Efficacy analysis of anti-thymocyte globulin regimens with different timing strategies for matched sibling donor hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To compare the effects of two administration time strategies for rabbit antihuman thymocyte immunoglobulin (rATG) of 5mg/kg total dose in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) . Methods: This study retrospectively analyzed the clinical data of 32 patients who received MSD-HSCT with 5 mg/kg rATG conditioning regimen at the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from October 2020 to April 2022. The patients were classified into two groups: the 4d-rATG group (16 cases), who received antithymocyte globulin (ATG) from day -5 to day -2, and the 2d-rATG group (16 cases), who received ATG from day -5 to day -4. Between the two groups, the transplantation outcomes, serum concentrations of active antithymocyte globulin (ATG) in patients from -4 days to 28 days after graft infusion (+28 days), and the reconstitution of lymphocyte subsets on days +30, +60, and +90 were compared. Results: The cumulative incidences of acute graft-versus-host disease at 100 days after graft infusion were 25.0% (95% CI 7.8% -47.2% ) and 18.8% (95% CI 4.6% -40.2% ) (P=0.605) in the 4d-rATG group and 2d-rATG group, respectively. The 1-year cumulative incidences of chronic graft-versus-host disease were 25.9% (95% CI 8.0% -48.6% ) and 21.8% (95% CI 5.2% -45.7% ) (P=0.896). The 1-year cumulative incidence of relapse was 37.5% (95% CI 18.9% -65.1% ) and 14.6% (95% CI 3.6% -46.0% ) (P=0.135), and the 1-year probabilities of overall survival were 75.0% (95% CI 46.3% -89.8% ) and 100% (P=0.062). The total area under the curve (AUC) of serum active ATG was 36.11 UE/ml·d and 35.89 UE/ml·d in the 4d-rATG and 2d-rATG groups, respectively (P=0.984). The AUC was higher in the 4d-rATG group than that in the 2d-rATG group (20.76 UE/ml·d vs 15.95 UE/ml·d, P=0.047). Three months after graft infusion, the average absolute count of CD8(+) T lymphocytes in the 4d-rATG group was lower than that in the 2d-rATG group (623 cells/μl vs 852 cells/μl, P=0.037) . Conclusion: The efficiencies of GVHD prophylaxis in MSD-PBSCT receiving 4d-ATG regimen and the 2d-rATG regimen were found to be similar. The reconstruction of CD8(+)T lymphocytes in the 2d-rATG group was better than that in the 4d-rATG group, which is related to the lower AUC of active ATG after transplantation.

Kinetics of MDSC in Patients Treated Steroids-Ruxolitinib as the First Line Therapy for aGVHD / 中国实验血液学杂志

OBJECTIVE@#To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876).@*METHODS@#We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23).@*RESULTS@#Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4+CD29+ T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4+CD29+ T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8+CD28- T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8+CD28- T / CD8+CD28+ T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P3=0.01, P7=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P3=0.0351; P7=0.0142; P14=0.0369).@*CONCLUSION@#We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China / 中华医学杂志(英文版)

BACKGROUND@#There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.@*METHODS@#From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.@*RESULTS@#Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).@*CONCLUSIONS@#Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.

The Relationship between HIF1α and WTAP Expression Level in t(8;21) Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the relationship between hypoxia inducible factor 1 (HIF1α) and Wilms' tumor 1associating protein (WTAP) expression level in t(8;21) acute myeloid leukemia cells.@*METHODS@#The t(8;21) acute myeloid leukemia cell lines, including SKNO-1 and Kasumi-1 were treated by Echinomycin for 24 h, RT-qPCR and Western blot were used to detect the expression levels of WTAP mRNA and the protein. The CoCl @*RESULTS@#The expression level of WTAP mRNA and the protein in the echinomycin treated group was significantly lower than those in the control group (P<0.01). The expression level of WTAP protein in the CoCl@*CONCLUSION@#The inhibition of HIF1-α could down-regulates the expression of WTAP, while the up-regulation of HIF1α could up-regulates the expression of WTAP, which shows that there is a positive correlation of HIF1α and WTAP expression. This result suggesting that HIF1α may be involves in the expression regulation of WTAP gene.

Value of SQLE Expression in Prognostic Evaluation of Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the relationship between the expression level of SQLE and the prognosis of patients with acute myeloid leukemia (AML) through large sample data.@*METHODS@#The data of genome, transcriptome, gene chip expression, and clinical information were statistically analyzed in multiple cohorts of AML patients with large samples.@*RESULTS@#It was found that the expression level of SQLE gene in tumor cells of AML patients was significantly higher than that of healthy controls (P=0.001). In the three AML corhort, the SQLE high expression group showed a worse therapeutic outcome (OS, P=0.009, P=0.0001, P=0.006; EFS, P=0.005, P=0.001). The unvariate and multivariate survival prognosis analysis indicated that the high expression of SQLE suggests lower event-free survival rate (EFS, HR=1.551, P<0.05) and overall survival rate (OS, HR=1.484, P<0.05). At the same time, it was also found that among different risk subgroups, the expression of SQLE in high risk group was higher (P<0.001, P=0.01), while the patients with high SQLE expression, who received allogeneic HSCT, had longer overall survival time (P=0.006).@*CONCLUSION@#The up-regulation SQLE expression suggests a poor prognosis for the patients with AML.

Increased risk of cardio-cerebrovascular disease after hematopoietic cell transplantation in patients with previous history / 中华医学杂志(英文版)

BACKGROUND@#The impacts of previous cardio-cerebrovascular disease (pre-CCVD) on the outcomes of hematopoietic cell transplantation (HCT) are not well described. Patients with pre-CCVD may often be poor candidates for HCT. This study aimed to investigate the impact of pre-CCVD on transplant outcomes.@*METHODS@#A retrospective study was conducted between patients with and without pre-CCVD who consecutively received allogeneic or autologous HCT between November 2013 and January 2020 with a matching of age and disease status. The cardiovascular complications and HCT outcomes of the two groups were evaluated and compared. The primary endpoints were post-transplant cardio-cerebrovascular disease (post-CCVD) and non-relapse mortality (NRM). We used a multivariable Cox proportional hazard model and the Fine-Gray competing risk regressions for analyses to estimate the hazard ratios (HRs).@*RESULTS@#The outcomes of 23 HCT recipients with pre-CCVD were compared with those of 107 patients in the control group. No significant differences were noted in terms of engraftment, overall survival (OS) (67.00% vs. 67.90%, P = 0.983), or relapse (29.78% vs. 28.26%, P = 0.561) between the pre-CCVD group and the control group. The cumulative incidences of 2-year NRM were similar between patients with pre-CCVD and the controls (14.68% vs. 17.08%, P = 0.670). However, pre-CCVD was associated with an increased incidence of post-CCVD (HR: 12.50, 95% confidence interval [CI]: 3.88-40.30, P < 0.001), which was an independent risk factor for increased NRM (HR: 10.29, 95% CI: 3.84-27.62, P < 0.001) and inferior OS (HR: 10.29, 95% CI: 3.84-27.62, P < 0.001).@*CONCLUSIONS@#These findings suggest that the existence of pre-CCVD before transplantation might not result in increased mortality directly but superpose the toxicity of the transplantation procedure, leading to a risk of post-CCVD. Post-CCVD was a powerful predictor for high NRM and inferior OS. Further risk stratification of pre-CCVD is needed to reduce NRM in various transplantation settings.

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study / 中华医学杂志(英文版)

BACKGROUND@#Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.@*METHODS@#This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR.@*RESULTS@#A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.@*CONCLUSION@#Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients.@*CLINICAL TRIAL REGISTRATION@#ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.

Comparison of outcomes after human leukocyte antigen-matched and haploidentical hematopoietic stem-cell transplantation for multiple myeloma / 中华医学杂志(英文版)

Background@#Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs).@*Methods@#Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up.@*Results@#Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90–30.10%) and 24.2% (95% CI, 13.81–34.59%) for the MRD group and 16.80% (95% CI, 1.71–31.89%) and 28.70% (95% CI, 8.71–48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ2 = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24–71.36%) and 45.4% (95% CI, 33.44–57.36%), and 65.6% (95% CI, 47.18–84.02%) and 26.8% (95% CI, 7.59–46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ2 = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD.@*Conclusion@#Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

Comparison of outcomes after human leukocyte antigen-matched and haploidentical hematopoietic stem-cell transplantation for multiple myeloma / 中华医学杂志(英文版)

BACKGROUND@#Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs).@*METHODS@#Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up.@*RESULTS@#Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90-30.10%) and 24.2% (95% CI, 13.81-34.59%) for the MRD group and 16.80% (95% CI, 1.71-31.89%) and 28.70% (95% CI, 8.71-48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24-71.36%) and 45.4% (95% CI, 33.44-57.36%), and 65.6% (95% CI, 47.18-84.02%) and 26.8% (95% CI, 7.59-46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD.@*CONCLUSION@#Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

Clinical outcomes of peripheral blood stem cell transplantation for aggressive peripheral T-cell lymphoma / 中华血液学杂志

Objective: To evaluate clinical outcomes of autologous and allogeneic peripheral blood stem cell transplantation (PBSCT) for aggressive peripheral T-cell lymphoma (PTCL). Methods: From June 2007 to June 2017, clinical data of PTCL patients who underwent PBSCT were assessed retrospectively. Results: Among 41 patients, 30 was male, 11 female, and median age was 38(13-57) years old. Seventeen patients with autologous PBSCT (auto-PBSCT) and 24 patients with allogeneic PBSCT (allo-PBSCT) were enrolled in this study. Eight patients (8/17, 47.1%) in auto-PBSCT group were ALK positive anaplastic large cell lymphoma (ALCL), 7 patients (7/24, 29.2%) with NK/T cell lymphoma and 9 patients (9/24, 37.5%) with PTCL-unspecified (PTCL-U) in allo-PBSCT group (P=0.035). There were 58.8% patients (10/17) in complete response (CR) status and 11.8% (2/17) in progression disease (PD) status before transplantation in auto-PBSCT group, and 8.3% (2/24) in CR status and 45.8% (11/24) in PD status before transplantation in allo-PBSCT group (P=0.026). The 2-years cumulative overall survival (OS) were (64.0±10.8)% and (53.5±9.7)% for auto-PBSCT and allo-PBSCT respectively (P=0.543). The 2-years cumulative disease-free survival (DFS) were (57.1±12.4)% and (53.5±10.6)% for auto-PBSCT and allo-PBSCT respectively (P=0.701). In patients with dead outcomes after PBSCT, 83.3% (5/6) of death cause was relapse in auto-PBSCT and 41.7% (5/12) of death cause was relapse in allo-PBSCT. Conclusion: Both auto-PBSCT and allo-PBSCT were effective for PTCL. Allo-PBSCT maybe was better than auto-PBSCT for high-risk PTCL with poor prognosis.

The challenge for allogeneic hematopoietic stem cell transplantation in acute leukemia/ myelodyplastic syndrom with TP53, TET2 or DNMT3A gene mutations / 天津医药

@#Recently, much gene mutations have been detected in patients with acute leukemia or myelodysplastic syndrome (MDS) using next-generation sequencing (NSG) technology. Some of them are proved to be important prognostic markers. It has been showed that TP53, TET2 or DNMT3A gene mutations are associated with poor prognosis in acute leukemia or MDS patients. The prognosis of these patients is poor with short remission and survival. Allogeneic hematopoietic stem cell transplantation is the only way to cure these patients. However, the outcomes after transplantation are inferior to those in patients without these mutations. The hypomethylating agents or immune targeting therapy might improve their prognosis when combined with the present strategies. Here, the impact of TP53, TET2 and DNMT3A gene mutations on the prognosis after chemotherapy or transplantation is reviewed.

Peripheral T-cell Lymphomas: Updates in Allogeneic Hematopoietic Stem Cell Transplantation / 中华医学杂志(英文版)

Objective@#Peripheral T-cell lymphomas (PTCLs) confer dismal prognosis and no consensus has been established on the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to its rarity and heterogeneity. The purpose was to review key points of allo-HSCT for PTCLs, including indication, times of transplantation, conditioning regimen, graft versus host disease prophylaxis, and treatment of relapse.@*Data Sources@#A comprehensive search in PubMed and Cochrane up to February 28, 2018, with the keywords "Peripheral", "T", "Lymphoma", and "Transplantation" was done.@*Study Selection@#Relevant articles including HSCT for PTCLs were carefully reviewed.@*Results@#Promising data have been reported from advances in transplant technology and more and more PTCLs patients with poor prognosis could benefit from allo-HSCT.@*Conclusion@#Allo-HSCT is a useful choice for patients with refractory/relapsed PTCLs or high-risk new diagnosed PTCLs.

Clinical Characteristics, Treatment and Prognosis of PTLD after allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics of patients with post-transplantation lymphoproliferative disease (PTLD) after allogeneic peripheral blood hematopoietic stem cell transplantation, and to improve the understanding and diagnosis of PTLD.</p><p><b>METHODS</b>The clinical data of 244 patients underwent allogeneic hematopoietic stem cell transplantation in the General Hospital of PLA from May 2014 to April 2017 were analyzed retrospectively. The follow-up time was up to November 30, 2017. The incidence, risk factors, treatment and survival of patients with PTLD were statistically analyzed.</p><p><b>RESULTS</b>Among the 244 cases the PTLD occurred in 22 cases, the incidence rate was 9.02%, 5 of them were diagnosed by pathology, and 17 were diagnosed clinically. All of them had EB virus infection. They were all ATG user, either underwent related haploidentical hematopoietic stem cell transplantation or unrelated hematopoietic stem cell transplantation, 20 cases were treated with rituximab or rituximab combined with γ-globulin, glucocorticoid, ERV+CTL, chemotherapy and 17 showed the effective response, with a total effective rate of 85%. The median follow-up time was 122 days, the median survival time was 5 months (1-22 months) and the total survival rate was 50%.</p><p><b>CONCLUSION</b>The incidence of PTLD after allogeneic peripheral blood hematopoietic stem cell transplantation closely relates with EB virus infection. The application of ATG in the preconditioning scheme is a high risk factor for the onset of PTLD. In the case of no pathological diagnosis, clinical and laboratory examinations should be actively combined so as to define clinical diagnosis. The riturimab should be used more and more for patients with PTLD.</p>

Efficacy and Safety of Unmanipulated Haploidentical Related Donor Allogeneic Peripheral Blood Stem Cell Transplantation in Patients with Relapsed/Refractory Acute Myeloid Leukemia / 中华医学杂志(英文版)

<p><b>Background</b>Studies of haploidentical-related donor (HRD) stem cell transplantation using a combination of peripheral blood stem cells (PBSCs) and bone marrow as the graft have reported encouraging results for patients with hematological diseases. However, few studies specifically reported transplantation of only PBSCs from HRDs among patients with relapsed or refractory acute myeloid leukemia (AML). Here, the long-term outcomes and side effects of unmanipulated HRD PBSC transplantation (HRD-PBSCT) for relapsed/refractory AML were analyzed.</p><p><b>Methods</b>We performed a retrospective analysis of the outcomes in relapsed/refractory AML patients who underwent PBSCT from HRDs (n = 36).</p><p><b>Results</b>Thirty-one (86.1%) patients in the HRD-PBSCT group achieved platelet recovery. The cumulative incidence of acute graft-versus-host disease (aGVHD) in the HRD-PBSCT group was 40.00%, and the cumulative incidence of grades 2-4 aGVHD in this group was 13.33%. A total of 13 patients in the HRD-PBSCT group had recurrent disease at a median of 183 days after transplantation (range: 10-1700 days), reaching cumulative incidences of relapse of 50.28% at 5 years. On multivariate analysis, donor age and patient age >40 years were independent risk factors for inferior disease-free survival or overall survival (P < 0.05). The results of the present study demonstrate rapid and complete neutrophil engraftment, a low incidence of grade 2-4 aGVHD, and promising survival rates in patients after HRD-PBSCT. Thus, granulocyte colony-stimulating factor-primed PBSCs may be a reliable graft source in unmanipulated HRD-HSCT under myeloablative conditioning when no matched sibling donor is available.</p><p><b>Conclusions</b>Our results support the feasibility, effectiveness, and tolerability of PBSCs as a graft source in unmanipulated HRD transplantation under myeloablative conditioning in patients with leukemia.</p>

Analysis of Efficacy and Related Factors of Acquired Deep Molecular Response in Chronic Myeloid Leukemia Patients Treated with TKI / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and related factors of acquired deep molecular response(DMR) for treating patients with chronic myeloid leukemia(CML) by using TKI.</p><p><b>METHODS</b>The clinical data of 131 TKI-treated patients with CML were analyzed retrospectively. The therapeutic effects of each time-points were evaluated, and the related factors of MRwere analyzed.</p><p><b>RESULTS</b>The median follow up-time of 131 cases with CML was 24 months (6-120 months), among them the treatment of 30 patient was converted to nilotinib after a median of 12 months (1-69.6 months) with imatinib, and 13 patient was converted to dasatinib treatment after a median of 31.2 month (3.1-87.6 months) with imatinib. After treatment for 3, 6 and 12 month, the rate of major cytogenetic response (MCyR) was 78%, 79.4% and 95.9%, and the complete cytogenetic response (CCyR) rate was 48.8%, 66.7% and 73.5%, respectively. 60% patients obtained BCR-ABL<10% at 3 months, 56.3% patients obtained BCR-ABL<1% at 6 months, 55.2% patients obtained BCR-ABL<0.1% at 12 months. In continued imatinib therapy group, 53 patients (60.9%) obtained MR, and 33 cases (37.9%) obtained stable MR. Multivariate analysis showed that sex, WBC count at the time of diagnosis and BCR-ABLlevel at 3 months were independent factors for obtaining MR. The 3-month BCR-ABLlevel was an independent factor to obtain stable MR. 18 cases (40.9%) in the second-generation TKI group received MRand the 3-month BCR-ABLlevel was also an independent predictor for MR.</p><p><b>CONCLUSION</b>The excellent cytogenetic and molecular responses are observed in CML patients treated with cmatinib. Conversion to second-generation TKI therapy for patients with resistant or intolerant to imatinib also can achieve a satisfactory response and a higher rate of deeper molecular remission. The higher incidence of early molecular response predicting MRand stable MRis achieved.</p>

A Retrospective Study of Ph Negative Adolescent and Young Adults with Acute B Lymphoblastic Leukemia in Two Centers / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the therapeutic efficacy of different consolidation therapies after induction remission on Ph negative adolescent and young adults with acute B lymphoblastic leukemia, and to explore the effect of different risk factors on prognosis.</p><p><b>METHODS</b>The treatment and efficacy of 80 Ph negative B-ALL in patients of 16-39 years old in the Hematology Department of 301(65 cases) and 309(15 cases) hospital from 1999 to 2016 are retrospectively analyzed. The patients received combined induction chemotherapy of 4 or 5 chemotherapeutic drugs (VDCLP/ VDLP/ DOLP/ IOLP). After remission patients received consolidation protocols of 3-5 cycls, and then received allo-HSCT or haploidentical HSCT. The median follow-up time was 29 (6-153) months.</p><p><b>RESULTS</b>HSCT was carried out after CR1. The 5-year OS and EFS of allo-HSCT group(n=29) was (73±16)% and (67±17)%, respectively, while those of haploidentical-HSCT group(n=20) were (53±22)% and (53±22)%, respectively, and those of pediatric-inspired protocols(n=31) was (63±17)% and (50±18)%, respectively. The difference between OS and EFS in 3 group was not statistically significant(P>0.05). The re-remission rate of recurrent patients was (50±23)%. On the one side, the cumulative incidence of TRM of pediatric-inspired protocol was better than that of HSCT (P<0.05). On the other side, the cummulative incidence of relapse (CIR) of pediatric-inspired protocol was poorer than that of HSCT, yet without significant difference (P>0.05). The median remission time of CR2 in patients was 14(2-36) months. Univariate and multivariate analysis were performed in 65 patients, and showed an abnormal result of CD13 or CD33 positive, CD22 negative, indicating a poor prognosis(P<0.05).</p><p><b>CONCLUSION</b>In the adolescent and young adult patients with PhB-ALL treated by pediatric-inspired protocols, the survival time is similar with that in allo-HSCT group. However, more prospective clinical studies of random control test(RCT) should be carried out.</p>

Comparison of Clinical Outcomes between P190 and P210 Trans-cripts in Adult Ph Chromosome Positive Acute Lymphoblastic Leukemia in the New Era of TKI / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the differences of clinical characteristics and outcome between p190 and p210 transcripts in adult Ph chromosome positive acute lymphoblastic leukemia patients in the new era with tyrosine kinase inhibitor (TKI) treatment, so as to provide an insight for improving the prognostic stratification and individualized treatment of the Ph(+) ALL patients.</p><p><b>METHODS</b>The clinical data of 65 patients were analysed retrospectively, these patients were diagnosed as Ph(+) ALL and treated with conventional chemotherapy plus TKI treatment with or without hematopoietic stem cell transplantation (HSCT) from January 2005 to December 2014 in our hospital, then the differences of clinical features and prognosis were compared between the p190 (n = 41) and the p210 group (n = 24).</p><p><b>RESULTS</b>The p190 group had lower platelet count than the p210 group (46.3 × 10(9)/L vs 65 × 10(9)/L) (P = 0.084); the leukemic blast cells in bone marrow at diagnosis was slightly higher in p190 group than that in p210 group (88.4% vs 76.8%) (P = 0.096); the other clinical features, such as sex, age, white blood cells, hemoglobin, leukemic blast cells in peripheral blood, and BCR-ABL/ABL expression level were not significantly different between these two groups. As to the response to treatment, the complete remission rate (CR) after induction therapy was 80% (32/40) and 87% (20/23) respectively in the p190 and p210 group, no significant difference was seen (P = 0.732). The time from induction to the first complete remission (CR1) was not significantly different either (28 days vs 29 days) (P = 0.922). The recurrence rate was 61% (20/33) in the p190 group and 43% (9/21) in the p210 group, but the difference was not significantly different (P = 0.202). However, the duration of remission in p190 group was shorter than that in p210 group, whether from the time of initial diagnosis to relapse (212 days vs 274 days) (P = 0.077) or from the time of CR1 to relapse (146 days vs 242 days) (P = 0.084). For the prognosis, the p190 group presented with a shorter 5 year-survival rate (P = 0.016) as well as event-free survival rate (P = 0.085).</p><p><b>CONCLUSION</b>The p190 group tends to have lower peripheral blood platelet count and higher percentage of leukemic blasts in bone marrow at diagnosis; while the CR rate and the time from induction to CR1 are not significantly different; however, the p190 group is more likely to relapse at a relatively early stage, and the 5 year-survival rate and event-free survival rate are lower in p190 group than that in p210 group, indicating that the patients carrying p190 transcript are probably necessary to receive more intensive therapy such as HSCT as early as possible after achieving CR1, which can promisingly improve the overall prognosis of the Ph(+) ALL patients.</p>

Therapeutic Efficacy Analysis of Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation for 14 Adult Patients with T Lymphoblastic Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic efficacy of allogeneic peripheral blood hematopoietic stem cell transpdantation (allo-HSCT) for T lymphoblastic lymphoma (T-LBL).</p><p><b>METHODS</b>The clinical data of 14 adult patients with T-LBL treated with allo-HSCT were collected, the hematopoietic reconstruction, survival and relapse, as well as overall survival (OS) rate, event-free survival (EFS) rate of 1, 3 and 5 years were analysed retrospectively.</p><p><b>RESULTS</b>All the patients were engrafted with neutrophil successfully, the median time of absolute neutrophil count >0.5 × 10(9)/L was 13 (10-19) d; 13 patients were engrafted with platelets successfully, the median time of Plt count >20 × 10(9)/L was 17 (12-62) days. The acute GVHD occurred in 6 patients, but among them only 1 case with 3 grade of aGVHD; out of 14 patients, 5 developed chronic GVHD. The transplant-related mortality at 100 days was 7.1% (1/14), mainly from coronary heart disease and pulmonary infection. The median follow-up time was 26.5 months, the estimated 1, 3 and 5 year OS rate was 85.7%, 47.6% and 38.1%, respectively, and estimated 1, 3 year EFS rate was 85.7%, 34.4% and 34.1%, respectively. The relapse rate was 42.8% (6/14) and the median relapse time was 22.5% months after transplantation. Up to now, 7 patients still survive, 1 patient out of them have survived for 103 months.</p><p><b>CONCLUSION</b>The allo-HSCT is a safe and effective method for treatment of T-LBL.</p>

Clinical Characteristics of 30 Hodgkin's Lymphoma Patients with Extranodal Involvement / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics, treatment outcomes, prognosis, delayed toxicity of Hodgkin's lymphoma with extranodal Involvement.</p><p><b>METHODS</b>Thirty patients newly diagnosed as Hodgkin's lymphoma with extranodal involvement from April 2008 to September 2014 were retrospectively analyzed.</p><p><b>RESULTS</b>Twenty-seven patients suffered from the advanced-stage diseases, their major pathological changes were nodular sclerosis and mixed cellular type, the most commonly involeved extranodal sites were the lung and bones, followed by the liver, stomach and intestine. The common clinical presentation was assotiated with the involved organs. Multivariate analysis showed that albumin and the international prognostic score (IPS) were independent prognostic factors for 5-year DFS rate, the 5-year OS rate was only associated with IPS. Out of 20 patients received chemotherapy, 10 received the combined modality therapy. At the median follow-up of 51 months, the estimated 5-year OS and PFS rates were 89.3% and 78.9%, respectively. Delayed toxicities were observed in 3 patients, including Ewing's sarcoma of llium, hyperplasia of mammary glands and diabetes millitus. 5 patients kept fertility, no interstitial lung disease, lung cancer and cardiovascular disease occurred. It was not found that patients died from the treatment-related complications.</p><p><b>CONCLUSION</b>The therapeutic strategies for the Hodgkin's lymphoma patients with extranodal involvement should be similar to normal Hodgkin's lymphoma.</p>

Role of Mesenchymal Stem Cells in Preventing GVHD: A Meta-Analysis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of mesenchymal stem cells (MSC) in the prevention of graft versus host disease (GVHD) after hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>Randomized controlled trials (RCT) were identified from PubMed (1950.1-2014.3), EMbase (1970.1-2014.3), Cochrane Central Register of Controlled Trials (CENTRAL, issue 4, 2014) of the Cochrane Library, China Biological Medicine (CBM, 1978.1-2014.3). References of retrieved articles were also identified. The quality of each RCT was evaluated by the Cochrane collaboration's tool for assessing the risk of bias. Data analysis was performed with Review Manager 5.1 to evaluate the efficacy of MSC in the prevention of GVHD after HSCT.</p><p><b>RESULTS</b>A total of 3 English articles involving 117 patients were included. Meta-analysis indicated that MSC did not reduce the incidence of acute GVHD and chronic GVHD (RR:0.44, 95% CI: 0.08 to 2.51, P = 0.35; RR:0.85, 95% CI: 0.54 to 1.33, P = 0.47). However, MSC did not increase occurrence of relapse and cytomegalovirus infection (RR:1.52, 95% CI:0.63 to 3.68, P = 0.35;RR:1.05, 95% CI:0.72 to 1.53, P = 0.78). Finally, MSC did not improve overall survival rate of patients received HSCT (RR:1.06, 95% CI:0.79 to 1.43, P = 0.71).</p><p><b>CONCLUSION</b>MSC may have a preventive effect on GVHD in patients undergoing HSCT. However, the evidence is weak due to the small sample sizes. Thus, a reliable conclusion about the preventive effect of MSC on GVHD at the moment has not been made, further larger, high quality, randomized and controlled trials are warranted.</p>