Hematopoietic Cell Transplantation-specific Comorbidity Research Articles

Pretransplantation Inflammatory and Nutritional Status in Elderly Allogeneic Hematopoietic Stem Cell Transplantation: Prognostic Value of C-Reactive Protein-to-Albumin Ratio

There are no clear criteria for selecting elderly patients with hematologic malignancies eligible for allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to evaluate inflammatory and nutritional status biomarkers as prognostic indicators of allogeneic HSCT in elderly patients. We compared the prognostic effects of 4 representative pretransplantation biomarkers: C-reactive protein-to-albumin ratio (CAR), Glasgow Prognostic Score (GPS), prognostic nutritional index (PNI), and albumin-to-globulin ratio (AGR). A total of 143 patients age ≥60 years who underwent their first allogeneic HSCT for a hematologic malignancy were enrolled between 2010 and 2020 in our single-center cohort. The median patient age was 65 years (range, 60 to 72 years). Pretransplantation high CAR, high GPS, and low PNI scores were associated with poor overall survival (OS), but the AGR was not associated with OS. Among the 4 biomarkers, CAR stratified OS most significantly (P < .001). Multivariate analyses identified only high CAR as an independent prognostic factor associated with OS (hazard ratio [HR], 1.98; P = .031) and showed that a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score ≥3 also was associated with OS (HR, 2.04; P = .012). High CAR was correlated with poor performance status, male sex, and high Disease Risk Index, but not with high HCT-CI score. When the patients were stratified into 3 groups according to a composite risk assessment using CAR and HCT-CI, the 3-year OS decreased significantly with increasing scores (82.8%, 50.3%, and 27.0%, respectively; P < .0001). In conclusion, CAR is the most useful prognostic indicator among the inflammatory and nutritional status biomarkers for allogeneic HSCT in elderly patients. Inflammatory and nutritional status in the elderly may be important prognostic factors for allogeneic HSCT independent of HCT-CI score.

Development of an umbilical cord blood transplantation–specific nonrelapse mortality risk assessment score

AbstractHigher rate of nonrelapse mortality (NRM) remains yet to be resolved in umbilical cord blood transplantation (UCBT). Considering that UCBT has some unique features compared with allogeneic hematopoietic cell transplantation from other graft sources, a UCBT-specific NRM risk assessment system is required. Thus, in this study, we sought to develop a UCBT-specific NRM Risk Assessment (CoBRA) score. Using a nationwide registry database, we retrospectively analyzed 4437 recipients who had received their first single-unit UCBT. Using the backward elimination method, we constructed the CoBRA score in a training cohort (n = 2687), which consisted of recipients age ≥55 years (score 2), hematopoietic cell transplantation–specific comorbidity index ≥3 (score 2), male recipient, graft-versus-host disease prophylaxis other than tacrolimus in combination with methotrexate, performance status (PS) 2 to 4, HLA allele mismatch ≥ 2, refined Disease Risk Index high risk, myeloablative conditioning, and CD34+ cell doses < 0.82 × 105/kg (score 1 in each). The recipients were categorized into 3 groups: low (0-4 points), intermediate (5-7 points), and high (8-11 points) groups according to the CoBRA score. In the validation cohort (n = 1750), the cumulative incidence of NRM at 2 years was 14.9%, 25.5%, and 47.1% (P < .001), and 2-year overall survival (OS) was 74.2%, 52.7%, and 26.3% (P < .001) in the low, intermediate, and high groups, respectively. In summary, the CoBRA score could predict the NRM risk as well as OS after UCBT. Further external validation will be needed to confirm the significance of the CoBRA score.

Acute kidney injury in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant: a cohort study

BackgroundAutologous hematopoietic stem cell transplant plays an important role in multiple myeloma (MM) treatment. Increasing incidence of MM and growing awareness of acute kidney injury (AKI) as a complication of hematopoietic stem cell transplant results in the need to better understand AKI in these patients. We aimed to evaluate incidence, risk factors and 5-year prognostic impact of AKI in MM patients undergoing autologous hematopoietic stem cell transplant.MethodsRetrospective cohort study. AKI was defined by the KDIGO classification using creatinine and urinary output criteria. We used survival analysis methods considering competing events for risk factors and disease-free survival, Cox proportional regression for overall survival and stepwise regression methods for multivariable models.ResultsWe analyzed data regarding 143 patients. The cumulative incidence of AKI and moderate-to-severe AKI was 49.7% and 14.1%, respectively. Factors with independent impact on AKI were obesity (HR: 1.83, 95% CI 1.07–3.11; p = 0.026), Hematopoietic cell transplantation—specific comorbidity index (HCT-CI) ≥ 2 (HR: 1.85, 95% CI 1.08–3.17), chronic kidney disease (CKD) (HR: 2.06, 95% CI 1.05–4.04), amyloidosis (HR: 2.25, 95% CI 1.25–4.06), mucositis grade 3–4 (HR: 2.19, 95% CI 1.25–3.86) and exposure to nephrotoxic drugs (HR: 2.0856, 95% CI 1.04–4.19). Moderate-to-severe AKI had an impact (HR: 1.62, 95% CI 1.15–2.31) on 5-year overall survival.ConclusionAcute kidney injury affects almost half of MM patients undergoing autologous hematopoietic stem cell transplantation, and reduction in urinary output allows early diagnosis in almost a quarter of the patients. Obesity, HCT-CI ≥ 2, CKD, amyloidosis, mucositis grade 3–4 and exposure to nephrotoxic drugs are significant risk factors. Moderate-to-severe AKI is associated with lower 5-year overall survival.Graphical abstract

Evolving Racial/Ethnic Disparities in AML Survival in the Novel Therapy Era: Real-World Evidence of Improved Survival in Older Patients with the Largest Improvement in Non-Hispanic Black Patients

Introduction: The approval of venetoclax (VEN)-based frontline therapy for acute myeloid leukemia (AML) in November 2018 marks a new era of AML care. Racial/ethnic disparities have been increasingly recognized in AML with historically inferior outcomes reported in non-Hispanic Black (NHB) patients relative to non-Hispanic White (NHW) patients. The advances of novel therapeutics offer an unprecedented opportunity to narrow the care gaps between patient groups; but they also create new challenges related to testing, clinical decision-making, and care coordination. Currently, little is known about the impact of race/ethnicity on the recent advances in AML management. We performed a retrospective analysis leveraging real-world data to examine the magnitude and mechanisms of racial/ethnic disparities in modern AML care. Methods: Adult patients from Flatiron Health, a nationwide, electronic health record derived, de-identified database, with AML diagnosed between January 2014 to December 2018 (Pre era) and January 2019 to October 2022 (Post era) who identified as NHW, NHB or Hispanic and received at least one line of anti-leukemic therapy were included. Overall survival (OS) was defined from the time of therapy initiation to the time of death. Multivariable Cox regression models were used to compare the hazards of death for NHB and Hispanics relative to NHW. Predicted survival curves were then computed. Pre-planned sensitivity analyses including patients with 1) no ethnicity information, 2) no anti-leukemic therapy, and 3) care gap &amp;gt;100 days from diagnosis to induction were performed. Results: 2998 patients in Pre era (2566 NHW, 221 NHB, 211 Hispanics) and 2098 patients in Post era (1809 NHW, 162 NHB, 127 Hispanics) were included. Older patients with more comorbidities and worse disease biology (Table 1) were treated in Post era. After adjusting for race/ethnicity, age and Hematopoietic Cell Transplant Specific Comorbidity Index (HCT-CI), patients in Post era had a 10% decrease in the hazard of death compared to Pre era (HR 0.90, 95% CI 0.83-0.96). The difference was driven by OS benefits observed in patients aged &amp;gt;70 years (HR 0.82, 95% CI 0.75-0.91). NHB and Hispanics were younger at diagnosis than NHW in both eras. Lower socioeconomic status was observed in NHB and Hispanics. No difference in ELN2017 risk stratification was observed (Table 1). After adjusting for age and HCT-CI, NHB had a 22% increased hazard of death compared to NHW in Pre era (HR 1.22, 95% CI 1.04-1.43); whereas Hispanics had comparable outcomes (HR 1.01, 95% CI 0.84-1.21). Strikingly, the survival disparity between NHB and NHW in Pre era was not observed in Post era with predicted 2-yr OS rate being 45.3% and 39.9%, respectively (HR 0.86, 95% CI 0.69-1.08) (Figure 1). Predicted 2-yr OS rates improved for NHB patients in both ≤70 years (42.3% vs. 53.2%) and &amp;gt;70 years group (13.6% vs. 37.0%). No significant change in OS was observed in Hispanics between Pre and Post era (Figure 1). Results of all sensitivity analyses were consistent with primary analyses. Molecular testing at diagnosis significantly differed by eras across race/ethnicity groups (overall 66.4% vs. 82.9%, p&amp;lt;0.001). In contrast, molecular testing occurred more frequently in NHB at relapse in Post era (45.6% vs. 65.4%, p=0.020). Despite being older, more NHW received allogeneic transplant than NHB in Pre era (25.8% vs. 18.6%, p=0.046). In Post era, NHW were more likely to receive VEN-based induction therapy (46.9%, 37.0%, 35.4% in NHW, NHB and Hispanic, respectively, p= 0.003). Among patients who were tested and qualified, no difference was observed in the use of gemtuzumab ozogamicin, CPX-351, FLT3 inhibitors or IDH1/2 inhibitors across race/ethnicity. Conclusions: In this large, real-world dataset, we demonstrate OS improvements in the era of modern AML care, particularly among patients &amp;gt;70 years though their outcomes remain inferior to younger patients. Intriguingly, the largest OS improvement was observed in NHB, where the OS disparity between NHB and NHW in Pre era appears to have been mitigated. Hispanics have not experienced similar OS improvement in modern AML care. Ongoing analyses are focused on examining the mechanisms of survival trends observed with focus on assessing the contribution(s) of patient-, disease biology- and treatment-related factors in order to identify potential targets for intervention. • Dr. Kelly Getz and Dr. Catherine Lai contributed equally

Impact of Diabetes Mellitus in Hospital Outcomes Among Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation: A NIS 2016 to 2020 Database Study

Impact of Diabetes Mellitus in Hospital Outcomes among Patients with Multiple Myeloma undergoing stem cell transplantation: A NIS 2016 to 2020 database Study. Background. Diabetes Mellitus (DM) is one of the comorbidities included in the Hematopoietic Cell Transplant-Specific Comorbidity Index (HCT-CI), which predicts the risk of non-relapse mortality (NRM) and overall mortality (OM) after transplantation. Therefore, they refrained from getting an Autologous stem cell transplant (ASCT) due to the concern of higher toxicity. However, limited data exist to assess this association. In this analysis, we intend to find the impact of DM on hospital outcomes in MM undergoing ASCT. Methods: A retrospective analysis of the NIS database was conducted using International Classification of Diseases (ICD-10) codes to identify hospitalization with ASCT for multiple myeloma and obesity with BMI &amp;gt; 30 kg/m2. STATA version MP14.2 was used for analysis. We used Fischer's exact test to compare proportions, the student's t-test to compare continuous variables, and multivariate regression analysis to calculate the adjusted odds ratio after controlling age, gender, primary payer, and CCI. Transplant complication includes (transplant rejection, transplant failure, and transplant infection). Results: Among 31,390 hospitalizations, 5475 (17.44%) were Diabetic. The mean age to get ASCT was 63 vs. 61, P &amp;lt; 0.001) with DM and without DM. Both groups had male predominance, with Caucasians being the most common race. The mean Charlson comorbidity index (CCI) in DM was 3 vs. 2.32 without DM. After Multivariate analysis, we found ICU admission (AOR: 0.28, 95% CI: 0.14-0.54, P &amp;lt;0.001), length of hospital stay (16.53 vs. 16.79, P &amp;lt;0.001) and acute kidney injury (AOR: 0.70, 95% CI: 0.56-0.87, P = 0.02) was significantly decreased with DM. However, there was no significant difference in the rate of blood transfusion (AOR: 0.87, 95% CI: 0.68-1.11, P = 0.87), transplant complication (AOR: 0.66, 95% CI: 0.42-1.01, P = 0.06), hospital mortality (AOR: 0.45, 95% CI: 0.19-1.03, P = 0.06). The only increase in the patient with DM was Mean hospital charges ($206,796.4 vs. $200,878.3, P = 0.013). Conclusion: This analysis shows that while some complications were decreased, blood transfusion rate and hospital mortality were not significantly affected. The study highlights the potential implications of DM in this patient population and warrants further investigation to individualize and optimize transplant outcomes.

Applicability and validation of different prognostic scores in allogeneic hematopoietic cell transplant (HCT) in the post-transplant cyclophosphamide era

We investigated the predictive capacity of six prognostic indices [Karnofsky Performance Status (KPS), Hematopoietic Cell Transplant-Specific Comorbidity Index (HCT-CI), Disease Risk Index (DRI), European Bone Marrow Transplantation (EBMT) and Revised Pre-Transplantation Assessment of Mortality (rPAM) Scores and Endothelial Activation and Stress Index (EASIX)] in 205 adults undergoing post-transplant cyclophosphamide (PTCy)-based allo-HCT. KPS, HCT-CI, DRI and EASIX grouped patients into higher and lower risk strata. KPS and EASIX maintained appropriate discrimination for OS prediction across the first 2 years after allo-HCT [receiver operating characteristic curve (area under the curve (AUC) > 55 %)]. The discriminative capacity of DRI and HCT-CI increased during the post-transplant period, with a peak of prediction at 2 years (AUC of 61.1 % and 61.8 %). The maximum rPAM discriminative capacity was at 1 year (1-year AUC of 58.2 %). The predictive capacity of the EBMT score was not demonstrated. This study validates the discrimination capacity for OS prediction of KPS, HCT-CI, DRI and EASIX in PTCy-based allo-HCT.

Adverse impact of delay of platelet recovery after autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma and multiple myeloma

Background aimsThe prognostic impact of platelet recovery after autologous hematopoietic cell transplantation (AHCT) on clinical outcomes remains to be elucidated. We aimed to clarify the impact of platelet recovery on clinical outcomes, risk factors of delayed platelet recovery and the necessary dose of CD34+ cells for prompt platelet recovery in each patient. MethodsUsing a nationwide Japanese registry database, we retrospectively analyzed clinical outcomes of 5222 patients with aggressive non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). ResultsAt a landmark of 28 days after AHCT, a delay of platelet recovery was observed in 1102 patients (21.1%). Prompt platelet recovery was significantly associated with superior overall survival (hazard ratio [HR] 0.32, P < 0.001), progression-free survival (HR 0.48, P < 0.001) and decreased risks of disease progression (HR 0.66, P < 0.001) and non-relapse/non-progression mortality (HR 0.19, P < 0.001). The adverse impacts of a delay of platelet recovery seemed to be more apparent in NHL. In addition to the dose of CD34+ cells/kg, disease status, performance status and the hematopoietic cell transplant-specific comorbidity index in both diseases were associated with platelet recovery. We then stratified the patients into three risk groups according to these factors. For the purpose of achieving 70% platelet recovery by 28 days in NHL, the low-, intermediate- and high-risk groups needed more than 2.0, 3.0 and 4.0 × 106 CD34+ cells/kg, respectively. In MM, the low-risk group needed approximately 1.5 × 106 CD34+ cells/kg, whereas the intermediate- and high-risk groups required 2.0 and 2.5 × 106 CD34+ cells/kg to achieve about 80% platelet recovery by 28 days. ConclusionsA delay of platelet recovery after AHCT was associated with inferior survival outcomes.

Validation of the Transplant Conditioning Intensity (TCI) Score for Allogeneic Hematopoietic Cell Transplantation

Introduction: Since non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT) is influenced by the conditioning regimen, it is essential to precisely calculate its intensity for any patient. Therefore, the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) registry previously developed the Transplant Conditioning Intensity (TCI) score to define conditioning regimens based on the sum of the doses (weight scores) for every component of the pre-transplantation regimen. HCT patients (pts) were stratified by a 3-index scheme with a low [1-2], intermediate [2.5-3.5] or high [4-6] TCI-score. (Bone Marrow Transplantation 2020; 55:1114) When tested in a large registry dataset of acute myeloid leukemia (AML) pts >45 years of age, TCI grouping was highly predictive for early and 2-year NRM, and better compared with the classical 2-index reduced intensity conditioning/ myeloablative conditioning (RIC/MAC) classification. The aim of the current study was to validate using a distinct dataset, the ability of the original TCI classification scheme to predict post-HCT NRM. Methods: TCI score was applied to a timely distinct cohort reported to the EBMT as the one used to establish the TCI classification scheme. We tested the impact of TCI in predicting early (day 180) NRM (defined as any death without previous relapse) in 55-75 years of age AML first complete remission (CR-1) pts who were transplanted between 2018 and 2021. Included pts were allografted with peripheral blood stem cells (PBSC, 96.4%) or bone marrow (BM, 3.6%) from a matched sibling donor (MSD, 25%) or unrelated donor (UD, 75%). NRM at 2 years was a secondary endpoint. Results: 4,312 AML pts (median age 63.4, interquartile range 59.5-67.2) were assigned to a TCI category, as previously described. 49% of the pts received a low [1-2], 47% an intermediate [2.5-3.5] but only 4% of the pts received a high [4-6] TCI-score regimen. As expected, there was an inverse relationship between age, Karnofsky status and hematopoietic cell transplant-specific comorbidity index (HCT-CI) and TCI group (p<0.0001). Besides a higher prevalence of MSD transplantations in the high (40%) as compared to low (21.6%) and intermediate (26.4%) TCI-groups (p<0.0001), pts were well balanced within TCI groups regarding other transplant and patient characteristics. The day (d)100, d180 and 2-year NRM ranged from 4.8-12.5%, 8.9-17%, and 17.4-23.9% between low, intemediate and high TCI scores, respectively. In univariate analysis, TCI provided a highly significant risk stratification for early and 2-year NRM (p<0.0001 for all pairwise comparisons between groups) (Figure 1). In the multivariate Cox regression analysis adjusted for age, Karnofsky status, HCT-CI and other variables, there was a significant increase in risk of early NRM with each TCI group (Table 1). Compared to low TCI, pts receiving intermediate and high score TCI regimens had a significantly increased risk for d180 NRM (hazard ratio [HR] 1.34, 95% CI, 1.03-1.74, p=0.029 and HR 2.37, 1.39-4.06, p<0.002, respectively). The HRs for d180 NRM pts receiving a high TCI [4-6] score regimen was 1.77 (1.06-2.97, p=0.029) when compared to the intermediate TCI [2.5-3.5] group. As expected, early NRM was also significantly influenced by incremental age, Karnofsky status score <90 and HCT-CI >=3. TCI grouping was also significantly associated with overall NRM. Similar results were found when the analysis was restricted to pts aged between 55 and 65 years (N=2,640). There was good concordance between RIC/MAC and low/high TCI score grouping, whereas 49% of the MAC pts and 51% of the RIC pts were re-classified as having received a reduced toxicity conditioning regimen with a TCI score of 2.5-3.5. Conclusion: Here, we validated in an independent patient cohort, the recently proposed 3-group TCI score for its ability to predict early NRM in AML pts >55 years of age. TCI predicts early NRM independently of other known prognostic factors such as age, Karnofsky, or HCT-CI. Compared to the current RIC/MAC classification model, the TCI provides a finer and more precise tool which may be easily calculated for any patient to offer safer transplantation especially in older and unfit pts. TCI may be used as a new, well-defined, and standard terminology for conditioning intensity in registry databases, in the literature and in clinical trials. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Risk and Predictive Factors for Candidemia After Allogeneic Hematopoietic Cell Transplantation: JSTCT Transplant Complications Working Group

Although antifungal prophylaxis that covers Candida species is a standard of care in allogeneic hematopoietic cell transplantation (HCT), candidemia mainly caused by non-albicans Candida species still occurs and is associated with a high mortality rate. This study aimed to evaluate the risk factors for candidemia after allogeneic HCT. Particularly, we evaluated the impact of patient factors such as hematopoietic cell transplantation–specific comorbidity index (HCT-CI) and performance status (PS) in addition to well-recognized risk factors including donor type, delayed engraftment, and graft-versus-host disease (GVHD). By using data from a Japanese transplant registry database, we analyzed 26,236 pediatric and adult patients with hematological malignancies who underwent their first allogeneic HCT. The posttransplant period was divided into early (days 0-40), late (days 41-100) and very late (days 101-365) phases. The 1-year cumulative incidence of candidemia was 1.8%. When we analyzed pretransplantation factors, age ≥40 years (hazard ratio [HR] 1.85), male (HR 1.34), HCT-CI (HCT-CI 1-2, HR 1.56; HCT-CI ≥ 3, HR 2.21), PS ≥ 2 (HR 2.01), high-risk disease (HR 1.78) and donor type including HLA-mismatched related donor (MMRD) (HR 1.96), HLA-mismatched unrelated donor (HR 2.05), and cord blood (CB) (HR 2.85) were significantly associated with an increased incidence of candidemia. Focusing on the early phase (days 0-40), HCT-CI, PS, high-risk disease and CB transplantation together with engraftment and severe acute GVHD significantly affected the development of candidemia. In the late phase (days 41-100), higher HCT-CI, male, and donor type including MMRD, and CB were associated with the occurrence of candidemia together with acute GVHD and disease relapse. In the very late phase (days 101-365), HCT-CI ≥ 3 and high-risk disease significantly affected the occurrence of candidemia together with acute and chronic GVHD, and disease relapse. In addition to well-recognized risk factors including donor type, engraftment and GVHD, patient factors such as HCT-CI and PS were associated with the development of candidemia, which suggests that severely ill patients with transplantation-associated complications are more likely to develop candidemia.

The effect of comorbidity on survival and collected CD34 + cell counts in autologous hematopoietic stem cell transplant patients

ObjectiveIn this study, we aimed to report the effectiveness of hematopoietic cell transplantation–specific comorbidity index (HCT-CI) and GATMO scores in predicting overall survival (OS) who underwent autologous stem cell transplantation (ASCT). Material and methodsThe data of 263 MM and 204 lymphoma patients who underwent ASCT in the last 11 years were retrospectively analyzed. ResultsNeutrophil engraftment time, thrombocyte engraftment time and collected CD34+ cell counts were similar in MM patients with HCT-CI>2 and HCT-CI≤2 (all p>0.05). Although the estimated median OS of MM patients with HCT-CI ≤2 tended to be higher than those with HCT-CI>2, this difference was not statistically significant (52.8 vs 45 months, p=0.172). No effect of GATMO score on CD34 + count, engraftment times and OS in MM patients was detected (p>0.05). The effect of HCT-CI score on lymphoma patients was examined, it was found that the neutrophil engraftment time was longer (p=0.039) and the number of collected CD34+ cells was lower (p=0.02) in patients with HCT-CI>2 than those with HCT-CI≤2. While the estimated median OS of lymphoma patients with HCT-CI≤2 was 51.5 months, the estimated median OS of patients with HCT-CI>2 was 9.5 months (p=0.012). When lymphoma patients were divided into four groups according to their GATMO scores, the OS of the four groups was found to be different from each other (p<0.001). ConclusionHCT-CI and GATMO scores predict OS in lymphoma patients but not MM patients.

The Simplified Comorbidity Index: a new tool for prediction of nonrelapse mortality in allo-HCT

AbstractIndividual comorbidities have distinct contributions to nonrelapse mortality (NRM) following allogeneic hematopoietic cell transplantation (allo-HCT). We studied the impact of comorbidities individually and in combination in a single-center cohort of 573 adult patients who underwent CD34-selected allo-HCT following myeloablative conditioning. Pulmonary disease, moderate to severe hepatic comorbidity, cardiac disease of any type, and renal dysfunction were associated with increased NRM in multivariable Cox regression models. A Simplified Comorbidity Index (SCI) composed of the 4 comorbidities predictive of NRM, as well as age >60 years, stratified patients into 5 groups with a stepwise increase in NRM. NRM rates ranged from 11.4% to 49.9% by stratum, with adjusted hazard ratios of 1.84, 2.59, 3.57, and 5.38. The SCI was also applicable in an external cohort of 230 patients who underwent allo-HCT with unmanipulated grafts following intermediate-intensity conditioning. The area under the receiver operating characteristic curve (AUC) of the SCI for 1-year NRM was 70.3 and 72.0 over the development and external-validation cohorts, respectively; corresponding AUCs of the Hematopoietic Cell Transplantation–specific Comorbidity Index (HCT-CI) were 61.7 and 65.7. In summary, a small set of comorbidities, aggregated into the SCI, is highly predictive of NRM. The new index stratifies patients into distinct risk groups, was validated in an external cohort, and provides higher discrimination than does the HCT-CI.

A New Risk Assessment Tool for Allogeneic Hematopoietic Stem Cell Transplantation

Introduction:Allogeneic hematopoietic stem cell transplantation (HSCT), can be curative for many hematologic disorders. However, HSCT is still associated with significant risks. HSCT outcomes are dependent on patient, disease and transplant related factors. There are a number of assessment tools being used to predict outcomes. Some use patient related variables such as the hematopoietic cell transplantation specific comorbidity index (HCT-CI), some use disease-related variables such as the disease-risk index (DRI) and some others incorporate combined variables. We aimed to incorporate disease, patient comorbidities, donor, and transplant characteristics into one comprehensive prognostic model to predict 2 year disease-free survival (DFS).Methods:273 consecutive patients (162 males, 111 females) receiving an initial HSCT from 2010 and 2016 were identified and retrospectively analyzed. Median age was 56 years (range 18-76 years) and a broad representation of hematologic disorders (119 AML, 46 ALL, 60 MDS, 18 NHL, 30 other) were included. All pts received peripheral blood as graft source. The majority received an unrelated donor transplant (166) and were conditioned with a myeloablative regimen (199).The dataset was randomly split in a 2:1 ratio to create training and testing dataset prior to data analysis. Variables under consideration as predictors of 2 year disease-free survival included: patient (age, sex, blood type, CMV status, Karnofsky Performance Status, HCT-CI), donor (age, sex, blood type, CMV status), disease (type, time since diagnosis, Disease Risk Index), and transplant (prep regimen, year of transplant, related/unrelated, match/mismatch) characteristics. Using the training dataset, a lasso penalized Cox regression was applied with the penalty parameter being derived as the mean of 1,000 iterations of 10-fold cross-validation. Patient risk scores was computed from the model and used to stratify patients based on a median split of risk scores; survival differences were evaluated using the log-rank test. Model performance was evaluated in the training and testing datasets by deriving time-dependent AUC curves, evaluating survival differences by risk strata, and comparing predicted to observed survival probabilities at 2 years.Results:Karnofsky Performance Status (<90, 90+), Disease Risk Index (Low, Intermediate/High), HCT-CI (Low, Intermediate/High), prep regimen (RIC/Non-myeloablative, myeloablative), and donor age (<30, 30+) were selected by the model. More specifically, lower performance status (HR 1.3), higher Disease Risk Index (HR 1.4), higher HCT-CI (HR 1.3), RIC/non-myeloablative prep regimen (HR 1.1), older donor age (HR 1.1) were associated with poorer disease-free survival. The prognostic model derived from the training dataset demonstrated good discrimination for the prediction of 2 year DFS with a median AUC value of 0.72 (IQR 0.69-0.73). When applied to the testing dataset, an AUC value of 0.73 was obtained. Across time, results were relatively consistent between 1 and 2 years post-transplant. A significant difference between the two risk strata was evidenced in the training and testing dataset (Figure 1, p<0.01). Comparison of predicted and observed survival probabilities at 2 years demonstrated agreement in both datasets.Conclusion:This comprehensive prognostic model is able to stratify patients into high risk and low risk groups with significantly different outcome. The inclusion of additional variables in the model increased accuracy (higher AUC) relative to existing models, which highlights the importance of taking into consideration additional constructs when trying to predict DFS. Further independent validation of our findings is necessary. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Grip Strength Changes in Bone Marrow Transplant Patients

Emerging evidence that cancers survivors may experience premature aging has prompted epidemiology research aimed at the characterization of key premature aging phenotypes. Physical functioning data relevant for premature aging phenotype classification in cancer survivors, however, remain scarce. We assessed the burden of dynapenia, a key sarcopenia indicator, and muscle strength loss in the understudied population of bone marrow transplant (BMT) patients. This study involved secondary analyses of data from patients who underwent bone marrow transplant (BMT) in a cancer Institute in South Florida (June 2018-April 2019) with traditional hematopoietic cell transplantation specific comorbidity index (HCT-CI) scores and other relevant information. T-tests for paired data assessed pre- vs. post-BMT changes in grip strength (GS) (n=9). Prevalence of dynapenia (GS<27Kg and <16Kg) in pre-BMT (n=20) and post-BMT (n=9) periods were calculated. Median age [25th-75th percentiles] age was 61 [55-68] years old. Fifty-percent were females. GS and HCT-CI scores were not correlated. Mean GS loss after BMT was 6.4 Kg (95% confidential interval: 2.5-10.4 Kg, p-value=.003) in post-BMT (median-time-after-BMT: 90 days) minus pre-BMT (median-time-before-BMT: 62 days) comparison. Proportion with dynapenia increased from 10% (1/10) to 20% (1/5) in women, and 10% (1/2) to 75% (3/4) in men. We observed substantial muscle strength loss and dynapenia burden in patients who underwent BMT. Considering that dynapenia is a major, potentially modifiable risk factor for frailty, which is not captured by HCT-TI, we speculated that dynapenia-related targeted assessments and interventions – preventive and/or rehabilitative – could offer complementary approaches for treatment enhancement in BMT patients.

Pretransplant Plasma Brain Natriuretic Peptide and N-Terminal Pro-Brain Natriuretic Peptide Are More Useful Prognostic Markers of Overall Survival after Allogeneic Hematopoietic Cell Transplantation Than Echocardiography

Pretransplant Plasma Brain Natriuretic Peptide and N-Terminal Pro-Brain Natriuretic Peptide Are More Useful Prognostic Markers of Overall Survival after Allogeneic Hematopoietic Cell Transplantation Than Echocardiography

Autologous Stem Cell Transplantation for Multiple Myeloma Patients Aged ≥ 75 Treated with Novel Agents

Introduction Autologous stem cell transplantation (ASCT) has been used for treating multiple myeloma (MM) for over three decades and is generally reserved for patients younger than 65 years of age. The definition of transplant eligible is ill-defined and different centers have different policies to determine which patients are transplant eligible. Some centers have an age cut-off, others use clinical judgment, and some use various frailty scores (a scoring system based on comorbidities and physical and cognitive assessments) aiming to objectively assess transplant eligibility. There are limited data about outcomes in patients ≥ 75 years. Aim To report on outcomes of ASCT in a cohort of patients with MM aged 75 years or older. Methods Retrospective study of all consecutive MM patients aged ≥ 75 years that underwent ASCT at Mayo Clinic, Rochester, Minnesota. Stem cell transplantation at our center is routinely performed as an outpatient, with patients being hospitalized when deemed clinically necessary upon physician review. Results Between October 2005 and March 2020, 46 patients aged 75 years or older, received an ASCT at Mayo Clinic, Rochester. The median hematopoietic stem cell transplantation specific comorbidity index (HCT-CI) was 0 (range 0-6) with 8 patients having HCT-CI of 5 or 6. Median time from diagnosis to ASCT was 6.45 months (IQR 5.2-10.52) and 54% received reduced intensity conditioning with melphalan 140 mg/m2. All patients except one (that was treated with dexamethasone only) received induction with novel agents (listed in table 1) and 6 patients (13%) received doublet induction. All others received triplet induction. 46% of patients completed the ASCT without requiring hospitalization and 54% (n=25) of patients required hospitalization with a median duration of hospital admission of 9 days (IQR 5-13). Reasons for hospitalization included fever or infection (32%), cardiac arrhythmia (36%) and dehydration (32%). Overall response rate was 100% with a complete response seen in 57% of patients and 16 patients achieving MRD negative sCR. Median overall survival and progression free survival for the cohort were 82 months and 33 months, respectively. One patient died within 100 days of transplant representing a 2% 100-day mortality rate. Univariable cox regression model that evaluated the effect of gender, high risk cytogenetics, hemoglobin, renal function and melphalan dose did not detect any variable that was predictive of OS or PFS (Table 3). Conclusions ASCT is efficacious and can be safely delivered in the outpatient setting in carefully screened patients aged 75 or above. An arbitrary cutoff for age should not be used to exclude patients from ASCT, rather a careful assessment of "physiological age" including performance status and co-morbidities is required by an experienced treating team. Disclosures Kumar: Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Cellectar: Other; Carsgen: Other, Research Funding; Dr. Reddy's Laboratories: Honoraria; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; Kite Pharma: Consultancy, Research Funding; Novartis: Research Funding; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; MedImmune: Research Funding; BMS: Consultancy, Research Funding; Tenebio: Other, Research Funding; Karyopharm: Consultancy; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genecentrix: Consultancy; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Adaptive Biotechnologies: Consultancy. Dispenzieri:Pfizer: Research Funding; Janssen: Research Funding; Alnylam: Research Funding; Intellia: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Dingli:Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Karyopharm Therapeutics: Research Funding; Apellis: Consultancy; Sanofi-Genzyme: Consultancy; Millenium: Consultancy. Kapoor:Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Celgene: Honoraria; Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; GlaxoSmithKline: Research Funding. Gertz:Prothena: Other: personal fee; Medscape: Other: personal fee, Speakers Bureau; Appellis: Other: personal fee; Alnylam: Other: personal fee; Ionis/Akcea: Other: personal fee; Janssen: Other: personal fee; Research to Practice: Other; Sanofi: Other; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Proclara: Other; Springer Publishing: Patents &amp; Royalties; Celgene: Other; Physicians Education Resource: Other: personal fee; Aurora Bio: Other; Amgen: Other: personal fee; Annexon: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Abbvie: Other.

Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents

AbstractAlthough novel agents (NAs) have improved outcomes for patients with chronic lymphocytic leukemia (CLL), a subset will progress through all available NAs. Understanding outcomes for potentially curative modalities including allogeneic hematopoietic stem cell transplantation (alloHCT) following NA therapy is critical while devising treatment sequences aimed at long-term disease control. In this multicenter, retrospective cohort study, we examined 65 patients with CLL who underwent alloHCT following exposure to ≥1 NA, including baseline disease and transplant characteristics, treatment preceding alloHCT, transplant outcomes, treatment following alloHCT, and survival outcomes. Univariable and multivariable analyses evaluated associations between pre-alloHCT factors and progression-free survival (PFS). Twenty-four-month PFS, overall survival (OS), nonrelapse mortality, and relapse incidence were 63%, 81%, 13%, and 27% among patients transplanted for CLL. Day +100 cumulative incidence of grade III-IV acute graft-vs-host disease (GVHD) was 24%; moderate-severe GVHD developed in 27%. Poor-risk disease characteristics, prior NA exposure, complete vs partial remission, and transplant characteristics were not independently associated with PFS. Hematopoietic cell transplantation–specific comorbidity index independently predicts PFS. PFS and OS were not impacted by having received NAs vs both NAs and chemoimmunotherapy, 1 vs ≥2 NAs, or ibrutinib vs venetoclax as the line of therapy immediately pre-alloHCT. AlloHCT remains a viable long-term disease control strategy that overcomes adverse CLL characteristics. Prior NAs do not appear to impact the safety of alloHCT, and survival outcomes are similar regardless of number of NAs received, prior chemoimmunotherapy exposure, or NA immediately preceding alloHCT. Decisions about proceeding to alloHCT should consider comorbidities and anticipated response to remaining therapeutic options.

Predominant low Hematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) score in a Mexican referral center: a selection bias caused by limited-resources?

IntroductionTo date, many studies have validated the Hematopoietic Cell Transplantation Specific Comorbidity Index (HCT-CI) scoring system in allogeneic hematopoietic stem cell transplantation (allo-HSCT), but studies from developing countries remain scarce. Objective: The aim of this study was to evaluate and categorize Mexican patients using the HCT-CI at a referral center.MethodsOne hundred and nineteen consecutive patients undergoing allo-HSCT at the National Institute of Medical Sciences and Nutrition in Mexico City were included. Patients were classified according to the HCT-CI scores.ResultsThe median age was 31 years and most were males (56%). Most patients had hematological malignancies (73%) and a low HCT-CI score (72%). The non-relapse mortality and survival were predicted according to the score.ConclusionsThis is one of the few studies to evaluate the HCT-CI in adults with HLA-matched donors in a developing country and our findings suggest that the high percentage of patients with a low HCT-CI scores, contrary to international reports, could be explained by different comorbidities and demographics, but mainly due to stricter filters applied to HSCT candidates and consequently, a potential selection bias caused by limited resources.

Prospective evaluation of alternative donor from unrelated donor and cord blood in adult acute leukemia and myelodysplastic syndrome.

A prospectively registered observational study was conducted to assess the significance of allogeneic hematopoietic stem cell transplantation from highly HLA-matched unrelated donors (UD) and cord blood (CB) on outcomes in adult acute leukemia (AL) and myelodysplastic syndrome (MDS). Between 2007 and 2015, 231 transplant-eligible patients were registered for a phase 2 study of alternative donor transplantation. After registration, a sufficient time period was given to find appropriate UD. Patients received CB transplantation (CBT) if an appropriate UD was unavailable. In total, 119 patients received CBT (106 AL and 13 MDS) and 91 patients received UD transplantation (UDT) (86 AL and 5 MDS). The median age was 39 years in both groups. The primary objective was overall survival (OS); secondary objectives included cumulative incidences of non-relapse mortality (NRM) and relapse, and disease-free survival. Diagnosis, disease status at transplantation, refined disease risk index, and hematopoietic cell transplant-specific comorbidity index did not differ between UDT and CBT. In multivariate analyses, graft source was not a significant risk factor for all objectives. In adjusted analyses, UDT and CBT showed similar OS, NRM, and relapse in this prospective study. CB can be a comparable alternative stem cell source to UD by achieving a timely transplant.

Outcomes of Allogeneic Stem Cell Transplant for Elderly Patients with Hematologic Malignancies

Reduced-intensity conditioning (RIC) regimens, improved HLA matching, and better supportive care allow allogeneic stem cell transplant (alloSCT) to be offered to older patients. Only a small percentage of eligible patients between ages 65 and 74 years actually undergo alloSCT, and comprehensive outcome data from the aging population are still lacking. We examined the outcome of older patients who underwent alloSCT using melphalan-based RIC for hematologic malignancies at our institution. We identified 125 patients older than 65 years (median, 69; range, 66 to 77) who underwent matched related donor, matched unrelated donor, or combined haploidentical/umbilical cord alloSCT between 2012 through November, 2017. Among them, 52 (41.6%) and 70 (56%) had, respectively, intermediate and high/very high Center for International Blood and Marrow Transplant Research (CIBMTR) disease risk index (DRI). One hundred six patients (85%) received fludarabine/melphalan-based RIC regimen with either antithymocyte globulin (ATG) or alemtuzumab. The median time to neutrophil engraftment was 13 days (range, 8 to 37) and platelet engraftment 17 days (range, 9 to 169). The cumulative incidence of nonrelapse mortality was 11.5% at 100 days and 30.1% and 34.8% at 1 and 2 years, respectively. The cumulative incidence of relapse was 35% and 40% at 1 and 2 years. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) at day 100 and 6 months was 29.5% and 34.5%, and chronic GVHD at 6, 12, and 24 months was 2.5%, 5.2%, and 6.3%, respectively. With a median follow-up of 32 months, the 1-, 2-, and 3-year progression-free survival (PFS) was 34.6%, 24.4%, and 16.5%, respectively. The graft GVHD-free survival was 24.6%, 16.1%, and 9.3%, respectively. The 1-, 2-, and 3-year overall survival (OS) was 44.5%, 30.7%, and 26.5%, respectively. In multivariable analysis, low albumin was predictive of poor PFS and OS and high hematopoietic cell transplantation-specific comorbidity index, and CIBMTR DRI was predictive of worse graft GVHD-free survival. Among long-term survivors the median Karnofsky performance status was 80. Older patients, even when referred with advanced disease, can benefit from melphalan-based alloSCT with HLA-matched or alternative donor sources without discernible impact of donor source on outcome. Using alemtuzumab- or ATG-based in vivo T cell depletion, the incidence of chronic GVHD is extremely low. Performance status in survivors is excellent. Better predictors for outcome in this patient population need to be identified.

Non-Myeloablative Allogeneic Stem Cell Transplant in Acute Myeloid Leukemia: Graft-Versus-Host Disease Potentiates Graft-Versus-Leukemia Effect and Improves Overall Survival

Introduction: Non-myeloablative conditioning regimens enable elderly and younger patients with significant comorbidities to undergo allogenic stem cell transplant (allo SCT). These regimens allow for the benefit of graft-versus-leukemia (GVL) effect with reduced toxicity. A retrospective analysis of 94 patients with acute myeloid leukemia (AML) who received a non-myeloablative transplant with fludarabine (25 mg/m2 days -7 through -3)/cyclophosphamide (1000 mg/m2 days -7 and -6) (Flu/Cy) conditioning was conducted to evaluate patient outcomes. Methods: Ninety-four patients with AML underwent non-myeloablative allo SCT with Flu/Cy conditioning at Penn State Cancer Institute between 2007 and 2015 were retrospectively analyzed. The patients were deemed ineligible for myeloablative or reduced intensity conditioning transplants due to advanced age or significant comorbidities. Most unrelated donor patients (n=69) received tacrolimus/sirolimus/methotrexate as graft-versus-host disease (GVHD) prophylaxis. Overall survival (OS) and disease-free survival (DFS) were assessed with Kaplan-Meier survival curves and log rank tests, and non-relapse mortality (NRM) and relapse rates (RR) were assessed with cumulative incidence of competing events and Gray test. Cox proportional hazard regression with stepwise selection was used for multivariate analysis. Results: Patients with AML underwent Flu/Cy conditioning for allo SCT from either a matched related donor (MRD) (n =16), matched unrelated donor (MUD) (n=54), or mismatched unrelated donor (MMUD) (n=24). Evaluation of AML status immediately prior to allo SCT identified 79 patients in complete remission, 10 patients with non-remission, and 5 patients with primary induction failure. There were 11 patients with hematopoietic cell transplantation specific comorbidity index (HCT-CI): 0, 14 patients with HCT-CI: 1-2, and 69 patients with HCT-CI: ≥3. Post-transplant analysis identified: 48 patients with grade 0, 31 patients with grade I, and 15 patients with grade II-IV acute graft-versus-host disease (aGVHD). Furthermore, 52 patients were without chronic GVHD (cGVHD), 15 experienced limited cGVHD, and 13 experienced extensive cGVHD. One-year OS and DFS were 41.3% (95% CI: 31.3-51%) and 27.7% (95% CI: 18.7-37.4%), respectively. One-year NRM and RR were 12.9% (95% CI: 0.68-21%) and 59.5% (95% CI: 48.2-69.1%). There were no statistically significant differences in NRM between patients with varying comorbidity indices. One-year OS for patients in complete remission versus non-remission prior to transplant was 45.3% versus 20.0% (p&lt;0.01), and was significantly greater in patients with grade I versus grade II-IV aGVHD (45.2% versus 17.8%, p&lt;0.05). Patients with cGVHD showed a lower RR compared to patients without cGVHD (1-year RR 20.4% vs 48.5%, p&lt;0.05). Patients who achieve a chimerism ≥90% within 100 days of transplant achieved a better OS and lower RR compared to patients with a chimerism &lt;90% (1-year OS 51.3% versus 21.4%, p&lt;0.01; 1-year RR 44.0% vs 89.3%, p&lt;0.01, respectively). Multivariate analysis identified grade I aGVHD (versus grade II-IV, p&lt;0.01), cGVHD (versus no cGVHD, p&lt;0.05), and chimerism ≥90% (versus &lt;90%, p&lt;0.05) as independent factors for improved OS. Conclusions: The primary endpoint for this retrospective analysis was OS following non-myeloablative allo SCT for AML utilizing Flu/Cy conditioning. Although RR was high (59.5%), this conditioning regimen resulted in rapid stem cell recovery and low NRM. There were no significant differences in NRM between patients with lower (0, or 1-2) and higher (≥3) HCT-CI and patients receiving MRD, MUD or MMUD. This confirms that Flu/Cy conditioning is safe, especially for patients with multiple comorbidities and receiving MMUD. This analysis also identified a significant improvement in OS for patients with grade I as compared to grade II-IV aGVHD. Also, patients with cGVHD showed a significantly reduced RR. Collectively, the improved survival for patients with grade I aGVHD and cGVHD may be associated with a more robust GVL effect. Additionally, patients who achieve a higher chimerism showed a reduced RR. This study highlights the tolerability of Flu/Cy and the importance of balancing GVHD and GVL effects; future studies are needed to evaluate the addition of maintenance therapies to overcome higher RR occurring with this regimen. Disclosures Naik: Celgene: Other: Advisory board. Zheng:Pfizer: Research Funding. Claxton:Daiichi Sankyo Co. and Ambit Biosciences Corp, Astellas Pharma, Novartis Pharmaceuticals, Incyte Corporation, Cyclacel Pharmaceuticals, Inc, Celegene Corporation, Medimmune, Inc, Merck Sharp &amp; Dohme Corp., Gilead Sciences, Inc.: Research Funding.