short report

The clinical impact of staging bone marrow examination on treatment decisions and prognostic assessment of lymphoma patients

Dan Painter,1 Alexandra Smith,1 Ruth de Tute,2 Simon Crouch,1 Eve Roman1 and Andrew Jack2 1

Epidemiology and Cancer Statistics Group,

University of York, York, and 2Haematological Malignancy Diagnostic Service, Leeds Cancer Centre Leeds, Leeds, UK Received 28 November 2014; accepted for publication 16 February 2015 Correspondence: Andrew Jack, Haematological Malignancy Diagnostic Service Bexley Wing, St James’s University Hospital, Leeds LS9 7TF, UK.

Summary This study investigates the value of performing a staging bone marrow in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and classical hodgkin lymphoma (CHL). The results of 3112 staging bone marrow examinations were assessed for impact on prognostic assessment and critical treatment decisions. The detection of marrow involvement altered the disease-specific prognostic index for 43% of DLBCL, 62% of FL and 06% of CHL but marrow involvement in DLBCL was an independent prognostic factor. Knowing the marrow status potentially changed treatment in 92 patients, detection of these patients would have required 854 examinations to be performed.

Keywords: lymphoma, bone marrow examination, prognosis, flow cytometry.

E-mail: [email protected]

A bone marrow staging examination is performed in most patients presenting with lymphoma. Marrow involvement is important in assessing the stage of disease and calculating the International Prognostic Index (IPI) for diffuse large B-cell lymphoma (DLBCL), the Follicular Lymphoma International Prognostic Index (FLIPI) and the Hasenclaver Index (HIPI) for Classical Hodgkin Lymphoma (CHL). The presence of marrow involvement can affect the decision to administer central nervous system (CNS) prophylaxis in DLBCL patients and patients with stage 1 DLBCL may receive a reduced number of courses of chemotherapy with radiotherapy. Radiotherapy may be given with curative intent in stage1 follicular lymphoma (FL). Although the risks of bone marrow examination are low (Bain, 2006), the routine use of this procedure involves inconvenience to patients and financial costs. The purpose of this study was to investigate the clinical impact of information obtained from this procedure in patients with DLBCL, FL and CHL and to consider whether a more targeted approach is possible without detriment to clinical outcome.

a population of 36 million that is representative of the UK as a whole. Details of data collection methods have been previously published. (Smith et al, 2010) The primary diagnosis of lymphoma and the examination of the bone marrow were carried out at the Haematological Malignancy Diagnostic Service in the Leeds Cancer Centre. Bone marrow examination included morphological assessment of a marrow aspirate and trephine biopsy, flow cytometry using a standard 6- or 8-colour method, supplemented where required by immunocytochemistry on the trephine biopsy and molecular investigations where indicated. Each examination was assigned to one of five diagnostic categories:

Patients and methods

1 No evidence of disease. 2 Concordant disease where the same disease was present in the bone marrow and the presentation diagnostic biopsy. 3 Discordant disease where a different B-cell lymphoproliferative disorder was present in the marrow and presentation biopsy 4 Flow only disease where marrow was morphologically normal but a B-cell lymphoproliferative disorder was detectable by flow cytometry. 5 Primary Marrow Presentation where the marrow examination was the first diagnostic biopsy.

The data were obtained from the Haematological Malignancy Research Network (HMRN), which has systematically collected clinical and outcome data from all patients presenting in Yorkshire and the Humber since September 2004. This is

Information on survival was routinely collected from the Medical Research Information Service (MRIS). Survival was calculated on a time-to-event analysis with patients being followed for a minimum of 2 years until 31 July 2013.

ª 2015 John Wiley & Sons Ltd British Journal of Haematology, 2015, 170, 175–178

First published online 29 April 2015 doi: 10.1111/bjh.13412

Short report

Results A total of 3750 patients with DLBCL (n = 2201), FL (n = 885) and CHL (n = 664) presented during the study period. Adequate samples were obtained from 1774 (805%) DLBCL, 768 (868%) FL and 570 (858%) CHL patients, involvement being confirmed in 124%, 414% and 88% respectively. The patients who did not have marrow examination had a higher mean age (DLBCL 758 vs. 658: FL 695 versus 631: CHL 515 vs. 468 years).

The impact of bone marrow involvement on prognostic assessment Sufficient information was available to calculate the diseasespecific prognostic index in 2764 patients; the results for these patients are shown in Table I. Three hundred and eighteen DLBCL patients (208%) were in the high IPI category irrespective of the marrow status. Of the remaining patients, the marrow examination increased the IPI score by one category for 56 patients and by two categories for a further ten patients. Obtaining this information required 1207 marrows to be performed.

However, multivariate analysis showed that concordant marrow involvement was a poor prognostic factor independent of IPI [Age-adjusted hazard ratio (AHR) 29; 95% confidence interval (CI) 23–35 P < 0001] and was worse for those who presented with marrow disease (AHR 37; 95% CI 20– 67 P < 0001). For those with marrow disease detected by flow cytometry only the outcome was also worse (AHR 15; 95% CI 10–22 P = 005). This effect was greatest in those with Intermediate/high or High IPI scores. (Fig 1) and was specific to bone marrow involvement rather extranodal disease. Patients with involvement of two non-marrow extranodal sites had a median survival of 73 years but where one of these sites was bone marrow the median survival was 104 years. Two-hundred and sixty-eight FL patients were in the high FLIPI category irrespective of marrow disease and of the remaining 43 had their FLIPI score increased by one category when marrow results were included. This required 425 bone marrows to be performed. In CHL the impact of the marrow examination was negligible with only three patients moving to the moderate to high-risk category.

100

Intermediate/High risk

383 (553) 5 (07) 17 (25)

496 (908) 1 (02) 1 (02)

288 (416) 0 (00)

30 (55) 18 (33)

HR = 2.4, 95% CI = 1.6–3.5, P =

The clinical impact of staging bone marrow examination on treatment decisions and prognostic assessment of lymphoma patients.

This study investigates the value of performing a staging bone marrow in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL)...
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