Kliniken & Institute … Institute Institute of Human… Research Department of Human… Acute Lymphoblastic… Diagnostics

MRD Diagnostik



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Acute Lymphoblastic Leukaemia (ALL) is the most common of childhood malignancies, representing 31% of all cancer cases in children younger than 15 years. In Germany, approximately 600 children are diagnosed with ALL each year. ALL is caused by the over-proliferation of lymphoid progenitor cells, arrested at early stages of B- or T-lymphocyte development. The disease can be classified into two different types: Common acute lymphoblastic leukaemia (B-ALL) and Acute Lymphoblastic Leukaemia (T-ALL). The two forms occur at different stages of lymphocyte development and in different cell lineages. In B-ALL, the tumour is derived from the B cell lineage and is caused by the over-proliferation of Pre- B cells. T-ALL is a malignancy of Thymocyte cells, which are progenitors for T lymphocytes (see Figure). B-ALL is more common than T-ALL representing 80-85% of all childhood ALL.


Treatment for ALL has markedly improved over the last 20 years, with modern chemotherapy treatments able to induce complete remission in 95-98% of children with the disease. However, approximately 20-30% of patients in remission have been found to later suffer a relapse, giving an overall survival rate of 80%. The relatively high rate of relapse means that patients in remission require careful monitoring to detect any indication of relapse. Most patients retain low levels of malignant cells, known as minimal residual disease (MRD), during and after cytotoxic treatment. It has been shown that levels of MRD significantly correlate with the probability of relapse in any particular patient i.e. that patients shown to have a high level of MRD have a higher risk of relapse than those with lower MRD levels. Therefore, measuring the levels of MRD can give a good indication of the treatment response and probability of relapse of any given patient.

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Bild: RQ-PCR-Experiment eines IgH-Rearrangements (mittels Sonde) mit einer Nachweisgrenze von 10-5 und der Messung eines Therapiezeitpunkts (R1); MNC (mononuklearer Zellhintergrund). 


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Fabienne Baumann (med. tech. Laboratoriumsassistentin)


Anne Camminady (med. tech. Laboratoriumsassistentin)


Claudia Holzschuh (Wissenschaftliche Hilfskraft)


Nicola Passow (med. tech. Laboratoriumsassistentin)


Camie Schmitt (med. tech. Laboratoriumsassistentin)


Ehemalige Mitarbeiter





Prof. Dr. M. Schrappe (ALL-BFM-Studie 95 + 2000) Klinik für Allgemeine Pädiatrie, Universität Kiel


Prof. Dr. D. Hölzer (GMALL 06/99+ 07/03-Studie) Med. Klinik II, Universität Frankfurt


Prof. Dr. M. Kneba (GMALL 06/99+ 07/03-Studie) Med. Klinik II, Universität Kiel


ESG-MRD-ALL (European Study Group on Minimal Residual Disease Detection in Childhood acute lymphoblastic Leukaemia)


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Ausgewählte Publikationen:


van Dongen JJ, Seriu T, Panzer-Grumayer ER, Biondi A, Pongers-Willemse MJ, Corral L, Stolz F, Schrappe M, Masera G, Kamps WA, Gadner H, van Wering ER, Ludwig WD, Basso G, de Bruijn MA, Cazzaniga G, Hettinger K, van der Does-van den Berg A, Hop WC, Riehm H, Bartram CR: Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood. Lancet. 1998 352: 1731


Pongers-Willemse M.J., Seriu T., Stolz F., Corral L., Gameiro P., Pisa P., Gonzales M., Bartram C.R., Panzer-Grümayer E.R., Biondi A., San Miguel J.F., van Dongen J.J.M.: Primers and protocols for standardized detection of minimal residual disease in acute lymphoblastic leukemia using immunoglobulin and T cell receptor gene rearrangements and TAL1 deletions as PCR targets. Leukemia 13, 110-118, 1999.

Nakao M., Janssen J.W.G., Flohr T., Bartram C.R.: Rapid and reliable quantification of minimal residual disease in acute lymphoblastic leukemia using rearranged immunoglobulin and T-cell receptor loci by LightCycler technology. Cancer Res. 60, 3281-3289, 2000.

Biondi A., Valsecchi M.G., Seriu T., D’Aniello E., Willemse M.P., Fasching K., Pannunzio A., Gadner H., Schrappe M., Kamps W.A., Bartram C.R., van Dongen J.J.M., Panzer-Grümayer E.R.: Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM-Study Group. Leukemia 14, 1939-1943, 2000.

Willemse M.J., Seriu T., d'Aniello E., Hop W.C.J., Panzer-Grümayer E.R., Biondi A., Schrappe M., Kamps W.A., Masera G., Gadner H., Riehm H., Bartram C.R., van Dongen J.J.M.: Detection of minimal residual disease identifies differences in treatment response between T-ALL and precursor-B-ALL. Blood 99, 4386-4393, 2002.


Brüggemann M, Raff T, Flohr T, Gökbuget N, Nakao M, Droese J, Lüschen S, Pott C, Ritgen M, Scheuring U, Horst HA, Thiel E, Hoelzer D, Bartram CR, Kneba M; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006 Feb 1;107(3):1116-23.


van der Velden VH, Cazzaniga G, Schrauder A, Hancock J, Bader P, Panzer-Grumayer ER, Flohr T, Sutton R, Cave H, Madsen HO, Cayuela JM, Trka J, Eckert C, Foroni L, Zur Stadt U, Beldjord K, Raff T, van der Schoot CE, van Dongen JJ; European Study Group on MRD detection in ALL (ESG-MRD-ALL). Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia. 2007 Apr;21(4):604-11.


Flohr T., Schrauder A., Cazzaniga G., Panzer-Grümeyer R., van der Velden V., Fischer S., Stanulla M., Basso G., Niggli F.K., Schäfer B., Sutton R., Koehler R., Zimmermann M., Valsecchi M.G., Gadner H., Masera G., Schrappe M., van Dongen J.J.M., Biondi A., Bartram C.R.: Minimal residual disease – directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP – BFM ALL 2000 for childhood acute lymphoblastic leukemia. Leukemia 22, 771-782, 2008

Schwarz A.K., Stanulla M., Cario G., Flohr T., Sutton R., Möricke A., Anker P., Stroun M., Welte K., Bartram C.R., Schrappe M., Schrauder A.: Quantification of free total plasma DNA and minimal residual disease detection in the plasma of children with acute lymphoblastic leukemia (ALL). Ann. Hematol. 88, 897-905, 2009

Conter V.*, Bartram C.R.*, Valsecchi M.G., Schrauder A., Panzer-Grümayer R., Möricke A., Arico M., Zimmermann M., Mann G., De Rossi G., Stanulla M., Locatelli F., Basso G., Niggli F., Barisone E., Henze G., Ludwig W.D., Haas O.A., Cazzaniga G., Koehler R., Silvestri D., Bradtke J., Parasole R., Beier R., van Dongen J.J.M., Masera G., Biondi A., Schrappe M.: Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia (ALL): results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood (in press) 2010