Outcomes of the transformation of follicular lymphoma to diffuse large B-cell lymphoma in the rituximab era: A population-based study.

BACKGROUND: Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a common complication of follicular lymphoma (FL) and is usually associated with a dismal outcome. However, the survival rate of these patients has improved over the last 20 years with the introduction of rituximab. This study aimed to access the outcome of transformation to DLBCL (t-DLBCL) from FL in a retrospective series that began after the widespread use of rituximab use. In addition, we also compared survival between t-DLBCL and primary DLBCL (p-DLBCL) in the same timeframe. METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with primary FL and patients with p-DLBCL between 2000 and 2020. Patients who had a subsequent diagnosis of DLBCL at least 2 months after FL diagnosis were identified as t-DLBCL. RESULTS: Finally, we identified 50,332 FL and 95,933 p-DLBCL. With a median follow-up of 119 months, 1631 patients developed t-DLBCL. The median time from FL diagnosis to t-DLBCL was approximately 4 years. The post-transformation survival (PTS) rate at 5 years was 49.6%, with a median PTS of 56 months. Older age, advanced stage, and early transformation were associated with worse PTS. Furthermore, t-DLBCL receiving chemotherapy or combined modality as initial therapy before HT was also associated with worse PTS, while the result was inverse when taking the impact of initial management strategy at HT into account. Taking t-DLBCL and p-DLBCL as a whole, comparable survival was observed between p-DLBCL and t-DLBCL receiving radiation or watch-and-wait as initial therapy prior to HT. CONCLUSION: The outcome of t-DLBCL in the rituximab era was better than historical series before the rituximab era. Due to the good prognosis, we did not recommend autologous stem cell transplantation for t-DLBCL receiving watch-and-wait or radiation as initial therapy before HT.

A synergistic impact of body mass index and gamma gap on heart failure and mortality rate among older patients with coronary artery disease: a prospective study with 10-year follow-up.

PURPOSE: This prospective study with 10-year follow-up aimed to analyze potential impact of body mass index (BMI) and gamma gap on heart failure and mortality rate in older patients with coronary artery disease (CAD). METHODS: There were 987 consecutive older patients with CAD included and divided into four groups according to BMI and gamma gap levels. RESULTS: Median age was 86 years. The highest proportion of heart failure (46.2%) and the highest mortality rate (84.4%) was observed in patients with low BMI and high gamma gap, whereas the lowest proportion of heart failure (18.9%) and the lowest mortality rate (62.9%) was observed in those with high BMI and low gamma gap. After full adjustment in multivariate Logistic regression analysis, heart failure was most common in patients with low BMI and high gamma gap compared with those with high BMI and low gamma gap (hazard ratio [HR]: 2.82, 95% confidence interval [CI]: 1.79-4.48, P < 0.05). Meanwhile, multivariate Cox regression analysis showed that mortality rate was the highest in those with low BMI and high gamma gap compared with patients with high BMI and low gamma gap (HR: 1.65, 95% CI: 1.32-2.07, P < 0.05). CONCLUSION: The combination of low BMI and high gamma gap could further promote heart failure and increase mortality rate in older patients with CAD. Future studies should explore the underlying mechanisms linking low BMI, high gamma gap, and mortality rate, as well as the potential benefits of nutritional and immunological interventions to improve health prognosis in older patients with CAD.

Machine learning-based models to predict one-year mortality among Chinese older patients with coronary artery disease combined with impaired glucose tolerance or diabetes mellitus.

PURPOSE: An accurate prediction of survival prognosis is beneficial to guide clinical decision-making. This prospective study aimed to develop a model to predict one-year mortality among older patients with coronary artery disease (CAD) combined with impaired glucose tolerance (IGT) or diabetes mellitus (DM) using machine learning techniques. METHODS: A total of 451 patients with CAD combined with IGT and DM were finally enrolled, and those patients randomly split 70:30 into training cohort (n = 308) and validation cohort (n = 143). RESULTS: The one-year mortality was 26.83%. The least absolute shrinkage and selection operator (LASSO) method and ten-fold cross-validation identified that seven characteristics were significantly associated with one-year mortality with creatine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and chronic heart failure being risk factors and hemoglobin, high density lipoprotein cholesterol, albumin, and statins being protective factors. The gradient boosting machine model outperformed other models in terms of Brier score (0.114) and area under the curve (0.836). The gradient boosting machine model also showed favorable calibration and clinical usefulness based on calibration curve and clinical decision curve. The Shapley Additive exPlanations (SHAP) found that the top three features associated with one-year mortality were NT-proBNP, albumin, and statins. The web-based application could be available at https://starxueshu-online-application1-year-mortality-main-49cye8.streamlitapp.com/ . CONCLUSIONS: This study proposes an accurate model to stratify patients with a high risk of one-year mortality. The gradient boosting machine model demonstrates promising prediction performance. Some interventions to affect NT-proBNP and albumin levels, and statins, are beneficial to improve survival outcome among patients with CAD combined with IGT or DM.

WGCNA and molecular docking identify hub genes for cardiac aging.

Background: Cardiac aging and ageing-related cardiovascular diseases remain increase medical and social burden. Discovering the molecular mechanisms associated with cardiac aging is expected to provide new perspectives for delaying aging and related disease treatment. Methods: The samples in GEO database were divided into older group and younger group based on age. Age-associated differentially expressed genes (DEGs) were identified by limma package. Gene modules significantly associated with age were mined using weighted gene co-expression network analysis (WGCNA). Protein-protein interaction networks (PPI) networks were developed using genes within modules, and topological analysis on the networks was performed to identify hub genes in cardiac aging. Pearson correlation was used to analyze the association among hub genes and immune and immune-related pathways. Molecular docking of hub genes and the anti-aging drug Sirolimus was performed to explore the potential role of hub genes in treating cardiac aging. Results: We found a generally negative correlation between age and immunity, with a significant negative correlation between age and b_cell_receptor_signaling_pathway, fc_gamma_r_mediated_phagocytosis, chemokine signaling pathway, t-cell receptor signaling pathway, toll_like_receptor_signaling_pathway, and jak_stat_signaling_pathway, respectively. Finally, 10 cardiac aging-related hub genes including LCP2, PTPRC, RAC2, CD48, CD68, CCR2, CCL2, IL10, CCL5 and IGF1 were identified. 10-hub genes were closely associated with age and immune-related pathways. There was a strong binding interaction between Sirolimus-CCR2. CCR2 may be a key target for Sirolimus in the treatment of cardiac aging. Conclusion: The 10 hub genes may be potential therapeutic targets for cardiac aging, and our study provided new ideas for the treatment of cardiac aging.

Incidence and risk factors for febrile neutropenia of patients with diffuse large B-cell lymphoma receiving R-CHOP-21 in China.

OBJECTIVE: Febrile neutropenia (FN) is a serious complication of patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP-21. The prophylactic use of granulocyte colony-stimulating factors (G-CSFs) can significantly reduce the risk of FN. International guidelines recommend G-CSFs for patients receiving chemotherapy with FN risk of 20% or 10 to 20% with defined risk factors. However, there are few studies on the incidence and risk factors of FN in patients with DLBCL receiving R-CHOP-21, especially in patients without primary G-CSF prophylaxis. METHODS: We conducted a retrospective analysis for the clinical data of 103 patients with DLBCL who underwent first R-CHOP-21 without primary G-CSF prophylaxis. The objective of the assessment was the incidence and risk factors of FN after the first chemotherapy cycle. RESULTS: After the first chemotherapy cycle, the incidence of FN was 20.4%. Multivariate analysis showed that age ≥ 65 years, bone marrow involvement, albumin < 35 g/L, and average relative dose intensity ≥ 80% were independent risk factors for FN. According to risk factors, we created a risk score system. The incidence of FN in the low-, intermediate- and high-risk groups was 5.6%, 17.2%, and 61.9%, respectively. CONCLUSION: Our data indicated that R-CHOP-21 itself is associated with a high-risk regiment for FN. We recommend that intermediate/high-risk patients should actively consider primary G-CSF prophylaxis to reduce the incidence of FN after chemotherapy.

Case report: First report of haploidentical allogeneic hematopoietic stem cell transplantation from donors with mild alpha-thalassemia for acute leukemia.

For acute leukemia (AL) with adverse prognostic factors, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the standard care option after the first complete remission. Meanwhile, as the success of haploidentical HSCT (haplo-HSCT), haploidentical donors (HIDs) become a reliable choice. However, there have been no reports on haplo-HSCT from HIDs with mild alpha(α)-thalassemia for AL yet. In the present report, we first describe two cases of successful haplo-HSCT from HIDs with mild α-thalassemia for AL.

Using extracellular vesicles derived from human umbilical cord mesenchymal stem cells for a topical coating promotes oral mucositis healing in rats.

Background: Oral mucositis (OM) affects the quality of life and therapeutic outcomes of cancer patients. More effective drugs and methods for treating OM are urgently required for clinical application. Extracellular vesicles can play important roles in cutaneous wound healing. However, their role in OM remains unclear. Our aim was to investigate the function and mechanisms of topical coatings of extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUC-MSC-EVs) in OM. Methods: HUC-MSC-EVs were isolated by differential ultracentrifugation. We used glacial acetic acid to induce the formation of OM in rats. HUC-MSC-EVs were covered on the OM topically once a day. Rats' body weights were measured on alternative days. The healing degree of OM was evaluated with macroscopic observations and histological examinations. We also analyzed the mechanisms of hUC-MSC-EVs when promoting the healing of OM. The expression levels of NF-κB, IL-6, TNF-α, and IL-1ß in mucosal tissue were evaluated using immunohistochemistry. Results: The median healing time of OM in the blank control, rhaFGF, 0.25 µg/µL EVs, 0.75 µg/µL EVs, and 1.50 µg/µL EVs groups was 14, 11, 10, 7, and 11 days, respectively. The most significant effect of hUC-MSC-EVs in promoting healing was at the concentration of 0.75 µg/µL. The median healing scores in the 0.75 µg/µL EVs group were 4 on day 5 and 3 on day 8 (*P<0.05 vs. the blank control group). After modeling, the body weight of rats started to recover from day 8 in the blank control group and day 4 in the 0.75 µg/µL EVs group. The 0.75 µg/µL EVs group showed lower immunostaining intensity of NF-κB, IL-6, and TNF-α on day 5 and 8 (*P<0.05 vs. the blank control group). However, there was no significant difference between the blank control group and the 0.75 µg/µL EVs group in IL-1ß. Conclusions: Our results showed for the first time that coating hUC-MSC-EVs topically can promote healing of OM because it may inhibit the activation of the NF-κB signaling pathway.

[Clinical Characteristics and Risk Factors of Invasive Fungal Infections in Acute Leukemia Patients in Tropical Regions].

OBJECTIVE: To analyze the clinical characteristics and risk factors of invasive fungal infection (IFI) occurenced in patients with acute leukemia (AL) during treatment in tropical regions. METHODS: The clinical data of 68 AL patients admitted to the Hainan Hospital of PLA General Hospital from April 2012 to April 2019 was retrospectively analyzed. Logistic regression analysis was used to analyze the factors affecting the occurrence of IFI in AL patients. RESULTS: Among the 68 patients, 44 were acute myeloid leukemia, 24 were acute lymphoblastic leukemia, 39 were male, 29 were female and the median age was 41(13-75) years old. The 68 patients received 242 times of chemotherapy or hematopoietic stem cell transplantation(HSCT), including 73 times of initial chemotherapy or inducting chemotherapy after recurrence, 14 times of HSCT, 155 times of consolidating chemotherapy. Patients received 152 times of anti-fungal prophylaxis, including 77 times of primary anti-fungal prophylaxis and 75 times of secondary anti-fungal prophylaxis. Finally, the incidence of IFI was 31 times, including 24 times of probable diagnosis, 7 times of proven diagnosis, and the total incidence of IFI was 12.8%(31/242), the incidence of IFI in inducting chemotherapy was 24.66%(18/73), the incidence of IFI in HSCT patients was 28.57% (4/14), the incidence of IFI in consolidating chemotherapy was 5.80% (9/155). Multivariate analysis showed that inducting chemotherapy or HSCT, the time of agranulocytosis ≥7 days, risk stratification of high risk were the independent risk factors for IFI in AL patients during treatment in tropical regions. CONCLUSION: The incidence of IFI in patients with AL in the tropics regions is significantly higher than that in other regions at homeland and abroad. Anti-fungal prophylaxis should be given to the patients with AL who have the high risk factors of inducting chemotherapy or HSCT, time of agranulocytosis ≥7 days and risk stratification of high risk.

The effect of the detection of minimal residual disease for the prognosis and the choice of post-remission therapy of intermediate-risk acute myeloid leukemia without FLT3-ITD, NPM1 and biallelic CEBPA mutations.

BACKGROUND: Intermediate-risk acute myeloid leukemia (IR-AML) without FLT3-ITD, NPM1 and biallelic CEBPA mutations (here referred to as NPM1mut-negCEBPAdm-negFLT3-ITDneg AML) is a clinically heterogeneous disease. The optimal post-remission therapy (PRT) is unclear for patients with NPM1mut-negCEBPAdm-negFLT3-ITDneg AML who achieved first complete response (CR1). This study aims to explore clinical and molecular factors that can help determine the prognosis of those patients and their choice of PRT. METHODS: We retrospectively analyzed 28 patients with NPM1mut-negCEBPAdm-negFLT3-ITDneg AML who received induction chemotherapy and achieved CR1. For PRT, 17 patients received post-remission chemotherapy (PR-CT) and 11 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). RESULTS: For patients with NPM1mut-negCEBPAdm-negFLT3-ITDneg AML, multivariate analysis indicated that allo-HSCT and negative minimal residual disease (MRDneg) before PRT were favorable prognostic factors of overall survival (OS) (allo-HSCT, P = 0.002; MRDneg, P = 0.018); whereas relapse was an adverse prognostic factor of OS (P = 0.003). Log-rank analysis showed that allo-HSCT significantly improved their OS and RFS compared with PR-CT (OS, P < 0.001; RFS, P = 001). Otherwise, allo-HSCT improved the OS and RFS of patients with NPM1mut-negCEBPAdm-negFLT3-ITDneg AML, whether they obtained MRDpos or MRDneg before PRT (OS: MRDneg, P = 0.036; MRDpos, P = 0.012; RFS: MRDneg, P = 0.047; MRDpos, P = 0.030). CONCLUSION: For patients with NPM1mut-negCEBPAdm-negFLT3-ITDneg AML, MRDneg before PRT and allo-HSCT were favorable prognostic factors of OS. Whether they obtain MRDneg or not, allo-HSCT is the preferred PRT.

[Single Center Analysis of Bloodstream Infection Clinical Characteristics and Prognosis in Patients with Hematological Malignancies in the Tropics].

OBJECTIVE: To analyze the characteristics, prognosis and risk factors of bloodstream infection in patients with hematological malignancies in the tropics, so as to provide evidence for the prevention and treatment of bloodstream infection. METHODS: The clinical features, blood culture results and prognosis of patients with bloodstream infection in patients with hematological malignancies admitted to Hainan Hospital of PLA General Hospital were retrospectively studied. RESULTS: The most common primary infection site of the 81 patients with hematological malignancies was lung (46.91%), followed by PICC (11.11%). The detection rate of Gram-positive bacteria and Gram-negative bacteria in the blood culture was 60.98% and 30.02%, respectively. Coagulase-negative staphylococci was the most common Gram-positive bacteria resulting in bloodstream infection in our study. Of the Gram-negatives, Klebsiella pneumoniae (34.38%) was predominant, followed by Escherichia coli (18.75%) and Pseudomonas aeruginosa (18.75%). Gram-positive bacteria was highly sensitive (100%) to vancomycin, linezolid and tigecycline. Study showed that Gram-negative bacteria had low sensitive to quinolones, in particular, the resistance rate of Escherichia coli to quinolones was as high as 83.33%. In terms of overall survival (OS), the 30-days OS of patients with Gram-negative and Gram-positive septicemia was 77.42% and 92.00%, respectively. There was no statistically significant difference between the two groups. Multivariate analysis revealed that septic shock (P=0.001, RR=269.27) was an independent risk factor for 30-day mortality, and remission status (P=0.027, RR=0.114) was an independent predictor of a favourable outcome of bloodstream infection in patients with hematological malignancies. CONCLUSION: Gram-positive bacteria are the main pathogens causing bloodstream infections in patients with hematological malignancies in the tropics. Improving the care of PICC is an important measure to reduce the incidence of bloodstream infection in patients with hematological malignancies in the tropics. A correct treatment relieving disease and effective prevention and treatment of septic shock can reduce mortality of patients with bloodstream infection in patients with hematological malignancies in the tropics.

Potential effect of epigenetic drugs in the treatment of multiple-site extramedullary plasmacytoma involving the respiratory system: a case report and review of the literature.

We report the case of a 23-year-old man with a medical history of idiopathic thrombocytopenic purpura (ITP) and newly diagnosed with the Epstein-Barr virus (EBV)-positive multiple-site extramedullary plasmacytoma (EMP), which involves the respiratory system. The patient was referred to our hospital because of progressive nasal congestion and nasal mass. Nasopharyngoscopy and bronchoscopy were performed. The biopsy pathological hematoxylin and eosin (HE) staining indicated plasma cell myeloma, and further immunohistochemistry CD99(+), CD79a(+), CD38(+), MUM-1(+), and Lambda(+) confirmed the diagnosis. The patient's bone marrow was normal, and hypercalcemia, renal insufficiency, anemia, evident bone lesions were not observed. Serum immunoglobulin quantification, serum protein electrophoresis, and blood and urine light chain quantification were all within the normal range. The serum immunofixation electrophoresis was negative, and the serum-free light chain was normal. These results could rule out multiple myeloma (MM) and prove to be EMP involving the nasal cavity, main bronchus, lung, and left hip. No desired effect was achieved after receiving PAD (bortezomib, adriamycin, and dexamethasone) and VRD (bortezomib, lenalidomide, and dexamethasone) treatments. Even if the tumor was remarkably relieved after receiving the 2-course CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen, secondary resistance to CHOP unfortunately occurred in this case. We attempted to apply epigenetic therapy in the treatment of refractory multiple EMP. Although no complete remission (CR) was achieved, the maximum standard uptake value (SUVmax) in tumor lesions was significantly lower than before, and the patient's symptoms significantly improved. The patient tolerated decitabine and chidamide. We speculated that epigenetic drugs have potential effect in the treatment of multiple-site EMP.

[Clinical Characteristics and Prognosis of Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the clinical characteristics of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and the factors affecting overall survival (OS) time. METHODS: The clinical data of 14 R/R DLBCL patients admitted to the Hainan Hospital of Chinese PLA General Hospital from April 2012 to March 2019 were analyzed retrospectively and the overall response rate (ORR) after the end of different treatments was estimated. Kaplan-Meier method was used to describe the survival curve, and Log-rank test was used to compare whether different survival curves showed statistically different. RESULTS: There were 8 males and 6 females with a median age of 51 (26-75) years old and the median course of treatment before R/R was 7 (4-13). Finally, 11 patients achieved remission, 6 patients of which showed complete remission, and 5 patients showed partial remission, with the median ORR duration at 2.5 (0-51) months. All patients in the group of ibrutinib combined with second-line chemotherapy achieved remission (4/4), it was equivalent to the high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDC-AHSCT) group (4/4), which was significantly higher than that of the other second-line group (3/6). The median OS time of patients was 17 (6-76) months. The survival of patients receiving ibrutinib combined with second-line chemotherapy and HDC-AHSCT was significantly better than that of patients not receiving ibrutinib combined with second-line chemotherapy and HDC-AHSCT. Normal lactate dehydrogenase, IPI score＜3 at diagnosis, and CR/PR after treatment could improve the survival time of patients. CONCLUSION: The duration of remission for R/R DLBCL patients is short and the prognosis is very poor. The survival time of patients with high level of lactate dehydrogenase, IPI score≥3 at diagnosis and SD/PD after treatment is significantly shortened. Ibrutinib combined second-line chemotherapy and HDC-AHSCT can improve the efficacy and survival of R/R DLBCL patients.

[Clinical Analysis of Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of 12 Patients with Acute Leukemia in Tropical Area].

OBJECTIVE: To analyze the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of acute leukemia in the tropical area. METHODS: Twelve acute leukemia patients who were underwent allo-HSCT from April 2013 to November 2018 in Hainan Hospital of Chinese PLA General Hospital were selected, including 5 cases of acute lymphoblastic leukemia (ALL) and 7 case of acute myeloid leukemia (AML). Three cases received HLA matched sibling hematopoietic stem cell transplantation, 8 cases received haploidentical hematopoietic stem cell transplantation, 1 cases received partially mismatched unrelated hematopoietic stem cell transplantation. Pretreatment regimen: 9 cases received modified BU/CY+ATG pretreatment regimen, 3 cases received BU/CY pretreatment regimen. Graft-versus-host disease (GVHD) prevention regimen: all patients received cyclosporine A, mycophenolate mofetil combined with short-term methotrexate regimen. The clinical efficacy of allo-HSCT in treatment of acute leukemia in the tropical area was analyzed by detecting hematopoietic reconstitution, GVHD, infection, relapse and survival after transplantation. RESULTS: All the 12 patients achieved granulocyte reconstruction and megakaryocyte reconstruction. The median time of granulocyte reconstruction was 11.5 (6-14) days, and the median time of megakaryocytic reconstruction was 12.5 (10-22) days. Within 100 days after transplantation, the acute GVHD occurved in 8 cases, including 6 cases of Ⅱ-Ⅳ degree acute GVHD and 2 cases of Ⅲ-Ⅳ degree acute GVHD, 11 cases survived more than 100 days after transplantation, and the chronic GVHD occurred in 1 case, which was mildly limited. Pulmonary infection occurred in 7 cases, cytomegaloviremia occurred in 6 cases, EB viremia occurred in 6 cases, and hemorrhagic cystitis occurred in 5 cases. 2 cases relapsed and eventually died, and the remaining 10 patients survived without disease until the date of follow-up. The median follow-up time was 4 (1-68) months, 83.3% (10/12) survived without disease, and 16.7% (2/12) relapsed. CONCLUSION: Allo-HSCT is an effective method for the treatment of acute leukemia in adults. Leukemia patients should be transplanted as soon as possible after remission. The incidence of pulmonary fungal infection in transplanted patients in tropics is high, therefore the prevention and treatment of fungal infection should be strengthened.

[Clinical Characteristics and Prognosis of U2AF1 Mutation in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the incidence, clinical features of U2AF1 gene mutation in patients with acute myeloid leukemia(AML) and its effect of prognosis. METHODS: A total of 161 patients with AML were enrolled. The second-generation sequencing method was used to detect U2AF1 gene mutation, and the relationship between U2AF1 mutation and clinical features, prognosis was analyzed. RESULTS: The mutation rate of U2AF1 gene in 161 AML patients was 3.73%. The counts of peripheral blood leukocytes and platelets in the U2AF1 gene mutation group were lower than those in the wild type group. The complete response rate of U2AF1 gene mutation group was 66.67%, while that in wild type group was 55.48%, which shows no significant difference between the two groups (P=0.70). The median EFS of wild type group and the mutant group was not reached and reached to 133 days, respectively (P=0.03), while the medium OS in two groups was not reached and reached to 210 days (P=0.01). CONCLUSION: The AML patients with U2AF1 mutation positive have a poor prognosis as compared with the wild type group, which may be a poor prognostic factor for acute myeloid leukemia.

S1PR5 regulates NK cell responses in preventing graft-versus-host disease while preserving graft-versus-tumour activity in a murine allogeneic haematopoietic stem cell transplantation model.

Graft-versus-host disease (GVHD) remains a major complication following allogeneic haematopoietic stem cell transplantation (allo-HSCT) leading to high transplant-related mortality. Natural killer (NK) cells have been found to mitigate GVHD without attenuating the graft-versus-tumour (GVT) activity in the murine model of haematopoietic stem cell transplantation. Sphingosine-1-phosphate receptor 5 (S1PR5) is a very important chemokine receptor on NK cells that governs NK cell distribution in vivo and trafficking at lesion sites. Our preliminary studies showed that the incidence of GVHD was negatively correlated with S1PR5 expression in the NK cells of patients after allo-HSCT. In the present study, we found that S1PR5 deficiency in murine NK cells blocked the migration of NK cells from the bone marrow to the GVHD target organs and attenuated the inhibitory effects on the alloreactive T cells, especially CD3+ CD8+ T cells, which may be the reason why the loss of S1PR5 in NK cells could aggravate GVHD in recipient mice. Furthermore, we also demonstrated that the absence of S1PR5 expression in NK cells did not interfere with the antitumour effects of NK cells and T cells in vivo. Taken together, our data indicate that S1PR5 plays an essential role in balancing GVHD and GVT activity.

Outcome and Prognostic Factors of High-Risk Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND Allogeneic transplantation remains one of the best therapies for high-risk acute myeloid leukemia (HR-AML). MATERIAL AND METHODS This study retrospectively analyzed 126 patients with HR-AML after allogeneic hematopoietic stem cell transplantation (allo-HCST). RESULTS The disease-free survival (DFS) rates of 1 year and 3 years were 58.83% (95%CI: 50.75-68.20%) and 53.09% (95%CI: 44.59-63.22%) respectively. The cumulative relapse rates of 1 year and 3 years were 21.1% (95%CI: 14.4-28.8%) and 25.9% (95%CI: 18.1-34.5%) respectively. The cumulative incidences of III to IV acute graft-versus-host disease (aGVHD) for 100 days was 8.70% (95%CI: 4.6-14.5%). The cumulative rate of extensive chronic graft-versus-host disease (cGVHD) for 1-year was 4.1% (95%CI: 1.5-8.7%). The cumulative transplantation related mortality rate of 1 year and 3 years were 20.1% (95%CI: 13.6-27.6%) and 21.0% (95%CI: 14.3-28.6%) respectively. Univariate analysis revealed that lower overall survival was correlated with age, bacterial or fungal infection, disease status at transplantation, III-IV aGVHD, post-transplantation lymphoproliferative disorders (PTLD), white blood cell engraftment, and extramedullary involvement (P<0.05). The results of multivariate analysis were that the aforementioned factors were also related to lower overall survival except for PTLD (P<0.05). The results of univariate and multivariate analysis were that extramedullary involvement, III-IV aGVHD, and status pre-transplantation influenced DFS (P<0.05). The risk factors for relapse were status pre-transplantation and extramedullary involvement by univariate and multivariate analysis (P<0.05). CONCLUSIONS HR-AML has inferior prognosis. Our study indicated the necessity of achieving remission status prior to hematopoietic stem cell transplantation, and administration of preventive treatments on high-risk patients after hematopoietic stem cell transplantation. In addition, adequate prevention and treatment of complications are needed.

Haploidentical, Unmanipulated Granulocyte Colony-Stimulating Factor (G-CSF)-Primed Peripheral Blood Stem Cell Transplants for Acute Myeloid Leukemia (AML) in Remission: A Single Center Experience.

BACKGROUND Data about application of related haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) on patients with high-risk or intermediate-risk acute myeloid leukemia (AML) in the first complete remission (CR1) are lacking. In this study, we report the outcomes of using unmanipulated haploidentical allogeneic peripheral blood stem cell transplantation (haplo-PBSCT) as post-remission therapy for patients with high-risk or intermediate-risk AML in CR1. MATERIAL AND METHODS From January 2008 to July 2016, 33 patients diagnosed as high-risk or intermediate-risk AML in CR1 undergoing haplo-PBSCT in our institution were enrolled for analysis. The cumulative incidence of platelet and neutrophil recovery, the occurrence of acute graft-versus-host-disease (GVHD) and chronic GVHD, relapse and non-relapse mortality were assessed. Patients' survival rates were estimated using the Kaplan-Meier method. RESULTS The cumulative incidence of grade 2-4 acute GVHD, overall and extensive chronic GVHD was 18.2%, 9.1%, and 6.1%, respectively. 2-year probability of relapse was 9.1%. Disease-free survival and overall survival at 2 years were 72.7% and 75.8%, respectively. CONCLUSIONS Our results showed that unmanipulated haploidentical transplantation with G-CSF primed PBSC alone as a graft source could be an acceptable alternative post-remission treatment for high-risk or intermediate-risk AML patients in CR1 lacking a matched donor.

ABO Blood Type Incompatibility Is Not a Risk Factor of Outcomes for Acute Myeloid Leukemia (AML) Patients After Unmanipulated Haplo-identical Peripheral Blood Hematopoietic Stem Cell Transplantation.

BACKGROUND Haplo-identical hematopoietic stem cell transplantation (HSCT) has provided potential donors for patients lacking available HLA-matched donors. ABO blood type compatibility has been reported to be associated with HSCT outcomes. However, few studies have investigated the role of ABO compatibility in haplo-identical HSCT of AML patients. MATERIAL AND METHODS We retrospectively analyzed 42 adult acute myeloid leukemia (AML) patients who received unmanipulated haplo-identical peripheral blood HSCT at the Chinese PLA General Hospital between Jan 2013 and Dec 2017. We analyzed the role of ABO compatibility in engraftment, transfusion requirements, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia, acute graft-versus-host disease (GVHD), overall survival (OS), transplantation-related mortality (TRM), relapse, chronic GVHD, and post-transplant lymphoproliferative disorder (PTLD). RESULTS There were no significant differences between the ABO-matched group and the ABO-mismatched group in terms of engraftment, transfusion requirements, CMV and EBV viremia, OS, TRM, relapse, PTLD, and chronic GVHD. Univariate analysis revealed ABO incompatibility is not an independent risk factor of engraftment, transfusion requirements, CMV and EBV viremia, OS, TRM, relapse, PTLD, and chronic GVHD. We found a significantly higher cumulative incidence of aGVHD in the matched group compared with the mismatched group (80.95% vs. 42.86%, p=0.020). In multivariate analysis, ABO mismatch was associated with decreased risk of acute GVHD within 100 days after transplant (hazard ratio 0.492, 95% confidence interval 0.2123-1.14). However, the difference was not statistically significant (p=0.099). CONCLUSIONS This study demonstrated ABO incompatibility is not an independent risk factor of outcomes for AML patients who received unmanipulated haplo-identical peripheral blood HSCT. ABO compatibility might have limited value in haplo-identical donor selection.

Outcome of Rituximab-Based Treatment for Post-Transplant Lymphoproliferative Disorder After Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience.

BACKGROUND Post-transplant lymphoproliferative disorder (PTLD) is a rare complication following solid organ transplantation and allogeneic hematopoietic stem cell transplantation (Allo-HSCT), which gives rise to high mortality rates. MATERIAL AND METHODS This was a single-center retrospective analysis based on 27 patients who were diagnosed with PTLD following Allo-HSCT between January 1, 2007 and June 2018 at the Chinese PLA General Hospital. The purpose of this analysis was to investigate responses and prognostic factors of rituximab-based treatment. RESULTS Twenty-seven patients were treated with rituximab. Among them, 20 of 27 patients (74.07%) had a complete response, 2 of 27 patients (7.41%) had a partial response, 5 of 27 patients (18.52%) had no response, and 22 of 27 patients (81.48%) cleared Epstein-Barr virus (EBV) copies. There were no obvious side effects. The 1-year overall survival (OS) estimate was 46.8% (95% CI, 23.1-65.5%). Univariate analysis revealed that lower OS was correlated with Eastern Cooperative Oncology Group (ECOG) score standard (3-4), Epstein-Barr virus (EBV) viral load (≥106 copies/mL), bacteria or fungal infection, and EBV reactivation were positive after treatment with 1 or 2 doses of rituximab (P<0.05). Multivariate analysis showed that each of the following were independently associated with lower OS (P<0.05): female, ECOG score standard (3-4), and EBV reactivation were positive after treatment with 1 or 2 doses of rituximab. CONCLUSIONS Our results demonstrated that rituximab-based treatment was a safe and effective strategy for patients who were diagnosed with PTLD following Allo-HSCT. The identified prognostic factors may help to detect which PTLD patients are at a higher risk of mortality.

Single- Versus Double-Unit Umbilical Cord Blood Transplantation for Hematologic Diseases: A Systematic Review.

Controversial results exist regarding the clinical benefits of single- vs double-unit umbilical cord blood transplantation (UCBT) in patients with hematologic diseases. A systematic review was conducted to evaluate this issue. The PubMed, Embase, and Cochrane Library databases were searched up to May 2018. A total of 25 studies including 6571 recipients were identified. Although double-unit UCB contained higher doses of total nucleated cells and CD34+ cells, it offered no advantages over single-unit UCB in terms of hematologic recovery, including the rate and speed of neutrophil and platelet engraftment. Double-unit UCBT was associated with higher incidences of grades II-IV acute and extensive chronic graft-vs-host disease, accompanied by a lower relapse incidence, which may be attributed to a graft-vs-graft effect induced by double-unit UCB. However, transplant-related mortality, disease-free survival, and overall survival were comparable between single- and double-unit UCBT. Although double-unit UCBT confers no clinical advantages over single-unit UCBT, certain patients, such as those at high risk of relapse, might benefit from double-unit UCBT, a possibility that needs to be clarified in future randomized trials.