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Thrombotic microangiopathy (TMA) has been described as severe complication after hematopoietic stem cell transplantation (HSCT). The principal aim of this study was to focus the incidence and the outcome of TMA in the era of more complex HSCTs.

One hundred nine patients with hematologic malignancies, undergoing bone marrow transplants (BMT) from unrelated donors, were randomized in 2 consecutive trials to receive or not to receive antithymocyte globulin (ATG) in the conditioning regimen, as follows: (A) 54 patients (median age, 28 years; 39% with advanced disease) were randomized to no ATG (n = 25) versus 7.5 mg/kg rabbit ATG (Thymoglobulin; Sangstat, Lyon, France) (n = 29) ; (B) 55 patients (median age, 31 years, 71% with advanced disease) were randomized to no ATG (n = 28) versus 15 mg/kg rabbit ATG (n = 27). Grade III-IV graft-versus-host disease (GVHD) was diagnosed in 36% versus 41% (P = .8) in the first and in 50% versus 11% (P = .001) in the second trial. Transplant-related mortality (TRM), relapse, and actuarial 3-year survival rates were comparable in both trials. In fact, despite the reduction of GVHD in the second trial, a higher risk for lethal infections (30% vs 7%; P = .02) was seen in the arm given 15 mg/kg ATG. Extensive chronic GVHD developed overall more frequently in patients given no ATG (62% vs 39%;P = .04), as confirmed by multivariate analysis (P = .03). Time to 50 × 109/L platelets was comparable in the first trial (21 vs 24 days; P = .3) and delayed in the ATG arm in the second trial (23 vs 38 days;P = .02). These trials suggest that (1) 15 mg/kg ATG before BMT significantly reduces the risk for grade III-IV acute GVHD, (2) this does not translate to a reduction in TRM because of the increased risk for infections, and (3) though survival is unchanged, extensive chronic GVHD is significantly reduced in patients receiving ATG.

One hundred nine patients with hematologic malignancies, undergoing bone marrow transplants (BMT) from unrelated donors, were randomized in 2 consecutive trials to receive or not to receive antithymocyte globulin (ATG) in the conditioning regimen, as follows: (A) 54 patients (median age, 28 years; 39% with advanced disease) were randomized to no ATG (n = 25) versus 7.5 mg/kg rabbit ATG (Thymoglobulin; Sangstat, Lyon, France) (n = 29); (B) 55 patients (median age, 31 years, 71% with advanced disease) were randomized to no ATG (n = 28) versus 15 mg/kg rabbit ATG (n = 27). Grade III-IV graft-versus-host disease (GVHD) was diagnosed in 36% versus 41% (P= .8) in the first and in 50% versus 11% (P= .001) in the second trial. Transplant-related mortality (TRM), relapse, and actuarial 3-year survival rates were comparable in both trials. In fact, despite the reduction of GVHD in the second trial, a higher risk for lethal infections (30% vs 7%; P= .02) was seen in the arm given 15 mg/kg ATG. Extensive chronic GVHD developed overall more frequently in patients given no ATG (62% vs 39%;P= .04), as confirmed by multivariate analysis (P= .03). Time to 50 × 109/L platelets was comparable in the first trial (21 vs 24 days; P= .3) and delayed in the ATG arm in the second trial (23 vs 38 days;P= .02). These trials suggest that (1) 15 mg/kg ATG before BMT significantly reduces the risk for grade III-IV acute GVHD, (2) this does not translate to a reduction in TRM because of the increased risk for infections, and (3) though survival is unchanged, extensive chronic GVHD is significantly reduced in patients receiving ATG.

Hepatitis B virus (HBV)-infected individuals are occasionally used as donors for bone marrow transplantation (BMT). We studied the rate of HBV infection and the clinical expression of the associated liver disease in patients receiving marrow from HBsAg+donors. We performed a retrospective survey in 14 BMT units in Italy in which all BMTs performed between 1984 and 1994 were reviewed and those involving HBsAg+donors were identified. Donors and recipients were analyzed for HBV markers and liver disease. A total of 24 of 2,586 patients (0.9%) had received an HBsAg+marrow. HBsAg became detectable in 22% of pre-BMT HBsAg-patients, but only 5.5% became chronic HBsAg carriers. Anti-genemia developed more frequently in anti-HBs-compared with anti-HBs+patients independently of passive prophylaxis with hyperimmune anti-HBs Ig, although the difference was not significant. Severe liver failure with death occurred in 21% of patients, which was a value greater than that generally observed after BMT in our units (3.7%). Patients with an anti-HBe+donor had higher frequency of liver failure (28% v0%) and alanine aminotransferase peaks as compared with those of patients with an HBeAg+donor. Liver failure was not observed in anti-HBs+recipients. The use of HBsAg+donors, particularly if anti-HBe+, increases the risk of severe liver disease in BMT recipients. Anti-HBs positivity may prevent severe liver damage.

WHO classification and WPSS score (JCO2007;25:3503) have been recently proved to have prognostic significance in myelodysplastic syndromes (MDS), but their impact on the outcome of patients (pts) receiving allogeneic stem-cell transplantation (allo-SCT) is still to be clarified. We retrospectively evaluated the prognostic value of WHO classification and WPSS at the time of transplant in 406 MDS pts who underwent allo-SCT between 1990 and 2006. Patients were reclassified according to the WHO criteria: 30 had refractory anemia (RA/RARS), 54 refractory cytopenia (RCMD/RS), 51 RA with excess blasts (RAEB), type 1 and 95 RAEB type 2. One hundred twenty-seven pts were classified as acute myeloid leukemia (AML). The median recipient age was 48 years (range 17–67). There were 281 HLA-matched sibling and 125 unrelated donor SCT. One hundred forty-three pts (35%) received a reduced intensity regimen (RIC). Considering WHO categories, the probability of OS at 5-years was 0.8 in RA/RARS, 0.52 in RCMD/RS, 0.48 in RAEB-1, 0.26 in RAEB-2 and 0.29 in AML, while the probability of RFS at 5-years was 0.92, 0.78, 0.74, 0.47 and 0.44 respectively. The cumulative probability of TRM was 0.43. We performed a Cox analysis with WHO category, cytogenetics, transfusion dependency, recipient age, disease status, type of donor and type of conditioning as covariates. WHO classification had a significant effect on both OS (P=0.017), and RFS (P=0.01). Cytogenetic risk significantly affected RFS (P=0.04), while had a borderline effect on OS (P=0.09). A regular transfusion dependency before SCT was associated with a reduced OS (P=0.01) and increased TRM (P=0.037), while no significant effect on RFS was noticed. Age and stage of the disease at transplant showed a significant effect on OS (P=0.02 and P=0.04, respectively). RIC and active disease at transplant were associated to a reduced probability of RFS (P=0.02 and P=0.017 respectively). Age and use of myeloablative conditioning were significant risk factors for TRM (P=0.018 and P=0.032 respectively). The WPSS score, based on MDS-WHO category, cytogenetics and transfusion dependency at the time of SCT, was calculated for 171 pts. WPSS showed a prognostic significance on both OS and RFS in a Cox analysis with age of recipient, disease status, type of donor and type of conditioning as covariates (P=0.02 and P=0.01). Focusing the analysis on 84 MDS pts without excess blasts, multilineage dysplasia and regular transfusion-dependency significantly affected post-transplant OS (P=0.005 and P=0.009, respectively), and were associated to an increased TRM. In this clinical setting, WPSS allowed to identify 2 major groups of pts (very-low/low vs. intermediate risk) with significant different OS and TRM (P=0.013 and P=0.039). In conclusion, these data show that WHO classification and WPSS have a relevant prognostic value for the post-transplantation outcome of MDS pts and should be taken into account in transplantation decision-making, especially in subjects with less advanced disease. The independent negative effect of transfusion dependency strengthens the rationale to examine the consequences of iron overload and the potential benefit of chelation therapy in MDS transplant setting.

Background HLA-matching between patient and donor is critical for outcome of haematopoietic stem cell transplantation (HSCT) performed from an unrelated donor, together with other non-HLA factors. A 10/10-matched donor is the most suitable for HSCT, when possible; however, a certain degree of HLA-incompatibility has to be accepted when such a donor is not available. Aim of the study This is a prospective multicenter GITMO study in which patients were enrolled as 6/6” matched (matched at loci A, B at low resolution level and DRB1 at high resolution) or as “5/6” matched (one low-resolution mismatch (MM) at locus A or B). High resolution typing is now available as well. Patients. Eligible were patients with a haematological malignancy, aged > 18 years old, activating an unrelated donor search in Italy from January 1999 to June 2006. Patients with chronic myeloid leukaemia were excluded from the analysis. A total of 1069 patient-donor pairs were analyzed; median follow-up for alive pts was 23 months (range: 3–96). According to disease status at HSCT, pts were classified as “early” (de novo acute myeloid or lymphoblastic leukemia in first complete remission, n=241) and “advanced” (all others, n=828) pts. Univariate and multivariate analysis with Cox regression included main non-HLA factors known to be associated with HSCT outcome. No differences in overall survival (OS) was observed between 5/6-matched (n=101) and 6/6-matched (n=968) pts (fig.1). There was a non-statistically significant trend toward a lower relapse-related death (RRD) in 5/6-matched compared to 6/6-matched pts was observed (5y-RRD: 18% vs 24%, respectively; p=0.13). We then proceeded to test the effect of the C locus: in multivariate analysis, the presence of an antigenic MM at locus C was associated with a worse OS, regardless of matching at loci A or B (RR 1.18, 95% C.I.: 1.00–1.40, p=0.05); the presence of a MM at locus B and/or C significantly affected transplant-related mortality (TRM) (RR 1.57, 95% C.I.: 1.02–2.44, p=0.04; RR 1.31, 95% C.I.: 1.04–1.65, p=0.02, respectively), MM at locus B or C was also associated with development of grade II-IV acute graft-versus-host disease (aGVHD) on multivariate analysis, together with “non-use” of ATG (ATG use: RR 0.70, 95% C.I. 0.52–0.95, p=0.02). Conclusions, The outcome of so called 5/6 and 6/6 HLA matched unrelated donor transplants is comparable: this may be due to the fact that the C locus is not taken in to account in the “5/6 or 6/6” definition. Indeed a mismatch at locus C is associated with worse outcome. MM at locus B or C, but not at locus A, increases the risk of developing grade II-IV aGVHD. Use of ATG reduces aGVHD rates, thus attenuating the adverse effect of MMs at loci B and C on HSCT outcome.

BackgroundHLA-matching between patient and donor is critical for outcome of haematopoietic stem cell transplantation (HSCT) performed from an unrelated donor, together with other non-HLA factors. A 10/10-matched donor is the most suitable for HSCT, when possible; however, a certain degree of HLA-incompatibility has to be accepted when such a donor is not available.

WHO classification and WPSS score (JCO 2007; 25:3503) have been recently proved to have prognostic significance in myelodysplastic syndromes (MDS), but their impact on the outcome of patients (pts) receiving allogeneic stem-cell transplantation (allo-SCT) is still to be clarified. We retrospectively evaluated the prognostic value of WHO classification and WPSS at the time of transplant in 406 MDS pts who underwent allo-SCT between 1990 and 2006. Patients were reclassified according to the WHO criteria: 30 had refractory anemia (RA/RARS), 54 refractory cytopenia (RCMD/RS), 51 RA with excess blasts (RAEB), type 1 and 95 RAEB type 2. One hundred twenty-seven pts were classified as acute myeloid leukemia (AML). The median recipient age was 48 years (range 17–67). There were 281 HLA-matched sibling and 125 unrelated donor SCT. One hundred forty-three pts (35%) received a reduced intensity regimen (RIC). Considering WHO categories, the probability of OS at 5-years was 0.8 in RA/RARS, 0.52 in RCMD/RS, 0.48 in RAEB-1, 0.26 in RAEB-2 and 0.29 in AML, while the probability of RFS at 5-years was 0.92, 0.78, 0.74, 0.47 and 0.44 respectively. The cumulative probability of TRM was 0.43. We performed a Cox analysis with WHO category, cytogenetics, transfusion dependency, recipient age, disease status, type of donor and type of conditioning as covariates. WHO classification had a significant effect on both OS (P=0.017), and RFS (P=0.01). Cytogenetic risk significantly affected RFS (P=0.04), while had a borderline effect on OS (P=0.09). A regular transfusion dependency before SCT was associated with a reduced OS (P=0.01) and increased TRM (P=0.037), while no significant effect on RFS was noticed. Age and stage of the disease at transplant showed a significant effect on OS (P=0.02 and P=0.04, respectively). RIC and active disease at transplant were associated to a reduced probability of RFS (P=0.02 and P=0.017 respectively). Age and use of myeloablative conditioning were significant risk factors for TRM (P=0.018 and P=0.032 respectively). The WPSS score, based on MDS-WHO category, cytogenetics and transfusion dependency at the time of SCT, was calculated for 171 pts. WPSS showed a prognostic significance on both OS and RFS in a Cox analysis with age of recipient, disease status, type of donor and type of conditioning as covariates (P=0.02 and P=0.01). Focusing the analysis on 84 MDS pts without excess blasts, multilineage dysplasia and regular transfusion-dependency significantly affected post-transplant OS (P=0.005 and P=0.009, respectively), and were associated to an increased TRM. In this clinical setting, WPSS allowed to identify 2 major groups of pts (very-low/low vs. intermediate risk) with significant different OS and TRM (P=0.013 and P=0.039). In conclusion, these data show that WHO classification and WPSS have a relevant prognostic value for the post-transplantation outcome of MDS pts and should be taken into account in transplantation decision-making, especially in subjects with less advanced disease. The independent negative effect of transfusion dependency strengthens the rationale to examine the consequences of iron overload and the potential benefit of chelation therapy in MDS transplant setting.

The prognosis of patients with acute myeloid leukemia (AML) failing to standard induction chemotherapy is very poor, and only a minority of such patients will be ultimately cured after salvage chemotherapy. The precise role of allogeneic stem cell transplantation (alloSCT) in primary refractory AML has not been extensively assessed and it is not commonly indicated in this setting. In this regard, we analyzed the outcome and eventual prognostic factors in a series of adult patients who received an undepleted allograft from an HLA-identical sibling using a myeloablative conditioning for a primary refractory “de novo” AML (i.e., patients who never achieved complete response (CR) before transplantation). Overall, 361 patients (median age: 39; range: 17–71; 60% male) fulfilling these criteria and registered to the EBMT during the period 1990–2004 were included in the study. Median interval from diagnosis to transplant was 132 days (24–360) and the median number of induction courses was 2 (1–5). Percentage of bone marrow (BM) blasts at time of SCT was 20% (0–93). Most patients with available information (n=126, 35%) harbored an intermediate-risk cytogenetics (67%). Stem-cell source was peripheral blood (PB) in 61% of cases, and conditioning regimen did not contain TBI in 59% of the procedures. Following alloSCT, 218 patients (60%) achieved CR and 143 failed to respond. After a median follow-up of 26 months, 3 and 5-year overall survival was 24±2% and 19±3%, respectively. Of note, among the subset of patients achieving CR after alloSCT, overall survival and leukemia-free survival at 3-year was 37±3% and 33±3%, respectively, whereas none of those patients failing to alloSCT survived further than 10 months after transplant. The comparison of main characteristics between subgroups of patients according to response attained after alloSCT only disclosed a shorter interval from diagnosis (126 vs. 143 days, p=0.01) in the subset of responding patients. Moreover, a lower WBC count at diagnosis, inferior to median value (3-yr OS: 27±6% vs. 15±5%; RR: 2.08, 95% CI: 1.05–4.17; p=0.03), and a BM involvement of blast cells <20% at time of transplantation (3-yr OS: 35±8% vs. 10±5%; RR: 2.13, 95% CI: 1.12–4; p=0.02) were the only variables associated to a longer survival. In conclusion, allogeneic SCT is a reasonable alternative for a subset of patients with AML failing to primary induction chemotherapy who have an available HLA-identical sibling. Thus, a low WBC count at diagnosis and a low degree of BM infiltration at transplant were predictive of a more favorable outcome in the subgroup of 56 patients with this information available. Confirmation of this finding in a larger proportion of patients would be helpful to identify those patients with AML who could benefit from an allogeneic transplantation in a refractory status.

Early alloSCT of pts with MDS before transformation usually results in a 50% EFS, but the nonrelapse mortality (NRM) has precluded a general application of alloSCT for patients with RA. Introduction of RIC has allowed the application of alloSCT to more advanced ages. This study evaluated the impact of recipient age, transplant year, interval between diagnosis and SCT (Dx-SCT), cytogenetic characteristics, T-cell depletion (TCD), type of donor, and the intensity of the conditioning regimen on the outcome of alloSCT. The study population consisted of 374 pts, 244 of whom have received a transplant from an HLA-id. sibling. None of the pts had progressed to advanced stages of MDS. 83 Pts received TCD grafts and 102 pts received SCT after RIC. 58 Pts were <20 yrs, 52 between 20–30, 66 between 30–40, 95 from 40–50 and 103 pts >50 yrs. 86 Pts received SCT before 1996, 125 in 1997–2001, and 163 pts more recently. 184 Pts have been transplanted with a Dx-SCT of <12 months, and 190 >12 months. Cytogenetic data were available for 197 pts, 85 of whom had cytogenetic abnormalities. The overall 5-year survival was 50% (SE: 3%). Relapse occurred in 44% pts resulting in a 5-year relapse risk of 21% (SE: 3%). NRM was the cause of failure in 120 pts resulting in a 5-year NRM of 41% (SE: 3%). The survival after SCT with matched related and unrelated donors was 54% and 48% resp. Young age was associated with better survival in the univariate model (p=0.04). An association exists between various factors such as between age and regimen type, transplantation year, or donor type. Therefore the outcome of the multivariable analyses was based on Cox models with age, transplant year, type of donor, Dx-SCT, stem cell source, and regimen type as main factors. Variables with a significant impact on survival were transplant year with an improved survival in more recently performed SCT (HR=0.95/year; p=0.05), TCD (HR=1.5; p=0.03) and Dx-SCT >12 months (HR=1.4; p=0.05) while higher age (HR=1.1/10 years; p=0.08) and RIC (HR=1.0; p=1.0) did not influence outcome significantly. The HR of RIC for relapse-free survival was 1.2; p=0.5. The fully adjusted estimate for relapse after RIC was HR=4.1 (p=0.002). The NRM was lower after RIC: HR 0.7 (P=0.22), but this difference was not significant. The donor type and the source of stem cells did not influence significantly any of the outcome variables. This data show that alloSCT results in excellent outcome nowadays, even at older age and using matched unrelated donors. The relatively high relapse rate observed after RIC warrants prospective studies.

Early alloSCT of pts with MDS before transformation usually results in a 50% EFS, but the nonrelapse mortality (NRM) has precluded a general application of alloSCT for patients with RA. Introduction of RIC has allowed the application of alloSCT to more advanced ages. This study evaluated the impact of recipient age, transplant year, interval between diagnosis and SCT (Dx-SCT), cytogenetic characteristics, T-cell depletion (TCD), type of donor, and the intensity of the conditioning regimen on the outcome of alloSCT. The study population consisted of 374 pts, 244 of whom have received a transplant from an HLA-id. sibling. None of the pts had progressed to advanced stages of MDS. 83 Pts received TCD grafts and 102 pts received SCT after RIC. 58 Pts were <20 yrs, 52 between 20–30, 66 between 30–40, 95 from 40–50 and 103 pts >50 yrs. 86 Pts received SCT before 1996, 125 in 1997–2001, and 163 pts more recently. 184 Pts have been transplanted with a Dx-SCT of <12 months, and 190 >12 months. Cytogenetic data were available for 197 pts, 85 of whom had cytogenetic abnormalities. The overall 5-year survival was 50% (SE: 3%). Relapse occurred in 44% pts resulting in a 5-year relapse risk of 21% (SE: 3%). NRM was the cause of failure in 120 pts resulting in a 5-year NRM of 41% (SE: 3%). The survival after SCT with matched related and unrelated donors was 54% and 48% resp. Young age was associated with better survival in the univariate model (p=0.04). An association exists between various factors such as between age and regimen type, transplantation year, or donor type. Therefore the outcome of the multivariable analyses was based on Cox models with age, transplant year, type of donor, Dx-SCT, stem cell source, and regimen type as main factors. Variables with a significant impact on survival were transplant year with an improved survival in more recently performed SCT (HR=0.95/year; p=0.05), TCD (HR=1.5; p=0.03) and Dx-SCT >12 months (HR=1.4; p=0.05) while higher age (HR=1.1/10 years; p=0.08) and RIC (HR=1.0; p=1.0) did not influence outcome significantly. The HR of RIC for relapse-free survival was 1.2; p=0.5. The fully adjusted estimate for relapse after RIC was HR=4.1 (p=0.002). The NRM was lower after RIC: HR 0.7 (P=0.22), but this difference was not significant. The donor type and the source of stem cells did not influence significantly any of the outcome variables. This data show that alloSCT results in excellent outcome nowadays, even at older age and using matched unrelated donors. The relatively high relapse rate observed after RIC warrants prospective studies.

The prognosis of patients with acute myeloid leukemia (AML) failing to standard induction chemotherapy is very poor, and only a minority of such patients will be ultimately cured after salvage chemotherapy. The precise role of allogeneic stem cell transplantation (alloSCT) in primary refractory AML has not been extensively assessed and it is not commonly indicated in this setting. In this regard, we analyzed the outcome and eventual prognostic factors in a series of adult patients who received an undepleted allograft from an HLA-identical sibling using a myeloablative conditioning for a primary refractory “de novo” AML (i.e., patients who never achieved complete response (CR) before transplantation). Overall, 361 patients (median age: 39; range: 17–71; 60% male) fulfilling these criteria and registered to the EBMT during the period 1990–2004 were included in the study. Median interval from diagnosis to transplant was 132 days (24–360) and the median number of induction courses was 2 (1–5). Percentage of bone marrow (BM) blasts at time of SCT was 20% (0–93). Most patients with available information (n=126, 35%) harbored an intermediate-risk cytogenetics (67%). Stem-cell source was peripheral blood (PB) in 61% of cases, and conditioning regimen did not contain TBI in 59% of the procedures. Following alloSCT, 218 patients (60%) achieved CR and 143 failed to respond. After a median follow-up of 26 months, 3 and 5-year overall survival was 24±2% and 19±3%, respectively. Of note, among the subset of patients achieving CR after alloSCT, overall survival and leukemia-free survival at 3-year was 37±3% and 33±3%, respectively, whereas none of those patients failing to alloSCT survived further than 10 months after transplant. The comparison of main characteristics between subgroups of patients according to response attained after alloSCT only disclosed a shorter interval from diagnosis (126 vs. 143 days, p=0.01) in the subset of responding patients. Moreover, a lower WBC count at diagnosis, inferior to median value (3-yr OS: 27±6% vs. 15±5%; RR: 2.08, 95% CI: 1.05–4.17; p=0.03), and a BM involvement of blast cells <20% at time of transplantation (3-yr OS: 35±8% vs. 10±5%; RR: 2.13, 95% CI: 1.12–4; p=0.02) were the only variables associated to a longer survival. In conclusion, allogeneic SCT is a reasonable alternative for a subset of patients with AML failing to primary induction chemotherapy who have an available HLA-identical sibling. Thus, a low WBC count at diagnosis and a low degree of BM infiltration at transplant were predictive of a more favorable outcome in the subgroup of 56 patients with this information available. Confirmation of this finding in a larger proportion of patients would be helpful to identify those patients with AML who could benefit from an allogeneic transplantation in a refractory status.

Introduction Thrombotic thrombocytopenic purpura (TTP) might costitute a severe complication after hematopoietic stem cell transplantation (HSCT) with a variable incidence depending on different diagnostic criteria adopted in the past. Patients and Methods The current study enrolled 551 consecutive patients (pts) (314 males, median age 29 years) undergoing HSCT from January 2000 to April 2005 from HLA match (m) or mismatch (mm) family donor (350/551) and unrelated donor (201/551) for malignant (501/551) or non malignant diseases (50/551). The diagnosis of TTP was performed on the basis of homogeneous five clinical and seven laboratory criteria. Univariate (by chi square test and Fisher’s exact test) or multivariate (by logistic regression method) analyses were performed to evaluate the effect of some candidate risk factors on both TTP occurrence and outcome. Results Sixty four of 551 pts presented TTP (11,6%) at a median time of 47 days post-HSCT; 59/64 were affected by malignant and 5/64 by non malignant diseases. Multivariate analysis showed GVHD >II° (p=0,0001), stem cell donors (m/mm unrelated or mm related) (p=0,024), female gender (p=0,0186),TBI-based conditioning regimen (p=0,03) and status of hematological remission (p=0,03) as factors influencing the occurrence of TTP. Only three predicting factors for TTP outcome have been demonstrated statistically significative by multivariate analysis: age (p=0,0186), stem cell donors (m/mm unrelated or mm related) (p=0,01) and TTP index (p=0,018). The TTP mortality rate was 40% while the outcome after TTP diagnosis was partially influenced by TTP treatment. In particular, Defibrotide seemed to be a promising drug in univariate analysis compared with alternative therapies for 34 alive and good responders pts out of 64 TTP pts. Conclusions The study underlines the possibility to identify those patients who are more prone to develop post-HSCT TTP, complication still frequent (11,6%) when homogeneous diagnostic criteria are adopted. TTP outcome seems to be conditioned by some peculiar risk factors as adult age, m/mm unrelated or mm related donors HSCTs. Prospective randomized therapeutic trials, focusing on the possible advantage of Defibrotide versus other treatments, should be encouraged.

Introduction

Background . We have reported that rabbit antithymocyte globulin (ATG Sangstat-Genzyme) prevents acute and chronic graft versus host disease (GvHD) in patients undergoing an unrelated donor transplant (Blood2001; 98 (10): 2942–2947). Patients had entered two consecutive randomized trials: in trial-1, 54 patients were randomized to non-ATG (n=25) or 7.5mg/kg rabbit ATG (n=29). In trial-2, 28 patients were randomized in the non-ATG arm and 27 in the ATG 15mg/kg arm. Aim of the study: to assess the risk of extensive chronic GvHD, bronchiolitis obliterans , quality of life, survival and transplant related mortality (TRM) 4 years later. Patients. Seventy five patients survived 100 days after BMT, and were available for analysis : in trial-1 there were 20 patients per arm, in trial-2 there were respectively 18 and 17 patients. The median follow up was 7.4 years for trial-1 and 5.3 years for trial-2. Each patients was updated and assessed for survival, chronic GvHD, for bronchiolitis , relapse of the original disease and quality of life. Results. Results are given in percentage, in the order non-ATG vs ATG patients. At last follow up chronic GvHD (limited+extensive) was scored in 74% vs 33% respectively for non-ATG and ATG of patients in trial 1 (p=0.01) and in 61% vs 29% in trial-2 (p=0.06): when the two trials are combined cGvHD is scored in 68% vs 31% of non-ATG vs ATG patients (p=0.002). Extensive chronic GvHD was scored in both trials in 35% and 13% of patients (0.03). Bronchiolitis was present at last follow up in trial-1 in 50% vs 0% (p=0.01), and in 33% vs 8% in trial-2 (p=0.1). Combined data show bronchiolitis in 40% vs 4% of non-ATG vs ATG patients (p=0.002). Median timing of bronchiolitis was 1155 days. When patients developed bronchiolitis, the mortality was high (50%). Quality of life was assessed by looking at proportion of patients with Karnowski score of 100% at last follow up: the proportion was 37% vs 91% patients in trial-1 (p=0.02), it was 75% vs 100% patients in trial-2 (p=0.2) and overall in 56% vs 95% of all non-ATG vs ATG patiens (p=0.007). Relapse related deaths were 13% in the non-ATG and 11% in the ATG group. Survival: the actuarial survival at 5 years in trial-1 is 48% vs 53% (non-ATG vs ATG) and in trial-2 30% vs 41%. The actuarial TRM is 48% vs 40%, and in trial-2 it is 62% vs 47% (non-ATG vs ATG patients). Actuarial 5 year TRM in patients surviving one year (late TRM) is 28% vs 4% (p=0.02). Conclusions. This updated analysis of two randomized GITMO trials, confirms with longer follow up, that ATG pre-transplant produces (1) a significant reduction of chronic GvHD (from 68% to 31%) and (2) a significant reduction of extensive chronic GvHD (from 35% to 13%). As a consequence quality of life is significantly improved in ATG patients. This study also shows that ATG reduces the risk of chronic bronchiolitis (from 40% to 4%), and late TRM (beyond one year) (from 28% to 4%). These data give strong support for the inclusion of ATG in the conditioning regimen of unrelated transplants: dosing and timing should be considered (Blood2003; 102 (11); 242a) and could be tested in a prospective trial. This work was supported by Fondazione CARIGE, GENOVA

Background.We have reported that rabbit antithymocyte globulin (ATG Sangstat-Genzyme) prevents acute and chronic graft versus host disease (GvHD) in patients undergoing an unrelated donor transplant (Blood 2001; 98 (10): 2942–2947). Patients had entered two consecutive randomized trials: in trial-1, 54 patients were randomized to non-ATG (n=25) or 7.5mg/kg rabbit ATG (n=29). In trial-2, 28 patients were randomized in the non-ATG arm and 27 in the ATG 15mg/kg arm.