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Query: UMLS:C0021311 (Infection)
 38,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study investigated the efficacy, safety, and clinical benefit of alemtuzumab (Campath-1H) for patients with relapsed or refractory B-cell chronic lymphocytic leukemia exposed to alkylating agents and having failed fludarabine therapy. Ninety-three patients received alemtuzumab in 21 centers worldwide, with the aim to obtain an overall response rate of at least 20%. Dosage was increased gradually (target 30 mg, 3 times weekly, for a maximum of 12 weeks). Infection prophylaxis was mandatory, beginning on day 8, and continuing for a minimum of 2 months after treatment. Responses were assessed at weeks 4, 8, and 12, and patients were followed for 34 months. Overall objective response in the intent-to-treat population (n = 93) was 33% (CR 2%, PR 31%). Median time to response was 1.5 months (range, 0.4-3.7 months). Median time to progression was 4.7 months overall, 9.5 months for responders. At data cut-off, 27 patients (29%) were alive; overall median survival was 16 months (95% CI: 11.8-21.9) and 32 months for responders. Nineteen responders survived more than 21 months. Clinical benefit was observed both in responders and in patients with stable disease. The most common adverse events were related to infusion, generally grade 1 or 2 in severity, occurring mainly in the first week. Grade 3 or 4 infections were reported in 25 patients (26.9%). However, only 3 (9.7%) of 31 patients who responded to alemtuzumab treatment developed grade 3 or 4 infections on the study. Alemtuzumab induced significant responses in these patients with clinical benefit in the majority and with acceptable toxicity in a high-risk group.
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PMID:Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. 1198 7

Infections remain a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia. These patients are predisposed to infection due to the immune compromise inherent to the primary disease and to therapy-related immunosuppression. The introduction of purine analogs and agents such as Campath-1H into the therapeutic armamentarium for chronic lymphocytic leukemia has altered the spectrum of infections. Although bacterial infections are most common, opportunistic infections, such as those caused by Candida, Pneumocystis and herpesviruses, may occur, related to T-cell immunosuppression induced by these agents. We will review the pathogenesis of infection, spectrum of infections, risk factors for infection and approaches for infection prophylaxis and therapy.
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PMID:Update on prophylaxis and therapy of infection in patients with chronic lymphocytic leukemia. 1211 37

This phase II study determined the efficacy and safety of alemtuzumab, a humanized anti-CD52 monoclonal antibody, delivered subcutaneously as first-line therapy, over a prolonged treatment period of 18 weeks in 41 patients with symptomatic B-cell chronic lymphocytic leukemia (B-CLL). Injections were administered subcutaneously 3 times per week, from week 2 to 3 onward. An overall response rate (OR) of 87% (95% CI, 76%-98%; complete remission [CR], 19%; partial remission [PR], 68%) was achieved in 38 evaluable patients (81% of intent-to-treat population). CLL cells were cleared from blood in 95% patients in a median time of 21 days. CR or nodular PR in the bone marrow was achieved in 66% of the patients and most patients achieved this after 18 weeks of treatment. An 87% OR (29% CR) was achieved in the lymph nodes. The median time to treatment failure has not yet been reached (18+ months; range, 8-44+ months). Transient injection site skin reactions were seen in 90% of patients. Rigor, rash, nausea, dyspnea, and hypotension were rare or absent. Transient grade IV neutropenia developed in 21% of the patients. Infections were rare, but 10% patients developed cytomegalovirus (CMV) reactivation. These patients rapidly responded to intravenous ganciclovir. One patient, allergic to cotrimoxazole prophylaxis, developed Pneumocystis carinii pneumonia. Alemtuzumab is highly effective as first-line treatment in patients with B-CLL. Prolonged treatment is important for maximal bone marrow response. Subcutaneous administration induced very few "first-dose" flulike symptoms and may reduce health care costs in comparison with the intravenous infusions.
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PMID:Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). 1213 Apr 84

Respiratory virus infections can cause serious morbidity and mortality after conventional allogeneic stem cell transplantation. However, the incidence and outcome of these infections after reduced intensity conditioning has not been reported. Between 1997 and 2001, 35 episodes of respiratory virus infections were noted in 25 of 83 transplant recipients conditioned with fludarabine, melphalan and Campath-1H, and 80% of them received early antiviral therapy. Parainfluenza virus (PIV) 3 was the commonest isolate (45.7%) followed by respiratory syncytial virus (37%). Patients with myeloma were more susceptible to these infections [odds ratio (OR) 4.1, P = 0.01] which were often recurrent in patients with severe acute or chronic graft-versus-host disease (GVHD) (OR 10.6, P = 0.03). Infection within the first 100 d (OR 5.0, P = 0.05) and PIV 3 (OR 9.2, P = 0.01) isolation were risk factors for developing lower respiratory infection. Although more than half of the episodes progressed to lower respiratory infection, the mortality was only 8%. This could have been due to early initiation of antiviral therapy, but the attenuation of pulmonary damage due to the reduced-intensity conditioning, low incidence of GVHD and, paradoxically, the low CD4+ T-cell subset in this setting might also have been contributory factors.
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PMID:Respiratory virus infections in transplant recipients after reduced-intensity conditioning with Campath-1H: high incidence but low mortality. 1247 97

Immunosuppression for immunologically high-risk renal transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody, has shown promise in tolerogenic induction protocols, requiring minimal maintenance immunosuppression. In this prospective, open-label, randomized, controlled trial, we enrolled 21 high immunological risk patients (i.e., panel reactive antibody>20% or previous transplant). Patients received either single-dose alemtuzumab given before graft reperfusion, with tacrolimus monotherapy, or four doses of Thymoglobulin with tacrolimus, mycophenolate, and steroids. Median follow-up was 377 days. One patient in the Thymoglobulin group who suffered primary graft nonfunction died. One-year cumulative graft survival was 85.7% for the alemtuzumab group and 87.5% for the Thymoglobulin group. Two alemtuzumab and three Thymoglobulin patients suffered rejection episodes. Infection rates were similar. Early results of this ongoing study indicate that a tolerogenic protocol with alemtuzumab induction and tacrolimus maintenance monotherapy is safe in immunologically high-risk renal transplant patients.
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PMID:Alemtuzumab (Campath 1H) induction with tacrolimus monotherapy is safe for high immunological risk renal transplantation. 1756 26

Here we report on our experience with subcutaneous (SQ) Alemtuzumab in an uncontrolled study in highly HLA-sensitized patients (HS). From 3/05-4/07, 54 HS patients received Alemtuzumab 30 mg SQ as induction. Patient and graft survival, AR episodes, serum creatinines, absolute lymphocyte counts, monthly PCR monitoring for viruses, AE/SAEs and infectious complications were monitored. No patient to date has developed acute injection-related reactions after SQ Alemtuzumab; however, bone marrow suppression was occasionally seen requiring reduction or elimination of mycophenolate mofetil approximately 1-2 months posttransplant. Patient and graft survival at 12 M was 98%/96%, respectively. AR episodes occurred in 35% with 20% being C4d+ AMR. Mean SCrs at 12 M were 1.4 +/- 0.3 mg/dL. The nadir ALC was 0.17 +/- 0.19 within 24 h and sustained up to 365 days posttransplant. Infections occurred in eight patients (five with polyoma BK viremia [PBK], one CMV/PBK and two CMV viremia). SQ Alemtuzumab was well tolerated and resulted in prolonged lymphocyte depletion. Compared to our previous experience with daclizumab and rabbit ATG induction in HS patients, single-dose SQ Alemtuzumab was more cost effective, showed similar infection rates and did not reduce the AMR rates posttransplant. Although uncontrolled, these observations suggest that induction therapy with Alemtuzumab appears feasible and indeed promising, but awaits more definitive study.
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PMID:Analysis of subcutaneous (SQ) alemtuzumab induction therapy in highly sensitized patients desensitized with IVIG and rituximab. 1797 66

The treatment of steroid-refractory acute graft-versus-host disease (aGVHD) remains a clinical challenge, for which no standard therapy exists. Alemtuzumab is a humanized anti-CD52 monoclonal antibody (mAb) that has been successfully used as part of conditioning regimens for hematopoietic stem cell transplantation (HSCT) to prevent GVHD. The purpose of this study was to evaluate the safety and efficacy of alemtuzumab in treating steroid-refractory aGVHD (>or=grade II) following HSCT. Eighteen patients received subcutaneous alemtuzumab 10 mg daily on 5 consecutive days. Response was assessed at day 28 following initiation of alemtuzumab. Eight patients had grade II aGVHD, 8 had grade III, and 2 had grade IV. The main organ involved was the liver in 4 patients, gastrointestinal (GI) tract in 5, skin in 3, skin and liver in 3, and skin and GI tract in 3. Fifteen patients (83%) responded to alemtuzumab, including 6 (33%) with complete response. All 3 unresponsive patients died of GVHD. Ten of 15 responders are alive at median follow-up of 11 months (range: 3-24). Infections occurred in 14 patients, including cytomegalovirus (CMV) reactivation in 11. Grade 3 neutropenia and thrombocytopenia occurred in 6 and 4 patients, respectively. Alemtuzumab was well tolerated, and induces promising response rates in steroid-refractory aGVHD.
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PMID:Alemtuzumab for the treatment of steroid-refractory acute graft-versus-host disease. 1815 56

Infection is a significant cause of morbidity and death in patients with chronic lymphocytic leukemia (CLL). Increased infectious events may arise from the multiple courses of immunosuppressive therapy and progressive deterioration of a patient's immune system over the course of disease. The humanized, anti-CD52 monoclonal antibody alemtuzumab (Campath or Campath-1H) has shown notable activity for both untreated and fludarabine-refractory CLL. The antibody not only targets malignant cells but also affects normal, healthy immune cells. The cumulative effects of the malignancy and successive courses of treatments adversely impinge on a patient's defense response to certain bacterial, fungal, and viral infections. In this review article, we provide an overview of common infectious events associated with alemtuzumab therapy in CLL. We also discuss recommendations for effectively monitoring and managing infections in CLL patients.
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PMID:Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab. 1868 48

BACKGROUND.: Alemtuzumab and rabbit antithymocyte globulin (rATG) are commonly used for induction of immunsuppression for kidney and pancreas transplantation, but the two agents have not been compared directly. METHODS.: We conducted a prospective randomized single-center trial comparing alemtuzumab and rATG induction in adult kidney and pancreas transplantation in patients treated with similar maintenance immunosuppression. RESULTS.: Between February 1, 2005, and September 1, 2007, 222 patients randomly received either alemtuzumab (n=113) or rATG (n=109) induction; 180 (81%) underwent kidney alone, 38 (17%) simultaneous pancreas-kidney, and 4 (2%) pancreas after kidney transplants. Of 180 kidney-alone transplants, 152 (84%) were from deceased donors, including 61 (34%) from expanded criteria donors. Retransplantation, human leukocyte antigen match, antibody titer, expanded criteria donors, race, cytomegalovirus status, delayed graft function, and immunologic risks were similar between the two induction groups. With a median follow-up of 2 years (minimum 1 year), overall patient, kidney, and pancreas graft survival rates were 96%, 89%, and 90%, respectively. Survival, initial length of stay, and maintenance immunosuppression (including early steroid elimination) were similar between alemtuzumab and rATG groups, but biopsy-proven acute rejection (BPAR) episodes occurred in 16 (14%) alemtuzumab patients compared with 28 (26%) rATG patients (P=0.02). Late BPAR (>12 months after transplant) occurred in 1 (8%) alemtuzumab patient and 3 (11%) rATG patients (P=NS). Infections and malignancy were similar between the two induction arms. CONCLUSION.: Alemtuzumab and rATG induction therapies were equally safe, but alemtuzumab was associated with less BPAR.
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PMID:A randomized trial of alemtuzumab versus antithymocyte globulin induction in renal and pancreas transplantation. 1992 Jul 81

A total of 1,859 intestinal transplants was reported to UNOS during the past 20 years (1,822 deceased, and 37 living donors). Forty-three US transplant centers reported at least one intestinal transplant, among them, Jackson Memorial Hospital, Nebraska Medical Center and University of Pittsburgh Medical Center were the 3 largest centers, each performing more than 300 cases. The University of Illinois Medical Center performed the most (N = 24) living donor intestinal transplants. The one-, five-, and ten-year graft survival rates of all recipients are 71%, 45%, and 32%. The longest surviving adult intestine transplant is 19 years posttransplant and the longest surviving pediatric transplant is 18 yrs. Both were simultaneous intestine and liver transplants from deceased donors. The first living-donor intestine transplant was reported to UNOS in 1995. The patient received an intestine-alone transplant which functioned for 501 days. The longest surviving living donor intestine transplant is still functioning after 11 years. Among transplants that included the intestine, 37% were intestine-alone transplants, 30% included intestine+liver+pancreas, and 24% were intestine+liver. One-, 5-, and 10-year graft survival rates of intestine-alone recipients were 80%, 44% and 26%; while those for Intestine+liver and intestine+liver+pancreas, were, 62%, 45%, 36%, and 69%, 48%, 33%, respectively. HLA mismatches seemed to have no effect on graft survival for primary intestinal graft recipients, but the most poorly matched (5-6-HLA antigen mismatches) regraft recipients had notably lower graft survival rates. Patients who received ABO blood type compatible intestinal grafts from an "O" donor had a significantly lower graft survival than AB recipients of an A or B donor or those who received ABO identical transplants. Only 4 ABO incompatible intestinal transplants have been reported and all of them have failed. The first ABO incompatible transplant in the US was performed in 1990 and the graft survived for 7 days. The longest survival of an ABO incompatible transplant was 3.5 years. Ischemic time of intestine, patient's and recipient's CMV status had no effect on graft survival. Patients with a history of rejection episodes posttransplant or who had been previously transplanted had significantly lower graft survival rates. Acute rejection, chronic rejection and infection were among the major causes of graft failure. Infection, multiple organ system failure and graft rejection were the major causes of patient death. Induction therapy was used for 67% of all intestine recipients, which is lower than for kidney (83%) but higher than for liver recipients (59%). Thymoglobulin remained the most commonly used antibody since its introduction into intestine transplantation in 1999. In recent years, more patients received Zenapax/Simulect (anti-IL-2 receptor), Campath (anti-CD52) and Rituximab (anti-CD20). These antibodies were usually used in combination with other immunosuppressants. Patients receiving steroids and Campath induction therapy had higher graft and patient survival than other protocols. Prograft, steroids, Cellcept and Rapamycin were the 4 major immunosuppressants used in maintenance therapy. Prograft and steroids have been used more than 20 years since the initiation of the UNOS intestine database in 1990. Among all maintenance immunosuppression protocols, Prograft+steroids (43%), Prograft-alone (14%), Prograft+steroids+ Cellcept (11%), and Prograft+steroids+Rapamycin (6%) are the top 4 major protocols. Patients on Prograft+steroids+Rapamycin had the highest graft and patient survival rates, while those on steroids alone had the lowest.
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PMID:Intestine and multivisceral transplantation in the United States: a report of 20-year national registry data (1990-2009). 2052 78


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