Abstract Autologous stem cell transplantation (ASCT) is an important treatment for Peripheral T-cell lymphoma (PTCL) patients both during front and salvage therapy. We retrospectively compared the outcomes of 52 PTCL patients treated with CEAC (n=28), BEAM (n=14) and IEAC (n=10) regimens followed by ASCT at our center between 2012 and 2021. Although the time of neutrophil engraftment in CEAC group was earlier than that in IEAC group ( P =0.042) and platelet infusion in BEAM group was significantly more than CEAC group ( P =0.042), there were no significant difference in platelet engraftment, hematopoietic engraftment and red blood cells infusion among the 3 groups. The transplantation related mortality rate (TRM) and the early overall response rate (ORR) was 3.8% and 85.7% respectively. The 5-year OS and PFS was 62.8% (95% CI: 54.8%-70.8%) and 61.0% (95% CI: 53.1%-68.9%) respectively. There was no significant difference in TRM, ORR and survival among the 3 groups. Univariate and multivariate analysis showed that high PIT score (＞1) and non-CR at 3 months after ASCT were common risk factors for OS ( P =0.036 and 0.007) and PFS ( P =0.021 and 0.012). In conclusion, CEAC and IEAC regimen can be used as alternative conditioning regiments for ASCT in PTCL patients, and their efficacy and safety are comparable to BEAM regiment. Patients with high PIT score and failure to reach CR early after ASCT had worse outcomes.
Abstract Autologous stem cell transplantation (ASCT) is an important treatment for peripheral T-cell lymphoma (PTCL) patients both during front and salvage therapy. In order to explore the appropriate conditioning regiments and seek ways to improve the efficacy and safety of PTCL, we retrospectively compared the outcomes of 52 PTCL patients treated with CEAC (lomustine, etoposide, cytarabine and cyclophosphamide; n = 28), BEAM (carmustine, etoposide, cytarabine and melphalan; n = 14) and IEAC (idarubicin, etoposide, cytarabine and cyclophosphamide; n = 10) regimens followed by ASCT at our center between 2012 and 2021. Although the time of neutrophil engraftment in CEAC group was earlier than that in IEAC group ( P = 0.042) and platelet infusion in BEAM group was significantly more than CEAC group ( P = 0.042), there were no significant difference in platelet engraftment, hematopoietic engraftment and red blood cells infusion among the 3 groups. The transplantation related mortality rate (TRM) and the early overall response rate (ORR) was 3.8% and 85.7% respectively. The 5-year OS and PFS was 62.8% (95% CI: 54.8–70.8%) and 61.0% (95% CI: 53.1–68.9%) respectively. There was no significant difference in TRM, ORR and survival among the 3 groups. Univariate and multivariate analysis showed that high PIT score (the T cell lymphoma prognostic index, > 1) and failure to reach complete response (non-CR) at 3 months after ASCT were common risk factors for OS ( P = 0.036 and 0.007) and PFS ( P = 0.021 and 0.012). In conclusion, CEAC and IEAC regimen can be used as alternative conditioning regiments for ASCT in PTCL patients, and their efficacy and safety are comparable to BEAM regiment. Patients with high PIT score and non-CR early after ASCT had worse outcomes.
Extranodal NK/T-cell lymphoma (ENKL) is aggressive and resistant to chemotherapy and radiotherapy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for high-risk lymphomas owing to its associated graft-versus-lymphoma (GVL) effect. However, its application to ENKL is limited. We aim to summarize the characteristics of allo-HSCT for ENKL and, more importantly, evaluate whether allo-HSCT could offer any benefits for ENKL.A systematic review and data analysis were performed to evaluate the performance of allo-HSCT in the treatment of ENKL using studies obtained from PubMed, Medline, and Embase from January 2000 to December 2019 in the English language.A total of 136 cases from 17 eligible publications were included in this study. It was found that after allo-HSCT, with an average follow-up time of 34 months (range: 1-121 months), 37.5% (52) of 136 patients had acute graft-versus-host disease (GVHD) and 31.6% (43) had chronic GVHD. Furthermore, 35.3% (48) of the patients were reported to have relapsed, but 2 of those relapsed only locally and achieved complete remission (CR) again with additional irradiation, chemotherapy, and donor lymphocyte infusions for one and rapid tapering and discontinuation of cyclosporine for the other, earning more than one year of extra survival. Finally, of the 136 patients, 51.5% (70) died because of primary disease progression (42.9%), infection (20.0%), GVHD (11.4%), organ failure (7.1%), hemorrhage (4.3%), and other causes (not specified/unknown) (14.3%).Allo-HSCT may be a treatment option for advanced or relapsed/refractory ENKL, but its role still requires more rigorous future studies.Ekstranodal NK/T-hücreli lenfoma (ENKL) agresiftir ve kemoterapi ve radyoterapiye dirençlidir. Allojenik hematopoetik kök hücre transplantasyonu (allo-HSCT), ilişkili graft-lenfoma (GVL) etkisi nedeniyle, yüksek riskli lenfomalara yönelik potansiyel olarak iyileştirici bir tedavidir. Bununla birlikte, ENKL’ye uygulanması sınırlıdır. Bu çalışmada ENKL için allo-HSCT’nin/AHKHN’nin özelliklerini özetlemeyi ve daha da önemlisi allo-HSCT’nin ENK için herhangi bir fayda sağlayıp sağlamayacağını değerlendirmeyi amaçlıyoruz.Ocak 2000’den Aralık 2019’a kadar İngilizce dilinde PubMed, Medline ve Embase literatürleri kullanılarak allo-HSCT’nin ENKL’ye performansını değerlendirmek için sistematik bir inceleme ve veri analizi gerçekleştirildi.Bu çalışmaya 17 uygun yayından toplam 136 olgu dahil edildi. 1) allo-HSCT’den sonra, 34 aylık ortalama takip süresine göre (aralık: 1-121 ay), 136 hastanın %37,5’inde (52) akut graft-versus-host hastalığı (GVHD), %31,6’sında (43) kronik GVHD vardı; 2) rapor edildiğinde, hastaların %35,3’ünde (48) relaps vardı, ancak bunlardan ikisi sadece lokal olarak nüks etti ve bunlardan birine ek ışınlama, kemoterapi, donör lenfosit infüzyonu ile tekrar tam remisyon (CR) sağladı, diğerine siklosporinin hızlı azaltılması ve kesilmesi bir yıldan fazla ekstra sağkalım kazandırdı; 3) 136 hastanın %51,5’i (70) primer hastalık ilerlemesi (%42,9), enfeksiyon (%20,0), GVHD (%11,4), organ yetmezliği (%7,1), kanama (%4,3) ve diğerleri (belirtilmedi/bilinmiyor) (%14,3) nedeniyle öldü.Allo-HSCT, ilerlemiş veya nükseden/refrakter ENKL için bir tedavi seçeneği olabilir, ancak rolü hala daha titiz gelecek çalışmaları gerektirmektedir.
Measurable residual disease (MRD) is widely used as a therapy-stratification factor for acute myeloid leukemia (AML), but the association of dynamic MRD with postremission treatment (PRT) in patients with intermediate-risk AML (IR-AML) has not been well investigated.
Objective
To investigate PRT choices based on dynamic MRD in patients with IR-AML.
Design, Setting, and Participants
This cohort study examined 549 younger patients with de novo IR-AML in the South China Hematology Alliance database during the period from January 1, 2012, to June 30, 2016, including 154 who received chemotherapy, 116 who received an autologous stem cell transplant (auto-SCT), and 279 who received an allogeneic SCT (allo-SCT). Subgroup analyses were performed according to dynamic MRD after the first, second, and third courses of chemotherapy. The end point of the last follow-up was August 31, 2020. Statistical analysis was performed from December 1, 2019, to September 30, 2020.
Exposures
Receipt of chemotherapy, auto-SCT, or allo-SCT.
Main Outcomes and Measures
The primary end points were 5-year cumulative incidence of relapse and leukemia-free survival.
Results
Subgroup analyses were performed for 549 participants (314 male participants [57.2%]; median age, 37 years [range, 14-60 years]) according to the dynamics of MRD after 1, 2, or 3 courses of chemotherapy. Comparable cumulative incidences of relapse, leukemia-free survival, and overall survival were observed among participants who had no MRD after 1, 2, or 3 courses of chemotherapy. Participants who underwent chemotherapy and those who underwent auto-SCT had better graft-vs-host disease–free, relapse-free survival (GRFS) than those who underwent allo-SCT (chemotherapy: hazard ratio [HR], 0.35 [95% CI, 0.14-0.90];P = .03; auto-SCT: HR, 0.07 [95% CI, 0.01-0.58];P = .01). Among participants with MRD after 1 course of chemotherapy but no MRD after 2 or 3 courses, those who underwent auto-SCT and allo-SCT showed lower cumulative incidence of relapse (auto-SCT: HR, 0.25 [95% CI, 0.08-0.78];P = .01; allo-SCT: HR, 0.08 [95% CI, 0.02-0.24];P < .001), better leukemia-free survival (auto-SCT: HR, 0.26 [95% CI, 0.10-0.64];P = .004; allo-SCT: HR, 0.21 [95% CI, 0.09-0.46];P < .001), and overall survival (auto-SCT: HR, 0.22 [95% CI, 0.08-0.64];P = .005; allo-SCT: HR, 0.25 [95% CI, 0.11-0.59];P = .001) vs chemotherapy. In addition, auto-SCT showed better GRFS than allo-SCT (HR, 0.45 [95% CI, 0.21-0.98];P = .04) in this group. Among participants with MRD after 1 or 2 courses of chemotherapy but no MRD after 3 courses, allo-SCT had superior cumulative incidence of relapse (HR, 0.10 [95% CI, 0.06-0.94];P = .04) and leukemia-free survival (HR, 0.18 [95% CI, 0.05-0.68];P = .01) compared with chemotherapy, but no advantageous cumulative incidence of relapse (HR, 0.15 [95% CI, 0.02-1.42];P = .10) and leukemia-free survival (HR, 0.23 [95% CI, 0.05-1.08];P = .06) compared with auto-SCT. Among participants with MRD after 3 courses of chemotherapy, allo-SCT had superior cumulative incidences of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.16 [95% CI, 0.08-0.33];P < .001; leukemia-free survival: HR, 0.19 [95% CI, 0.10-0.35];P < .001; overall survival: HR, 0.29 [95% CI, 0.15-0.55];P < .001) and auto-SCT (relapse: HR, 0.25 [95% CI, 0.12-0.53];P < .001; leukemia-free survival: HR, 0.35 [95% CI, 0.18-0.73];P = .004; overall survival: HR, 0.54 [95% CI, 0.26-0.94];P = .04). Among participants with recurrent MRD, allo-SCT was also associated with advantageous cumulative incidence of relapse, leukemia-free survival, and overall survival compared with chemotherapy (relapse: HR, 0.12 [95% CI, 0.04-0.33];P < .001; leukemia-free survival: HR, 0.24 [95% CI, 0.10-0.56];P = .001; overall survival: HR, 0.31 [95% CI, 0.13-0.75];P = .01) and auto-SCT (relapse: HR, 0.28 [95% CI, 0.09-0.81];P = .02; leukemia-free survival: HR, 0.30 [95% CI, 0.12-0.76];P = .01; overall survival: HR, 0.26 [95% CI, 0.10-0.70];P = .007).
Conclusions and Relevance
This study suggests that clinical decisions based on dynamic MRD might be associated with improved therapy stratification and optimized PRT for patients with IR-AML. Prospective multicenter trials are needed to further validate these findings.
BackgroundTo investigate the regulation mechanism of hematopoiesis of Siwu paste (SWP) in anemia rats, which is a classic Chinese prescription used for nourishing blood or blood deficiency over 1000 years.MethodsBlood cell and biochemical analysis were used to evaluate the hematopoietic function of SWP in anemia rats. The intestinal microbial composition was analyzed with 16S rRNA gene sequencing, and the metabolites were profiled using UPLC-TripleTOF system nontargeting metabolomics.ResultsSWP can improve the levels of red blood cells, hemoglobin, platelet, hematocrit value, white blood cells, lymphocyte, EPO, TPO, and GM-CSF in anemia rats, and significantly change the microbial community and its metabolites. The correlation analysis of intestinal microbiota-hematopoietic efficacy shows that 13 kinds of different intestinal flora were related to hematopoietic efficacy, in which Prevotella_1, Prevotella_9, Lactobacillus, and norank_f__Muribaculaceae were significantly positively correlated with hematopoiesis, nine kinds of intestinal flora are negatively correlated with hematopoietic effect. Compared with anemia rats, 218 potential metabolic biomarkers and 36 metabolites with significant differences were identified in the SWP treatment group, and the key metabolites were mainly amino acids and lipids. An in-depth analysis of metabolic pathways showed that SWP mainly affected 7 metabolic pathways, including aminobenzoic acid degradation and tryptophan metabolism.ConclusionThe study provides novel insights into the regulation of hematopoiesis of SWP in anemia rats that were correlated with gut microbiota and the metabolites, which through the restoration of the firmicutes/bacteroidetes ratio.
Purpose: To investigate the clinical characteristics, etiology, and risk factors of bacterial bloodstream infection (BSI) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients.This study also aimed to provide a clinical basis for early identification of high-risk patients and optimization of empirical antimicrobial treatment.Patients and Methods: This is a retrospective study of clinical data during agranulocytosis from 331 patients with hematological malignancies who underwent allo-HSCT at our institute between January 2016 and December 2022.The incidence, distribution and drug resistance patterns, and the risk factors of BSI were analyzed.Results: Among the 331 HSCT patients, 250 had febrile neutropenia and 45 cases were found to have BSI.The incidence of BSI in patients with agranulocytosis fever was 18% (45/250).A total of 48 pathogens were isolated during BSI episodes, gram-negative bacteria (GNB) accounted for 70.8% (34/48), gram-positive bacteria (GPB) for 29.2% (14/48).Multivariate analysis revealed that ≥grade 2 acute graft-versus-host disease (aGVHD) and previous BSI within 6 months before HSCT were independently associated with an increased occurrence of BSI.Coagulase-negative staphylococci (CoNS) and Escherichia coli were the most commonly isolated GPB and GNB, respectively.A total of 32 GNB were tested for drug susceptibility, the detection rate of carbapenem-resistant Enterobacteriaceae (CRE) was 12.5% (4/32), and extended-spectrum β-lactamase (ESBL) accounted for 56.3% (18/32).Conclusion: BSIs are still a common and severe complication after allo-HSCT.In our center, BSIs in allo-HSCT patients are dominated by gram-negative bacteria and the resistance rate to carbapenem drugs is high.Risk factors for BSI during agranulocytosis were previous BSI within 6 months before HSCT and ≥grade 2 aGVHD.
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