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In the last decade, the number of older patients undergoing allogeneic Hematopoietic Cell Transplantation (alloHCT) has increased substantially. Analyzing the long-term outcomes of these patients poses new methodological challenges since their population mortality (the risk of mortality that they would have faced in the absence of their disease and treatment) is non-negligible. Interpreting all non-relapse mortality (NRM) as treatment-related mortality cannot be justified in this older population. An additional problem in the analysis of the causes of death is that individual adjudication as to treatment-related complications is often impossible. Although more common in transplant recipients, both cardiac deaths and cancer also occur frequently in the general population in this age group. For these reasons, we propose to extend the analysis of standard outcomes with statistical methods to estimate the size of population- and treatment-related mortality in heterogeneous populations. We analyzed the outcomes of two large cohorts of patients whose data had been collected by the European Society for Blood and Marrow Transplantation: (1) myelodysplastic syndromes or secondary acute myeloid leukemia (n=6434, median age 56 years), and (2) chronic lymphocytic leukemia (n=2589, median age 55 years). We focused on patients who had survived for two years after alloHCT without relapse or progression. We used integrated methods from relative survival and multi-state models to estimate what proportion of mortality can be attributed to disease relapse and what to the expected general population mortality. A key assumption was that the risk of mortality of the patient cohorts, apart from that associated with the disease and its treatment, was similar to that of the age-, sex-, calendar year- and country-matched general population. The remaining mortality, excess non-relapse mortality, can then be interpreted as closely approximating to treatment-related mortality, where 'treatment' refers both to treatment prior to transplantation and to alloHCT and its sequelae. The figures illustrate the probabilities of these events for the MDS cohort. This non-parametric model was then extended to a Cox model where we also assessed the impact of age and other risk factors on the different components of mortality. Combining relative survival and multi-state models gives more insight into the different causes of mortality and the impact of age and other risk factors on them. We show that for older patients, a substantial part of NRM is actually attributable to population mortality, information which should hopefully lead to more informed discussions regarding the risk of alloHCT and improvement of long-term care. [ABSTRACT FROM AUTHOR]

• The DIPSS was not predictive of survival in myelofibrosis secondary to essential thrombocythemia or polycythemia vera after stem cell transplantation. • The MYSEC-PM predicted survival and showed improved prognostic ability. • Although performance of the MYSEC-PM was still moderate, risk stratification may be improved by incorporating clinical, mutational, and transplant-related factors. We aimed to validate the MYelofibrosis SECondary to PV and ET prognostic model (MYSEC-PM) in 159 patients with myelofibrosis secondary to polycythemia vera (PV) and essential thrombocythemia (ET) from the European Society for Blood and Marrow Transplantation registry undergoing transplantation from matched siblings or unrelated donors. Furthermore, we aimed to test its prognostic performance in comparison with the Dynamic International Prognostic Scoring System (DIPSS). Score performance was analyzed using the concordance index (C): the probability that a patient who experienced an event had a higher risk score than a patient who did not (C >.5 suggesting predictive ability). Median follow-up of the total cohort was 41 months (range, 34 to 54), 45 months in post-PV and 38 months in post-ET myelofibrosis. Survival at 1, 2, and 4 years was 70% (95% CI, 63% to 77%), 61% (95% CI, 53% to 69%), and 52% (95% CI, 43% to 61%) for the total cohort; 70% (95% CI, 59% to 80%), 61% (95% CI, 49% to 73%), and 51% (95% CI, 38% to 64%) for post-PV; and 71% (95% CI, 61% to 81%), 61% (95% CI, 50% to 72%), and 54% (95% CI, 42% to 66%) for post-ET myelofibrosis (P =.78). Overall, the DIPSS was not significantly predictive of outcome (P =.28). With respect to the MYSEC-PM, overall survival at 4 years was 69% for the low-risk, 55% for the intermediate 1-risk, 47% for the intermediate 2-risk, and 22% (0% to 45%) for the high-risk groups. The prognostic model was predictive of survival overall (P =.05), whereas groups with intermediate 2 and high risk showed no significant difference (P =.44). Assessment of prognostic utility yielded a C-index of.575 (95% CI,.502 to.648) for the DIPSS, whereas assessment of the MYSEC-PM resulted in a C-statistics of.636 (95% CI,.563 to.708), indicating improvement in prediction of post-transplant survival using the new MYSEC-PM. In addition, transplantations from an unrelated donor in comparison with an HLA-identical sibling showed worse outcome (P =.04), and transplant recipients seropositive for cytomegalovirus in comparison with seronegative recipients (P =.01) showed worse survival. In conclusion, incorporating transplant-specific and clinical and mutational information together with the MYSEC-PM may enhance risk stratification. [ABSTRACT FROM AUTHOR]

In this retrospective analysis we evaluated the outcome of 313 patients aged ≥ 70 years in the registry of the European Group for Blood and Marrow Transplantation with myelodysplastic syndrome (MDS; n = 221) and secondary acute myeloid leukemia (n = 92) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from related (n = 79) or unrelated (n = 234) donors. Median age at HSCT was 72 years (range, 70 to 78). Conditioning regimen was nonmyeloablative (n = 54), reduced intensity (n = 207), or standard intensity (n = 52). Allogeneic HSCT for MDS patients ≥ 70 years was increasingly performed over time. Although during 2000 to 2004 only 16 patients received HSCT, during 2011 to 2013 the number of transplantations increased to 181. The cumulative incidence of nonrelapse mortality at 1 year and relapse at 3 years was 32% and 28%, respectively, with a 3-year overall survival rate of 34%. Good performance, determined by Karnofsky performance status, and recipients' seronegativity for cytomegalovirus was associated with 3-year estimated overall survival rates of 43% ( P  = .01) and 46% ( P  = .002), respectively. Conditioning intensity did not impact survival. After careful patient selection, allogeneic HSCT can be offered to patients older than 70 years with MDS. [ABSTRACT FROM AUTHOR]

Highlights • We performed a retrospective review of 56 myelofibrosis patients transplanted from mismatched family donors. • Neutrophil engraftment at a median of 20days was observed in 82%. • Low rates of acute GVHD grades II to IV were observed in 28% (16% to 40%) and grades III to IV in 9% (2% to 16%). • Chronic GVHD at 1 year was found in 45% (32% to 58%). • Overall survival at 2years was 56% (41% to 70%). Abstract This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34+ cell dose was 4.8 × 106/kg (range, 1.7 to 22.9; n = 43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28days was 82% (range, 70% to 93%), at a median of 21days (range, 19 to 23). At 2years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% (95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion. [ABSTRACT FROM AUTHOR]