Background:some study has been confirmed more HLA dispariety between donor and patients has a stronger anti‐leukemia effect acute leukemia in some subgroupAims:To identified whether haploidentical donor(HID) have better graft‐versus‐leukemia effects than matched unrelated donor(MUD) and Identical sibling donors(ISD) in allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in complete remission(CR).Methods:With this background, Between April 2012 and December 2016, consecutive 480 patients with AML in complete remission(CR) who underwent allogeneic HSCT in our center were analyzed retrospectively. donor sources were HID in 316 (65.8%) cases. MUD in 78(16.2%)cases,ISD in 86(17.9%) cases. The median age was 23(range,1.1 to 65) years. Male to female was 263: 217. The median disease course was 8 (range,2 to 57) months. 368(76.6%) cases transplant at CR1 and 112(23.3%) patients at CR2. according to cytogenetic risk stratification,83(17.2%) in poor risk,264(55.0%) in intermediate risk,133(27.7%) in favourable risk.64(13.3%) patients with FLT3‐ITD.Myeloablative conditioning regimens were administered with either Busulfan (Bu) plus Cyclophosphamide (Cy)/Fludarabine (Flu)‐based in 449(93.5%) patients or total body irradiation (TBI) plus Cy/Flu in 31 (6.4%) patients. Antithymocyte globulin was used in MUD and HID‐HSCT. unmanipulated bone marrow(BM) and peripheral blood stem cells (PBSC) for ISD and HID HSCT,only PBSC for MUD transplant were applied as the grafts. GVHD prophylaxis included mycophenolate mofetil(MMF), cyclosporine‐A with short‐term methotrexate for HID and MUD‐HSCT. MMF are not included in ISD‐HSCT.Results:The survivor median follow‐up time were 38(18–74)months, there were similar 5‐year OS (74.7 ± 3.0% vs 86.0 ± 4.3% vs 77.9 ± 4.5%,P = 0.497) and DFS (74.1 ± 3.0% vs 76.6 ± 7.0% vs 76.7 ± 4.6%, P = 0.729)among HID,MUD,ISD‐cohorts.there were no difference relapse(14.3 ± 2.9%vs11.8 ± 7.1%vs9.2 ± 3.3%,P = 0.857) and NRM (13.2 ± 2.0%vs5.3 ± 3.2% vs13.2 ± 2.0%,P = 0.695) among three donor type. We performed univariate analysis the impact of donor type on OS and LFS,relapse in patients at each disease stage such as: patients age(≤18y or 19–40y or>40y), white blood cell at diagnosis (<50 × 109/L or ≥50 × 109/L),cause of disease (primary or sencodary),cytogenetics risk stratification (low or intermediate or high), FLT3‐ITD (with or none),NCCN risk stratification(low or intermediate or high),CRstatus(CR1or CR2),MRD(negative or positive), Extramedullary lesions (with or none), we found no significant differences in OS,LFS,relapse due to donor type. performed multivariate analysis for all patients of pretransplantation variables showed secondary AML, MRD positive were two adverse factor related to OS. MRD positive, HCT‐CI ≥2 were two risk factor associated to DFS. the patients with MRD positive,disease status in CR2,NCCN in higher risk, HCT‐CI ≥2 were associated with cumulative incidence of relapse(CIR).the patients age over 40‐y was only risk factor related to TRM.Summary/Conclusion:HID‐HSCT compared to MUD and ISD had similar graft verse leukemia effect on allo‐HSCT for AML in CR status and on its each disease stage.

Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD + ) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 10 5 /kg and were eventually settled at 1 × 10 5 /kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD + patients achieved MRD − . All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD − with a median follow-up time of 206 (45–427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 10 5 /kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.

Objective: To investigate the effect of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) pre-conditioning on prognosis of acute myeloid leukemia in first complete remission (CR(1)-AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and to explore the value of MRD monitoring by MFC in the prognosis evaluation on allo-HSCT in CR(1)-AML. Methods: Between April 2012 and March 2015, consecutive 186 patients with CR(1)-AML who underwent allo-HSCT were analyzed retrospectively. MRD in BM before conditioning was detected by eight-color MFC. Any level of residual disease was considered to be MRD positive. Results: ①Of 186 patients, MRD was negative in 151 patients, positive in 35 patients (<1% in 25 patients and 1% to 3% in 10 patients) . ② With the median follow up of 18 (5-41) months, two-year DFS was 80.0% (95%CI 68.5%-92.3%) . Univariate analysis showed that MRD positive patients had lower DFS[62.9% (95%CI 50.6%-75.2%) vs 88.9% (95%CI 76.6%-100.0%) , P<0.001], higher relapse[11.4% (95%CI 4.1%-29.0%) vs 3.3% (95% CI 0.6%-20.9%) , P=0.003] and higher NRM [25.7% (95% CI 8.1%-43.3%) vs 7.9% (95% CI 1.3%-26.5%) , P=0.001] after HSCT compared with that of MRD negative patients. Secondary AML showed lower DFS than primary AML [60.0% (95% CI 42.4%-76.6%) vs 86.0% (95% CI 68.4%-100.0%) , P=0.004]. ③Multivariate analysis indicated that MRD positive pre-HSCT was the independent risk factor on DFS [HR=4.565 (95%CI 2.918-9.482) , P<0.001], relapse [HR=5.854 (95%CI 1.538-22.288) , P=0.010] and NRM [HR=3.379 (95%CI 1.361-8.391) , P=0.009] after allo-HSCT in CR(1)-AML. Conclusion: MRD positive pre-conditioning was the only negative impact factor for patients with CR(1)-AML after allo-HSCT. MRD by MFC can be used to assess the prognosis of CR(1)-AML after allo-HSCT.

Invasive fungal infections (IFIs) are a major cause of mortality among allogeneic hematopoietic stem cell transplantation (allo‐HSCT) patients. Thanks to the widespread use of secondary antifungal prophylaxis (SAP), a history of IFI is not an absolute contraindication to allo‐HSCT. However, IFI recurrence remains a risk factor for transplant‐related mortality.

To determine the risk factors for survival in haploidentical hematopoietic stem cell transplantation (haplo-HSCT), the clinical outcomes of a large series of haplo-HSCT in our hospital are analyzed. From April 2002 to April 2010, consecutive 440 patients with hematological malignancies who underwent haplo-HSCT were included. The median age was 23 (3-59) years old. The diagnosis included AML (39.8%), ALL (35.9%), MDS (3.6%), CML (16.1%), and others (4.6%). Transplants at CR1 or CML-CP1, ≥ CR2 or CML-CP2/AP, and advanced disease (refractory/relapsed acute leukemia or CML-BC) were 33.4%, 40.9% and 25.7%. HLA mismatched at 1, 2, 3 loci was 13.2 %, 27.5%, 59.3%, respectively. All patients received unmanipulated combined marrow and peripheral blood for transplant after BUCy2/CyTBI plus ATG conditioning. Prophylaxis and treatment of GVHD were reported previously (Dao-Pei Lu et al., Blood 2006; 107:3065). Steady hematopoietic reconstitution was seen in 98.6% of recipients. The cumulative incidences of grade II to IV acute GVHD and chronic GVHD were 32.6%, 61.3%. With the median follow-up of 32 (3-99) months, 2-year overall survival (OS) rates were 76.1%, 59.8% and 31.1% in CR1 or CML-CP1, ≥ CR2 or CML-CP2/AP and advanced disease, respectively. Univariate analysis showed that lower CD34+ cell infused (< 2.85 × 106/kg) has much poor OS compared with higher CD34+ cell transplanted (> 2.85 × 106/kg) (p = 0.006); Transplants in sex-mismatched donor-recipient pair has remarkable worse 2-year OS (37.6% in male donor to female recipient, 55.3% in female donor to male recipient) compared with sex-matched transplants (65.6%) (p = 0.000). Multivariate analysis showed that disease status before transplant, CD34+ cell infused and sex-matched or not between donor and recipient were pivotal impact factors on survival. In conclusion, our clinical results from a large series of haplo-HSCT demonstrate that advanced disease, low CD34+ cell infused, and sex-mismatched between donor and recipient are the risk factors for OS.

Objective:In present clinical study,morbidity and mortality of CMV disease after pre-emptive therapy with anti-viral drugs and CMV specific cytotoxic T lymphocytes(CMV-CTLs)in allo-HCT recipients were investigated.Method:From January 2007 to January 2009,334 patients who received allo-HCT were studied(matched sibling 100,unrelated 88,haploidentical 146).Plasma CMV DNA was monitored 1 to 2 times weekly with real time quantitative polymerase chain reaction(RQ-PCR).Ganciclovir was used for 8 days during conditioning.Either Ganciclovir or Foscarnet was used as front-line pre-emptive therapy when plasma CMV DNA turned to positive.Combination of Ganciclovir and Foscarnet or CMV-CTLs were administrated if the patients failed to front-line pre-emptive therapy.Result:Overall 100-day cumulative incidence of CMV viremia was 69.1%(231/334)with median time of day 33(range,day 11 to 79).Much lower incidence of CMV viremia was found in matched sibling transplant(33.3%)compared with unrelated(88.6%)and haploidentical(82.1%)transplants(P0.01).Total 29.4%(68/231)patients received combined anti-viral medicines and 12.1%(28/231)patients were managed with CMV-CTLs with median cell dose 1.87×105 /kg(range,2.4 103to 8.0×106/kg).CMV DNA became negative in 93.9%(217/231)patients after pre-emptive therapy.Fourteen patients developed CMV disease(enteritis 12 cases,interstitial pneumonia 1 case,encephalitis 1 case).Overall 100-day cumulative incidence of CMV disease was only 3.8%.Only 4 patients(1.7%)died of CMV disease(they are all enteritis).Univariate and multivariate analysis showed that alternative donors and gradeⅡ~Ⅳ acute GVHD were the risk factors for CMV reactivation.Conclusion:Viremia which is determined by RQ-PCR guided pre-emptive therapy with anti-viral medicines and CMV-CTLs significant reduces morbidity and mortality of early CMV disease in allo-HCT patients,even in the setting from alternative donors.

Haploidentical HCT can achieve nearly comparable therapeutic effects with HLA matched sibling HCT and may induce more potent graft-versus-tumor effects. We tested whether the outcomes for adults and children were different in haploidentical HCT and sought predictors of HCT success. Patients (pts) aged 1-65 yrs receiving myeloablative conditioning regimens with 2 to 3 antigen HLA-mismatched family member donors between 2000 and 2005 were included. 137 pts (50 children and 87 adults) were reported to CIBMTR and 181 pts (68 children and 113 adults) were from Dao-Pei Hospital in China. The CIBMTR cohort was 53% AML, 31% ALL, 9% CML, and 7% MDS, with 26% early, 24% intermediate and 50% advanced disease. More than 80% of adults and children received either ATG or in vitro T cell depletion (TCD). Median FU of survivors was 40 months for children and 38 months for adults. In the Chinese cohort there were 31% AML, 35% ALL, 28% CML, and 6% MDS with 48% early, 27% intermediate and 25% with advanced disease. All pts received ATG before HCT. Median FU of survivors was 49 months for children and 47 months for adults. In univariate analyses, 3 year survival in children and adults was 19 (95% CI [8-32])% and 24 [15-35]% in the CIBMTR cohort, p=NS and 54 [43-66]% and 53 [44-62]% in the Chinese cohort, p=NS, respectively. CIBMTR and Chinese data were analyzed separately because of differences in outcomes and pt and HCT characteristics. In the CIBMTR cohort, four subgroups were compared (Adult-No TCD; Child-No TCD; Adult-TCD, Child-TCD) due to a significant interaction between age and TCD. With TCD, adults had a higher mortality rate than children (RR 1.75, [1.08-2.84], p=0.023). However, that age effect was not observed in pts without TCD. Disease stage was also predictive of survival (p<0.001). In the Chinese cohort, Karnofsky score ≥90 was associated with better survival (RR 0.35, [0.22-0.54], p<0.001) as well as lower TRM, lower relapse and higher DFS. No significant differences were found between children and adults in TRM, relapse, DFS or survival. Our results suggest that adults and children have similar outcomes after haplo-identical HCT. In vitro TCD in adults is associated with worse outcomes in the cohort reported to CIBMTR. Other prognostic factors such as advanced disease stage in the CIBMTR cohort and Karnofsky score in the Chinese cohort are consistent with those identified in studies of HLA-matched donors.

Objective Explore the feasibility of HLA matched hemopietic stem cell transplants for the treatment of T cell acute lymphocytic leukemia.Methods Between January 2004 and February 2009,nine patients with T cell acute lymphocytic leukemia(ALL)received hemopietic stem cell transplants(HSCT)with HLA matched sibling donors.Stem cell sources were G-CSF mobilized bone marrow combined with peripheral blood(n=7)or G-CSF mobilized peripheral blood(n=2).Six patients were conditioned with busulfan(BU)12 mg/kg and cyclophosphamide(CY)3.6 g/m2 and three patients were conditioned with TBI 770 Gy and cyclophosphamide(CY)3.6 g/m2.Graft versus host disease(GVHD)prophylaxis regimen consisted of cyclosporin-A(CSA),methotrexate(MTX)and mycophenolate mofetil(MMF).Results Patients received a median of 6.97×108/kg(6.34×108～9.20×108/kg)mononuclear cells(MNC).The median time of ANC0.5×109/L was day 14(12～19),and BPC20.0×109/L was day 13(1～17).All the patients got engraftment successfully and attained CR.Acute GVHD gradeⅡoccurred in 1(11.1%)patients,no acute Ⅲ～Ⅳ GVHD occurred and extensive chronic GVHD did in 4(44.4%)patients.Five patients were alive and well after 199～1936 days follow-up.Conclusion Allogeneic stem cell transplant appears to be effective for the treatment of T cell acute lymphocytic leukemia.

The hematopoietic SCT (HSCT) activity in nine Asian countries/regions was surveyed to overview the current situation. Data of 58 113 HSCTs (allogeneic: 63% vs autologous: 37%) performed between 1986 and 2006 by 432 transplant teams were collected. The number of HSCTs has been increasing in the past two decades in most countries/regions. The increase in allogeneic HSCTs is greater than in autologous HSCTs. The proportion of unrelated donors among allogeneic HSCTs in 2006 varied widely from <1% (Iran and Vietnam) to 62% (Japan). The use of each stem cell source, that is, BM, PBSC, cord blood and others (including co-infusion of BM and PBSC), also varied widely (36, 58, 0.1 and 6% in HSCT from related donors, respectively, and 53, 11, 35 and 1% in HSCT from unrelated donors, respectively). HSCTs have been continuously increasing for all indications except for chronic myelogenous leukemia and solid tumors. Hemoglobinopathy is a common indication among non-malignant diseases in many Asian countries/regions except for China, Japan and Korea. This survey clearly shows the recent progress of HSCTs in Asia and also some differences in donor and stem cell selection and disease application among countries/regions.

Human leukocyte antigen (HLA)-mismatched/haploidentical blood and marrow transplants (haplo-BMT) from family donors have been intensively studied because of the decreasing family size in mainland China, and also because the Chinese Marrow Donor Program is still not big enough. The protocol for unmanipulated haplo-BMT has been designated as 'GIAC' by Dr DP Lu--'G' represents granulocyte colony-stimulating factor mobilisation; 'I' stands for immunosuppression during pre-conditioning being prolonged and intensified; 'A' stands for the use of antithymocyte globulin; 'C' means combined use of bone marrow and peripheral blood as the graft. Haplo-BMT with GIAC regimen has been shown to be feasible for many applications as reported in 2004. Under this protocol, haplo-BMT has achieved comparable outcomes in terms of severe acute graft-versus-host disease (GVHD), chronic GVHD, relapse, treatment-related mortality (TRM), disease-free survival (DFS), and overall survival with HLA-identical sibling transplantation. The probabilities of DFS at 2 years in haplo-BMT setting were 70.7%, 49.6%, 22.2% in standard-risk, high-risk, advanced disease groups, respectively. As the third party cells, cord blood co-infusion could significantly reduce the incidence and severity of acute GVHD, and also 100-day TRM. The majority of refractory cytomegalovirus, Epstein-Barr virus and aspergillus infections can be controlled by adoptive cellular therapy. Many patients who early relapsed after BMT and failed, or are ineligible for standard therapy, have been salvaged with dendritic cell-primed cytokine-induced killer cells. With these new strategies, the lower TRM and improved DFS have been attained. Therefore, it is better to consider haplo-BMT for the patients with otherwise incurable haematological malignancies at earlier stage, when matched sibling or unrelated donors are not available.

The aim of this work was to develop a potential ecological risk index to be used as a diagnostic tool for heavy metal contaminated agricultural soils control purposes in mining areas.Taking consideration that the main-road for ecological risk of heavy metal contamination of soil is soil-vegetation-man.The environmental bioavailability largely determines the environmental impact of metal contaminated soils.Using environmental bioavailability explain the environmental toxicity sensitivity of the heavy metals in the soil-vegetation-man ecological system.The model is following: RI=Σmi=1Eri,with Eri= Cif×Tib×Tie.RI= the requested potential ecological risk index for soil;Eri = the potential ecological risk factor for the given substance(i);Cif= the degree of contamination,Cif=Ci/ Cio,Ci= the metal concentration in the soil,Cio= the metal concentration for samples from referring area;Tie= the element toxic-response factor for the given substance: Zn=1,Pb=4,Cd=15,Cu=2,Cr=11,Ni=3.Tib=(Rib / Pib)1/2;Tib =the environment bioavailbability ratio factor,Tib =(Rib / Pib)1/2,Rib =[water soluble fraction + exchangeable fraction/total concentration of the metal in soil](100%] for the samples of contaminated soil,Pib=[water soluble fraction + exchangeable fraction/total concentration of the metal in soil]×100%] for samples from referring area.

Syngeneic BMT was first performed successfully in China in 1964. In 1981, allogeneic BMT was applied in an acute leukemia patient with success. Since then, the number of BMTs has been increasing gradually, especially since the 1990s. More than 2000 stem cell transplants per year have been performed in recent years in more than 50 BMT units in mainland China. A survey of 16 BMT units from 1986 to 2005 indicates that the predominant types of transplantation performed are identical sibling (36%), related mismatched/haploidentical (11.2%), unrelated (7.5%) and autologous (44.5%) and that the distribution of disease entities and prevalent diseases being transplanted are AML (31%), ALL (16.1%), CML (19.1%) and lymphoid malignancy (22.2%). The number of transplants from unrelated donor or related mismatched/haploidentical donor has increased significantly in the past 5 years. BM and G-CSF-mobilized peripheral blood are used about equally often as a source of hematopoietic stem cells, or they are used in combination. Umbilical cord blood is used least often. Leukemias for allogeneic and lymphoid malignancies for autologous BMT continue to increase, but the increase in BMT for CML has been slow since 2004. By the end of 2007, HLA data were available on more than 700,000 individuals in the Chinese Marrow Donor Program, and 800 stem cell donations have been carried out from these. Related HLA-mismatched/haploidentical BMT has achieved comparable outcomes in terms of severe acute GVHD, chronic GVHD, relapse, treatment-related mortality, disease-free survival (DFS) and overall survival (OS) with HLA-identical sibling transplantation in the author's two BMT units. Cord blood co-infusion as the third-party cells could significantly reduce the incidence and severity of acute GVHD, steroid-refractory acute GVHD and extensive chronic GVHD without an increase in leukemia relapse and could improve DFS and OS.

Objective To investigate the efficacy of haploidentical blood and marrow transplantation (haplo-BMT) in the treatment of advanced chronic myeloid leukemia (CML).Methods From November 2002 to October 2007,35 patients with advanced CML received haplo-BMT.Eleven patients achieved the second chronic phase (CP2) after treatment with imatinib or chemotherapy or both before pre-conditioning,but there were 13 cases in accelerated phase (AP) and 11 patients in blast phase (BP) at the time of transplantation.By the last follow-up date October 31,2011,the median follow-up time among living patients was 67 months (range,49 to 100 months).Results The cases of HLA-antigen mismatched between donors and recipients as 1,2,and 3 antigens were 1,12,and 22 respectively.The number of mean mononuclear cells and CD34+ cells was (7.19+ 1.37) × 108/kg and (2.54± 1.50) × 106/kg,respectively.All but one patient achieved durable hematopoietic reconstitution. Hyperacute graft-versus-host disease (GVHD) occurred in 28.6％ (10/35) patients.The cumulative incidence of grade Ⅱ to Ⅳ acute GVHD was 48％.Among 27 patients who survived longer than 100 days after transplant,16 (60 ％) had chronic GVHD.Fiveyear overall survival (OS) rate was 46.2％ and 45.5％ in CML-AP and BP (P =0.97),respectively.Five-year probability of OS rate was 81.8％,30.8％ and 27.3％ in patients with CML-CP2,CML-AP and BP at transplant,respectively.The OS of CML-CP2 was significantly higher than CML-AP and BP at transplant (P＜0.01 ).Conclusion Haplo-BMT is a feasible therapeutic mean for patients with advanced CML who have no matched donors available.It is better to perform haplo-BMT at CML-CP2 other than CML-AP or BP.