Alemtuzumab ; Antibodies, Monoclonal, Humanized ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Prolymphocytic, T-Cell ; Transplantation, Autologous

OBJECTIVETo investigate the effect of Campath-1H induction on immunosuppression in small intestine transplantation.

METHODSClinical data of a patient who underwent small intestine transplantation were retrospectively summarized.

RESULTSIntraoperative Campath-1H induction by intravenous injection was administered. Triple immunosuppression(FK506, MMF and methylprednisolone) was used postoperatively. The lymphocyte and leukocyte decreased significantly following Campath-1H induction, and returned to normal after adjusting the dose of immunosuppressant and use of colony stimulating factor. There were no acute rejection, graft versus host disease, or severe infection during the immediate postoperative period. The patient recovered and discharged.

CONCLUSIONIntraoperative Campath-1H induction and postoperative triple immunosuppression using FK506, MMF, and methylprednisolone may prevent rejection and graft versus host disease in the early stage after small intestine transplantation.

Adult ; Alemtuzumab ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Graft Rejection ; prevention & control ; Humans ; Immunosuppression ; Immunosuppressive Agents ; therapeutic use ; Intestine, Small ; transplantation ; Male ; Retrospective Studies

BACKGROUNDAlemtuzumab has been used in organ transplantation and a variety of hematologic malignancies (especially for the treatment of B-cell chronic lymphocytic leukemia). However, serious infectious complications frequently occur after treatment. The reason for increased infections postalemtuzumab treatment is unknown at this stage. We explore the effect of alemtuzumab on intestinal intraepithelial lymphocytes (IELs) and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment.

METHODSTwelve male cynomolguses were randomly assigned to either a treatment or control group. The treatment group received alemtuzumab (3 mg/kg, intravenous injection) while the control group received the same volume of physiological saline. Intestinal IELs were isolated from the control group and the treatment group (on day 9, 35, and 70 after treatment) for counting and flow cytometric analysis. Moreover, intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay.

RESULTSThe numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 × 10 8 and 1.35 ± 0.09 × 10 8 , respectively; P < 0.05) and were not fully restored until day 70 after treatment. There were significant differences among four groups considering IELs subtypes. In addition, the proportion of apoptotic IELs after alemtuzumab treatment was significantly higher than in the control group (22.01 ± 3.67 and 6.01 ± 1.42, respectively; P < 0.05). Moreover, the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment.

CONCLUSIONSAlemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model. The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment. Notably, intestinal barrier function may be disrupted after alemtuzumab treatment.

Alemtuzumab ; Animals ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Apoptosis ; drug effects ; Flow Cytometry ; Intestines ; cytology ; Lymphocytes ; drug effects ; Macaca fascicularis ; Male ; Microscopy, Electron, Transmission

OBJECTIVETo report preliminary experience of the protocol of combining Campath 1H induction with low-dose monotherapy of tacrolimus and no steroid in two cases of small bowel transplantation.

METHODSCampath 1H 30 mg was infused during the small bowel transplantation, and the patients were given 1 gram of methylprednisolone followed by the Campath 1H and another gram of methylprednisolone before reperfusion. Tacrolimus was infused just after the reperfusion. The tacrolimus was administered from vein first and then from gut tract, the blood tacrolimus level was controlled at 10 to 15 microg/L within the first 3 months after the operation, and reduced to 5 microg/L thereafter.

RESULTSThe two recipients have survived more than 1 year, one received surgical closure of intestinal graft terminal stoma 13 months after the transplantation. One episode of indeterminate to mild acute rejection was verified by pathology through routine ileoscopical biopsy in each cases, and one episode of mild to moderate acute rejection occurred 8 months after the transplantation, and the patients recovered after low dose or bolus steroid therapy. The peripheral lymphocyte counts and monocyte counts decreased greatly after Campath 1H was given, and recovered very slowly thereafter. No sign of infection and graft versus host disease (GVHD) was found, and the grafted intestine achieved excellent function. The total parenteral nutrition was ceased on the day 21 and 14 after the operation, respectively, and the patients lived on oral intake to maintain nutrition status.

CONCLUSIONSIt's showed that the protocol combining Campath 1H induction with low-dose monotherapy of tacrolimus without steroid in small bowel transplantation can control graft rejection effectively without increasing the opportunity of infection, no sign of GVHD is found, and the grafted intestine could achieve excellent function.

Alemtuzumab ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm ; therapeutic use ; Drug Therapy, Combination ; Female ; Graft Rejection ; prevention & control ; Humans ; Immunosuppressive Agents ; therapeutic use ; Intestine, Small ; transplantation ; Male ; Tacrolimus ; therapeutic use ; Young Adult

BACKGROUNDImmunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody, was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients.

METHODSIn this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients (panel reactive antibody > 20%). They were divided into two groups: alemtuzumab group (trial group) and anti-thymocyte globulin (ATG) group (control group). Patients in the alemtuzumab group received intravenous alemtuzumab (15 mg) as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab (15 mg) was given. The control group received a bolus of rabbit ATG (9 mg/kg), which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil (MMF). Acute rejection (AR) and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up. χ(2) test, t test and Kaplan-Meier analysis were performed with SPSS17.0 software.

RESULTSMedian follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar (P > 0.05). White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months (P < 0.05). One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary infection or cardiac and pulmonary failure. Cumulative 2-year graft survival rate was 90.9% in the alemtuzumab group and 81.8% in ATG group (P > 0.05) respectively. There was one graft failure in the alemtuzumab group and two graft failures in ATG group, with all graft failures at tributed to rejection episodes. The alemtuzumab group had a 2-year cumulative freedom from rejection rate of 81.8%, compared with 72.7% for the ATG group (P > 0.05).

CONCLUSIONAlemtuzumab induction therapy for highly sensitized kidney transplant recipients is an effective and safe protocol yielding an acceptable acute rejection rate.

Adult ; Aged ; Alemtuzumab ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm ; therapeutic use ; Antilymphocyte Serum ; therapeutic use ; Female ; Graft Rejection ; immunology ; Graft Survival ; immunology ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Treatment Outcome ; Young Adult

BACKGROUNDAlemtuzumab, a humanized CD52 monoclonal antibody, with its profound lymphocyte depletion property, was expected to be a promising induction therapy agent for kidney transplantation (KTx). However, currently no consensus is available about its efficacy and safety. The aim of this meta-analysis was to make a profound review and an objective appraisal of this issue.

METHODSRelevant papers were searched, essentially in the PubMed database and the Cochrane library. After a thorough review, randomized controlled trials (RCTs) comparing the outcome of KTx using alemtuzumab induction therapy (test group) with a control group were collected according to the inclusion criteria. Data of general characteristic of studies and major outcomes of Ktx were extracted and meta-analyses were performed with RevMan 4.2 software. The odds ratio (OR) with a 95% confidence intervals (CI) was the principle measurement of effect.

RESULTSFive RCTs were included. The chi square test showed no significant between-study heterogeneity, thus fixed effect model was employed. Sub-group analysis with studies including alemtuzumab induction followed by a tacrolimus-based immunosuppressive regimen showed that the acute rejection rate (ARR) was lower relative to the control (OR = 0.59, 95% CI 0.34 - 1.01, P = 0.05). However, meta-analysis with all included studies revealed that neither ARR nor patient/graft survival rates differ significantly between the test and the control group, but the cytomegalovirus (CMV) infection rate was higher in the test group (OR 2.50, 95% CI 1.22 - 5.12, P = 0.01). A great number of the test group recipients safely remained on a regimen that was steroid-free and with a reduced dose of conventional immunosuppressive drugs.

CONCLUSIONSAlemtuzumab induction therapy for KTx was an effective and safe protocol in the tested follow-up period. Steroid avoidance and a dose reduction of conventional immunosuppressive drugs after alemtuzumab induction therapy may have clinical importance. However, high quality RCTs with larger population and longer follow-up are needed for a more accurate and objective appraisal of this novel protocol.

Alemtuzumab ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm ; pharmacology ; therapeutic use ; Cost-Benefit Analysis ; Graft Rejection ; prevention & control ; Graft Survival ; drug effects ; Humans ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Kidney Transplantation ; economics ; immunology ; methods ; Randomized Controlled Trials as Topic ; Survival Rate

Alemtuzumab ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antibodies, Neoplasm ; therapeutic use ; Antigens, CD ; metabolism ; Antigens, CD7 ; metabolism ; Antigens, Neoplasm ; metabolism ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CD3 Complex ; metabolism ; CD5 Antigens ; metabolism ; CD52 Antigen ; Chromosome Aberrations ; Chromosome Deletion ; Cyclophosphamide ; therapeutic use ; Diagnosis, Differential ; Doxorubicin ; therapeutic use ; Glycoproteins ; metabolism ; Hodgkin Disease ; metabolism ; pathology ; Humans ; Lymphoma, Large-Cell, Anaplastic ; metabolism ; pathology ; Lymphoma, T-Cell, Peripheral ; drug therapy ; genetics ; metabolism ; pathology ; Neoplasm Recurrence, Local ; Prednisone ; therapeutic use ; Receptors, CXCR3 ; metabolism ; Survival Rate ; Vincristine ; therapeutic use