Progress in the treatment of ocular graft-versus-host disease / 中华实验眼科杂志

Allogeneic hematopoietic stem cell transplantation is an effective therapy for the treatment of hematological benign and malignant tumors, but the occurrence of graft-versus-host disease (GVHD) will affect the whole organs and tissues, causing serious damages to the patient's body.This not only seriously affects the life quality of patients, but also increases the mortality of patients after transplantation.Ocular GVHD is a manifestation of ocular rejection, and 60%-90% of patients with chronic GVHD are accompanied by ocular GVHD, the manifestations of which are dry eye, conjunctivitis, keratitis, and so on.Severe ocular GVHD can cause vision loss.But there is no unified treatment standard at present.The commonly used treatments include artificial tears, autologous serum eye drops, topical glucocorticoid, topical immunosuppressive agents, punctal occlusion, and contact lens wearing.The treatment progress of ocular GVHD was reviewed in this article.

Efficacy comparison of sequential treatment with first-line administration of second-generation and first-generation tyrosine kinase inhibitors in patients with Ph+ acute lymphoblastic leukemia followed by allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph +ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared.@*Results@#Of 76 Ph+ ALL patients, first-generation TKI was administered in 57 cases, second-generation TKI in 19 cases, including 10 cases of nilotinib and 9 cases of dasatinib. There was no significant difference in age, WBC counts, additional chromosomal abnormalities, time form diagnosis to transplantation, transplantation type, conditioning regimen or TKI initiation time between the two groups. Complete remission (CR) rates at the fourth week of induction therapy in first-generation TKI group and second-generation TKI group was 93.0% and 94.7% (P=1.000), respectively. Major molecular response (MMR, BCR-ABL/ABL reduce 3 log) rates meanwhile were 46.0% and 40.0% (χ2=0.169, P=0.681). Relapse rates before transplantation were 14.0% and 10.5% (P=1.000). MMR rates before transplantation were 54.4% and 68.2% (χ2=1.152, P=0.283). The 2-year overall survival (OS) rates of first-generation and second-generation TKI group were 62.0% and 94.7% (χ2=5.765, P=0.016), 2-year event-free survival (EFS) rates were 46.3% and 84.2% (χ2=5.644, P=0.018), respectively. Univariate analysis showed that second-generation TKI could improve OS (HR=0.126, 95%CI 0.017-0.939, P=0.043). Multiple factors analysis showed that second-generation TKI (HR=0.267, 95%CI 0.081-0.873, P=0.029) and MMR before transplantation (HR=0.496, 95%CI 0.254-0.968, P=0.040) were good independent prognostic factors of EFS.@*Conclusions@#There was significant difference in the efficacy of second-generation TKI and first-generation TKI for Ph+ ALL patients treated by allo-HSCT. First-line administration of second-generation TKI showed better efficacy than that of first-generation TKI for Ph+ ALL patients.

Efficacy comparison of sequential treatment with first-line administration of second-generation and first-generation tyrosine kinase inhibitors in patients with Ph+ acute lymphoblastic leukemia followed by allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph +ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared. Results: Of 76 Ph+ ALL patients, first-generation TKI was administered in 57 cases, second-generation TKI in 19 cases, including 10 cases of nilotinib and 9 cases of dasatinib. There was no significant difference in age, WBC counts, additional chromosomal abnormalities, time form diagnosis to transplantation, transplantation type, conditioning regimen or TKI initiation time between the two groups. Complete remission (CR) rates at the fourth week of induction therapy in first-generation TKI group and second-generation TKI group was 93.0% and 94.7% (P=1.000), respectively. Major molecular response (MMR, BCR-ABL/ABL reduce 3 log) rates meanwhile were 46.0% and 40.0% (χ2=0.169, P=0.681). Relapse rates before transplantation were 14.0% and 10.5% (P=1.000). MMR rates before transplantation were 54.4% and 68.2% (χ2=1.152, P=0.283). The 2-year overall survival (OS) rates of first-generation and second-generation TKI group were 62.0% and 94.7% (χ2=5.765, P=0.016), 2-year event-free survival (EFS) rates were 46.3% and 84.2% (χ2=5.644, P=0.018), respectively. Univariate analysis showed that second-generation TKI could improve OS (HR=0.126, 95%CI 0.017-0.939, P=0.043). Multiple factors analysis showed that second-generation TKI (HR=0.267, 95%CI 0.081-0.873, P=0.029) and MMR before transplantation (HR=0.496, 95%CI 0.254-0.968, P=0.040) were good independent prognostic factors of EFS. Conclusions: There was significant difference in the efficacy of second-generation TKI and first-generation TKI for Ph+ ALL patients treated by allo-HSCT. First-line administration of second-generation TKI showed better efficacy than that of first-generation TKI for Ph+ ALL patients.

Feasibility study of transplantation of penile corpus cavernosum and major pelvic ganglion in renal subserous region / 北京大学学报(医学版)

Objective:To study the feasibility of transplantation of normal rat penile corpus cavernosum and major pelvic ganglion (MPG)into the renal subserous region of a Nu /Nu mouse based on allograft technology.Methods:Penile corpus cavernosum and MPG,harvested from Sprague-Dawley (SD)rats under sterile condition,were transplanted underneath the kidney capsule of Nu /Nu mice through the mi-crosurgery instruments and surgery microscope.The histopathologic changes and cellular proliferation in the transplanted penile corpus cavernosum and MPG were then analyzed at the end of 1week and 4 weeks after transplantation.Histological staining and immunohistochemical staining were used to evaluate the main outcome measures.Results:After 1 week,the tissue morphology of the transplanted corpus caverno-sum underneath the kidney capsule of Nu /Nu mice was consistent with normal penile corpus cavernosum, and blood could be observed in the penis cavernous sinus of the graft;after 4 weeks,the mophorlogy of the tranplanted corpus cavernosum near the kidney was consistent with normal penile corpus cavernosum, while fibrosis was noteworthy in the graft away from the kidney,but blood could still be seen in the penis cavernous sinus.After 1 week,the tissue morphology of the transplanted MPG was consistent with normal MPG,multiple islet-like cell clusters could be seen in the transplanted MPG in the renal subserous re-gion,and angiogenesis could be observed near the kidney;after 4 weeks,a network of blood vessels was clearly visible away from the kidney,and islet-like cell clusters were still clearly observed in the trans-planted MPG.In addition,ki67 positive cells were observed in the transplanted penile corpus cavernosum and MPG after 4 weeks of transplantation,which indicated that there was still cell proliferation activity in the grafts.Conclusion:The transplanted corpus cavernosum and MPG underneath the kidney capsule of Nu /Nu mice could survive at least 4 weeks.Moreover,the inner structure of the transplanted corpus ca-vernosum and MPG was close to the normal tissue.The underlining mechanism may be related to the lo-cal microenvironment underneath the kidney capsule of Nu /Nu mice and the neovascularization in the transplanted grafts.

Control study of fludarabine instead of cyclophosphamide in modified busulfan-cyclophosphamide as a myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation for treatment of acute leukemia / 白血病·淋巴瘤

Objective To evaluate the fludarabine instead of cyclophosphamide in modified busulfancyclophosphamide (mBuCy) regimen as a new myeloablative conditioning regimen for the treatment of acute leukemia patients receiving allogeneic hematopoietic stem cell transplantation (HSCT).Methods The clinic data of 45 acute leukemia patients undergoing allogeneic HSCT were analyzed.Among them,23 patients received mBuCy as conditioning regimen and 22 patients received BuFlu regimen (fludarabine 40 mg·m-2·d-1 for 5 days,instead of cyclophosphamide in mBuCy).Hematopietic engraftment,regimen-related toxicity (RRT),graft-versus-host disease (GVHD),infection condition,non relapse mortality,and overall survival were compared between the two groups.Results All patients achieved hematopoietic reconstitution and complete donor chimerism except for one patient of mBuCy group died of cerebral hemorrhage during conditioning.The incidence of RRT was no significant differences (P ＞ 0.05).In BuFlu group,the incidence of virus infection was higher (P =0.009),and the incidence of Ⅲll-Ⅳ aGVHD were 26.l ％ (6/23) and 4.5 ％ (1/22) (P =0.046) in mBuCy and in BuFlu group respectively.With a median follow up of 41 months,the incidence of non relapse mortality in mBuCy group was 17.4 ％ (4/23) and in BuFlu group was 9.1％ (2/22) (P =0.665).In mBuCy group and in BuFlu group,the relapse rates were 30.3 ％ (7/23) and 40.9 ％ (9/22) (P =0.474),the 5-year overall survival rates were (55.1±11.9) ％ and (61.4±10.8) ％ (P =0.659),and disease-free survival rates were (44.5±12.1) ％ and (22.1±12.3) ％ (P =0.747),respectively.Conclusions Fludarabine instead of cyclophosphamide in mBuCy regimen as a new myeloablative conditioning regimen has well tolerance,lower incidence of sever GVHD,satisfied overall survival,but the risk of infection and replase should be considered.

Progress in diagnosis and treatment of acute graft versus host disease / 白血病·淋巴瘤

Graft versus host disease is the most common complication of allogeneic hematopoietic stem cell transplantation.It includes two different types,i.e.acute and chronic types.Acute graft versus host disease (aGVHD) is the immune response of T cells from the donor to unmatched major histocompatibility complex (MHC) from the host.It has unique pathogenesis and pathological changes and complex clinical manifestations with multiple organs involved.This paper reviewed the progress from home and abroad in diagnosis and treatment of acute graft versus host disease.

Gender mismatch, use of anti-thymoglobulin, and occurrence of graft-versus-host disease in preparative regimen are associated with high incidence of post-engraftment hemorrhagic cystitis in allogeneic hematopoietic stem cell transplantation / 白血病·淋巴瘤

Objective To evaluate the risk factors of developing post-engraftment hemorrhagic cystitis (HC) in patients receiving allogeneic stem cell transplantation (allo-HSCT).Methods Retrospective data was collected from 92 patients with acute leukemia (acute myeloid leukemia 41 and acute lymphoblastic leukemia 51) who underwent allo-HSCT from 2000 to 2010,and the association of pre-transplantation parameters with the incidence of post-engraftment HC was analyzed.Results Forty-three patients had HLA-matched donors and 49 had unrelated donors.Of these patients,25 developed HC at a median of 35 days (day +20 to +65) after allo-HSCT.In the univariate analysis,unrelated donor,gender mismatch (female donor to male recipient),conditioning containing busulfan,graft-versus-host disease (GVHD),prophylaxis with cyclosporine (CSA) + methotrexate (MTX) + mycophenolate mofetil (MMF),use of anti-thymoglobulin (ATG) and development of GVHD were associated with increased incidence of HC.In the multivariate study,gender mismatch (P =0.001),use of ATG (P ＜ 0.001),and GVHD (P =0.007) remain as independent factors for the increased risk of HC.More importantly,with these 3 factors,it is able to classify patients into 4 groups with risk of postengraftment HC at (7.7±4.6) ％,(22.9±7.1) ％,(48.2±10.5) ％,and 100.0 ％,respectively.Conclusion This retrospective study identified the gender mismatch,use of ATG in the preparation regimen,and aGVHD as important risk factors to predict the development of post-engraftment HC.Based on these risk factors,it is possible to classify patients into different risk groups for post-engraftment HC.Prospective study with a large cohort of patients is warranted to confirm the findings.Future clinical trial for HC prevention and treatment must be carried out on the intermediate and high-risk patients.

Preliminary study on IL-7Rα intervening acute graft-versus-host disease after mice allogeneic bone marrow transplantation / 白血病·淋巴瘤

Objective To establish a mouse model of acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation,and using exogenous interleukin-7 receptor alpha (IL-7Rα) intervene mice aGVHD and analyse its possible mechanism.Methods The BALB/C (H-2d) female mice as recipients were grouped by rat: the irradiation group (group A),irradiation transplantation group (group B) and IL-7Rα in the intervention group (group C),each 10.ALL mice were accepted 9 Gy60Co total body irradiation.1×107 bone marrow cells and 2×107 spleen cells of donor C57BL/6 (H-2b) via the tail vein were infused to recipient mice.The signs of the recipient mice,hematopoietic functional recovery and survival time of change,and pathology,chimerism and cytokine levels in checkwere observed.Results Mice in A group after irradiation were gradually death,in group B and group C mice after transplantation had typical aGVHD symptoms,but lighter signs and a longer survival time of Group C than in group B.WBC count in Group C was +14 d (4.53± 0.21) ×109/L,+21 d (3.63±0.06) ×109/L,+28 d (4.31±0.04) ×109/L,was hematopoietic recovery compared with Group B [+14 d (1.81±0.05) ×109/L,+21 d (1.32±0.04) ×109/L,+28 d (1.76±0.04) ×109/L],the difference was statistically significant (t =0.237,0.108,0.359,P ＜ 0.05).The pathological results of liver,spleen,skin histopathology in group C were better than group B.Chimera implants,plasma IL-7 levels after transplant +7 d,concentration was significantly increased.IL-7 concentration in group C was +14 d (194.32±1.02) pg/ml,+21 d (131.63±1.54) pg/ml and in group B was +14 d (330.24±8.08) pg/ml,+21 d (184.09±2.05) pg/ml,the difference was statistically significant (t =1.590,1.285,P ＜0.05).Conclusion The stable aGVHD mouse model was established.In aGVHD early,plasma IL-7 levels were significantly increased.Exogenous IL-7Rαcan reduce the plasma IL-7 levels,thereby reducing the incidence of aGVHD after allogeneic bone marrow transplantation.

Role of stem cell transplantation in multiple myeloma in the era of novel agents / 白血病·淋巴瘤

Autologous stem cell transplantation (ASCT) has been considered as frontline therapy for patients with multiple myeloma (MM) based on the increased rate of response and prolonged progression-free survival compared with conventional chemotherapy.In the recent years,the favorable results shown by newdrug-based multidrug inductions,consolidations,and long-term maintenance approaches have challenged the role of ASCT.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has shown to be a potentially curative treatment for MM.However,the effectiveness of high-dose conditioning with conventional allo-HSCT is compromised by transplant-related mortality (TRM).Nonmyeloablative transplantation has showed reduced TRM and promising graft-versus-myeloma effects,but rates of acute and chronic graft-versus-host disease remain high.This article provides an overview of clinical trials and aims to define the role of stem cell transplantation in the era of novel agents.

Allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome: indications and controversy of pre-transplant chemotherapy / 白血病·淋巴瘤

The indications for myelodysplastic syndrome (MDS) to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT) were established on the basis of FAB diagnosis,International Prognosis Scoring System (IPSS) and World Health Organization Prognosis Scoring System (WPSS).It was recommended that patients of IPSS intermediate risk Ⅱ and of high risk should receive allo-HSCT at diagnosis,and those with intermediate risk Ⅰ and of low risk might benefit from deferred transplantation.Dynamic monitoring of marrow morphology and the risk of disease are needed for appropriate timing of transplant.Patients of intermediate risk and low risk with low platelet count,pneutropenia or blood infusion dependence are indicated for transplantation.The advantage of chemotherapy pre-HSCT in those indicated patients has been controversial.Up to now,there has been few data showing benefit of pre-chemotherapy or hypomethylating therapy.

Research on the relationship between disease composite index and the prognosis of allogeneic hematopoietic stem cell transplantation / 白血病·淋巴瘤

Objective To assess the impact of a composite index which combines the prognosis of specific hematologic malignancies and the disease remission state pre-transplant on the efficacy of allogeneic hematopoietic stem cell transplantation.Methods A total of 148 patients who underwent allogeneic hematopoietic stem cell transplantation from Jan,2007 to Feb,2012 in the Blood and Marrow Transplantation Center of Ruijin Hospital were included in this retrospective analysis.According to the composite score,patients were classified into low-risk group (n =17),medium-risk group (n =100) and high-risk group (n =31).The overall survival (OS),event free survival (EFS),treatment related mortality (TRM) and relapse rate (RR) were analyzed.Results Significant difference had been found on OS (76.5 ％ vs 66.0 ％ vs 41.9 ％,P =0.002),EFS (70.6 ％ vs 57.0 ％ vs 32.3 ％,P =0.001) and RR (41.9 ％ vs 27.0 ％ vs 5.9 ％,P ＜ 0.001) among the three groups.However,there was no impact on treatment related mortality (23.5 ％,17.0 ％,29.0 ％,P =0.190).Multivariate analysis suggested that the composite index affecting the OS,EFS and RR of allogeneic hematopoietic stem cell transplantation (P =0.005,P =0.001,P ＜ 0.001),but not the TRM (P =0.666).To some extent,it was an independent prognosis index on RR.Conclusion The composite index is closely related to the efficacy of allogeneic hematopoietic stem cell transplantation.

The risk factors and prognosis of transplant-associated thrombotic microangiopathy following acute graft-versus-host disease / 中华内科杂志

Objective To investigate the risk factors and prognosis of transplant-associated thrombotic microangiopathy (TA-TMA) following acute graft-versus-host disease (aGVHD),and to evaluate the factors that might influence the prognosis of TA-TMA.Methods A nested case-control study was designed.Cases with TA-TMA (n =33) and controls (n =77) matched for age at allogeneic hematopoietic stem cell transplantation (allo-HSCT) and length of follow-up were identified from a cohort of 356 patients who suffered from aGVHD after allo-HSCT between 2009 and 2011.Results The median time to presentation of TA-TMA was 3.5 (1.2-23.0) months post-HSCT.The median time from diagnosis and first-line treatment failure of aGVHD to TA-TMA diagnosis was 25 (7-257) days and 15 (5-257) days,respectively.aGVHD occurring beyond 60 days after allo-HSCT,initial grade Ⅲ-Ⅳ aGVHD,first-line treatment failure and receiving tacrolimus as second-line treatment were independently associated with the occurrence of TA-TMA,and patients with two or more risk factors were at higher risk (OR =210.0,P =0.000).Twenty-two (66.7％) TA-TMA patients died.Progressive TA-TMA was the significantly adverse factor affccting the survival of TA-TMA cases.None of therapies could improve prognosis of patients with TA-TMA.Conclusion Many characteristics of aGVHD were associated with TA-TMA,which help us to identify the individuals who are at higher risk of developing TA-TMA following aGVHD and to select the more reasonable GVHD therapeutic strategies.

The efficacy and safety of recombinant human granulocyte colony stimulating factor primed donor peripheral cell harvest in treatment of poor graft function after allogeneic stem cell transplantation / 中华内科杂志

Objective To assess the efficacy and safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) primed donor peripheral blood stem cell (PBSC) on the treatment of poor graft function (PGF) after allogeneic stem cell transplantation(allo-HSCT).Methods The patients diagnosed as PGF after allo-HSCT and transfused with rhG-CSF primed PBSC from January 2003 to November 2012 were retrospectively analyzed.Hematological response was assessed at day 30 after transfusion.Graft versus host disease (GVHD) was assessed until 6 months after transfusion.Results There were 28 patients including 21 men and 7 women with a median age of 28 (12-50) years old.Of these patients,16 were diagnosed as primary PGF.The median number of transfused mononuclear cells was 2.0 (1.0-5.8) ×108/kg.Totally 42.9％ (12/28) patients achieved good response.Eight patients (28.6％) developed GVHD.Sixteen patients (57.1％) survived.Age (≤/＞ 28 years),gender,donor type (matched sibling/mismatched related),additional conditioning regimen prior to transfusion,time of neutrophil engraftment (≤/＞ 18 days) time of transfusion (≤/＞ 100 days after allo-HSCT) and number of mononuclear cells (≤/＞ 2.0 × 108/kg) did not impact hematological response.However,response rate of primary PGF (4/16) was significantly lower than that of secondary PGF (8/12) (P =0.022).Conclusion Transfusion of PBSC mobilized by rhG-CSF could be considered as an option to treat secondary PGF after allogeneic stem cell transplantation.

Controversies on the allogeneic immunotherapy to optimize the graft-versus-tumor effect / 白血病·淋巴瘤

Cellular immunodeficiency is an important factor related to relapse of hematological malignancy post stem cell transplantation. On the other hand, allogeneic stem cell transplantation can be considered the adoptive immunotherapy, which can overcome the host immunodeficiency and promote graftversus-tumor (GVT) effect for elimination of minimal residual disease and prevention of relapse. How to optimize the GVT induction is required to be defined more clearly. In this review, advance knowledge concerning the optimized and clinical setting of GVT induction from 2011 ASH annual meeting is summarized.

Clinical observation of allogeneic hematopoietic stem cell transplantation for 20 patients with hematologic malignancies / 白血病·淋巴瘤

ObjectiveTo evaluate the efficacy of allogeneic stem cell transplantation (allo-HSCT) in treatment of hematologic malignancies and observe hematopoietic reconstitution, graft versus host disease (GVHD) occurrence,transplant-related complications and the outcome of disease.Methods20 patients with hematologic malignancies cured by allo-HSCT were analyzed retrospectively. 15 males and 5 females patients were enrolled, and the median age was 39(8-59)years. Mobilization of donor’ s stem cells using rhG-CSF program 3 days before transplantation.Conditioning regimen:the patients with HLA-matched used modified Bu/Cy programs,the patients with HLA-mismatched (with 1 to 3 loci mismatched) used the modified Bu/Cy+ ATG program;the patient with T-ALL and the patient with MM used Flu+Bu/Cy program. GVHD prevention programs: mycophenolate mofetil + cyclosporine + short course methotrexate. Results20 patients were successfully engrafted,the median time of absolute neutrophil count (ANC) ＞ 0.5×109/L was 13 (12-17) days,the median time of Plt ＞ 20×109/L was 16(12-23)days, and the hematopoietic reconstitution was rapid in those patients who were transplanted by the donors with the collected amount of CDh cells ＞ 2.5× 106/kg (recipient body weigh) or the collected amount of mononuclear cell ＞ 5.0×10s/kg (recipient body weigh).No severe hemolytic reaction occurred in 11 cases of blood group incompatibility between donor and recipient after transplantation,11 cases (55 ％) developed acute GVHD (aGVHD):4 cases Ⅰ degree aGVHD,4 cases Ⅱ degree aGVHD,2 cases Ⅲ degree aGVHD,1 case Ⅳ degree aGVHD,all patients were improved after treatment.All patients attained complete remission (CR) after transplantation.Follow-up 6 (2-14) months,1 patient died in 5 months after transplantation because of leukemia relapse, 1 case died in 4 months after transplantation because of self-disabling autoimmune hemolytic cyclosporine, chronic GVHD(cGVHD)and multiple organ failure,the remaining patients still were in CR state.ConclusionAllo-HSCT is the effective way to treat hematologic malignancies. Engraftment is closely related with the quantity of hematopoietic stem cells from donor.Blood group incompatibility was not an obstacle for transplantion.Relapse,GVHD,infection are the major cause of death after transplantation.

The efficacy and safety of rituximab in treatment of Epstein-Barr virus disease post allogeneic hematopoietic stem-cell transplantation / 中华内科杂志

Objective To investigate the efficacy and safety of rituximab on Epstein-Barr virus (EBV) disease post allogeneic hematopoietic stem-cell transplantation.Methods A retrospective analysis was performed based on clinical data of 26 patients diagnosed as EBV disease and received rituximab from June 2006 to March 2012 in People's Hospital,Beijing University.Eleven patients were diagnosed as posttransplant lymphoproliferative disorders (PTLD) by histopathology and remaining 15 were diagnosed as probable EBV disease.Patients received a rituximab dose of 375 mg/m2 once a week.Efficacy was evaluated as revised response criteria for non-hodgkin lymphoma (NHL),and side effects during infusion were evaluated by Common Terminology Criteria for Adverse Events.Results Patients received 78 infusions with a median of 3 (1-6) infusions in each.There were no severe side effects during the infusion of rituximab.The 1st,2nd,3rd,4th,8th week cumulative complete remission (CR) were (11.5 ± 6.3)％,(42.2 ±10.2) ％,(64.4 ± 10.0) ％,(74.6 ± 9.4) ％,(87.3 ± 7.9) ％,respectively.The overall response rate was 84.5％,and the CR rate was 73.1％.The CR rate was higher among patients with single organ involved than those with multiple organs involved (10/10 vs 9/16,P =0.023).The CR rate was higher in patients with probable EBV disease than those with PTLD (13/15 vs 6/11,P =0.095),while there was no statistically significant difference.The incidence of one-year and two-year overall survival since onset of rituximab were (55.7 ± 10.2)％ and (39.6 ± 12.4)％,respectively.Survival rate was higher among the patients with single organ involved than those with multiple organ involved (8/10 vs 5/16,P =0.041).Survival rate was higher in patients with probable EBV disease than those with PTLD(11/15 vs 2/11,P =0.015).Conclusions Rituximab appears to be safe and effective for EBV disease.Due to a potential good response in probable EBV disease,we suggest rituxmab should be given based on probable EBV disease;meanwhile the pathological results should get early if possible.Prospective trial is needed to provide evidence so as to define optimal therapy of rituxmab.

A comparison of toxicity and efficacy between busulfan plus fludarabine and busulfan plus cyclophosphamide for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia / 中华内科杂志

Objective To compare the transplant-related toxicity and the efficacy of busulfan/fludarabine (Bu/Flu) and busulfan/cyclophosphamide (Bu/Cy) as conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia(AML) in the first complete remission (CR1).Methods Totally 32 AML-CR1 patients underwent allo-HSCT were divided into Bu/Cy (Bu 3.2 mg· kg-1 · d-1,7-4 days before transplantation; Cy 60 mg · kg-1 · d-1,3-2 days before transplantation) and Bu/Flu (Bu 3.2 mg · kg-1 · d-1,5-2 days before transplantation; Flu 30 mg · m-2·d-1,6-2 days before transplantation) groups.The regimen-related toxicity (RRT),incidence and severity of graft-versus-host disease (GVHD),3-year cumulative relapse rate,non-relapse mortality (NRM),3-year event-free survival (EFS) rate and overall survival (OS) rate were compared between the two groups.Results The median follow-up duration was 617.5 (6-1261) days.All patients achieved successful engraftment on 30 day after transplantation.There were no significant differences in the median time to neutrophil engraftment (P =0.121) and platelet engraftment (P =0.171) between the two groups.The median duration of neutrophil count under 0.1 × 109/L and platelet count under 20 × 109/L in the Bu/Cy group were significantly longer than those in the Bu/Flu group (P =0.000 and P =0.047).The incidence of grades Ⅱ-Ⅳ RRT were 68.8％ and 25.0％ (P =0.032) in the Bu/Cy and the Bu/Flu groups,respectively.There were no significant differences in the incidence of acute GVHD (P =0.149),chronic GVHD (P =0.149),incidence of NRM (P =0.333),3-year cumulative relapse rates (P =0.834),3-year EFS rate (P =0.362) and OS rate (P =0.111) between the two groups.Conclusion Compared with Bu/Cy,Bu/Flu is a myeloablative condition regimen with milder bone marrow suppression and lower RRT incidence rate in allogeneic HSCT for AML-CR1 patients without compromising the efficacy.

Transplantation of allogeneic mesenchymal stem cells into skin expansion / 中华医学美学美容杂志

Objective To investigate the feasibility of transplantation of mesenchymal stem cell (aisc) into expanion skin. Methods MSCs were isolated from porker's bone marrow and cultured in vitro. Pigs were randomly divided into four groups: Group A was injected with MSCs on the local expansion; Group B was injected with MSCs from ear vein; Group C was planted expander only; Group D was the contronl group. Each side of pig's spinal column was implanted with three expander in groups A, B and C. The same volume of NS was injected at the fixed time, the marked area measured after 7, 14, 28 days of expansion, the difference of those area was compared between groups. The differentiation of BM-MSC was detected by immunofluorescence. Results Flow-cytometric analysis showed that these BMSCs expressed CD90 and CD29 highly but did not express CD34 or CD45. The expansion area (cm2) of groups A, B, C and D was 34.05±0. 92, 31.83±l. 07,30. 10±0.79, and 18. 27±0.25, respectively (P＜0. 01). Immunofluorescence showed that the positive expression rate of CD31, PCNA in groups A and B was higher than that in groups C and D, in which the expression was the highest in group A. Conclusions Allogeneic transplantation of BM-MSC can promote skin expansion and the effect of local transplantation group is most significant.

Outcomes following HSCT using fludarabine replacing cyclophosphamide as a new preconditioning regimen for treatment of hematologic malignancies / 中华器官移植杂志

Objective To evaluate the hypothesis of fludarabine replacing cyclophosphamide as a new myeloablative preconditioning for the treatment of malignant hematologic diseases in aged and/or intolerable patients receiving allogeniec stem cell transplantation (allo-HSCT). Methods Between January 2008 and November 2008,12 patients, who were intolerant to standard conditioning regimen, received allo-HSCT with HLA identical sibling (n = 9) or mismatched family donors (n = 3),including 1 case of acute lymphoblastic leukemia with Ph chromosome (Ph+ ALL) ,6 cases of acute myelogenous leukemia (AMD,3 cases of myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB) and 2 cases of chronic myelogenous leukemia (CML). Stem cell sources were G-CSF mobilized peripheral blood alone (n = 1) ,or with G-CSF mobilized bone marrow (n - 11), with a median of 6. 68 (4. 35 - 7. 86) × 10~8/kg MNC and 1. 50 (0. 31 - 3. 91) × 10~6/kg CD34~+ cells. Eleven patients received revised busulfan and fludarabine regimen with/without antithymocyteglobulin(ATG),and the rest one received TBI and fludarabine regimen. GVHD prophylaxis included cyclosporin A, mycophenolate mofetil and methotrexate. Results Results All patients were well tolerated to the regimen without serious regimen related toxicity. The median time of ANC≥0. 5 × 10~9/L was day 17. 5 (11 - 23), and that of BPC≥20. 0 ×10~9/L was day 14. All patients except one got donor engraftment successfully and attained CR. With a median follow-up of 418 (62-554) days, 10 of 12 patients were alive and disease-free. Conclusion Fludarabine replacing cyclophosphamide as a new preconditioning regimen is well tolerated and safe for allo-HSCT, especially in older patients or/and those with severe concurrent medical conditions.

Relationship of tumor necrosis factor gene polymorphism and acute graft-versus-host disease after unrelated ailogeneic hematopoietic stem cell transplantation / 中华内科杂志

Objective To explore the relationship between tumor necrosis factor (TNF) gene polymorphisms in donors and recipients and the incidence and severity of acute graft-versus-host diseases (aGVHD) after unrelated allogeneic hematopoietic stem cell transplantation (alIo-HSCT). Methods Single nucleotide polymorphisms (SNPs) of TNFα-238 (G/A), TNFα-857 (C/T), TNFα-863 (C/A), TNFα-1031 (T/C), TNFβ + 252 (A/G) were analyzed by Multiplex SNaPshot analysis in 76 pairs of donors and recipients. Results Transplantation involving donors with TNFα-857 CC genotype resulted in a higher incidence of grade Ⅱ-Ⅳ aGVHD than donors with CT genotype (91.3% vs 8. 7% , P =0. 039). In the 23 patients with grade Ⅱ-Ⅳ aGVHD, no patients had TNFβ +252 AA genotype, 19 (82.6%) had GA genotype and 4 (17.4%) had GG genotype. There was a significant difference in the distribution pattern of the TNFβ +252 (AA, GA and GG) genotypes in these patients (P =0.03). There was no significant association of TNFα-238 (G/A), TNFα-863 (C/A) and TNFα-1031 (T/C) polymorphisms with the risk of aGVHD. Conclusion These results suggest donor TNFα-857 CC genotype is related to a higher incidence of grade Ⅱ -Ⅳ aGVHD, and patients with TNFβ +252 AA genotype have protection against the risk of grade Ⅱ -Ⅳ aGVHD.