Allogeneic hematopoietic stem cell transplantation in patients aged 60-79 years in Germany (1998-2018): a registry study

Incidences of diseases treated with transplantation frequently peak at higher age. The contribution of age to total risk of transplantation has not been estimated amidst an aging society. We compare outcomes of 1,547 patients aged 70-79 years and 9,422 patients aged 60-69 years transplanted 1998-2018 for myeloid, lymphoid and further neoplasia in Germany. To quantify the contribution of population mortality to survival, we derive excess mortality based on a sex-, year- and agematched German population in a multistate model that incorporates relapse and graft-versus-host-disease (GvHD). Overall survival, relapse-free survival (RFS) and GvHD-free-relapse-free survival (GRFS) is inferior in patients aged 70-79 years, compared to patients aged 60-69 years, with 36% (95% Confidence Interval [CI]: 34-39%) versus 43% (41-44%), 32% (30- 35%) versus 36% (35-37%) and 23% (21-26%) versus 27% (26-28%) three years post-transplant (P1 year relapse-free is 6.7 (median, 95% CI: 4.5-9.4, 70-79 years) versus 9 (8.4-10.1, 60-69 years) years since landmark. Three years after RFS of one year, excess NRM is 14% (95% CI: 12-18%) in patients aged 70-79 versus 12% [11-13%] in patients aged 60-69, while population NRM is 7% (6-7%) versus 3% (3-3%). Mortality for reasons other than relapse, GvHD, or age is as high as 27% (24-29%) and 22% (22-23%) four years after transplantation. In conclusion, survival amongst older patients is adequate after allogeneic stem cell transplantation

Impact of Pre-Transplant Ruxolitinib in Myelofibrosis Patients on Outcome after Allogeneic Stem Cell Transplantation

Abstract Introduction Ruxolitinib is the first approved drug for treatment of myelofibrosis. Major effects are reduction in spleen size and improvement of constitutional symptoms. Because spleen size and constitutional symptoms may influence outcome after allogeneic stem cell transplantation (ASCT), ruxolitinib is recommended before stem cell transplantation in order to reduce therapy-related morbidity and mortality and improve outcome (EBMT/ELN recommendation, Leukemia 2015) The aim of this retrospective study was to evaluate the impact of pretreatment with ruxolitinib in comparison to transplantation of ruxolitinib-naïve MF patients with regard to outcome after ASCT. Patients and methods We included 171 myelofibrosis patients (pts) with a median age of 59 years (r: 28 - 74) who received ASCT between 2000 and 2015 from related (n = 25), matched (n=94) or mismatched (n=52) unrelated donor. Stem cell source were more peripheral blood stem cells (n = 167) than bone marrow (n = 4). All patients received busulfan-based reduced intensity conditioning. While 113 pts (66%) did not receive ruxolitinib, 58 pts (34%) received ruxolitinib at any time point prior to ASCT. The median daily dose of ruxolitinib was 30mg (range 10-40mg) and the median duration of treatment was 28 days (range 12-159 days). In 11 pts ruxolitinib was stopped before stem cell transplantation because of no response or loss of response, while in 35 pts ruxolitinib was given until start of conditioning and in 12 pts ruxolitinib was given until stable engraftment. GvHD prophylaxis consisted of CNI plus short course MTX or MMF and anti-lymphocyte globulin. According to dynamic IPSS (DIPSS) (n = 170) the patients were either low (n = 2), intermediate-1 (n = 37), intermediat-2 (n = 81), or high risk (n = 38). 74 patients (43%) were transfusion dependent. Results As the median follow up was shorter for patients treated with ruxolitinib (15 vs 73 months, p&lt;0.001), we analyzed only 2 years RFS, OS, NRM and relapse incidence. Primary graft failure was seen in 2 pts in the ruxolitinib and 3 in the non-ruxolitinib group. The median leukocyte engraftment was 13 days (r., 9-32) in the ruxolitinib and 14 days (r., 7-34) in the non ruxolitinib group (p=0.7). The median age in the ruxolitinib group was slightly older ( 62 vs 58 years , p= 0.09). The incidence of acute GvHD grade I to IV was significantly lower in the ruxolitinib group (49% vs 64%, p=0.05), while aGvHD grade II-IV (33% vs 44%, p=0.14) and grade III/IV (23% vs 25%, p=0.48), did not differ significantly. The CI of NRM at 1 year was 18% (95% CI: 6-30%) for the ruxolitinib group and 22% (95% CI: 14-30%) for the non-ruxolitinib group (p=0.58), and the CI of relapse at 2 years was 8% (95% CI: 0-16%) vs 20% (95%CI: 12-28%, p=0.25). The 2 years RFS and OS was 66% (95%CI: 50-82%) and 69% (95%CI: 51-87) for the ruxolitinib group and 59% (95% CI: 49-69%) and 70% (95% CI:62-78%) for the non-ruxolitinib group (p=0.29 and p=0.45, respectively). Within the ruxolitinib group (n=53), 24 pts responded to ruxolitinib (more than 25% spleen size reduction), while 29 pts did not respond or lost response prior to stem cell transplantation. Here, no significant difference could be seen between the responding and non-responding group for NRM (19% vs 17%, p=0.69), Relapse (4% vs 13%, p=0.62), RFS (61% vs 72%, p=0.81) and OS (63% vs 75%, p=0.89). In a multivariate analysis including ruxolitinib treatment as variable there was a non-significant trend in favor for ruxolitinib pretreatment regarding NRM (HR 0.79; 95%CI: 0.38-1.66, p=0.54), relapse (HR 0.48; 95%CI: 0.18-1.31, p=0.15), RFS (HR 0.55; 95%CI: 0.29-1.03, p=0.06) and OS (HR 0.83; 95%CI: 0.41-1.67, p=0.61). Conclusions These results suggest that ruxolitinib pretreatment in myelofibrosis patient does not negatively influence outcome after allogeneic stem cell transplantation. To confirm the observed favorable trend in outcome after ruxolitinib treatment more patients and a longer follow-up is needed. Disclosures Crysandt: Novartis: Other: Travel grant. Stelljes:Pfizer: Consultancy. Kröger:Novartis: Honoraria, Research Funding. </jats:sec

Allogeneic Stem Cell Transplantation in Patients Aged ≥70 Years: Epidemiology, Outcomes, and Risk Factors Based on the German Registry for Stem Cell Transplantation (DRST)

Abstract Introduction. Malignant diseases treated with allogeneic hematopoietic stem cell transplantation (alloHSCT) predominantly occur beyond the 7 th decade of life. Numerical age per se is not regarded an adverse risk factor in alloHSCT. In an aging society, interventions historically deemed high risk are increasingly used in elder patients. Methods. Epidemiology, outcomes and risk factors of patients aged ≥70 years undergoing alloHSCT in Germany 1999-2019 and registered with the DRST/EBMT database were analyzed retrospectively. Baseline patient, disease, and transplant data were collected from MED-A forms. Centers were contacted to provide additional treatment and follow-up information. Results. Between 1999 and 2019, 1648 patients aged ≥70 years (median 72, range 70-79.7; 585 female) were transplanted in 50 German centers. More than 90% of all patients were transplanted 2010-2019. Centers transplanted between 2 and 192 patients, with 14 centers contributing &amp;lt;10 and 4 centers contributing &amp;gt;100 patients each. Most patients suffered acute leukemia (1084, 65.8%) or MDS/MPN (410, 24.9%). Karnofsky index before start of conditioning was 100% (n=230, 14%), 90% (n=651, 39.5%), 80% (n=480, 29.1%), 70% (n=94, 5.7%), &amp;lt;70% (n=55, 3.3%). Myeloablative conditioning was chosen in 25.6%. Total body irradiation was used for 305 patients (18.6%). Conditioning contained antithymocyteglobulin in 49.6%. Donors were unrelated for 85.5%. Median donor age was 37 (18-79) years. Patient CMV IgG was positive in 63.1% and the constellation 'negative donor, positive patient' was present in 19.9%. Median overall survival (OS) and disease free survival (DFS) was 408/ 344 days. With a median follow up of 536 days for surviving patients, Kaplan Meier estimates of OS/ DFS were 52.6%/ 48.5% and 40.9%/ 38.6% at 1 and 2 years. In a competing risk analysis, cumulative incidence of non-relapse-mortality (NRM)/ relapse (RI) was 22.2%/ 29.3% at 365 days. Frequency of acute graft versus host disease (GvHD) II-IV was 25.1% and chronic limited/ extended GvHD 11.7%/ 14.8%. Karnofsky performance score, CMV IgG matching, acute and chronic GvHD and stem cell source showed a prognostic impact on OS, DFS, RI and/ or NRM (Table 1). Underlying disease did not impact outcome, neither did age amongst patients at an age of 70-80 years. To compare with outcome in the decade below (60-69 years), an analysis after matching for underlying disease, CMV relation, and Karnofsky index included 2728 patients (each 1364 patients 60-69 and ≥70 years of age). For each year of life, univariate HR for OS and DFS were 1.01 [95%CI 1.001-1.023, p=0.035] and 1.01 [95%CI 0.99-1.02, p=n.s.], respectively, in this matched-pair analysis. The cumulative HR (OS, DFS) for both age groups was 1.16 [95%CI 1.05-1.28, p&amp;lt;0.01] and 1.13 [95%CI 1.02-1.24, p=0.016] for patients ≥70 years. Conclusion. AlloHSCT is increasingly used to treat elder patients in Germany with a sharp increase during the last decade. Age per se is a modest adverse risk factor for adult patients after alloHSCT with slightly increased mortality in patients 70-80 versus those at 60-69. Further research might concentrate on patient selection and further reduction of procedural toxicity. Figure 1 Figure 1. Disclosures Schetelig: Roche: Honoraria, Other: lecture fees; Novartis: Honoraria, Other: lecture fees; BMS: Honoraria, Other: lecture fees; Abbvie: Honoraria, Other: lecture fees; AstraZeneca: Honoraria, Other: lecture fees; Gilead: Honoraria, Other: lecture fees; Janssen: Honoraria, Other: lecture fees . Einsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding. Stelljes: Pfizer: Consultancy, Research Funding, Speakers Bureau; Medac: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau. Dreger: AbbVie: Consultancy, Speakers Bureau; Bluebird Bio: Consultancy; Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy; AstraZeneca: Consultancy, Speakers Bureau; Gilead Sciences: Consultancy, Speakers Bureau; BMS: Consultancy; Riemser: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau. Wulf: Takeda: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Clinigen: Consultancy, Honoraria. Scheid: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria; Roche: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bethge: Novartis: Consultancy, Honoraria, Speakers Bureau; Kite-Gilead: Consultancy, Honoraria, Speakers Bureau; Miltenyi Biotec: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. </jats:sec