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The role of in vivo T-cell depletion on reduced-intensity conditioning allogeneic stem cell transplantation from HLA-identical siblings in patients with follicular lymphoma

Purpose To analyze the outcome of allogeneic transplantation for mycosis fungoides and Sézary syndrome (MF/SS) in terms of nonrelapse mortality (NRM), relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) and to identify factors associated with the outcome. Patient and Methods Sixty patients with MF (n = 36) and SS (n = 24) who received a first allogeneic hematopoietic cell transplantation (HCT) from a matched related (mRD; n = 45) or unrelated donor (mUD; n = 15) between 1997 and 2007 and who were registered in the European Group for Blood and Marrow Transplantation database were analyzed: 37 men and 23 women, median age 46.5 years (range, 22 to 66 years). Forty-four patients had TNM stage IV, and 40 patients were at advanced phase at transplantation. Forty-four patients received reduced-intensity conditioning (RIC) regimens, and 25 underwent T-cell depletion (TCD). Results Allogeneic transplantation in MF/SS offers an estimated OS of 66% at 1 year and 54% at 3 years, primarily driven by donor type, disease phase, and type of conditioning. RIC decreased NRM (relative risk [RR] = 4.7; P = .008) without increasing REL, leading to a higher OS (RR = 2.8; P = .03). Advanced-phase disease increases REL (RR = 3.0; P = .03) and reduces PFS (RR = 4.4; P = .002) and OS (RR = 3.5; P = .023). Recipients of mRD allogeneic HCT had better PFS (RR = 2.7; P = .006) and OS (RR = 4.0; P = .001) than their mUD counterparts. The risk of REL increases with TCD (RR = 3.2; P = .005). Some patients who experience relapse can successfully undergo rescue treatment with donor lymphocyte infusions. Conclusion Allogeneic transplantation is a valid therapeutic alternative for high-risk patients with advanced-stage MF/SS. Our data also suggest the existence of a clinically relevant graft-versus-lymphoma effect in MF/SS.

To evaluate the outcome of a large series of patients who received high-dose treatment (HDT) for follicular lymphoma (FL), 693 patients undergoing HDT (total-body irradiation (TBI)-containing regimen: 58%; autologous bone marrow (BM)/peripheral blood progenitor cells (PBPCs): 378/285 patients) were included in the study. A total of 375 patients (54%) developed recurrent lymphoma, 10-year progression-free survival (PFS) being 31%. On multivariate analysis, younger age (P=0.003) and HDT in first complete remission (CR1) (P

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA)-compatible sibling donors is a potential curative treatment for hematological and non-hematological malignancies. Nevertheless, high mortality rates may be associated with this therapy, especially in older patients, those with other comorbidities or who receive a second HSCT. Patients and methods: We analyzed the factors associated with transplant-related mortality (TRM) and overall survival in 157 consecutive adult patients (104 males and 53 females) who received a HSCT [29 bone marrow (BM) transplantation and 128 peripheral blood (PB) transplantation] from a HLA-identical sibling between January 1995 and March 2002 in our institution. One hundred patients received a standard conditioning prior to HSCT (STAND) and 57 patients received a reduced-intensity conditioning (RIC) HSCT. Fifty-eight patients were in an early phase at transplant and 99 in a non-early phase. Median age was 46 yr (16–66), and 90 patients (57%) were >45 yr of age. Results: Patients in the RIC group were older than those in the STAND group, and had a higher proportion of non-early disease phases including a prior autologous HSCT in 39%. Median follow-up for survivors was 28 and 15 months in the STAND and RIC groups (P

Over a 3-year period, 145 patients ineligible for myeloablative conditioning underwent reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (SCT) from an HLA-identical sibling in a prospective study. The median age was 54 years, 88 patients were male and 61 patients were beyond the early-intermediate phase of their disease. The 100-day probability of developing grade II-IV acute graft-versus-host disease (GVHD) was 34%, and the 1-year probability of developing chronic extensive GVHD was 41%. The 1-year probabilities of transplant-related mortality (TRM), overall (OS) and progression-free survival were 20, 60 and 52%, respectively. Multivariate analyses found a better OS in: (i) patients60 years; and (ii) recipients of a first SCT; and a higher TRM in: (i) age60 years, (ii) recipients of a prior autologous SCT, and (iii) an ECOG performance status1. The 1-year TRM in patients with 0 or 1 and2 of the above-mentioned adverse prognostic factors were 17 vs 53%, respectively (P0.001). In summary, our study shows that elderly patients have a higher TRM following an RIC protocol. However, age by itself should not preclude these RIC transplants, since TRM appears to be unacceptably high only in the presence of additional adverse factors.

Thyroid dysfunction in adult patients late after autologous and allogeneic blood and marrow transplantation

on behalf of Eurocord-Netcord and the Lymphoma Working Party and the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation; International audience; We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97%, respectively; P

Reduced-intensity conditioning (RIC) regimens for allogeneic haematopoietic stem cell transplantation (SCT) have been shown to lead to engraftment of donor stem cells without the severe extra-haematological toxicities of traditional myeloablative transplants. Between December 1998 and December 2000, 76 patients underwent a RIC peripheral blood SCT in a prospective multicentre study. The median age was 53 years, and 57 patients were beyond the early phase of their disease. The conditioning regimens consisted of fludarabine (150 mg/m2) plus melphalan (140 mg/m2) or busulphan (10 mg/kg). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A plus short-course methotrexate. The preparative regimens were well tolerated. All patients experienced severe pancytopenia, but haematological recovery was prompt in all but two cases (early deaths). The 100-d probability of developing grade II–IV acute GVHD was 32% (10% grade III–IV), and the 1-year probability of developing chronic extensive GVHD was 43%. Early complete donor chimaerism was observed in 52/68 patients, and 16 evaluable patients were in complete chimaerism 1 year post transplant. With a median follow-up of 283 d (355 in 48 survivors), the 1-year probability of transplant-related mortality was 20%, and the 1-year overall and progression-free survivals were 60% and 55% respectively. In conclusion, RIC regimens lead to low early toxicity after allografting, with stable donor haematopoietic engraftment, with an apparent low risk of acute GVHD. Chronic GVHD, however, develops in a significant proportion of patients.

International audience; Both auto-SCT and reduced intensity allo-SCT (RIST) are employed in the treatment of relapsed follicular lymphoma (FL). We have analysed the outcome of these two transplant procedures when used as a first transplant in this setting. We conducted a retrospective comparison of 726 patients who underwent an auto-SCT and 149 who underwent a RIST as a first transplant procedure for relapsed FL as reported to the Lymphoma Working Party of the European Bone Marrow Transplant. The non-relapse mortality (NRM) was significantly worse for patients undergoing a RIST (relative risk (RR) 4.0, P

BACKGROUND High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT. METHODS Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed. RESULTS Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (

Background: Limited experience is available on the feasibility and efficacy of autologous stem-cell transplantation (ASCT) in patients with mantle cell lymphoma (MCL) beyond 65 years. Design and methods: We analysed 712 patients with MCL treated with ASCT from 2000 to 2007 and reported to the European Group for Blood and Marrow Transplantation registry. Patients >65 years were compared with patients

Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is currently considered the standard of care for those patients with HL that relapse after autologous HSCT. Several studies have shown that fit patients with chemosensitive disease can benefit from alloHSCT using and identical sibling (SIB) or matched-unrelated (MUD) donors. Recently, encouraging results have been obtained using haploidentical donors (HAPLO) and post-transplantation cyclophosphamide (ptCY) as graft-versus-host disease prophylaxis (GVHD). Because information regarding the results of alloHSCT using alternative donors is still scarce, we aimed to compare outcome of umbilical cord blood (UCB) and HAPLO transplants with conventional SIB and MUD for HL. Patients and methods: Information of patients older than 17y with HL who received an alloHSCT from a SIB, MUD (8/8 antigen matched), UCB or a ptCY-based HAPLO between 2010-2013 was downloaded from the EBMT and GETH databases. Results: 773 patients with HL were identified meeting the inclusion criteria. 339 received a transplant from a SIB donor, 276 from a MUD, 101 from HAPLO, and 47 from UCB. A significant higher number of patients treated with alloHSCT from UCB and HAPLO donors received reduced intensity (RIC) regimens in comparison to SIB and MUD (76% and 88% vs. 69% and 69%, respectively, p=0.001). Bone marrow was more frequently used as source of stem cells in the HAPLO group in relation to SIB and MUD (61% vs 10% and 11%, respectively, p=0.001), Other variables such as sex, age, performance status, chemorefractory disease, and previous autologous SCT were balanced. Median follow-up after alloHSCT for all patients was 12 months (1-60). The 1-year probabilities of overall survival (OS) and progression-free survival (PFS) were 80% and 49% after SIB transplant, 69% and 54% after MUD, 65% and 40% after UCB, and 73% and 56% after HAPLO, respectively. The 1-year probabilities of non-relapse mortality (NRM) and relapse rate (RR) were 12% and 38% after SIB, 21% and 25% after MUD, 20% and 40% after UCB, and 18% and 27% after HAPLO. Multivariate analysis showed that, in comparison with standard SIB alloHSCT, UCB was associated with a trend to a higher NRM (p=0.08) and RR (p=0.06), leading to a significant lower OS and PFS (p=0.009, HR 2.1, 95% CI 1.2-3.6; p=0.02, HR 1.6, 95% CI 1.1-2.3; respectively). NRM was also significantly higher after MUD (p=0.004, HR 1.8, 95% CI 1.2-2.6), but in contrast, RR was lower (p=0.003 HR 0.6, 95%CI 0.5-0.9) with a lower OS (p=0.002, HR 1.6, 95% CI 1.2-2.1) and no significant differences in PFS. No significant differences were observed between HAPLO and SIB in NRM, RR, PFS and OS. Conclusions: This registry study suggests that in adults with advanced HL, the outcome of pt-CY-based HAPLO HSCT may be comparable to that of conventional SIB alloHSCT and MUD across multiple centers and conditioning regimens. These findings need to be corroborated by longer follow-up. Figure 1. Figure 1. Disclosures Peggs: Autolus: Consultancy, Equity Ownership; Cellectis: Research Funding. Milpied:Celgene: Honoraria, Research Funding. Afanasiev:CELLTRION, Inc.: Research Funding. Russell:Therakos: Other: shares. Sureda:Takeda: Consultancy, Honoraria, Speakers Bureau.

We report the results of a prospective study of a reduced-intensity conditioning (RIC) regimen followed by allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA-identical sibling in 37 patients with acute myeloid leukemia (AML; n = 17) or myelodysplastic syndrome (MDS; n = 20). The median age was 57 years, and 22 (59%) were beyond the early phase of their disease. The incidence of grade II to IV acute graft-versus-host disease (GVHD) was 19% (5% grade III-IV), and the 1-year incidence of chronic extensive GVHD was 46%. With a median follow-up of 297 days (355 days in 24 survivors), the 1-year probability of transplant-related mortality was 5%, and the 1-year progression-free survival was 66%. The 1-year incidence of disease progression in patients with and without GVHD was 13% (95% CI, 4%-34%) and 58% (95% CI, 36%-96%), respectively (P = .008). These results suggest that a graft-versus-leukemia effect plays a crucial role in reducing the risk of relapse after a RIC allograft in AML and MDS.

Iron overload (IO) is associated with free radical generation and tissue damage. Our main objective was to ascertain if very high levels (VHL) of ferritin (>/=3000 microg/l) and transferrin saturation (TS) >/=100% during conditioning had an impact on overall survival (OS) and transplant-related mortality (TRM) after a haematopoietic stem cell transplantation (HSCT). Levels of ferritin and TS were measured at days -7 and -4, respectively, in 25 patients who underwent HSCT after CY/TBI. The group consisted of 20 men and five women with a median age of 40 years. Fifteen patients were autotransplanted and 10 allotransplanted. Nine of them had a diagnosis of AL, six of CML and 10 of lymphoma. Thirteen of them were in early and 12 in advanced status of disease. VHL of ferritin and TS >/=100% were associated with a decreased OS (P = 0.001 and P = 0.006, respectively) and an increased TRM (P = 0.003 and P = 0.004, respectively) in univariate survival analysis. Both variables remained significant at multivariate analysis for OS (P = 0.03 and 0.02, respectively) and TS was an independent factor for TRM (P = 0.01). Ferritin was very close to achieving statistical significance for TRM (P = 0.06) in multivariate analysis. In conclusion, VHL of ferritin and TS >/=100% at conditioning are associated with an increase in toxic deaths after transplant.

Purpose To analyze the outcome, including nonrelapse mortality (NRM), relapse rate (RR), progression-free survival (PFS), and overall survival (OS), of patients with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) relapsed after an autologous stem-cell transplantation (ASCT) and treated with an allogeneic stem-cell transplantation (allo-SCT). Patients and Methods The European Group for Blood and Marrow Transplantation database was scanned for a first allo-SCT in relapsed DLBCL after a previous ASCT between 1997 and 2006. Other inclusion criteria were age at allo-SCT ≥ 18 years and availability of an HLA-identical sibling or a matched unrelated donor. A total of 101 patients (57 males; median age, 46 years) were included. Median follow-up for survivors was 36 months. Results Myeloablative conditioning regimen was used in 37 patients and reduced intensity conditioning (RIC) was used in 64 patients. Three-year NRM was 28.2% (95% CI, 20% to 39%), RR was 30.1% (95% CI, 22% to 41%), PFS was 41.7% (95% CI, 32% to 52%), and OS was 53.8% (95% CI, 44% to 64%). NRM was significantly increased in patients ≥ 45 years (P = .01) and in those with an early relapse (< 12 months) after ASCT (P = .01). RR was significantly higher in refractory patients (P = .03). A time interval to relapse after ASCT of < 12 months was associated with lower PFS (P = .03). The use of RIC regimens was followed by a trend to a lower NRM (P = .1) and a trend to a higher RR (P = .1), with no differences in PFS and OS. No differences were seen between HLA-identical siblings and matched unrelated donors. Conclusion Allo-SCT in relapsed DLBCL after ASCT is a promising therapeutic modality. Patients with a long remission after ASCT and with sensitive disease at allo-SCT are the best candidates for this approach.

Purpose The role of autologous stem-cell transplantation (ASCT) in Waldenström macroglobulinemia (WM) is not defined. The aim of this study was to analyze the results of ASCT in patients with WM and to determine the prognostic factors that have a significant impact on outcome. Patients and Methods We analyzed 158 adult patients with WM reported to the European Group for Blood and Marrow Transplantation (EBMT) between January 1991 and December 2005. Median time from diagnosis to ASCT was 1.7 years (range, 0.3 to 20.3 years), 32% of the patients experienced treatment failure with at least three lines of therapy, and 93% had sensitive disease at the time of ASCT. Conditioning regimen was total-body irradiation–based in 45 patients. Median follow-up for surviving patients was 4.2 years (range, 0.5 to 14.8 years). Results Nonrelapse mortality was 3.8% at 1 year. Ten patients developed a secondary malignancy, with a cumulative incidence of 8.4% at 5 years. Relapse rate was 52.1% at 5 years. Progression-free survival (PFS) and overall survival were 39.7% and 68.5%, respectively, at 5 years and were significantly influenced by number of lines of therapy and chemorefractoriness at ASCT. The achievement of a negative immunofixation after ASCT had a positive impact on PFS after ASCT. When used as consolidation at first response, ASCT provided a PFS of 44% at 5 years. Conclusion ASCT is a feasible procedure in young patients with advanced WM. ASCT should not be offered to patients with chemoresistant disease and to those who received more than three lines of therapy.

Purpose Allogeneic stem-cell transplantation (alloSCT) is a curative therapeutic option for patients with low-grade lymphoid malignancies. Information regarding alloSCT in Waldenström macroglobulinemia (WM) is limited. This study presents the long-term outcome of a large series of patients with WM treated with alloSCT. Patients and Methods A total of 86 patients received allograft by using either myeloablative (MAC; n = 37) or reduced-intensity conditioning (RIC; n = 49) regimens and were retrospectively studied. The median age was 49 years (range, 23 to 64 years); 47 patients had received three or more previous lines of therapy, and eight patients had experienced failure on a prior autologous stem-cell transplantation. A total of 59 patients (68.6%) had chemotherapy-sensitive disease at the time of alloSCT. Median follow-up of the surviving patients was 50 months (7 to 142 months). Results Nonrelapse mortality (NRM) at 3 years was 33% for MAC and 23% for RIC. The overall response rate was 75.6%. The relapse rates (RRs) at 3 years were 11% for MAC and 25% for RIC. Fourteen patients received donor lymphocyte infusions (DLIs) for disease relapse. PFS and OS at 5 years were 56% and 62% for MAC and 49% and 64% for RIC, respectively. The occurrence of chronic graft-versus-host disease (cGVHD) was associated with a higher NRM and a lower RR, leading to an improvement in PFS. Conclusion alloSCT can induce durable remissions in a selected population of young and heavily pretreated patients with WM. The low RR, the achievement of additional disease responses after DLIs, and the lower RR in patients developing cGVHD suggest the existence of a clinically relevant graft-versus-WM effect.

Purpose To analyze the long-term outcome in terms of nonrelapse mortality (NRM), relapse rate (RR), progression-free survival (PFS), and overall survival (OS) in patients with angioimmunoblastic T-cell lymphoma (AITL) treated with allogeneic stem-cell transplantation (alloSCT). Patients and Methods Forty-five patients with AITL who had undergone an alloSCT between January 1998 and December 2005 and were registered in the European Group for Blood and Marrow Transplantation database were analyzed. Median age was 48 years (range, 23 to 68 years), 34 patients had received ≥ two lines of chemotherapy before alloSCT, and 11 patients had experienced treatment failure with a prior autologous stem-cell transplantation. Twenty-five patients underwent a myeloablative alloSCT, and 20 underwent a reduced-intensity alloSCT. Donors were HLA-identical siblings in 26 patients. Twenty-seven patients were allografted in chemotherapy-sensitive disease, and 18 were allografted in refractory disease. Results The cumulative incidence of NRM was 18%, 22%, and 25% at 3, 6, and 12 months, respectively. Patients with poor performance status had a significantly higher NRM (P = .01). RR was estimated as 16% and 20% at 2 and 3 years, respectively, and was lower in patients developing chronic graft-versus-host disease (cGVHD). PFS and OS rates were 62% and 53% and 66% and 64% at 1 and 3 years, respectively, and were significantly better in chemotherapy-sensitive patients. Conclusion AlloSCT represents a valid therapeutic option for patients with AITL. Both the lower RR after transplantation as well as the decreased RR in patients developing cGVHD after the alloSCT suggests the existence of a clinically relevant graft-versus-lymphoma effect.

Autologous stem cell transplantation (ASCT) has been successfully used in HIV-related lymphoma (HIV-Ly) patients on highly active antiretroviral therapy. We report the first comparative analysis between HIV-Ly and a matched cohort of HIV− lymphoma patients. This retrospective European Group for Blood and Marrow Transplantation study included 53 patients (66% non-Hodgkin and 34% Hodgkin lymphoma) within each cohort. Both groups were comparable except for the higher proportion of males, mixed-cellularity Hodgkin lymphoma and patients receiving granulocyte colony-stimulating factor before engraftment and a smaller proportion receiving total body irradiation-based conditioning within the HIV-Ly cohort. Incidence of relapse, overall survival, and progression-free survival were similar in both cohorts. A higher nonrelapse mortality within the first year after ASCT was observed in the HIV-Ly group (8% vs 2%), predominantly because of early bacterial infections, although this was not statistically significant and did not influence survival. Thus, within the highly active antiretroviral therapy era, HIV patients should be considered for ASCT according to the same criteria adopted for HIV− lymphoma patients.

Background The role of reduced intensity conditioning allogeneic stem transplantation (RICalloSCT) in the management of patients with Hodgkin's lymphoma remains controversial. Design and Methods To further define its role we have conducted a retrospective analysis of 285 patients with HL who underwent a RICalloSCT in order to identify prognostic factors that predict outcome. Eighty percent of patients had undergone a prior autologous stem cell transplantation and 25% had refractory disease at transplant. Results Non-relapse mortality was associated with chemorefractory disease, poor performance status, age >45 and transplantation before 2002. For patients with no risk factors the 3-year non-relapse mortality rate was 12.5% compared to 46.2% for patients with 2 or more risk factors. The use of an unrelated donor had no adverse effect on the non-relapse mortality. Acute graft versus host disease (aGVHD) grades II-IV developed in 30% and chronic GVHD in 42%. The development of cGVHD was associated with a lower relapse rate. The disease progression rate at one and five years was 41% and 58.7% respectively and was associated with chemorefractory disease and extent of prior therapy. Donor lymphocyte infusions were administered to 64 patients for active disease of whom 32% showed a clinical response. Eight out of 18 patients receiving donor lymphocyte infusions alone had clinical responses. Progression-free and overall survival were both associated with performance status and disease status at transplant. Patients with neither risk factor had a 3-year PFS and overall survival of 42% and 56% respectively compared to 8% and 25% for patients with one or more risk factors. Relapse within six months of a prior autologous transplant was associated with a higher relapse rate and a lower progression-free. Conclusions This analysis identifies important clinical parameters that may be useful in predicting the outcome of RICallCalloSCT in Hodgkin's lymphoma.

Purpose To compare the clinical outcome in terms of nonrelapse mortality (NRM), relapse rate (RR), overall survival (OS), and progression-free survival (PFS) in patients with relapsed Hodgkin's lymphoma (HL) treated with reduced-intensity conditioning (RIC) or myeloablative conditioning followed by allogeneic stem-cell transplantation (alloSCT). Patients and Methods A total of 168 patients with HL undergoing a first alloSCT (RIC, n = 89; myeloablative conditioning, n = 79) between January 1997 and December 2001 and registered in the European Group for Blood and Marrow Transplantation database were analyzed. Results NRM was significantly decreased in the RIC group (hazard ratio [HR], 2.85; 95% CI, 1.62 to 5.02; P < .001). OS was better in the RIC group (HR, 2.05; 95% CI, 1.27 to 3.29; P = .04) and there was a trend for better PFS in the RIC group (HR, 1.53; 95% CI, 0.97 to 2.40; P = .07). RR was higher in the RIC group in univariate but not in multivariate analysis. The development of chronic graft-versus-host disease (GVHD) significantly decreased the incidence of relapse, which translated into a trend for a better PFS. Conclusion The lower incidence of NRM in the RIC group is encouraging, particularly because these patients experienced adverse pretransplantation characteristics more frequently. This analysis also indicates the existence of a graft-versus-HL effect correlated to the development of GVHD. Additional efforts to reduce the high RR seen in both groups of patients will be necessary to improve the modest PFS (31% v 27%) and OS (59% v 36%) for patients prepared with RIC or myeloablative conditioning.

Allogeneic HCT from a CCR5 Δ32/Δ32 unrelated donor by Hutter et al provides the only evidence to date of long term control of HIV infection, and a compelling argument in favor of homozygous CCR5 Δ32reconstitution as the key mechanism driving resistance to infection 6 years after stopping antiretroviral therapy (ART). Low prevalence of Δ32/Δ32 genotype ( A 36 year-old man with HIV-1 infection from 2009 was diagnosed with DLBCL stage IIA in 2012. The patient had no illnesses associated with AIDS, good disease control and adherence to ART, with No HLA-matched sibling donors were available. Two CCR5 Δ32/Δ32 CB units (CBU) identified at the StemCyte inventory (Covina, CA) were HLA-compatible with the patient at the 4/6 level. A myeloablative CB alloHCT was performed using the single CCR5 Δ32/Δ32 CBU with higher cellularity (#1; Table 1) plus CD34+ cells from a haploidentical brother. The patient provided informed consent and IRB approved the alloHCT and research protocol. During HCT, ART combined abacavir, lamivudine and raltegravir. Neutrophil engraftment, 100% derived from the haploidentical donor, occurred on day +11. Post-thawing analysis of CBU#1 showed very poor clonogenic capacity, and donor switch to CB-origin failed, with persistently low CB-chimera Long term monitoring and target organs and tissues analysis of viral reservoir will not be possible in this case. However, our data suggest that CCR5 Δ32/Δ32 CB HCT can successfully eliminate HIV-1 and render the recipient's T cells resistant to HIV-infection. Thus, they strongly support the use of CB as a platform for a broader application of this curative technology to other HIV-1 infected individuals. Abstract 1261. Table 1. Patient, Donor and Cell Product Characteristics Recipient Haploidentical Brother CBU #1 CBU #2 Year of birth or collection 1975 1971 2008 2008 CCR5 genotype WT / WT WT / Δ32 Δ32 / Δ32 Δ32 / Δ32 HLA typing - HLA A 01:01 / 68:01 11 / 68 01:01 / 03:01 01:01 / 02:XX - HLA B 08:01 / 07:02 35 / 07 08:01 / 07:02 08:01 / 07:02 - HLA DR 03:01 / 13:01 01 / 13 03:01 / 14:01 03:01 / 14:01 Cell products content Pre-HCT Controls Post Thawing # Pre-HCT Controls Post Thawing # CD34 (x105/kg) − 40 ¤ 0.7 0.52 0.73 0.22 TNC (x107/kg) − − 2.53 2.05 1.98 1.64 CFU-GM (x104/kg) − − 1.02 * 0.11 0.12 * Nil Total CFU (x104/kg) − − 2.13 * 0.21 0.42 * Nil ¤ Purified by Miltenyi positive selection to include Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Most studies indicate that ABO incompatibility has no effect on the clinical outcome after allogeneic peripheral blood progenitor cell (PBPC) transplantation (allo-PBPCT). However, it carries additional risks of hemolytic reactions, delayed red blood cell (RBC) engraftment, and pure red cell aplasia (PRCA). Data on these events after reduced intensity conditioning (RIC) regimens are limited, but recent studies have suggested a higher transplant-related mortality (TRM) and morbidity in this setting.We investigated the impact of ABO-matching on the outcome of 77 patients included in a prospective RIC allo-PBPCT protocol, focusing on engraftment, transfusion requirements, graft-versus-host disease, TRM, and survival.There were 17 (22%) minor and 8 (10%) major ABO-incompatible transplants. No graft failures were observed. After major ABO-incompatible grafts, RBC engraftment was delayed, longer thrombocytopenia periods were documented, and transfusion requirements increased. A transient mild hemolysis occurred in 10 patients, 7 (41%) minor and 3 (37%) major ABO-mismatched. A PRCA was observed in a O+ patient with a pretransplant anti-Jka, grafted from an A + Jka+ donor. Graft-versus-host disease, disease progression, and TRM were not affected by ABO matching.ABO incompatibility was not associated with clinically relevant hemolysis after the RIC protocol used and did not impair the clinical outcome. PRCA was only observed in one patient, with a non-ABO RBC allo-antibody.

Objectives The aim of this study was to compare two approaches used to reduce transplant-related mortality (TRM) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in elderly patients. Patients and methods Data from 50 patients, 45 years of age or older, consecutively treated with an HLA-identical sibling allo-PBSCT at the Hospital de Sant Pau were analyzed. We have compared the outcome of patients treated with conventional myeloablative regimens and CD34 + -selected cells (CD34 + group; n=23) with those receiving reduced-intensity conditioning regimens, consisting of fludarabine (150 mg/m 2 ) plus an alkylating agent, followed by unmanipulated grafts (RIC group; n=27). Patient characteristics were well balanced between the two groups, although patients in the RIC group were slightly older. Results The incidence of acute graft-vs-host disease (GVHD) was similar in both groups. The 1-year cumulative incidence of extensive chronic GVHD was 38% in the RIC group and 17% in the CD34 + group ( p =0.2). After a median follow-up of 28 months, there were no differences in the relapse rate. Patients in the RIC group had a lower TRM, with a cumulative incidence of 7% vs 30% at 6 months and 15% vs 39% at 1 year ( p =0.05). The Kaplan-Meier estimates of PFS at 2 years was 67% in the RIC group and 43% in the CD34 + group ( p =0.09) and the OS was 69% vs 43% ( p =0.05), respectively. Conclusion CD34 + cell selection reduced the risk of extensive cGVHD but was associated with a higher TRM. Although the number of patients is limited, our study suggests that this approach should be restricted to relatively young patients, as better outcomes can be achieved in elderly patients using RIC strategies.

Allogeneic hematopoietic stem cell transplantation is the only curative therapy for myelodysplasia (MDS). To identify factors influencing transplantation outcome, we studied 452 recipients of HLA-identical sibling transplants for MDS from 1989 to 1997, reported to the International Bone Marrow Transplant Registry. Patients with treatment-related MDS or unclassified MDS were excluded. Median age was 38 years (range, 2-64 years). Sixty percent had refractory anemia with excess blasts (n = 136) or with excess blasts in transformation (n = 136). Conditioning regimens included total body irradiation in 199 (44%) cases. Marrow was T-cell depleted for 58 (13%) transplants. Cumulative incidences of neutrophil engraftment, grades II-IV acute graft-versus-host disease (GVHD), and chronic GVHD were 91% (95% confidence interval [CI], 88%-93%), 36% (95% CI, 31%-40%), and 39% (95% CI, 33%-44%), respectively. Three-year transplantation-related mortality (TRM), relapse, disease-free survival, and overall survival rates were 37% (95% CI, 32%-42%), 23% (95% CI, 19%-27%), 40% (95% CI, 36%-45%), and 42% (95% CI, 37%-47%), respectively. Multivariate analyses showed that young age and platelet counts higher than 100 x 10(9)/L at transplantation were associated with lower TRM and higher disease-free and overall survival rates. Relapse incidence was higher in patients with high percentages of blasts in the marrow at transplantation or presentation, with high International Prognostic Scoring System scores at diagnosis, and with T-cell-depleted transplants. These findings indicate that transplantation from an HLA-identical sibling offers the possibility of long-term, disease-free survival to patients with MDS. Best candidates are younger patients with a low percentage of blasts and preserved platelet counts.

High-flux/high-efficiency (HF/HE) dialysis is associated with improved clearance for larger molecules, which include a wide variety of middle molecules and water-soluble vitamins. Our study attempted to measure in vivo clearances of serum pyridoxal-5'-phosphate (PLP), the active metabolite of vitamin B6, on standard cuprophan versus cellulose triacetate HF/HE dialysis for patients maintained on 10 mg daily pyridoxine supplements. A longitudinal evaluation of PLP after 3 months on HF/HE dialysis was performed simultaneously. The average in vivo PLP clearance for six patients on standard hemodialysis increased by more than 50%, from 86 +/- 61.7 mL/min using a cuprophan membrane to 173 +/- 90.2 mL/min using a cellulose triacetate dialyzer, at average blood flows of 375 mL/min (P < 0.05). Levels of PLP decreased from a baseline of 50 +/- 13.8 ng/mL to 24 +/- 9.7 ng/mL (P < 0.05) after 3 months of HF/HE treatments; the levels returned to 45 +/- 6.4 ng/mL on resumption of standard dialysis treatments. Although not achieving statistical significance, the average hematocrit increased from 31.2% +/- 1.66% to 32.7% +/- 1.24% while on HF/HE dialysis without an increase in erythropoietin requirements. We conclude that HF/HE dialysis treatments can have a dramatic impact on vitamin B6 homeostasis. Further investigation to evaluate the effects of different membranes and reprocessing should be performed on more heterogeneous patient populations in whom compliance problems with diet and vitamin supplementation may exist. The increased clearance of vitamin B6 may have significantly more detrimental effects in these settings.

Abstract 688 Prognosis of Mantle cell lymphoma (MCL) has recently improved by the use of combination of monoclonal anti-CD20 immunotherapy, high-dose cytarabine containing regimen and autologous stem cell transplantation (ASCT). During the last decade the use of TBI, as part of the conditioning regimen of ASCT, has drastically decreased. This attitude is questionable since first, MCL cell lines exhibit a high sensitivity to radiotherapy in vitro and second, a retrospective study including 18 patients suggested that TBI may improve the EFS after ASCT in MCL (Milpied et al, BMT 1998). Aim. We performed a large retrospective study from the EBMT registry to assess the role of TBI in the conditioning regimen of ASCT in MCL. Patients and methods. All patients who underwent an ASCT between 2000 and 2007 in complete or first partial remission (CR/PR1) registered within the EBMT data-base with complete MedB forms available were eligible for this study. Results. Altogether 418 patients met the eligibility criteria. Median age was 51 years (range 29 to 65 years). At diagnosis 93% of the patients presented with a stage III/IV disease. Most of the patients (85%) had received one line of chemotherapy prior to ASCT. According to reported treatments, 122 patients (31%) had received Rituximab (R) and high-dose cytarabine (HD-Cyt) before transplantation and 111 patients (29%) had not received any of these drugs. At transplant, 283 patients (68%) were in CR and 135 (32%) in PR1. Conditioning regimen for ASCT contained TBI in 152 patients (36.5%) and consisted on a BEAM-based chemotherapy in 92% of the 266 patients transplanted with a non-TBI regimen. Stem cell source was peripheral blood for 99.3% of patients. With a median follow-up of 29 months, median overall and disease free survival (OS and DFS) of all patients were 99 and 57 months, respectively. Disease status at transplant appeared as a significant predictive factor for DFS and relapse incidence (RI) but at the time of analysis had no impact on OS. In comparison to patients transplanted in CR, those transplanted in PR1 had an impaired DFS (median DFS 52 months versus 40 months, respectively) (RR= 1,53, 95% CI 1.10–2.14, p=0.01) with an increased incidence of relapse (RR= 1.49, 95% CI 1.04–2.13, p= 0.03). Since we found a significant interaction between the use of TBI and disease status on the incidence of relapse, all further analysis were stratified on disease status at transplant. The use of R and HD-Cyt before ASCT or TBI in the conditioning of ASCT did not have any impact on OS, DFS and RI of patients transplanted in CR. In contrast, for patients transplanted in PR1, pre-transplant treatment with R and HD-Cyt was associated with a prolonged DFS in comparison to those who did not receive these treatments (median DFS 52 months versus 27 months, respectively, p=0.0891). Moreover, in patients in PR1 at transplant, the use of TBI was associated with a significant reduction of the incidence of relapse in both univariate and multivariate analysis (p=0.034 and RR= 0.409, 95% CI 0.213–0.786, p=0.007, respectively). There was a trend to a better DFS in patients transplanted in PR1 with TBI (median DFS 60 months with TBI versus 33 months without TBI, p=0.123). At the time of analysis, overall survival and non relapse mortality (NRM) were similar between patients who received TBI and those who did not. Three secondary malignancies were reported in this series of patients with two occurring in the TBI group Conclusion. In this retrospective series of autografted MCL, the risk of relapse after ASCT is mainly dependant on the disease status at transplant. TBI or other radiotherapy-based conditioning can be probably avoided in patients transplanted in CR but should still be considered in patients who can not achieve a better response than PR at transplant. Disclosures: No relevant conflicts of interest to declare.

Abstract 363 Matched unrelated donor stem cell transplantation (MUD-SCT) has recently become a therapeutic option for patients with B cell diffuse large cell lymphoma (DLBCL) who fail other conventional therapies and do not have a matched sibling donor available. We present retrospective data of 473 DLBCL patients, 285 males and 188 females, aged 18 to 69 years (median 46 years), treated with matched sibling (n=301) or matched unrelated (n=172) SCT between January 2000 and December 2007 and reported to the EBMT registry. Median time from diagnosis to allograft was 25 months (range 2 – 203). Fifty-seven percent of the patients had failed previous autologous SCT, and 12% were transplanted in chemorefractory disease. After a median follow up of 41 months, the estimated 3-year non-relapse mortality (NRM), relapse rate (RR), progression free survival (PFS) and overall survival (OS) for the whole series were 37%, 32%, 31% and 40%, respectively. There were no statistically significant differences in patient age, disease status at transplantation, stem cell source and intensity of conditioning regimen between the Sib and the MUD cohorts (summarized in Table 1).However, a higher number of patients undergoing MUD have already failed an autograft (66% vs 52%, p=0.004), and T cell depleted grafts were more frequently used in the MUD cohort. Acute GvHD occurred in 48% of patients treated with a sib allograft vs 54% in those receiving a MUD (p=n.s). Interestingly, there were no statistically significant differences in NRM and RR between the Sib and the MUD groups (3 yr NRM=38% vs 37%, RR approached 38% vs 34%), resulting in a similar 3-year PFS and OS (32% vs 29% and 42% vs 35%, respectively). Multivariate analysis identified refractory disease (p = 0.001, RR 3.2; CI=1.3-3.5), poor performance status (p = 0.017, RR 1.9; CI=1.1-3.4) and age at transplantation > 50 years (p = 0.015, RR1.5; CI=1.1-2.1) as independent adverse prognostic factors for NRM and time from diagnosis to SCT < 36 months (p = 0.02, RR 1.5; CI=1.1-2.1), a previously failed autologous SCT (p = 0.026, RR .4; CI=1.1-1.9), refractory disease (p = 0.003, RR 2; CI=1.3-3.1), poor performance status (p = 0.0001, RR 3.5; CI=2.1-5.6) and T cell depletion (p = 0.001, RR 2; CI=1.3-2.9) as adverse prognostic factors for RR. A previous autologous SCT, poor performance status and refractory disease at transplantation were found to be significantly associated with a shorter PFS (p=0.04, RR 1.3; CI=1-1.6; p=0.0001, RR 2.4; CI=1.6-3.4; p=0.000,RR 2.1; CI=1.5-2.9, respectively) and refractory disease (p=0.0001, RR 2.2; CI=1.6-3.1) and poor performance status at the time of SCT (p=0.0001, RR 2.5; CI=1.7-3.6) with a shorter OS. Patients allografted from MUD tended to have a slightly increased risk of overall mortality in multivariate analysis, but this was not statistically significant (p=0.06, RR 1.2; CI=0.95-1.6). In conclusion, MUD SCT provides a curative option, not significantly inferior to that obtained with a matched sibling transplant, for selected patients with DLBCL who have failed conventional therapies, including autograft. Similarly, the type of conditioning regimen was not found to have a significant impact on patient outcome. Table 1. Clinical characteristics Sib vs MUD Sib (n = 301) MUD (n= 172) p Age (median, years) 46 45 N.S. Previous ASCT 48% 33% 0.004 Refractory disease 12% 12% N.S. Poor P.S. 13% 7% 0.06 RIC/CC 57%/43% 56%/42% N.S. SC source BM/PB 20%/80% 22%/78% N.S. ATG/ALG 15% 46% ASCT. Autologous stem cell transplantation; PS. Performance status; RIC. Reduced intensity conditioning; CC. Conventional conditioning; SC. Stem cell; BM. Bone marrow; PB. Peripheral blood; ATG/ALG. Anti-thymocyte globulin/ALG. Anti-lymphocyte globulin. Disclosures: No relevant conflicts of interest to declare.

8060 Background: Autologous stem cell transplantation (ASCT) is the standard of care for patients with HL relapsing after conventional chemotherapy (CT). Nevertheless, a significant proportion of p...

Abstract 663 We have recently reported encouraging results after unrelated cord blood (UCBT) for patients with lymphoid malignancies (Rodrigues et al, 2009). Progression free survival (PFS) was improved in patients with chemosensitive disease, who have received a higher CD34 cell dose, and low-dose TBI in the preparative regimen. However, whether outcomes after reduced intensity conditioning (RIC) UCBT are comparable to outcomes after RIC-MUD for lymphoid malignancies remains to be defined. We studied 359 adult patients with lymphoma or chronic lymphocytic leukemia (CLL) who received an UCBT (n=75) or a MUD (n=284) after a RIC regimen between January 2000 and December 2006, and registered in the EBMT and/or the Eurocord databases were analyzed. In the MUD group, we included only patients receiving peripheral blood stem cells and with a 6/6 or a 8/8 match. Patients from 111 centers were included: UCBTs were performed in 28 centers and MUD transplants in 98 centers. Only 15 centers performed both types of transplant. One hundred sixty eight patients had a non-Hodgkin lymphoma (NHL), 108 had Hodgkin's lymphoma (HL), and 83 had CLL. In the UCBT group, patients were slightly younger (median age 44 vs. 48 in the MUD group, P=0.05), aggressive histologies and HL were more frequent (P=0.04), and more patients underwent the transplant in refractory or chemoresistant disease (P Disclosures: No relevant conflicts of interest to declare.

Abstract 4355 Little is known about the additional benefit of Autologous Stem Cell Transplantation (ASCT) as consolidation treatment of NHL in 1st CR in HIV+ patients. We herein report a comparative analysis of HIV+ patients with a LBCL treated with chemotherapy (chemo) followed by ASCT and a matched cohort of HIV+ patients treated with chemo alone. Methodology Retrospective, registry-based, matched cohort study. ASCT cohort: patients with diffuse large B-cell (DLBC) or plasmablastic NHL treated with ASCT in 1st CR after standard chemo and reported to the EBMT Registry. Chemo cohort: For each patient within the ASCT cohort we selected two controls from the HIV+ patients with NHL GESIDA/PETHEMA registry. Patients in both cohorts were in 1st CR following front-line or rescue (for partially responding patients) chemo and were matched according to histology, IPI and the use of Rituximab. We compared overall survival (OS), disease free survival (DFS) and cumulative incidence (CI) of relapse between both cohorts. These primary outcomes were defined according to the EBMT. OS was computed from diagnosis while DFS and CI of relapse were computed from 3 weeks after the last standard chemo cycle administered (end of chemo). Results The ASCT cohort included 10 patients diagnosed between 1999 and 2005. The Chemo cohort included 20 patients, 16 diagnosed between 1999 and 2005. Both cohorts were comparable for the main clinical and patient features (Table 1). The median (range) follow-up (FU) time since the end of chemo for surviving patients was 56 months (mo) (24-106) in the ASCT cohort vs 37 mo (8-107.5) in the Chemo cohort; P=.28. Five years (yr) OS for the ASCT cohort and the Chemo cohort were 68.5% [CI95%: 39-98] and 46.5% [CI95%: 18-75], respectively; P=.6. Three yr DFS for the ASCT cohort and the Chemo cohort were 70% [CI95%: 41.5-98.5] and 59.5% [CI95%: 29-86]; respectively; P=.4. The CI of relapse in the ASCT cohort and the Chemo cohort were 21% [CI95%: 0-47] and 27% [CI95%: 2-51], respectively; P=.8 Conclusions In this retrospective registry-based, matched cohort study of HIV+ patients with large B-cell NHL we found a non-significant effect of ASCT as consolidation treatment in 1st CR patients, in terms of survival and relapse incidence. Nevertheless, due to the observed favorable tendency, future analysis including a higher number of patients and, eventually, randomized clinical studies, should be performed to further clarify these observations. Disclosures: No relevant conflicts of interest to declare.

Abstract 874 Allogeneic HCT is potentially curative in FL, but wide adoption of this treatment is limited by its toxicity and donor availability. Improvements in HLA-matching have improved the safety of unrelated donor (URD) HCT. We compared the outcomes of 702 recipients of allogeneic HCT for FL (198 URD and 504 sibling donors (sib)) from 171 centers world-wide reporting to the CIBMTR or EBMT between 1997 and 2005. Recipients of mismatched, cord blood or ex vivo T-cell depleted grafts were excluded. Overall and progression-free survival (OS and PFS), transplant-related mortality (TRM) and relapse/progression outcomes were analyzed using Cox proportional hazards regression models with donor type (sib vs. URD) as the main effect. URD HCT was performed more frequently after 2001. Comparing to the sib group, URD HCT recipients were more likely to receive reduced intensity conditioning (70% vs. 54%), antithymocyte globulin or alemtuzumab (in vivo T-cell depletion) or tacrolimus-based graft-versus host disease (GVHD) prophylaxis, and have a longer interval from diagnosis to HCT (median 49 vs. 32 months). URD HCT recipients had poorer risk FL with more pre-transplant chemotherapy, including previous autologous HCT (36% vs. 16%) and prior exposure to rituximab (66% vs. 43%) compared with sib HCT recipients. Adjusted probabilities for three-year PFS and OS were 49% vs. 60% (p=0.02) and 54% vs. 69% ( p 4 lines of therapy or prior autologous HCT). Additionally, in vivo T-cell depletion was associated with a higher risk of relapse/progression and treatment failure. Reduced intensity conditioning was associated with lower TRM, but did not impact other outcomes. In conclusion, this study shows that URD HCTs are performed later in the treatment course for FL, in higher risk patients, most commonly with reduced intensity conditioning, and are associated with worse PFS and OS compared to sib HCT. Considerations for future studies include the use of URD allogeneic HCT earlier in the course of treatment for FL and avoiding T cell depleting agents in the conditioning regimen.Outcome#URD/SibURD vs. sib RR1 (95% CI)P TRM197/5002.04 (1.43 - 2.90) Disclosures: No relevant conflicts of interest to declare.

Both autologous stem cell transplantation (autoSCT) and reduced intensity allogeneic stem cell transplantation (RIST) may be considered as treatment options in patients with relapsed follicular lymphoma (FL). It is currently unknown which transplant strategy is optimal in patients with FL. We have therefore conducted a retrospective comparison of patients who have undergone an autoSCT or a RIST. Adult patients undergoing a 1st transplant procedure and reported to the EBMT between Jan 1998 and Dec 2005 were included. 1394 patients underwent an autoSCT and 110 a RIST with median ages of 51 (20–73) and 50 (32–65) respectively. Patients undergoing a RIST had significantly more advanced disease (stage IV 74% vs 60% p=0.01) and B symptoms (39% vs 27% p=0.05) at diagnosis but there was no difference in the size of the largest mass or the LDH. The median time from diagnosis to transplant was 27 months for the whole group but was significantly longer for patients undergoing a RIST (34 months vs 26 months p=0.005). Patients undergoing a RIST had received more lines of prior therapy (61% 3 or more lines vs 34% for those undergoing autoSCT p

Patients (pts) suffering from mature (peripheral) T-cell lymphoma are known to have a poor outcome compared to pts with aggressive B-cell lymphoma when receiving conventional therapies. However, case reports and single centre experiences show promising results of allogeneic stem cell transplantation (allo SCT) for these pts. We here present a retrospective analysis of 103 pts with mature T-cell lymphoma who received an HLA-identical allo SCT in EBMT centres between 2000 and 2005. Histological subtypes of the patients were anaplastic large cell lymphoma (n=25; 4 anaplastic lymphoma kinase [ALK] positive, 11 ALK negative, 10 ALK unknown), peripheral T-cell lymphoma unspecified (n=51), angioimmunoblastic T-cell lymphoma (n=18) and aggressive T-cell lymphoma unspecified (n=9). Patients with primary cutaneous T-cell lymphoma or T-lymphoblastic lymphoma were excluded. Median follow up for surviving patients was 40 months (6–98), median age at allo SCT 42 years (18–68) and median time to allo SCT 17 months (3–233). 39 pts had failed a prior autologous SCT; 68 pts had chemosensitive disease at allo SCT (of these 15 in CR1) and 30 pts had chemorefractory or untested relapsed or progressive disease. Donors were HLA identical siblings for 73 and matched unrelated donors for 30 pts; 82 pts received peripheral blood stem cells. 54 pts were treated with reduced intensity conditioning before SCT. The cumulative incidence (CI) of acute graft versus host disease (GvHD) 100 days after SCT was 52% and had no effect on non-relapse mortality (NRM) or relapse rate (RR). 34 of 74 evaluable pts experienced chronic GvHD (14 limited, 20 extensive), CI 46% at 2 years. Introducing chronic GvHD as a time dependent covariate, this factor was associated with a higher NRM (p This retrospective analysis on allo SCT in peripheral T-cell lymphoma shows an encouraging low RR but efforts have to be made to reduce NRM. Prospective studies are warranted to further define pts who will profit from an early allo SCT.

Patients (pts) with mature (peripheral) T-cell lymphoma are known to have a poor prognosis when receiving standard conventional chemotherapy. This leads many physicians to regard high dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) as standard therapy for these pts. We here present a retrospective analysis on 424 pts with mature T-cell lymphoma who have received HDT and ASCT in EBMT centres between 2000 and 2005. Patients with primary cutaneous or immature (lymphoblastic) lymphoma were not included. Histological subtypes were anaplastic large cell lymphoma (ALCL, n=98, 23.1%; 19 anaplastic large cell kinase (ALK) positive, 42 ALK negative and for 37 pts the ALK status was unknown), peripheral T-cell lymphoma (PTCLu, n=176, 41.5%), angioimmunoblastic T-cell lymphoma (n=120, 28.3%) and aggressive T-cell lymphoma unspecified (n=30, 7.1%). Median age at ASCT was 51 years (17.2–73.5), median time from diagnosis to ASCT was 9 months (4–99), and median follow up for surviving pts was 36 months (0.4–99). 268 pts (63%) were male. 1/3 received HDT and ASCT after only one previous treatment line. 35% of the pts were treated in CR1, and 52% in chemosensitive disease worse than CR1. At the time point of ASCT only 12 pts (2.8%) had a poor performance status. 9% of the pts received total body irradiation as part of the conditioning regimen. At 3 years after ASCT non relapse mortality (NRM) was 7.4% and the relapse rate (RR) was 43.1%. In multivariate COX analysis for NRM refractory disease (p

Mantle cell lymphoma (MCL) is a disease associated with a poor prognosis characterised by inevitable relapse following both conventional chemotherapy and autologous stem cell transplantation (SCT). The role of reduced intensity allogeneic stem cell transplantation (RIST) in MCL remains controversial. We have conducted a retrospective study of RIST in MCL as reported to the EBMT registry in an attempt to define factors predicting the outcome of this procedure. Between 1998 and 2006 279 patients with MCL received a RIST with 210 procedures performed after the year 2001. 219 (78%) were male and the median age at transplant was 55 years (range 30–71). At diagnosis 97% had stage IV disease and 39% had B symptoms. Patients had received a median of 3 lines (range 1–9) of prior therapy and 119 (43%) had undergone a previous autologous SCT. The median time from diagnosis to transplant was 30 months (range 3–161). The disease status at transplant was; complete remission 124, partial remission 95, refractory disease 32 and untested relapse 17. The performance status at transplant was poor in 15 patients. Conditioning for RIST was achieved with fludarabine+alkylating agent in 66%, fludarabine+TBI in 13%, and a variety of other reduced intensity regimens in 20%. Transplants were performed from 193 matched family donors, 60 matched unrelated donors and 22 mismatched donors who provided peripheral blood stem cells in 252 cases and bone marrow in 26. T cell depletion with either CAMPATH or ATG was performed in 85 transplants. 274 patients were evaluable for engraftment of whom 272 engrafted with 4 secondary graft failures. Acute graft versus host disease (GVHD) developed in 149 patients (grade I 45, grade II 52, grade III/IV 50, unknown extent 2). Of 214 patients at risk 30 developed limited chronic GVHD and 58 extensive chronic GVHD. There were 91 transplant related deaths with infection and GVHD accounting for 51 of these deaths. The resulting 100 day, 1 year and 3 year non-relapse mortality rates were 13, 32 and 41% respectively. NRM was associated with poor PS at transplant (RR=3.7 p=0.001) and transplantation prior to 2002 (RR= 1.7 p=0.02) but age, prior transplantation and donor relationship had no significant impact. Sixty one patients relapsed at a median time of 7 months (range 1–50 months) post transplant. The cumulative incidence of relapse at 1 years and 4 years was 19% and 31% respectively. Disease relapse was associated with refractory disease at transplant (RR=4.5 p

7036 Background: Matched unrelated donor stem cell transplant (MUD-SCT) provides the only potentially curative option for patients with follicular lymphoma (FL) who fail conventional therapies and ...

AITL is a rare peripheral T-cell lymphoma characterised by an aggressive behaviour, which primarily affects the elderly. Chemotherapy regimens fail to alter the high relapse rate and overall survival hardly exceeds 25% at 5 years. To date, there is no information on the potential role of allogeneic stem cell transplantation (allo-SCT) in the management of AITL. We report the outcome of 39 patients with a median age of 47 years (24–68), who underwent an allo-SCT between 1995 and 2004 for AITL, and were reported to the EBMT registry. The median time from diagnosis to transplant was 10 months (4–72). Thirty-four patients (87%) had previously received two or more treatment lines, and 16 patients (41%) a previous autologous SCT. Fifteen patients (38%) had a primary refractory disease, 13 (33%) were transplanted in partial remission and the remaining patients were in complete remission (CR) (mostly in 2nd and 3rd CR). Twenty-four patients were transplanted from an HLA-identical sibling and 15 from a matched unrelated donor. A myeloablative conditioning regimen (MAC) was used in 21 patients (cyclophosphamide + total body irradiation in 14), while 18 patients received fludarabine-based reduced intensity conditionings (RIC). Peripheral blood was the source of stem cells in 35 patients (90%). Three patients failed to engraft (one patient in the RIC group). Twenty-one patients (54%) developed acute graft versus host disease (grade I-II, n=16; grade III-IV, n=5). Twenty-eight patients (72%) achieved a CR after the allogeneic procedure. Nine patients died from transplant related mortality (TRM) and 5 patients from disease progression. The cumulative incidence of TRM at 12 months was 19% for the MAC and 26% for the RIC group. After a median follow-up for the surviving patients of 20 months (6–74), 25 patients are alive. Relapse rates at 1 and 3 years were estimated at 10% and 18% for the MAC and 16 and 20% for the RIC patients. Progression free survival rates at 3 years were 67% and 50% and the overall survival at the same time 71% and 56% for the MAC and RIC group of patients, respectively. Although follow up is rather short, these data suggest that allo-SCT results in good overall response and is associated with a low relapse rate in this group of poor risk heavily pre-treated and rather elderly group of AITL patients. Allo-SCT could be considered a therapeutic option for eligible high-risk AITL patients. Nevertheless, the impact of this approach should be further explored in prospective collaborative studies.

Several authors have reported ASCT as a feasible, safe and effective treatment in HIV associated lymphoma patients (pts) receiving Highly Active Antiretroviral Therapy (HAART), particularly when being autografted with chemosensitive disease. To gain a better understanding of the usefulness of ASCT in HIV+ Lymphoma pts a retrospective comparative study (HIV+ vs HIV- lymphoma pts with ASCT) has been performed using the EBMT-LWP Registry. Methodology: Registry-based, retrospective, individually matched case-control analysis. Within the participating centres one or two HIV- controls for each HIV+ pt were selected from the registry with the following inclusion criteria: Known HIV serological status at ASCT, lymphoma (HL or NHL), ASCT performed between 1999 and 2006 and pts over 18 years of age. Two cohorts (HIV+ vs HIV-) were matched for histology, IPI at diagnosis (NHL), stage at diagnosis, disease status at ASCT, age at ASCT, year and country of ASCT. Results: 40 HIV+ lymphoma pts undergoing an ASCT were matched with 46 HIV- pts. Pts and transplant features are shown in table 1. With a median follow up of 36 mo, the differences regarding OS and PFS were not significant: 62% for HIV+ vs 69% for controls, and 56.5 vs 58%, respectively. No differences were seen regarding HL and NHL pts. An overall TRM of 10% was observed in the HIV cohort, mainly related to infections, while no cases of TRM were seen within the control arm. Since survival rates between the HIV+ and the matched HIV- lymphoma populations remained comparable, the HIV condition should not preclude these pts from being treated according to the same criteria as the HIV negative lymphoma population. Nevertheless, infectious complications should be cautiously followed within the HIV+ lymphoma pts undergoing an ASCT. Patients and transplant features HIV+ HIV- n=40 % n=46 % Age [Median (range)] in years 41.4 (29.2–62.5) 44 (16–62.4) p= NS Male sex 35 87.5 25 54.3 p=0.001 Histology DLBCL 24 60 25 54.3 p= NS Burkitt lymphoma 2 5 2 4.3 p= NS T-cell NHL 2 5 3 6.6 p= NS HL 12 30 16 34.8 p= NS Disease status at ASCT Complete remission (CR) 21 (12 in CR1) 52.5 (30 in CR1) 20 (11 in CR1) 43.5 (24 in CR1) p= NS Chemosensitive disease 16 40 25 54.3 p= NS Chemorefractory disease 3 7.5 1 2.2 p= NS CD34+ cells infused mill/kg [median (range)] 4.9 (1.6–21.2) 4.8 (0.9–21.2) p= NS G-CSF prior to engraftment 36 90 21 46 p= 0.0001 Neutrophil engraftment 39 98% 46 100 p= NS Cause of Death Relapse/progression 9 60% 10 84% p=0.08 Secondary malignancy 1 6.7% 1 8% p= NS Transplant-related deaths 4 26.7% 0 0% p=0.06 Other 1 6.7% 1 8% p= NS

Background: Autologous stem cell transplantation (ASCT) has been used as a standard treatment in the management of patients (pts) with relapsed/refractory Hodgkin’s lymphoma (HL) in the last few decades. Long-term side effects of this treatment such as secondary malignancies (SM), organ failure and infertility attract scientific interest. Very little data is available on late events among pts with HL treated with ASCT. Material and Methods: We retrospectively analysed HL pts treated with an ASCT and registered in the European Group for Blood and Marrow Transplantation (EBMT) Database. Further inclusion criteria were: age at ASCT ≥ 18 years and time of transplantation between 1985 and 1995. Additionally, pts treated with tandem protocols have been excluded. The frequency of late events including incidence of secondary malignancies and non-relapse related mortality (NRM) was evaluated. Univariate and multivariate analyses of risk factors for SM and NRM were performed. Results: 2289 pts (median age at ASCT 30 years, range 18 – 70) were evaluated; 1408 (61.5%) pts were male. Most patients (76.9%) were in complete or partial remission at the time of transplantation and 23.1% of pts were transplanted with refractory or progressive disease. BEAM was the conditioning regimen most frequently used (57.3%) followed by CBV (29.4%) and other chemotherapy regimens (8.7%); TBI was given to 4.7% of pts. Median follow-up for all pts was 47 months (range 0 – 240). Progression free survival and overall survival at 5 years for the whole series were 39.9% and 46.8%, respectively. 988 pts (43.3%) relapsed after a median time of 8.5 months post-ASCT, 787 of them died and 201 are alive after a relapse. 312 pts died without previous relapse or progression (NRM). The main causes of death were relapse/progression (34%), transplant related mortality (11.4%) and SM (1.5%). Cumulative risk at 10 years for NRM was 14.4%. Sex, disease status at ASCT, year of ASCT (1985 – 1990 vs. 1990 – 1995), stem cell source (BM vs. PB), age > 40 years, conditioning with CBV, conditioning including TBI and time of ASCT after diagnosis > 48 months were significant prognostic factors in multivariate Cox regression analysis for NRM. SM were diagnosed in 74 pts (3.2%): solid tumours in 33 pts (1.4%), MDS/acute leukaemias in 35 pts (1.5%) and NHL in 6 pts. Cumulative risk at 10 years for SM was 4.4%, for solid tumours 2.2% and for MDS/acute leukaemia 1.7%. The significant risk factors in multivariate Cox regression analysis for SM were age at ASCT > 40 years, time from diagnosis to ASCT > 48 months and conditioning with CBV (p 40 years was the only significant risk factor for solid tumours and MDS/acute leukaemias in Cox multivariate analysis. Conclusions: ASCT remains the standard treatment for patients with refractory/relapsed HL. The cumulative risk at 10 years for NRM and for SM was 14.4% and 4.4%, respectively. The cumulative risk for SM among evaluated patients is higher compared with that reported among HL patients after first line treatment and is expected to increase over time due to the rather short median observation time and the slow progression of solid malignancies.

Waldenström’s macroglobulinaemia (WM) is a relatively rare disorder that primarily affects elderly patients. Conventional therapies for symptomatic WM result in response rates of up to 70%. However, complete responses are rare and the disease remains incurable. Due to the indolent nature of the disease and the older age of patients the role of autologous stem cell transplantation (ASCT) in the treatment of patients with WM has not been analyzed in large series. In this retrospective multicenter study we report the outcome of 201 WM patients (132 male, 69 female), who underwent ASCT between 1992 and 2005. The median age at transplant was 53 years (22–73) and the median time from diagnosis to transplant was 18 months (3–239). Forty patients (20%) were in 1st maximum response (MR1), 24 (12%) in ≥MR2, 83 (41%) in PR1, 27 (13%) in ≥PR2 and 27(14%) were primary refractory to treatment. Conditioning regimens were BEAM (44%), TBI/Cyclophosphamide or Melphalan (28%), Melphalan (14%), BuCy (2%) and others (12%). The source of stem cells was PB in 188, BM in 10, and both in 3 patients. All patients but 3 had successful engraftment. With a median follow-up of 26 months (5–163), 112 (56%) patients are alive and free of disease, 73 (36%) patients have relapsed after a median of 14 months (1–110) post ASCT. Fifty-two patients died, 36(18%) from disease progression and 16(8%) from treatment toxicity. Non- relapse mortality was 6% at 1 year. The actuarial OS was 86% at 1 year, 75% at 3 years, and 61% at 5 years. The probability of relapse was 20% at 1 year, 38% at 3 years and 55% at 5 years with an estimated PFS of 74%, 54% and 33% at 1, 3, and 5 years respectively. Multivariate analysis revealed that, chemosensitive disease at the time of ASCT was the most important factor for NRM (p