Dose Of rATG Research Articles

Phase 2 Multicenter Trial of Rabbit Anti-Thymocyte Serotherapy In Myelodysplastic Syndrome: Rate of Hematological Improvement Associated with Pre-Treatment Disease Duration

AbstractAbstract 602 Introduction:T–cell depleting regimens that contain anti-thymocyte globulin (ATG) have been used for the treatment of myelodysplastic syndrome (MDS) suggesting a link between immune dysregulation and ineffective hematopoiesis in a subset of patients. Pre-treatment clinical features such as younger age, shorter duration of red cell transfusion dependence, and HLADR15 genotype were identified as response co-variates in a single institutional experience with equine ATG (eATG). We report results from the first US multicenter study examining rabbit (rATG) for the treatment of MDS. Methods and Patients:This study was a non-randomized, multicenter Phase II clinical trial of rATG (Thymoglobulin®) designed to examine the response and safety of this agent in MDS patients. The primary endpoint was IWG 2000 response rate with secondary analyses of duration of response, time to response, time to progression and tolerance. rATG 2.5 mg/kg/day was administered IV for 4 doses. The relationship between response and variables such as age, bone marrow cellularity, HLA-DR15, karyotype, blood counts, and disease duration were also investigated. Eligible patients had severe neutropenia (ANC < 1000), severe anemia (untransfused hemoglobin <9 g/dl), anemia requiring transfusion, or thrombocytopenia (platelet count < 50,000/mm3) plus the presence of 10% bone marrow blasts in patients with int-2. Patients with chronic myelomonocytic leukemia (CMML) and lab abnormalities were excluded. Statistical methods include Wilcoxon rank-sum test, Kaplan-Meier survival curve and log-rank test. Results:Between Aug.2004 and May 2010, 39 MDS patients were enrolled: 24 patients were eligible for treatment, and 21 evaluable for response. Drop out occurred due to initiation of therapy off study (n=5), non-compliance (n=1), death prior to treatment (n=2), and failure to meet eligibility criteria (n=7). IPSS risk categories in the evaluable patients included low-risk (n=6, 29%), int-1 (n=12, 57%), and int-2 (n=3, 14%). Infusion-related reactions were the most common adverse event, generally occurring with the first dose of rATG. There were 3 deaths among treated patients related to infection, including 1 patient with neutrophil hematologic improvement (HIN). Nine (43%) of the 21 evaluable patients experienced HI. Twelve (57%) were non-responsive including patients with stable disease (n=7, 33%) and disease progression (n=5, 24%) including 3 with excess blasts (n=2) or prior history of cancer treatment (n=1). The median time to response was 75 days (range 3 days–3.7 months) and median duration of response was 7.2 months (range 2–22+ months) with a median follow up of 20 months. Two patients maintained HI at the time of this analysis and response was extended in two patients by initiating cyclosporine As shown in Fig. 1, progression free survival (PFS) was greater in responders compared to non-responders (median PFS in responders 1 vs 0.23 year), but did not reach statistical significance (p=0.1). The mean age at treatment for evaluable patients was 64 years (median 66, range 44–79), however, age was not a significant co-variate for HI (median age in responders 65 years, non-responders 66, p=0.5). Only 4 patients had the HLADR15 allele, among whom 3 achieved HI (75%). Other factors such as IPSS, cytopenias, LDH, karyotype, age-adjusted bone marrow cellularity, and M:E ratio showed no association with HI in univariant analyses. Responding patients had a shorter time from diagnosis to treatment (responders median 8 months vs non-responders median 41.8 months, (p=0.18). [Display omitted] Conclusions:This multicenter study provides evidence that rATG is safe and has significant activity in MDS that warrants further study. Although independent of age, a pretreatment rATG response algorithm inclusive of HLADR15 and duration of disease appears to be similar to prior predictive models of eATG response. These results suggest that T-cell depleting rATG therapy may produce the best clinical outcome when implemented early in the disease process and further suggests that T-cell hematological suppression may contribute to the initiation of MDS pathogenesis. Support:This trial was conducted by the Bone Marrow Failure-Rare Disease Clinical Research Network (BMF-RDCRN 5406) sponsored by the NIH and Genzyme, Corp. This trial was registered at www.clinicaltrials.gov (NCT00466843). Disclosures:Epling-Burnette:Genzyme: Consultancy, Research Funding. Maciejewski:Genzyme Corp: Research Funding.

Total and Active Rabbit Antithymocyte Globulin (rATG;Thymoglobulin®) Pharmacokinetics in Pediatric Patients Undergoing Unrelated Donor Bone Marrow Transplantation

Rabbit antithymocyte globulin (rATG; Thymoglobulin®) is currently used to prevent or treat graft-versus-host disease (GVHD) during hematopoietic stem cell transplantation (HSCT). The dose and schedule of rATG as part of the preparative regimen for unrelated donor (URD) bone marrow transplantation (BMT) have not been optimized in pediatric patients. We conducted a prospective study of 13 pediatric patients with hematologic malignancies undergoing URD BMT at St. Jude Children's Research Hospital from October 2003 to March 2005, to determine the pharmacokinetics and toxicities of active and total rATG. The conditioning regimen comprised total body irradiation (TBI), thiotepa, and cyclophosphamide (Cy); cyclosporine (CsA) and methotrexate (MTX) were administered as GVHD prophylaxis. Patients received a total dose of 10 mg/kg rATG, and serial blood samples were assayed for total rATG by enzyme linked immunosorbent assay (ELISA) and active rATG by florescein activated cell sorting (FACS). We found that our weight-based dosing regimen for rATG was effective and well tolerated by patients. The half-lives of total and active rATG were comparable to those from previous studies, and despite high doses our patients had low maximum concentrations of active and total rATG. There were no occurrences of grade iii-iv GVHD even in patients having low peak rATG levels, and the overall incidence of grade II GVHD was only 15%. None of the patients had serious infections following transplantation. These data support the use of a 10 mg/kg dose of rATG in children with hematologic malignancies because it can be administered without increasing the risk of graft rejection, or serious infection in pediatric patients with a low rate of GVHD. These conclusions may not apply to patients with nonmalignant disorders.

Evaluation of Rabbit Antithymocyte Globulin (rATG) Dose-Intensity in Patients Undergoing Allogeneic Stem Cell Transplantation (ASCT) Following Reduced Intensity Conditioning (RIC) with Fludarabine, Busulfan and rATG (FBA)

We evaluated the effects of two doses of rATG (6.0 versus 7.5mg/kg/total dose) in patients undergoing RIC. All patients (n = 54) were conditioned with F (30 mg/m2/day, days -7 to -3), B (0.8 mg/kg/dose IV x 8 doses) and either 7.5mg/kg of rATG (7.5rA) (n = 39) or 6.0mg/kg of rATG (6rA) (n = 15), followed by micro-dose methotrexate and tacrolimus. Median age was 57 years. 76% (N = 41) had high-risk disease. 10 patients (18%) received mismatched allografts. 47 patients (87%) received grafts from unrelated donors. All patients engrafted neutrophils and platelets promptly (median 15 and 17 days, respectively). One patient had secondary graft failure, and another AML patient previously only treated with decitabine experienced secondary graft rejection. Both of these patients received 7.5rA. Compared to patients receiving 7.5rA, ones receiving 6rA had fewer EBV (25% vs. 13%; p-value = 0.3) CMV (61% vs. 25%; p-value = 0.05) and BK-viral (26% vs. 0%; p-value = 0.03) reactivations and lower rates of relapse (33% vs. 6.6%; p-value = 0.04), non-relapse mortality (28% vs. 0%; p-value = 0.008), grade II-IV acute GVHD (33% vs. 13%; p-value = 0.1) and chronic GVHD (45% vs. 13%; p-value = 0.03). None of the 6rA patients developed PTLD. Chimerism analysis showed 100% donor CD33+ chimerism at all time points and median donor CD3+ chimerism of 94%, 97%, 99% and 100% at days +30, +60, +90 and +180. No difference was seen in the two rATG doses. 40 patients (74%) were in CR after ASCT. The median follow-up of surviving patients is 12 months (range 1–28 months). Compared to patients receiving 7.5rA, ones receiving 6rA showed trends toward improved 1-yr overall survival (63% vs. 100% p-value = 0.06) and progression free survival (47% vs. 91% p-value = 0.06). Our preliminary data suggests that 6rA promotes effective donor cell engraftment, without compromising GVHD control compared to 7.5rA, and may be associated with lower rates of infectious complications and disease relapse.

Assessment of Rabbit Antithymocyte Globulin (rATG) Dose-Intensity in Patients with Hematological Malignancies Undergoing Allogeneic Stem Cell Transplantation (ASCT) Following Reduced Intensity Conditioning (RIC) with Fludarabine, Busulfan and rATG (FBA)

Incorporation of rATG in RIC regimens not only reduces rates of graft-versus-host disease (GVHD), but it also promotes effective engraftment of donor cells. However rATG at doses ≥7.5mg/kg, is associated with significant infectious complications (Hamadani M. ASH 2007). We hence embarked on a strategy designed to evaluate lower dose (6mg/kg) rATG in patients (pts) undergoing RIC with FBA. All pts (n=47) were conditioned with F (30 mg/m2/day, days-7 to -3), B (0.8 mg/kg/dose IV × 8 doses) and either 7.5mg/kg of rATG (7.5rA) (n=39) or 6mg/kg of rATG (6rA) (n=8), followed by micro-dose methotrexate and tacrolimus. Criteria for selection included advanced age (>55yrs), prior autograft, and/or high co-morbidity index (median 1, range 0–4). There were 31 male and 16 female pts with a median age of 57 years (range 24–70 yrs). Diagnoses included AML (N=17), NHL (N=10), Hodgkin's lymphoma (N=4), CML (N=5), advanced CLL (N=8), and others (N=3). 74% (N=35) had high-risk disease. Six pts had previously undergone autologous SCT. 36% had a Karnofsky performance status of 70 or 80% at the time of transplant. 9 pts (19%) had one or more antigen or allele level mismatches with their donors. Stem cell source included peripheral blood (N=43) or bone marrow (N=4). 42 pts (89%) received grafts from unrelated donors. All pts engrafted neutrophils and platelets promptly (median 15 and 17 days, respectively). One patient had secondary graft failure, and another AML patient previously only treated with decitabine experienced secondary graft rejection. Both of these patients received 7.5rA. Overall rates of grade II–IV and III–IV acute GVHD were 27% (N=13) and 17% (N=8) respectively. 17 pts (41%) developed chronic GVHD but extensive chronic GVHD was seen in only 21% (N=9). Day 100 and overall non-relapse mortality (NRM) was 6% (N=3) and 23% (N=11). Causes of death included disease progression=6, post-transplant lymphoproliferative disorder (PTLD)=2, GVHD=3, infection=4, and others=2. CMV, EBV, and BK-virus reactivation occurred in 55% (N=26), 25% (N=12) and 21% (n=10) respectively. Compared to pts receiving 7.5rA, ones receiving 6rA had fewer CMV (61% vs. 25%; p-value=0.05) and BK-viral (25% vs. 0%; p-value=0.03) reactivations and lower rate of relapse (33% vs. 12.5%; p-value=0.20), NRM (28% vs. 0%; p-value=0.01), and acute GVHD (33% vs. 0%; p-value=0.01). None of the 6rA pts developed PTLD. Overall lineage-specific chimerism analysis showed 100% donor CD33+ chimerism at all time points (days 30, 60, 90, and 180) and median donor CD3+ chimerism of 94%, 97%, 99% and 100% at days +30, +60, +90 and +180. No difference was seen in the two rATG doses. 36 pts (76%) were in CR after ASCT. The median follow-up of surviving patients is 12 months (range 3–26 months). Rates of overall survival (OS) and progression free survival (PFS) at 1year are 66% and 52% respectively. Using the Log-Rank test, OS and PFS was not statistically significant between recipients of matched and mismatched grafts, and between pts with high-risk or standard-risk disease. In conclusion, our preliminary data suggests that 6rA promotes effective donor cell engraftment, without compromising GVHD control, and may be associated with lower rates of infectious complications and disease relapse. Systematic evaluation of rATG dose de-escalation is continuing at our institution.

Randomized Trial of Single-Dose Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation: An Interim Report

The optimal dosing protocol for rabbit anti-thymocyte globulin (rATG) induction in renal transplantation has not been determined, but evidence exists that rATG infusion before renal allograft reperfusion improves early graft function. Infusing a large rATG dose over a short interval has not previously been evaluated for its effect on renal function and allograft nephropathy in a prospective, randomized comparison against conventional rATG induction. Between April 20, 2004 and December 26, 2007 we enrolled renal transplant patients into a prospective, randomized, nonblinded trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment=160) followed after 6 months by calcineurin-inhibitor withdrawal. Primary endpoints are renal function by calculated glomerular filtration rate (GFR) and chronic allograft nephropathy at protocol biopsy. We now present the early GFR data of all 160 patients and safety and efficacy data of the first 142 patients with 6 months follow up and before calcineurin inhibitor withdrawal (average follow up=23.3+/-11.6 months). There were no differences between groups in rATG-related adverse events, patient and graft survival, acute rejection, or chronic allograft nephropathy rate at 6 months. Calculated DeltaGFR (POD 1-4) was significantly better in the single-dose group (P=0.02), with a trend toward improved renal function from months 2 to 6 in recipients of deceased donor kidneys (P=0.08). This study demonstrates that administering 6 mg/kg of rATG over 24 hr is safe and is associated with improved early renal function compared with administering rATG in alternate-day doses.

Thymoglobulin Dose Optimization for Induction Therapy in High Risk Kidney Transplant Recipients

Thymoglobulin (rATG) has become the agent of choice for induction therapy in high immunological risk kidney transplant recipients. However, its optimal dosing in this subgroup has not been studied. To evaluate the effect of total rATG dosing on graft outcomes in such patients, we conducted a retrospective cohort study of 96 adult patients who received repeat transplants (85%) or had panel reactive antibody more than 40% (19%) and were maintained on tacrolimus, mycophenolate mofetil, and steroid. Group 1 (n=33) received less than or equal to 7.5 and group 2 (n=63) received more than 7.5 mg/kg rATG. Graft and patient survival, incidence of acute rejection (AR), and 12-month serum creatinine (SCr) were examined. The groups were comparable regarding demographics, donor source, retransplantation, panel reactive antibody, and human leukocyte antigen mismatch. Group 2 had more African Americans (44.4% vs. 21.2%, P=0.03). During the 25.4+/-18.0 months follow-up graft survival was 82.5% and 79.4%, respectively (P=0.54). Three in group 1 and four in group 2 died (P=0.65). The incidence of biopsy proven AR during the first 12-months did not differ between the groups (9.5% vs. 8.8%, respectively, P=0.9). SCr at 12 months was 1.6+/-0.7 in group 1 and 1.8+/-1.0 in group 2 (P=0.3). There was no independent association between rATG dose and graft survival (hazard ratio: 0.85, P=0.79, 95% CI: 0.26-2.7 for group 2 vs. 1) or 1-year SCr (regression coefficient=0.02 for ln(SCr), P=0.3; 95%CI: -0.01 to 0.6). Our results suggest that in high risk kidney transplant recipients total rATG doses less than or equal to 7.5 mg/kg are safe and effective in achieving a low rate of AR and graft outcomes comparable to higher doses.

A Randomized Trial of Rabbit Anti-Thymocyte Globulin, Given on Day+7 after Alternative Donor Transplants.

Background. We have shown that the risk of transplant mortality (TRM) can be predicted by using laboratory values, on day+7 after an allogeneic hemopoietic stem cell transplant (HSCT) (Sormani et al, Bone Marrow Transpl.2003). TRM in patients with low, intermediate and high risk on day+7, is 15%, 40% and 69%: increased mortality is mainly, but not exclusively, due to increased acute graft versus host disease (GvHD). In a pilot study we have shown that a small dose of rabbit anti-thymocyte globulin (rATG) (Thymoglobulin, Genzyme), was feasible and reduced GvHD and TRM.Aim of the study. We have therefore opened a randomized trial testing this hypothesis in patient undergoing an unrelated donor HSCT, with rATG (7.5 mg/kg) in the conditioning regimen.Patients. 170 were eligible: all patients received rATG 3.75 mg/kg x2 pre-transplant, and on day+7 they were scored and randomized to receive an additional dose of rATG (1,25 mg/kg day +7 and day+9) (n=84) or to receive no further treatment (n=86) (control arm). The two groups were balanced for age, disease phase and day+7 score.Results. The predictive value of day+7 score on TRM was confirmed in the control arm (18% vs 42% for intermediate and high risk patients, p=0.03), whereas in the day+7 ATG arm, there was no difference (29% vs 29%, p=1.0). TRM was overall reduced from 35% in the control arm to 29% in the ATG day+7 arm (p=0.37) : the difference was more pronounced in patients with early disease and high risk on day 7 (35% vs 15% p=0.08). Acute GvHD grade III–IV was reduced overall from 16% to 6% (p=0.04), and chronic GvHD was reduced 32% to 14% (p=0.02). In multivariate COX analysis TRM and overall survival was predicted by risk score day7 and disease phase.Conclusions. We confirm that patients with different risk of TRM can be identified on day+7 after HSCT. Administration of rATG on day+7 can influence the risk of TRM, by reducing acute and chronic GvHD. Additional intensified supportive care (including anti-infectious therapy) may further reduce TRM in patients with a high risk score on day+7.

A Pilot Trial of Two Dose Levels of Rabbit Antithymocyte Globulin, (rATG), Thymoglobulin, as Part of a Myeloablative-Conditioning for a HLA Identical Matched Related Donor Stem Cell Transplant (SCT) with Cyclosporine (CsA) as Graft Versus Host Disease (GvHD) Prophylaxis.

To determine the role of rATG to modify the development of acute GvHD we conducted a randomized, prospective, open-label, multi-center pilot study in patients with ALL or AML in first or second remission. CsA was the only agent used for GvHD prophylaxis. Patients (N=22) were randomized (1:1) to receive either 4.5 mg/kg or 8.5 mg/kg of ATG during the preparative regimen. The rATG infusions were completed on Day -1, within 18 hours prior to SCT on Day 0. The low (N=11) and high dose groups (N=11) were comparable for age, diagnosis and remission status. The mean age was 41.4 and 39.6 years in the low and high dose groups respectively. In both groups 6/11 patients had AML and 5/11 had ALL. All patients received a fully ablative preparative regimen from a HLA matched related donor. Results: Mean time to neutrophil engraftment was 6.5 and 7.3 days for the low and high dose arms, respectively. The incidence of Grade &amp;gt; II acute GvHD was 0/11 for the low dose arm and 3/11 for the high dose arm. Infections were seen in 9/11 patients in both groups. The cumulative number of hospitalization days was 30.4 and 47.6 days (p=n.s.) in the low and high dose groups respectively. The overall survival at 180 days was 63.6 % in the low dose group and 54.5 % in the high dose group (p=n.s.). The disease free survival (DFS) at day 180 was 54.5% in both groups. The treatment related mortality (TRM) was 18.2 % in the low dose and 45.5 % in the high dose (p=n.s.) The relapse rate was 18.2 % in the low dose group and 0% in the high dose group (p=n.s). Conclusion: This pilot study suggests that rATG may modify the development of serious acute GvHD in patients who received a fully ablative SCT. The low, combined, 3/22, incidence of acute GvHD (13.6%) in patients who received rATG(Thymoglobulin) and post transplant CsA suggests that this combination is an acceptable regiment for GvHD prophylaxis. The lower dose of rATG, 4.5 mg/kg, was as effective and was associated with a lower TRM as compared to the higher, 8.5mg/kg dose. The use of rATG administered during the preparative regimen was well tolerated and may provide an effective alternative to methotrexate when used as part of an ablative conditioning regimen in HLA identical related donor SCT.

Experience With Alternate-Day Thymoglobulin Induction in Pancreas Transplantation With Portal-Enteric Drainage

The purpose of this study was to retrospectively review outcomes in patients undergoing pancreas transplantation (PTX) with a novel induction protocol of alternate-day thymoglobulin (rATG) in combination with tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. From January 2002 through January 2005, we performed 55 PTXs in 53 patients. The first dose of rATG (1.5 mg/kg) was given intraoperatively, and subsequent doses were given on alternate days until therapeutic TAC levels (>8 ng/mL) were achieved. All patients underwent PTX with enteric drainage, including 51 with portal and 4 with systemic venous drainage. Patients received a minimum of 2 and maximum of 6 doses of rATG induction (median 3 doses). The patient group had a mean age of 42.8 years and included 40 simultaneous kidney–PTX, 11 sequential PTX after kidney, and 4 PTX-alone transplant recipients. Patient, kidney, and pancreas graft survival rates are 96%, 96%, and 84%, respectively, with a mean follow-up of 21 months. The incidence of acute rejection was 18%; there were no graft losses due to isolated acute rejection. The incidence of infection was 60%, but there were no cases of polyomavirus or Epstein-Barr virus infection and only 6 cases (11%) of cytomegalovirus infection. The composite endpoint of no rejection, graft loss, or mortality was attained by 71% of patients. At present, 94% of surviving patients are both dialysis and insulin-free, including 5 successful PTX retransplants. These findings suggest that PTX with portal-enteric drainage and alternate day rATG induction may result in excellent intermediate-term outcomes.

Long-Term Evolution of Lymphocytes Subsets After Induction Therapy Based on Continuous Versus Discontinuous Administration of Anti-Thymocyte Globulins in Renal-Transplant Patients

The aim of our retrospective study was to assess the long-term evolution of lymphocyte subsets after two modes of administration of anti-thymocyte globulin (ATG) after renal transplantation. Methods Before 1993, patients (group I, n = 93) received fixed doses of RATG (1 mg/kg per day) for 8 consecutive days. Thereafter, RATG was either continued at the same dose for 15 days, in cases of delayed graft function, or was infused every other day at the same dose until the serum creatinine level became <150 μmol/L. After 1993, patients (group II, n = 66) received RATG at full dose (1 mg/kg per day) during the first 3 days and, thereafter, doses were adapted to target a CD2 T-cell count <50/mm 3. RATG cumulative dose was significantly higher among group I than group II (9.7 ± 4.5 versus 7.4 ± 3.2 mg/kg, P = .0002). Results In both groups, total lymphocyte and T lymphocyte subset (CD4, CD8, CD2, CD3) counts decreased significantly during the first month after transplantation, increasing slowly between the first month and the third year posttransplantation. Thereafter it rose rapidly, which was greater in group II. At last follow up, total lymphocyte, T lymphocyte subsets and NK cell counts were similar to those observed before transplantation. At all monitoring times, T lymphocyte, B lymphocyte, and NK cell counts were similar in both group, except for the total lymphocyte count at 6 months and CD4 T lymphocyte count at 1 year, which were significantly higher in group II compared to group I. Conclusion Induction therapy based on continuous or discontinuous administration of ATG is associated with profound depletion of T, B, and NK cells during the first 3 years, followed by a progressive reconstitution of the lymphocyte pool after 5 years.

Comparison of Induction Based on Continuous vs Discontinuous Administration of Antithymocyte Globulins in Renal Transplant Patients: Efficacy and Long-Term Safety

This retrospective study sought to compare two modes of administration of antithymocyte globulin (RATG) after renal transplantation. Methods Before 1993, group I patients ( n = 93) received fixed doses of RATG (1 mg/kg per day) for 8 consecutive days. Thereafter, RATG was either continued at the same dose for 15 days, in cases of delayed graft function, or was infused every other day at the same dose until serum creatinine level became <150 μmol/L. After 1993, group II patients ( n = 66) received RATG at full dose (1 mg/kg per day) during the first 3 days and thereafter the doses were adjusted to target a CD2 T-cell count <50/mm 3. Both groups received steroids, azathioprine, and cyclosporine. The mean follow-up after transplantation was 117 ± 31 months in group I and 93 ± 19 months in group II. Results The RATG cumulative dose and consequently cost were significantly higher among group I than group II patients. Long-term patient and graft survival were similar in both groups. The rate of acute graft-rejection episodes was significantly higher among group I than group II patients. At 7 years posttransplantation, the serum creatinine level and creatinine clearance were similar in the two groups. The rate of cytomegalovirus infection, as well as the cumulative incidence of severe infections and cancers were also similar in both groups. Among the cancers, skin neoplasms represented 30% in group I and 26% in group II ( P = ns). Conclusion Adjusting RATG doses according to the CD2 lymphocyte count is safe, and a less expensive than using full doses.

NO DEATHS, FEW REJECTIONS IN THE SHORT-TERM ASSESSMENT OF HEART TRANSPLANTATION USING ATG INDUCTION

A201 Aims: The aim of this single centre analysis was to evaluate short term benefits of rabbit antihuman thymocyte globulin (rATG) induction therapy associated with cyclosporine, MMF and steroids, after cardiac transplantation. Methods: During 2003, there were 23 heart transplants carried out at Nantes hospital. Data on these 23 recipients was collected up to March 2004, giving a mean length of follow-up of 7.3 months (range: 1.3-13.3). Results: The mean donor age was 35.6 years (13-53), the mean ICU stay was 108 hours (24-500) and all these donors were hemodynamically stable. The recipients comprised 17 males and 6 females with a mean age of 45 years (13-64) and 41% were over age 50. The indications for transplantation were ischemic cardiomyopathy (11), dilated cardiomyopathy (10), valvular pathology (1) and congenital heart disease (1). Patient status before transplantation was poor : all of them had a grade IV NYHA status, 10 were still at home; 13 were hospitalised, 4 of whom were on assisted circulation and 1 intubated. For all recipients, the cardiac transplantation was their first. The 23 grafts were flushed and cold stored with Celsior solution, the mean CIT was 2.9 hrs (1.7-4.2). Five patients needed a ventricular assist device. All patients received the first dose of rATG (Thymoglobuline, SangStat) after declamping on day 0, followed by daily infusions depending on E-rosette count for another 4 to 5 days (giving a mean first dose of 2.3 mg/kg and a mean cumulative dose of 5.45 mg/kg). Steroids started from D0, MMF (CellCept, Roche) and cyclosporine (Neoral, Novartis) had delayed introduction with the mean start day being 5-6 and 2-3 respectively (cyclosporine was started when creatinine <200 μmol/l). All patients received antibacterial and antifungal prophylaxis, antiviral prophylaxis was based on donor/recipient CMV status. Thymoglobuline tolerability was good: no anaphylaxis, no first dose syndrome and no thrombocytopenia or neutropenia necessitating temporary discontinuation of the product. The mean recipients’ ICU stay was 12.5 days (4-57). Only 12 patients suffered at least one infection which included 5 pneumonias (2 with septicaemia, 1 with septicaemia and mediastinitis). No malignancies occurred. Only one patient (4.3%) experienced rejection (two consecutive grade 2 acute rejections, both resolved after steroid treatment). At the end of follow-up period, all patients were alive with a grade I NYHA status, mean serum creatinine 118 μmol/l (69-187) and none required dialysis. In the same year, 3 patients received Heart-Lung transplants and 5 Lung transplants. The same immunosuppressive regimen was followed. All these patients were also still living at March 2004. Conclusions: In conclusion, the use of Thymoglobuline combined with cyclosporine, MMF and steroids in the protocol described above, results in excellent efficacy over this short follow-up with 100% graft and patient survival, few side effects and few rejections. The low rejection rate in combination with a low infection rate suggests optimal immunosuppression with this regimen.