Bone Marrow Staging For Lymphoma: A Re-Evaluation Of Clinical Utility

Bone marrow examination is an established component of the process used to stage patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and classical Hodgkin Lymphoma (CHL); and it is a general requirement of clinical trials. The procedure involves significant discomfort and inconvenience to the patient, as well as expense for the NHS, and this study was designed to evaluate the clinical utility of the information derived from staging bone marrow examinations. All patients presenting with DLBCL (n=1908), CHL (n=604) and FL (n=770) between 1^st Sept 2004 and 31^st August 2011 in the UK's population-based (3.6M) study area (Haematological Malignancy Research Network - www.hmrn.org) were included. Comprehensive clinical data, including diagnostic, prognostic, outcome and socio-demographic information are available for all patients. All diagnostic and staging specimens are reported in a single specialist haematopathology laboratory (the Haematological Malignancy Diagnostic Service – www.hmds.info). HMDS routinely undertake morphology and flow testing on bone marrow aspirate and trephine biopsies; while further molecular and cytogenetic tests are carried out at clinical discretion. This study aimed to assess the impact of bone marrow examination on the calculation of disease specific prognostic indices.

Bone marrow examinations were performed in 85% of patients, providing morphological evidence of disease in 10.2% of DLBCL, 7.2% of CHL and 36.5% of FL. In 18 patients with DLBCL and 16 patients with CHL the bone marrow was the presenting site of disease and this was associated with a very poor clinical outcome. In DLBCL knowledge of the bone marrow result increased the IPI by 1 point in 4.0% and by 2 points in 1.1% of cases. Similarly, the Hasenclaver index increased by 1 point in 3.6% of CHLs and the FLIPI increased by 1 point in 9.0% of FLs. In the case of DLBCL, 70% of these patients had an IPI score of >2 before the results of the marrow examination were added. As well as the assessment of prognosis, the results of bone marrow examination are a component of a number of key clinical decisions. Patients with stage 1 FL are routinely treated with radiotherapy with curative intent. In the absence of a bone marrow result, an additional 27 patients would have potentially been treated with radiotherapy. The 5 year relative survival (corrected for underlying population mortality rates) of this group was similar to those with stage 2 disease on watch and wait, and was slightly inferior to that seen in true stage 1 disease. Similarly, patients with stage1A DLBCL may be treated with 3 courses of R-CHOP and radiotherapy in preference to 6 or 8 courses of R-CHOP alone. In our data , lack of knowledge of the bone marrow result would not have affected the classification of this group in. In DLBCL the decision to give prophylaxis to prevent CNS relapse may be based on 2 or more extranodal sites, including bone marrow, involved at presentation. In this group, this decision could have been affected in 51 cases.

In the UK the approximate cost of taking and reporting a bone marrow is around $900. When used routinely the cost could approach $25,000 per patient whose IPI score is increased by the results of examination; the figure for CHL is $44,000. It is, therefore, difficult to justify the cost effectiveness of this approach. In newly presenting patients with lymphoma, bone marrow examination should be reserved for those with unexplained cytopenia, and those who may potentially require radiation therapy for early stage FL or CNS prophylaxis in DLBCL.