ALBERT

Description: Background: t-MDS/AML is the leading cause of non-relapse mortality after aHCT for NHL. Older age at aHCT, exposure to total body irradiation (TBI), and low number of CD34+ cells infused are associated with an increased risk of developing t-MDS/AML. However, over the past decade, aHCT has been increasingly used for older patient populations (potential for increase in t-MDS/AML risk). On the other hand, use of TBI has declined and number of CD34+ cells infused has increased (potential for decrease in t-MDS/AML risk). The impact of these changes in aHCT clinical practice on t-MDS/AML risk has not been assessed, and is addressed here. Methods: Information regarding t-MDS/AML diagnosis was procured from medical records and California Cancer Registry to ensure near-complete capture of events. Competing risk analysis was used to describe the cumulative incidence of t-MDS/AML, and to evaluate the role of host and aHCT-related factors in the development of t-MDS/AML. In order to understand the impact of changing clinical practices, patients were classified into those transplanted in the early era (1986-2002) vs. recent era (2003-2009). Results: A total of 1,261 consecutive patients received aHCT for NHL between 1986 and 2009 at City of Hope, and were followed for development of t-MDS/AML until 12/31/2011. Median age at aHCT was 50y (range, 5-78). Compared with patients transplanted in early era, those transplanted in recent era were more likely to be ≥50y at aHCT (recent era: 65% vs early era: 44%, p

Description: Introduction: Hematopoietic cell transplantation (HCT)-related factors, such as total body irradiation (TBI) used for conditioning, graft-versus-host disease (GvHD), and prolonged exposure to calcineurin-inhibitors, can result in high risk for subsequent skin cancers in long-term survivors. Previous studies examining skin cancers after HCT have largely focused on patients transplanted in earlier eras (

Description: The role of pre-HCT self-reported QOL on long-term survival in autologous and allogeneic HCT recipients is not well understood. Although pre-HCT comorbidity is now a well-established indicator of post-HCT short-term outcome, patient-reported pre-HCT QOL may provide additional information for predicting long-term survival after HCT. This study examined the relationship between pre-HCT QOL scores and overall survival (OS), non-relapse mortality (NRM), and disease-related mortality (DRM) in patients who received their first allogeneic or autologous HCT at City of Hope between 2001 and 2005. Four domains of QOL (physical, psychological, social, and spiritual well-being; scale of 0 [worst] to 10 [best]) were assessed prior to HCT using the City of Hope-QOL instrument. Cox regression analysis was used to identify QOL domains associated with long-term survival, adjusted for demographic, clinical, and transplant-related variables. HCT-Comorbidity-Age Index (HCT-CAI) (Sorror et al. 2014) was also assessed in allogeneic HCT recipients. Vital status was determined using medical records and linkage with the National Death Index. OS probabilities were estimated using the Kaplan-Meier estimator. Analyses were conducted by stem cell source. The cohort comprised 103 allogeneic HCT recipients (median age at HCT, 42 years; 51% males; median follow-up since HCT, 7.6 years; 55 deaths) and 141 autologous HCT recipients (median age at HCT, 50 years; 56% males; median follow-up, 7.1 years; 59 deaths). The diagnoses included acute leukemia (n=45), chronic leukemia (n=20), lymphoma (n=14) and other hematologic conditions (n=24) in allogeneic HCT recipients and acute leukemia (n=24), lymphoma (n=76), myeloma (n=35), and other hematologic conditions (n=6) in autologous HCT recipients. All autologous and 81.5% of allogeneic HCT patients received myeloablative conditioning agents. OS: In allogeneic HCT recipients, OS adjusted for significant covariables increased with higher pre-HCT physical well-being score (Hazard Ratio [HR]=0.76 per point increase, p=0.003). Of note, HCT-CAI was not associated with OS in the multivariate model (HR=1.1, p=0.39). The hazard of death for physical well-being scores below the 75th percentile was 3.7 times that above this percentile (p=0.002). Survival rates at 5 and 10 years after HCT for physical well-being scores below the 75th percentile were 51% and 38%, respectively, compared to 72% (p=0.062) and 68% (p=0.018), respectively, above the 75th percentile. OS was also independently worse in males, unrelated donor HCT recipients, patients with acute leukemia vs. other diagnoses, absence of chronic GvHD, and pre-HCT income of $20K to $100K vs. $100K. In autologous HCT recipients, adjusted OS varied non-linearly with pre-HCT physical well-being score (p=0.03), with OS being significantly lower in the lowest (worst) quartile of pre-HCT physical well-being score (HR=2.4, p=0.004) compared to those with better scores. Survival rates at 5 and 10 years after HCT in the lowest quartile were 53% and 47%, respectively, compared to 70% (p=0.048) and 62% (p=0.065) for those with scores above the lowest quartile. Older age at HCT, other diagnoses vs. lymphoma, high risk of relapse at pre-HCT, cyclophosphamide as conditioning agent vs. no cyclophosphamide were also independently associated with worse OS. Other QOL domains were not significant for either HCT types. NRM: In allogeneic HCT recipients, NRM was not associated with HCT-CAI (HR=1.18, p=0.11) adjusted for chronic GvHD and stem cell donor relatedness. However, adjusted OS increased for higher pre-HCT physical well-being score (HR=0.8, p=0.06). NRM was higher for those with physical well-being score below the 75th percentile (HR=7.3, p=0.007) compared to those with scores above the 75thth percentile. In autologous HCT recipients, no QOL domains were significant. DRM: None of the QOL domains for either HCT types, or HCT-CAI in allogeneic HCT recipients were significant after accounting for salient clinical and demographic factors. This study shows that patient-reported pre-HCT physical well-being scores provide information not captured by medical factors that can aid in predicting long-term OS and NRM in allogeneic and OS in autologous HCT patients. Effort to incorporate such evaluation as part of the routine assessment preceding HCT may be useful in developing patient selection and intervention strategies. Disclosures Forman: Mustang Therpapeutics: Other: Construct licensed by City of Hope.

Description: Introduction: Advances in treatment strategies and supportive care have resulted in a growing number of survivors of allogeneic hematopoietic cell transplantation (allo-HCT). In this population, central nervous system (CNS) complications represent a major cause of morbidity and mortality in the immediate post-HCT setting. However, there is a paucity of knowledge regarding the incidence and risk factors for CNS complications developing years after HCT. Potential mediators of late-occurring CNS toxicity could include previous exposure to radiation or drugs (e.g. fludarabine, Busulfan, and calcineurin inhibitors), infections resulting from immunodeficiency or tissue barrier breakthrough, bleeding due to thrombocytopenia, or CNS recurrence of primary malignancy. The current report addresses the existing gap in literature by comprehensively evaluating the role of demographic, HCT-related therapeutic exposures, graft versus host disease (GVHD) and its management, as well as post-HCT comorbidities in the development of late-occurring (〉1 year) CNS complications after allo-HCT. Methods: A retrospective cohort study design was used to describe the cumulative incidence of CNS complications (Common Terminology of Adverse Events Grade 3-5: seizure disorder, stroke, encephalopathy), and to examine the role of demographic, disease-related and conditioning factors in 1,543 one-year survivors who underwent allo-HCT at City of Hope between 1995 and 2010. Next, a nested case-control approach (1:2 match: age at HCT, sex, length of follow-up) was used to evaluate the role of post-HCT exposures and comorbidities on long term risk. Cumulative incidence was calculated taking into consideration the competing risk of death. Multivariable regression analysis was used to calculate hazard ratios (HR) and odds ratios (OR), as well as 95% confidence intervals (CI), adjusted for relevant covariates. Results: Median follow-up for the entire cohort was 5.2 years (range: 1-18.9 years), representing 9,850 person-years of follow-up. Fifty-five survivors developed 83 CNS complications at a median of 2.5 years (range: 1-14.4 years) from allo-HCT; 53% were female; underlying diagnoses at allo-HCT: ALL (29%), AML (20%), Lymphoma (15%), CML (12%), other (24%); HCT conditioning: busulfan/cytoxan (11%), total body irradiation/etoposide (25%), fludarabine/melphalan (36%), other (29%). Ten-year cumulative incidence of CNS complications was highest (9.9%) for females who underwent allo-HCT for ALL (Figure). Diagnosis of ALL (HR: 2.3 [CI 1.1-4.7]), and conditioning with fludarabine/melphalan (HR: 5.3 [CI 1.2-23.6]) were significant predictors of CNS complications, independent of age. Post-HCT risk factors: Multivariable regression analysis adjusting for disease relapse and GVHD status revealed a significantly higher risk of CNS complications in survivors who were on mycophenolate mofetil or sirolimus (OR: 4.5 [CI 1.4-15.1]), who developed hypertension (OR: 3.5 [CI 1.3-9.3]), or thrombocytopenia (OR: 3.1 [CI 1.2-8.1]) in the years following allo-HCT. Five-year overall survival was significantly worse in patients who developed CNS complications when compared to those who did not (53.8% vs. 73.6%, p

Description: Background: alloHCT is offered with curative intent to patients with malignant as well as some nonmalignant hematologic diseases, and conventionally-computed survival estimates are offered for prognosticating outcomes. However, conventionally-computed survival and mortality risk estimates do not account for patients' elapsed survival time which, among other factors, could affect subsequent mortality. Conditional survival overcomes these limitations by calculating the probability of survival after having already survived a certain period of time - such data are unavailable for alloHCT recipients. We describe conditional survival and cause-specific mortality (disease-related [DRM], non-disease-related [NDRM], and GvHD-related) after alloHCT to provide clinically relevant information for patients who have survived 6 mos, 1, 2, 5, and 10y after alloHCT. Methods: From 1976 to 2013, 4,315 consecutive patients underwent alloHCT for hematologic diseases at a single institution. Vital status and cause of death were determined using the National Death Index Plus and medical records. Results: Diagnoses included acute leukemia (54%), chronic leukemia (17%), lymphoma (11%), myelodysplastic syndrome (10%), severe aplastic anemia (5%), and other hematologic diseases (3%); median age at HCT was 38.5y (0.3-75.4). As of December 31, 2014, 1841 patients were still alive in whom the median follow-up was 8.5y (0.2-36.6). Of 2,474 deaths (57% of cohort) for whom causes of deaths are available, 42% was due to primary disease, 30% to graft versus host disease (GvHD), 12% to infection, 5% to cardiopulmonary diseases, 3% to subsequent malignant neoplasm (SMN), and 8% to other causes. Conventionally-computed probabilities of survival at 5, 10, 15, and 20y after alloHCT were 48%, 43%, 40%, and 34%, respectively. On the other hand, for patients who had survived 6 mo, 1, 2, 5, 10y after alloHCT, 5-y conditional survival rates were 62%, 72%, 80%, 88% and 93%, respectively (Figure A). Overall, the cohort was at a 24-fold (Standardized Mortality Ratio [SMR]=24.1, 95%CI=23.1-25.0) risk of any death, compared to the general population; the risk of death from pulmonary complications was 31-fold, that from SMN was 31-fold, and that from cardiovascular complications was 3.5-fold. SMR and cause-specific conditional mortality rates by primary diagnosis are shown in the Table. Significantly elevated risk of all-cause mortality persisted in patients who survived 5 and 10y post alloHCT (SMR=3.7, 2.6, respectively, p