Cytogenetics and flow for myeloma – pro

A recent workshop was conducted to agree on guidelines for use of FISH in myeloma. These recommendations arose from a workshop organized for the European Myeloma Network, held at the Royal Marsden Hospital, London on March 11th 2005. 31 European laboratories were represented at the meeting.

These recommendations are intended to apply only to newly diagnosed cases of myeloma or frank relapse cases. The use of FISH to monitor response to high dose therapy, or to study diseases such as MGUS or primary amyloidosis where only a small proportion of the plasma cells may belong to the abnormal clone is still considered to be a research tool, and different criteria may need to be used.

The purpose of the workshop was to agree rules for FISH in myeloma but consideration was also given to conventional cytogenetic studies. It was agreed that these should not be discouraged but that, especially in a multi-centre setting, full cytogenetic studies were often impracticable due to the poor quality of samples and the poor ratio of number of man-hours required for the analysis to the number of patients on whom an abnormal result is obtained.

It was felt very strongly that much still needs to be learned about the significance of chromosome abnormalities in myeloma. For this reason, FISH results should not yet be used to make treatment decisions, except in the context of a clinical trial. The workshop also made 14 technical recommendations which are not applicable to this issue.

In conclusion, FISH for myeloma is still an investigational modality. A number of guidelines and reviews mention FISH but do not definitively address its place in myeloma diagnosis and management.

At present, in multiple myeloma, the use of conventional cytogenetics is currently restricted to clinical research studies and the differential diagnosis of unusual cases, because it tends to represent cells that admix rather than myelooma cells. However, certain FISH markers correlate well with prognosis and can be used in treatment decisions. Specifically, translocations involving the immunoglobulin heavy chain gene (IGH) at 14q32 and either monosomy or deletions of chromosome 13 (which can also be picked up on cytogenetics)  have been reported in a significant number of patients from both cytogenetic and interphase fluorescence in situ hybridization (FISH) studies. The CPT codes refer to the technical components of tests and panels of different markers and individual better established tests are difficult to separate from less established ones. Medicare currently covers cytogenetics and FISH for multiple myeloma. NCCN also recommends cytogenetics and FISH.

In conclusion, cytogenetics and FISH(88271) are tepidly supported by the workshop. Only one special stain(88313), iron, is documented.

More recenlty, it is recommended by Bird et al that a diagnosis of myeloma be confirmed by the demonstration of an aberrant plasma cell phenotype and/or monoclonality. Plasma cell phenotyping may be performed by flow cytometry and/or immunohistochemistry on trephine sections. Using an aspiratewith various cell types in it  confounds the results.

Jennifer M. Bird et al, Guidelines for the diagnosis and management of multiple myeloma 2011. British Journal of Haematology Volume 154, Issue 1, pages 32–75, July 2011

Fonseca R, Barlogie B, Bataille R, Bastard C, Bergsagel PL, Chesi M, Davies FE, Drach J, Greipp PR, Kirsch IR, Kuehl WM, Hernandez JM, Minvielle S, Pilarski LM, Shaughnessy JD Jr, Stewart AK, Avet-Loiseau H.Genetics and cytogenetics of multiple myeloma: a workshop report.Cancer Res. 2004 Feb 15;64(4):1546-58.

N. C. Gutierrez, J. L. Garcia, J. M. Hernandez, E. Lumbreras, M. Castellanos, A. Rasillo, G. Mateo, J. M. Hernandez, S. Perez, A. Orfao, et al.
Prognostic and biologic significance of chromosomal imbalances assessed by comparative genomic hybridization in multiple myeloma
Blood, November 1, 2004; 104(9): 2661 – 2666.

Harrison, Christine J. (2003) Cytogenetics of multiple myeloma: interpretation of fluorescence in situ hybridization results. British Journal of Haematology 120(6) Br J Haematol. 2009 Oct;147(1):22-42. Epub 2009 Aug 10.

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