Mendonça de Pontes Robéria, Flores-Montero Juan, Sanoja-Flores Luzalba, Puig Noemi, Pessoa de Magalhães Roberto J, Corral-Mateos Alba, Salgado Anna Beatriz, García-Sánchez Omar, Pérez-Morán José, Mateos Maria-Victoria, Burgos Leire, Paiva Bruno, Te Marvelde Jeroen, van der Velden Vincent H J, Aguilar Carlos, Bárez Abelardo, García-Mateo Aranzazú, Labrador Jorge, Leoz Pilar, Aguilera-Sanz Carmen, Durie Brian, van Dongen Jacques J M, Maiolino Angelo, Sobral da Costa Elaine, Orfao Alberto
Internal Medicine Postgraduate Program, Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-617, Brazil.
Cytometry Service, Institute of Paediatrics and Puericultura Martagão Gesteira (IPPMG), Faculty of Medicine, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-912, Brazil.
Cancers (Basel). 2021 Apr 3;13(7):1704. doi: 10.3390/cancers13071704.
B-cell regeneration during therapy has been considered as a strong prognostic factor in multiple myeloma (MM). However, the effects of therapy and hemodilution in bone marrow (BM) B-cell recovery have not been systematically evaluated during follow-up. MM (n = 177) and adult (≥50y) healthy donor (HD; n = 14) BM samples were studied by next-generation flow (NGF) to simultaneously assess measurable residual disease (MRD) and residual normal B-cell populations. BM hemodilution was detected in 41 out of 177 (23%) patient samples, leading to lower total B-cell, B-cell precursor (BCP) and normal plasma cell (nPC) counts. Among MM BM, decreased percentages (vs. HD) of BCP, transitional/naïve B-cell (TBC/NBC) and nPC populations were observed at diagnosis. BM BCP increased after induction therapy, whereas TBC/NBC counts remained abnormally low. At day+100 postautologous stem cell transplantation, a greater increase in BCP with recovered TBC/NBC cell numbers but persistently low memory B-cell and nPC counts were found. At the end of therapy, complete response (CR) BM samples showed higher CD19 nPC counts vs. non-CR specimens. MRD positivity was associated with higher BCP and nPC percentages. Hemodilution showed a negative impact on BM B-cell distribution. Different BM B-cell regeneration profiles are present in MM at diagnosis and after therapy with no significant association with patient outcome.
治疗期间的B细胞再生被认为是多发性骨髓瘤（MM）的一个重要预后因素。然而，在随访期间，治疗和血液稀释对骨髓（BM）B细胞恢复的影响尚未得到系统评估。通过新一代流式细胞术（NGF）对177例MM患者和14例成年（≥50岁）健康供体（HD）的BM样本进行研究，以同时评估可测量的残留疾病（MRD）和残留正常B细胞群体。在177例患者样本中有41例（23%）检测到BM血液稀释，导致总B细胞、B细胞前体（BCP）和正常浆细胞（nPC）计数降低。在MM患者的BM中，诊断时观察到BCP、过渡/幼稚B细胞（TBC/NBC）和nPC群体的百分比低于HD。诱导治疗后BM BCP增加，而TBC/NBC计数仍异常低。在自体干细胞移植后第100天，发现BCP有更大增加，TBC/NBC细胞数量恢复，但记忆B细胞和nPC计数持续较低。治疗结束时，完全缓解（CR）的BM样本与非CR样本相比，CD19 nPC计数更高。MRD阳性与更高的BCP和nPC百分比相关。血液稀释对BM B细胞分布有负面影响。MM患者在诊断时和治疗后存在不同的BM B细胞再生模式，与患者预后无显著关联。
