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1.
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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2.
Diagnostic efficiency of metagenomic next-generation sequencing for suspected infection in allogeneic hematopoietic stem cell transplantation recipients
Huang, J., Zhao, Y., Jiang, C., Han, D., Pan, Z., Zhang, Z., Wang, L., Chen, W., Li, S., Zhao, Y., et al
Frontiers in cellular and infection microbiology. 2023;13:1251509
Abstract
INTRODUCTION Immunosuppression predisposes allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients to infection. Prompt and accurate identification of pathogens is crucial to optimize treatment strategies. This multi-center retrospective study aimed to assess the ability of metagenomic next-generation sequencing (mNGS) to detect causative pathogens in febrile allo-HSCT recipients and examined its concordance with conventional microbiological tests (CMT). METHODS We performed mNGS and CMT on samples obtained from 153 patients with suspected infection during allo-HSCT. Patients were grouped based on their neutropenic status at the time of sampling. RESULTS The mNGS test was more sensitive than CMT (81.1% vs. 53.6%, P<0.001) for diagnosing clinically suspected infection, especially in the non-neutropenia cohort. mNGS could detect fungi and viruses better than bacteria, with a higher sensitivity than CMT. Immune events were diagnosed in 57.4% (35/61) of the febrile events with negative mNGS results, and 33.5% (48/143) with negative CMT results (P=0.002). The treatment success rate of the targeted anti-infection strategy was significantly higher when based on mNGS than on empirical antibiotics (85% vs. 56.5%, P=0.004). CONCLUSION The mNGS test is superior to CMT for identifying clinically relevant pathogens, and provides valuable information for anti-infection strategies in allo-HSCT recipients. Additionally, attention should be paid to immune events in patients with negative mNGS results.
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3.
Clinical Characteristics, Microbiology, and Risk Factors for Mortality of Pre-Engraftment and Post-Engraftment Bloodstream Infection in Hematopoietic Stem Cell Transplantation Recipients
Chen, W., Zhao, Y., Luo, Y., Yu, J., Fu, H., Lai, X., Liu, L., Ye, Y., He, J., Sun, J., et al
Infection and drug resistance. 2022;15:6893-6905
Abstract
BACKGROUND Bloodstream infection (BSI) is a common and serious complication that may lead to high mortality during the different phases after hematopoietic stem cell transplant (HSCT). We investigated BSI in patients undergoing HSCT to provide an appropriate clinical anti-infection experience and improve the prognosis of recipients with BSI after HSCT. METHODS A total of 105 patients with BSI after HSCT at our center from January 2015 to June 2020 were included in this retrospective study. We analyzed the clinical and microbiological data, and the risk factors for mortality at 3 months after BSI. RESULTS Of the 1141 HSCT recipients, 105 (9.2%) patients presented with 122 episodes of BSI, of which we isolated 85 (65.9%) gram-negative bacteria, 32 (24.8%) gram-positive bacteria and 12 (9.3%) fungi. Multidrug-resistant bacteria (MDR) were more than 70% of all pathogens and carbapenem-resistant organisms (CRO) were 25.6%. There were 55 episodes of BSI in the pre-engraftment phase and 67 episodes in the post-engraftment phase. The mortality of post-engraftment BSI was significantly higher than that of pre-engraftment (56.7% vs 32.7%, p = 0.005). Through multivariate analysis, the independent risk factors for all-cause mortality at 3 months after BSI were higher levels of procalcitonin (PCT), failure to cover appropriate antibiotics timely, and CRO BSI in pre-engraftment period or multidrug-resistant gram-negative bacteria (MDRGNB) BSI in post-engraftment period. CONCLUSION Although the incidence of BSI was lower after HSCT, MDR-dominated BSI had a high mortality rate. Rapid identification of infection or pathogens' classification with various testing methods and the more sensible and timely antibiotic cover are critical to the outcome of BSI after HSCT.
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4.
Changes in the medical-seeking pattern and daily behavior of hematopoietic stem-cell transplant recipients during the COVID-19 epidemic: An online survey in Hubei Province, China
Xie, R., Zhang, Y., Huang, Z., Cheng, S., Guo, J., Zhang, Y., Liu, M., Zhu, X., You, Y., Zou, P., et al
Frontiers in public health. 2022;10:918081
Abstract
BACKGROUND To curb the spread of the coronavirus disease 2019 (COVID-19) epidemic, the Chinese government shut down Wuhan city from January 23rd to April 8th, 2020. The COVID-19 epidemic not only leads to widespread illness but also affects the diagnosis and treatment of hematopoietic stem-cell transplant (HSCT) recipients. OBJECTIVE To investigate the medical-seeking pattern and daily behavior changes in Hubei Province during the COVID-19 epidemic in Hubei Province during the lockdown. METHODS We conducted a multicenter, cross-sectional, web-based investigation among 325 HSCT recipients by online questionnaires in Hubei Province during the COVID-19 epidemic. RESULTS A total of 145 complete responses were collected both before and during the epidemic questionnaires. The participants from pre-epidemic group preferred to go to hospital (68.29%) when they experienced influenza-like symptoms. The majority of the patients elected to take oral drugs by themselves (40%) or consulted their attending physicians online or by telephone during the lockdown (23.33%). 64.83% had difficulties in purchasing drugs during the lockdown, which was significantly higher than the proportion of the pre-epidemic group (24.83%) (P < 0.05). The participants preferred to purchase drugs online (23.40%) and decrease or withdraw drugs (18.09%) during the epidemic. The number of participants received regular re-examinations during the epidemic decreased sharply. The proportion of wearing masks and isolating themselves at home increased significantly during the epidemic. No statistic difference was observed in the incidence of graft-versus-host disease (GVHD)complications in participants between the during the epidemic group and the pre-epidemic group. In our study, six patients were confirmed to have COVID-19, and half of them died due to COVID-19-related complications. CONCLUSION The medical-seeking pattern and daily behavior of HSCT recipients changed during the lockdown; the methods of self-protection, online consultation and drug delivery can help patients receive necessary follow-up and reduce the occurrence of COVID-19.
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5.
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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6.
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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7.
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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8.
The Clinical Efficacy and Safety of Stem Cell Therapy for Diabetes Mellitus: A Systematic Review and Meta-Analysis
Zhang, Y., Chen, W., Feng, B., Cao, H.
Aging and disease. 2020;11(1):141-153
Abstract
Diabetes mellitus (DM) is a chronic metabolic disease with high morbidity and mortality. Recently, stem cell-based therapy for DM has shown considerable promise. Here, we undertook a systematic review and meta-analysis of published clinical studies to evaluate the efficacy and safety of stem cell therapy for both type 1 DM (T1DM) and type 2 DM (T2DM). The PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and ClinicalTrials.gov databases were searched up to November 2018. We employed a fixed-effect model using 95% confidence intervals (CIs) when no statistically significant heterogeneity existed. Otherwise, a random-effects statistical model was used. Twenty-one studies met our inclusion criteria: ten T1DM studies including 226 patients and eleven T2DM studies including 386 patients. Stem cell therapy improved C-peptide levels (mean difference (MD), 0.41; 95% CI, 0.06 to 0.76) and glycosylated hemoglobin (HbA1c; MD, -3.46; 95% CI, -6.01 to -0.91) for T1DM patients. For T2DM patients, stem cell therapy improved C-peptide levels (MD, 0.33; 95% CI, 0.07 to 0.59), HbA1c (MD, -0.87; 95% CI, -1.37 to -0.37) and insulin requirements (MD, -35.76; 95% CI, -40.47 to -31.04). However, there was no significant change in fasting plasma glucose levels (MD, -0.52; 95% CI, -1.38 to 0.34). Subgroup analyses showed significant HbA1c and C-peptide improvements in patients with T1DM treated with bone marrow hematopoietic stem cells (BM-HSCs), while there was no significant change in the mesenchymal stem cell (MSC) group. In T2DM, HbA1c and insulin requirements decreased significantly after MSC transplantation, and insulin requirements and C-peptide levels were significantly improved after bone marrow mononuclear cell (BM-MNC) treatment. Stem cell therapy is a relatively safe and effective method for selected individuals with DM. The data showed that BM-HSCs are superior to MSCs in the treatment of T1DM. In T2DM, MSC and BM-MNC transplantation showed favorable therapeutic effects.
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9.
Liver GVHD is Associated with Poor Survival Among Allogeneic Hematopoietic Stem Cell Transplant Recipients
Modi, D., Christine Ye, J., Surapaneni, M., Singh, V., Chen, W., Jang, H., Deol, A., Ayash, L., Alavi, A., Ratanatharathorn, V., et al
American journal of hematology. 2019
Abstract
Liver GVHD is common in patients with post-transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred. Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post-transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and "non-liver GVHD" group which consisted of other etiologies of post-transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post-transplant liver dysfunction following AHSCT 124 patients developed liver GVHD and 125 were in "non-liver GVHD" group. The incidence of acute and chronic liver GVHD at 1-year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (HR, 1.76; P=0.008) and related donor (HR, 1.68; P=0.004) as independent risk factors for liver GVHD. The time varying covariate cox regression analysis with competing risk event demonstrated that liver GVHD was independently associated with higher non-relapse mortality, and adverse relapse-free and overall survival. Total 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting. This article is protected by copyright. All rights reserved.
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10.
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.