BACKGROUND:The CD4+CD25+FOXP3+Treg cells have immunosuppression effect, and it is speculated that these cells may restrain the occurrence of acute graft-versus-host disease. OBJECTIVE:To observe the variety of the CD4+CD25+FOXP3+Treg cells in the peripheral blood from donors before and after granulocyte colony stimulating factor mobilization, and study the relationship between CD4+CD25+FOXP3+Treg cells and acute graft-versus-host disease. METHODS:Ninety patients with malignant blood diseases who undertook al ogeneic hematopoietic stem celltransplantation and their donors were observed. Granulocyte colony stimulating factor 5μg/kg was injected subcutaneously into the donor per 12 hours for 5 days, and the stem cells were col ected before and after mobilization. The ratio of CD4+CD25+FOXP3+Treg cells in the peripheral blood was detected before and after mobilization with flow cytometry, and the ratio of these cells in the stem cellsuspension was measured by the same method. The patients were divided into two groups according to the CD4+CD25+FOXP3+Treg cells ratio:high dosage group (≥5%) and low dosage group (<5%). The incidence of acute graft-versus-host disease was observed in the two groups after transplantation. RESULTS AND CONCLUSION:The ratio of the CD4+CD25+FOXP3+Treg cells in the donor before and after mobilization were 11.3%and 1.5%,respectively, and there was a significant difference (P<0.05). The ratio of the CD4+CD25+FOXP3+Treg cells was 3.4%in the patients with acute graft-versus-host disease, and 15.7%in the patients with no acute graft-versus-host disease, showing a significant difference (P<0.05). After hematopoietic reconstitution, the incidence of acute graft-versus-host disease was 18.4%in the high dosage group and 48.1%in the low dosage group, and there was a significant difference between the two groups (P<0.05). Therefore, the granulocyte colony stimulating factor can lower the ratio of CD4+CD25+FOXP3+Treg cells in the human peripheral blood. The increase in CD4+CD25+FOXP3+Treg cells can restrain the occurrence of acute graft-versus-host disease.

BACKGROUND:The prognosis of malignant hematologic diseases has improved greatly with the application of the hematopoietic stem cell transplantation. Peripheral blood stem cell transplantation (PBSCT) has been used as an alternative to bone marrow transplantation (BMT).OBJECTIVE:To observe curative effect and clinical outcome in 53 patients with hematological malignancy undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT) or autologous peripheral blood stem cell transplantation (auto-PBSCT).DESIGN:Randomized controlled study.SETTING:BMT Center, Hematology Department of the First Affiliated Hospital of Zhengzhou University.PARTICIPANTS:From July 2003 to May 2006, 53 patients (33 males and 20 females) with a median age of 37 years underwent PBSCT. Thirty-five patients received allo-PBSCT, including 13 of acute myelocytic leukemia (AML), 7 of acute lymphocytic leukemia (ALL), 10 of chronic myelocytic leukemia (CML), 2 of multiple myeloma (MM), and 3 of myelodysplastic syndrome (MDS). Eighteen patients underwent auto-PBSCT, including 7 AML, 6 ALL, 2 MM, and 3 non-Hodgkin lymphoma (NHL). Thirty-three donors (20 males and 13 females) with a median age of 35 age in the allo-PBSCT were HLA-identical siblings, 2 donors (5.7%) had one mismatch. Sixteen allografts were sex mismatched. Study was authorized by the Ethic committee of the hospital, and all patients had signed an inform consent.METHODS:① PBSC were mobilized with granulocyte colony-stimulating factor (G-CSF) or chemotherapy combined with G-CSF. A median of 6.2×106 CD34+ cells/kg was infused for allo-PBSCT and 3.0×106 CD34+ cells/kg was infused for auto-PBSCT. Amended BU/CY was used as conditioning regimen in allo-PBSCT and MAC was used in auto-PBSCT. Methotrexate (MTX) combined with cyclosporine A (CsA) and mycophenolate mofetil (MMF) was used as graft-versus-host disease (GVHD) prophylaxis. ALG was used in 1 patient with 1 locus mismatched in allo-PBSCT. ② Time to engraftment was calculated from the time of transplantation to neutrophil recovery ≥ 0.5×109 L-1 and platelet recovery ≥ 20×109 L-1, GVHD and relapse were observed until 1 year of follow-up.MAIN OUTCOME MEASURES:① Time to neutrophil and platelet recovery; ② GVHD occurrence after transplantation; ③ outcome of treatment.RESULTS:All the 53 patients were analyzed. ① Engraftment of neutrophils (> 0.5×109 L-1) and platelets (> 20×109 L-1) was achieved at a median of 13 days for neutrophils and 19 days for platelets in auto-PBSCT, and 12 days and 15 days respectively in allo-PBSCT. ② In allo-PBSCT, I-VI acute GVHD occurred in 31.4% cases, and chronic GVHD developed in 71.4% cases. ③ The relapse rate was 38.9% in auto-PBSCT, and 5.7% in allo-PBSCT. CONCLUSION:PBSCT can provide rapid hematopoietic reconstitution. It is an important method to cure the malignant hematologic diseases.

Objective To investigate the effect of postremission consolidation therapy with intermedium-dose cytarabine (MDAC) in elderly patients with acute myelogenous leukemia (AML). Methods Clinical data of 61 elderly AML patients (except M3) in postremission who achieved complete remission (CR) in two period of remission induction program were retrospectively analyzed. Results There were 26 cases in MDAC group and 35 cases in standard-dose cytarabine (SDAC) group. In MDAC group and SDAC group, the relapse free survival (RFS) time were 42.7 months and 16.0 months respectively (P= 0.002), the overall survival (OS) time were 44.6 months and 18.2 months respectively (P= 0.004), and the cumulative relapse frequencies rates were 26.9 % (7/26) and 54.3 % (19/35) respectively (x 2= 4.567, P= 0.033). However, 3 years OS rate of the two groups were 23.1%(6/26) and 8.6%(3/35) (x 2=2.496, P=0.114) , and there was no significant difference in the incidence of adverse reactions between the two groups (all P > 0.05). Conclusion MDAC could improve RFS and OS for the elderly AML patients in postremission who received CR in the early stage, and the incidence of adverse reactions is similar to that of SDAC.

BACKGROUND:For pediatric patients with aplastic anemia in China, it is difficult to find human leucocyte antigen-matched sibling donors that are mostly replaced by parental donors.
OBJECTIVE:To retrospectively analyze the clinical efficacy and safety of parental haploidentical peripheral blood hematopoietic stem cel transplantation in children with relapsed and refractory severe aplastic anemia.
METHODS:Seventeen children with relapsed and refractory severe aplastic anemia who had no matched sibling or unrelated donor and failed to respond to immunosuppressive therapy were subjected to parental haploidentical peripheral blood hematopoietic stem cel transplantation. A conditioning regimen of fludarabine+cyclophosphamide+rabbit anti-human thymocyte immunoglobulin antibody and the triple therapy of methotrexate, cyclosporine A and mycophenolate mofetil were applied to prevent graft-versus-host disease.
RESULTS AND CONCLUSION: (1) Of the 17 children, 16 cases (94%) reached hematopoietic reconstitution, and the median time of neutrophils≥ 0.5×109/L and platelets≥ 20×109/L was 13 (11-15) days and 17 (12-28) days, respectively. (2) Incidence of acute graft-versus-host disease was 47% (8 of 17 cases), including 29% (5/17) of grades I-II and 18% (3/17) of grades III-IV. Incidence of chronic graft-versus-host disease was 41% (7/17). (3) With a median folow-up duration of 268 (43-753) days, the overal survival rate was 70.6% (12/17). Five dead cases (29%) belonged to transplantation-related death, including one case of fungal skin infections, one case of graft-versus-host disease, three cases of severe lung infection. No relapse case was reported. These findings indicate that if there are no matched sibling or unrelated donors and the immunosuppression effect is poor, parental haploidentical peripheral blood hematopoietic stem cel transplantation is a safe and effective salvage treatment for children with relapsed and refractory severe aplastic anemia.

BACKGROUND:Cytokine induced kil er cells therapy as an effective means of adoptive immunotherapy, becomes a new way to treat acute myeloid leukemia. But, the researches about sequential cytokine induced kil er cells therapy after autologous peripheral blood stem celltransplantation in acute myeloid leukemia patients are stil less, which deserve further research.
OBJECTIVE:To observe the clinical efficiency and safety of sequential cytokine induced kil er cells therapy after autologous peripheral blood stem celltransplantation in acute myeloid leukemia M2 patients.
METHODS:Total y 45 patients with low-or intermediate-risk acute myeloid leukemia M2 were recruited in this study. Among them, 19 patients received sequential cytokine induced kil er cells therapy after autologous peripheral blood stem celltransplantation and 26 patients only received autologous peripheral blood stem celltransplantation. The relapse rate, disease-free survival, and overal survival were compared between two groups, and safety of cytokine induced kil er cells therapy was observed.
RESULTS AND CONCLUSION:(1) Compared with the patients only receiving autologous peripheral blood stem celltransplantation, the relapse rate was lower (21.05%vs. 38.46%;P<0.05), and elevated percentages of the disease-free survival and overal survival were observed in the patients receiving sequential cytokine induced kil er cells therapy after autologous peripheral blood stem celltransplantation (P<0.05). (2) The 19 patients who received sequential cytokine induced kil er cells therapy after autologous peripheral blood stem celltransplantation al completed the treatment scheme successful y. Only four patients appeared to have chil s and fever, and no more side effects were observed. These findings suggested that the sequential cytokine induced kil er cells therapy after autologous peripheral blood stem celltransplantation can improve the disease-free survival and overal survival of low-or intermediate-risk acute myeloid leukemia M2 patients without remarkable side effects, which is a safe, effective and feasible way for the treatment of acute myeloid leukemia M2.

Objective To observe curative effect and clinical outcome in 30 recipients undergoing allogcneic peripheral blood stem cell transplantation (PBSCT) combined with bone marrow transplantation (BMT). Methods 30 patients with a median age of 32.6 years underwent allo-HSCT, of which 11 patients with AML, 14 patients with ALL, and 5 patients with CML They all have a HLA-identical sibling. PBSCswere mobilized with G-CSF. Three hundreds milliliter bone marrow blood was transplanted to the patients on the day that the PBSC was transplanted. Amended Bu/Cy was used as the conditioning regimen. MTXcombined with CsA and MMF was used as GVHD prophylaxis. Results A median number of mononuclear cells of (5.13±2.6)x10~8/kg recipient's weight was collccted from peripheral blood, and (1.3±0.6)x10~8/kgrecipient' s weight from bone marrow blood. Engraftment of neutrophils and platelets was achieved at a median of (12.1±3.25) days and (14±5.33) clays respectively. Ⅰ - Ⅱ acute GVHD occurred in 40.0 % cases,Ⅲ - Ⅳ acute GVHD occurred in 3.3 % cases, and chronic GVHD developed in 43.3 % cases. Severe cGVHD developed in 3.3% cases. The 2 years disease free survival rate (DFS) by the day of transplantation was 72.0 %. Conclusion PBSCT combined with BMT was effective to cure leukemia. The results also suggested that PBSC recipients had an lower incidence of aGVHD and cGVHD as compared with previous reports.

Objective To analyze the clinical characteristics and prognostic factors of elderly patients with cytogenetically normal acute myeloid leukemia (CN-AML). Methods A total of 104 initial CN-AML patients were enrolled in this retrospective study. The clinical characteristics were collected and analyzed retrospectively. Factors affecting complete remission (CR) were analyzed by using chi square test. Univariate and multivariate analyses of prognostic factors were performed by using Kaplan-Meier and Cox hazard regression model respectively. Results After the first chemotherapy, 72 of 104 patients were able to be evaluated the efficacy, the CR rate was 38.9%(28/72) and total response rate was 55.6%(40/72). The white cell count<100 × 109/L and NPM1 mutation were related to a higher CR rate [59.4%(38/64) vs. 12.5%(1/8), 83.3%(10/12) vs. 36.4%(8/22), P<0.05]. Among 104 patients, the median overall survival (OS) was 6.9 months. Univariate analysis results demonstrated that age≥70 years, secondary AML, white cell count≥100×109/L, FLT3-ITD mutation, CD7 expression, achieving CR beyond 2 cycles of induction therapy and CCI score≥2 were influence factors on OS. In multivariable analysis, FLT3-ITD mutation (HR=7.61, 95%CI 1.80-32.11, P= 0.006) and achieving CR beyond 2 cycles of induction therapy (HR= 10.11, 95 % CI 2.38-43.03, P=0.002) were independent prognostic factors for OS in elderly patients with CN-AML. Conclusion The prognosis of elderly patients with CN-AML is the result of the combined effect of many factors, FLT3-ITD mutation and achieving CR beyond 2 cycles of induction therapy are independent prognostic factors in elderly patients with CN-AML.

Objective To analyze the clinical features and prognosis of CD34-positive and CD34-negative adult patients with acute T-lymphoblastic leukemia (T-ALL),and to explore the value of CD34 expression for prognosis of patients with T-ALL.Methods 75 adult patients diagnosed with T-ALL from January 2012 to July 2015 in the Department of Hematology,the First Affiliated Hospital of Zhengzhou University,were analyzed retrospectively.According to the expression of CD34,the patients were divided into CD34-positive group and CD34-negative group,and then the clinical characteristics and prognosis of both groups were analyzed.Results In 75 patients,CD34-positive group had 24 (32.0 ％) patients and CD34-negative group had 51 (68.0 ％) patients.Between the two groups,there was no significant difference in these factors,such as sex,age,infiltration of liver,spleen and lymph nodes,thrombocytopenia,high white blood cell count,abnormal karyotype,complete remission within 4 weeks and central nervous system leukemia (CNSL).The proportions of patients with hemoglobin (Hb) ＜ 90 g/L and expression of myeloid lineage marker were higher in the CD34-positive group than those in the CD34-negative group (x2 =5.888,P=0.015;x2 =10.758,P =0.001,respectively).There were only 18 patients treated with hematopoietic stem cell transplantation (HSCT),57 patients were not.In patients without HSCT,the median survival time in the CD34-positive group and CD34-negative group was significant different (5 months vs.32 months,x2 =9.172,P =0.002).Conclusions CD34 expression in adult patients with T-ALL appears to be associated with Hb ＜ 90 g/L and the expression of myeloid lineage markers.For the patients without HSCT,CD34 is likely negatively related with the prognosis.

Objective To investigate the clinical features and prognosis of patients with acute leukemia (AL) in pregnancy.Methods The clinical data of 39 cases of acute leukemia in pregnancy at the First Affiliated Hospital of Zhengzhou University from January 2010 to April 2017 were collected.The clinical characteristics and prognosis were analyzed retrospectively.Results Except one case diagnosed before pregnancy,the incidence rates of AL in early,middle and late stage of pregnancy were 23.7 ％ (9/38),52.6 ％ (20/38) and 23.7 ％ (9/38),respectively.31 patients received chemotherapy and the complete response (CR) rates of AL patients in early,middle and late stage of pregnancy were 71.4 ％ (5/7),94.1％ (16/17),and 100.0 ％ (7/7),respectively.Among all the cases,31 patients received a miscarriage or induction of labor,and 8 cases had live births delivered by cesarean section.Twenty-two patients had abnormal karyotypes,which was mainly related to specific chromosomal rearrangement.Acute myeloid leukemia (AML) patients expressed high levels of CD117,CD13,CD33,and CD38,and acute lymphoblastic leukemia (ALL) patients had high expression of CD19,CD38,CD22,cCD79a,and CD58.After induction therapy,10 cases got positive minimal residual disease (MRD),7 of which achieved CR.After that,4 cases recurred,and 7 cases died in total.On the other hand,all the 19 MRD-negative patients achieved CR.Then,5 cases recurred,and 9 cases died intotal.In all patients,29 were AML while the other 10 were ALL,the CR rates in AML and ALL were 95.7 ％ (22/23) and 75.0 ％ (6/8),and the 1-year and 2-year survival rate were 53.1％ and 26.4 ％,respectively.The survival rate of AML patients was higher than that of ALL patients.Conclusions The clinical characteristics of AL patients in pregnancy are complicated and comprehensive treatment is needed.MDR is an important indicator of prognosis,and the prognosis of ALL is worse than that of AML.