Minimal residual disease

An important demonstration of the efficacy of a MAb in minimal residual disease was achieved usiug MAb 17-lA (directed against the EGP-2 or EpCAM antigen as described previously) in patients with stage III colorectal cancer. Following surgical resection, MAb therapy reduced the overall death rate by 32% and the rate of recurrence by 23% [122]. 

Encouraging results with MAb-drug conjugates were seen in a phase I study with a conjugate of calicheamicin yli and a humanized anti-CD33 MAb in patients with refractory or relapsed AML [131]. Results support further evaluation in a setting of newly diagnosed or minimal-residual disease. 

Minimal Residual Disease, Viral Load, and Gene Quantitation. 221... 

With relevance to the administration of thiopurines in the early course of childhood ALL, the BFM Study Group reported on the association of TPMT genotype and minimal residual disease (MRD) in 810 children with childhood ALL enrolled into their trial ALL-BFM 2000 (206). In this trial, DNA-based MRD analysis after induction and after consolidation treatment was used for risk-adapted treatment stratification. A 4-week cycle of 6-MP was applied in-between these two MRD measurements. In patients homozygous for the TPMT 1 allele or those heterozygous for a variant TPMT allele, MRD levels on treatment day 33 were equally distributed between the groups. However, when MRD levels were assessed on treatment day 78, after administration of consolidation... 

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Ciudad J, San Miguel JF, Lopez-Berges MC et al. Prognostic value of immunophenotypic detection of minimal residual disease in acute lymphoblastic leukemia. J Clin Oncol 1998 16 3774-3781. 

Foroni L, Harrison JC, Hoffbrand AV et al. Investigation of minimal residual disease in chidhood and adult acute lymphoblastic leukemia by molecular analysis. Br J Haematol 1999 105 7-24. 

Coustan-Smith E, Sancho J, Hancock ML et al. Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia. Blood2000 96 2691-2696. 

Dworzak MN, Frbschl G, Printz D et al. Austrian Berlin-Frankfurt-Munster Study Group. Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia. B/oorf2002 99 1952-1958. 

Nyvold C, Madsen HO, Ryder LP et al. Nordic Society for Pediatric Hematology and Oncology. Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and an excellent outcome. Blood2002 99 1253-1258. 

Alemtuzumab has shown impressive results in refractory or relapsed CLL as well as up-front therapy for untreated CLL (35). The use of alemtuzumab to eradicate minimal residual disease of CLL is also reasonable (36). The role of Fey receptor polymorphisms on the clinical activity of alemtuzumab for CLL has not been extensively studies and will be discussed later. 

Montillo M, Schinkoethe T, Elter T. Eradication of minimal residual disease with alemtuzumab in B-cell chronic lymphocytic leukemia (B-CLL) patients the need for a standard method of detection and the potential impact of bone marrow clearance on disease outcome. Cawcer/wvext 2005 23 488-496. 

Nakao, M. Janssen, J. W. 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. 2000, 60(12), 3281-3289. 

Anastasi, J, Thangavelu, M., Vardiman, J. W., Hooberman, A L., Bian, M L., Larson, R. A, and Le Beau, M M. (1991) Interphase cytogenetic analysis detects minimal residual disease m a case of acute lymphoblastic leukemia and resolves the question of origin of relapse after allogeneic transplantation. Blood 77, 1087-1091. 

Heiss MM, Simon EH, Beyer BC, Gruetzner KU, Tarabichi A, Babic R, et al. Minimal residual disease in gastric cancer Evidence of an independent prognostic relevance of urokinase receptor expression by disseminated tumor cells in the bone marrow. J Clin Oncol 2002 20(8) 2005-2016. 

However, despite this great effort, cancer metastasis still remains the main cause of morbidity and death for cancer patients. This indicates that more studies are required to develop powerful strategies to fight what is known as the minimal residual disease , which will eventually develop into overt disease and finally kill... 

Conventional cytogenetics, FISH, and RT-PCR have been reliably used for the laboratory detection of the t(9 22). RT-PCR detection is possible in up to 95% of cases, and may detect up to 10% of cases missed by conventional cytogenetics, and is an important modality for minimal residual disease detection. Recently, quantitative real-time PCR-based approaches have improved the ability to detect and quantify BCR-ABL transcripts in CML patients (Figure 39-15 Color Plate 4]). The recent availability the tyrosine kinase inhibitor imatinib mesylate for CML is an important development in the treatment of CML and further underscores the importance of methods for sensitive and specific identification and quantification of the BCR-ABL fusions in patients with a clinical suspicion of a CML. 

Bose S, Deininger M, Gora-Tybor J, Goldman JM, Melo JV. The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals biologic significance and implications for the assessment of minimal residual disease. Blood 1998 92 3362-7. 

Moppett J, Burke GA, Steward CG, Oalchill A, Goulden NJ. The clinical relevance of detection of minimal residual disease in childhood acute lymphoblastic leukaemia. J Clin Pathol 2003 56 249-53. 

Steenbergen EJ, Verhagen OJ, van Leeuwen EF, van den Berg H, Behrendt H, Slater RM, et al. Prolonged persistence of PCR-detectable minimal residual disease after diagnosis or first relapse predicts poor outcome in childhood B-precursor acute lymphoblastic leukemia. Leukemia 1995 9 1726-34. 

Detection of translocations, such as BCL-2 in follicular lymphomas, can be used clinically to monitor for minimal residual disease. In patients with follicular lymphoma who received monoclonal antibody-purged autologous bone marrow transplantation, those whose bone marrow was negative by PCR for the BCL-2 rearrangement after purging had significantly longer freedom from recurrence than those whose bone marrow remained PCR positive." ... 

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