Hematopoietic Cell Transplantation Comorbidity Index Score Research Articles

Outcome after autologous transplantation in the terms of comorbidity for patients with lymphoproliferative diseases: Single center experience.

e19502 Background: Autologous stem cell transplantation (ASCT) improves survival in patients with myeloma and lymphoma but is associated with morbidity and nonrelapse mortality (NRM). Hematopoietic cell transplant comorbidity index (HCT-CI) was shown to predict risk of NRM and survival after allogeneic transplantation. We tested the utility of HCT-CI as a predictor of NRM and overall survival (OS) in patients undergoing ASCT. Methods: We analyzed outcomes of 220 patients after high-dose melphalan and high –dose anti lymphoma chemotherapy during year 2000 to 2015. Individual comorbidities were prospectively collected at the time of ASCT. The impact of HCT-CI and other potential prognostic factors, including Karnofsky performance score (KPS), on NRM and survival were studied in multivariate Cox regression models. Results: HCT-CI score was 0, 1, 2, 3, and >3 in 42%, 18%, 13%, 13%, and 14% of the study cohort, respectively. Subjects were stratified into 3 risk groups: HCT-CI score of 0 (42%) versus HCT-CI score of 1 to 2 (32%) versus HCT-CI score > 2 (26%). Higher HCT-CI was associated with lower KPS < 90 (33% of subject’s score of 0 versus 50% in HCT-CI score > 2). HCT-CI score > 2 was associated with melphalan dose reduction (22% versus 10% in score 0 cohorts). One-year NRM was low at 2% (95% confidence interval, 1% to 4%). On multivariate analysis, overall survival was inferior in groups with HCT-CI score of 1 to 2 (relative risk, 1.37, [95% confidence interval, 1.01 to 1.87], P = .04) and HCT-CI score > 2 (relative risk, 1.5 [95% confidence interval, 1.09 to 2.08], P = .01). Factors that affect OS in the autologous recipients among lymphoma and myeloma patients were: HCT-CI, Karnofsky score, number of CD34+ cells/kg and time from diagnosis until transplant (p<0.05). Factors that affect TRM/NRM were HCT-CI, ECOG, Karnofsky score and number of hospital days and body weight.(p<0.05). Conclusions: ASCT for MM and lymphoma is associated with low NRM, and death is predominantly related to disease progression. Comorbidity evaluation during autologous transplantation for lymphoproliferative diseases can be a useful tool in predicting transplant outcome.

Treatment Selection of Elderly Acute Myeloid Leukemia Patients Guided by HCT-CI Score

To explore the feasibility of guiding the individalized treatment strategy for elderly AML patients by using hematopoietic cell transplantation-comorbidity index(HCT-CI) score. The clinical and biological data of 165 elderly (260 years) AML patients in department of hematology of the first affiliated hospital of Wenzhou medical universtity from January 2000 to December 2014 were analyzed retrospectively. The AML patients were divided into 3 groups: score 0-1, 2-3 and ≥4 according to HCT-CI, then the patients in each group again were divided into standard chemotherapy group, low dose chemotherapy group and support therapy group accoriding to therapeutic regimens, and the efficacy of above mentioned 3 kinds of treatment and their effects on survival of ealderly AML patients were compared, the prognostic risk factors for patients were analyzed further. A total of 165 patients (100%) were followed-up, and the mean follow-up time was 309 days, median survival time was 210 days. The survival analysis showed that the patients in HCT-CI score 0-1 group and 2-3 group banefited from chemotherapy, while the survival analysis of the HCT-CI score ≥4 group showed that there were no significant differance in survival rate between support therapy and chemotherapy groups. The complete remission rate and early mortality of patients received low dose or standard dose chemotherapy in HCT-CI score 0-1, 2-3 and ≥4 groups were not significantly different. Univariate analysis and multivariante analysis of COX ratio risk model showed that the EOCG-PS≥2, WBC≥100×107/L at initial diagnosis and HCT-CI score ≥4 were the independent risk factor affecting the prognosis of elderly AML patients. The median survival time of patients received chemotherapy and support therapy was 840 and 150 d(P<0.01) in HCT-CI score 0-1 group respectively, 210 and 60 days (P<0.01) in HCT-CI score 2-3 group respectively, 130 and 90 days (P>0.05) in HCT-CI score ≥4 group, respectively. The HCT-CI score can be used as simple and feasible evaluation criteria to judge the selection of individualized treatment strategy for elderly AML patients.

Prognostic Value of the Hematopoietic Cell Transplantation Comorbidity Index for Patients Undergoing Reduced-Intensity Conditioning Cord Blood Transplantation

The Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) has been validated as a tool for evaluating the risk of treatment-related mortality (TRM) in HLA-matched sibling and matched unrelated donor bone marrow and peripheral blood stem cell transplantation patients. However, the role of the HCT-CI after cord blood transplantation (CBT) has not been fully investigated. In this analysis, we sought to evaluate the predictive value of the HCT-CI in patients undergoing reduced-intensity conditioning (RIC) CBT. Between 2006 and 2013, HCT-CI scores were prospectively tabulated for patients with hematologic malignancies sequentially enrolled on multicenter RIC CBT studies coordinated by the Fred Hutchinson Cancer Research Center: 151 patients with acute myeloid leukemia/myelodysplastic syndrome (n = 101), chronic myeloid leukemia (n = 3), acute lymphocytic leukemia (n = 24), non-Hodgkin lymphoma (n = 8), Hodgkin lymphoma (n = 3), and other hematologic malignancies (n = 12) underwent RIC CBT and were included. Two patients received a single CBT and the remaining 149 received a double CBT. All patients received cyclosporine and mycophenolate mofetil for graft-versus-host disease prophylaxis. Median HCT-CI for the whole group was 3 (range, 0 to 8). Using the HCT-CI categories of low (0), intermediate (1 or 2), and high risk (>3), there was no significant difference in TRM between the 3 groups. However, when the patients were divided into 2 groups, HCT-CI ≤ 3 or > 3, the incidence of TRM at 3 years after transplantation was 26% (95% confidence interval [CI], 17 to 36) in the HCT-CI ≤ 3 group versus 50% (95% CI, 30 to 67) in the HCT-CI > 3 group (P = .01). Overall survival for patients with HCT-CI ≤ 3 was 40% (95% CI, 27 to 51) versus 29% in patients with HCT-CI >3 (95% CI, 12 to 48) (P = .08). Our study demonstrates that HCT-CI score > 3 is associated with an increased risk of TRM at 3 years after transplantation in patients undergoing RIC CBT. Because of the significant risk of TRM in patients with HCT-CI > 3 compared with risk for those with HCT-CI ≤ 3, patients with an HCT-CI score >3 should be counseled before undergoing RIC CBT.

Comprehensive Analysis of Pre-Transplant Pulmonary Function Test Parameters Including FEV1, FVC, DLco, FEF50%/75%, Frc, RV and TLC As Prognostic Factors for Long-Term Outcomes after Allogeneic Transplantation

BackgroundThe pulmonary function test (PFT) is an integral part of the assessment of patients prior to hematopoietic cell transplantation (HCT). The HCT comorbidity index (HCT-CI) is a routinely used scoring system using PFTs to determine patient outcomes post HCT. FEV1 and DLCO are used as determinants distinguishing between moderate (DLCO or FEV1 66-80%) and severe dysfunction (DLCO or FEV1 ≤ 65%). While there is a supportive evidence of its use in HCT, there is a debate on stratification of the current threshold of PFTs. Our study attempted to analyze the prognostic impact of each parameter of PFT on outcomes including overall survival (OS), relapse and non-relapse mortality (NRM) including FEV1, FVC, DLCO, FEF50%/75%, FRC, RV as well as TLC.MethodsA retrospective review was conducted to analyze pre-transplant PFT values with respect to transplant outcomes in 605 patients receiving allogeneic HCT at Princess Margaret Cancer Centre from 2004 to 2013. PFT results were collected within 30 days prior to HCT. PFT parameters include % predicted FEV1, DLCO, TLC, RV, RV/TLC, FRC, FVC, FEV1/FVC, FEF50% and FEF75%. The main outcomes include OS, cumulative incidence of relapse (CIR) and NRM. The cut-off values in each PFT parameters with respect to OS were calculated using binary recursive partitioning (rpart) method provided by rpart package using R. Each PFT parameter was analyzed for correlation with other PFT parameters using Pearson’s correlation test. All the statistical tests were done using EZR and SPSS. OS analysis was done using Kaplan-Meier method, and OS was compared according to the new cutoff derived from rpart and according to the cutoff used in the HCT-CI score. Then prognostic stratification power was compared between these two cutoffs. For the multivariable analysis, all variables were included in the model with the exception of those already included in the HCT-CI score. For the outcome of OS, Cox prop ortional hazard regression model was adopted. Six clinical variables were included in the multivariate analysis including: pre-transplant FEV1 <81%, conditioning regimen (reduced intensity vs myeloablative), age ≥60 yrs (vs < 60 yrs), disease risk index (DRI) (high/very high risk vs intermediate vs low risk), GVHD prophylaxis (without or with T-Cell Depletion (TCD)), and HLA mismatch vs matched.ResultsOut of 605 patients, OS rate was 46% at 3 years. NRM was 35.6% and relapse rate was 21.0% at 3 years. For correlation among PFT parameters, FEV1 was significantly associated with TLC (r=0.51), FVC (r=0.79), FEF75 (r=0.58) and FEF50 (r=0.68), and was chosen as a surrogate of OS for further analysis. Univariate analysis for the PFT parameters expressed as continuous variables revealed that OS was associated with FEV1, FVC and TLC, while not with other parameters (i.e. DLCO, FEF50%, FEF70%, FRC or RV). Using recursive partitioning, the optimal value for the best stratification of OS was found: FEV1 at 81%, FEV1/FVC at 92%, and TLC as 88%. The OS rate at 3 years in the group with FEV1 ≥81% was 49.9%, versus FEV1 <81%, 36.6% (p=0.001, HR 0.674). Meanwhile, the group with FEV1 ≥80% showed an OS of 49.2% at 3 years, while with FEV1 between 66-80% and ≤65% showed an OS of 38.1% and 33.5% at 3 years, respectively. (p=0.003, HR 0.774). We then compared the risk stratification power of the new FEV1 cutoff derived from rpart with the cutoff used in the HCT-CI score (65% and 80%). Using C-statistic, it was found that the new cutoff from rpart showed better risk stratification compared to that form HCT-CI score (P<0.01, C-statistic 2.4279). Multivariate analysis confirmed that pre-transplant FEV1 <81% is an independent prognostic factor for OS. The patients with pre-transplant FEV1 <81% showed 48% higher risk of death compared to those with higher FEV1 (p=0.001; HR 1.478). The other prognostic factors included HLA mismatch (p=0.001; HR 1.817]), and DRI (overall p=0.03; p=0.007 between low vs intermediate/high/very high risk).Conclusions1. FEV1 at 81% is a significant and reliable parameter amongst all the PFT parameters affecting HCT outcomes.2. DLCO does not predict long-term HCT outcomes in our cohort.3. Compared to FEV1 cutoff per HCT-CI scoring system, the new cutoff of 81% FEV1 provides better risk stratification power for long-term outcomes after allogeneic HCT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of Obesity on Outcomes of Elderly Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Myeloid Malignancies

BackgroundAllogeneic hematopoietic cell transplantation (AHCT) is a high risk treatment option for patients (pts) with myeloid malignancies. Advanced age and obesity can impact outcomes after AHCT. Previous registry studies of all age groups found that obesity does not affect AHCT outcomes. However, obesity can hasten age-related decline in physical function and exacerbate comorbid conditions in older pts. In this study we evaluated outcomes of both non-obese and obese elderly pts undergoing AHCT for myeloid malignancies.MethodsWe performed a retrospective, single-center analysis of all pts age≥60 who underwent unrelated or related AHCT for myeloid malignancies (acute myeloid leukemia [AML], myelodysplastic syndrome [MDS], or myeloproliferative neoplasms [MPN]) between 2010 and 2015. Descriptive statistics were used to measure baseline characteristics. A hematopoietic cell transplant co-morbidity index (HCT-CI) score was calculated for all pts. Acute graft-versus-host disease (aGVHD) was defined as occurring in <100 days after transplant (Tx) and chronic GVHD (cGVHD) as occurring ≥100 days. Pts were stratified by body mass index (BMI) ≥30 or <30. Comparative analysis was done using chi-squared and Fischer’s exact tests. The Kaplan-Meier method was used to calculate overall survival (OS) and progression free survival (PFS), which were estimated from date of AHCT to death, progression, or last follow-up. A log-rank test was used to compare OS and PFS of pts with BMI≥30 to those with BMI<30.ResultsOf 86 pts that met inclusion criteria, 41 pts (48%) had a BMI≥30 and 45 pts (52%) had BMI<30 (Table 1). Among the BMI≥30, 15 pts had BMI≥35 (range 30-49). Median age at Tx was 66 years in both groups. There was no difference in mean age, sex, cytogenetic risk (good, intermediate, poor), disease indication (AML, MDS, MPN), donor (related vs unrelated), and KPS≥90 in the two groups. In pts with BMI≥30, 46% (N=19) underwent myeloablative conditioning compared to 29% (N=13) in the BMI<30 (p=0.09). GVHD prophylaxis included tacrolimus (tac) in all pts except one who received post-transplant Cytoxan. There were 3 pts with BMI≥30 with <8/8 unrelated donor who received ATG in addition to tac. Pre-Tx bone marrow biopsy revealed that 3 pts (7%) in the BMI≥30 group had >5% blasts and 9 pts (20%) had >5% blasts in the BMI<30 group (p=0.12). There were significantly more pts in the BMI≥30 group with a HCT-CI score≥3 (30 pts vs 13 pts, p<0.01). When excluding points for obesity, there were still more pts with a BMI≥30 with a HCT-CI≥3 (25 pts vs 13 pts, p<0.01).The median OS was 36 months (m) for BMI<30 pts and 24 m for BMI≥30 (Figure 1), but this was not statistically significant (p=0.55). Median PFS was 10.1 m in the BMI<30 group and 13.6 m in the ≥30 group (p=0.93) (Figure 2). Sixteen pts (36%) with BMI<30 had aGVHD while only 8 pts (20%) with BMI>30 (p=0.10). One-year cumulative incidence of cGVHD was 56% (BMI≥30) vs 38% (BMI<30), p=0.09. Among pts admitted for Tx (N=76) mean length of stay (LOS) was 25 days in BMI<30 and 26 days in BMI≥30 (p=0.64). There were more pts (34% vs 16%) with BMI≥30 who were re-admitted within 30 days of discharge (p=0.045).We performed an exploratory analysis of pts with BMI≥35 (N=15) compared to all other pts with BMI<35 to see if outcomes were worse only in those with morbid obesity. Again, we found no difference in age, sex, intensity of conditioning, indication for Tx, or disease status prior to Tx between the two groups. There were more pts with HCT-CI≥3 in the BMI≥35 group (p=0.047). The median OS was not reached (NR) in the ≥35 group while it was 23.7 m in the <35 group (p=0.08). Median PFS was also NR in the ≥35 group but was 10.8 m in the <35 group (p=0.19). There was no difference in aGVHD or cumulative incidence of cGVHD at 1 year. Interestingly the LOS among hospitalized pts was longer in the ≥35 group at 28.5 days vs 25.2 days (p=0.09) and there were more pts readmitted within 30 days of completing their Tx in the BMI≥35 group (47% vs 20%, p=0.03).ConclusionsIn elderly pts (age>60) with myeloid malignancies undergoing AHCT, outcomes were not affected by either obesity or morbid obesity. Obesity was associated with increased re-hospitalization within 30 days of discharge after Tx. Morbidly obese pts had a trend towards a longer hospitalization stay and an increased rate of readmissions within 30 days of discharge from their Tx. In elderly pts, BMI should not preclude consideration of a curative AHCT. [Display omitted] [Display omitted] [Display omitted] DisclosuresHamadani:Takeda: Research Funding. Shah:Oncosec: Equity Ownership; Exelixis: Equity Ownership; Geron: Equity Ownership.

Impact of Somatic Mutations on Clinical Outcomes Following Flamsa-Bu Conditioning and Allogenic Stem Cell Transplantation in Patients with Poor-Risk Myeloid Malignancies

Allogeneic stem cell transplantation (allo-SCT) offers a potentially curative option for eligible patients with poor-risk myeloid malignancies. The prognostic impact of specific mutations such as TP53 is unclear in this context1,2. We report the prognostic impact of mutations in a panel of 19 genes (covering entire coding regions of DNMT3A, CEBPA, GATA2, TET2, TP53 and mutation hot spots of ASXL1, BRAF, CBL, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, NPM1, NRAS, PTPN11, RUNX1 and WT1) identified by targeted sequencing in patients undergoing allo-SCT with FLAMSA-Bu conditioning.Twenty-one patients (10 male, 11 female; median age 55 years; range 36-64 years) were included and identified as having poor risk disease on the basis of acute myeloid leukemia (AML) with primary induction failure (n=5), myelodysplasia (MDS) with high or very high risk R-IPSS scores (n=8, 4 of whom had therapy related MDS), therapy related acute myeloid leukemia with MLL rearrangement (n=1), intermediate-2 or high risk prognostic score for chronic myelomonocytic leukemia (CMML) (n=4), blast crisis of chronic myeloid leukemia (n=1), primary myelofibrosis with blasts > 10% on bone marrow trephine (n=1), mixed phenotype acute leukemia (T/myeloid) with complex karyotype (n=1). Overall, complex karyotypes were detected in 8/21 (38.1%) patients. The median Hematopoietic Cell Transplantation-Comorbidity Index score was 4 (range 0-10).All 21 patients underwent allo-SCT with fludarabine, cytarabine, amsacrine, busulphan, and anti-thymocyte globulin (FLAMSA-Bu) conditioning. Twelve (57.1%) received stem cells from fully HLA matched unrelated donors. Neutrophil engraftment occurred at a median of 24 days (range 11-124 days) and platelet engraftment at a median of 26 days (range 10-221 days) post-transplant. Seven (33.3%) patients developed acute graft versus host disease (GVHD). Ten (47.6%) patients received planned donor lymphocyte infusions.Genomic DNA was available from 16/21 patient samples and was sequenced using the Ion-Torrent platform. Somatic driver mutations were identified in 13/16 (81.2%) patients, 10 of whom had two or more driver mutations. TET2 mutations were the most common lesion, detected in 6/16 (37.5%) cases, followed by RUNX1, ASXL1 and DNMT3A in 3/16 (18.8%) patients each.Ten (47.6%) patients remain alive and disease-free after a median of 19.3 months follow-up. Two treatment-related deaths occurred; one from sepsis in the context of steroid-refractory GVHD and a second patient died of toxoplasmosis infection. Nine (42.9%) patients have relapsed post allo-SCT, three of whom remain alive following salvage therapy. The median progression free survival (PFS) is 841 days and the median overall survival (OS) has not yet been reached. Patients with therapy-related myeloid neoplasms trended towards shorter PFS and OS compared with all other diagnosis (396 vs 841 days, p=0.54; 373 days vs undefined, p=0.11, respectively). All four CMML patients have relapsed at a median of 694 days post FLAMSA-Bu allo-SCT. The median PFS for de novo AML and MDS has not been reached.Monosomal karyotype was associated with a non-significant trend towards shortened PFS (148 days vs 751 days, p=0.11). Cases with TET2 mutations trended towards a shorter PFS compared with wild-type TET2 (751 days vs undefined, p=0.6407) but this did not reach statistical significance. No difference was observed in PFS between TP53 mutated vs wild-type TP53 cases (517 days vs 751 days, p=0.99).FLAMSA-Bu allo-SCT remains a viable treatment option for selected patients with de novo AML and MDS, even patients in whom multiple or adverse somatic mutations are detected. Conversely, durable remissions are uncommon for patients with therapy-related myeloid neoplasms or CMML. These patients may benefit from consideration for alternative treatment strategies.

Disease Risk Index (DRI) Score Stratification and Composite End-Point GvHD-Free Relapse-Free Survival (GRFS) May Optimize Transplant Decision-Making Process in Haploidentical Stem Cell Transplantation

IntroductionPre-transplant risk assessment is a crucial issue to improve the HCT decision-making process. Several transplant-related models have been designed to optimize decision-making about suitable candidates for allogeneic HCT. The refined Disease Risk Index (DRI) was developed to stratify disease risk acrosshistologiesand HCT regimens. However, few recipients of haploidentical HCT were originally included in the DRI study cohorts. In 2015 a first large cohort of non-myeloablativehaploidentical HCT with post-transplant cyclophosphamide (PTCy) confirmed the validity of DRI also in this setting.Beside this, in the past few years the novel composite end point of GVHD-free, relapse-free survival (GRFS) after HCT spreads out. GRFS acknowledge that both survival and rates of grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death are clinically meaningful. GRFS therefore represents ideal recovery from HCT and a measure of cure without ongoing morbidity.MethodsWe analyzed risk-stratified GRFS according to the refined DRI in haploidentical HCT at our Center, where it was exploited - since 2006 - asirolimus-based,calcineurininhibitor-free prophylaxis of GvHD to allow the safe infusion of unmanipulated haploidentical HCT.We analyze data collected between 2006 and 2014 including 207 adult pts. Data were prospectively collected in Institutional database. A written consent was given by pts allowing the use of medical records for research in accordance with the Declaration of Helsinki.All consecutive pts receiving a haplo HCT as 1st allogeneic transplantation were included - pts receiving haplo HCT as 2nd or 3rd HCT were excluded from the present analysis.ResultsBaseline characteristics of the 207 pts are outlined in table 1.With 4-year median follow-up, 4-year probabilities of transplant related mortality (TRM),relapse, progression-free survival (PFS), and overall survival (OS) were 25,8%, 42,5%, 31,7%, and 34,4%, respectively. Day-100 cumulative incidence of grade II-IV and III-IV acute graft-versus-host-disease (GvHD) were 30,1% and 15,5% respectively. The 4-year cumulative incidence of chronic GvHD was 33,5% (moderate-severe chronic GvHD 26,2%).Considering the composite end point of GRFS, for the entire population the 4-year GRFS was 17,8%.By refined DRI group, low-intermediate (n 69), high (n 105), and very high (n 33) risk groups had 4-year GRFS estimates of 31,1%, 13,7%, and 3,0% (p < .0001), with corresponding 4-year OS estimates of 56,7%, 28,9%, and 6,1% (p < .0001).On a multivariable Cox model we considered as covariates age, host/donor sex mismatch, host/donor CMV status, stem cell source, conditioning intensity, GvHD prophylaxis ATG-based versusPTCy-based, DRI stratification, HCT Comorbidity Index Score (HCT-CI).On multivariable analyses, the DRI was statistically significantly associated with GRFS, OS, PFS, relapse, TRM and grade II to IV acute GvHD (ref table 2).HCT-CI was statistically significantly associated with GRFS, OS, PFS and TRM. Conditioning intensity was associated with PFS and relapse, while GvHD prophylaxis (PTCyvs ATG) was only associated with OS.Interestingly no risk factors were clearly emerging for chronic GvHD.ConclusionsThe combination of a refined DRI and GRFS provide a valid tool to improve the HCT decision-making process and will help optimize patient outcomes. [Display omitted] [Display omitted] DisclosuresCiceri:MolMed SpA: Consultancy.

Clinical Characteristics, Biological Markers and Comorbidity Indexes As Predictors of Transplant-Related Mortality after Allogeneic Hematopoietic Stem Cell Transplantation: Which One Should We Choose?

Treatment-related mortality (TRM) after allogeneic hematopoietic stem cell transplantation (HSCT) is a major concern and remains difficult to predict adequately. Several pre-transplant characteristics of patients and disease are associated with TRM. Comorbidity indexes, including pre-transplant assessment of mortality (PAM) and the hematopoietic cell transplantation comorbidity index (HCT-CI), have been developed in an attempt to predict TRM. Biologic markers, such as ferritin, C-reactive protein (CRP) and, more recently, telomere length, also correlate with TRM. However, the cumulative impact of these factors on TRM has not been addressed. Here, we investigated the impact of pre-transplant clinical factors, comorbidity indexes and biologic markers on TRM in 670 consecutive patients from a single center who received a first allogeneic HSCT between January 2006 and June 2012. Clinical factors considered were: year of transplantation, donor and recipient ages, gender and CMV serological status, disease risk (based on the American Society for Blood and Marrow Transplantation Request for Information 2006 risk scoring schema), stem cell source, and HLA matching. Comorbidities were evaluated by PAM and HCT-CI, and coded prospectively for all patients by a single observer. HCT-CI and PAM scores were ranked into previously published categories (0, 1-2, ≥3 for HCT-CI and 9-16, 17-23, 24-30 and 31-44 for PAM; Sorror, Blood 2005; Parimon, Annals Intern. Med. 2006). Ferritin, CRP and biological data for comorbidity indexes were recorded within 2 weeks prior to HSCT. Recipient telomere lengths were determined in peripheral blood leukocytes by qPCR and adjusted for age by the telomere attrition rate observed in donors.Our analysis categorized the population into quartiles and divided patients into 2 groups: shorter telomeres (first quartile) versus longer telomeres (upper 3 quartiles). The entire patient cohort was subsequently divided into 3 groups by data availability: Group 1 (G1), the entire population (n=670) for whom all clinical data were available; G2, 488 patients with clinical and comorbidity index data (pulmonary function tests were not systematically performed during the early study period); and G3, for whom pre-transplant telomere length was available (n=178). Univariate and multivariate methods developed by Fine and Gray for competing risks studies were used to assess prognostic TRM factors, with relapse as a competing event. Table 1 shows patient characteristics. Significant differences between G1 and G2 were found for mean donor and recipient ages, sex mismatch, HLA matching, stem cell source, disease risk, and year of transplantation. Median follow-up was 36 months, overall survival at 5 years for the entire cohort was 60%, and TRM was 18%. In G1, factors significantly associated with higher TRM in multivariate analysis were: recipient age (HR, 1.02, 95%CI [1.0-1.03], p=0.005), CMV seropositive recipient/seronegative donor (R+/D-) (HR, 1.98, 95%CI [1.34-2.92], p=0.001) and mismatched unrelated donor (MMUD) (HR, 2.28, 95%CI [1.38-3.74], p=0.001). In G2, the same factors [recipient age (HR, 1.01, 95%CI [1.00-1.03], p=0.027), CMV R+/D- (HR, 1.91, 95%CI [1.22-2.99], p=0.005), MMUD (HR, 2.55, 95%CI [1.48-4.42], p=0.001)] were associated with higher rates of TRM, whereas PAM showed a trend for higher TRM (HR, 1.41, 95%CI [0.99-1.99], p=0.05). HCT-CI, ferritin, and CRP were not associated with TRM. In G3, only MMUD (HR, 2.82, 95%CI [1.06-7.46], p=0.037) was associated with higher TRM. However, in analysis restricted to patients transplanted from an HLA-matched related or unrelated donor, recipient age (HR, 1.03, 95%CI [1.00-1.06], p=0.027) and telomere length (HR, 2.45, 95%CI [1.07-5.59], p=0.033) were independently associated with higher TRM. This is the first study to investigate the impact of clinical and biological pre-transplant factors and comorbidity indexes on TRM after allogeneic HSCT in a large cohort of patients. Best results were obtained with young patients transplanted from an HLA-matched donor, with CMV other than R+/D-. High comorbidity scores (evaluated by PAM) were marginally associated with higher TRM. In G3 (pre-transplant telomere length available), only HLA-mismatch was significantly associated with higher TRM. [Display omitted] DisclosuresPeffault De Latour:Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; Alexion: Consultancy, Honoraria, Research Funding.

Distribution and Impact of Comorbidities on Survival and Leukemic Transformation in Myeloproliferative Neoplasm (MPN)-Associated Myelofibrosis (MF)

Introduction. Myelofibrosis is a disease characterized by aberrant bone marrow function with eventual fibrosis. Current widely-used disease prognostic indices, such as the Dynamic International Prognostic Scoring System (DIPSS) do not take into account comorbidities, which may have significant effects on patient survival as well as disease course. We sought to describe the comorbidity distribution in this patient population and assess the impact of comorbidities as scored by two different widely used scales in clinical practice, the Adult Comorbidity Evaluation 27 (ACE-27) and the Hematopoietic Cell Transplant Comorbidity Index (HCT-CI), on overall survival and leukemic transformation in myelofibrosis. A score of 3 on ACE-27 or ≥3 on HCT-CI generally indicates a high burden (severe) comorbidities.Methods. We conducted a retrospective study of 309 patients seen at the MPN program at the Princess Margaret Cancer Centre, with a confirmed diagnosis of myelofibrosis [primary myelofibrosis (PMF), post-essential thrombocytopenia (PET-MF) or post-polycythemia vera (PPV-MF)]. Patients were seen from 1999-2014 with a median follow-up time of 2 years. Time to death and leukemic transformation was examined from the date of first presentation to our centre. Our primary aim was to examine the impact of comorbidity scores, as assessed by ACE-27 and the HCT-CI, on overall survival. In a secondary analysis we examined the impact of comorbidity scores on leukemic transformation. Multivariable Cox proportional hazards models were constructed for the primary and secondary outcomes. A series of descriptive analyses were carried out examining the distribution of various comorbidities as captured by the two scales.Results. The most common comorbidities captured by ACE-27 were hypertension (n=92, 22.3%), diabetes mellitus (n=43, 10.4%), venous disease (n=26, 6.3%), solid tumour including melanoma (n=26, 6.3%), and angina/coronary artery disease (n=23, 5.6%). The most common comorbidities captured by HCT-CI were cardiac (n=49, 17.3%), diabetes (n=43, 15.2%), mild hepatic (n=28, 9.9%), cerebrovascular disease (n=25, 8.8%), prior solid tumour (n=24, 8.5%). The distribution of comorbidity scores as compared between scales is shown in Table 1.A total of 78 patients (25.2%) experienced the primary outcome of interest, which was all-cause death. For the primary outcome of overall survival, there were differences across groups of patients with different comorbidity scores using ACE-27 or HCT-CI, with the highest severity groups having worse outcomes (Figure 1). Progressively increasing DIPSS categories (Low, Intermediate-1, Intermediate-2, and High risk) were also associated with worse overall survival. On multivariable survival analysis, an ACE-27 score of 3 when compared to a lower score of 0-1 was associated with an almost two-fold increase in the risk of all-cause death [HR 1.95 (95% CI 1.06-3.58), p=0.03]. On multivariable analysis, an HCT-CI score of 3+ when compared with 0-1 was marginally significantly associated with an increased risk of all-cause death [HR 1.60 (95% CI 0.96-2.68), p=0.07]. Interaction terms were tested between the scores and age at presentation and no effect of age on survival across varying severities of comorbidities was found. In our secondary analysis, there was no impact of the ACE-27 or HCT-CI on leukemic transformation.Conclusions. ACE-27 picked up severe co-morbidities in 13% of patients in our cohort while HCT-CI picked up severe comorbidities in 23%. Although the incidence of severe co-morbidities was lower when assessed by ACE-27, the overall impact on survival of severe comorbidities as assessed by both scores is likely to be similar. The presence of severe comorbidities at the time of diagnosis conferred a significant survival disadvantage in patients with myelofibrosis, but had no impact on progression to leukemic transformation. [Display omitted] [Display omitted] DisclosuresPanzarella:Cellgene: Consultancy. Schimmer:Novartis: Honoraria. Schuh:Amgen: Membership on an entity's Board of Directors or advisory committees. Yee:Novartis Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gupta:Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Research Funding.

Pre-Transplant Psychosocial Assessment and Outcomes of Allogeneic Hematopoietic Cell Transplantation in Adults

Patients under consideration for allogeneic hematopoietic cell transplantation (HCT) undergo comprehensive evaluation, including psychosocial assessment, to evaluate their candidacy for transplant. Psychosocial factors such as presence of availability of a consistent care-partner, mental health needs, psychological issues such as depression and severe anxiety, and compliance can impact risks of toxicity and adverse outcomes including survival. However, instruments to objectively characterize psychosocial status in this population are generally lacking. Our group has previously assessed the Psychosocial Assessment of Candidates for Transplant (PACT) scale, originally developed for solid organ transplant recipients, to screen for psychosocial risk factors in allogeneic HCT patients (Foster et al, BMT, 2009). The PACT captures information in four domains (social support, psychological health, lifestyle factors, and patients understanding of the transplant process). The overall impression of the patient's suitability for transplantation is assigned a final PACT score ranging from 0 (poor candidate) to 4 (excellent candidate). We conducted a retrospective cohort study of 404 adult allogeneic HCT recipients (median age 50 [range, 18-73] years) between 2003 and 2014 at our institution to evaluate the association of PACT scale with other baseline clinical and sociodemographic factors and quality of life (QOL) prior to HCT, and its association with HCT outcomes. Patients were predominantly male (54%), White (89%), had acute leukemia/MDS (77%), had unrelated donor (55%), and received myeloablative regimens (78%). Based on ZIP code of residence, median annual household income for our cohort was $49,159 and 80% resided in Rural Urban Commuting Area designated urban area. Final PACT rating was poor/borderline (0-1) in 21 (5%), acceptable (2) in 87 (22%), good (3) in 177 (44%), and excellent (4) in 119 (29%) recipients. Significantly higher PACT ratings were observed in patients who were White (P=0.004), had higher household income (p=0.019), higher Karnofsky performance score (P=0.011), and low risk HCT-Comorbidity Index score (P=0.007). Final PACT rating was weakly correlated with the pre-HCT FACT BMT total QOL score (R=0.22), including its subdomains. A trend towards more days alive and outside the hospital in the first 100 days post-HCT was seen in patients with higher final PACT score (median 58, 65, 66, and 70 days for scores 0-1, 2, 3, and 4) in both univariable (P=0.07) and multivariable (P=0.09) analysis. At 1-year after HCT, cumulative incidence of non-relapse mortality for patients with PACT score 0-1 was 33%, for score 2 was 24%, for score 3 was 27% and score 4 was 16%. The 1-year overall survival probability for the four groups was 57%, 60%, 59% and 67%, respectively. In multivariable analysis that adjusted for patient and disease characteristics (including race/ethnicity, household income, place of residence and pre-HCT QOL), final PACT rating was associated with non-relapse mortality (HR 0.82 per point increase [95% CI, 0.69-0.98], P=0.03), but not with overall survival (HR 0.91 [95% CI, 0.79-1.05], P=0.18). There was no association between final PACT rating and neutrophil or platelet engraftment, acute or chronic graft-versus-host disease, or relapse. In conclusion the PACT scale provides prognostic information for NRM independent of clinical and other sociodemographic factors as an indicator of psychosocial adjustment post-HCT. The PACT scale can serve as a useful tool for screening adult patients for psychosocial risk factors prior to allogeneic HCT and may identify patients who need additional social support and resources to minimize risks of mortality after transplantation. DisclosuresNo relevant conflicts of interest to declare.

Comorbidities, not age, are predictive of survival after autologous hematopoietic cell transplantation for relapsed/refractory Hodgkin's lymphoma in patients older than 50years.

Autologous hematopoietic cell transplantation (AHCT) is the standard of care for young patients with relapsed/refractory (R/R) Hodgkin's lymphoma (HL). However, there is limited experience of its efficacy and feasibility in older patients. The characteristics and outcomes of 121 patients aged ≥50years (42 of them are ≥60years old) with R/R HL who underwent AHCT were reviewed. After a median follow-up of 3.1years, overall survival (OS) and progression-free survival (PFS) at 5years were 64 and 55%, respectively, with no differences between 50-59-year-old and ≥60-year-old patients. Hematological and extra-hematological toxicities after AHCT were comparable between the two groups of age. In univariate analysis, poorer OS and PFS were associated with disease status other than complete remission, hematopoietic cell transplantation comorbidity index (HCT-CI) scores >1, and Charlson Comorbidity Index (CCI) scores >1. HCT-CI scores >1 were also associated with a higher risk of grade 3-4 extrahematologic toxicity. In multivariate analysis, HCT-CI and CCI remained significantly associated with OS and PFS after adjustment for disease status. Our data show that AHCT can be performed in selected patients with R/R HL ≥50years with acceptable outcome and toxicity. Comorbidities appear to impact AHCT outcome more than age.

Post-relapse survival after haploidentical transplantation vs matched-related or matched-unrelated hematopoietic cell transplantation.

Relapse remains a major cause of mortality among patients receiving allogeneic hematopoietic cell transplantation (HCT). The impact of donor type on post-relapse survival (PRS) has not been widely examined. We compared the survival outcomes for patients relapsing after haploidentical donor transplantation (HIDT) using post-transplant cyclophosphamide with those relapsing after matched-related donor transplantation (MRDT) or matched-unrelated donor transplantation (MUDT) at our institution. Two hundred and thirty-seven consecutive HCT recipients with relapse occurring after HIDT (N=48), MUDT (N=87) and MRDT (N=102) were included in this analysis. Median age was 49 years (19-77 years) and the median time to relapse was 156 days (12-2465) after HCT. HIDT recipients had similar median time to relapse (5.8 vs 4.8 vs 5.5 months, P=0.638) compared with MUDT and MRDT, respectively. One-year PRS was worse among HIDT recipients compared with MRDT and MUDT (17% vs 46% vs 40%, P<0.05). In a multivariate analysis, time to relapse (<3 vs >3 months post transplant), no use of donor lymphocyte infusion (DLI) following relapse, higher Dana Farber disease risk index and HCT comorbidity index scores at the time of transplant and delayed platelet engraftment post transplant were all predictive of worse PRS. This analysis shows that 1-year PRS is inferior among HIDT when compared with MRDT or MUDT. Lower use of DLI after HIDT may have contributed to this inferior survival.

Combined model of the EBMT score modified model and the HCT-CI improves the stratification of high-risk patients undergoing unmanipulated haploidentical blood and marrow transplantation

Both European Group for blood and marrow transplantation risk score (EBMT score modified model) and hematopoietic cell transplantation comorbidity index (HCT-CI) are suitable for evaluating patients undergoing unmanipulated haploidentical blood and marrow transplantation (HBMT), while the predictive capacity of the combined model following haploidentical transplantation is still unknown. In this study, we calculated and validated 322 consecutive unmanipulated HBMT patients. Patients in groups with HCT-CI scores of 0 or 1–2 exhibited similar overall survival (OS), non-relapse mortality (NRM), and relapse rates, independent of their EBMT score modified model. In the group in which patients’ HCT-CI scores were ≥3, patients with high EBMT score modified model showed lower OS (p = 0.003) and higher NRM (p = 0.001) than did patients with low EBMT score. In conclusion, this combined model can be used to predict outcomes and may improve the stratification of high-risk patients following unmanipulated HBMT.

Hematopoietic Cell Transplantation Comorbidity Index As Prognostic Variable in Patients with Invasive Fungal Infections

Introduction.Invasive fungal infections (IFI) represent a major limiting factor for the successful outcome of hematologic patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Consequently, the identification of pre-transplant clinical risk factors for IFI may be considered a tool of paramount importance leading to targeted prophylactic measures and improved treatment strategies. Aim of the present study was to evaluate the pre-transplant hematopoietic cell transplantation co-morbidity index (HCT-CI) risk score and its impact on the outcome of HSCT recipients who develop an IFI.Methods.Between January 2009 and March 2015, 301 consecutive patients with complete HCT-CI risk score assessment, who received a first allogeneic HSCT in a single Stem Cell Transplantation Center, were analyzed. Overall, 62% of the patients had an acute leukemia and donor source was an alternative donor in 67% of the cases; 58% of the patients had a low or intermediate HCT-CI risk score (0-2) whereas 42% of the patients had a high HCT-CI score (≥3).Results.In the present cohort the median overall survival (OS) was 35 months, with a median follow-up of 24 (1-77) months from HSCT. The cumulative incidence of IFI (possible-probable-proven) at 1 year was 14% with a trend towards a higher cumulative incidence of IFI among patients with a high HCT-CI (17%) compared to patients with HCT-CI 0-2 (11%; p=0.052). A significant better 2-year OS (67%) was observed in patients who received HSCT from matched related donor (MRD) compared to alternative donors (matched unrelated donor, MUD, and haploidentical HSCT) who showed a 2-year OS of 56% (p= 0.004). A statistically significant difference in 2-year OS was also observed in patients transplanted in early disease phase compared to patients who received the graft in advanced phase, 70% vs 53%, respectively (p=0.007). Moreover, patients with low-intermediate HCT-CI showed a significant better 2-year OS (70%) compared to patients with high HCT-CI (46%; p<0.001). Similarly, survival at 2 years post-HSCT, was significantly higher in patients with no evidence of IFI (66%) compared to patients with IFI (33%; p<0.001). Dividing the patients with IFI on the basis of HCT-CI score, the subgroup with high HCT-CI had a significantly shorter 2-year OS (19%) than patients with an IFI and low or intermediate HCT-CI (50%; p<0.001) (figure 1). Univariate analysis for OS demonstrated that age ≥ 55 years (p=0.045), the use of an alternative donor (p=0.004), an advanced disease phase at HSCT (p=0.041) and the presence of IFI (p<0.001) were significantly associated with a worse outcome. Moreover, in univariate analysis the HCT-CI score showed a significant association with OS (p<0.001), with a hazard ratio of 1.89 in the group with a HCT-CI score ≥ 3. Adjusting in a multivariate model, the use of an alternative donor (HR 1.70; p=0.009), a HCT-CI ≥ 3 (HR 1.82; p=0.001) and the presence of IFI (HR 2.22; p<0.001) were significant predictors of worse 2-year OS. Further, a pre-transplant high HCT-CI (HR 2.71; p <0.001) and the development of IFI (HR 3.69; p<0.001) were significant independent risk factors for non-relapse mortality (NRM), while IFI was a significant predictor for infectious-related mortality (IRM) with a HR 3.37 (p= 0.010).Conclusions.The results of the present study highlight the additional prognostic value of HCT-CI on the outcome of HSCT patients who developed an IFI. These findings may lead to the consideration of whether patients with a high HCT-CI score may be candidates for an intensive diagnostic work-up or a specific antifungal prophylaxis. Larger studies are required to address this issue. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Safety and Efficacy of Autologous Hematopoietic Cell Transplantation for Elderly Patients with Lymphoma: Chemosensitive Disease Rather Than Age or Co-Morbidity Index Predicts Outcome

Introduction: High dose chemotherapy (HDT) and autologous hematopoietic cell transplantation (AHCT) are considered standard of care as first line therapy in mantle cell lymphoma (Dreyling et al., 2005; Geisler et al., 2012) and in first line refractory and chemosensitive relapse Non-Hodgkin Lymphoma (NHL) (Philip et al., 1995) . The development of hematopoietic cell transplant comorbidity index (HCT-CI) (Sorror et al., 2009) for recipient selection and transplant risk evaluation have impacted on patient selection. Over the last decade, most transplant program have seen an increase in the median age of AHCT recipients(McCarthy et al., 2013). Limited data are available to optimise elderly patients selection for transplantation while minimising the risk of treatment related toxicity and mortality (TRM). The goal of this study was to identify factors impacting the safety and efficacy of AHCT in the elderly NHL patients in order to better select those who will benefit from this intervention. Method: This is a single center, retrospective study examining outcomes of AHCT in elderly patients (≥60 years old) with NHL. Between January 1st, 2008 and January 1st, 2015, 90 patients met the inclusion criteria and were included in the study. Patients signed an informed consent and the ethics committee of our institution approved the study. Progression-free-survival (PFS) and overall survival (OS) were analyzed according to age at time of transplantation, HCT-CI, lymphoma histology and disease status at time of transplant. Toxicities were analyzed according to age and HCT-CI. Results: Median age at time of NHL diagnostic was 60 years (range 42 to 68) and 63 years at time of transplant (range 60 to 69). One third (33%) of our cohort was ≥65 years old. Histologic sub-type was mainly composed of follicular (36%), mantle cell (20%) and large B-cell lymphoma (38%). 50% of patients had high-risk disease and 31% had low risk disease. HCT-CI was low-risk in 34%, intermediate risk in 40% and high-risk disease in 26%. BEAM/BEAC conditioning regimen was used in 94%. The median graft CD34+/kg cell dose infused was 4.87. The median time to neutrophil engraftment was 10 days (range 8 to 14 days) and platelet recovery was 16 days (range 11 to 43 days). The incidence of febrile neutropenia was 92% with 2% admission to the intensive care unit (ICU) with no difference between patients younger or ≥65 years old. Our cohort received a median of 8 days of antibiotics (range 0 to 41 days). Absolute lymphocyte count &lt; 0,3 X 103 cells/uL at 14 days after transplant was associated with higher incidence of septic choc (p=0,024) and ICU admission (p=0,034). Age ≥65 year was not associated with an increase TRM and was surprisingly associated with less total parenteral nutrition (p=0,046) and narcotics uses (P=0,011). The median length of stay was 26 days. The median follow-up was 27 months (range, 1 to 87), median PFS of 46 months (Confidence Interval (CI); 95%, 24,4-67,6) (graph 1) and OS not reached (graph 2). The estimated 5 years OS is 62% and PFS is 40%. Transplant related mortality (TRM) was only 1% at 100 days and 2% at 1year after transplant. The only 2 patients who died from TRM died from cardiac arrest (1 month) and from an unknown cause (3 months). The 1-year progression rate was 30% (graph 3) and mortality rate only 12%. Progressive disease status following first line therapy was associated with a worse PFS compared to the achievement of a complete remission (Hazard Ratio (HR) 2,77; CI 95%, 1,18; 6,49). Progressive disease status at time of transplant was also associated with a lower PFS (HR 9,30: CI 95% 2,55 to 33,92) and OS (HR 13,44: CI 95% 2,68 to 67,48). HCT-CI score did not correlate with OS. International Prognostic Index (IPI), age and treatment type did not influence PFS or OS. Surprisingly, HCT-CI score did not correlate with toxicities, morbidity or mortality. Conclusion: In this single center retrospective study of elderly patients with NHL, AHCT was proven to be safe and effective. Progressive disease at the time of transplant was associated with worse PFS and OS. HCT-CI did not allow the categorization of patients in different prognostics group. Lymphocyte count at day 14 could identify patients at significant risk of complications. Our data suggest that age alone should not exclude patients from transplantation. However, HDT and AHCT should be reserved to chemosensitive patients and avoided in the elderly patient with progressive disease. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

Refined Disease Risk Index (DRI) and Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) Predict Survival after Haploidentical Stem Cell Transplantation: A Comparative Study with EBMT Risk Score in 220 Consecutive Patients

BackgroundOptimization of pre-transplant risk assessment is a crucial issue to improve the allo-HSCT decision making process. Actually 3 major algorithms are in use in clinical practice: the EBMT risk score, the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score and - more recently introduced - the refined Disease Risk Index (DRI).DRI was defined to calibrate HSCT outcome across studies and centers. It was developed as a tool to assign patients into risk groups based on disease type and status at the time of transplantation. The aim of the DRI is to provide a robust tool that can be used for prognostication, for the analysis and interpretation of retrospective data, whether conducted in single-center, multicenter, or registry settings, or within the context of the federally mandated center outcome reporting. The DRI can also be used for the stratification of patients entering prospective HCT clinical trials.DRI is not a fixed tool but instead it was conceived to be refined by the transplant community as new information becomes available.Here we are presenting the results of a retrospective study designed to evaluate the 3 aforementioned score in stratification and prognostication of transplant outcome after a haploidentical HSCT (haplo-HSCT).Patients and MethodsWe included 220 adult patients (pts - 138 male, 82 female) who underwent a haplo-HSCT for hematologic malignancies, between 2006 and 2014 and were reported to our Institutional database. Risk assessment score and outcome analysis included all consecutive pts receiving an haplo-HSCT as 1st allogeneic transplantation. Pts receiving haplo-HSCT as 2nd or 3rd HSCT were excluded from the present analysis. Median age was 49 years (range, 15-77). The cohort included a broad representation of diseases (138/220 acute leukemia, 30 Hodgkin lymphoma); 62 pts were in complete remission at transplant, 158 were presenting active disease.Conditioning regimens mostly rely upon the combination of treosulfan plus fludarabine (201/220) and total body irradiation (range 200 - 400 cGy) was utilized in 52 patients. GVHD prophylaxis consisted mostly of an mTor inhibitor (rapamycin) combined with mycophenolate mofetil. The majority of patients received peripheral blood stem cells from a family haploidentical donor as stem cell source, while only 4 patients received bone marrow transplant.A written consent was given by pts allowing the use of medical records for research in accordance with the Declaration of Helsinki.ResultsThe median follow-up for survivors was 37 months (r 6-107). The overall survival (OS) at 2-y was 35% and the transplant related mortality at 100-days 23%. The 2y OS according to EBMT / HCT-CI / DRI risk score are reported in table 1.a and figure 1.The evaluation of the HCT-CI impact after DRI stratification was able to show a significant difference in outcome showing better survival for pts with low DRI score and low HCT-CI score as expected (table 1.b).DiscussionRefined DRI score and HCT-CI score predict survival after haplo-HSCT. The integrated application of refined DRI and HCT-CI may improve the definition of transplant eligibility for pts candidate to allogeneic HSCT form alternative donors including family haploidentical source.Table 1aEBMT score0-3% pts4-5%pts> 5%ptsp51%1734%5127%320.07HCT-CI score0-23-4>/= 548%5936%310%100.0001DRI scoreLow-IntermediateHighVery-High61%3227%515%170.0001Table 1bHCT-CI 0-4HCT-CI >/=5pDRILow-Intermediate64%0%0.0001DRIHigh-Very High29%0% [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Comparative Effectiveness of Fludarabine and Busulfan Versus Fludarabine and 400 cGy Total Body Irradiation Reduced Intensity Conditioning Regimens for Allogeneic Hematopoietic Cell Transplantation for AML/MDS

Reduced intensity conditioning for allogeneic hematopoietic cell transplantation (alloHCT) has become a standard approach for older patients and for those with co-morbidities that prohibit myeloablative conditioning. The optimal conditioning regimen for patients with AML or MDS undergoing such transplants is not clear. Therefore we performed a single center, retrospective analysis comparing busulfan (100 mg/m2/day on days -5, -4, -3, -2) and fludarabine (40 mg/m2/day on days -5, -4, -3, -2) (BuFlu) versus fludarabine (30 m2/day on days -5, -4, -3) and 400 cGy total body irradiation (200 cGy on days -1 and 0) (FluTBI) conditioning. All of the BuFlu transplants were performed as inpatient hospitalizations while all of those with FluTBI were performed as an outpatient. A total of 71 patients in two cohorts were included. The first study cohort consisted of 38 patients (23 AML, 15 MDS) who received FluTBI from 3/2004-4/2010, and the second included 33 (20 AML, 13 MDS) patients conditioned with FluBu from 6/2010-12/2013. The groups had similar disease risk and HCT comorbidity index scores. The BuFlu patients were older (median age 65 [range, 34-73] vs. 61[range, 44-70] years, P=0.03), but there were no other differences in patient or disease characteristics. All patients received peripheral blood stem cells as the graft source. The donor sources were 53% matched related (MRD) and 47% matched unrelated (MUD) for FluTBI patients and 58% MRD and 42% MUD for BuFlu patients. The BuFlu group received more red blood cell (RBC) transfusions (median 4 vs. 2, P=0.02), but there were no differences in platelet transfusion requirements. Platelet recovery was longer for patients receiving BuFlu than FluTBI (median 16 vs. 12 days, P=0.004), but there was no difference in cumulative incidence of neutrophil recovery. The respective median number of days hospitalized in the first 100 days post-transplant was 22 vs. 10 days (P<0.001) and in the first year was 40 vs. 16 days (P<0.001). Post-transplant outcomes are shown in the Table. The most common causes of death were relapse and infection for both the FluTBI (44% and 13%) and BuFlu (57% and 14%) groups. Quality of life assessments using the FACT-BMT were performed pre-alloHCT, at day 100, 6 months and 1 year. There was no difference in physical, social, emotional, and functional well-beings, additional concerns, trial outcome index or total score between the two groups at baseline or any of the follow-up timepoints. We conclude that alloHCT using FluTBI or BuFlu reduced intensity conditioning regimens results in comparable outcomes in patients with AML/MDS. The greater RBC transfusion requirement and need for inpatient hospitalization with the BuFlu regimen have implications for healthcare resource utilization. Future prospective investigation comparing these regimens with larger patient cohorts and cost-effectiveness analyses are warranted.Table 1Patient outcomesVariableFluTBI N (%)BuFlu N (%)P-valueT-cell complete donor chimerism29 (78)26 (81)0.83Graft failure/rejection3 (8)3 (9)0.87Grade II-IV acute GvHD13 (34)17 (52)0.24Grade III-IV acute GvHD3 (8)6 (18)0.21Any Chronic GvHD16 (42)14 (42)0.91Extensive chronic GvHD8 (21)13 (39)0.06CMV reactivation12 (32)13 (39)0.66Fungal Infection2 (5)1 (3)0.83Relapse (2-years)20 (53)17 (52)0.96100 day mortality13 (95% CI 6-29 )9 (95% CI 3-26 )0.59Non-relapse mortality (2-years)29 (95% CI 15-44)29 (95% CI 14-45)0.56Relapse mortality (2-years)34 (95% CI 20-49)36 (95% CI 20-53)0.86Overall survival (2-years)37 (95% CI 22-52)35 (95% CI 19-51)0.73 DisclosuresMajhail:Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

Abstract 3430: Toxicity and long-term outcomes of elderly patients with refractory or relapsed diffuse large B cell lymphoma undergoing autologous stem cell transplantation

Abstract Background: High-dose immunochemotherapy followed by autologous stem cell transplantation (Auto-SCT) is the standard treatment for fit individuals with refractory or relapsed diffuse large B cell lymphoma (DLBCL). We conducted a retrospective study to investigate toxicities and long-term clinical outcomes of elderly pts with relapsed or refractory DLBCL undergoing Auto-SCT. Methods: All pts with relapsed or refractory DLBCL undergoing Auto-SCT at our institution between November 2008 and November 2013 were included in the analysis. Prior treatment, secondary age-adjusted international prognostic index (saa-IPI), response to salvage treatment, Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), Cumulative Illness Rating Scale for Geriatrics (CIRS-G), and stem cell collection yields were recorded for each patient. Treatment complications and long-term clinical outcomes were compared between two age groups (65+ vs. &amp;lt;65 years). Results: 81 individuals underwent Auto-SCT for refractory or relapsed DLBCL. The median age was 60.1 years (24-75 years) and 26 individuals were over 65 years at the time of transplantation. The majority of pts (77%) received salvage therapy with rituximab, ifosfamide, carboplatin, and etoposide followed by AutoSCT with carmustine, cyclophosphamide, and etoposide conditioning. Pts aged greater than 65 years had similar baseline CIRS-G comorbidity scores compared to the younger cohort, but they were more likely to have HCT-CI scores of 3 or more (45% vs. 20%, p = 0.015). The advanced aged group had fewer stem cells collected (4.2 vs 6.1 x106 cells, p = 0.01), despite a trend toward higher number of apheresis sessions (3.2 vs 2.7 days, p = 0.13). However, the two groups experienced similar duration of Auto-SCT hospitalization (21.3 vs 20.9 days), time to neutrophil recovery (10.6 vs 10.4 days), and time to platelet recovery (13.1 vs. 13.1 days). The two groups also experienced similar frequency of blood stream infections, pneumonia, ICU transfers, and hospital readmissions (p = 0.61). One death occurred in each group within the first 100 days (100-day TRM 2.5%), with two additional aged individuals experiencing late deaths due to myeloid neoplasms. After adjusting for age, comorbidities and saa-IPI, response to salvage immunochemotherapy (CR vs. non-CR) remained the only significant predictor of PFS using proportional hazard modeling (HR 0.32, p = 0.002). Conclusions: While prospective clinical trials utilizing Auto-SCT for relapsed large B cell lymphomas have excluded pts over the age of 65, our results suggest selected individuals with advanced age experience an acceptable level of treatment toxicity and have clinical outcomes comparable to younger counterparts. Response to salvage immunochemotherapy, not age, appears to be the strongest predictor of long-term outcomes following Auto-SCT in the setting of relapsed DLBCL. Citation Format: Scott F. Huntington, Boyu Hu, Daniel J. Landsburg, Anthony R. Mato, Sunita D. Nasta, Stephen J. Schuster, Edward A. Stadtmauer, Jakub Svoboda. Toxicity and long-term outcomes of elderly patients with refractory or relapsed diffuse large B cell lymphoma undergoing autologous stem cell transplantation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3430. doi:10.1158/1538-7445.AM2015-3430

Patient age, remission status and HCT-CI in a combined score are prognostic for patients with AML undergoing allogeneic hematopoietic cell transplantation in CR1 and CR2

For AML, older age, advanced disease and increased hematopoietic cell transplant comorbidity index (HCT-CI) are associated with worse prognosis following allogeneic hematopoietic cell transplantation (HCT). This single-center retrospective study investigated the influence of pre-transplant characteristics on outcomes of 387 patients undergoing allogeneic HCT for AML in CR1 and CR2. The multivariable analysis model for overall survival (OS) included age (hazard ratio (HR)=2.24 for ages 31-64 years and HR=3.23 for age ⩾65 years compared with age ⩽30 years, P=0.003), remission status (HR=1.49 for CR2 compared with CR1, P=0.005) and HCT-CI score (HR=1.47 for ⩾3 compared with <3, P=0.005). Transplant year was significantly associated with OS (P=0.001) but this did not influence the model. A weighted score was developed with age ⩽30, CR1 and HCT-CI score <3 receiving 0 points each, and CR2 and HCT-CI score ⩾3 receiving 1 point each. Ages 31-64 received 2 points, age ⩾65 received 3 points. Scores were grouped as follows: scores 0-1 (low risk, n=36), score 2 (intermediate-low risk, n=147), score 3 (intermediate-high risk, n=141) and scores 4-5 (high risk, n=63) with 3-year OS of 71%, 55%, 42% and 29% for scores 0-1, 2, 3 and 4-5, respectively (P<0.0001). The score predicted nonrelapse mortality (P=0.03) but not cumulative incidence of relapse (P=0.18). This model should be validated for the pre-HCT assessment of AML patients in CR1 and CR2.

Prospective Validation of the Predictive Power of the Hematopoietic Cell Transplantation Comorbidity Index: A Center for International Blood and Marrow Transplant Research Study

Prospective validation of the hematopoietic cell transplantation–comorbidity index (HCT-CI) using contemporary patients treated with hematopoietic cell transplantation (HCT) across the Unites States is necessary to confirm its widespread applicability. We performed a prospective observational study including all patients (8115 recipients of allogeneic and 11,652 recipients of autologous HCT) who underwent a first HCT that was reported to the Center for International Blood and Marrow Transplant Research between 2007 and 2009. In proportional hazards models, increased HCT-CI scores were independently associated with increases in hazard ratios for nonrelapse mortality (NRM) (P < .0001) and overall mortality (P < .0001) among recipients of allogeneic HCT. HCT-CI scores of ≥3 were uniformly associated with higher risks for outcomes in both allogeneic and autologous HCT and in all subgroups, regardless of diagnoses, age, and conditioning intensity. Recipients of allogeneic HCT with scores of 1 and 2 who were ages < 18 years or were treated with lower intensity conditioning regimens had similar outcomes compared with those with a score of 0. Higher risks for overall mortality, but not for NRM, were observed among recipients of autologous HCT with scores of 1 and 2 versus 0. Our results confirm the validity the HCT-CI in both allogeneic and autologous HCT. The index should be used as a valid standard-of-care health measure in counseling patients for HCT, in clinical trial design, and in adjusting outcome analyses.