al. Efficacy and safety of frontline therapy with “FCR” regimen for chronic lymphocytic leukemia outside clinical trials: Israeli CLL Study Group Experience. Blood. 2014;124:5659.
   Web of Science ®Google Scholar
• Bouvet E, Borel C, Oberic L, et al. Impact of dose intensity on outcome of fludarabine, cyclophosphamide, and rituximab regimen given in the first-line therapy for chronic lymphocytic leukemia. Haematologica. 2013;98:65–70.
   PubMed Web of Science ®Google Scholar
• Howard DR, Munir T, McParland L, et al. Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL. Leukemia. 2017;21. DOI:10.1038/leu.2017.96
   PubMed Web of Science ®Google Scholar
• Ahmadi T, Schuster SJ. Variations on the fludarabine, cyclophosphamide, and rituximab combination in chronic lymphocytic leukemia therapy: what have we learned? JCO. 2009;27:479–480.
   PubMed Web of Science ®Google Scholar
• Foon KA, Boyiadzis M, Land SR, et al. Chemoimmunotherapy with low-dose fludarabine and cyclophosphamide and high dose rituximab in previously untreated patients with chronic lymphocytic leukemia. JCO. 2009;27:498–503.
   PubMed Web of Science ®Google Scholar
• Lamanna N, Jurcic JG, Noy A, et al. Sequential therapy with fludarabine, high-dose cyclophosphamide, and rituximab in previously untreated patients with chronic lymphocytic leukemia produces high-quality responses: molecular remissions predict for durable complete responses. J Clin Oncol. 2009;27:491–497.
   PubMed Web of Science ®Google Scholar
• Moreton P, Kennedy B, Lucas G, et al. Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol. 2005;23:2971–2979.
   PubMed Web of Science ®Google Scholar
• Kwok M, Rawstron AC, Varghese A, et al. Minimal residual disease is an independent predictor for 10-year survival in CLL. Blood. 2016;128:2770–2773.
   PubMed Web of Science ®Google Scholar
• Kovacs G, Robrecht S, Fink AM, et al. Minimal residual disease assessment improves prediction of outcome in patients with chronic lymphocytic leukemia (CLL) who achieve partial response: comprehensive analysis of two phase III studies of the German CLL Study Group. J Clin Oncol. 2016;34:3758–3765.
   PubMed Web of Science ®Google Scholar
• Oncology Working Party of the European Medicines Agency Appendix 4 to the guideline on the evaluation of anticancer medicinal products in man, Revision 2 Minimal residual disease as an endpoint in chronic lymphocytic leukaemia studies (EHMA/CHMP/629967/2014). [cited 2017 Apr 25]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2016/02/WC500201945.pdf
   Google Scholar
• Rossi D, Rasi S, Spina V, et al. Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. Blood. 2013;121:1403–1412.
   PubMed Web of Science ®Google Scholar
• Baliakas P, Hadzidimitriou A, Sutton LA, et al. Recurrent mutations refine prognosis in chronic lymphocytic leukemia. Leukemia. 2015;29:329–336.
   PubMed Web of Science ®Google Scholar
• Guieze R, Robbe P, Clifford R, et al. Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL. Blood. 2015;126:2110–2117.
   PubMed Web of Science ®Google Scholar
• Zenz T, Mertens D, Dohner H, et al. Molecular diagnostics in chronic lymphocytic leukemia – pathogenetic and clinical implications. Leuk Lymph. 2008;49:864–873.
   PubMed Web of Science ®Google Scholar
• Seiler T, Dohner H, Stilgenbauer S. Risk stratification in chronic lymphocytic leukemia. Semin Oncol. 2006;33:186–194.
   PubMed Web of Science ®Google Scholar
• Tam CS, Wierda W, O'Brien SM, et al. The clinical significance of chromosome 17p deletion in chronic lymphocytic leukemia: a study of 180 consecutive patients. JCO. 2008;26:7035.
   Web of Science ®Google Scholar
• Burger JA, Keating MJ, Wierda WG, et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2014;15:1090–1099.
   PubMed Web of Science ®Google Scholar
• Byrd JC, Brown JR, O'Brien SM, et al. Randomized comparison of ibrutinib versus ofatumumab in relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma: results from the phase III RESONATE trial. J Clin Oncol. 2014;32.
   Web of Science ®Google Scholar
• Stilgenbauer S, Schnaiter A, Paschka P, et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood. 2014;123:3247–3254.
   PubMed Web of Science ®Google Scholar
• Rossi D, Rasi S, Fabbri G, et al. Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia. Blood. 2012;119:521–529.
   PubMed Web of Science ®Google Scholar
• Oscier DG, Rose-Zerilli MJ, Winkelmann N, et al. The clinical significance of NOTCH1 and SF3B1 mutations in the UK LRF CLL4 trial. Blood. 2013;121:468–475.
   PubMed Web of Science ®Google Scholar
• Weissmann S, Roller A, Jeromin S, et al. Prognostic impact and landscape of NOTCH1 mutations in chronic lymphocytic leukemia (CLL): a study on 852 patients. Leukemia. 2013;27:2393–2396.
   PubMed Web of Science ®Google Scholar
• Bo MD, Del Principe MI, Pozzo F, et al. NOTCH1 mutations identify a chronic lymphocytic leukemia patient subset with worse prognosis in the setting of a rituximab-based induction and consolidation treatment. Ann Hematol. 2014;93:1765–1774.
   PubMed Web of Science ®Google Scholar
• Pozzo F, Bittolo T, Arruga F, et al. NOTCH1 mutations associate with low CD20 level in chronic lymphocytic leukemia: evidence for a NOTCH1 mutation-driven epigenetic dysregulation. Leukemia. 2016;30:182–189.
   PubMed Web of Science ®Google Scholar
• Villamor N, Conde L, Martinez-Trillos A, et al. NOTCH1 mutations identify a genetic subgroup of chronic lymphocytic leukemia patients with high risk of transformation and poor outcome. Leukemia. 2013;27:1100–1106.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996;87:4990–4997.
   PubMed Web of Science ®Google Scholar
• Hayat A, O'Brien D, O'Rourke P, et al. CD38 expression level and pattern of expression remains a reliable and robust marker of progressive disease in chronic lymphocytic leukemia. Leuk Lymphoma. 2006;47:2371–2379.
   PubMed Web of Science ®Google Scholar
• Rawstron AC, Villamor N, Ritgen M, et al. International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia. 2007;21:956–964.
   PubMed Web of Science ®Google Scholar
• Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343:1910–1916.
   PubMed Web of Science ®Google Scholar
• van Dongen JJ, Langerak AW, Bruggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17:2257–2317.
   PubMed Web of Science ®Google Scholar
• Hamblin TJ, Davis Z, Gardiner A, et al. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94:1848–1854.
   PubMed Web of Science ®Google Scholar
• Rosenquist R, Ghia P, Hadzidimitriou A, et al. Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: updated ERIC recommendations. Leukemia. 2017;31:1477–1481.
   PubMed Web of Science ®Google Scholar
• Ghia P, Stamatopoulos K, Belessi C, et al. ERIC recommendations on IGHV gene mutational status analysis in chronic lymphocytic leukemia. Leukemia. 2007;21:1–3.
   PubMed Web of Science ®Google Scholar
• Quinn FM, Waldron D, O'Brien D, et al. Detection of mutations in SF3B1 in chronic lymphocytic leukaemia patients by reverse transcription (Rt) polymerase chain reaction and high resolution melt curve analysis, an alternative approach to next generation sequencing for routine molecular diagnostic laboratories? Blood. 2015;126:5283.
   Web of Science ®Google Scholar
• Elhassadi E, Browne P, O'Brien D, et al. High resolution melt (Hrm) curve analysis of P53 mutations in chronic lymphocytic leukemia (Cll) patients. Haematologica. 2015;100:418–419.
   PubMed Web of Science ®Google Scholar
• Santacruz R, Villamor N, Aymerich M, et al. The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy. Haematologica. 2014;99:873–880.
   PubMed Web of Science ®Google Scholar
• Shanafelt TD, Witzig TE, Fink SR, et al. Prospective evaluation of clonal evolution during long-term follow-up of patients with untreated early-stage chronic lymphocytic leukemia. JCO. 2006;24:4634–4641.
   PubMed Web of Science ®Google Scholar
• Landau DA, Tausch E, Taylor-Weiner AN, et al. Mutations driving CLL and their evolution in progression and relapse. Nature. 2015;526:525–530.
   PubMed Web of Science ®Google Scholar
• Larrayoz M, Rose-Zerilli MJ, Kadalayil L,et al. Non-coding NOTCH1 mutations in chronic lymphocytic leukemia; their clinical impact in the UK CLL4 trial. Leukemia. 2017;31:510–514.
   PubMed Web of Science ®Google Scholar
• Pospisilova S, Gonzalez D, Malcikova J, et al. ERIC recommendations on TP53 mutation analysis in chronic lymphocytic leukemia. Leukemia. 2012;26:1458–1461.
   PubMed Web of Science ®Google Scholar