The Value of Bone Marrow Flow Cytometry for Diagnosis, Evaluation of Hematologic Response, and Monitoring of Non-Measurable Disease in AL Amyloidosis Patients

BACKGROUND. In 8–20 % of patients with systemic AL amyloidosis (AL-A), a non-measurable disease is diagnosed which is characterized by low serum concentration of paraprotein and free light chains (FLCs). The standard immunochemical methods are not sufficiently robust in such clinical situation to evaluate the response to therapy and subsequent monitoring of the disease.

AIM. To compare clinical and laboratory characteristics of AL-A patients with measurable and non-measurable diseases as well as to estimate the diagnostic value of multicolor flow cytometry of bone marrow (BM) in non-measurable AL-A.

MATERIALS & METHODS. This prospective study enrolled 108 patients with newly diagnosed systemic AL-А, 20 (18.5 %) of them with a non-measurable disease (the difference between involved and uninvolved FLCs < 50 mg/L, paraprotein level < 10 g/L). All patients underwent clinical and laboratory examination including immunochemical analysis and 10-color flow cytometry of BM.

RESULTS. In patients with non-measurable AL-A, severe cardiac failures occurred significantly less frequently (stage III: 16.7 % vs. 33.4 %; p = 0.03), whereas the rates of kidney and other organ involvements did not considerably differ. The median plasma cell (PC) count in non-measurable and measurable AL-A was 3.4 % and 5.2 %, respectively (p = 0.36) with the proportion of aberrant PCs in the total PC count being significantly lower in non-measurable disease (median 70.0 % vs. 92.2 %; p = 0.01). No correlation between the involved FLC concentration and the number of aberrant PCs was observed in non-measurable AL-A, while in measurable disease this correlation appeared to be significant (p = 0.003). The study demonstrated that the changes in aberrant PC clone by flow cytometry better correlated with the clinical response than with the changes of immunochemical parameters. Thus, the 5-year overall survival of patients with non-measurable and measurable AL-A did not differ (68 % and 61 %, respectively; p = 0.77). However, the 4-year clinical-progression-free (without vital organ dysfunction) survival was significantly lower in non-measurable disease, i.e., 23 % vs. 47 % (p = 0.04), which demonstrates that the standard immunochemical criteria alone used for response evaluation cannot provide sufficient control of the disease.

CONCLUSION. Multicolor flow cytometry of BM is an effective additional method of diagnosis and monitoring of non-measurable AL-A disease, which allows to determine the tumor clone and objectively assess the therapy efficacy in cases when immunochemical methods appear to be limited. It seems to be advisable to regard flow cytometry as part of standard examination for this category of patients aiming to improve the accuracy of diagnosis and the evaluation of hematologic response.

• Nelli Aleksandrovna Kashchavtseva National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0009-0001-9235-7853 (unauthenticated)
• I.G. Rekhtina National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0000-0001-5440-4340 (unauthenticated)
• I.V. Galtseva National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0000-0002-8490-6066 (unauthenticated)
• L.P. Mendeleeva National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167 https://orcid.org/0000-0002-4966-8146 (unauthenticated)

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