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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.
Busulfan for allogeneic hematopoietic stem cell transplantation in children with severe aplastic anemia: A retrospective study
Si, Y., Luo, R., Qin, M., Du, Z., Zhang, X., Wang, Y., Chen, W., Gu, W., Xing, G., Dou, L., et al
Acta haematologica. 2023
Abstract
Introduction This retrospective study aimed to compare a range of conditioning regimens in children with severe aplastic anemia (SAA) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the Seventh Medical Center of PLA General Hospital between January 2008 and June 2017. Methods Patients were categorized into the Bu (Bu + Flu + Cy + ATG-F regimen) and control (Flu + Cy + ATG-F) groups, with a median follow-up time after HSCT of 3.5 (range, 3.1-6.2) and 3.7 (3.2-5.9) years in the Bu and control groups, respectively. Results No differences were observed between the two groups regarding the median time of peripheral blood neutrophil and platelet engraftment (P = 0.538 and P = 0.491); the 28-day engraftment rates of neutrophils were similar (P = 0.199) although higher for platelets with Bu (P = 0.044). Additionally, graft failure was 0% and 20.0% in the Bu and control groups, respectively (P = 0.004). In both groups, the incidence of grades ⅡI-Ⅳ (or grades Ⅱ-Ⅳ) acute graft-versus-host disease (GVHD) and chronic GVHD was not significantly different (P > 0.05). Moreover, the 3-year overall survival and failure-free survival did not show significant differences (P = 0.670 and P = 0.908). Discussion In children with SAA undergoing allo-HSCT, conditioning regimen with Bu + Flu + Cy + ATG-F is capable of enhancing the myeloablation effect, promoting donor hematopoietic stem cell engraftment, and reducing the graft failure rate. Furthermore, it does not increase the incidence of complications, including GVHD.
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3.
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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4.
Risk factors, treatments and outcomes of patients with light chain amyloidosis who relapse after autologous stem cell transplantation
Zhang, Y., Guo, J., Chen, W., Zhao, L., Huang, X.
Bone marrow transplantation. 2023
Abstract
Relapse after ASCT is an important factor affecting the long-term prognosis of patients with AL amyloidosis. However, the risk factors of relapse are unknown and there are limited studies on treatment outcomes of these patients. We retrospectively reviewed 170 patients with AL amyloidosis who underwent ASCT between 2010 and 2021. Seventy-six patients confirmed as relapse and the median time from ASCT to relapse was 39 months. On multivariate analysis of variables before and after ASCT, lambda restricted, dFLC >30 mg/L pre ASCT, reduced dose melphalan and dFLC >10 mg/L at 6 months after ASCT were independent risk factors for relapse, and achieving CR after induction therapy and renal response after ASCT were protective factors. Most relapsed patients were treated with bortezomib-based regimens (50%) followed by daratumumab-based regimens (22.2%) and other chemotherapy regimens (13.9%). The overall hematological response in evaluable patients was 68.2% with 56.8% achieving CR/VGPR. The median PFS and OS from post-transplant relapse were 25 months and 81 months, respectively. Patients receiving bortezomib or daratumumab showed a better survival compared to other chemotherapy regimens. In conclusion, this study identified independent risk factors of post-transplant relapse and demonstrated the superiority of bortezomib or daratumumab treatment for these patients. CLINICAL TRIAL REGISTRATION NCT04210791.
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5.
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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6.
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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7.
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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8.
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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9.
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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10.
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).