Antithymocyte Globulin Therapy Research Articles

UP-03.034 Is There a Relation Between Post Kidney Transplantation Antithymocyte Globulin Therapy and Wound Healing Disturbance?

UP-03.034 Is There a Relation Between Post Kidney Transplantation Antithymocyte Globulin Therapy and Wound Healing Disturbance?

Worsening Bradycardia Following Antithymocyte Globulin Treatment of Severe Aplastic Anemia

Immunosuppressive regimens, which include antithymocyte globulin (ATG), are widely used for the treatment of severe aplastic anemia (SAA). However, bradycardia has been reported only as a rare side effect of ATG therapy in the manufacturer's product information and, in rare cases, in the adult literature. We present an adolescent with SAA and preexisting bradycardia who underwent immunosuppression therapy with ATG, methylprednisolone, and tacrolimus and developed profound sinus bradycardia with successive doses of ATG.

Efficacy and safety of single and multiple dose antithymocyte globulin induction treatment in living related renal transplantation

Introduction The aim of the study was to compare the safety and efficacy of two regimens of induction therapy with antithymocyte globulin (ATG)-Fresenius in living related renal transplant recipients. Methods Eighty-seven patients were allocated into group 1 receiving single dose ATG (9 mg/kg b.w., 15 patients), group 2, multiple dose ATG (9 mg/kg b.w. intraoperatively plus 3 mg/kg b.w. for the next 4 days, 53 patients), group 3 on triple immunosuppression alone (20 patients). Maintenance immunosuppression consisted of cyclosporine (CsA) or tacrolimus (Tac), mycophenolate mofetil, corticosteroids. Results Demographic data was similar for all groups. In comparison to groups 1 and 2, patients from group 3 had lower immunologic risk, although insignificant. One patient: 6.6% from group 1; nine: 16.9% from group 2; and three: 15% from group 3 exhibited acute rejection (AR) and five patients: one from group 1, and three from group 2 delayed graft function (DGF). Mean creatinine clearance differed insignificantly between the groups during the follow-up period. Multiple dose ATG therapy was associated with leucopenia (six patients) and more frequent infections (group 1 vs 2: P = 0.03). Conclusion In kidney graft recipients without history of prior kidney transplantation or peak PRA lower than 50% single dose, ATG is as safe and equally efficient as multiple ATG doses in the prevention of AR and DGF but the same efficacy was achieved with triple immunosuppression.

Treatment of childhood aplastic anemia with antithymocyte globulin, management of side effects and long-term follow-up

To evaluate the efficacy of antithymocyte globulin (ATG) based immunosuppression therapy for childhood aplastic anemia, to reduce the adverse effects and to observe the long-term outcome. Thirty-five children with aplastic anemia (AA) were enrolled in this study. Six of the cases had very severe AA (VSAA), 11 had severe AA (SAA)-I, 8 had SAA-II and 10 had moderate AA (MAA). All these patients were treated with ATG plus Cyclosporin A (CSA). The following measures were taken during the ATG therapy: infection of the patients had been controlled before ATG treatment. Comprehensive anti-allergic measures were implemented. Close attention was paid to the hemorrhage related with platelet reduction caused by ATG and severe infection of the patients. Shortly after the ATG usage, all the patients had a significant decrease of absolute peripheral lymphoblast count by more than 60 percent. With a mean follow-up time of 28 months, the total effective rate was 77.14% (27/35), significant response rate was 57.14%(20/35). There was no significant difference among VSAA, SAA and MAA groups in the response rate. Adverse reactions included the following: (1) 48.6% (17/35) patients presented mild anaphylactoid reaction during the first day of ATG treatment; (2) 42.9%(15/35) cases presented serum sickness 5 - 11 days after the last dose of ATG with a mean duration of 3.6 days, all the patients were cured effectively with methylprednisolone; (3) 25.7% (9/35) patient's peripheral blood platelet count was reduced, might be caused by ATG, to below 10 × 10(9)/L, but no patient had severe hemorrhagic complication after platelet transfusion was performed; (4) 22.9%(8/35)of patients got infection within a month after ATG therapy, including 3 cases with clinical septicemia, all the 3 cases recovered after antibiotics treatment. There was no ATG treatment-related death in this series. ATG is a very effective therapy for children with SAA and MAA. Comprehensive measures are needed to prevent and handle the side effects to avoid treatment-related death. Long-term supportive therapy and proper follow up contribute to the favourable outcomes of the patients.

Low-Dose Rabbit Antithymocyte Globulin Induction Therapy Results in Prolonged Selective Lymphocyte Depletion Irrespective of Maintenance Immunosuppression

Rabbit antithymocyte globulin therapy (rATG) is a potent lymphocyte-depleting agent commonly used following renal transplantation to reduce the risk of acute rejection. Standard doses (7–10 mg/kg) of rATG result in profound lymphopenia and predispose patients to infection and malignancy. The effects of lower doses of rATG (LoD-rATG, 3–5 mg/kg) on peripheral blood lymphocytes (PBL) are as yet unknown. In this prospective clinical trial, PBL subsets were characterized by flow cytometry over 12 months following LoD-rATG therapy. All patients were initially treated with standard doses of tacrolimus, mycophenolic acid, and prednisone. At 3 months, patients were randomized to either lower doses of tacrolimus or sirolimus to examine the effects of maintenance immunosuppression on PBL reemergence. LoD-rATG therapy resulted in prolonged suppression of CD19 + B cells, total CD3 + T cells, as well as naïve and memory CD4 + T cell and CD4/CD25/Foxp3 + T-regulatory subsets irrespective of chronic immunosuppressive therapy. Selective depletion was only noted in the CD4CD45RA + naïve T-cell subset resulting in an altered memory/naïve CD4 + ratio. LoD-rATG failed to deplete CD8 + T cells, which increased their relative contribution to the total CD3 + pool. All other lymphocyte subsets maintained near normal proportions. Thus, LoD-rATG therapy may lessen the adverse effects of full dose rATG while maintaining overall efficacy.

Antithymocyte treatment of steroid-resistant acute rejection in renal transplantation

To evaluate the outcome of early (ER <3 months) and late (LR >3 months) episodes of corticosteroid resistant acute allograft rejection (CRR) treated with anti-thymocyte globulin (ATG) in pediatric renal allograft recipients. Retrospective study of 15 children, mean age 13.2 y, who received ATG for the treatment of biopsy proven CRR over a 15 year period. Seven children received ATG for ER (median 26 days post transplantation) and 8 for LR (median 763 days). There was a significant improvement in the 3 month eGFR (70.3 ml/min/1.73m(2), SD 22.3, p = 0.018) when compared with the value prior to ATG treatment (23.3 ml/min/1.73m(2), SD 10.2) in the ER group. In the LR group (4 DSA positive) there was no improvement in the eGFR at 3 months (42 ml/min/1.73m(2), SD 10.5, p = 0.32) when compared with the value prior to ATG (38 ml/min/1.73 m(2), SD 9.7). At final review, eGFR in the ER group was 72.3 ml/min/1.73m(2) (SD 33) vs. 37.7 ml/min/1.73m(2) (SD 17.9) in the LR group after a mean follow up of 10.4 y and 1.2 y, respectively. ATG therapy in CRR is associated with reversal of rejection and excellent graft outcome in children with ER. The benefits remain uncertain in LR, the etiology of which is multifactorial.

Serious Infection Risk and Immune Recovery after Double-Unit Cord Blood Transplantation Without Antithymocyte Globulin

Factors contributing to infection risk after cord blood transplantation (CBT) include the use of anti-thymocyte globulin (ATG), prolonged neutropenia, and failure to transfer immunity. In the present study, we investigated the potential of double-unit CBT without ATG to reduce the risk of infection and evaluated the nature of serious infections in the first year after CBT using this approach. Seventy-two predominantly adult patients underwent CBT for hematologic malignancies; of these, 52 patients received myeloablative conditioning, and 20 received nonmyeloablative conditioning. The peak incidences of bacterial infections (32%), fungal infections (14%), and bacterial/fungal pneumonias (10%) occurred in the first 30 days posttransplantation. Three such infections contributed to early mortality. The peak incidence of viral infections was 31-60 days posttransplantation, affecting 30% of patients. Cytomegalovirus (CMV) was the most common viral infection. CMV infections occurring before day 120 (n = 23) had no relationship with graft-versus-host disease (GVHD), whereas CMV infections occurring after day 120 (n = 5), along with all cases of Epstein-Barr virus viremia (n = 5) and adenoviral enteritis (n = 2), occurred exclusively in the context of GVHD therapy or corticosteroid use for another indication. Viral infections had the highest lethality: 2 were a direct cause of death, and 3 contributed to death. Patients exhibited steady immune recovery, achieving a median CD3(+)4(+) T cell count >200 cells/μL by day 120 post-CBT, and no infection-related deaths occurred after day 120. Our results suggest that double-unit CBT without ATG is associated with prompt T cell recovery, and, unlike in CBT incorporating ATG, infection is rarely a primary cause of death. However, CBT without ATG is associated with a significant risk of GVHD, and serious infections remain a challenge, especially in the setting of GVHD. New strategies are needed to further reduce infectious complications after CBT; these will require earlier neutrophil recovery and more effective prevention of GVHD, ideally without the profound T cell depletion associated with ATG therapy.

Resolution of Severe Ipilimumab-Induced Hepatitis After Antithymocyte Globulin Therapy

Resolution of Severe Ipilimumab-Induced Hepatitis After Antithymocyte Globulin Therapy

Epstein-Barr virus-associated lymphoproliferative disorder developed after anti-thymocyte globulin therapy in a patient with bone marrow failure associated with T-cell large granular lymphocytic leukemia

Epstein-Barr virus-associated lymphoproliferative disorder developed after anti-thymocyte globulin therapy in a patient with bone marrow failure associated with T-cell large granular lymphocytic leukemia

Hepatofugal portal flow associated with acute rejection in living-donor auxiliary partial orthotopic liver transplantation: A report of one case and literature review

We report a case of reversible hepatofugal portal flow after auxiliary partial orthotopic liver transplantation (APOLT) from a living donor in this study. On postoperative day 6, continuous hepatofugal portal flow was observed in the grafted liver without portal thrombosis and obstruction of the hepatic vein. Based on histological findings, acute rejection was the suspected cause. The normal portal venous flow was restored after steroid pulse and antithymocyte globulin (ATG) therapies. The patient was discharged on the 30th postoperative day. It was concluded that hepatofugal flow after liver transplantation is a sign of serious acute rejection, and can be successfully treated by anti-rejection therapy.

Can the Preprocurement Pancreas Suitability Score Predict Ischemia-Reperfusion Injury and Graft Survival After Pancreas Transplantation?

Background Ischemia-reperfusion injury (IRI) is common after pancreas transplantation, leading to pancreatitis or thrombosis with the need for relaparotomy or even graft loss. Optimal donor selection may reduce the postoperative morbidity of IRI. The Eurotransplant preprocurement pancreas suitability score (P-PASS) seeks to identify ideal donors with a value <17. Owing to the organ shortage the waiting time for pancreas transplantation is increasing, a problem that may be addressed with the use of extended-criteria donors. We analyzed our pancreas transplantations regarding postoperative complications according to the P-PASS. To reflect IRI we used the peak C-reactive protein (CRP) levels during the first 3 postoperative days. Methods From January 2009 to July 2010, we transplanted 52 pancreas grafts, including, 50 simultaneous pancreas-kidney transplantations (SPK), 1 after a kidney graft, and 1 alone. For 3 SPK donors the P-PASS was not available. All transplantations were performed using systemic venous and enteric drainage. The immunosuppression protocol included antibody induction with antithymocyte globulin and maintenance therapy with steroids, tacrolimus, and mycophenolate mofetil. The peak CRP in the first 3 postoperative days was used as a marker for IRI. Results The mean P-PASS of our donors was 16.4 ± 2.6 (range, 12–22). We compared 24 patients receiving organs from “ideal” donors (P-PASS <17; ID) with 25 receiving grafts from extended-criteria donors (P-PASS ≥17; ED). There was no significant difference in the incidence of graft loss among ID versus ED grafts (20.8% vs 20.0%; P = 1.0). Comparing the rates of postoperative complications of patients, we did not observe a significant difference in graft thrombosis (4.2% vs 16.0%; P = .349), relaparotomy (29.2% vs 40.0%; P = .551), a pancreatic fistula (37.5% vs 28.0%; P = .543), or the length of hospital stay (36.5 ± 19.2 vs 37.4 ± 20.8 days; P = .875), respectively. Regarding IRI, there was no significant difference in peak CRP values (14.1 ± 5.5 vs 16.2 ± 6.0 mg/dL; P = .211). Conclusion This single center analysis failed to show that P-PASS significantly predicted pancreas graft survival, postoperative morbidity, or IRI severity. These findings suggested a chance to increase the donor pool using extended-criteria donors.

Long-Term Clinical Outcome of Patients with Acquired Aplastic Anemia In Brazil Using Cyclosporine-A (CSA) and Prednisone (PRED): 20 Years Follow-up From a Single Institution

AbstractAbstract 2234 Introduction/Background:Immunosuppressive therapy is the best alternative for patients with severe aplastic anemia (SAA) without matched sibling donor or with age > 40 years. Since 1988, an alternative protocol was developed with cyclosporine (CSA) and prednisone (PRED) due to irregularity in distribution of anti-thymocyte globulin (ATG) in Brazil. This study aims to show the results of this treatment on the quality of response, overall survival and development of clonal evolution. Materials and methods:384 patients diagnosed with SAA (Camitta and Bacigalupo criteria) were evaluable by medical records review from 12/1988 to 12/2008. The immunosuppressive therapy consisted of CSA: 12mg/kg/day BID from day (D)1- D8, then 7mg/kg/day BID until 1 year. After that CSA was progressively tapered (5% each month) and ultimately stopped usually by two years. CSA levels were kept between 200–400ng/ml. PRED: 2mg/kg/day from D1-D14 then 1mg/kg/day from D15- D45. From that day on PRED dose was tapered 20% each week. Sulfamethoxazole-trimethoprim and fluconazole were used for prophylaxis against Pneumocystis jiroveci (P carinni) and fungal diseases, respectively. Treatment response was defined as Table 1.Treatment evaluation was performed at 6 weeks, 3, 6 and 12 months and then yearly. At diagnosis: median age was 21 years (2-75), disease duration 95 days (2-4749), and median number of transfusions were 12 (0-200). Etiology was idiopathic in 78%. In peripheral blood, median hemoglobin was 7.4g/dL, granulocytes 580/uL, platelets 12.000/uL and reticulocyte 0.5% (corrected value). 60% of the patients had not been treated previously. Results:Overall survival was 61% ± 3 with a median follow-up of 7 years (range: 2 months - 23 years). Response to treatment: 51% had some degree of response, with good quality of life and transfusions independent (143 patients with complete response and 53 partial response). 36 patients had no response and there were 96 deaths. Fifty six patients have lost follow-up. Most patients achieved response between 3 and 6 months of therapy. In multivariate analysis the number of neutrophils ≥ 200/uL (p = 0.009), platelets ≥ 12.000/uL (p = 0.018), reticulocyte ≥ 0.5% (p <0.001) and starting treatment after 1997 (p = 0.002) had an impact on overall survival. Patients with 15 or more previous transfusions (p = 0.006) and age ≥ 40 years (p = 0.003) had lower survival. Overall survival was 63% ± 4 and 42% ± 6 for for patients with severe disease and very severe aplastic anemia (p <0.001). The subgroup analysis of patients under 10 years old had similar results. Among patients with response, thirty-four remained dependent of CSA. Cumulative incidence of relapse was 28% ± 4 within a median of 4.4 years. Hypertension, gingival hypertrophy and diabetes mellitus were common, but easily controlled. The rate of clonal evolution among this cohort was 7.81% (16 patients developed Paroxysmal Nocturnal Hemoglobinuria, 9 Myelodysplastic Syndrome and 5 Acute Myeloid Leukemia). Conclusion:This study, with a long follow-up, has demonstrated that the overall survival using CSA and PRED is similar to that reported with ATG therapy. Even patients with partial responses had achieved good quality of life, free from transfusions and infections. Survival was influenced by the neutrophils, platelet counts, reticulocyte, number of transfusions, age at diagnosis, and therapy started after 1997. The incidence of clonal evolution was lower when compared to reported trials with ATG + CSA.Table 1ResponseHemoglobin (g/dL)Neutrophils (/uL)Platelets (/uL)Complete>10>1000>100.000Partial>8>500>30.000No responseRequirement of red cells transfusion–Requirement of platelet transfusion Disclosures:Oliveira: Alexion: Speakers Bureau. Funke: Novartis, Bristol: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Pasquini: Novartis, Bristol: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Antithymocyte Globulin Induction Therapy in Heart Transplantation: Prospective Randomized Study of High vs Standard Dosage

Background In cardiac transplantation, high-dose antithymocyte globulin (ATG) induction therapy as short-term rejection prophylaxis has not been used. Objective To evaluate the efficacy and safety of intraoperative use of single high-dose ATG induction therapy after heart transplantation. Patients and Methods Fourteen patients received single high-dose ATG therapy plus shortened standard therapy (group1), and 16 patients received ATG standard therapy (group2). Results No perioperative deaths were reported. During follow-up, 3 deaths were recorded. Five- year patient survival was 92.8% in groupl vs 85.7% in group2 ( P = .34). The mean (SD) number of acute rejection episodes per patient was 2.5 (2.2) in the high-dose ATG group vs 2.7 (2.5) in the standard therapy group ( P = .83), with 5-year freedom from acute rejection of 45.5% in group 1 vs 35.6% in group 2 ( P = .85). Infections were observed in 6 patients in group1 and in 8 patients in group2 ( P = .69). Malignant disease was diagnosed in 1 patient in the high-dose group and 3 patients in the standard therapy group ( P = .35). Chronic allograft vasculopathy was recognized in 4 patients (28%) in group1 and 8 (50%) in group2 ( P = .05). Five-year actuarial freedom from allograft vasculopathy was 69.2% in the high-dose ATG group vs 50.0%% in the standard therapy group ( P = .35). Conclusions High-dose ATG for prevention of rejection episodes is safe and efficacious, with a lower rate of early and late complications, in particular, graft vasculopathy.

Epstein–Barr virus-related lymphoproliferative disorder induced by equine anti-thymocyte globulin therapy

Post-transplant lymphoproliferative disorder (PTLD) is generally caused by an uncontrolled B-cell proliferation induced by Epstein-Barr virus (EBV) in the setting of impaired EBV-specific T-cell immunity. PTLD has been described in allogeneic hematopoietic stem cell transplant (HSCT) and rarely in autologous HSCT. Anti-thymocyte globulin (ATG) is being increasingly utilized for acute rejection in organ transplantation, severe autoimmune diseases and aplastic anemia. Mainly, the use of rabbit ATG has been associated with PTLD, which is considered to be more immunosuppressive than equine ATG. The sole administration of equine ATG has rarely been associated with PTLD. Due to the increased use of these potent and novel immunosuppressive agents, it is paramount to be aware of these complications. We present a 55-year-old man with an autologous HSCT who presented with an unusual case of monoclonal plasmacytic PTLD. His lymphoproliferative disorder occurred 3years after his HSCT and 1month after the use of equine ATG administered for severe aplastic anemia. We review current concepts of EBV-PTLD, including risk factors, the potential for preemptive therapy and various management strategies.

Thymoglobulin Induction and Sirolimus Versus Tacrolimus in Kidney Transplant Recipients Receiving Mycophenolate Mofetil and Steroids

To define the role of mammalian target of rapamycin inhibitors in kidney transplantation, we compared efficacy and safety of two immunosuppressive regimens-a calcineurin inhibitor-free regimen with depletive induction versus a calcineurin inhibitor-based regimen. De novo renal allograft recipients were randomized before transplantation to receive sirolimus (SRL; n=71, group A) or tacrolimus (n=70, group B). All patients received mycophenolate mofetil and corticosteroids. In group A, patients received rabbit antithymocyte globulin induction. In group B, antithymocyte globulin therapy could be given in case of delayed graft function. The estimated glomerular filtration rate (GFR) (Nankivell's formula) at month 12 was the primary endpoint. GFR showed no significant difference at month 12, with 56.1 in group A versus 58.4 mL/min/1.73 m in group B. In functioning grafts, renal function was significantly better in the SRL group, with higher GFR values at months 1, 2, 3, 6, and 9 (P<0.05). At month 12, patient survival and incidence of biopsy-proven rejection were not different between groups (95.8% vs. 97.1%, and 16.9% vs. 12.9%, respectively). However, proportion of graft loss was higher with SRL at months 6 and 12 (11.3% vs. 0.0%, P=0.004; 14.1% vs. 4.3%, P=0.044, respectively). Adverse events and premature withdrawals were more frequent with SRL (P<0.001 and P<0.05, respectively), whereas cytomegalovirus infections were more frequent with tacrolimus (P<0.001). Patients treated with induction plus SRL, mycophenolate mofetil, and corticosteroids may obtain good renal function but have a higher risk of adverse events, drug withdrawal, and graft loss.

Acute renal failure following antithymocyte globulin therapy for aplastic anaemia—report of two cases and review of literature

Dear Editor, Immunosuppressive therapy with antithymocyte globulin (ATG) with ciclosporine is the standard of care in patients with aplastic anaemia who are not eligible for bone marrow transplantation. ATG is an animal protein and its predominant toxicities include allergic reactions and serum sickness. Acute renal failure attributable to ATG has rarely been described. We report two patients with aplastic anaemia who developed acute renal failure during ATG therapy. Both patients developed oliguric acute renal failure with temporal relation to ATG administration and absence of other etiological factors. One of the patients had complete recovery of renal function with supportive treatment while the other died of sepsis and multi-organ dysfunction.

Early diagnosis and treatment of invasive pulmonary aspergillosis following kidney transplantation

To investigate the early diagnosis and treatment of invasive pulmonary aspergillosis (IPA) infection following kidney transplantation. A retrospective analysis was carried out in 16 IPA patients after kidney transplantation from January 2002 to March 2008. There were 7 males and 9 females with a mean age of 42.9 years old. The prevalence of IPA was 2.21%. The induction therapy was given to 12 patients, 5 with CD25 monoclonal antibody and 7 with anti-thymocyte globulin (ATG). All 6 with acute pre-infection rejection were given the methylprednisolone sodium or ATG therapy. The intervals between transplantation and diagnosis were largely within 3 months. Persistent or intermittent fever was the main post-operative symptom. High resolution computed tomography (HRCT) of thorax and bronchoalveolar lavage fluid (BALF) for culture were the main evidence of clinical diagnosis. Amphotericin B (0.15 - 0.5 mg * kg(-1) * d(-1)) might be the major treatment for IPA because of its satisfactory initial therapeutic effect. The mortality rate was 7/16 (43.75%). Of the 9 surviving patients, 8 were treated before the test results were available. The clinical symptoms of IPA following kidney transplantation are atypical in the early stage so that it is easy to misdiagnoses and a high mortality rate ensues. Major risk factors for IPA include administration of ATG, CD25 monoclonal antibody and steroid boluses for prevention or treatment of allograft rejection; prolonged broad-spectrum antibiotic use after transplantation and environmental factors. Early diagnosis and empirical use of antifungal agents while waiting for a definitive diagnosis are imperative in achieving a favorable outcome.

Hairy cell leukemia responsive to anti-thymocyte globulin used as immunosuppressive therapy for aplastic anemia

Hairy cell leukemia (HCL) is occasionally misdiagnosed as aplastic anemia when only a few leukemic cells are present in the circulation. Here, we describe a patient with HCL who initially presented with pancytopenia and received a diagnosis of aplastic anemia. The patient was treated with immunosuppressive therapy including cyclosporine A and anti-thymocyte globulin (ATG). No blood cell transfusion was required for approximately 3 years after ATG therapy. She was referred to our hospital because of an abdominal mass and requiring periodic blood transfusions. A bone marrow biopsy at this time revealed proliferation of lymphocytes with a fried egg appearance and an increase in reticulin fibers that are typical findings of HCL. It is notable that our patient with a presumably long history of HCL and an increase in marrow reticulin fibers showed good recovery of hematopoiesis after cladribine therapy. Some HCL patients may receive an initial diagnosis of aplastic anemia and may show a good response to ATG masking the underlying HCL.

Majocchi's granuloma after antithymocyte globulin therapy in a liver transplant patient

Majocchi's granuloma (MG) is an atypical and uncommon presentation of dermatophytic infection involving the invasion of dermal and subcutaneous tissue by fungal organisms. It usually begins as a suppurative folliculitis and may culminate in the development of widespread granulomas. Immunosuppressed patients are at increased risk, especially those with T-cell deficiencies. We describe a case of inguinal MG in a liver transplant patient who had received antithymocyte globulin for acute rejection.

Cytomegalovirus Infection and Disease Following Renal Transplantation: Preliminary Report of Incidence and Potential Risk Factors

Cytomegalovirus (CMV) infection and disease are major causes of morbidity and mortality after renal transplantation. However, the incidence and potential risk factors are different in developing countries. We sought to determine the incidence and potential risk factors for CMV infection and disease in our center. We also sought to identify groups of recipients who may benefit from preemptive therapy. Forty renal transplant recipients were monitored regularly for CMV infection within 6 months after transplantation using CMV immunoglobulin (Ig) M and IgG titers, pp65 antigenemia, and CMV DNA by polymerase chain reaction (PCR). Thorough laboratory and physical examinations were performed to detect CMV disease. We evaluated the role of various factors in CMV infection and disease development using Cox regression and Kaplan-Meier statistical models. CMV infection and disease were detected in 33 (82.5%) and 10 (25%) subjects, respectively. Average time to infection and disease development was 4.7 and 11 weeks, respectively. PCR was the most accurate method of diagnosis in 22 (67%) cases. By comparison to other recipients, patients who received antithymocyte globulin (ATG) showed a significant decrease in time to disease development (P = .009). Upon multivariate survival analysis, ATG therapy remained an independent risk factor for CMV disease (odds ratio: 6.8; P = .02). Due to the low rate of progression from CMV infection to disease, it does not seem reasonable to perform preemptive therapy in all infected cases. ATG therapy was an independent risk factor for CMV disease. Recipients of this treatment would be proper candidates to receive preemptive therapy.