The 1st World Congress on Controversies in Hematology (COHEM) Rome, - PowerPoint PPT Presentation

The 1st World Congress on Controversies in Hematology (COHEM) Rome, Italy 3 September, 2010: CLL Is eradication of MRD feasible and worthwhile in CLL? Moderator: K. Rai, USA Yes: G. Marti, USA No: G. Gaidano, Italy

Bioethical Approach to MBL/MRD Analytical Validity Certitude: MRD Detection: BM Bx, IHC, 4-color FCM, consensus PCR, qPCR ASO Scientific-Medical or Clinical Validity: The Biology of MRD and Clinical Trial Considerations. Clinical Practice Benefit Utility: F, FR/FC, FRC, Earlier Rx: IIB Consolidation and Maintenance Paradigm Shift: Palliative to Control to Possible Cure

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13.5 10 5 10 5 75.7 Overall B cells 11.1 <PE-A>: Lambda-MONO PE 8.54 <APC-A>: CD5 APC 10 4 10 4 10 3 10 3 4.14 63.8 10 2 10 2 9.93 86 0 0 10 2 10 3 10 4 10 5 0 <PerCP-A>: CD19 PerCP Cy55 10 2 10 3 10 4 10 5 0 <FITC-A>: Kappa-MONO FITC 10 5 10 5 <PE-A>: Lambda-MONO PE Clone NR B cell <PE-A>: Lambda-MONO PE 10 4 10 4 10 3 10 3 10 2 10 2 0 0 10 2 10 3 10 4 10 5 0 10 2 10 3 10 4 10 5 0 <FITC-A>: Kappa-MONO FITC <FITC-A>: Kappa-MONO FITC

10 5 10 5 Over all B cell 82.1 <PE-A>: Lambda-MONO PE <APC-A>: CD5 APC 32.4 10 4 10 4 0.22 10 3 10 3 8.94 4.2 3.48 7.42 10 2 10 2 60.4 0 0 10 2 10 3 10 4 10 5 0 <PerCP-A>: CD19 PerCP Cy55 10 2 10 3 10 4 10 5 0 <FITC-A>: Kappa-MONO FITC 10 5 10 5 clone NR B cell <PE-A>: Lambda-MONO PE <PE-A>: Lambda-MONO PE 10 4 10 4 10 3 10 3 10 2 10 2 0 0 10 2 10 3 10 4 10 5 0 2 3 4 5

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Editorial Montserrat E. (2005) Treatment of chronic lymphocytic leukemia: achieving minimal residual disease-negative status as a goal. Journal of Clinical Oncology 23(13), 2884-2885. Called for Standardization and revision of 1996 NCI WG Response Guidelines MRD-CR?

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Hallek et al Guidelines for the diagnosis and treatment of CLL: a report from the International WS on Chronic Lymphocytic Leukemia updating the NCI WG 1996 guidelines; Blood, Jan 2008 On-Line MRD The complete eradication of the leukemia is an obvious desired end point. MC FCM and RT qPCR, have determined that many patients who achieved a complete response by the 1996 NCI-WG guidelines have detectable minimal residual disease (MRD)…Patients will be defined as having a clinical remission in the absence of MRD when they have blood or marrow with less than one CLL cell per 10 000 leucocytes. The blood generally can be used for making this assessment except …Future clinical trials that aim toward achieving long- lasting CRs should include at least one test to assess MRD because the lack of leukemia persistence using these sensitive tests seems to have a strong, positive prognostic impact.

What has emerged? Palliative versus control versus the realistic possibility of a cure MRD is a surrogate marker for comparing responses of differing therapies (Montillo, Schinkoethe, an Elter). MDR would be a maker for: PFS, TTT, OS Nodular PR benign and malignant; Predict favorable outcome Monitoring to predict clinical evolution Due to the correlation between the blood and marrow, for patient comfort, the blood should be the first site tested for MRD What is the single objection? Patients that achieve MRD- status may have less aggressive or more favorable biologic disease meaning a better clinical prognosis in the first place.

Andritsos L, Byrd J, Hewes B, Kipps T, Johns D, and Jan A. Burger. Preliminary results from a phase I dose escalation study to determine the maximum tolerated dose of plerixafor in combination with rituximab in patients with relapsed chronic lymphocytic leukemia. [Abstract 2010] What is AMD300, Perixafor or Mozobil? bicyclam molecule blocks CXCR4 and SDF-1 Mobilization of CD34 Stem Cells Endostial Stromal Niche: CXCR4/CXCL12 axis Block Protective Pro-Survival Effects Mobilize CLL and test for MRD