Bone Marrow Biopsy for the Initial Staging of Patients With Lymphoma: It’s Time to Eliminate This Procedure in Selected Patients

Staging systems for lymphoma were originally developed for patients with Hodgkin lymphoma (HL), to delineate the anatomic distribution of disease and enable the administration of potentially curative radiation therapy.[1,2] At the time, chemotherapy was for the hopeless, as it was of unknown benefit but quite toxic. As part of staging, all patients except those with obvious advanced disease were subjected to a staging laparotomy. Fortunately, the evaluation technology for patients with lymphoma has progressed over the years.

Insensitive intravenous pyelograms and ultrasounds, invasive lymphangiograms, and cumbersome gallium scans gave way to CT scans and, since 2000, [¹⁸F]-fluorodeoxyglucose (FDG)-positron emission tomography (PET), then FDG-PET-CT scans. However, one vestige of the historic persists, that being the dreaded bone marrow biopsy (BMB). Under local anesthesia, a small sample of bone from the pelvis is removed that is considered representative of the bone and marrow of the entire body. The procedure is performed as a reflex even when the likelihood of marrow involvement is low, such as in patients with limited-stage HL. Whether or not this procedure remains of sufficient value in staging in the PET era has recently come into question by an increasing number of studies and meta-analyses comparing the sensitivity of FDG-PET-CT with that of the trephine sample.[3-7]

In one of the larger experiences, El-Galaly et al reported on 454 patients with HL, including 41.6% with advanced-stage disease. PET-CT detected focal lesions in 82 (18%). Nevertheless, only 27 (6%) had a positive BMB and, in all of these, PET-CT identified advanced disease. Importantly, the results of the BMB upstaged only 5 patients, from stage III to IV. Therefore, BMB was irrelevant in directing a treatment strategy in the entire study population. Moreover, in that series, as well as others, no patients with early-stage disease had bone marrow involvement. In addition, almost all patients with advanced-stage disease and a positive bone marrow biopsy already had disease-related symptoms or other evidence of an advanced stage.

Similarly, in diffuse large B-cell lymphoma (DLBCL), PET-CT is more sensitive than BMB.[3,8-10] As with HL, patients with early-stage DLBCL rarely have marrow involvement; a positive BMB is generally identified in those with other evidence of advanced-stage disease or other factors consistent with a poor prognosis. Khan et al reported a series of 130 patients with DLBCL in which 27% had bone marrow involvement.[10] Of these patients, 94% were identified by PET-CT compared with 40% by BMB. BMB also failed to upstage any patients, and all patients with bone marrow involvement detected by BMB were also identified by PET-CT. Nevertheless, PET-CT may miss small amounts of involvement, especially in those with an indolent histology. Thus, a BMB is only indicated if identifying discordant histology is relevant for a clinical trial or for patient management, or if the results would alter treatment.

The data for PET-CT in assessing the bone marrow in other lymphoma histologies are insufficient to change the standard practice. However, a case could be made for eliminating the BMB as part of routine staging for patients with other evidence of advanced disease, and unless the results would impact patient management.

Thus, a PET-CT indicating bone or bone marrow involvement is sufficient to designate advanced-stage disease in HL or DLBCL, and those patients can be spared the anxiety and discomfort associated with an unnecessary BMB. For patients with limited disease, the low likelihood of bone marrow involvement greatly outweighs the need to subject large numbers of patients to the procedure. We are living in a time when the goals of treatment in HL and DLBCL are to maintain a high level of clinical efficacy while reducing the toxicities of our efforts. PET-based, risk-adapted strategies are resulting in a decrease in the number of patients subjected to unnecessary radiation, and a reduction in the rather arbitrary number of cycles of chemotherapy.[11,12] In the recently proposed revised staging and response criteria, a BMB is not recommended for the routine staging of these potentially curable histologies.[13] Clearly, eliminating a BMB in appropriate patients would be another step in the direction of minimizing the torture to which they are subjected.[14]

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

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