Kurzfassung: Patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) have a poor prognosis with conventional chemotherapy. In the present study, we retrospectively analyzed the outcome of patients with BPDCN who underwent allogeneic stem cell transplantation (allo-SCT) or autologous stem cell transplantation (auto-SCT). A total of 39 patients (allo-SCT, n = 34; auto-SCT, n = 5) were identified in the European Group for Blood and Marrow Transplantation registry. The 34 allo-SCT patients had a median age of 41 years (range, 10-70) and received transplantations from sibling (n = 11) or unrelated donors (n = 23) between 2003 and 2009. MAC was used in 74% of patients. Nineteen allo-SCT patients (56%) received transplantations in first complete remission. The 3-year cumulative incidence of relapse, disease-free survival, and overall survival was 32%, 33%, and 41%, respectively. By univariate comparison, being in first remission at allo-SCT favorably influenced survival, whereas age, donor source, and chronic GVHD had no significant impact. We conclude that high-dose therapy followed by allo-SCT from related or unrelated donors can provide durable remission even in elderly patients with BPDCN. However, it remains to be shown if graft-versus-malignancy effects can contribute significantly to BPDCN control after allo-SCT.

Kurzfassung: The clinical results, cellular immune reconstitution, and hematopoietic chimerism obtained after transplantation of recombinant human granulocyte colony-stimulating factor mobilized allogeneic peripheral blood stem cells (PBSCs) from genotypically human leukocyte antigen (HLA)-identical sibling (n = 36) or alternative family donors (n = 24) were prospectively compared in patients with hematologic malignancies. Thirty-two of 34 evaluable patients with HLA-identical sibling donors and all patients with alternative family donors achieved trilineage engraftment. The median time intervals to reach peripheral neutrophil counts 〈 500/μL (13 v 17 days) or 〈 1,000/μL (16 v 19 days) and unsupported platelet counts 〈 20,000/μL (11 v 15 days) or 〈 50,000/μL (19 v 24 days) as well as red blood cell and platelet transfusion requirements were not significantly different between both patient subsets. The cumulative probability of grades II through IV acute graft-versus-host disease (GVHD) for the 60 study patients was 48% ± 10% but ranged between 86% ± 12% in patients whose donors had at least one HLA-A,B,DR,DQ,DP antigen disparity in direction to acute GVHD, and 25% ± 9% in recipients of GVHD-matched transplants (P 〈 .003). The 2-year survival estimates were 54% ± 10% for patients with alternative family donors and 65% ± 9% for patients with HLA-identical sibling donors. Multivariate analysis identified the pretransplantation disease stage, patient age, and acute GVHD as independent predictors of overall and disease-free survival, whereas alternative family donors alone had no adverse effect on these clinical endpoints. Monthly monitoring of peripheral blood T-helper cell subsets, B cells, and monocytes during the first year posttransplantation showed a nearly identical course of immune cell reconstitution in both patient subsets. In addition, no differences in the proportions of complete chimeric patients were detectable between the two patient subsets by sex chromosome and variable number of tandem repeats analysis up to 12 months posttransplantation. In conclusion, PBSCs from alternative family donors represent an attractive source for allogeneic transplantation in patients lacking HLA-identical sibling donors and should be further evaluated in comparison with marrow transplants from alternative family donors.

Kurzfassung: Abstract 3328 Poster Board III-216 Introduction Relapse is a major cause of treatment failure after alloSCT against acute leukaemia, and no standard treatment has been established in this challenging situation. The introduction of reduced conditioning regimens, and the broader availability of alternative donors have increased the possibilities to perform a second alloSCT as salvage treatment, using different preparative regimen and/or different stem cell donors. Methods To evaluate the role of a second alloSCT (tx2) for the treatment of relapse after first alloSCT (tx1), we performed a nationwide retrospective analysis based on the German registry for stem cell transplantation (DRST). Datasets were completed by the reporting centres on request, following a specifically designed questionnaire. Results 212 patients (69% AML, 31% ALL), from 23 centres were included. Median age at tx1 was 37y. Donor at tx1 were HLA identical siblings (41%), matched unrelated (39%), mismatched family or unrelated (17%) or syngeneic donors (3%). Conditioning intensity at tx1 was standard (SIC, 62%), intermediate (intC, 25%) or reduced (RIC, 13%). Median remission after tx1 was 7 months, median time from relapse to tx2 was 74d. At tx2, patients were aplastic (4%), in CR (20%) or showed active disease (76%). In 59%, the same donor was used for tx1 and tx2, whereas a different donor was chosen in 41%. Conditioning at tx1/tx2 were SIC/SIC (14%), intC/intC (10%), (RIC/RIC (10%), less intensive at tx2 (mostly intC or RIC after SIC, 58%), or more intensive at tx2 (SIC after RIC or intC, 8%). Following tx2, CR was achieved in 56% of patients, out of which 81% relapsed again. Hence, leukemia was the most frequent cause of death. With a median FU of 23 months after tx2, median OS after tx2 is 117d. In a univariate analysis (log rank), OS after tx2 depended on stage at tx1 (CR vs. active disease, p 〈 .001), stage at tx2 (CR vs. aplastic/active disease, p=.011) and duration of remission after tx1 ( 〈 =6m (1y OS 5%) vs. 6-12m (15%) vs. 〉 12m (31%), p 〈 .001). No significant difference was observed regarding age ( median), AML vs. ALL, family versus unrelated donor, or time point of alloSCT (2002). Shift to an alternative donor did not improve the results either. In a multivariate analysis (Cox Regression Model), time of remission after tx1 was the only significant factor for OS (p 〈 .001, hazard ratio .51, 95%CI .49-.74). Conclusion Survival of acute leukemia after second allogeneic SCT is determined by the duration of remission after tx1. Using an alternative donor for tx2 did not improve the results in our series. Further analysis is required to evaluate the role of RIC regimen for tx2. Disclosures No relevant conflicts of interest to declare.

Kurzfassung: Abstract 3281 Poster Board III-1 Introduction: In the two consecutive German CML studies III and IIIA (recruitment periods from 1995 to 2001 and 1997 to 2004), eligible patients were assigned to early HSCT by genetic randomization according to availability of a matched related donor. After randomization, 113 patients of study III (84% of 135) and 144 of study IIIA (87% of 166) were eventually transplanted in first chronic phase (CP) using a related donor. Despite comparable transplantation protocols and most centers participating in both studies, survival probabilities in study IIIA were significantly better, even when adjusted for the established EBMT risk score (Gratwohl et al., Lancet 1998 [1]), p + 0.0097. For further explanation, the German Registry for Stem Cell Transplantation (DRST) and the Swiss Transplant Working Group for Blood and Marrow Transplantation (STABMT) were asked for data support. Patients and Methods: The main sample characteristics of the 257 transplanted CML study patients were also applied to the registry patients: diagnosis of CML between 1994 and 2004, first HSCT with a related donor performed in first CP between 1995 and 2004 at an age between 12 and 65 years, and blood or bone marrow as stem cell sources. Thus, additional data of 582 HSCT patients were retrieved from the two registries. Age, recipient sex, donor sex, time between diagnosis and HSCT, calendar year of HSCT, stem cell source, and HLA matching were investigated as potential predictive factors for survival. Then, a sample of patients with the same risk distribution as the 113 patients of study III was randomly drawn from the registry patients. By application of repeated resampling to this new patient group, bootstrap confidence intervals for survival probabilities at various times after HSCT were extractable. This provided the basis to judge whether the survival in study III could be seen as a typical random representation of a sample with an equivalent risk structure or not. The same method was applied to the 144 patients of study IIIA. Results: The 5-year survival probability of all 839 patients resulted in 73% (229 died). Median follow-up time of living patients was 6.7 years. Due to the characteristic plateau of post-transplant survival probabilities, the predictive influence was judged by the Kaplan-Meier method and the log rank statistic. Also consideration of age and time between diagnosis and HSCT as continuous variables seemed less appropriate than working with categorizations. Furthermore, the previously published cut-points “1 year” for time from diagnosis to HSCT ([1] ) and “44 years” for age at HSCT (Maywald et al., Leukemia 2006) were independently confirmed to be the best. Cox model and logistic regression with survival status after 3 years both indicated that age at HSCT, HLA matching, time between diagnosis and HSCT, and calendar year of HSCT had independent statistically significant predictive influence on survival (p 〈 0.05). The first two factors had the strongest effects. Calendar year was only influential when distinction was made between HSCT until and after 1999. All possible combinations of the 4 factors could be summarized in 4 risk groups with significantly different survival probabilities (at 5 years: 87%, 76%, 63%, and 24%). Matched for the risk group distribution of study III [study IIIA], a maximum of 290 [428] registry patients could be drawn. For the 290 [428] patients, 5-year survival was 69% [77%] with a 95% bootstrap confidence interval from 63% to 74% [72% to 81%]. Thus, as for all yearly intervals within the first 5 years, the 5-year survival probabilities of studies III: 65% and IIIA: 79% lied within the corresponding confidence intervals. Conclusions: Along with the registry patients, the study data enabled the identification of age at HSCT, HLA matching, time between diagnosis and HSCT, and calendar year of HSCT as factors with independent predictive impact on survival which led to 4 risk groups with statistically significantly different survival probabilities. More favorable-risk patients in study IIIA stood for a better transplantation strategy. In consideration of these different risks, the survival probabilities in both studies did not significantly vary from those of registry samples with matched risk structures. Accordingly, an improved transplantation strategy along with random variation could be considered as an explanation of the significantly different survival probabilities between the two studies. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Equity Ownership. Hochhaus:Novartis, Bristol-Myers Squibb: Research Funding. Hasford:Novartis: Research Funding. Gratwohl:AMGEN, Roche, Bristol-Myers Squibb, Novartis, Pfizer: Research Funding; Novartis: Consultancy. German CML Study Group:Kompetenznetz Leukämie, European Leukemia Net, Roche, Essex, AMGEN: Research Funding.

Kurzfassung: Outcomes of highly purified CD34+ peripheral blood stem cell transplantation (PBSCT) for chronic phase chronic myeloid leukemia (CML) (n = 32) were compared with those of PBSCT (n = 19) and of bone marrow transplantation (BMT) (n = 22) in the HLA-compatible sibling donor setting. Median follow-up was 18 months after CD34+-PBSCT and unmanipulated PBSCT and 20 months after BMT. CD34+-PBSCT was associated with delayed T-cell immune reconstitution at 3 months and 12 months after transplantation compared with PBSCT (P  〈  .001) or BMT (not significant [NS]). The estimated probability of grades II to IV acute graft-versus-host disease (GVHD) was 60% ± 13% for the PBSCT group, 37% ± 13% for the BMT group, and only 14% ± 8% for the CD34+-PBSCT group (CD34-PBSCT versus BMT,P  〈  .01; and CD34-PBSCT versus PBSCT,P  〈  .001). The probabilities for molecular relapse were 88% for CD34+-PBSCT, 55% after BMT, and 37% after PBSCT (CD34+-PBSCT versus PBSCT,P  〈  .03). Cytogenetic relapse probability was 58% after CD34+-PBSCT, 42% after BMT, and 28% after PBSCT (NS). After CD34+-PBSCT, 26 of 32 patients received a T-cell add-back. Hematologic relapse occurred in 4 of 22 patients after BMT, in 3 of 19 patients after PBSCT, and in only 1 of 32 patients after CD34+-PBSCT. The occurrence of a hematologic relapse in patients receiving CD34+-PBSC transplants was prevented by donor leukocyte infusions, which were applied at a median of 4 times (range, 1-7 times) with a median T-cell dose of 3.3 × 106 × kg/body weight [at a median] beginning at day 120 (range, 60-690 days). The estimated probability of 3-year survival after transplantation was 90% in the CD34+-PBSCT group, 68% in the PBSCT group, and 63% in the BMT group (CD34-PBSCT versus BMT, P  〈  .01; and CD34-PBSCT versus PBSCT, P  〈  .03). Transplantation of CD34+-PBSCs with T-cell add-back for patients with CML in first chronic phase seems to be safe and is an encouraging alternative transplant procedure to BMT or PBSCT.

Kurzfassung: Aim: Dynamic assessment of trends over time in patient- and transplant-specific characteristics and outcomes for patients undergoing 1st allogeneic haematopoietic cell transplant (allo-HCT) for Myelofibrosis (MF). Methods and Results: A total of 4142 MF patients were analysed who underwent allo-HCT between 1995-2018 (24-year period) across 278 centres based on data reported to the European Society for Blood and Marrow Transplantation. For analysis, 4 cohorts were considered based on year of allo-HCT: & lt;2006 n=389 (9.4%), 2006-2010 n=910 (22%), 2011-2014 n=1148 (27.7%) and 2015-2018 n=1695 (40.9%). A steady increase in MF allo-HCT activity over time was apparent paralleled with increasing numbers of participating transplant centres. A total of 2603 (62.8%) patients were male, 3239 (78.2%) had Primary MF, 409 (9.9%) and 494 (11.9%) post-Polycythaemia Vera and post-Essential Thrombocythaemia MF, respectively. An increased median interval (lnterquartile range (IQR)) between diagnosis and transplant was evident over time ( & lt;2006 median 20.8 (8.9-62.2) months versus 36.2 (11.6-107.5) months in 2015-2018 period;p & lt;0.001), potentially reflecting increased availability of therapeutics in recent eras (untreated patients & lt;2006= 59.4% versus 2015-2018=23.7%). Median recipient age (IQR) increased over time by ~ a decade between earliest cohort and most recent: & lt;2006, 49.4 years (43.1-55.3) versus 59.3 years (53.4-64.8)2015-2018. Prior to 2006, patients & gt;60 years accounted for 8.7% of adults undergoing allo-HCT whereas for 2015-2018 this was 47%. Over time, increasing number of patients with a Karnofsky performance status (KPS) & lt;90 underwent allo-HCT ( & lt;2006=19.7% versus 36.1% 2015-18; p & lt;0.001). Peripheral Blood (PB) was the predominant stem cell source and utilisation increased over time, accounting for 74.8% & lt;2006 and 92.2% within 2015-2018 cohort. Cord blood utilisation was limited to & lt;1% throughout the 24-year study period. Significant shifts towards use of unrelated donors (URD) in more recent periods was apparent (p & lt;0.001). Moreover, increased use of mismatched related donors (MMRD) was particularly evident in 2015-2018 cohort; n=152 (9%) versus n=74 (3%) cumulative for other 3 cohorts combined; p & lt;0.001. Decreased use of myeloablative and TBI- based conditioning was evident over time (p & lt;0.001). Specifically, there was increased use of busulphan-based regimens ( & lt;2006: 44.2% versus 2015-2018: 72%). Regarding T cell depletion, trends demonstrated increased use of anti-thymocyte globulin (ATG) over time ( & lt;2006=37.3% vs 69.9% 2015-2018; p & lt;0.001). Median time to both neutrophil (median 18 days across all cohorts) and platelet engraftment was similar in all 4 cohorts, with no significant variation when stratified by period of transplantation. Allo-HCT outcomes, survival, GVHD and relapse endpoints are shown for all 4 cohorts in Table 1. Overall for the entire group, significant factors associated with worse OS, RFS and NRM remained older age and a poor KPS ( & lt;90). No significant differences between cohorts were noted for either estimated 3-year OS ( & lt;2006=55% (50-60%), 2006-2010=60% (56-63%), 2011-2014 and 2015-2018= 58% (55-61%); p=0.299) or non-relapse mortality (NRM (Table 1); p=0.523), despite increasing numbers of older, less fit patients, and more frequent HLA-mismatched transplants over time. To investigate survival findings in more detail an adjusted model will be presented including period of allo-HCT and transplant-related variables. Cumulative incidence of relapse at 3 years was similar across all cohorts, suggesting no significant changes with time. Most common causes of death across all 4 cohorts remained GVHD and infection. Of note, rates of acute (a)GVHD grade II-IV by day +100 decreased from the earliest cohort & lt;2006 compared to the later groups (p=0.027) as did rates of overall chronic (c) GVHD whereby this was evident in 57% (95% CI 52-62%) & lt;2006 cohort compared to 44% (95% CI 42-47%) in the 2015-2018 group, predominantly reflected by reductions in extensive cGVHD (Table 1). Conclusions: Despite a marked increase over this 24-year period in recipient age, RIC regimen utilisation and use of both URD and MMRD, this comprehensive analysis demonstrates stable OS and EFS rates. However, rates of GVHD have decreased over time, in particular extensive cGVHD. Further work is required to improve both the considerable NRM and relapse rates which remain significant. Disclosures McLornan: JAZZ PHARMA: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau; NOVARTIS: Honoraria, Speakers Bureau. Platzbecker:Amgen: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Geron: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding. Chevallier:Incyte Corporation: Honoraria. Martínez-Lopez:Altum, Hosea: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Vivia Biotech: Honoraria; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Roche: Speakers Bureau; Janssen: Speakers Bureau; Incyte: Research Funding, Speakers Bureau; Bristol Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding. Yakoub-Agha:Celgene: Honoraria; Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Janssen: Honoraria.