PCR Standardization

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Hi,

Not sure of this abstract has been posted. Its from the August 2008

Blood. Slowly but surely we are making our way towards more accurate

reporting of PCRs...in clinical trials for a start. We are still

quite a distance for regular CML management but its good to see

progress being made.

http://bloodjournal.hematologylibrary.org/cgi/content/abstract/112/3/5

16maxtoshow= & HITS=10 & hits=10 & RESULTFORMAT= & fulltext=druker & searchid=1 &

FIRSTINDEX=0 & sortspec=date & resourcetype=HWCIT

Cheers,

DX 11/98

Desirable performance characteristics for BCR-ABL measurement on an

international reporting scale to allow consistent interpretation of

individual patient response and comparison of response rates between

clinical trials

Branford*, Fletcher, CP Cross, C Muller,

s Hochhaus, Dong-Wook Kim, Jerald P. Radich, Giuseppe Saglio,

Fabrizio Pane, Suzanne Kamel-Reid, Y. Lynn Wang, D Press,

Lynch, Zbigniew Rudzki, M Goldman, and

Institute of Medical and Veterinary Science, Adelaide, South

Australia, Australia

National Genetics Reference Laboratory, University of Southampton,

Salisbury, United Kingdom

Medizinische Fakultat Mannheim, University of Heidelberg, Mannheim,

Germany

St 's Hospital, The Catholic University of Korea, Seoul, Korea,

Republic of

Fred Hutchinson Cancer Research, Seattle, WA, United States

Ospedale Universita di Torino, Turin, Italy

Hematology Unit, Ceinge and Dipartimento di Biochimica e

Biotecnologie Mediche, University of Naples Federico II, Naples, Italy

Princess Margaret Hospital, Toronto, Ontario, Canada

Weill Medical College of Cornell University, New York, NY, United

States

Oregon Health & Science University, Portland, OR, United States

Novartis Pharmaceuticals Australia, Sydney, Australia

Imperial College at Hammersmith Hospital, London, United Kingdom

* Corresponding author; email: susan.branford@....

An international basis for comparison of BCR-ABL mRNA levels is

required for the common interpretation of data derived from

individual laboratories. This will not only aid clinical decisions

for individual patients with CML but also assist the interpretation

of results from clinical studies. We aligned BCR-ABL values generated

by 38 international laboratories to an international reporting scale

(IS) where a major molecular response (MMR) is defined as 0.10%.

Alignment was achieved by application of laboratory-specific

conversion factors calculated by comparisons performed with patient

samples against a reference method. A validation procedure was

completed for 19 methods. We determined performance characteristics

(bias and precision) for consistent interpretation of MMR after IS

conversion. When methods achieved an average BCR-ABL difference of

±1.2-fold from the reference method and 95% limits of agreement

within ±5-fold, the concordance of MMR was 91%. These criteria were

met by 58% of methods. When not met, the MMR concordance was 74%.

However, irrespective of the precision, when the bias was ±1.2-fold

as achieved by 89% of methods, there was good agreement between the

overall rates of MMR. This indicates that the IS can deliver accurate

comparison of molecular response rates between clinical trials when

measured by different laboratories.