Prognostic Significance of Morphological Evaluation of Tumor Cells in Multiple Myeloma.
Authors: Al-sahmani Mohammed , Trnavska Irena , Antosova Monika , Antosova Libuse , Kissova Jarmila , Filkova Hana , Smetana Jan , Adam Zdenek , Pour Ludek , Krejci Marta , Zahradova Lenka , Bulikova Alena , Penka Miroslav , Kuglik Petr , Hajek Roman 
Published: October 2019

Abstract
Abstract 4889
Multiple myeloma (MM) is the second most common hematological malignancy. It is caused by clonal proliferation of terminally differentiated cells of B-lineage. Morphology assessment including the determination of plasma cell percentage in the bone marrow remains one of the basic diagnostic procedures even in the era of genomics. The objective of this study was to evaluate the prognostic impact of the presence of different plasma cell morphological subtypes on overall treatment response and long-term survival. We also analyzed whether this parameter can be correlated to other conventional prognostic/predictive markers. Our cohort consisted of 139 newly diagnosed MM patients who subsequently underwent autologous transplantation (AT) within the 4W and CMG 2002 clinical trials in a single center. Percentage of plasma cell subtypes in the bone marrow was evaluated based on the progressive nucleolus analysis, assessment of nuclear chromatin, and the nucleus/cytoplasm (N/C) ratio. A combination of these elements permits differentiation of eight subtypes P000-P111 and four subclassifications. Mature plasma cells (P000, P001) were found in 42.4% of patients; type I proplasmocytes (P010, P011, P100) in 38.1% of patients; and type II proplasmocytes (P101, P110) in 19.4% of patients. For patients undergoing AT, there was a statistically significant association between the presence of P000 subtype and overall treatment response whereas group of patients with overall therapeutic response ORR has lower number of mature plasma cell (P000 subtype) than patients without treatment response (median 24.0% vs. 36.0%, p = 0.032). Patients with <10% bone marrow infiltration by mature plasmocytes (P000 subtype) had shorter overall survival compared with patients with P000 percentage of ≥37% (46.8 months vs. 77.8 months; p = 0.020). The presence of <3% proplasmocytes (P110 subtype) was associated with longer time to progression compared with P110 ≥31% infiltration (median: 54.6 months vs. 22.4 months; p=0.045). Patients in ISS stage 1 or 2 had lower percentage of P010 (type I) proplasmocytes than patients in stage 3 (11.5% vs. 23.0%; p=0.030). In contrast, higher infiltration of P100 (type I) proplasmocytes and P101 (type II) proplasmocytes was observed in patients in 1-2 ISS stage compared with stage 3 patients (12.0% vs. 6.5%; p=0.015 for P100 and 1.0% vs. 0.0%; p=0.046 for P101). Patients without deletion of 13q14 chromosome had higher bone marrow percentage of mature P000 plasmocytes than patients with deletion of 13q14 (35% vs. 13%; p=0.014). Deletion of 13q14 was also associated with lower number of type II P110 proplasmocytes (36.5% vs. 6.0%; p=0.012). Despite advances in high-tech genomic technologies, evaluation of plasmocyte infiltration of the bone marrow still belongs to basic diagnostic procedures in MM and further morphological subtyping of plasmocytes should provide important prognostic information for MM patients treated by autologous stem cell transplantation. Supported by grants MSM 0021622434, MŠMT LC06027, MZCR NR9225-3 and IGA NR9225-3.

Disclosures
No relevant conflicts of interest to declare.