Treatment of severe aplastic anemia and hematopoietic stem cell transplantation / 器官移植

Severe aplastic anemia (SAA) is a severe bone marrow failure syndrome caused by multiple causes, which is clinically manifested with severe anemia, infection and bleeding. The complex pathogenesis of SAA has not been fully understood. SAA is characterized with acute onset, severe disease condition and rapid progression. At present, with the in-depth study of SAA and the improvement of diagnosis and treatment, the therapeutic strategy for SAA has been evolved from classical immunosuppressive therapy based on antithymocyte globulin and cyclosporine to the application of thrombopoietin receptor agonist and combined treatment based on allogeneic hematopoietic stem cell transplantation, which may promote the reconstruction of hematopoietic function of SAA patients to varying degree and significantly improve survival and clinical prognosis, becoming the research hotspot of SAA treatment. In this article, new advances in the treatment of SAA at home and abroad were reviewed.

Application progress of individualized immune induction therapy in kidney transplantation / 器官移植

The risk of early acute rejection after kidney transplantation is relatively high, which severely affects the quality of life of the recipients. In 2009, Kidney Disease: Improving Global Outcomes (KDIGO) recommended that immune inducers should be included in the immune-inducing regime before kidney transplantation, aiming to provide certain strength of immunosuppression during this critical phase and effectively reduce the incidence of acute rejection following kidney transplantation. At present, the selection, efficacy and safety of immune inducers remain controversial among transplantation centers around the world. In this article, clinical efficacy of monoclonal antibodies including interleukin-2 receptor antagonist, alemtuzumab, rituximab and polyclonal antibody antithymocyte globulin in immune induction therapy before kidney transplantation were compared and literature review was performed at home and abroad, aiming to provide reference for promoting the individualized selection of immune inducers for kidney transplantation and improving the quality of life of recipients.

Clinical application progress of immune induction regimen for kidney transplantation / 器官移植

With the development of immunosuppressants and optimization of immunosuppressive regimens, the survival rates of kidney transplant recipients and grafts have been significantly increased, whereas the incidence of acute rejection and delayed graft function have also been significantly reduced. However, the standard triple immunosuppressive regimen (calcineurin inhibitor+antimetabolite+glucocorticoid) still cannot effectively control the rejection of transplant kidney. Consequently, immune induction before transplantation has been proposed. Immune induction therapy may delay the application time and reduce the dosage of calcineurin inhibitor, lower the incidence of short-term acute rejection after operation, and improve the middle- and long-term prognosis of the recipients. In this article, research progresses on monoclonal antibody-based immune induction regimen, polyclonal antibody-based immune induction regimen and mesenchymal stem cell-based immune induction regime were investigated, aiming to provide reference for optimizing the immune induction regime for kidney transplantation.

Esclerosis múltiple: reacciones adversas a medicamentos en pacientes bajo ley 20850, Hospital Regional de Talca / Multiple sclerosis: adverse drug reactions in patients under law 20850, Hospital Regional de Talca

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, which occurs in up to 85% of cases as relapsing remitting (RR), with episodes of neurological dysfunction partially forwarded. Its treatment in Chile is financially protected by the Explicit Health Guarantees (GES) and Law 20,850 on high-cost diseases. The Regional Hospital of Talca (HRT) has 25 patients benefiting from Law 20,850 in treatment with second-line biologic therapy. Adverse reactions (RAM) to the use of these drugs have been described and to date there are no case reports or studies of significant adverse events in Chile. Objectives: To present the experience of the use of biologic therapy in EMRR in HRT, in relation to adverse events. METHODS: A review of the current guidelines in Chile for the treatment of relapsing-remitting multiple sclerosis and the protocol of law 20,850 was carried out, the clinical records of 25 patients benefiting from the law in the HRT were reviewed, with emphasis on the adverse events presented before First and second line therapies and the con sequences of these events on the continuity of therapy. RESULTS: Half of the patients who started their treatment with first-line drugs had adverse effects, of which 28% involved a change in therapy, the remaining changed from therapy due to failure to treatment. Of the 26 patients included in the sample, 24 are currently using second-line drugs. The profile of adverse effects should be a variable to consider when indicating a therapy for MS.

Therapeutic Outcome of Alemtuzumab in Korean Patients with Multiple Sclerosis: 2-Year Follow-Up

BACKGROUND AND PURPOSE: Alemtuzumab has shown high efficacy in clinical trials that primarily involved Western multiple sclerosis (MS) patients. To evaluate the therapeutic outcome of alemtuzumab in Korean patients with MS. METHODS: This study enrolled 23 consecutive patients who were treated with alemtuzumab from 2015 to 2018. Efficacy was evaluated using the annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS), and radiological activity. No evidence of disease activity (NEDA) was defined as no clinical relapse, no worsening of the EDSS score, and no radiological activity. The safety profiles were also assessed. RESULTS: The mean age was 36 years and 16 of the patients were female. Seventeen and 12 of 23 patients were followed up for 1 year and 2 years, respectively. The ARR was markedly reduced from 1.52 during the 1-year period preceding alemtuzumab administration to 0.21 after initiating alemtuzumab (p<0.001). During the first and second years after initiating alemtuzumab, EDSS worsening was observed in 3 (18%) and 0 (0%) patients, respectively, and radiological activity was exhibited in 9 (53%) and 4 (33%). NEDA was observed in 6 (35%) patients during the first year and in 8 (67%) patients during the second year. Intriguingly, one patient experienced 2 severe clinical exacerbations, which occurred at 10 months after the first and 10 months after the second infusion of alemtuzumab. Nineteen of the 23 patients exhibited infusion-associated reactions and 3 patients exhibited herpes zoster infection. Thyroid dysfunction occurred in two patients at 18 and 20 months after initiating alemtuzumab. CONCLUSIONS: Consistent with observations in Western populations, alemtuzumab therapy in Korean MS patients led to marked reductions of disease activity without unexpected safety issues.

Research progress on the therapy of T-cell prolymphocytic leukemia / 中国肿瘤临床

Prolymphocytic leukemia is a rare disease with typical characteristics, including aggressive progression and high mortality rate, and T-cell prolymphocytic leukemia (T-PLL) is regarded as an intractable subtype. Current therapeutic approaches mainly aim to improve their efficacy and remission against this disease. This paper presents a review about the research progress on T-PLL therapies. With remarkable research progress on leukemia pathogenesis, therapies for T-PLL have been greatly enhanced. Among treatment strategies, epigenetic therapy shows potential for clinical applications.

Alemtuzumab as graft-versus-host disease (GVHD) prophylaxis strategy in a developing country: lower rate of acute GVHD, increased risk of cytomegalovirus reactivation

Acute graft-versus-host disease (aGVHD) and cytomegalovirus reactivation are important complications after allogeneic stem cell transplantation (alloHSCT). Here, we evaluated the impact of treatment with alemtuzumab on the occurrence of aGVHD, cytomegalovirus reactivation and survival after alloHSCT. This was a prospective cohort study conducted at the allo-HSCT unit of Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil, from January 2009 to December 2011. Fifty-seven patients who underwent alloHSCT were included. Forty-five (79%) patients had a malignant disease. Alemtuzumab was administered before the conditioning regimen at a dose of 1 mg/kg in children and 30 mg/day for 2 days in adults or children weighing more than 40 kg (a total dose of 60 mg) with a non-malignant disease or patients with a malignant disease and high-risk for GVHD mortality. Alemtuzumab was used in 23 (40%) patients, of whom 17 received a reduced-intensity conditioning. Eleven patients presented aGVHD (grade 2–4) and only 1 of them received alemtuzumab. Cumulative incidence of aGVHD (grade 2–4) at day 100 after transplantation (D+100) was 4 for patients receiving alemtuzumab and 29% for patients not receiving alemtuzumab. Cumulative incidence of cytomegalovirus reactivation for patients receiving or not alemtuzumab was 62 and 38%, respectively. Sixteen patients died in the first 100 days after alloHSCT, most of them due to bacterial sepsis. Only 2 patients died of aGVHD until D+100. Overall survival was 50% without any impact of alemtuzumab. Alemtuzumab effectively controlled aGVHD but increased the risk of cytomegalovirus reactivation without improving survival.

Application of calcineurin inhibitor monotherapy in renal transplantation after alemtuzumab induction:a Meta-analysis / 器官移植

Objective To evaluate the clinical efficacy and safety of immunosuppression of calcineurin inhibitor monotherapy (AiCNIm)after alemtuzumab induction following renal transplantation.Methods Randomized control clinical trials related to application of AiCNIm (AiCNIm group ) and conventional triple regimes (Triple group ) for immunosupression after renal transplantation,published from 1 980 to December 31 201 4,were searched online from PubMed,Embase,Web of Science,Cochrance library and China National Knowledge Infrastructure (CNKI) databases.Meta-analysis was performed by Rev Man 5.2 software.Results Five randomized control studies consisting of 421 renal transplant recipients were included.The results of follow up for 6-1 2 months revealed that compared with the Triple group, the incidence of rejection response confirmed by acute rejection or aspiration biopsy in the AiCNIm group was significantly lower [relative risk (RR) =0.59,95% confidence interval (CI):0.40-0.89 ].However,there was no significant difference in the risk of renal allograft dysfunction (RR =0.85,95%CI:0.38-1 .87),death of recipient (RR =0.89,95%CI:0.30-2.67),infection (RR =1 .03,95%CI:0.91 -1 .1 7)and new-onset diabetes after transplantation (RR =0.62, 95%CI:0.29-1 .30)between two groups (all in P >0.05).Conclusions According to the existing evidence,application of calcineurin inhibitor monotherapy after renal transplantation exerts short-term immunosuppressive effect and high safety after alemtuzumab induction.

A meta-analysis to determine efficacy and safety of alemtuzumab in multiple scle-rosis / 中国免疫学杂志

Objective:To perform a meta-analysis of randomized controlled trials ( RCTs) in multiple sclerosis ( MS) patients to evaluate the efficacy and safety of alemtuzumab.Methods: We searched PubMed,EMBASE,the Cochrane Library and so on up to February 2015 using the keywords:′multiple sclerosis′or ′MS′and the drug names:alemtuzumab.Two authors independently selected the articles and extracted the data.We performed meta-analysis using Review Manager ( RevMan) version 5.3 software.Results:Three RCTs with a total of 1 695 patients were selected.Compared to the interferon beta,the number of gadolinium-enhancing lesions ( odds ratio (OR)=0.33,95% Confidence interval (CI)=[0.23,0.48],P<0.000 01),the cumulative probability of sustained disability (Or=0.51,95%CI=[0.38,0.69],P<0.000 1) and the proportion of patients who had at least one relapse of MS(Or=0.42,95%CI=[0.34,0.52],P<0.000 1) were significantly less in the alemtuzumab group,meanwhile the number of new T2-hyperintense lesions (Or=0.10,95%CI=[0.01,1.75],P=0.11) showed no significant difference.Comparing adverse events between two groups, alemtuzumab treatment did not increase the frequency of serious adverse events (Or=1.00,95% CI=[0.80,1.26],P=0.99) but increase the frequency of any adverse events (Or=2.29,95% CI=[1.40,3.75],P=0.001).Conclusion: Alemtuzumab is a relatively effective and safe treatment for MS.

Baja incidencia de enfermedad linfoproliferativa postrasplante renal con uso predominante de Alemtuzumab / Low incidence of limphoproliferative disease post kidney transplantation with prevalent use of Alemtuzumab

Introducción: Se conoce que la incidencia de malignidad es significativamente mayor en los pacientes trasplantados que en la población general. La incidencia de enfermedad linfoproliferativa post trasplante (PTLD) es aproximadamente de 1% a 2% en los receptores de trasplante renal. El objetivo principal de este estudio fue evaluar la incidencia de PTLD en el seguimiento de pacientes trasplantados de riñón entre el 2005 y el 2010. Material y Métodos: Se tomaron de forma retrospectiva los datos de pacientes trasplantados de riñón entre los años 2005 a 2010 para determinar el número de casos de PTLD según el esquema inductor usado. Resultados: Se trasplantaron 425 pacientes en el periodo 2005 - 2010. Recibieron alemtuzumab 76.2%, daclizumab 10.7%, basiliximab 3.6% y timoglobulina 2.4%. No recibieron inducción con anticuerpos el 7 %. Durante este tiempo se presentaron 2 casos de PTLD: 1 con mieloma múltiple y otro con linfoma. Uno de ellos recibió alemtuzumab y otro timoglobulina. Conclusiones: En esta cohorte de pacientes donde se usó predominantemente alemtuzumab, la incidencia de PTLD fue más baja que lo reportado en estudios previos.

Introduction: It is well known that the incidence of malignancy is significantly higher in transplanted patients than in general population. The incidence of lymphoproliferative disease post-transplantation (PTLD) is approximately of 1% to 2% in kidney transplantation recipients. The main objective of this study was to evaluate the PTLD incidence when monitoring kidney transplanted patients between the years 2005 and 2010. Material and Methods: Kidney transplanted patients' data was retrospectively taken between the years 2005 to 2010 in order to determine the number of PTLD cases according to the inductor scheme used. Results: 425 patients were transplanted between 2005 and 2010. They received alemtuzumab 76.2%,daclizumab 10.7%, basiliximab 3.6% and thymoglobulin 2.4%. The 7% did not receive antibody induction. During this period 2 cases of PTLD ocurred: One with multiple myeloma and the other with lymphoma. One of them had been treated with alemtuzumab and the other with thymoglobulin. Conclusions: The PTLD incidence in our group, where alemtuzumab was used predominantly as inductor, was very low; this might suggest that alemtuzumab is a medication that does not increase the risk of this kind of neoplasia.

Meta-analysis on the effect of Alemtuzumab on renal graft rejection and survival / 中华器官移植杂志

Objective To study the effect of Alemtuzumab on acute rejection (AR) and graft survival after kidney transplantation.Method Published domestic and foreign literatures regarding the effects of Alemtuzumab used on acute rejection and graft survival were reviewed,and Meta analysis was employed to analyze the Results.Odds ratio (OR) and its 95％ confidence interval (95％ CI) were used as the parameters to evaluate the therapeutic effects.The statistical analyses were performed with RevMan 5.1 software.Result A total of 9 pertinent research articles were reviewed.Meta-analysis of pooled results indicated that Alemtuzumab prevented the recipients of kidney transplantation from acute rejection effectively with half year prevention of OR 0.37 and 95％ CI 0.24-0.58 (P＜0.01),one year prevention of OR 0.43 and 95 ％ CI 0.29-0.64 (P＜0.01),and two year prevention of OR 0.69 and 95％ CI 0.47-1.02 (P ＜ 0.01),respectively.It was revealed that Alemtuzumab could reduce the incidence of acute rejection by 55％ in half year,51％ in one year and 28％ in two years,respectively.No statistically significant difference in graft survival was found between Alemtuzumab group and control group (OR =1.18,95％ CI 0.76-1.85,P =0.46).No statistically significant difference in patients' survival was found between Alemtuzumab group and control group (OR =0.94,95 ％ CI 0.52-1.72,P =0.85).Conclusion Alemtuzumab may effectively prevent the recipients of kidney transplantation from acute rejection,but not obviously influence the graft and patient survival.

Successful Erythropoietin Therapy after Alemtuzumab and Cyclosporin a Treatment for Epoetin-Induced Pure Red Cell Aplasia / 대한내과학회지

Pure red cell aplasia (PRCA) in adults is usually idiopathic, although some underlying conditions can cause PRCA. Immunosuppressive therapy (IST) is used to treat PRCA, but IST has side effects and may fail. The anti-CD52 monoclonal antibody alemtuzumab (ALM) was recently used to successfully treat therapy-resistant PRCA. We herein report successful treatment of secondary PRCA after erythropoietin therapy using ALM and cyclosporin A (CsA) in one patient. The total dose of ALM was 60 mg over 3 days (10, 20, and 30 mg, respectively) plus CsA for at least 6 months. The patient achieved a complete response 18 months after ALM-CsA treatment and his treatment could be changed to a different erythropoietin-stimulating agent.

Efficacy and safety of Alemtuzumab induction in kidney transplantation / 中华器官移植杂志

Objective To evaluate the efficacy and safety of alemtuzumab in renal transplant recipients treated with induction therapy. Methods Eighty-nine cadaveric renal transplant recipients in our department were randomly divided into experimental group (n = 43) treated with alemtuzumab induction, 15 mg i. v. and control group (n = 46). Main immunosuppressive therapy regimen consisted of steroids, tacrolimus or cyclosporine and mycophenolate mofetil in all recipients. Post-transplant kidney function, acute rejection,infection, DGF, graft survival, lymphocyte counts were recorded within 1 year. ATP values in CD4+ T cells after transplantation was determined by using Cylex ImmuKnow assay. Results There was significant difference in the incidence of biopsy-proven acute rejection, but no significant difference was found in ImmuKnow ATP values during 6 months after transplantation and lymphocyte counts during 3 months, graft survival and the incidence of infections between the two groups. Conclusion Induction therapy with alemtuzumab appeared to be effective in the prevention of acute rejection.

Cytomegalovirus Ventriculoencephalitis after Unrelated Double Cord Blood Stem Cell Transplantation with an Alemtuzumab-containing Preparative Regimen for Philadelphia-positive Acute Lymphoblastic Leukemia

Despite the prophylaxis and preemptive strategies using potent antiviral agents, cytomegalovirus (CMV) remains a major infectious cause of morbidity and mortality in allogeneic stem cell transplantation (SCT) recipients. Delayed immune reconstitution after SCT, such as cord blood and T-cell depleted SCT with the use of alemtuzumab, has been associated with an increased frequency of CMV disease as well as CMV reactivation. CMV disease involving central nervous system is an unusual presentation in the setting of SCT. We report a case of CMV ventriculoencephalitis after unrelated double cord blood SCT with an alemtuzumab-containing preparative regimen for Philadelphia-positive acute lymphoblastic leukemia.