The Impact Of MRD Of Peripheral Blood Autologous Hematopoietic Stem Cell Collection On The Prognosis Of Patients With Multiple Myelom

BACKGROUND:Autologous stem cell transplantation（ASCT）is the standard of care for transplant-eligible multiple myeloma（TEMM）.Most clinical guidelines recommend ASCT for patients who have achieved partial response（PR）,but whether it would result in the presence of tumor cells within the stem cell collection（SCC）in patients failing to achieve complete response（CR）and its impact on patient outcomes remain to be elucidated.OBJECTIVE:In this study,we aimed to evaluate the minimal residual disease（MRD）in patients with TEMM by comparing the number of tumor cells in SCC and bone marrow（BM）samples obtained before ASCT.We also aimed to investigate the effect of MRD in SCC samples on treatment responses and survival.METHODS:We analyzed clinical data of 89 patients with TEMM undergoing ASCT between January 1,2013 to May 31,2021 in our hospital.MRD evaluation of both bone marrow（mMRD）and SCC（cMRD）were carried out before ASCT.Response assessment was defined according to International Myeloma Working Group criteria.MRD was evaluated by multiparameter flow cytometry with 10-5 sensitivity.Time from ASCT to disease progression was defined as progression-free survival（PFS）and time from ASCT to death as overall survival（OS）.RESULTS:A total of 89 patients met the inclusion criteria.The median age is 54（3769）and 62.9%were males.There were 25 patients presenting high-risk cytogenetic abnormalities by FISH.Before ASCT 31.5%of patients achieved MRD negativity in BM and 76.4%in SCC.By comparing the MRD-positivity status with different sensitivity and numeric levels of tumor cells,we found the percentage of patients with MRDpositivity in SCC and the numeric level of tumor cells in SCC were much less than those in BM（P<0.05）.There are only 2.3%of patients achieving stable disease（SD）at the time of stem cell collection,with the rest achieving PR and above.However,monoclonal plasma cells were detected in SCC of patients who achieved PR and above.With only 9.1%of patients who achieved CR being cMRD-positive,while 35.7%and 32.0%of patients in VGPR and PR groups,respectively,were cMRD-positive,but there was no statistical difference in the levels of tumor PCs in these three groups（P>0.05）.Although a greater proportion of patients in cMRD-negativity group obtaining VGPR and above at the time of collecting stem cell,no correlation was found between the cMRD status and the depth of response achieved by patients after induction therapy and ASCT（P>0.05）.The median follow-up was 26.8 months.There was no correlation between the depth of pre-collection or pre-ASCT responses and survival（P>0.05）.The achievement of negative mMRD before ASCT was associated with longer PFS（P=0.008,55.9m vs 27.1m）but not OS（P=0.115,NR vs.58₉m）.Patients with different cMRD status before ASCT experienced the similar PFS（P=0.980,40.5m vs 76.4m for negativity vs positivity）and OS（P=0.885,NR vs 58.8m for negativity vs positivity）.In patients achieving CR for best response,the presence of MRD negativity predicted longer survival compared with MRD positive CR and VGPR or less in PFS（P<0.001,median PFS,55.9m vs 24.7m vs 27.1m）and OS（P=0.006,median OS,NR vs NR vs 41.6m）.CONCLUSION:Our results indicate that tumor cells are less likely to present in stem cell collection than in bone marrow before ASCT.Also,the levels of plasma cells in SCC are similar among patients who achieve different depths of response（PR,VGPR or CR）at the time of collection.The pre-ASCT response has no impact on prognosis and detectable cMRD with 10-5 sensitivity does not significantly predict the inferior postASCT response or shorter survival,so patients are eligible to collect stem cell when obtaining PR and better.