Clinicopathological and Prognostic Characteristics of CD33-Positive Multiple Myeloma.
Authors: Sahara Naohi , Ohnishi Kazunori , Ono Takaaki , Sugimoto Yuya , Kobaysahi Miki , Takeshita Kaori , Shigeno Kazuyuki , Nakamura Satoki , Naito Kensuke , Takeshita Akihiro , Ohno Ryuzo 
Published: April 2020

Abstract
In multiple myeloma (MM), there have been few reports about the CD33 expression on MM cells so far, showing that a part (6.5–12 %) of patients expressed CD33 on their MM cells. However in these reports, neither detailed clinical information nor its prognostic significance was described. Therefore, we analyzed the CD33 expression on MM cells from newly diagnosed patients by flow cytometry and the correlation with other clinical parameters to determine the clinicopathological significance of this molecule in MM. The CD33 expression on MM cells was studied in the bone marrow from newly diagnosed 63 patients with MM. The median age of the patients was 69 years (range 43–91). The monoclonal component was: IgG in 46%, IgA in 27%, and Bence Jones protein (BJP) in 22% of patients. The patients were distributed according to Durie-Salmon stage, as follows: stage I, 15%; II, 35%; III, 50%. Fifty-five of these patients were treated with either melphalan-prednisolone (n=23) or VMMD with (n=7), or without (n=20) interferon (IFN) a. Four patients were treated with VAD followed by auto-PBSCT. Heparinized bone marrow cells were obtained at diagnosis. Cells were incubated with FITC-labelled anti-CD38, PE-anti-CD13, anti-CD33, anti-CD49e, anti-CD56, Per CP-anti-CD45 or APC-anti-CD19 monoclonal antibody. Cells were gated by their forward and side scatter characteristics and strong CD38 expression (CD38++). An antigen was defined as positive when more than 20 % of MM cells expressed it. Of 63 patients evaluated for CD33 expression, 14 (22%) were positive and 49 (78%) were negative. Of 14 patients with CD33+ MM, more than 80% of MM cells were positive in 6 (9.5%). No significant differences were found between the two groups in terms of age, sex, bone lesion extension, presence of extramedullary involvement, or Durie-Salmon stage. In addition, several prognostic indicators such as the serum level of calcium, creatinine, WBC counts, prevalence of BJP in urine, and chromosomal aberrancies such as del(13q), t(4;14), or t(11;14) were similar in both groups of patients. On the other hand, the serum level of β2 microglobulin and LDH in the CD33+ patients were significantly higher than in the CD33− patients (P=0.002 and 0.001, respectively). In addition, the CD33+ patients had a higher incidence of anemia and thrombocytopenia (P=0.01 and 0.02, respectively). With a median follow up of 18 months, the estimated over all survival was significantly shorter in the CD33+ patients than the CD33− patients (median survival; 18 vs. 38 months, P=0.04). Especially, mortality within a year from diagnosis in the CD33+ patients was significantly higher than the CD33− patients(43 vs. 10 %, respectively, P=0.005). No correlation between CD33 and other surface markers such as CD13, CD45, CD49e, and CD56 was observed. We here found that CD33+ MM patients showed higher serum β2 microglobulin and LDH level and a higher incidence of anemia or thrombocytopenia with poor prognosis. These results suggest that CD33+ MM might be a discrete entity and CD33 might be a useful therapeutic target for these patients.