Significance of IgH Gene Rearrangement in Surveillance of Minimal Residual Disease after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Abstract

To investigate the value of immunoglobulin heavy chain (IgH) gene rearrangement in monitoring minimal residual disease (MRD) in multiple myeloma (MM) received autologous hematopoietic stem cell transplantation(auto-HSCT). The clinical data of 26 MM patients who received auto-HSCT in the Department of Hematology, Wuhan First Hospital from 2018 to 2022 were collected. IgH rearrangement was detected by multiplex PCR combined with capillary electrophoresis fragment analysis to evaluate minimal residual disease (MRD), and the outcome of the disease was analyzed statistically. Among the 26 MM patients, 18 were males and 8 were females, with a median age of 59(41-70) years. The median follow-up time after transplantation was 33 (7-52) months. Compared with the IgH rearrangement negative group (n=17), the proportion of CR and sCR of patients with IgH rearrangement positive in bone marrow samples before auto-HSCT at 3 months after transplantation was lower （1/9 vs 14/17）, and the duration of remission (DOR) after transplantation was shorter（10.78±4.35 vs 15.88±5.22 months）, with statistically significant difference in DOR between the two groups(P < 0.05). Compared with IgH rearrangement negative group (n=21), the proportion of CR and sCR of patients with positive IgH rearrangement results from peripheral blood stem cell collection at 3 months after transplantation was lower（0/5 vs 15/21）, the duration of remission (DOR) after transplantation was shorter（9.60±4.83 vs 15.19±5.11 months）, and the difference in DOR between the two groups was statistically significant (P < 0.05). During the follow-up period, 5 patients (5/9) with positive IgH rearrangement results in bone marrow specimens died, and all patients with negative IgH rearrangement results survived. Four patients (4/5) with positive IgH rearrangement results by peripheral blood stem cell samples died, while one patient (1/21) with negative IgH rearrangement results died. In both bone marrow and peripheral blood stem cell samples, the survival time of IgH rearrangement-positive patients after transplantation was shorter than that of IgH rearrangement-negative patients(P < 0.05). Logistic regression analysis showed that gender, disease stage, the proportion of bone marrow smear plasma cells at initial diagnosis, stem cell mobilization plan, efficacy evaluation before transplantation (≥CR and <CR), and CD34+ cell count had no effect on IgH rearrangement results of stem cell collection (P >0.05). By detecting IgH rearrangement of MM patients receiving auto-HSCT, the depth of MRD can be further evaluated, which has a certain guiding significance for the efficacy and prognosis of the disease.