Dr Nick Goulden
Current Post: (since January 1999 ) Consultant Senior Lecturer in Paediatric Haematology, Royal Hospital for Children Bristol and Department of Pathology and Microbiology, University of Bristol.
Qualifications: MB ChB Edinburgh 1986, MRCP UK 1990, PhD Bristol 1998, MRCPath 1998
Clinical and Research Interests: My clinical commitments involve the full time provision of benign and malignant (including bone marrow transplantation) paediatric haematology services to the Children’s Hospital and increasingly to other centres in Southwest England.
My PhD thesis focussed on the development of a widely applicable sensitive method of PCR of antigen receptor gene rearrangements for the detection of MRD in ALL. The most notable elements of my thesis were:
- Demonstration that the false negative rate due to clonal instability could be minimised by the use of multiple markers (Published in Blood 1994)
- MRD is a more specific marker of impending relapse than chimerism after BMT for childhood ALL (Runner up prize at BSH 1995)
- Use of MRD to prove that extramedullary disease is rarely, if ever, isolated. (Published in BJH 1996)
- Clearance of MRD early in therapy is a strong prognostic factor in children treated according to UKALL X and XI (Rapid publication in BJH 1998)
I have maintained an active interest in MRD research and I have endeavoured to expedite the introduction of quality assured MRD technology into clinical protocols in the following ways.
In a joint study sponsored by the LRF our group has compared MRD as defined by the simple insensitive fluorescent fingerprinting technique with the more sensitive but laborious probing method in samples from children treated on ALL 97. This study finished in June 2000. Clinical follow up is now adequate and results will be presented at ASH 2002.
I have continued the work I began with Dr Chris Knechtli to exploit the clinical value of a simple MRD test pre BMT to highlight those who require further intensification of treatment. This is the basis of the new UK relapse protocol R3 of which I am the MRD co-ordinator. Practical work for this study is undertaken by Dr John Moppett a LRF sponsored clinical training fellow under my supervision.
I am a founder member of the LRF sponsored European Pre BMT MRD group which has now joined the ESG on MRD. This has allowed a unique insight into the practical skills of the I-BFM group and facilitated development of the standardised RQ ASO PCR approach central to this application. In the longer term I hope this will lead to pan-European MRD based relapse protocols that will more precisely define the role of BMT.
I continue to publish in this field and in the last year have reviewed articles for the Lancet, BJH, Leukemia and BMT. I am a member of the MRC ALL task force.
Publications
Steward CG, Goulden NJ et al. A Polymerase Chain Reaction Study of the Stability of Ig Heavy Chain and T-cell Receptor d Gene Rearrangements Between Presentation and Relapse of Childhood B-Lineage Acute Lymphoblastic Leukaemia. Blood 83: 1355-1362 1994
Langlands K, Goulden NJ, et al. False positive residual disease assessment post-bone marrow transplant in acute lymphoblastic leukaemia. Blood 84 1352-1353 1994
Goulden NJ, et al PCR Assessment Of Bone Marrow Status At Isolated Extramedullary Relapse Of Childhood B-Precursor Acute Lymphoblastic Leukaemia. British Journal of Haematology 87 282-285 1994
Langlands K, Goulden NJ, et al. Solid-phase sequencing of PCR products resolved by polyacrylamide gel electrophoresis. BioTechniques 18 618-620 1995
Molloy K, Goulden NJ, et al. Evaluation of mixed chimerism in acute lymphoblastic leukaemia following unrelated donor BMT. Blood. 87(7):3027-31, 1996.
Goulden NJ et al. Minimal residual disease analysis for the prediction of relapse in children with standard risk acute lymphoblastic leukaemia. A British Journal of Haematology 100 235-244 1998
Marks D, Bird JM, Cornish JMM, Goulden NJ, et al Unrelated donor bone marrow transplantation for children ands adolescents with Philadelphia positive acute lymphoblastic leukaemia. Journal of Clinical Oncology 16 931-936 1998
Knechtli CJC, Goulden NJ, et al. Minimal residual status as a predictor of relapse after allogeneic bone marrow transplant for children with acute lymphoblastic leukaemia. British Journal of Haematology 102 860-876 1998.
Knechtli CJC, Goulden NJ, et al. Minimal residual disease status prior to allogeneic bone marrow transplantation is an important determinant of successful outcome for children and adolescents with acute lymphoblastic leukaemia. Blood. 1;92(11):4072-9 1998
Goulden NJ et al. Practical application of minimal residual disease assessment in childhood acute lymphoblastic leukaemia Annotation. British Journal of Haematology. 2001 Feb;112(2):275-81.