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OBJECTIVE: To assess the prognostic value of minimal residual disease on 19th day of induction chemotherapy (D19 MRD) and the risk factors of D19 MRD ≥ 1% in children with acute lymphoblastic leukemia (ALL) treated following the Chinese Children's Cancer Group ALL protocol. METHODS: We retrospectively analyzed the data of 243 children with ALL diagnosed between January 1, 2015 and December 31, 2018 in the Department of Pediatrics of Nanfang Hospital (Guangzhou China). Kaplan Meier-survival analysis was performed to compare the survival time between the patients with D19 MRD < 1% and those with D19 MRD ≥ 1%; logistic regression analyisis and Chi-square test were used to identify the risk factors of D19 MRD ≥ 1%. RESULTS: Compared with those with D19 MRD ≥ 1%, the children with D19 MRD < 1% had significantly better 3-year overall survival (100% vs 90.2%, P=0.004) and event-free survival (97.6% vs 71.6%, P < 0.001). Univariate analysis showed that the odds ratio (OR) for mediastinal invasion, T-cell immunophenotype, TEL/AML1 fusion gene and the presence of blasts in peripheral blood on the 5th day were 4.47 (95%CI: 0.275-72.968, P=0.034), 5.250 (95%CI: 1.950-14.133, P=0.02), 0.330 (95%CI: 0.112-0.970, P=0.036) and 4.407 (95%CI: 1.782-10.895, P=0.01), respectively. The initial risk stratification (P < 0.001), white blood cell grades (P=0.018) and its counts (P=0.027), and the number of blasts on the 5th day (P < 0.001) were significantly different between the two groups. Multivariate analysis showed that initial risk stratification as intermediate and high risks (OR=2.889, 95% CI: 1.193-6.996) and the presence of blasts in peripheral blood on the 5th day (OR=4.477, 95% CI: 1.692-11.843) were independent risk factors for poor early treatment response. CONCLUSION: D19 MRD ≥ 1% is a predictor of poor prognosis in children with ALL. Mediastinal invasion, T-cell immunophenotype and the presence of blasts in peripheral blood on the 5th day are all risk factors for poor early treatment response, while TEL/AML1 fusion gene is a protective factor; the initial risk stratification as intermediate to high risk and the presence of blasts in peripheral blood on the 5th day are independent risk factors for poor early treatment response of the patients.

Background: Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for thalassemia majorTM. Graft rejection (GR) and graft-versus-host disease (GVHD) are the primary obstacles to a successful outcome. Methods: We conducted a retrospective study of HSCT in 29 children (median age at transplantation: 6 years) with Beta-thalassemia (β-TM) after the combined infusion of granulocyte colony-stimulating factor-primed bone marrow (G-BM) and cord blood (CB) from the human leukocyte antigen (HLA)-identical sibling donors. We also compared the outcomes of the co-transplanted children with those of children with β-TM who received G-BM alone from an HLA-identical sibling donor (n = 26). Results: Compared to the G-BM transplant (G-BMT) recipients, those who received a co-transplant had a lower incidence of grade ≥II acute (17.24 vs. 30.7%, p = 0.047) and limited chronic (0 vs.15.4%, p = 0.022) GVHD as well as a lower incidence of GR (0 vs. 7.7%, p = 0.132). Neutrophil recovery time was faster in the co-transplant group (18.5 vs. 21 days, p = 0.04). All the patients were monitored until December 31, 2016; the median follow-up time was 74 months, and the 5-year thalassemia-free survival rate was 89.7% in the co-transplant group and 84.6% in the G-BMT-alone group (p = 0.590). Conclusions: A combined CB and G-BM graft from an HLA-identical sibling donor is an effective treatment option for TM in children, with less acute and chronic GVHD.

Background: For patients without HLA matched donor, Haploid stem cell transplantation with PTCY method has relatively higher risk of relapse and graft-versus-host disease (GVHD). Umbilical cord blood (UCB) is readily available and has helped expand the donor pool to almost all patients requiring a transplant. Meanwhile UCB transplant improves EFS in leukaemia with lower risk of relapse and GVHD. However, the clinical application of UCB is limited due to lower implantation rate because of its low dose of stem cells than other sources of hematopoietic stem cells (HSC). Aims: This study is to explore the feasibility and efficacy of post-transplantation fludarabine and cyclophosphamide to select and promote the unrelated UCB to engraft in combined transplantation of haploid and UCB stem cells for the treatment of childhood and adolescent leukemia. Methods: Total 40 children and adolescent patients with leukemia in Nanfang Hospital and Shenzhen Children's Hospital enrolled this study from Sept.2019 to Jun.2021. These patients were diagnosed as AML (20 HR, 5 IR, 2 relapsed AML), ALL (5 HR, 2 IR, 2 relapsed ALL), AL (1), JMML (2), MDS (1) and BPDCN (1) with a median age of 80 months (range 7 months -17 years). The biggest body weight reached to 77kg. The haploid stem cell was 5/10-9/10 mismatched and UCB was selected as 6/10-10/10 HLA matched or mismatched. The condition regimen was busulfan+fludarabine+CY+Ara-C. Haploid PBSC was infused in day0. All received PTCy 50 mg/kg and post-transplantation fludarabine 40mg/m 2 on days 3 and 4 along with tacrolimus or cyclosporine and mycophenolate mofetil for prophylaxis of acute GVHD. UCB was infused in day6. A median of haploid stem cells of 20.00×10 8/kg (13.00-32.10) of mononuclear cells was infused while a median of UCB cells of 4.32×10 7/kg (1.48-22.78) of total nucleated cells was infused. A median of CD34+ cells of haploid stem cells 13.00×10 6/kg (1.51-32.00) was infused while a median of CD34+ cells of UCB cells 1.74×10 5/kg (0.26-4.80) was infused. The survival rate, umbilical cord blood implantation rate, hematopoietic recovery and the rate of transplant-related complications were analyzed. Results: At a median follow-up of 8 months (range 1-21 months), there were 2/40（5%）cases of transplant-related death. All surviving patients were leukemia free, with one-year overall survival rate 92.8±5.0%. Among these patients, 37/40(92.5%, 95%CI: 84.0%~100.0%) of patients achieved complete chimerism of unrelated UCB cells and 3/40(7.5%, 95%CI: -1.0%~16.0%) of patients achieved mixed chimerism of unrelated UCB cells and haploid cells. In these transpltantation, the CD34+ cell dose of UCB less than 1.0×10 5/kg accounted for 10/40 (25.0%), and less than 2.0×10 5/kg accounted for 23/40 (57.5%).Two patients had primary poor graft function. Neutrophil reconstitution was achieved in 39/40 patients with a median time of 29 days (range 17 - 44 days) without G-CSF after transplantation. Platelet recovery was achieved in 37/40 patients with a median time of 37 days (range 8-92 days). There was a significant linear relationship between platelet recovery time and the dose of total nucleated cells and CD34+ cells in UCB（r=-0.368, P=0.025; r=-0.355, P=0.031）.The incidence of gradeⅠand gradeⅡGVHD was 32.5%（95%CI:17.3%-47.7%）and 42.5%（95%CI:26.5%-58.5%）, respectively. There was no grade Ⅲ-Ⅳ aGVHD and only 1/40(2.5%) case of extensive chronic GVHD. The incidence of chronic limited GVHD was 22.5% (95%CI: 9.0%-36.0%). Twenty-four of 40(60.0%, 95%CI:44.1%-75.9%) patients experienced clinically significant CMV reactivations or infections. One of 40（2.5%, 95%CI: -2.6%-7.6%）patients experienced EB virus reactivation. Two of 40（5.0%, 95%CI: -2.1%-12.1%）patients experienced human herpesvirus 6 infection. Thirteen of 40（32.5%, 95%CI: 17.3%-47.7%）patients presented with hemorrhagic cystitis. Conclusion: In our primary clinical study, post-transplantation fludarabine and cyclophosphamide could effectively select and promote the unrelated UCB to implant rather than haploid cells in combined transplantation of haploid and UCB stem cells even if the CD34+ cells of UCB less than 1.0×10 5/kg. Although acute GVHD was common but just milder degree and with lower incidence of EB virus reactivation. This new strategy has the potential to promote the wilder clinical use of unrelated UCB in the treatment of leukemia. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background:Hematopoietic stem cell transplantation(HSCT) is currently the only treatment shown to provide an effective, definitive cure for β-thalassemia major (TM). All over the world a major constraint is the lack of access to this therapy related to the lack of a suitable donor. Matched related donors are generally available only for a third of patients with TM.The need for alternative donors has therefore been explored in several ways-partially mismatched related donors, related haploidentical transplants,and matched or mismatched unrelated donors.Persisting concerns regarding high rejection rates and graft versus host disease (GVHD) need to be addressed through the evaluation of novel protocols in current and future studies.The effect of alloreactive clone destruction in post-transplant cyclophosphamide (Cy, PTCy) transplant resulted in low GVHD and high relapse but nice immuno-recovery and immuno-tolerance by keeping antivirus and regulatory T cells. Therefore, we developed a novel protocol for TM patients received HSCT form HLA mismatched donors. Patients and methods:Twenty patients received HSCT form HLA mismatched donors between May 2014 and May 2017,with median follow-up time of 38 months (range: 2-65months).The median age at transplant was 8 years (rang:4-13years). Of them, 15 patients received unrelated- donor peripheral blood stem cell transplant(UD-PBSCT) consisted of 13 HLA 9/10(HLA-A loci,DRB loci and DRQ loci mismatched are 8,2and2,respectively) and 2 HLA 8/10(1 HLA-A and DRB loci mismatched and 2 HLA-DRB and DRQ loci mismatched), another 5 patients received HLA 9/10 related-donor peripheral blood stem cell transplant (RD- PBSCT) consisted of 3 HLA-A loci and 2 HLA-DRB loci mismatched.Among them,3 patients received adopting bone marrow(BM) and/or unrelated-donor cord blood(UD-CB). Conditioning regimen included Thymoglobuline on day -10 to -8, Cy on day-7, Busulfan on day-6 to -4, Fludarabine on day-6 to -2 and Thiotepa on day-3. GVHD prophylaxis consisted of Cy on day+3 to +4, Mycophenolate mofetil and Tacrolimus from day+6. BM or UCB was infused on day+1.GVHD prophylaxis consisted of Cy on day+3 to+4, Mycophenolate mofetil and Tacrolimus from day+5. Results:The median infused total nucleated cell (TNC) dose was 24.8×108/kg (range: 9.0-40.2×108/kg). The median dose of infused CD34+ cells was 13.88×106/kg (range 2.89-38.76× 106/kg). All twenty patients had a successful engraftment with > 95% donor-derived cells by day 30 after transplantation.The median time to neutrophil recovery was 21 days (range 16-36days). The platelet and hemoglobin engraftment times were 14 days (range10-65days) and 15 days (range 8-48days), respectively.The cumulative incidences of grades Ⅱ-III acute GVHD (aGVHD) was 10.0% (2/20 patients).No patient developed grade IV aGVHD after transplantation. No extensive or limited chronic GVHD(cGVHD) was diagnosed among any patients in the group.The incidences of CMV and EBV antigenmia were 10.0% (2/20) and 0%(0/20), respectively. All of the 20 patients were alive without TM, and overall survive(OS)and thalassemia free survive (TFS) were 100% and 100%, respectively.We also compared the outcomes of PTCy protocol with fifty-two patients with β-TM received one or two locis HLA mismatched HSCT by use of the NF-08-TM protocol(see Li et al., Blood 2012).OS and TFS were higher in the PTCy group(100%vs.90.4%,p Conclusion: PTCy protocol leaded to 100% OS and TFS with low GR and GVHD rate compared with the NF-08-TM protocol in patients with β-TM who received HSCT form HLA mismatched donors. A large-cohort study with extending follow-up time should be developed in the future. Disclosures No relevant conflicts of interest to declare.

OBJECTIVE: To assess the effects of liver and cardiac iron overload detected by magnetic resonance imaging (MRI) T2* on hematopoietic stem cell transplantation in children with β-thalassemia major. METHODS:Summary of 380 cases of β-thalassemia major patients more than 5 years old in Nanfang hospital, southern medical university from 2012 to 2019.Iron concentrations in the liver and heart were calculated based on MRI T2* test results of liver and heart. Age, serum ferritin, left ventricular ejection fraction (LVEF), and liver function were compared to evaluate the effect of iron overload on organ function in patients with β-thalassemia major before transplantation.168 patients underwent allogeneic hematopoietic stem cell transplantation, 48 were HLA-mismatched transplantation, and 120 were HLA-identical allogeneic hematopoietic stem cell transplantation.To analysis the influence between implantation rate, hematopoietic reconstruction time, mortality, and common complications after transplantation such as graft-versus-host disease, hepatic venous obstruction, infection, immune hemolysis, and pancytopenia and liver and cardiac iron overload detected by magnetic resonance imaging (MRI) T2*. RESULTS:Myocardial iron overload occurred in 73 cases (19.2%), including 29 cases of cardiac T2*15~20 ms (mild), 23 cases of 10~14 ms (moderate), and 21 cases of CONCLUSION:Magnetic resonance imaging (T2*) is an effective and non-invasive method to detect the iron overload in the heart and liver caused by blood transfusion in β-thalassemia patients. Iron overload can have adverse effects on hematopoietic stem cell transplantation,and effective iron removal before transplantation can improve the success rate of transplantation.Quantitative assessment of iron overload in the liver and heart by MRI can be used as a necessary examination before transplantation. Disclosures No relevant conflicts of interest to declare.

Background: Hematopoietic stem cell transplantation(HSCT) is currently the only curative treatment for thalassemia major (TM). Cord blood (CB) from a sibling has different characteristics from marrow and has potential advantages and disadvantages as a stem cell source. Methods: We conducted a retrospective study of fresh cord blood transplantation (F-CBT) from the matched human leukocyte antigen (HLA)-identical sibling donors in 35 children (median age at transplantation: 4 years, range:1-7 years) with β-TM from June 2010 to December 2016. The conditioning protocol included intravenous busulfan, cyclophosphamide, fludarabine, and thiotepa. Results:The median collected CB volume was 130ml (range: 79-209ml). The median infused total nucleated cell (TNC) dose was 9.38×107/kg (range: 2.73-18.91×107/kg). One patient had graft failure (GF) on +30day after F-CBT and one patient died from respiratory and heart failure that developed from a pulmonary infection. Of the 33 patients who had a successful engraftment, two patients developed grade II~III acute graft-versus-host disease(GVHD); and one with grade I extensive chronic GVHD was observed during the long-term follow-up period. The median time to neutrophil recovery was +27 days (range: +14 to +49days). The platelet and hemoglobin engraftment times were +33 days (range: +19 to +73 days) and +26 days (range: +11 to +74 days), respectively. All the patients were followed up by December 31, 2017; the median follow-up time was 45 months, and the estimated 5-year overall survival (OS) and TM-free survival (TFS) of F-CBT were 97.1% and 94.2%, respectively. Conclusions: F-CBT from a matched HLA-identical sibling donor is an effective treatment option for β-TM in children with less GVHD. Disclosures No relevant conflicts of interest to declare.

Purpose:Splenectomy can improve the quality of life of patients with β-thalassaemia major to some extent, but also increase some unpredictable risk.In order to understand the effects of splenectomy before transplantation on hematopoietic stem cell transplantation reconstruction time, infection, graft versus host disease and hepatic veno-occlusive disease of matched sibling and unrelated hematopoietic stem cell transplantation, the following studies were conducted. Methods:A retrospective analysis of 80 β-thalassaemia major patients in the southern hospital between January 2012 and December 2017 for matched hematopoietic stem cell transplantation, and 35 of them had a splenectomy before the transplant. Cox model adjustment, t test and χ2 test were used to compare the incidence of neutrophil implantation time, hemoglobin implantation time, platelet implantation time, infection, graft versus host disease and hepatic vein occlusion. Results:Neutrophilic granulocytes and platelets were implanted more rapidly in patients who underwent splenectomy than those who did not (P < 0.05).There was no significant difference in the incidence of infection, graft versus host disease and hepatic vein occlusion. Conclusion: For level of Ⅱ-Ⅲ β-thalassaemia major patients, hypersplenism can cause delayed reconstruction of hematopoietic stem cell transplantation, while before transplantation splenectomy to speed up the implantation of hematopoietic stem cell transplantation, and does not increase the incidence of complications after transplantation. Disclosures No relevant conflicts of interest to declare.

Background: Peripheral blood stem cells (PBSC) are increasingly used as a source of stem cells for either autologous or allogeneic hematopoietic transplantation in children.Although technically similar to adult procedures, PBSC harvest may be difficult in young children, especially in the very small children. Aim: In this study, we aimed to evaluatethe safety and efficacy of harvesting peripheral blood hematopoietic stem cells in very small children,and to provide a guideline. Methods: Between Jan 2013 to Mar 2016, we evaluated 118 children weighing 20 kg or less, with the smallest patient weighing 11 kg. The patients had a median age of 59 months and included 72 children with thalassemia major and 46 young donors. The granulocyte-colony stimulating factor (G-CSF) analogs were used at a dose of 10 mg/kg/day administered subcutaneously once a day and receiving oral calcium for five days before harvesting. Blood was withdrawn at a mean rate of 30-40 ml/min through a temporaryfemoral vein catheter (12 or 14 guage) to ensure adequate blood flow and returned through a larger catheter in a peripheral vein.Total nucleated cells(TNC) and CD34+ cells were estimated in the peripheral blood before collection of the apheresis product. Results: We collected sufficient products from all the children with one to three apheresis procedures. No serious complication was detected in all children and all aphereses were completed within 4 hours.The volume of blood per kilogram processed for each apheresis ranged from 55 to 160ml (median, 85ml). The median number of TNC and CD34+ cells collected were 12×108/kg and 15×106/kg per apheresis, respectively. Conclusions:We conclude that collection of PBSC is a safe and practical procedure in children, even in very small children. Disclosures No relevant conflicts of interest to declare.

Background : Adrenal leukodystrophy is one of the beta oxidation peroxidase disease, an x-linked recessive heredity, can lead to very long chain fatty acids in tissue accumulation, result in adrenal and cerebral white matter of the progressive deterioration. Hematopoietic stem cell transplantation (HSCT) is a curative treatment for early childhood cerebral type of X-ALD. We report two cases of haploid hematopoietic stem cell transplantation for the treatment of adrenal leukodystrophy. Methods: Two patients were male, 5 years old, 6 years old, respectively, by the gene diagnosis of adrenal leukodystrophy.Case 1 received father haploid bone marrow and peripheral blood stem cell(HLA7/10 match)combine with unrelated umbilical cord blood(HLA 9/10 match). Case 2 received sister haploid bone marrow and peripheral blood stem cell(HLA5/10 match)combine with unrelated umbilical cord blood(HLA 7/10 match).Case 1 conditioning regimen use cyclophosphamide, fludarabine and thiotepa.Case 2 conditioning regimen use cyclophosphamide , busulfan ,fludarabine , rabbit anti-human thymocyte immunoglobulin and thiotepa.Case 1 bone marrow infused total nucleated cell dose was 2×108/kg (CD34+:0.75%,CD3+:1.67%), peripheral blood stem cell infused total nucleated cell dose was 29×108/kg (CD34+:0.19%,CD3+:4.96%), unrelated umbilical cord blood infused total nucleated cell dose was 1.16×108/kg (CD34+:0.44%). Case 2 bone marrow infused total nucleated cell dose was 0.89×108/kg (CD34+:0.74%,CD3+:2.29%), peripheral blood stem cell infused total nucleated cell dose was 25.85×108/kg (CD34+:0.5%,CD3+:15.23%), unrelated umbilical cord blood infused total nucleated cell dose was 0.39×108/kg (CD34+:0.93 %). GVHD prophylaxis Case 1 used mycophenolate mofetil,sirolimus,while Case 2 used mycophenolate mofetil,tacrolimus and sirolimus. Results: The absolute neutrophil count (ANC) greater than 0.5×109/L of two patients were 21 and 23 days , case 1 had a successful engraftment with father donor-derived as case 2 had a successful engraftment with umbilical cord blood donor-derived.Follow-up time of 35 months and 3 months respectively,Case 1 Check head MRI again show a smaller lesionswhile Case 2 progression-free.Two cases' C24:0, C26:0, C24:0 / C22:0, C26:0 / C22:0 of plasma decline than before transplantation. Conclusion: In the absence of HLA-match donor, haploid bone marrow and peripheral blood stem cell combined unrelated umbilical cord transplantation is a effective method of treatment of adrenal leukodystrophy, but which will successful engraftment need more further studies. Disclosures No relevant conflicts of interest to declare.

Background : Fludarabine and busulfan as a reduced-toxicity Conditioning regimen has been widely used for hematopoietic stem cell transplantation(HSCT) in pediatric β-thalassemia patients,however,the data of transplant-related infections in this population are scare. Methods:This retrospective study assessed the clinical features of infections in 265 children who received HSCT in pediatric department of Nanfang Hospital from January 2011 to December 2015,including 151 with allogeneic hematopoietic stem cell transplantation(allo-HSCT) from unrelated donors(UDs) who are all well-matched human leukocyte antigens, 87 with HSCT from matched sibling donors(MSDs),27 with genetic haploid transplantations from matched donors(father donors=13,mother donors=13,aunt donor=1). the median age was 6 years(range:1.7 to 16 years),and the ratio of male to female patients was 1.6(163:102).The median follow-up time was 35 months(range:8-68 months). Results: The cumulative incidence of neutrophil recovery was 97.70%,98.01% and 100% in MSD-HSCT,UD-PBSCT and genetic haploid,respectively.Most of the infections took place in the oral cavity(58.72%),respiratory tract, digestive tract and skin.Bacteremia developed in 46(17.36%) patients and 67.39% happened within 30 day of transplantation,the median time was +3 day(rang-2 to +11) when Bone marrow is barren period. G_ bacteria(68%) were the most commom causes of infections;Escherichia coli,Klebsiella pneumoniae and Pseudomonas aeruginosa accounted for the most of G- bacteria infections.Fungal turn out in 16(6.04%) patients,25% of the people was diagnosed with a probable,invasive fungal disease.The cumulative incidence of cytomegalovirus(CMV) and herpes zoster was 4.9% and17.36% .The cumulative incidence of grade II-IV aGVHD was 4.26%.17 patients died,9 of them suffered GVHD and complicated with severe pneumonia, 3 due to infection complicated with heart failure,4 of them were attributed to severe infections lead to multiple organ failure,and one appeared pancytopenia 6 months after transplantation , combined EB virus infection, cytomegalovirus infection, However, the use of MabThera treatment ineffective ,he died of liver failure,and brain hemorrhage.The estimate 5-year overall survival were 95%,94% and 84% in MSD-HSCT,UD-PBSCT and genetic haploid,respectively. Conclusions:In conclussion,our data suggests that the myeloablative conditioning regimen transplantation based on fludarabine and busulfan provided an effective measure for pediatric β-thalassemia patients with infections comparable to other transplant center reports but higher overall survival and disease free survival. More efforts should be made to rational use of antimicrobial drugs, empirical antifungal agents and strengthen the mouth, lungs, anus and other vulnerable parts of the care ,especially after the transplant neutropenic period. Disclosures No relevant conflicts of interest to declare.

Background: Cytokines and infection are closely related. One of the hot spots is the indexes which can early diagnose and predict prognosis of febrile neutropenia patients with acute leukemia. It is importment to find predictors of infection in febrile neutropenia patients. Aim: To investigate the variation of CRP(C-reactive protein), IL-6(interleukin 6), IL-8(interleukin 8) and IFN-γ (interferon γ) in children with acute leukemia before and after febrile neutropenia, and evaluate the reliability of plasma interleukin (IL) and CRP levels as indicators of febrile neutropenia patient. Methods: We selected 40 cases of children with acute leukemia from Pediatric department of Nanfang Hospital,Southern Medical University,including 27 cases of acute lymphoblastic leukemia(67.5%),13 cases of acute myeloid leukemia(32.5%). The mean age was 7 years(range:1-14).We used Luminex immunoassay to detected levels of cytokines, which include CRP, IL-6, IL -8 and IFN-γ. Serum samples were collected before chemotherapy(T0),3 days after chemotherapy(T1), 1 day after confirmation of febrile neutropenia, (T2), 3 days after febrile neutropenia (T3), 7 days after febrile neutropenia (i.e. the use of antibiotics 7 days,T4), recovery after chemotherapy(T5). Results: Compared T1、T5 to T0, the levels of CRP, IL-6 were no statistically significant(P>0.05). Compared T1 to T0, the levels of IFN-γ and IL -8 were statistically significant(P=0.005 and P=0.002); Compared T5 to T0 and T5 to T1, the levels of IFN-γ and IL-8 were no statistically significant(P>0.05). In T0, T1 and T5 phase, the levels of IL-6, IL-8, IFN-γ and CRP were not correlated (P>0.05). Compared T2, T3 to T0, the level of CRP increased significantly after infection early in the fever, and the level of CRP increased in 24 hours.Compared T2, T3 to T0, the levels of IL-6, IL-8 were statistically significant, the level of IL-8 decreased after infection, but the level of IL-6 level increased in 24 hours.There were significant positive correlation between CRP and IL-6 in T2, T3 and T4 phase. Conclusions. The level of CRP increased significantly after infection early in the fever, and the level of CRP increased in 24 hours. the level of IL-8 decreased after infection,but the level of IL-6 level increased in 24 hours.The levels of CRP, IL-8 and IL-6 can be useful markers to identify febrile neutropenia in children with acute leukemia. Disclosures No relevant conflicts of interest to declare.

Background: Research has shown that the relationship between cytokines and graft versus host disease is close, but there are still a lot of cytokines and graft versus host disease relationships which are not clear. At the same time, thalassemia patients with graft versus host disease may exist in particularity. Objects: To investigate the relationship between some cytokines and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in β-thalassemia major patients. Methods: The study included 16 patients who developed graft-versus-host disease (GVHD) after receiving hematopoietic stem cell transplantation in the Department of Pediatrics in Nanfang Hospital between the time period of 2011 July to 2015 March. We observed the dynamic variation of interleukin 6 (IL-6), interleukin 8(IL-8), interleukin 12(IL-12), tumor necrosis factor-α(TNF- α) and macrophage migration inhibitory factor(MIF) in 16 patients before onset of GVHD, when GVHD occurred, at fourth and seventh day after onset of GVHD, and when GVHD almost disappeared. Results: There was a significant difference in serum levels of interleukin-6, interleukin-12, tumor necrosis factor-α, macrophage migration inhibitory factor at different times. The highest levels of different cytokines appeared when GVHD occurred, followed by those at seventh day after it occurred. There was also a significant difference in serum levels of interleukin-8 at different times, and the highest level appeared at fourth day after GVHD occurred. There is a significant positive correlation between IL-6 and IL-12,IL-12 and TNF-α,IL-12 and MIF,TNF- α and MIF when GVHD occurred. There is a significant positive correlation between IL-12 and TNF-α when GVHD occurred and on the fourth day . There is a significant positive correlation between IL-12 and TNF-α,IL-12 and MIF,TNF-α and MIF when GVHD appeared on the seventh day. There is a significant positive correlation between IL-6 and IL-12,IL-12 and TNF-α,IL-12 and MIF,TNF-α and MIF when GVHD almost disappeared. Conclusion: The dynamic expression of IL-6,IL-8,IL-12,TNF-α and MIF can estimate the immune function of β-thalassemia major patients who develops graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, and can be used as the immunobiology indicators for the early diagnosis of graft-versus-host disease. IL-6, IL-8, IL-12, TNF-α and MIF may have correlation with each other in different time of graft versus host disease. Disclosures No relevant conflicts of interest to declare.

Background: Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for thalassemia major (TM). Bone marrow (BM) and cord blood (CB) are biologically different stem cell sources. Methods: We analyed the results of a retrospective study of HSCT in 29 chlidren (median age at transplantation was 6 years old) with β-TM after the combined infusion of G-CSF primed bone marrow (BM) and cord blood (CB) from the same transplantation to outcomes in children with β-TM who had received BM (n=26).Patients treated with bone marrow transplant (BMT)were closely matched to the co-transplant group in terms of age, human leucocyte antigen (HLA) matching and duration of follow-up.Compared to BMT group, the donors in co-transplant group were younger (median age 2 vs. 4 years old, p=0.015) Results: In the co-transplant group,the mean total nucleated cells (TNC) was 2.63×108/kg(range,1.26-3.72×108/kg) and the CB was 0.39×108/kg(range,0.27-0.71×108/kg), respectively.The mean TNC (3.02 vs. 2.79×108/kg, p=0.532) and CD34+cells (7.55 vs. 6.94×106/kg, p=0.227) were insignificantly difference between the co-transplant group and BMT group. Of the 53 patients who had successful engraftment,patients who received a co-transplant had a lower incidence of ≥ grade II acute (3.3 vs. 20.8, p=0.047) and chronic(0vs.16.7%,p=0.022) graft versus host disease (GVHD) compared to BM transplant (BMT) recipients. There was no graft rejection (GR) after co-transplant, but GR happened two patients (7.7%) in BMT group(p=0.132).We found insignificant difference in neutrophils (18.7vs.19.9 days, p= 0.956) and platelet (24.7vs. 26.2 days, p=0.235) engraftment time between the co-transplant and BMT group. All patients were followed up until june 30, 2014, the 5 year probability of overall survival (OS), transplant free survival (TFS) and transplant-related mortality (TRM) were similar for the two groups. The 5-year probability of OS and TFS were 89.7% and 89.7% in the co-transplant group, 92.3%and 84.6% after BMT (P=0.740 and 0.573, respectively). Conclusions: Our data suggest that the lower risk of GVHD is retained with co-transplant group. The incidence of GR lower in the co-transplant group, although a larger cohort of patients will be needed to confirm this inital obser-vation.Here,we suggest transplantation of G-CSF primed BM a,nd CB of same sibling appears to be a feasible and effective strategy to further optimize outcomes of HSCT for TM with decreasing the risk of the occurrence of GVHD. Disclosures No relevant conflicts of interest to declare.