520
Views
1
CrossRef citations to date
0
Altmetric
Review Article

Minimal residual disease in chronic lymphocytic leukemia: A consensus paper that presents the clinical impact of the presently available laboratory approaches

, , , , , , , , , , , , , , , , , , & show all
Pages 329-345 | Received 19 Feb 2018, Accepted 08 Apr 2018, Published online: 25 May 2018

References

  • A V. Sur la resorption du pusuaet sur l'alteration du sang dans les maladies clinique de persection nenemant. Premier observation. Rev Med. 1827;2:216.
  • R V. Weisses Blut und Milztumoren. I Med Z. 1846;5:157.
  • Rubin AD, Schultz E. Surface immunoglobulins on lymphocytes in leukemia. N Engl J Med. 1972;287:989–990.
  • Fialkow PJ, Najfeld V, Reddy AL, et al. Chronic lymphocytic leukaemia: clonal origin in a committed B-lymphocyte progenitor. Lancet. 1978;2:444–446.
  • Salsano F, Froland SS, Natvig JB, et al. Same idiotype of B-lymphocyte membrane IgD and IgM. Formal evidence for monoclonality of chronic lymphocytic leukemia cells. Scand J Immunol. 1974;3:841–846.
  • Fu SM, Winchester RJ, Feizi T, et al. Idiotypic specificity of surface immunoglobulin and the maturation of leukemic bone-marrow-derived lymphocytes. Proc Natl Acad Sci USA. 1974;71:4487–4490.
  • Schroer KR, Briles DE, Van Boxel JA, et al. Idiotypic uniformity of cell surface immunoglobulin in chronic lymphocytic leukeima. Evidence for monoclonal proliferation. J Exp Med. 1974;140:1416–1420.
  • Rai KR, Sawitsky A, Cronkite EP, et al. Clinical staging of chronic lymphocytic leukemia. Blood. 1975;46:219–234.
  • Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA: Cancer J Clin. 2007;57:43–66.
  • Torre LA, Siegel RL, Ward EM, et al. Global cancer incidence and mortality rates and trends–an update. Cancer Epidemiol. Biomarkers Prev.: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2016;25:16–27.
  • Mortality GBD, Causes of Death C. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1459–1544.
  • Cartwright RA, Gurney KA, Moorman AV. Sex ratios and the risks of haematological malignancies. Br J Haematol. 2002;118:1071–1077.
  • Dores GM, Anderson WF, Curtis RE, et al. Chronic lymphocytic leukaemia and small lymphocytic lymphoma: overview of the descriptive epidemiology. Br J Haematol. 2007;139:809–819.
  • Molica S. Sex differences in incidence and outcome of chronic lymphocytic leukemia patients. Leuk Lymphoma. 2006;47:1477–1480.
  • Cerhan JR, Vachon CM, Habermann TM, et al. Hormone replacement therapy and risk of non-Hodgkin lymphoma and chronic lymphocytic leukemia. Cancer Epidemiol. Biomarkers Prev.: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002;11:1466–1471.
  • Tamura K, Sawada H, Izumi Y, et al. Chronic lymphocytic leukemia (CLL) is rare, but the proportion of T-CLL is high in Japan. Eur J Haematol. 2001;67:152–157.
  • Yuille MR, Matutes E, Marossy A, et al. Familial chronic lymphocytic leukaemia: a survey and review of published studies. Br J Haematol. 2000;109:794–799.
  • Scarfo L, Ghia P. What does it mean I have a monoclonal B-cell lymphocytosis?: recent insights and new challenges. Semin Oncol. 2016;43:201–208.
  • Scarfo L, Ferreri AJ, Ghia P. Chronic lymphocytic leukaemia. Crit Rev Oncol/Hematol. 2016;104:169–182.
  • Rawstron AC, Bennett FL, O'Connor SJ, et al. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med. 2008;359:575–583.
  • Rawstron AC, Yuille MR, Fuller J, et al. Inherited predisposition to CLL is detectable as subclinical monoclonal B-lymphocyte expansion. Blood. 2002;100:2289–2290.
  • Nieto WG, Almeida J, Romero A, et al. Increased frequency (12%) of circulating chronic lymphocytic leukemia-like B-cell clones in healthy subjects using a highly sensitive multicolor flow cytometry approach. Blood. 2009;114:33–37.
  • Marti G, Abbasi F, Raveche E, et al. Overview of monoclonal B-cell lymphocytosis. Br J Haematol. 2007;139:701–708.
  • Wierda WG, Zelenetz AD, Gordon LI, et al. NCCN Guidelines Insights: chronic lymphocytic leukemia/small lymphocytic leukemia, version 1.2017. J Natl Compr Canc Netw. 2017;15:293–311.
  • Kravic-Stevovic T, Bogdanovic A, Boskovic D, et al. Ribosome-lamella complexes in the peripheral blood of patients with chronic lymphocytic leukemia are associated with serological immune deficiency. Ultrastruct Pathol. 2010;34:31–34.
  • Lee S, Graham LM, Chan G, et al. A diagnostic mystery solved by electron microscopy: a case of an "atypical" lymphoproliferative disorder. Ultrastruct Pathol. 2012;36:362–365.
  • Nagy-Simon T, Tatar AS, Craciun AM, et al. Antibody conjugated, raman tagged hollow gold-silver nanospheres for specific targeting and multimodal Dark-Field/SERS/Two Photon-FLIM imaging of CD19(+) B Lymphoblasts. ACS Appl Mater Interfaces. 2017;9:21155–21168.
  • Thakral B, Konoplev S. "Soccer ball" cells to "donut" cells: an unusual case of Richter syndrome. Blood. 2017;130:2358.
  • Quesada AE, Konoplev S. Classical Hodgkin lymphoma arising in a patient with chronic lymphocytic leukemia (Richter syndrome). Blood. 2017;130:2151.
  • Jamroziak K, Tadmor T, Robak T, et al. Richter syndrome in chronic lymphocytic leukemia: updates on biology, clinical features and therapy. Leuk Lymphoma. 2015;56:1949–1958.
  • Baliakas P, Kanellis G, Stavroyianni N, et al. The role of bone marrow biopsy examination at diagnosis of chronic lymphocytic leukemia: a reappraisal. Leuk Lymphoma. 2013;54:2377–2384.
  • Sah SP, Matutes E, Wotherspoon AC, et al. A comparison of flow cytometry, bone marrow biopsy, and bone marrow aspirates in the detection of lymphoid infiltration in B cell disorders. J Clin Pathol. 2003;56:129–132.
  • Dezorella N, Kay S, Baron S, et al. Measurement of lymphocyte aggregation by flow cytometry-physiological implications in chronic lymphocytic leukemia. Cytometry. 2016;90:257–266.
  • Ozet M. Immunophenotyping of chronic lymphocytic leukemia. Clin Lab. 2017;63:1621–1626.
  • Rawstron AC, Fazi C, Agathangelidis A, et al. A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study. Leukemia. 2016;30:929–936.
  • Tees MT, Flinn IW. Chronic lymphocytic leukemia and small lymphocytic lymphoma: two faces of the same disease. Expert Rev Hematol. 2017;10:137–146.
  • Craig FE. The utility of peripheral blood smear review for identifying specimens for flow cytometric immunophenotyping. Int J Lab Hematol. 2017;39:41–46.
  • Sandes AF, de Lourdes Chauffaille M, Oliveira CR, et al. CD200 has an important role in the differential diagnosis of mature B-cell neoplasms by multiparameter flow cytometry. Cytometry B Clin Cytom. 2014;86:98–105.
  • Kohnke T, Wittmann VK, Bucklein VL, et al. Diagnosis of CLL revisited: increased specificity by a modified five-marker scoring system including CD200. Br J Haematol. 2017;179:480–487.
  • Palumbo GA, Parrinello N, Fargione G, et al. CD200 expression may help in differential diagnosis between mantle cell lymphoma and B-cell chronic lymphocytic leukemia. Leuk Res. 2009;33:1212–1216.
  • Challagundla P, Medeiros LJ, Kanagal-Shamanna R, et al. Differential expression of CD200 in B-cell neoplasms by flow cytometry can assist in diagnosis, subclassification, and bone marrow staging. Am J Clin Pathol. 2014;142:837–844.
  • Rahman K, Kumar P, Gupta R, et al. Role of CD200 in differential diagnosis of mature B-cell neoplasm. Int J Lab Hematol. 2017;39:384–391.
  • Rawstron AC, Kreuzer KA, Soosapilla A, et al. Reproducible diagnosis of Chronic Lymphocytic Leukemia by flow cytometry: an European Research Initiative on CLL (ERIC) & European Society for Clinical Cell Analysis (ESCCA) harmonisation project. Cytometry Part B, Clinical Cytometry. 2018;94:121–128.
  • Baskar S, Kwong KY, Hofer T, et al. Unique cell surface expression of receptor tyrosine kinase ROR1 in human B-cell chronic lymphocytic leukemia. Clin Cancer Res: Off J Am Assoc Cancer Res. 2008;14:396–404.
  • Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343:1910–1916.
  • Put N, Konings P, Rack K, et al. Improved detection of chromosomal abnormalities in chronic lymphocytic leukemia by conventional cytogenetics using CpG oligonucleotide and interleukin-2 stimulation: a Belgian multicentric study. Genes Chromosom Cancer. 2009;48:843–853.
  • Vargova K, Pesta M, Obrtlikova P, et al. MiR-155/miR-150 network regulates progression through the disease phases of chronic lymphocytic leukemia. Blood Cancer J. 2017;7:e585.
  • Gonzalez-Gascon YMI, Hernandez-Sanchez M, Rodriguez-Vicente AE, et al. Characterizing patients with multiple chromosomal aberrations detected by FISH in chronic lymphocytic leukemia. Leuk Lymphoma. 2018;59:633–642.
  • Murphy EJ, Neuberg DS, Rassenti LZ, et al. Leukemia-cell proliferation and disease progression in patients with early stage chronic lymphocytic leukemia. Leukemia. 2017;31:1348–1354.
  • Kim JA, Hwang B, Park SN, et al. Genomic profile of chronic lymphocytic leukemia in Korea identified by targeted sequencing. PLoS One. 2016;11:e0167641.
  • Nguyen-Khac F, Borie C, Callet-Bauchu E, et al. Cytogenetics in the management of chronic lymphocytic leukemia: an update by the Groupe francophone de cytogenetique hematologique (GFCH). Ann Biol Clin. 2016;74:561–567.
  • Dighiero G, Hamblin TJ. Chronic lymphocytic leukaemia. Lancet. 2008;371:1017–1029.
  • Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002;99:15524–15529.
  • Sava GP, Speedy HE, Di Bernardo MC, et al. Common variation at 12q24.13 (OAS3) influences chronic lymphocytic leukemia risk. Leukemia. 2015;29:748–751.
  • Hui H, Fuller KA, Chuah H, et al. Imaging flow cytometry to assess chromosomal abnormalities in chronic lymphocytic leukaemia. Methods. 2018;134–135:32–40.
  • Gonzalez-Gascon YMI, Hernandez-Sanchez M, Rodriguez-Vicente AE, et al. A high proportion of cells carrying trisomy 12 is associated with a worse outcome in patients with chronic lymphocytic leukemia. Hematol Oncol. 2016;34:84–92.
  • Skowronska A, Austen B, Powell JE, et al. ATM germline heterozygosity does not play a role in chronic lymphocytic leukemia initiation but influences rapid disease progression through loss of the remaining ATM allele. Haematologica. 2012;97:142–146.
  • Marasca R, Maffei R, Martinelli S, et al. Clinical heterogeneity of de novo 11q deletion chronic lymphocytic leukaemia: prognostic relevance of extent of 11q deleted nuclei inside leukemic clone. Hematol Oncol. 2013;31:88–95.
  • Dohner H, Stilgenbauer S, James MR, et al. 11q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis. Blood. 1997;89:2516–2522.
  • Austen B, Skowronska A, Baker C, et al. Mutation status of the residual ATM allele is an important determinant of the cellular response to chemotherapy and survival in patients with chronic lymphocytic leukemia containing an 11q deletion. J Clin Oncol. 2007;25:5448–5457.
  • Slager SL, Rabe KG, Achenbach SJ, et al. Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL. Blood. 2011;117:1911–1916.
  • Wang DM, Miao KR, Fan L, et al. Intermediate prognosis of 6q deletion in chronic lymphocytic leukemia. Leuk Lymphoma. 2011;52:230–237.
  • Vladareanu AM, Ciufu C, Neagu AM, et al. The impact of hepatitis viruses on chronic lymphoproliferative disorders – preliminary results. J Med Life. 2010;3:320–329.
  • Vasile D, Vladareanu AM, Bumbea H. Peripheral T and NK cell non-hodgkin lymphoma a challenge for diagnosis. Maedica (Buchar). 2014;9:104–108.
  • Chapiro E, Lesty C, Gabillaud C, et al. "Double-hit" chronic lymphocytic leukemia: an aggressive subgroup with 17p deletion and 8q24 gain. Am J Hematol. 2018;93:375–382.
  • Barrientos JC. Sequencing of chronic lymphocytic leukemia therapies. Hematol Am Soc Hematol Educ Program. 2016;2016:128–136.
  • Rossi D, Terzi-di-Bergamo L, De Paoli L, et al. Molecular prediction of durable remission after first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia. Blood. 2015;126:1921–1924.
  • Binet JL, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48:198–206.
  • Rai KR, Peterson BL, Appelbaum FR, et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000;343:1750–1757.
  • 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. J Clin Oncol. 2005;23:4079–4088.
  • Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371:213–223.
  • Hallek M. Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and treatment. Am J Hematol. 2017;92:946–965.
  • Innocenti I, Autore F, Pasquale R, et al. Treatment approach for elderly and unfit patients with chronic lymphocytic leukemia. Expert Rev Hematol. 2017;10:1069–1076.
  • Chanan-Khan AA, Zaritskey A, Egyed M, et al. Lenalidomide maintenance therapy in previously treated chronic lymphocytic leukaemia (CONTINUUM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2017;4:e534–e543.
  • Wilkes GM. Drug essentials. An alkylating agent for CLL and NHL. Oncology (Williston Park, NY). 2009;23:55–56.
  • Knauf W. Bendamustine in the treatment of chronic lymphocytic leukemia. Expert Rev Anticancer Ther. 2009;9:165–174.
  • Mauro FR, Carella AM, Molica S, et al. Fludarabine, cyclophosphamide and lenalidomide in patients with relapsed/refractory chronic lymphocytic leukemia. A multicenter phase I-II GIMEMA trial. Leuk Lymphoma. 2017;58:1640–1647.
  • Howard DR, Munir T, McParland L, et al. Clinical effectiveness and cost-effectiveness results from the randomised, Phase IIB trial in previously untreated patients with chronic lymphocytic leukaemia to compare fludarabine, cyclophosphamide and rituximab with fludarabine, cyclophosphamide, mitoxantrone and low-dose rituximab: the Attenuated dose Rituximab with ChemoTherapy In Chronic lymphocytic leukaemia (ARCTIC) trial. Health Technol Assess. 2017;21:1–374.
  • Wendtner CM, Gregor M. Current perspectives on the role of chemotherapy in chronic lymphocytic leukemia. Leuk Lymphoma 2018;59:300–310.
  • Voorhies BN, Stephens DM. What is optimal front-line therapy for chronic lymphocytic leukemia in 2017? Curr Treat Options Oncol. 2017;18:12.
  • Landau DA, Tausch E, Taylor-Weiner AN, et al. Mutations driving CLL and their evolution in progression and relapse. Nature. 2015;526:525–530.
  • Al-Sawaf O, Fischer K, Herling CD, et al. Alemtuzumab consolidation in chronic lymphocytic leukaemia: a phase I/II multicentre trial. Eur J Haematol. 2017;98:254–262.
  • Schweighofer CD, Ritgen M, Eichhorst BF, et al. Consolidation with alemtuzumab improves progression-free survival in patients with chronic lymphocytic leukaemia (CLL) in first remission: long-term follow-up of a randomized phase III trial of the German CLL Study Group (GCLLSG). Br J Haematol. 2009;144:95–98.
  • Farahani M, Bokharaei-Salim F, Ghane M, et al. Prevalence of occult hepatitis C virus infection in Iranian patients with lymphoproliferative disorders. J Med Virol. 2013;85:235–240.
  • Coppola N, Pisaturo M, Guastafierro S, et al. Increased hepatitis C viral load and reactivation of liver disease in HCV RNA-positive patients with onco-haematological disease undergoing chemotherapy. Digestive Liver Disease: Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2012;44:49–54.
  • 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. J Clin Oncol. 2012;30:980–988.
  • Lundin J, Porwit-MacDonald A, Rossmann ED, et al. Cellular immune reconstitution after subcutaneous alemtuzumab (anti-CD52 monoclonal antibody, CAMPATH-1H) treatment as first-line therapy for B-cell chronic lymphocytic leukaemia. Leukemia. 2004;18:484–490.
  • Herter S, Herting F, Mundigl O, et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and of atumumab in vitro and in xenograft models. Mol Cancer Ther. 2013;12:2031–2042.
  • Thompson PA, Burger JA. Bruton's tyrosine kinase inhibitors: first and second generation agents for patients with Chronic Lymphocytic Leukemia (CLL). Expert Opin Investig Drugs. 2018;27:31–42.
  • Ayed AO, Parikh SA. Management of patients with chronic lymphocytic leukemia at high risk of relapse on ibrutinib therapy. Leuk Lymphoma. 2017;1–10.
  • Vladareanu AM, Cisleanu D, Dervesteanu M, et al. Myeloma cells with asurophilic granules–an unusual morphological variant – case presentation. J Med Life. 2008;1:74–86.
  • Bagacean C, Tempescul A, Patiu M, et al. Atypical aleukemic presentation of large granular lymphocytic leukemia: a case report. Ott. 2017;10:31–34.
  • Awan FT, Byrd JC. New strategies in chronic lymphocytic leukemia: shifting treatment paradigms. Clin Cancer Res: Off J Am Assoc Cancer Res. 2014;20:5869–5874.
  • Collett L, Howard DR, Munir T, et al. Assessment of ibrutinib plus rituximab in front-line CLL (FLAIR trial): study protocol for a phase III randomised controlled trial. Trials. 2017;18:387.
  • Jain P, Keating MJ, Wierda WG, et al. Long-term follow-up of treatment with ibrutinib and rituximab in patients with high-risk chronic lymphocytic leukemia. Clin Cancer Res. 2017;23:2154–2158.
  • Chanan-Khan A, Cramer P, Demirkan F, et al. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. Lancet Oncol. 2016;17:200–211.
  • Waldron M, Winter A, Hill BT. Pharmacokinetic and pharmacodynamic considerations in the treatment of chronic lymphocytic leukemia: ibrutinib, idelalisib, and venetoclax. Clin Pharmacokinet. 2017;56:1255–1266.
  • Jones JA, Robak T, Brown JR, et al. Efficacy and safety of idelalisib in combination with ofatumumab for previously treated chronic lymphocytic leukaemia: an open-label, randomised phase 3 trial. Lancet Haematol. 2017;4:e114–e126.
  • Slinger E, Thijssen R, Kater AP, et al. Targeting antigen-independent proliferation in chronic lymphocytic leukemia through differential kinase inhibition. Leukemia. 2017;31:2601–2607.
  • 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.
  • Kovacs G, Robrecht S, Fink AM, et al. Minimal residual disease assessment improves prediction of outcome in patients with ChronicLymphocytic 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.
  • Schwarzbich MA, McClanahan F, Gribben J. Allogeneic transplantation for chronic lymphocytic leukemia in the age of novel treatment strategies. Oncology. 2016;30:526–533, 540.
  • Kharfan-Dabaja MA, El-Asmar J, Awan FT, et al. Current state of hematopoietic cell transplantation in CLL as smart therapies emerge. Best Pract Res Clin Haematol. 2016;29:54–66.
  • Esteve J, Villamor N, Colomer D, et al. Stem cell transplantation for chronic lymphocytic leukemia: different outcome after autologous and allogeneic transplantation and correlation with minimal residual disease status. Leukemia. 2001;15:445–451.
  • Dreger P, Dohner H, Ritgen M, et al. Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010;116:2438–2447.
  • Moreno C, Villamor N, Colomer D, et al. Clinical significance of minimal residual disease, as assessed by different techniques, after stem cell transplantation for chronic lymphocytic leukemia. Blood. 2006;107:4563–4569.
  • Bottcher S, Ritgen M, Dreger P. Allogeneic stem cell transplantation for chronic lymphocytic leukemia: lessons to be learned from minimal residual disease studies. Blood Rev. 2011;25:91–96.
  • Ritgen M, Bottcher S, Stilgenbauer S, et al. Quantitative MRD monitoring identifies distinct GVL response patterns after allogeneic stem cell transplantation for chronic lymphocytic leukemia: results from the GCLLSG CLL3X trial. Leukemia. 2008;22:1377–1386.
  • Ritgen M, Stilgenbauer S, von Neuhoff N, et al. Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR. Blood. 2004;104:2600–2602.
  • Aalbers AM, Aarts MJ, Krol AD, et al. The beneficial local and abscopal effect of splenic irradiation in frail patients with chronic lymphocytic leukaemia. Neth J Med. 2016;74:122–129.
  • Frinc I, Dima D, Chitic M, et al. Transthoracic ultrasonography for the follow-up of a chronic lymphocytic leukemia patient with chemotherapy-induced immunosuppression prior to allogeneic stem cell transplantation. A case report. Med Ultrasonogr. 2017;19:330–332.
  • Frinc I, Ilies P, Zaharie F, et al. Transthoracic ultrasonography for the immunocompromised patient. A pilot project that introduces transthoracic ultrasonography for the follow-up of hematological patients in Romania. Romanian J Internal Med = Revue Roumaine De Medecine Interne. 2017;55:103–116.
  • Porter DL, Hwang WT, Frey NV, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7:303ra139.
  • 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.
  • Dimier N, Delmar P, Ward C, et al. A model for predicting effect of treatment on progression-free survival using MRD as a surrogate endpoint in CLL. Blood. 2018;131:955–962.
  • Sayala HA, Rawstron AC, Hillmen P. Minimal residual disease assessment in chronic lymphocytic leukaemia. Best Pract Res Clin Haematol. 2007;20:499–512.
  • Mattarucchi E, Spinelli O, Rambaldi A, et al. Molecular monitoring of residual disease in chronic myeloid leukemia by genomic DNA compared with conventional mRNA analysis. J Mol Diagn: JMD. 2009;11:482–487.
  • Moravcova J, Nadvornikova S, Sieglova Z, et al. Do transcriptionally silent BCR-ABL cells persist in CML patients in molecular remission after stem cell transplantation? Leukemia. 2001;15:997–999.
  • Sekiya Y, Xu Y, Muramatsu H, et al. Clinical utility of next-generation sequencing-based minimal residual disease in paediatric B-cell acute lymphoblastic leukaemia. Br J Haematol. 2017;176:248–257.
  • Ladetto M, Bruggemann M, Monitillo L, et al. Next-generation sequencing and real-time quantitative PCR for minimal residual disease detection in B-cell disorders. Leukemia. 2014;28:1299–1307.
  • Innao V, Allegra A, Russo S, et al. Standardisation of minimal residual disease in multiple myeloma. Eur J Cancer Care (Engl). 2017;26. DOI: 10.1111/ecc.12732
  • Shin S, Hwang IS, Kim J, et al. Detection of immunoglobulin heavy chain gene clonality by next-generation sequencing for minimal residual disease monitoring in B-lymphoblastic leukemia. Ann Lab Med. 2017;37:331–335.
  • Kotrova M, van der Velden VHJ, van Dongen JJM, et al. Next-generation sequencing indicates false-positive MRD results and better predicts prognosis after SCT in patients with childhood ALL. Bone Marrow Transplant. 2017;52:962–968.
  • Gaipa G, Cazzaniga G, Valsecchi MG, et al. Time point-dependent concordance of flow cytometry and real-time quantitative polymerase chain reaction for minimal residual disease detection in childhood acute lymphoblastic leukemia. Haematologica. 2012;97:1582–1593.
  • Schrappe M. Minimal residual disease: optimal methods, timing, and clinical relevance for an individual patient. Hematol Am Soc Hematol Educ Program. 2012;2012:137–142.
  • Hillmen P. Beyond detectable minimal residual disease in chronic lymphocytic leukemia. Semin Oncol. 2006;33:S23–S28.
  • Robertson LE, Huh YO, Butler JJ, et al. Response assessment in chronic lymphocytic leukemia after fludarabine plus prednisone: clinical, pathologic, immunophenotypic, and molecular analysis. Blood. 1992;80:29–36.
  • Vuillier F, Claisse JF, Vandenvelde C, et al. Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements. Leuk Lymphoma. 1992;7:195–204.
  • Lenormand B, Bizet M, Fruchart C, et al. Residual disease in B-cell chronic lymphocytic leukemia patients and prognostic value. Leukemia. 1994;8:1019–1026.
  • Cabezudo E, Matutes E, Ramrattan M, et al. Analysis of residual disease in chronic lymphocytic leukemia by flow cytometry. Leukemia. 1997;11:1909–1914.
  • 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.
  • Rawstron AC, Kennedy B, Evans PA, et al. Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. Blood. 2001;98:29–35.
  • Stehlikova O, Chovancova J, Tichy B, et al. Detecting minimal residual disease in patients with chronic lymphocytic leukemia using 8-color flow cytometry protocol in routine hematological practice. Int J Lab Hematol. 2014;36:165–171.
  • Rawstron AC, Bottcher S, Letestu R, et al. Improving efficiency and sensitivity: European Research Initiative in CLL (ERIC) update on the international harmonised approach for flow cytometric residual disease monitoring in CLL. Leukemia. 2013;27:142–149.
  • Raponi S, Della Starza I, De Propris MS, et al. Minimal residual disease monitoring in chronic lymphocytic leukaemia patients. A comparative analysis of flow cytometry and ASO IgH RQ-PCR. Br J Haematol. 2014;166:360–368.
  • Rawstron AC, de Tute R, Jack AS, et al. Flow cytometric protein expression profiling as a systematic approach for developing disease-specific assays: identification of a chronic lymphocytic leukaemia-specific assay for use in rituximab-containing regimens. Leukemia. 2006;20:2102–2110.
  • Sartor MM, Gottlieb DJ. A single tube 10-color flow cytometry assay optimizes detection of minimal residual disease in chronic lymphocytic leukemia. Cytometry B Clin Cytom. 2013;84:96–103.
  • Farren TW, Giustiniani J, Fanous M, et al. Minimal residual disease detection with tumor-specific CD160 correlates with event-free survival in chronic lymphocytic leukemia. Blood Cancer J. 2015;5:e273.
  • Dowling AK, Liptrot SD, O'Brien D, et al. Optimization and validation of an 8-color single-tube assay for the sensitive detection of minimal residual disease in b-cell chronic lymphocytic leukemia detected via flow cytometry. Lab Med. 2016;47:103–111.
  • Short NJ, Keating MJ, Wierda WG, et al. Fludarabine, cyclophosphamide, and multiple-dose rituximab as frontline therapy for chronic lymphocytic leukemia. Cancer. 2015;121:3869–3876.
  • Montillo M, Cafro AM, Tedeschi A, et al. Safety and efficacy of subcutaneous Campath-1H for treating residual disease in patients with chronic lymphocytic leukemia responding to fludarabine. Haematologica. 2002;87:695–700.
  • Del Poeta G, Del Principe MI, Buccisano F, et al. Consolidation and maintenance immunotherapy with rituximab improve clinical outcome in patients with B-cell chronic lymphocytic leukemia. Cancer. 2008;112:119–128.
  • Wendtner CM, Ritgen M, Schweighofer CD, et al. Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission–experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG). Leukemia. 2004;18:1093–1101.
  • Bosch F, Abrisqueta P, Villamor N, et al. Rituximab, fludarabine, cyclophosphamide, and mitoxantrone: a new, highly active chemoimmunotherapy regimen for chronic lymphocytic leukemia. J Clin Oncol. 2009;27:4578–4584.
  • 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.
  • Wierda WG. Minimal residual disease provides treatment focus for next chronic lymphocytic leukemia advances. J Clin Oncol. 2016;34:3722–3723.
  • Moreno C, Ritgen M, Rawstron A. Is MRD eradication a desirable goal in CLL? Best Pract Res Clin Haematol. 2010;23:97–107.
  • Caballero D, Garcia-Marco JA, Martino R, et al. Allogeneic transplant with reduced intensity conditioning regimens may overcome the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene and chromosomal abnormalities (11q- and 17p-). Clin Cancer Res: Off J Am Assoc Cancer Res. 2005;11:7757–7763.
  • 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.
  • 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.
  • Logan AC, Gao H, Wang C, et al. High-throughput VDJ sequencing for quantification of minimal residual disease in chronic lymphocytic leukemia and immune reconstitution assessment. Proc Natl Acad Sci USA. 2011;108:21194–21199.
  • Logan AC, Zhang B, Narasimhan B, et al. Minimal residual disease quantification using consensus primers and high-throughput IGH sequencing predicts post-transplant relapse in chronic lymphocytic leukemia. Leukemia. 2013;27:1659–1665.
  • Campbell PJ, Pleasance ED, Stephens PJ, et al. Subclonal phylogenetic structures in cancer revealed by ultra-deep sequencing. Proc Natl Acad Sci USA. 2008;105:13081–13086.
  • Sarantopoulos S, Stevenson KE, Kim HT, et al. Recovery of B-cell homeostasis after rituximab in chronic graft-versus-host disease. Blood. 2011;117:2275–2283.
  • Varghese AM, Rawstron AC, Hillmen P. Eradicating minimal residual disease in chronic lymphocytic leukemia: should this be the goal of treatment? Curr Hematol Malig Rep. 2010;5:35–44.
  • Nabhan C, Coutre S, Hillmen P. Minimal residual disease in chronic lymphocytic leukaemia: is it ready for primetime? Br J Haematol. 2007;136:379–392.
  • Evans PA, Pott C, Groenen PJ, et al. Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2007;21:207–214.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.