Efficacy and Safety of Posaconazoleon for Primary Antifungal Prophylaxis against Invasive Fungal Disease in Patients with Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and clinical safety of posaconazoleon primary antifungal prophylaxis against invasive fungal disease (IFD) in patients with stem cell transplantation.</p><p><b>METHODS</b>At the start from preconditioning regimen, 45 patients without IFD were administered with posaconazoleon until neutrophils greater than 0.5×10/L, 35 patients treated with micafungin were enrolled in control group. The incidence, risk factors of IFD and side effects of medicines were evaluated.</p><p><b>RESULTS</b>Of the total 80 patients, 13(16%) had IFD within 100 days after allo-HSCT. The overall survival was significantly different between patients with or without IFD by Kaplan-Meier survival curve analysis (P<0.05). Out of the 45 cases in posaconazoleon group, IFD occurred in 4 cases (9%). In contrast, the incidence of IFD in control group was 26%(9 out of 35) (P<0.05). The risk factors of IFD and side effects were not significantly different between 2 groups(P>0.05).</p><p><b>CONCLUSION</b>The primary prevention efficancy of IFD by posaconazoleon after allo-HSCT is much better than that of micafungin with well tolerability and satisfactory efficacy.</p>

Hematopoietic Reconstitution and Prognosis of HLA Matched and Haploidentical Hematopoietic Stem Cell Transplantation Using Modified FC/ATG Conditioning for Treatment of Severe Aplastic Anemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyse the feasibility and compare differences between hematopoietic reconstitution and prognosis of patients with severe aplastic anemia(SAA) after matched sibling donor (MSD) or haploidentical family donor (HFD) hematopoietic stem cell transplantation (HSCT) using the modified FC/ATG conditioning.</p><p><b>METHODS</b>The clinical data of 56 patients with SAA who received HSCT in First Affiliated Hospital of Chinese PLA General Hospital from January 2011 to June 2016 were analyzed retrospectively. The hematopoietic reconstitution, graft verus host disease (GVHD), transplantation related toxicity (TRT) and prognosis after transplantation were compared. Furthermore, the modifed conditioning FC/ATG included low-dose cyclophosphamide (total dose 100 mg/kg), infustion of third-party donor-derived mesenchymal stem cells.</p><p><b>RESULTS</b>All 56 patients with MSD-HSCT or HFD-HSCT achieved hematopoietic reconstitution. Among them, not only the recovery of neutrophils and platelets, but also the incidences of III-IV aGVHD, extensive cGVHD and TRT were not significantly different (the P value were 0.58, 0.61, 0.73, 0.73 and 0.67, respectively). After following-up for 32(2-66) months, 48 patients alive well, the 1-year overall survival rates were 86% in HFD-HSCT group and 89% in MSD-HSCT group, respectively (P=0.58).</p><p><b>CONCLUSION</b>After HSCT using the modifed FC/ATG conditioning, patients with SAA achieved stable engraftment, low toxicity, mild GVHD and excellent outcomes. Furthermore, the HFD-HSCT achieved comparable outcomes to MSD-HSCT and may be served as an alternate therapy for patients with SAA.</p>

Clinical Efficacy of Autologous Hematopoietic Stem Cell Transplantation Using Tumor-ablative Conditioning Regimen for Patients with Refractory/Relapsed Non-Hodgkin's Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the safety and effectiveness of autologous hematopoietic stem cell transplantation (auto-HSCT) using tumor-ablative conditioning regiment for patients with refractory/relapsed non-Hodgkin's lymphoma.</p><p><b>METHODS</b>The clinical data of 16 patients with refractory/relapsed non-Hodgkin's lymphoma received above-mentioned therapeutic regimen from January 2013 to July 2015 was analyzed retrospectively, and conditioning-related toxicity, engraftment, infection, relapse and survival rate were evaluated.</p><p><b>RESULTS</b>No conditioning-related organs' failure and mortality were found. Only 1 patient had not been engrafted, and the engraftment rate was 93.7%. The incidence of serious infection was 31.2%. The median follow-up was 20.5(1-30) months, and 3 patients died, out of them 2 patients died of relapse. Two year overall survival (OS) , disease-free survival (DFS) and relapse rates were 80.2%, 74.5% and 20.6% respectively.</p><p><b>CONCLUSION</b>Auto-HSCT using tumor-ablative conditioning regimen is safe and effective for patients with refractory/relapsed non-Hodgkin's lymphoma, and it possess a certain effect for reducing disease relapse after transplantation.</p>

Clinical Efficacy of Decitabine Combined with CAG Regimen for Myelodysplastic Syndrome-RAEB and Refractory Acute Myeloid Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic efficacy and side effects of treating patients with myelodysplastic syndrome-RAEB (MDS-RAEB) and with refractory acute myeloid leukemia (AML) by using decitabine combined with CAG regimen.</p><p><b>METHODS</b>Clinical data of 21 patients with MDS-RAEB or refractory AML from July 2011 to July 2014 were analyzed retrospectively. Among 21 patients there were 4 cases of MDS-RAEB and 17 cases of refractory AML; 12 cases were beyond 60 years old; 13 cases had high-risk karyotypes. All the patients received decitabine combined with CAG regimen consisting of decitabine 20 mg/(m(2) · d), d 1-5; aclarubicin 10 mg/d, d 6-13; cytarabine 20 mg/d, d 6-19; G-CSF 300 µg/d, d 6-19.</p><p><b>RESULTS</b>After 1 cycle of treatment with DCAG regimen, the outcome of 21 patients showed that 8 cases achieved complete remission (42.1%), 8 cases achieved partial remission (42.1%), 2 cases achieved hematologic improvement, 1 cases achieved non-remission and 2 cases died; and the 1 year overall survival rate was 67.5%. The outcome of 12 patients beyond 60 years old showed that 6 cases achieved complete renission (60%, 6/10), and the 1 year overall survival rate was 62.5%. The outcome of 13 patients with high-risk karytype showed that 6 cases achieved complete renission (54.5%, 6/11), and the 1 year overall survival rate was 61.5%. The main adverse event was myelosuppression, and non-hematological toxicity included liver dysfunction and gastrointestinal tract reaction.</p><p><b>CONCLUSION</b>Decitabine combined with CAG regimen is effective and safe for treatment of MDS-RAEB and refractory AML patients, which can prolong lives of patiens with refractory hematological diseases.</p>

Transplantation of umbilical cord mesenchymal stem cells combined with haploidentical hematopoietic stem cells for 36 patients with refractory/relapsed myeloid leukemia / 中国实验血液学杂志

This study was purposed to analyse the clinical efficacy of transplantation of umbilical cord mesenchymal stem cells (UC-MSC) combined with haploidentical hematopoietic stem cells (haplo-HSCT) for patients with refractory/relapsed myeloid leukemia. The clinical data of 36 patients received transplantation of UC-MSC combined with haplo-HSCT from January 2007 to June 2013 were summarized retrospectively, the engraftment, GVHD and 2 years-overall survival (OS) were analysed. The results showed that the median times of neutrophil count>0.50×10(9)/L and platelet count>20×10(9)/L were 12.0 days and 14.0 days, respectively. Grade III to IV aGVHD occurred in 5 out of 36 patients (13.8%). cGVHD occurred in 12 out of 32 patients (37.5%) and extensive cGVHD occurred in 2 patients. Additionally, only 3 patients (8.3%) experienced relapse. The 2-year OS rate of patients was 76.9%. It is concluded that the transplantation of UC-MSC combined with haplo-HSCT has good therapeutic efficacy for patients with refractory/relapsed myeloid leukemia, and may be served as a therapeutic method especially for patients with high risk and without well matched donor.

Association of XRCC1 genetic polymorphism with susceptibility to non-Hodgkin's lymphoma / 中国实验血液学杂志

The purpose of this study was to explore the association between X-ray repair cross-complementing group 1 (XRCC1)gene polymorphism and non-Hodgkin's lymphoma risk. A total of 282 non-Hodgkin's lymphoma (NHL) patients and 231 normal controls were used to investigate the effect of three XRCC1 gene polymorphisms (rs25487, rs25489, rs1799782) on susceptibility to non-Hodgkin's lymphoma. Genotyping was performed by using SNaPshot method. All statistical analyses were done with R software. Genotype and allele frequencies of XRCC1 were compared between the patients and controls by using the chi-square test. Crude and adjusted odd ratios and 95% confidence intervals were calculated by using logistic regression on the basis of genetic different models. For four kinds of NHL, subgroup analyses were also conducted. Combined genotype analyses of the three XRCC1 polymorphisms were also done by using logistic regression. The results showed that the variant genotype frequency was not significantly different between the controls and NHL or NHL subtype cases. Combined genotype analyses of XRCC1 399-280-194 results showed that the combined genotype was not associated with risk of NHL overall, but the VT-WT-WT combined genotype was associated with the decreased risk of T-NHL (OR: 0.21; 95%CI (0.06-0.8); P = 0.022), and the WT-VT-WT combined genotype was associated with the increased risk of FL(OR:15.23; 95%CI (1.69-137.39); P = 0.015). It is concluded that any studied polymorphism (rs25487, rs25489, rs1799782) alone was not shown to be rela-ted with the risk of NHL or each histologic subtype of NHL. The combined genotype with mutation of three SNP of XRCC1 was not related to the risk of NHL. However, further large-scale studies would be needed to confirm the association of decreased or increased risk for T-NHL and FL with the risk 3 combined SNP mutants of XRCC1 polymorphism.

Clinical observation of haploidentical-hematopoietic stem cell transplantation combined with human umbilical cord-derived mesenchymal stem cells for severe aplastic anemia-II / 中国实验血液学杂志

This study was purposed to investigate the efficacy and safety of haploidentical hematopoietic stem cells (allo-HSCT) transplantation combined with human umbilical cord-derived mesenchymal stem cell infusion (hUC-MSC) for severe aplastic anemia-II (SAA-II). Eight SAA-II patients received haploidentical allo-HSCT, the G-CSF mobilized peripheral hematopoietic stem cells and bone marrow haploidentical hematopoietic stem cells were selected as graft, the human umbilical cord-derived mesenchymal stem cells (hUC-MSC) were infused as the third party. Conditioning regimen consisted of rabbit anti-thymic lymphocytes protein(ATG), cyclophosphamide(CTX) and fludarabine(Flu). For two patients out of 8 SAA-II patients the conditioning regimen was combined with busulfan(BU). The graft versus host disease(GVHD) was prevented with CSA, MTX, ATG, CD25 and mycophenolate mofetil. The results showed that the average number of nucleated cells were 9.13×10(8)/kg, and number of CD34(+)cells were 3.76×10(6)/ kg. All the 8 SAA-II patients achieved hematopoietic reconstitution. The average time of neutrophils count>0.5×10(9)/L was 11.9 days, and average time of Plt level >20×10(9)/L was 14.6 days. The incidence of acute GVHD of I-II grade was 25%, and that of III-IVgrade was 12.5%, the transplantation-related mortality was 25%. It is concluded that haploidentical allo-HSCT combined with umbilical cord MSC infusion is an effective approach to cure SAA.

Clinical study on recombinant humanized anti-CD25 monoclonal antibody used for treating steroid-resistant acute graft versus host disease following allo-hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was purposed to investigate the efficacy and feasibility of recombinant humanized anti-CD25 monoclonal antibody for treating steroid-resistant acute graft-versus-host disease (aGVHD ) following allo-hematopoietic stem cell transplantation (allo-HSCT) . Twenty-one cases with II-IV grade steroid-resistant aGVHD after allo-HSCT were treated by intravenous injection of recombinant humanized anti-CD25 monoclonal antibody at a dose of 1 mg/(kg·d) on days 1, 4, 8. Injection was repeated after 1 week for the patients who did not achieve CR. The results indicated that 13 cases (61.9%) got complete response (CR), 4 cases out of them have been still in disease-free survival, 8 cases have been in survival with mild cGVHD, 1 cases died from AML relapse, 6 cases (28.57%) got partial response (PR), 3 cases out of them have been in survival with mild cGVHD, 3 case died from pulmonary infection, 2 cases without response died from GVHD. Overall response rate was 90.5% and long term survival rate was 71.48%. There were no infusion-associated side-effects after treatment with recombinant humanized anti-CD25 monoclonal antibody.It is concluded that recombinant humanized anti-CD25 monoclonal antibody is effective and feasible for treatment of steroid-refractory grade II-IV aGVHD after allo-HSCT.

Transplantation of haploidentical-hematopoietic stem cells combined with two kind of third part cells for chronic aplastic anemia: one case report / 中国实验血液学杂志

This study was purposed to investigate the safety and effectivity of haploidentical stem cell transplantation for chronic aplastic anemia (CAA) by using two kind of third part cells: umbilical cord derived mesenchymal stem cells (hUC-MSC) and haploidentical umbilical cord blood cells. The patient is a girl of 12 year old with CAA for 11 years. The donor was her mother. Graft come from haploidentical hematopoietic bone marrow and peripheral blood mobilized with granulocyte colony-stimulating factor (G-CSF). The human umbilical cord derived mesenchymal stem cells and the haploidentical umbilical cord blood cells were transferred as third pard of cell. The graft-versus-host disease (GVHD) was prevented with CsA, MTX, ATG, CD25 and mycophenolate mofetil. The results indicated that the infused numbers of MNC and CD34(+) cells of donor were 7.92×10(8)/kg and 3.78×10(6)/kg, respectively. The numbers of neutrophils and platelets were over 0.5×10(9)/L and 20×10(9)/L on days 12 and 14, respectively. On day 35 the chimeras accounted for 94%. No serious complications appeared up to now. In conclusion, the preliminary results suggest that transplantation of haploidentical hematopoietic stem cells combined with two kind of third part cells is safe and satisfactory.

Efficacy of donor's purified CD34(+) cells for treatment of poor graft function following allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was aimed to evaluate the efficacy and safety of donor's purified CD34(+) cells for treatment of secondary poor graft function (PGF) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Ten patients suffering from secondary PGF after allo-HSCT in our hospital from January 2009 to December 2011 were treated with the donor's purified and G-CSF mobilized CD34(+) cells. All the patients were observed for infusion-related complication and survival status. CliniMACS system was used to separate cells, the results of sorting purified and recovery rate were calculated and statistically analysed. The results showed that the purified of CD34(+) cells reached to (89.31 ± 1.73)%, and the recovery rate reached to (93.27 ± 8.14)%; 10 patients in the process of infusion did not suffer from seriously adverse complications, all of them obtained hematopoietic recovery, neither GVHD nor infection occurred after infusion of donor's purified CD34(+) cells. It is concluded that using CliniMACS system for donor's peripheral CD34(+) separation, both the purified and recovery of CD34(+) cells are satisfied, and the infusion of donor's purified CD34(+) cell is a safe and effective method to treat secondary PGF after allo-HSCT.

Clinical analysis of high risk and refractory malignant hematologic diseases treated with haploidentical hematopoietic stem cell transplantation combined with umbilical cord mesenchymal stem cells using modified conditioning regimen / 中国实验血液学杂志

This study was aimed to investigate the efficacy of haploidentical hematopoietic stem cell transplantation (hi-HSCT) combined with umbilical cord mesenchymal stem cells (MSC) using modified conditioning regimen for the treatment of patients with refractory and relapsed or high risk malignant hematologic diseases, the clinical efficacy in 30 patients with refractory and relapsed or high risk malignant, who voluntarily received HSCT was analyzed. Among the 30 patients there were 4 relapsed cases and 26 cases of high risk malignant hematologic diseases. The above-mentioned patients included 15 AML, 9 ALL, 3 pro T lymphoblast lymphoma/leukemia, 1 spleen boundary zone lymphoma IVB, 1 NK/T lymphoma and 1 Burkitt lymphoma IVB. The results showed that the implantation was achieved in all 30 cases, among them 19 cases (63%) had aGVHD and 6 cases (20%) had III-IV aGVHD, 8 cases (32%) had cGVHD including 1 case of extensive and 7 cases of limited. Three cases relapsed at 300 days (128-455 d) after transplantation. 8 cases died, among them 1 case died of relapse, 2 cases died of IV aGVHD with relapse, 5 cases died of infection and organ failure. It is concluded, the efficacy of hi-HSCT combined with umbilical cord MSC for treatment of patients with refractory and relapsed or high risk malignant hematologic diseases is favorable.

Efficacy of haploidentical allogeneic bone marrow hematopoietic stem cell transplantation combined with umbilical cord blood derived mesenchymal stem cells for severe aplastic anemia / 中国实验血液学杂志

The aim of this study was to investigate the effect of haploidentical allogeneic bone marrow or peripheral blood hematopoietic stem cell transplantation (allo-HSCT) combined with umbilical cord blood mesenchymal stem cell (MSC) infusion in treatment of severe aplastic anemia (SAA). Five SAA patients received haploidentical allo-HSCT combined MSC infusion. HSC and MSC were collected from bone marrow or peripheral blood of haploidentical donors and umbilical cord blood respectively. After transplantation, the clinical hematopoietic reconstitution and early complications were monitored. The results indicated that all the 5 patients achieved hematopoietic reconstitution. The average time for WBC count > 2×10(9)/L was 13.8 days, and average time for Plt level > 20×10(9)/L was 17.8 days. The STR-PCR detection of patient peripheral blood at day 30 after transplantation showed that engraftment was complete donor's gene type. The communication with 1 patient was broken off because of his epilepsy, other 4 patients are all alive in diseases-free state. In conclusion, the haploidentical allo-HSCT combined with umbilical cord MSC infusion is an effective approach to cure SAA, which needs to be further studied in a large number of cases.

Curative efficacy analysis of allo-HSCT using conditioning regimen of FLAG combined with modified BUCY for refractory and relapsed patients with hematologic malignancies / 中国实验血液学杂志

This study was aimed to investigate the curative efficacy of allogenetic hemopoietic stem cell transplantation (allo-HSCT) using FLAG and modified BUCY conditioning regimen for patients with refractory and relapse or high risk hematologic malignancies. The therapeutic effect of allo-HSCT with FLAG and modified BUCY conditioning regimen on 10 patients with hematologic malignancies was analyzed. 10 patients included 2 cases of relapse (1 early relapse, 1 progression) and 7 cases of refractory (2 CR(2), 1 CR(3) and 2 PR and 1 NR) and 1 CR(1) with high risk. Among 10 cases 8 cases was diagnosed as AML, 1 case as pro-T lymphoblast lymphoma/leukemia and 1 case as spleen marginal zone lymphoma. The results showed that implantation of all the patients was successful. The relapse-free median survival time of 8 cases was 164 days (57 - 442 days) and survived up to now, 2 cases died (1 case died of pulmonary infection, 1 case died of fungus pulmonitis). In conclusion, the curative efficacy of allo-HSCT using FLAG and modified BUCY conditioning regimen for patients with refractory and relapsed hematologic malignancies is satisfactory.

Prophylactic effect of CsA, MTX, MMF combined with ATG on GVHD in patients underwent unrelated peripheral blood hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was aimed to investigate the prophylactic effect of CsA, MTX and MMF combined with ATG on graft versus host disease (GVHD) after unrelated donor peripheral blood hematopoietic stem cell transplantation (URD-PBHSCT). 33 patients underwent URD-PBHSCT with unrelated donor of HLA matched or 1 locus mismatched. The clinical data of all cases were retrospectively analyzed. URD-PBHSCT recipients received cyclosporin A+short term MTX+mycophenolate mofetil (MMF)+antithymocyte globulin to prevent GVHD (URD-ATG group), while 13 out of 33 patients were given additionally anti-CD25 antibody (URD-ATG+CD25 group). The results showed that engraftment was successfully achieved in 100% of all patients. In URD-ATG+CD25 group and URD-ATG group, the incidence of aGVHD were 23.07% and 45%, the incidence of cGVHD were 0 and 47.4% respectively. The latter was significantly higher than the former (p<0.05). The relapse rate in URD-ATG+CD25 group and URD-ATG group were 53.84% and 15% respectively, the former was significantly higher than the latter (p<0.05). The analysis on disease status of patients before transplantation displayed that the relapse rate of patients in progression status was significantly higher than that of patients in stable status (p<0.01), while the relapse rate of patients in progression status in URD-ATG+CD25 group reached to 100%. The overall survival (OS) at 1 year of patients in URD-ATG+CD25 group and URD-ATG group were 53.8% and 75% respectively, the OS at 5 years of patients in URD-ATG+CD25 group and URD-ATG group were 38.8% and 65% respectively, the OS of patients in URD-ATG group was higher than that of patients in URD-ATG+CD25 group (p<0.05). Simultaneously the OS of patients with progression status before transplantation declined obviously. It is concluded that adopting CsA+MTX+MMF+ATG as the prophylaxis of GVHD for UDR-PBSCT is effective. Reducing the dose of ATG may be good for patient in progression status.

Prediction of the GVHD after allo-HSCT by sequence similar matching method / 中国实验血液学杂志

This study was aimed to investigate the role of sequence similar matching (SSM) method in prediction of GVHD after HLA unmatched allogeneic hematopoietic stem cell transplantation (allo-HSCT). The data from 23 patients undergoing HLA unmatched allo-HSCT were analyzed and calculated by SSM method. The results showed that the incidence of acute and severe GVHD were significantly less in the allo-HSCT cases with total SSM value less than 55. In conclusion, the SSM method can be used to predict GVHD in the HLA-unmatched allogeneic hematopoietic stem cell transplantation.

Influence of granulocyte-colony stimulating factor combined with adrenocortical steroid and/or immunosuppressants on immune system of donor mice during hematopoietic stem cell mobilization / 第二军医大学学报

Objective: To explore the influence of granulocyte-colony stimulating factor (G-CSF) combined with adrenocortical steroid and/or immunosuppressants on immune system of donor mice during hematopoietic stem cell mobilization. Methods: The donor C57BL/6 mice were divided into 4 groups according to the mobilization strategies, namely, the G-CSF group (250 μg/kg for 4 days), G-CSF (250 μg/kg for 4 days) + methylprednisolone group (100 mg/ kg on day 3), G-CSF (250 μg/kg for 4 days) + methylprednisolone group (100 mg/kg on day 3) + cyclosporine A (100 mg/kg on day 3), and PBS control group. The post-mobilization T lymphocytes of C57BL/6 mice and the splenocytes of BALB/c mice were subjected to mixed lymphocyte reactions (MLR). The levels of IFN-γ, IL-4, and TGF-β 1 were determined in the supernatants of donor mice splenocytes by ELISA method and the mRNA levels of IFN-γ and IL-4 were determined by RT-PCR. Results: The results showed that the MLR-inhibitory activities in the 3 G-CSF mobilized groups were 42 %, 21 %, and 39 %, respectively; all lower than that in PBS control group (68%). IFN-γ levels in the 3 G-CSF mobilized groups were lower than that in PBS control group, but he levels of IL-4 and TGF-β 1 were significantly higher than those in PBS group(P<0.01), with no significant difference found between the 3 G-CSF mobilized groups. RT-PCR analysis found that the expression of IFN-y mRNA was obviously decreased and the expression of IL-4 was obviously increased (P<0.01). Conclusion: G-CSF combined with adrenocortical steroid and/or immunosuppressants can decrease the allogenic reaction of T lymphocytes and change the types of secreted cytokines in donor mice during hematopoietic stem cell mobilization, which may induce immune resistance in the recipients.