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The Lugano classification (LC) [1] provided outstanding improvements in lymphoma staging and response evaluation. Adoption of universally applicable principles for clinical research and general practice benefits disease assessment and implementing more effective therapies [1, 2]. Since the publication of the LC in 2014, positron emission tomography–computed tomography (PET-CT) has been increasingly employed in lymphoma staging [2,3,4], with possible omission of bone marrow biopsy (BMB) for staging in numerous lymphoma subtypes [1, 3, 5]. Notable entities in which PET-CT staging does not allow BMB omission are follicular lymphoma (FL) and T-cell lymphomas (TCL) [4, 6].
Availability of PET-CT for lymphoma staging and response evaluation is relatively scarce in the developing world [5, 7, 8]. Even in countries with access to PET-CT, uneven distribution in favor of large urban areas is often seen [7]. In Brazil, while legislation mandates access to PET-CT in the public system since 2014, and in the private setting since 2010, timely performing of PET-CT without charge to patients is still frequently troubling. The current demand for BMB as a consequence of limited access to PET-CT in the developing world is yet to be determined [5, 8].
Joinville is a 600,000-inhabitant city in southern Brazil with only one PET scanner, set up at a private health facility. In Santa Catarina state, only one public hospital has PET-CT availability. This negatively impacts lymphoma management for a population in excess of 7 million. BMB is available at all hematology treatment centers in our state. Cedap is an accredited laboratory in northern Santa Catarina, and the main pathology provider for the largest public and private oncology treatment centers in Joinville.
To determine the current impact of BMB on lymphoma prognostication and management, we retrospectively assessed all BMB samples from patients with concurrent lymphoma diagnosis at Cedap in the 5-year period (2015–2019) after the LC. Bone marrow infiltration (BMI) at disease staging required immunohistochemistry determination of the lymphoma subtype established at diagnosis. Electronic health charts were reviewed as part of the SCQ-NeoH project, after approval by ethics review boards. All lymphoma diagnoses were in accordance with the WHO classification [9]. Exclusion criteria were lymphoma diagnosis before 2015 or after 2020, age below 18 years, and absence of medical follow-up by the hematology service after lymphoma diagnosis.
Fifty-seven patients with BMI diagnosed at lymphoma staging through BMB were included (Table 1). Median age was 55 years (range: 27–80), 65% were male (n = 37), and 70% of patients were managed in the public health system (n = 40). Lymphoma subtypes among patients with BMI diagnosed through BMB were FL (n = 18, 32%), mantle cell lymphoma (MCL, n = 9, 16%), DLBCL (n = 7, 12%), Burkitt (BL, n = 5, 9%), classic Hodgkin lymphoma (cHL, n = 4, 7%), other low-grade (n = 8, 14%) or high-grade B cell lymphomas (n = 4, 7%), and TCL (n = 2, 4%). Lymphoma staging before BMB indicated localized disease in 23 patients (40%), modifying initially proposed chemotherapy in 12 cases (31%). At diagnosis, 44% of patients (n = 25) had unremarkable complete blood counts, and 32% had normal lactate dehydrogenase levels (LDH, n = 17).
Median follow-up time was 26 months. Twenty-two patients had relapsed or refractory disease (29%) and 6 patients died from disease progression. Nine patients died with severe sepsis, two with heart failure, one with tumor lysis syndrome, and one with intracranial bleeding. For cHL, DLBCL, FL, and MCL patients (n = 38), using IPS, R-IPI, FLIPI, and MIPI prognostic scores, OS was inferior to initially predicted in 11 patients (29%) and superior in 4 (11%), with median predicted OS of 65 months (± 28.41) and median observed OS of 34 months (± 28.61) (p < 0.01). With the exception of MCL patients, due to absence of PFS data using MIPI score, observed PFS was inferior to initially predicted in 5 patients (17%), with median predicted PFS of 55 months (± 6.57) and median observed PFS of 15 (± 7.13) (p < 0.01).
In the reported 5-year period, 198 lymphoma diagnoses were carried out at Cedap, with BMB being performed on 116 cases (59%). BMB positivity for BMI at lymphoma staging was 49% (n = 57). Remaining cases were staged mostly with PET-CT in the private setting and with CT-scan alone in the public health system. Yearly trends concerning PET-CT usage for lymphoma staging and response evaluation will be prospectively assessed in the continuation of this study.
Since the LC, lymphoma staging is still performed locally with BMB and CT scan in most patients. Limited timely access to PET-CT is in contrast with national legislation for both private and public health systems. BMI diagnosis through BMB changed treatment duration or choice of chemotherapy regimen in almost one-third of cases and was associated with inferior OS and PFS in comparison with expected survival using validated prognostic scores [10, 11]. BMI was not adequately anticipated by cytopenias, elevated LDH or clinical features. BMB is a time- and resource-consuming procedure, with patient discomfort and non-negligible risks. Even so, it could be performed in a timely manner for the majority of our lymphoma patients, with a favorable impact in disease management and prognostication. FL was the most frequent subtype in this patient population, which correlates with the need for routine BMB in its staging [6].
Limitations of this study include its retrospective nature, the lack of local lymphoma registries for better data accrual and comparison, the limited number of publications with comparable design [5], and the still-growing knowledge on PET-CT lymphoma assessment [1, 3, 4, 6]. While a consolidated analysis of all lymphoma cases in our region could not be completed, this study adds to efforts uncovering the scenario of lymphoma management in our country and other parts of the developing world. Health economics analyses on the cost of delaying lymphoma treatment, lacking PET-CT or using BMB instead of PET-CT are planned with prospective data, and comparable assessments in other regional realities should be encouraged. Advances in treatment and disease evaluation have increasingly benefitted lymphoma patients [1,2,3]. A broader view of how these strategies are translated to developing countries is key for improving health systems and patient outcomes in a more balanced manner [5, 8].
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ATF was supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) in conducting this study.
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Fortes, A.T., de Lacerda, M.P., de França, P.H.C. et al. Post-Lugano classification usage of bone marrow biopsy in the staging of lymphoma. J Hematopathol 14, 313–315 (2021). https://doi.org/10.1007/s12308-021-00476-2
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DOI: https://doi.org/10.1007/s12308-021-00476-2