Haploidentical Hematopoietic Stem Cell Transplantation for Paediatric Patients with X-linked Lymphoproliferative Syndrome.

The aim of this study was to investigate the prognostic factors of haploid hematopoietic stem cell transplantation in the treatment of X-linked lymphoproliferative syndrome. Seven children with X-linked lymphoproliferative syndrome diagnosed by XIAP gene analysis were enrolled. The conditioning regimens were tolerated in all seven patients, and the median time of neutrophil engraftment was 10 days (8-13 days), and that of platelet engraftment was 21 days (14-24 days). STR-PCR analysis on the peripheral blood cells showed complete donor origins. Four cases developed Grade I acute graft versus host disease (aGVHD), one developed Grade III aGVHD (intestinal tract), and two cases had limited chronic GVHD. Four cases had cytomegalovirus (CMV) reactivation, and two cases had Epstein-Barr virus (EBV) reactivation. One case was diagnosed as pneumocystosis, and thrombotic microangiopathy (TMA) occurred in three cases. During the follow-up period (median time of 42 months), one patient died of TMA and six patients survived. Statistical analysis showed that the status of disease remission and the positive result of virus in blood before transplantation were independent prognostic factors. Haplo-HSCT might be a curative option for children with refractory X-linked lymphoproliferative syndrome. Low-intensity conditioning regimens may reduce transplant-related mortality and improve overall survival.

[Clinical Biological Characteristics and Prognostic Factors of Children with Ph+ALL].

OBJECTIVE: To investigate the clinical biological characteristics of children with Ph+ ALL and the factors that affecting its prognostic. METHODS: 34 children with Ph+ ALL were selected retrospectively in the period from January 2006 to December 2017; the clinical biological characteristics, clinical efficacy for short-term and survival time for long-term were recorded and the related factors that affecting the clinical efficacy for short-term and survival time for long-term were evaluated. RESULTS: The median overall survival time was 16.5 months and the cumulative OS rates for 2 years and 5 years with followed-up were separately (61.57±7.09)%, (50.75±8.22)%. The median progression-free survival time was 13.5 months and the cumulative progression-free survival rates for 2 years and 5 years with followed-up were separately (54.49±6.77)%, (48.77±7.42)%. The early treatment response of patients with myeloid antigen expression were significantly lower than the patients without myeloid antigen expression (P＜0.05). The CR rate in one treatment course of patients with good response for early treatment response group were significantly higher than the patients with poor response for early treatment response (P＜0.05). The CR rate in one treatment course of the patients with TKI addition in induction therapy period group were significantly higher than the patients with chemotherapy used alone（P＜0.05）. The OS rate and PFS rate of patients in chemotherapy + TKI + allo-HSCT and chemotherapy + TKI group were significantly higher than the patients with chemotherapy used alone group（P＜0.05）. Univariate analysis showed that the factors affecting OS rate of children with Ph+ ALL for 2 years with followed-up included baseline WBC count level, LDH level, distances between lower hepatic margin and costal margin, distances between lower splenic margin and costal margin, combined myeloid antigen (+), early treatment response, FCM-MRD status after one treatment course, BCR-ABL status after one treatment course and TKI application (P＜0.05) and the factors that the affecting PFS rate of children with Ph+ ALL for 2 years with followed-up included LDH level, distances between lower hepatic margin and costal margin, distances between lower splenic margin and costal margin, combined myeloid antigen (+), early treatment response, FCM-MRD status after one treatment course, BCR-ABL status after one treatment course and TKI application (P＜0.05). Multivariate analysis showed that the distances between lower splenic margin and costal margin 3 cm were independent risk factors on OS rate and PFS rate of children with Ph+ ALL (P＜0.05). CONCLUSION: Children with Ph+ ALL possess unique clinical and biological features. The prognosis of patients with chemotherapy used alone is more poor, and the combination of chemotherapy and TKI can effectively increase the survival benefit; patients with Ph+ ALL combined with myeloid antigen (+) shows a poor early treatment response. while the distances between lower splenic margin and costal margin 3 cm are independent risk factors on clinical prognosis of children with Ph (+) ALL.

[Clinical Efficacy of Autologous Hematopoietic Stem Cell Transplantation Using Tumor-ablative Conditioning Regimen for Patients with Refractory/Relapsed Non-Hodgkin's Lymphoma].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Admissibility analysis for linear singular systems with time-varying delays via neutral system approach.

This paper studies the admissibility problem for a class of linear singular systems with time-varying delays. In order to highlight the relations between the delay and the state, the singular system is transformed into a neutral form. Then, an appropriate type of Lyapunov-Krasovskii functionals is proposed to develop a delay-derivative-dependent admissibility condition in terms of linear matrix inequalities. The derivation combines the Wirtinger-based inequality and reciprocally convex combination method. The present criterion is also for the stability test of retarded and neutral systems with time-varying delays. Some examples are provided to illustrate the effectiveness and the benefits of the proposed method.

[Clinical Efficacy of Decitabine Combined with CAG Regimen for Myelodysplastic Syndrome-RAEB and Refractory Acute Myeloid Leukemia].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Transplantation of umbilical cord mesenchymal stem cells combined with haploidentical hematopoietic stem cells for 36 patients with refractory/relapsed myeloid leukemia].

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.

[Clinical observation of haploidentical-hematopoietic stem cell transplantation combined with human umbilical cord-derived mesenchymal stem cells for severe aplastic anemia-II].

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.

Reduced intensity conditioning, combined transplantation of haploidentical hematopoietic stem cells and mesenchymal stem cells in patients with severe aplastic anemia.

We examined if transplantation of combined haploidentical hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) affected graft failure and graft-versus-host disease (GVHD) in patients with severe aplastic anemia (SAA). Patients with SAA-I (N = 17) received haploidentical HSCT plus MSC infusion. Stem cell grafts used a combination of granulocyte colony-stimulating factor (G-CSF)-primed bone marrow and G-CSF-mobilized peripheral blood stem cells of haploidentical donors and the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs), respectively. Reduced intensity conditioning consisted of fludarabine (30 mg/m2·d)+cyclosphamide (500 mg/m2·d)+anti-human thymocyte IgG. Transplant recipients also received cyclosporin A, mycophenolatemofetil, and CD25 monoclonal antibody. A total of 16 patients achieved hematopoietic reconstitution. The median mononuclear cell and CD34 count was 9.3×10(8)/kg and 4.5×10(6)/kg. Median time to ANC was >0.5×10(9)/L and PLT count >20×10(9)/L were 12 and 14 days, respectively. Grade III-IV acute GVHD was seen in 23.5% of the cases, while moderate and severe chronic GVHD were seen in 14.2% of the cases. The 3-month and 6-month survival rates for all patients were 88.2% and 76.5%, respectively; mean survival time was 56.5 months. Combined transplantation of haploidentical HSCs and MSCs on SAA without an HLA-identical sibling donor was safe, effectively reduced the incidence of severe GVHD, and improved patient survival.

[Transplantation of haploidentical-hematopoietic stem cells combined with two kind of third part cells for chronic aplastic anemia: one case report].

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.

[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].

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.

[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].

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 donor's purified CD34(+) cells for treatment of poor graft function following allogeneic hematopoietic stem cell transplantation].

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.

[Efficacy of haploidentical allogeneic bone marrow hematopoietic stem cell transplantation combined with umbilical cord blood derived mesenchymal stem cells for severe aplastic anemia].

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].

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.

[Prediction of the GVHD after allo-HSCT by sequence similar matching method].

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.