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Prognostic nomogram for multiple myeloma early relapse after autologous stem cell transplant in the novel agent era
Zhou, H., Jian, Y., Du, J., Liu, J., Zhang, Z., Yang, G., Wang, G., Tian, Y., Li, Y., Wu, Y., et al
Cancer medicine. 2023
Abstract
BACKGROUND The present study intended to establish a predictive nomogram for early relapse (ER) (<12 months) after autologous stem cell transplantation (ASCT) in the novel drug era for multiple myeloma (MM). PATIENTS AND METHODS The nomogram was designed and constructed to a retrospective clinical data of newly diagnosed MM patients received novel agent induction therapy and subsequent ASCT at three centers in China from July 2007 to December 2018. The retrospective study was conducted among 294 patients in the training cohort and 126 in the validation cohort. The nomogram's predictive accuracy was evaluated by the concordance index, calibration curve and decision clinical curve. RESULTS The study cohort included 420 newly diagnosed MM patients, and 100 (23.8%) were identified as having ER, including 74 in the training cohort and 26 in the validation cohort. According to the result of multivariate regression in the training cohort, the prognostic variables included in the nomogram were high-risk cytogenetics, LDH > UNL, and response less than very good partial response (VGPR) after ASCT. The calibration curve showed good fitness between the nomogram predictions and the actual observations and the nomogram was further validated by a clinical decision curve. The nomogram's C-index achieved 0.75 (95% CI, 0.70-0.80), which was higher than that of the Revised International Staging System (R-ISS) (0.62), ISS (0.59), and Durie-Salmon (DS) staging system (0.52). The discrimination ability of the nomogram in the validation cohort was superior to that of the other staging systems (C-index: 0.73 vs. R-ISS (0.54), ISS (0.55), and DS staging system (0.53)). DCA showed the prediction nomogram adds much more clinical utility. Different scores of the nomogram draw a distinction of OS. CONCLUSION The present nomogram could serve as a feasible and accurate prediction of ER in novel drug induction transplantation-eligible MM patients, which could help modify the post-ASCT strategy for patients at high risk of ER.
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Absolute Lymphocyte Count Prior to Lymphodepletion Impacts Outcomes in Multiple Myeloma Patients Treated with Chimeric Antigen Receptor T Cells
Liu, Y., Chen, W., Yu, M., Li, H., Cheng, H., Cao, J., Yan, Z., Shi, M., Zhu, F., Sun, H., et al
Transplantation and cellular therapy. 2022;28(2):118.e1-118.e5
Abstract
Chimeric antigen receptor (CAR) T cell therapy has shown unprecedented response rates in patients with relapsed/refractory (R/R) multiple myeloma (MM). However, the factors associated with immediate response and durable remission have not been fully elucidated. This study aimed to investigate the impact of prelymphodepletion (pre-LD) absolute lymphocyte count (ALC) on the outcomes of CAR T cell therapy and cytokine release syndrome (CRS). A receiver operating characteristic curve was used to determine the optimal cutoff value of pre-LD ALC. The correlation of pre-LD ALC with deep response (defined as very good partial response or better), CRS, and long-term outcomes was analyzed in 85 patients with R/R MM who received CAR T cell treatment. The median pre-LD ALC was 1.0 × 10(9)/L (range, 0.1 to 2.9× 10(9)/L). The optimal cutoff value of pre-LD ALC was 0.75 × 10(9)/L. Twenty-two patients (26%) had a low pre-LD ALC (<0.75 × 10(9)/L), and 63 patients (74%) had a high pre-LD ALC (≥0.75 × 10(9)/L). The deep response rate was significantly higher in patients with a high pre-LD ALC compared with patients with a low pre-LD ALC (76% versus 41%; P = .002). Patients with a low pre-LD ALC had significantly inferior overall survival (OS) and progression-free survival (PFS) compared with those with a high pre-LD ALC (median OS, 15.4 months versus not reached [P < .001]; median PFS, 8.4 months versus 27.3 months [P < .001]). No correlation between pre-LD ALC and CRS was observed. Our data indicate that pre-LD ALC may be a useful indicator to predict the outcomes of CAR T cell therapy in patients with R/R MM. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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Triplet RVd Induction for Transplant-Eligible Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis
Yang, G., Geng, C., Jian, Y., Zhou, H., Chen, W.
Advances in therapy. 2022
Abstract
INTRODUCTION The combination of lenalidomide, bortezomib, and dexamethasone (RVd) has become standard of care for transplant-eligible patients with newly diagnosed MM (NDMM). This study aimed to determine the efficacy of RVd as induction therapy in terms of response rates and survival outcomes of transplant-eligible patients with NDMM. METHODS The databases of Medline, Embase, and Cochrane Library were searched until February 1, 2021. Both randomized controlled trials (RCT) and non-RCTs from the available literature were extracted as one-arm data to assess the efficacy of each triplet regimen for the target patients in terms of response rates and survival rates for transplant-eligible patients with NDMM. Data was summarized as estimated pooled value regarding each evaluated index. Risk of bias of studies was assessed with standard methods. RESULTS The findings of 71 studies published from 2008 to 2020 were analyzed. For RVd induction, the overall response rate (ORR), very good partial response or better (≥ VGPR) rate, and complete response or better (≥ CR) rate after induction were 0.91 (95% CI 0.86-0.95), 0.23 (95% CI 0.17-0.29), and 0.56 (95% CI 0.51-0.61), respectively. Indirect comparisons in efficacy were made between RVd and other traditional triplet regimens. RVd induction led to a better ≥ CR rate than bortezomib, cyclophosphamide, and dexamethasone (VCd) regimen in both postinduction and post-ASCT phase, ≥ CR rate 0.11 (95% CI 0.08-0.15) and 0.21 (95% CI 0.12-0.32), respectively. The 1-year overall survival (OS) rate and 3-year OS rate of RVd regimen were longer than that of bortezomib, thalidomide, and dexamethasone (VTd), 0.97 (95% CI 0.94-0.98) vs 0.71 (95% CI 0.61-0.80), and 0.90 (95% CI 0.79-0.98) vs 0.70 (95% CI 0.64-0.75), respectively. CONCLUSIONS The RVd induction demonstrated confident response rates and survival benefits for transplant-eligible patients with NDMM.
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Pediatric acute myeloid leukemia patients with KMT2A rearrangements: a single-center retrospective study
Yang, W., Qin, M., Jia, C., Yang, J., Chen, W., Luo, Y., Jing, Y., Wang, B.
Hematology (Amsterdam, Netherlands). 2022;27(1):583-589
Abstract
PURPOSE Pediatric acute myeloid leukemia (AML) with KMT2A rearrangements has a very different prognosis. Poor outcomes cannot be avoided even after hematopoietic stem cell transplantation. In order to investigate the prognosis and efficacy, we conducted a retrospective analysis. PATIENTS AND METHODS We retrospectively analyzed a total of 32 children with KMT2A rearrangements AML treated in our hospital between January 2015 and February 2021. RESULTS The proportion of patients with KMT2A-rearranged in the medium-risk group of overall survival (OS) and event-free survival (EFS) was 100%. No differences in OS, EFS and cumulative incidence of relapse (CIR) were detected between the haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and full matched HSCT (P = 0.289, P = 0.303, P = 0.303). Acute graft-versus-host disease (aGVHD) was often detected in the haplo-HSCT cohort, while full matched HSCT had no obvious aGVHD, assessed as≤1 grade (P < 0.05). Patients in the medium-risk pediatric group could acquire 100% OS and EFS only after chemotherapy. There was no significant difference in OS, EFS and CIR between full matched HSCT and haploidentical transplantation in pediatric AML with KMT2A rearrangements, but full matched HSCT seemed to have a lower death rate. The severity of aGVHD in the full matched HSCT was less than that in the haploidentical transplantation group. CONCLUSION The primary choice of donor can be HLA-matched sibling donors or matched unrelated donors for children with AML with KMT2A rearrangements, and the secondary choice can be haploid donors.
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What Multiple Myeloma With t(11;14) Should Be Classified Into in Novel Agent Era: Standard or Intermediate Risk?
Gao, W., Du, J., Liu, J., Zhou, H., Zhang, Z., Jian, Y., Yang, G., Wang, G., Tian, Y., Li, Y., et al
Frontiers in oncology. 2020;10:538126
Abstract
OBJECTIVE To investigate the prognostic value of t(11;14) for de novo multiple myeloma (MM) patients in novel agent era. METHODS A total of 455 patients with fluorescence in situ hybridization (FISH), before treatments from three hospitals in China, were included in the study. All patients received autologous stem cell transplantation (ASCT) after induction therapy as consolidation. High risk (HR) cytogenetics were defined as t(4;14), t(14;16), and/or del 17p. RESULTS A total of 152 patients were in the HR group. Of patients without HR cytogenetics, 55 were in the t(11;14) group, and 248 were in the standard risk (SR) group without t(11;14). Gain in 1q21 was observed in 38.9% patients with t(11;14). There were no differences in median progression free survival (PFS) and overall survival (OS), respectively, between patients in the t(11;14) group and those in the SR group. Patients in the t(11;14) group had the longer median PFS and OS, respectively, compared with those in the HR group. Regardless of coexisting with 1q21 gain or not, patients in the t(11;14) group still had similar median PFS and OS compared to those in the SR group. Finally, multivariate analysis indicated that including 1q21 gain and bone marrow plasma cell with CD20 expression, no variables were found to predict the outcome of the t(11;14) group in our cohort. CONCLUSIONS These results confirm that outcomes of t(11;14) MM are similar to standard risk patients when they receive novel agent induction therapy consolidated by ASCT. Gain of 1q21 coexists with t(11;14) frequently. In addition, both bone marrow plasma cell with CD20 expression and 1q21 gain have no impact on median PFS or OS for patients with t(11;14).
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Gain of 1q21 is an adverse prognostic factor for multiple myeloma patients treated by autologous stem cell transplantation: A multicenter study in China
Gao, W., Jian, Y., Du, J., Li, X., Zhou, H., Zhang, Z., Yang, G., Wang, G., Tian, Y., Li, Y., et al
Cancer medicine. 2020;9(21):7819-7829
Abstract
BACKGROUND Autologous stem cell transplantation (ASCT) has been recommended as a standard approach for young multiple myeloma (MM) patients for decades, even in the era of novel agents. Gain of chromosome 1q21 is a common cytogenetic abnormality in MM, while its clinical prognostic value is still controversial. METHODS In this multicenter study, we retrospectively analyzed 1q21 gain in 446 newly diagnosed MM patients who received at least one ASCT from three large myeloma centers in China. RESULTS Of the all 446 patients, 1q21 gain was an adverse predictor of progression-free survival (PFS) (34 vs 56 months, P = .005) and overall survival (OS) (69 vs 100 months, P = .002). Gain of 1q21 was more likely to coexist with t(4;14), t(14;16), and del(13q). Nevertheless, isolated 1q21 gain still exhibited unfavorable effects on PFS (35 vs 66 months, P = .045) and OS (61 vs 100 months, P = .026). The coexistence of 1q21 gain and high-risk cytogenetics (HRCs) [del(17p), t(4;14),and/or t(14;16)] showed poor prognosis on both PFS and OS, while no additional adverse effect could be identified when compared with HRCs alone. Moreover, when coexisting with t(11;14), patients with 1q21 gain showed a comparable survival to those without 1q21 gain. For patients treated with novel induction regimens followed by ASCT, 1q21 gain also conferred an inferior prognosis. Multivariate analysis further confirmed 1q21 gain could independently predict shorter PFS and OS. CONCLUSION In conclusion, 1q21 gain is an adverse prognostic factor for MM patients received ASCT.
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Comparing the outcomes between TMLI and non-TMLI conditioning regimens for adult high-risk acute lymphoblastic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: a single-center experience
Zhao, X., Lu, X., Tang, L., Yan, H., Chen, W., Shi, W., Zhong, Z., You, Y., Xia, L., Hu, Y., et al
Leukemia & lymphoma. 2020;:1-9
Abstract
This study aimed to retrospectively evaluate the outcomes of adult patients with high-risk acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) with either total marrow and lymphoid irradiation (TMLI)-containing or non-TMLI conditioning regimen. Seventy adult patients with high-risk ALL who received allo-HSCT were enrolled in this study and divided into two groups based on the conditioning regimen type (TMLI group: n = 29 and non-TMLI group: n = 41). We noted significant statistical differences in the 1-year estimated cumulative incidence of relapse (25% vs. 46.5%, p = 0.018), the 1-year estimated overall survival (73.1% vs. 52.6%, p = 0.033) and disease-free survival (65.2% vs. 48.2%, p = 0.026) but found no considerable difference in transplant-related mortality (12% vs. 13.4%, p = 0.619) between patients in the TMLI and non-TMLI groups. The TMLI-containing regimen is safe and alternative for patients with high-risk ALL undergoing allo-HSCT.
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Immunoparesis recovery 1 year after ASCT is independently associated with favorable survival in patients with symptomatic multiple myeloma who undergo autologous stem cell transplantation
Gao, W., Li, J., Wu, Y., Li, Y., Leng, Y., Liu, A., Yang, G., Tian, Y., Wang, H., Wang, G., et al
Annals of hematology. 2019
Abstract
Immunoparesis is defined as a reduction in the levels of one, two, or three uninvolved immunoglobulins. However, there are very limited data on the incidence and prognostic significance of immunoparesis recovery 1 year after autologous stem cell transplantation (ASCT) in MM. We reviewed medical records of de novo MM patients who received ASCT at Beijing Chao Yang hospital. One hundred eight MM patients were included in the study. Conventional chemotherapy was administered as induction regimen in 16 patients (14.8%), whereas novel agents were used in 92 patients (85.2%). Most patients had immunoparesis at diagnosis (89.1%) and at the moment of ASCT as well (75%). After a median follow-up of 49 months, in the group with immunoglobulin recovery 1 year after ASCT, there was a trend towards longer progression-free survival (PFS) than in the group with immunoparesis (P = 0.054). And overall survival (OS) was significantly longer in patients with immunoparesis recovery (P = 0.004). In multivariate analysis, immunoparesis recovery 1 year after ASCT was independently associated with improved OS (P = 0.016). In conclusion, lack of immunoparesis recovery 1 year after ASCT in MM patients is associated with significantly shorter OS and this group of patients needs new treatment strategy to improve the prognosis.
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1q21 Gain Combined with High-Risk Factors Is a Heterogeneous Prognostic Factor in Newly Diagnosed Multiple Myeloma: A Multicenter Study in China
Li, X., Chen, W., Li, J., Chen, L., Fang, B., Feng, Y., Liu, J., Chen, M., Gu, J., Huang, B., et al
The oncologist. 2019
Abstract
BACKGROUND The prognostic value of 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Our aim was to investigate the prognostic value of 1q21 gain in a Chinese population. MATERIALS AND METHODS We retrospectively identified 565 patients with NDMM from multiple centers in China. RESULTS We detected 1q21 gain in 222 (39.3%) patients, among whom 144 had three copies of 1q21, 57 had four copies of 1q21, and 21 had at least five copies of 1q21. Copy number variation did not show any effect on the disease outcome. Multivariate analysis indicated that 1q21 gain was an independent factor for poor prognosis, but we found that 1q21 gain was strongly associated with other high-risk factors, such as del(17p), t(4;14), t(14;16), lactate dehydrogenase (LDH) level >300 U/L and International Scoring System (ISS) stage II-III (p < .001). Further analysis revealed that in the absence of other high-risk factors, isolated 1q21 gain resulted in similar progression-free survival (PFS; 52.0 vs. 52.8 months, p = .810) and overall survival (OS; not reached vs. not reached, p = .833); additionally, when present with other high-risk cytogenetic abnormalities or increased LDH levels, 1q21 gain lost its prognostic power. However, the presence of 1q21 gain increased the adverse impact of ISS stage. Furthermore, 1q21 gain predicted poor PFS and OS in patients who received bortezomib-based regimens. Moreover, autologous stem cell transplantation reversed the poor prognosis in patients with 1q21 gain. CONCLUSION Our results show that heterogeneity exists among patients with 1q21 gain and suggest that we should assess the impact of 1q21 gain on prognosis according to different treatment regimens and accompanying high-risk factors. IMPLICATIONS FOR PRACTICE 1q21 gain is one of the most common chromosomal aberrations in multiple myeloma (MM); however, the prognostic value of 1q21 gain remains controversial. This study investigated the prognostic value of 1q21 gain in a Chinese population with newly diagnosed MM. The results showed that heterogeneity exists among patients with 1q21 gain and suggested that the impact of 1q21 gain on prognosis should be assessed according to different treatment regimens and accompanying high-risk factors. These results could help stratify risk in patients with MM and guide treatment decisions.
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Recombinant human thrombopoietin improves the efficacy of intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor in mobilizing peripheral blood stem cells in patients with multiple myeloma: A cohort study
Wang, G., Chen, W., Wu, Y., Li, Y., Leng, Y., Liu, A.
Medicine. 2017;96(50):e9302
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Abstract
The combination of intermediate-dose cyclophosphamide (ID-CTX) and granulocyte colony-stimulating factor (G-CSF) fails to mobilize peripheral blood stem cells (PBSCs) in approximately 20% of treated patients with multiple myeloma (MM).In this cohort study, patients with MM underwent PBSC mobilization with either an ID-CTX plus G-CSF plus recombinant human thrombopoietin (rhTPO) regimen (72 patients; TPO group), or an ID-CTX plus G-CSF regimen (70 patients; non-TPO group).In the TPO group, the median CD34+ harvest was 5.36 x 10 per kg of body weight (0.50-22.39 x 10 per kg of body weight), with a harvest success rate of 91.7% (66/72), and an excellence rate of 55.6% (40/72). In the non-TPO group, the median CD34+ harvest was 3.30 x 10 per kg of body weight (0.20-21.14 x 10 per kg of body weight), with a harvest success rate of 75.7% (53/70), and an excellence rate of 25.7% (18/70). The median count of the CD34+ cells collected, success rate of collection, and excellence rate of collection were significantly higher in the TPO group than in the non-TPO group (P=.0001, P=.01, and P = .0001, respectively). Time to granulocyte and platelet engraftment was faster among patients in the TPO group than that in those from the non-TPO group. No platelet engraftment delay (>21 days) was observed among patients in the TPO group, while 3 patients in the non-TPO group displayed delayed platelet engraftment.Adding rhTPO to the ID-CTX chemotherapy plus G-CSF regimen improved treatment efficacy in mobilizing PBSCs for autologous hematopoietic stem cell transplantation.