High Hematopoietic Cell Transplantation Comorbidity Index Research Articles

HEALTHCARE UTILIZATION IN OLDER ADULTS (≥70 YEARS) UNDERGOING CELLULAR THERAPY FOR HEMATOLOGIC MALIGNANCIES

Abstract Increasingly, older adults are receiving hematopoietic cell transplant (HCT) and chimeric antigen receptor T-cell therapy (CAR-T), intensive therapies for treatment of hematologic cancers which typically require prolonged hospital admissions. Older adults are at high risk of increased healthcare utilization and complications of prolonged hospitalization [Mudge, J Am Geriatr Soc, 2019]. We identified patients age ≥70 years who received HCT or CAR-T in a primary outpatient transplant program at Vanderbilt University Medical Center between 1/1/19 and 12/31/20. Healthcare utilization, including all visits and admissions, was captured from the start of conditioning chemotherapy through early post-therapy. Thirty-eight patients met inclusion criteria; 26 (68%) received autologous HCT (autoHCT), 7 (18%) allogenic HCT (alloHCT), and 5 (13%) CAR-T. Twenty-four patients (63%) had high HCT-Comorbidity Index (HCT-CI). Eighteen (69%) autoHCT, 6 (86%) alloHCT, and no CAR-T patients had at least one unplanned admission. The median number of total hospital days (LOS) was 7.5 (2-14), 8 (4-62), and 9 (7-9) days, respectively. One-year mortality was 12% (3) in autoHCT, 43% (3) in alloHCT, and 0% in CAR-T. Low performance status and high HCT-CI did not correlate with LOS (p=0.58 and p=0.16, respectively) or number of outpatient visits (p=1, p=0.19). In conclusion, most patients who received auto- or alloHCT in a planned primary outpatient setting experienced at least one unplanned admission. LOS duration varied widely with shorter LOS among autoHCT patients. Further research is needed to identify factors among older adults (≥70 years) at risk of increased healthcare utilization during HCT or CAR-T.

Haploidentical Hematopoietic Cell Transplantation of Ex Vivo Tcrαβ-Depleted Grafts with CD45RA-Depleted Memory T Cell Add-Back Reduces Chronic Graft-Versus-Host Disease and Results in Favourable Gvhd-Relapse Free Survival: 5-Year Follow-up of 107 Patients Treated in a Multicenter Study in Singapore

Background: Haploidentical hematopoietic cell transplantation (HCT) provides an alternative option for patients without HLA-matched donors. Graft-versus-host disease (GVHD), engraftment failure, and infectious complications are main causes of non-relapse mortality (NRM). We hypothesized that selective depletion of TCRαβ+ and CD45RA+ naïve T cells will permit hematopoietic engraftment while effectively reducing GVHD and providing donor immune reconstitution through adoptive transfer of donor's mature NK cells, γδ T cells and CD45RO+ memory T cells. Methods: Mobilized PBSC products were divided into two fractions in 8-9 : 1-2 ratio and depleted using CliniMACS device after labelling with TCRαβ and CD45RA reagents (Miltenyi Biotec, Bergish-Gladbach, Germany) respectively. All except 13 patients received the standard conditioning regimen of fludarabine 160mg/m2 divided daily over 4 days, thiotepa 10mg/kg divided twice daily for 1 day, and melphalan 70 - 140 mg/m2 for 1 day, in combination with either total lymphoid irradiation 6 Gy (n=58) or 7.5 Gy (n=12) over 3 equal fractions, total body irradiation of 2 Gy (n=24), or thymoglobuline (n=2). Short term GVHD prophylaxis was given for 30 days to 1 patient using MMF, 95 using tacrolimus, and 2 using sirolimus. Results: Between January 2017 and July 2022, we transplanted 107 patients, including 100 adults (median age, 52 years; range 19- 70) and 7 children (median age, 13 years, range 7 - 17), with high risk AML (n=60), ALL (n=22), MDS (n=10), plasma cell neoplasm (n=3), mast cell leukemia (n=1), acute undifferentiated leukemia (n=1), CMMoL (n=2), CML (n=2), MPN (n=1) and lymphoma (n=5). Patients were infused with TCRαβ and CD45RA depleted grafts containing a median of 6.18 x 106 (range 2.13 - 20.78) CD34+ cells/kg, 0.00 x 104 (range 0 - 0.97) CD45RA+CD3+ cells/kg, and 1.21 x 106 (range 0.15 - 11.67) CD45RO+CD3+ cells/kg. TCRαβ depleted graft fraction contained a median of 0.37 x 104 (range 0 - 11.30) TCRαβ+ cells/kg, and 7.72 x 106 (range 0.62 - 42.00) TCRγδ+ cells/kg. Only 1 patient experienced primary graft failure with no secondary graft failures. All others had engraftment of ANC > 500 cells/µL at median of 12 days (range 8 - 25) and PLT > 20,000 cells/µL at median of 11 days (range 7 - 17). 10 patients with high donor-specific HLA antibodies (DSA) titres engrafted successfully after desensitisation with plasma exchange, rituximab, immunoglobulin, and irradiated donor buffy coat infusion (n=1). 38 patients (35%) developed acute GVHD of grade II - IV, with a cumulative incidence (CI) of grade II-IV and grade III-IV of 34%, and 12% respectively, at 180 days. Chronic GVHD was seen in only 4 patients at a 2-year CI of 5 % . 1-year CI of non-relapse mortality (NRM) and relapse were 18.4 % and 17.2%, respectively. 4 of the 22 NRM were attributed to aGVHD. Viral reactivation included CMV (n=39), HHV-6 (n=28), EBV (n=19), and adenovirus (n=8). 11 patients (11%) out of the 15 infection-related death (15%) occurred within 180 days. At a median follow up of 23 months (range 0.3- 67.1) in surviving patients, 2-year overall (OS), event-free (EFS), and GVHD-free/relapse-free (GRFS) survival were 69.9 %, 58.7 %, and 57.3 %, respectively (Figure 1). In multivariate analysis, HCT-comorbidity index (HCT-CI) has shown significant impact on OS (p=0.008), EFS (p=0.03), and NRM (p=0.002). Disease risk index (DRI) also showed significant impact on OS (p=0.042), EFS (p=0.02) and relapse (p=0.04). In contrast, NRM was only influenced by HCT-CI (p=0.002). In the subset analysis of 63 patients (adults, n= 58; children, n=5) with favorable HCT-CI score of 0/1 and low/intermediate risk DRI, the 2-year OS, EFS, and GRFS were 75.0 %, 68.6%, and 68.0 %, respectively (Figure 2). Conclusions: Our preliminary results suggest that RIC haplo-HCT with TCRαβ and CD45RA+ depleted grafts allow successful allograft in patients with high-risk haematological malignancies lacking suitable matched donors, including patients with high levels of DSA. Acute GVHD was generally abortive, leading to low incidence of chronic GVHD and favorable GRFS. Best outcomes are seen in patients with favourable HCT-CI and low/intermediate risk DRI. Further efforts are needed to reduce the risk of infection-related death in patients with high risk HCT-CI, and relapse risk in patients with high risk DRI, through optimization of conditioning regimen intensity, anti-microbial prophylaxis or prophylactic infusion of memory-cell DLI. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Novel Prediction Models of Nonrelapse Mortality in Patients Specific to Each Reduced-Intensity Conditioning before Allogeneic Hematopoietic Stem Cell Transplantation: A Multicenter Analysis from the Kanto Study Group for Cell Therapy (KSGCT)

Introduction Despite recent developments on various transplantation procedures and supportive therapy, nonrelapse mortality (NRM) after allogeneic stem cell transplantation (allo-SCT) remains an essential issue. In choosing the appropriate regimen for allo-SCT, decision-making information that considers the complexity of different risk factors is vital. The Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), which was initially derived and validated by investigators at the Fred Hutchinson Cancer Research Center to predict NRM, has become a widely validated tool for predicting outcomes in many transplant settings (Sorror et al. Blood. 2005). It can also stratify patients for the risk of other outcomes, including overall survival and graft versus host disease. Patients with a high HCT-CI score tend to prefer allo-SCT with reduced-intensity conditioning (RIC). Conversely, for those who has a low HCT-CI score but prefer allo-SCT with RIC, a prognostic indicator is unnecessary. Furthermore, the risk factors for NRM may differ among various conditioning regimens. Therefore, the current study aimed to establish a new prognostic model for patients specific to each RIC regimen before allo-SCT. Methods We performed a retrospective cohort study to develop prognostic models of NRM in patients conditioned with fludarabine/ busulfan (Flu/Bu) or fludarabine/melphalan (Flu/Mel). We selected patients who had leukemia and lymphoma in remission or had untreated or stable myelodysplastic syndrome and experienced initial allo-SCT relapse between 2007 and 2017 in the Kanto Study of Group for Cell Therapy. The primary outcome measure was 2-year NRM. Furthermore, we evaluated variables such as patient age, albumin value (Alb), liver function, renal function, respiratory function, ejection fraction (EF), C-reactive protein, stem cell source, donor type, usage of antithymocyte globulin, performance status (PS), recipient/donor sexes, time interval from diagnosis to transplant, usage of total body irradiation (TBI), and HCT-CI score. To identify a set of variables for Fine-Gray competing risk regression model, we used an Akaike Information Criterion (AIC)-based variable selection procedure. We assigned weights to individual parameters according to their prognostic significance in Fine-Gray models. The identified model's discriminative ability was assessed by Harrell's C-statistic. Results Among the 430 patients analyzed, 202 received Flu/Bu, and 228 received Flu/Mel. In Flu/Bu and Flu/Mel, the mean age was 60.6±6.2 and 57.8±8.5 years, the HCT-CI score ≤ 2 was observed in 77.2% and 78.1%, and 2-year NRM was found in 19.7% and 17.9% of the patients, respectively. Before transplantation, the most dominant parameters in Flu/Bu were Alb < 4.0 g/dL and EF < 55 %, whereas those in Flu/Mel were PS > 0, Alb < 4.0 g/dL, stem cell source, recipient/donor sexes and usage of TBI. Each of the abovementioned parameters, including PS > 0, was scored based on regression coefficients. To evaluate the 2-year NRM, we divided the total scores into several risk groups. In the Flu/Bu group, the NRM was 10.3 % in low (score 0, n = 69), 19.2 % in intermediate-1 (score 1, n =46), 25.4 % in intermediate-2 (score 2-3, n = 81) and 50.0 % in high (score 4-5, n = 6) scores. In the Flu/Mel group, the NRM was 8.6 % in low (score 0-2, n = 48), 15.2 % in intermediate (score 3-4, n = 139), and 37.4 % in high (score 5-8, n = 41) scores (Figure). Higher scores were strongly associated with worse NRM and survival. These models showed good discrimination, with C-statistic values of 0.64 in Flu/Bu and 0.67 in Flu/Mel. Conclusions Our prognostic models for NRM estimation can distinguish patients with a high NRM risk. To our knowledge, these models are the first prognostic models used to estimate NRM for standard-risk patients specific to each RIC regimen. This new simple index may help predict NRM and choose an appropriate conditioning regimen before allo-SCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A high hematopoietic cell transplantation comorbidity Index (HCT-CI) does not impair outcomes after non-myeloablative allogeneic stem cell transplantation in acute myeloid leukemia patients 60 years or older

For most acute myeloid leukemia (AML) patients an allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance of cure. The introduction of less toxic non-myeloablative conditioning (NMA) regimes enabled older and/or comorbid patients to be consolidated with an allogeneic HSCT. While the hematopoietic cell transplantation comorbidity index (HCT-CI) predicted outcomes in many younger patient cohorts its impact in older AML patients receiving NMA-HSCT remains unknown. Here we analyzed 289 AML patients 60 years or older (median age 66, range 60-77 years) undergoing NMA-HSCT (2 or 3 Gray total body irradiation and 3 days of fludarabine 30 mg/m2). HCT-CI risk was low, intermediate, or high in 36%, 31%, and 33% of patients, respectively. Non-relapse mortality (NRM), cumulative incidence of relapse (CIR), and overall survival (OS) did not differ between HCT-CI groups. The HCT-CI also did not impact outcomes when considering the European LeukemiaNet 2017 risk at diagnosis or the measurable residual disease (MRD) status at HSCT. Notably, MRD-negative older NMA-transplanted AML patients had a beneficial OS of 49% after 5 years. Since a higher HCT-CI did not impair outcomes, age or comorbidities per se should not impede NMA-HSCT, presenting a feasible consolidation option for this group of AML patients.

Room for Improvement: A 20-Year Single Center Experience with Allogeneic Stem Cell Transplantation for Myelodysplastic Syndromes

Allogeneic stem cell transplantation (allo-SCT) remains the only curative therapeutic approach for patients with myelodysplastic syndromes (MDS). The aim of the study was to assess the efficacy/safety of allo-SCT as well as to identify factors influencing post-transplant survival. One hundred and two MDS patients (median age: 48 years; 57 males) who underwent allo-SCT were retrospectively evaluated. Twenty seven patients were transplanted from HLA-matched sibling and 75 patients received grafts from unrelated donors. Peripheral blood was a source of stem cell for 79 patients. Reduced intensity conditioning was used in 64 subjects. Acute and chronic graft versus host disease (GvHD) developed in 61 and 19 of patients, respectively. In total, 61 patients have died. The causes of deaths included infectious complications (n = 30), steroid-resistant GvHD (n = 17), MDS relapse (n = 9) and transformation to AML (n = 5). Non-relapse mortality and cumulative incidence of relapse at 2 years were 49.8% and 9%, respectively. 41 patients are alive at last contact and present full donor chimerism. 38 patients remain in complete hematological remission (CHR), 3 patients had CHR with incomplete platelet recovery. Median follow-up from diagnosis of MDS and transplantation are 27.1 months and 7 months respectively. Overall survival and relapse-free survival were 41% at 2 years. Increased serum ferritin level > 1000 ng/ml, presence of acute GvHD, grades III–IV acute GvHD and high hematopoietic cell transplantation-comorbidity index were found to negatively influenced survival. Allo-SCT for MDS is feasible procedure with a proportion of patients to be cured.

Social Vulnerability Is a Clinically Important Predictor of Outcomes after Allogeneic Hematopoietic Cell Transplantation

Introduction: Allogeneic hematopoietic cell transplantation (HCT) is an established treatment for malignant and non-malignant hematologic diseases. However, HCT is not without risk; rates of non-relapse mortality (NRM) remain high during the first year after transplantation. Clinical prediction models have been developed to identify those at increased risk for NRM after HCT, but the impact of social determinants of health on transplant outcomes has not been well characterized. To address this gap, we evaluated the relationship between census tract-level social vulnerability and 1y NRM following HCT. Methods: Using a retrospective cohort design, this study included 1,602 patients living in California (CA) who underwent a first allogeneic HCT between 2013-2019 at City of Hope. Demographic, insurance, disease, treatment, and survival information was abstracted from the medical records. Social vulnerability according to the census tract was measured using the Social Vulnerability Index (SVI), a tool developed by the Center for Disease Control. SVI comprises 4 themes (socioeconomic status [SES], household composition & disability, minority status & language, and housing & transportation) constructed using 15 social and environmental variables from the US Census. This study used the overall SVI and individual theme scores which were ranked across the CA census tracts as percentiles; the scores ranged from 0 (least vulnerable) to 100 (most vulnerable). Scores were assigned to patients using their address at the time of HCT. Fine-Gray multivariable regression was used to evaluate the association between SVI, tertiles of SVI, and 1y NRM, adjusted for age at HCT, performance status, relapse risk (RR), human leukocyte antigen (HLA) match, and HCT-Comorbidity Index (HCT-CI). We also performed subgroup analysis to examine the risk of NRM across combined SVI and HCT-CI categories: 1) lower two SVI tertiles (low social vulnerability) and low (<3) HCT-CI score (reference); 2) low social vulnerability and high (≥3) HCT-CI score; 3) high social vulnerability (upper SVI tertile) and low HCT-CI score; 4) high social vulnerability and high HCT-CI score. Results: Median age at HCT for the cohort was 52.0 years (IQR 33.0-63.0); 55.8% were male; 44.6% were non-Hispanic white; 59.1% had private insurance. The most common diagnosis was acute myeloid leukemia (40.7%) and 54.1% received reduced intensity conditioning. In the first year after HCT, 357 patients died (NRM 15.3% [n=245], relapse-related 7.0% [n=112]). In multivariable analysis, there was a significant linear relationship between worsening overall SVI and the risk of 1y NRM (SVI coefficient=0.0056, 95% confidence interval [CI]: 0.001-0.010, p=0.017). Patients in the highest SVI tertile (most socially vulnerable) had a 1.4-fold (HR=1.41, 95%CI: 1.08-1.83, p=0.011) risk of 1y NRM compared to those in the lowest two SVI tertiles. When the 4 themes were evaluated individually, increased risk for 1y NRM was found for the highest SVI tertiles for SES (HR=1.43, 95% CI: 1.10-1.86, p=0.008), household composition & disability (HR=1.32, 95% CI: 1.02-1.71, p=0.036), and minority status & language (HR=1.40, 95% CI: 1.08-1.83, p=0.013). When the themes were considered together in one regression model, only the highest SVI tertile for SES retained significance. The one-year cumulative incidence of 1y NRM was highest (22.0%) for patients who had both high social vulnerability and a high HCT-CI score at HCT (Figure 1); in adjusted analysis, patients who had both high social vulnerability and HCT-CI scores were at a 1.6-fold (HR=1.64, 95% CI: 1.21-2.24, p=0.002) risk of 1y NRM compared to the rest of the patients. Conclusion: Among allogeneic HCT recipients, SVI, especially within the theme of SES, was an independent predictor of 1y NRM, after adjusting for RR, performance status, age at HCT, HLA match, and HCT-CI score. Patients with both the highest social vulnerability and high comorbidity had particularly increased risk of 1y NRM, suggesting that in addition to clinical risk factors, local social and environmental factors play an important role in health outcomes following HCT. These findings may inform more targeted approaches for needs assessment during and shortly after HCT, allowing for timely interventions to improve health outcomes in at-risk allogeneic HCT patients. [Display omitted] DisclosuresArtz: Radiology Partners: Other: Spouse has equity interest in Radiology Partners, a private radiology physician practice. Forman: Allogene: Consultancy; Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company.

HLA-Haploidentical Hematopoietic Cell Transplantation of Ex Vivo Tcrαβ-Depleted Grafts with CD45RA-Depleted Memory T Cell Add-Back in Adults and Children with Hematological Malignancies: 4-Year Follow-up of Multicenter Study in Singapore

Background: Haploidentical hematopoietic cell transplantation (HCT) provides an alternative option for patients without HLA-matched donors. Graft-versus-host disease (GVHD), engraftment failure, and infectious complications are main causes of non-relapse mortality (NRM). We hypothesized that selective depletion of TCRαβ+ and CD45RA+ naïve T cells will permit hematopoietic engraftment while effectively reducing GVHD and providing donor immune reconstitution through adoptive transfer of donor's mature NK cells, γδ T cells and CD45RO+ memory T cells.Methods: Mobilized PBSC products were divided into two fractions in 9:1 ratio and depleted using CliniMACS device after labelling with TCRαβ and CD45RA reagents (Miltenyi Biotec, Bergish-Gladbach, Germany) respectively. All except 6 patients received the standard conditioning regimen of fludarabine 160mg/m 2 divided daily over 4 days, thiotepa 10mg/kg divided twice daily for 1 day, and melphalan 70 - 140mg/m 2 for 1 day, in combination with either total lymphoid irradiation 6Gy (n=53) or 7.5Gy (n=12) over 3 equal fractions, or total body irradiation of 2Gy (n=17), or thymoglobulin (n=2). Short term GVHD prophylaxis was given for 30 days to 1 patient using MMF, 73 using tacrolimus, and 2 using sirolimus.Results: Between January 2017 and July 2021, we transplanted 85 patients, including 78 adults (median age, 48 years; range 20 - 70) and 7 children (median age, 13 years, range 7 - 17), with high risk AML (n=44), ALL (n=19), MDS (n=9), plasma cell neoplasm (n=4), mast cell leukemia (n=1), acute undifferentiated leukemia (n=1), CMMoL (n=2), CML (n=1) and lymphoma (n=2). Patients were infused with TCRαβ and CD45RA depleted grafts containing median of 6.19 x 10 6 (range 3.54 - 20.78) CD34+ cells/kg, 0.00 x 10 4 (range 0 - 0.97) CD45RA+CD3+ cells/kg, and 1.10 x 10 6 (range 0.15 - 11.67) CD45RO+CD3+ cells/kg. TCRαβ depleted graft fraction contained a median of 0.42 x 10 4 (range 0 - 11.30) TCRαβ+ cells/kg, and 7.61 x 10 6 (range 0.62 - 31.84) TCRγδ+ cells/kg. Only 1 patient experienced primary graft failure with no secondary graft failures. All others had engraftment of ANC > 500 cells/µL at median of 12 days (range 8 - 22) and PLT > 20,000 cells/µL at median of 11 days (range 7 - 17). 6 patients with high donor-specific HLA antibodies (DSA) titres engrafted successfully after desensitisation with plasma exchange, rituximab, and immunoglobulin.29 patients (34%) developed acute GVHD of grade II - IV (Gd II, n=20; Gd III, n=5; Gd IV, n=4), with a cumulative incidence (CI) of grade II-IV and grade III-IV of 31% (95% CI 21-42%) and 11% (95% CI 5-19%) respectively, at 100 days. Chronic GVHD was seen in only 4 patients at a 2-year CI of 6% (95% CI 2-13%).1-year CI of non-relapse mortality (NRM) and relapse were 22.7% (95% CI 13.9 - 32.9%) and 15.7% (95% CI 8.3 - 25.3%) respectively. 4 of the 17 NRM were attributed to aGVHD. Viral reactivation included CMV (n=32), HHV-6 (n=22), EBV (n=15), and adenovirus (n=8). 15 patients (17.6%) died of infection within 180 days, including 6 patients with fatal bacteraemia (bacteria, n=4; candidemia, n=2) and 1 patient from disseminated adenovirus infection. At a median follow up of 448 days (range 16- 1648) in surviving patients, 2-year overall (OS), event-free (EFS), and GVHD-free/relapse-free (GRFS) survival were 64.2 %, 54.0 %, and 49.0%, respectively (Figure 1).In multivariate analysis, only HCT-comorbidity index (HCT-CI) showed significant impact on OS (HR 3.38; 95% CI 1.42 - 8.02; p=0.0059), EFS (HR 2.62; 95% CI 1.18 - 5.76; p=0.0017), and NRM (HR 4.92; 95% CI 1.79 - 13.58; p=0.0021). Disease risk index (DRI) showed a trend in higher risk of relapse (HR 2.83; 95% CI 0.96 - 8.33; p=0.059). 2-year OS, EFS, and GRFS for the subset of 58 patients (adults, n=52; children, n=6) with HCT-CI score of 0 were 76.6 %, 63.4%, and 57.5 %, respectively (Figure 2).Conclusions: Our preliminary results suggest that RIC haplo-HCT with TCRαβ and CD45RA+ depleted grafts allow successful allograft in high-risk patients lacking suitable matched donors, including patients with high levels of DSA. Acute GVHD was generally abortive, leading to low incidence of chronic GVHD. Best outcomes are seen in patients with favourable HCT-CI. Further efforts are needed to reduce the risk of infection-related death in patients with high risk HCT-CI, and relapse in patients with high risk DRI, through optimization of anti-microbial prophylaxis or prophylactic infusion of memory-cell DLI. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Association of pre-existing comorbidities with outcome of allogeneic hematopoietic cell transplantation. A retrospective analysis from the EBMT

Risk assessment of allogeneic hematopoietic cell transplantation (allo-HCT) is hindered by the lack of current data on comorbidities and outcome. The EBMT identified 38,760 allo-HCT recipients with hematologic malignancies transplanted between 2010 and 2018 from matched sibling and unrelated donors with a full data set of pre-existing comorbidities. Multivariate analyses using the Cox proportional-hazards model including known risk factors for non-relapse mortality (NRM) were performed. We found that pre-existing renal comorbidity had the strongest association with NRM (hazard ratio [HR] 1.85 [95% CI 1.55–2.19]). In addition, the association of multiple pre-existing comorbidities with NRM was significant, including diabetes, infections, cardiac comorbidity, and pulmonary comorbidity. However, the HR of the association of these comorbidities with NRM was relatively low and did not exceed 1.24. Consequently, the risk of NRM was only moderately increased in patients with a high hematopoietic cell transplantation comorbidity index (HCT-CI) ≥ 3 (HR 1.34 [1.26–1.42]). In the current EBMT population, pre-existing non-renal comorbidities determined NRM after allo-HCT to a much lesser extent as compared with the underlying HCT-CI data. Improvements in management and supportive care as well as higher awareness based on the use of HCT-CI may have contributed to this favorable development.

Assessing Individual Comorbidities in Elderly Non-Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplant — Obesity Associated with Inferior Outcomes

Assessing Individual Comorbidities in Elderly Non-Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplant — Obesity Associated with Inferior Outcomes

Sarcopenia Is a Clinically Relevant and Independent Predictor of Adverse Outcomes after Allogeneic Hematopoietic Cell Transplantation

Introduction: Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for a growing number of adults with acute leukemia (lymphoblastic [ALL], myeloid [AML]) or myelodysplastic syndrome (MDS). However, the potent anti-leukemic effect of HCT needs to be balanced by the high risk of non-relapse mortality (NRM) during the first year after HCT. Pre-HCT risk calculators such as the HCT comorbidity index (HCT-CI) facilitate stratification of NRM risk, but high inter-user variability and limited predictive power has limited the routine use of this tool in the clinical setting. Sarcopenia (loss of lean muscle mass) is an important cause of age-related functional decline in the general population, and is a predictor of NRM in patients with solid tumors, independent of age or pre-treatment comorbidity. The prognostic importance of sarcopenia on post-HCT outcomes has received limited attention.Methods: Using a retrospective cohort design, 947 consecutive patients with acute leukemia or MDS, age ≥18y, who underwent a first HCT between 2007 to 2014 at City of Hope were included in the study. Skeletal muscle area was ascertained from pre-HCT abdominal computed tomography (CT) scans using image analysis software (SliceOmatic; Tomovision, Quebec, Canada). This report is limited to 868 (91.7%) patients with CT scans ≤150 days (d) prior to HCT (median: 28d [range: 0-150]). Measurements were made by trained researchers blinded to patient demographics and HCT outcome; 3rd lumbar vertebra was used as a landmark because of its high correlation with whole-body muscle mass (J Clin Oncol 2016 34:1339). Skeletal muscle index (SMI) was calculated as the ratio of skeletal muscle area (cm2) divided by height (m)2. Sex and body mass index-specific cutoff values of low SMI were used to identify patients with sarcopenia (J Clin Oncol 2013 31:1539). NRM at 1y was the primary endpoint, defined as time from HCT to death unrelated to relapse or disease progression; relapse/disease progression was considered a competing risk event. Length of hospitalization was the secondary endpoint, defined as time from HCT to hospital discharge; death prior to discharge was considered a competing risk event. Cumulative incidence of NRM was calculated taking into consideration competing risk. We used multivariable Fine and Gray regression analysis to calculate the hazard ratio (HR) estimates and 95% confidence intervals (CI), adjusted for relevant covariates (demographic, disease risk, donor source, conditioning intensity).Results: Median age at HCT was 51y (range: 18-74); 54.1% were male; 52.0% were non-Hispanic white; Diagnoses: ALL (N=233 [26.9%]), AML (N=468 [53.9%]), MDS (N=167 [19.2%]); 52.5% had a high (≥3) HCT-CI score; Donor type: matched related (43.7%), matched unrelated (51.2%), other (5.2%); 50.7% underwent myeloablative conditioning; 43.4% developed grades 2-4 acute graft versus host disease; 294 (34%) had sarcopenia pre-HCT and 299 (26%) patients died within the first year of HCT - NRM (N=132), relapse-related (N=97). Adjusted cumulative incidence of NRM at 1-year was higher for sarcopenic compared to non-sarcopenic patients (32.9% vs. 20.9%, p=0.003; Figure). Sarcopenia was associated with a 1.7-fold (HR=1.68 [CI: 1.27-2.39]) risk of NRM at 1y when compared to those with normal muscle mass. Median length of hospitalization was also longer (30d vs. 28d; p<0.001) in sarcopenic patients. Sarcopenia and HCT-CI : The risk of NRM was highest among patients with sarcopenia and a high HCT-CI score (HR=2.05 [CI: 1.23-3.42]); a high HCT-CI score with normal muscle mass was not associated with excess NRM risk (HR=1.30 [CI: 0.79-2.16]; referent: low HCT-CI, normal muscle mass).Conclusion: Sarcopenia is an important and independent predictor of NRM after HCT, with potential additional downstream impacts on health-economic outcomes such as length of hospitalization. Taken together, these data form the basis for real-time decision making prior to HCT (e.g. conditioning intensity, pre-habilitation), or during HCT (e.g. dietary optimization, increased supportive care services, resistance training), setting the stage for strategies to decrease the risk of treatment-related complications after HCT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognostički faktori kod starijih bolesnika sa akutnom mijeloidnom leukemijom

Introduction: Acute myeloid leukemia (AML) is characterized by pathological proliferation of myeloid lineages. It predominantly occurs in patients over 60 years of age, whose outcome is considerably worse, as compared to younger patients. Aim: The aim of the study was the analysis of the clinical characteristics of older patients with AML and their impact on the following: achieving complete remission (CR), overall survival (OS), early mortality (EM), and relapse. Materials and methods: This retrospective study included 94 patients with AML, treated with chemotherapy and palliative treatment, whose information was taken from their medical histories, upon treatment. The following clinical features were analyzed as risk factors for OS, CR, relapse and EM: leukocytes, the level of serum lactate dehydrogenase (LDH), performance status on the ECOG (Eastern Cooperative Oncology Group) scale, the European LeukemiaNet cytoplasmic risk group, the HCT-CI (hematopoietic cell transplantation - comorbidity index) and the NPM1/ FLT3-ITD (nucleophosmin 1/FLT3-internal tandem mutation) molecular status. For the identification of prognostic factors, the Cox regression analysis was used. Results: The average age of the patients was 69 years (range: 65 - 87). CR was achieved in 23 (46%) of the 50 patients (53.2%) who received intensive chemotherapy, with relapse occurring in 17/23 patients (73.9%). EM was reported in 17 patients (18.1%). Patients with ECOG PS &gt; 2 had a statistically significantly lower OS than patients with ECOG PS &lt; 2 (p = 0.030). Patients with HCT-CI &gt; 3 had a poorer OS than patients with HCT-CI &lt; 3 (p = 0.040). Serum LDH &gt; 450 U/I was found to be a factor, i.e., marker of unfavorable prognosis for the OS, as compared to LDH &lt; 450U/I (p = 0.044). Conclusion: The conclusion is that older AML patients with poorer ECOG PS, high HCT-CI, increased LDH levels have a poorer OS.

Outcomes and factors impacting use of axicabtagene ciloleucel in patients with relapsed or refractory large B-cell lymphoma: results from an intention-to-treat analysis

Data on real-world outcomes of axicabtagene ciloleucel (axi-cel) therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL) are limited. In this intent to treat (ITT) analysis, we reviewed records of 38 consecutive patients with R/R LBCL for whom axi-cel was intended. Twenty-seven (71%) patients received axi-cel and 11 (29%) did not. Patients in the non-axi-cel group had a higher hematopoietic cell transplantation comorbidity index (HCT-CI) (median 4 vs. 2, p = .04). Median overall survival for the ITT, axi-cel and non-axi-cel group was 10 (95% CI, 3.7 to 13), 13 (95% CI, 7.7 to N.R.) and 1 (95% CI, 0.4 to 3.7) month(s) respectively. Factors limiting axi-cel use were disease progression, sepsis, manufacturing failure and socioeconomic barrier in 6 (55%), 3 (27%), 1 (9%) and 1 (9%) patient(s) respectively. Additional strategies are needed to ensure all LBCL patients for whom chimeric antigen receptor (CAR) T-cell therapy is prescribed can receive this treatment.

Novel Prediction Models of Nonrelapse Mortality in Patients Specific to Each Myeloablative Conditioning before Allogeneic Hematopoietic Stem Cell Transplantation: A Multicenter Analysis from the Kanto Study Group for Cell Therapy (KSGCT)

Introduction Despite recent developments on various transplantation procedures and supportive therapy, nonrelapse mortality (NRM) after allogeneic stem cell transplantation (allo-SCT) remains an essential issue. In choosing the appropriate regimen for allo-SCT, decision-making information that considers the complexity of different risk factors is vital. The Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), which was initially derived and validated by investigators at the Fred Hutchinson Cancer Research Center to predict NRM, has become a widely validated tool for predicting outcomes in many transplant settings (Sorror et al. Blood. 2005). It can also stratify patients for the risk of other outcomes, including overall survival and graft versus host disease. Patients with a high HCT-CI score tend to prefer allo-SCT with reduced-intensity conditioning. Conversely, for those who prefer allo-SCT with myeloablative conditioning (MAC) and has a low HCT-CI score, a prognostic indicator is unnecessary. Furthermore, the risk factors for NRM may differ among various conditioning regimens. Therefore, the current study aimed to establish a new prognostic model for patients specific to each MAC regimen before allo-SCT. Methods We performed a retrospective cohort study to develop prognostic models of NRM in patients conditioned with cyclophosphamide/total body irradiation (Cy/TBI) or busulfan/cyclophosphamide (Bu/Cy). We selected patients who had leukemia and lymphoma in remission or had untreated or stable myelodysplastic syndrome and experienced initial allo-SCT relapse between 2007 and 2017 in the Kanto Study of Group for Cell Therapy (KSGCT). The primary outcome measure was 2-year NRM. Furthermore, we evaluated variables such as patient age, albumin, liver function, renal function, respiratory function, ejection fraction (EF), C-reactive protein (CRP), stem cell source, donor type, antithymocyte globulin use, performance status, recipient/donor sexes, time interval from diagnosis to transplant, and HCT-CI score. To identify a set of variables for Cox proportional hazards, we used an Akaike Information Criterion (AIC)-based variable selection procedure. We assigned weights to individual parameters according to their prognostic significance in Cox proportional hazard models. The identified model's discriminative ability was assessed by Harrell's C-statistic calculated using the bootstrap method. Results Among the 555 patients analyzed, 338 received Cy/TBI, and 217 received Bu/Cy. In Cy/TBI and Bu/Cy, the median age was 39 (11-60) and 44 (18-62) years, the HCT-CI score ≤ 2 was observed in 82.1% and 87.6%, and 2-year NRM was found in 13.5% and 16.0% of the patients, respectively. Before transplantation, the most dominant parameters in Cy/TBI were abnormal liver function (AST/ALT or bilirubin &amp;gt;upper limit of normal) and albumin value &amp;lt; 4.5g/dL, whereas those in Bu/Cy were age &amp;gt;40 years, EF &amp;lt; 65 %, and CRP ≥ 0.2 mg/dL. Internal validation with bootstrap resampling showed good discrimination, with C-statistic values of 0.70 (95% CI: 0.69-0.71) in Cy/TBI and 0.68 (95% CI: 0.67-0.69) in Bu/Cy. Each of the abovementioned parameters, including age &amp;gt;40 years, was scored as 1 point. To evaluate the 2-year NRM, we divided the total scores into three risk groups. In the Cy/TBI group, the NRM was 6.9% in low (score 0-1, n = 186), 19.5% in intermediate (score 2, n = 127), and 35.3% in high (score 3, n = 25) scores. In the Bu/Cy group, the NRM was 8.3% in low (score 0-1, n = 93), 21.7% in intermediate (score 2, n = 98), and 29.8% in high (score 3, n = 26) scores (Figure). Higher scores were strongly associated with worse NRM and survival. Conclusions Our prognostic models for NRM estimation can distinguish patients with a high NRM risk. To our knowledge, these models are the first prognostic models used to estimate NRM for standard-risk patients specific to each MAC regimen. This new simple index may help predict NRM and choose an appropriate conditioning regimen before allo-SCT. Figure 1 Disclosures Nakasone: Takeda Pharmaceutical: Honoraria; Otsuka Pharmaceutical: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; Janssen Pharmaceutical: Honoraria; Eisai: Honoraria; Chugai Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria. Fujisawa:Takeda Pharmaceutical Company Limited.: Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau; Otsuka Pharmaceutical: Speakers Bureau; Pfizer Japan Inc.: Research Funding, Speakers Bureau; Bristol-Myers Squibb Company: Speakers Bureau; Novartis Pharma KK: Research Funding, Speakers Bureau; Celgene: Speakers Bureau; Janssen Pharmaceutical K.K: Speakers Bureau; NIPPON SHINYAKU CO.,LTD.: Research Funding. Nakaseko:Novartis Pharma KK: Speakers Bureau; Pfizer Japan Inc.: Speakers Bureau. Kanda:Novartis: Honoraria; Kyowa Kirin: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceuticals: Honoraria; Alexion Pharmaceuticals: Honoraria; Shire: Honoraria; Daiichi Sankyo: Honoraria; Ono Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria, Research Funding; Mochida Pharmaceutical: Honoraria; Mundipharma: Honoraria; Sanofi: Honoraria, Research Funding; Meiji Seika Kaisha: Honoraria; Shionogi: Research Funding; Otsuka: Honoraria, Research Funding; Celgene: Honoraria; Chugai Pharma: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Janssen: Honoraria; Astellas Pharma: Honoraria, Research Funding; Sumitomo Dainippon Pharma: Honoraria; Pfizer: Honoraria, Research Funding; Merck Sharp &amp; Dohme: Honoraria.

Combining the Disease Risk Index and Hematopoietic Cell Transplant Co-Morbidity Index provides a comprehensive prognostic model for CD34+-selected allogeneic transplantation.

To determine outcomes based on both disease- and patient-specific factors, we evaluated a prognostic model combining the Disease Risk Index (DRI) and Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), an approach recently shown to predicted overall survival in a broad population of allograft recipients (1). This was a retrospective analysis of 506 adult recipients of first allogeneic HCT with CD34+ selected PBSCs from 7/8- or 8/8-matched donors for AML (n = 290), ALL (n = 72), or MDS (n = 144). The Kaplan-Meier method estimated OS and RFS. The cumulative incidence method for competing risks estimated relapse and non-relapse mortality (NRM). We evaluated the univariate association between variables of interest and OS and RFS using the log-rank test. Cox regression models assessed the adjusted effect of covariates on OS/RFS. Stratification of patients based on a composite of DRI (low/intermediate vs. high/very high) and HCT-CI (0-2 vs. ≥ 3) revealed differences in OS and RFS between the 4 groups. Compared with reference groups of patients with low/intermediate DRI and low or high HCT-CI, those with high DRI had a greater risk of death (HR 2.30; 95% CI 1.39, 3.81) and relapse or death (HR 2.50; 95% CI 1.55, 4.05) than patients with any HCT-CI but low/intermediate DRI (HR death 1.80; 95% CI 1.34, 2.43; HR relapse/death 1.68; 95% CI 1.26, 2.24). A model combining DRI and HCT-CI predicted survival after CD34+ cell-selected HCT. Application of this combined model to other cohorts, both in retrospective analyses and prospective trials, will enhance clinical decision making and patient selection for different transplant approaches. The data that support the findings of this study are available on request from the corresponding author, C Cho. In order to protect the privacy of research participants, the data are not publicly available.

African Americans with translocation t(11;14) have superior survival after autologous hematopoietic cell transplantation for multiple myeloma in comparison with Whites in the United States.

Multiple myeloma (MM) with the translocation t(11;14) may have inferior outcomes in comparison with other standard-risk MM, and it has been suggested to portend a worse prognosis in African Americans in comparison with Whites. This study used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of t(11;14) on the clinical outcomes of patients with MM of African American and White descent. This study evaluated 3538 patients who underwent autologous hematopoietic cell transplantation (autoHCT) for MM from 2008 to 2016 and were reported to the CIBMTR. Patients were analyzed in 4 groups: African Americans with t(11;14) (n = 117), African Americans without t(11;14) (n = 968), Whites with t(11;14) (n = 266), and Whites without t(11;14) (n = 2187). African Americans with t(11;14) were younger, had lower Karnofsky scores, and had more advanced stage MM with a higher Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). Fewer African Americans with t(11;14) (21%) had a coexistent high-risk marker in comparison with Whites with t(11;14) (27%). In a multivariate analysis, race and t(11;14) had no association with progression-free survival. However, overall survival was superior among African Americans with t(11;14) in comparison with Whites with t(11;14) (hazard ratio, 0.53; 95% confidence interval, 0.30-0.93; P = .03). Survival was also associated with female sex, stage, time from diagnosis to transplant, a low HCT-CI, and receipt of maintenance. Race may have a differential impact on the survival of patients with t(11;14) MM who undergo autoHCT and needs to be further studied.

Reduced-intensity conditioning is a reasonable alternative for Philadelphia chromosome-positive acute lymphoblastic leukemia among elderly patients who have achieved negative minimal residual disease: a report from the Adult Acute Lymphoblastic Leukemia Working Group of the JSHCT.

Reduced-intensity conditioning (RIC) regimens have been widely used for allogeneic hematopoietic cell transplantation (HCT) in elderly patients. After the emergence of tyrosine kinase inhibitor (TKI), most patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) now achieve negative results for minimal residual disease (MRD) at HCT. In this study, we evaluated patients aged 50 years or more with Ph-positive ALL who received TKI before HCT, achieved negative-MRD at HCT, and underwent their first allogeneic HCT between 2008 and 2017. In total, 90 and 136 patients who received myeloablative conditioning (MAC) and a RIC regimen, respectively, were included. The median age of patients with MAC and RIC was 54 and 60 years, respectively. Even in multivariate analyses, RIC was not significantly associated with overall mortality (hazard ratio [HR], 1.09; P = 0.724), hematological relapse (HR, 1.97; P = 0.170), or non-relapse mortality (HR, 0.84; P = 0.540). Subgroup analyses suggested that RIC resulted in superior overall survival due to a lower incidence of non-relapse mortality in patients with a poor performance status or a high HCT comorbidity index. In conclusion, RIC is a reasonable option for elderly patients with negative-MRD at HCT.

Myeloablative Vs Reduced-Intensity Conditioning for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Among Patients over 50 Years Old Who Achieved Negative Minimal Residual Disease

Reduced-intensity conditioning (RIC) regimen for allogeneic hematopoietic cell transplantation (HCT) has widely used in elderly patients to reduce the risk of treatment-related toxicities. Previous studies showed that RIC lead to lower non-relapse mortality (NRM), but higher relapse rate compared to myeloablative conditioning (MAC). Over the last decade, tyrosine kinase inhibitor (TKI) has dramatically improved the long-term outcomes for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) and many patients achieved negative results of minimal residual disease (MRD) at HCT. However, available data regarding the impact of conditioning intensity in patients with negative-MRD are limited. In this nationwide retrospective cohort study, we included patients over 50 years old with Ph-positive ALL who received TKI before HCT, achieved negative-MRD at HCT, and underwent their first allogeneic HCT between 2008 and 2017. Patients who received in vivo T-cell depletion or post-transplant cyclophosphamide were excluded. In this study, 90 and 136 patients received MAC and RIC regimen, respectively. MAC consisted of the vast majority of cyclophosphamide and total-body irradiation. Fludarabine and melphalan with or without low dose total-body irradiation (less than 4 Gy) were the majority of RIC regimen. The median age of patients with MAC and RIC was 54 and 60, respectively. Patient characteristics were not significantly different except for patient age and donor source between MAC and RIC groups. There were no significant differences on overall mortality, hematological relapse, and NRM, respectively (Figure). Even in multivariate analyses, RIC was not significantly associated with overall mortality (hazard ratio [HR], 1.09; 95% confidential interval [CI], 0.67-1.77; P = 0.724), hematological relapse (HR, 1.97; 95% CI, 0.75-5.15; P = 0.170), and NRM (HR, 0.84; 95% CI, 0.49-1.45; P = 0.540), respectively. Post-hoc analyses suggested that RIC resulted in the superior overall survival due to lower incidence of NRM in patients with poor performance status or high HCT comorbidity index. In conclusion, RIC is a reasonable option for patients over 50 years with negative-MRD at HCT.

Disease Risk Index (DRI) and Age but Not HCT Comorbidity Index (HCT-CI) Are Predictive of Overall Survival after Cord Blood Transplantation Supported By Haplo-CD34+ progenitor Cells

Introduction: Predictors routinely used to assess long-term survival after allogeneic hematopoietic cell transplantation (alloHCT) have not been specifically validated for pre-transplant risk assessment of patients getting cord blood transplantation supported by Haplo-CD34+ Progenitor cells as a myeloid bridge (haplo-cord). Methods: All consecutive adult patients with hematological malignancies who received an alternative donor alloHCT with a haplo-cord at Weill Cornell Medicine were included. Data was collected from an ongoing haplo-cord protocol (clinicaltrials.gov identifier 01810588). Plasma cell disorders were excluded. Age, CIBMTR Disease Risk Index (DRI), Karnofsky performance score (KPS), and HCT comorbidity index (HCT-CI) (routinely calculated since 06/2014), were assessed before alloHCT. The Kaplan-Meier method was used to estimate OS probabilities. Comparisons of OS were evaluated by the log-rank test. Significant predictors were considered in a Cox proportional hazards regression model using forward stepwise selection. A cumulative incidence function (CI) for relapse was calculated using a competing risk model for non-relapse mortality (NRM). We further validated our findings in the subgroup of patients with AML. Results: Between 06/2012 and 12/2018, 217 patients underwent haplo-cord transplantation. Indications for alloHCT included: 66% leukemia, 19% MDS/MPN, 15% Lymphoma. Median age was 58 yr (22% ≤ 40yrs, 33% between 41-59yrs, and 45% ≥ 60 yrs). 43% of patients were women. KPS score was ≥ 90 in 56%. DRI was high/very-high in 43% and low/intermediate in 56%. HCT-CI for 154 patients was 0 in 14%, 1-2 in 21%, 3-5 in 45% and ≥ 6 in 20%. Conditioning regimens included fludarabine with melphalan 45%, plus TBI 51%, other 4%. Median follow-up was 30 months. 2yr OS was 38% (95%CI 31-44%). 2yr CI of NRM was 35% and relapse 36%. Age (p=0.001), DRI (p&lt;0.001), and KPS (p=0.003) were associated with OS in univariate analysis(Figure 1). HCT-CI did not correlate with OS (p=0.53). In a multivariable model, only age ≥60 (HR 1.86, p=0.01) and high/very high DRI (HR 1.86, p&lt;0.001) remained predictive of OS. (Figure 2). Age ≥ 60 was associated with increased NRM at 2 yrs (45% vs 27%, p=0.01). High/very high DRI was associated with relapse at 2 years (51% vs 24%, p&lt;0.001). A subgroup analysis of 123 patients with AML showed consistent findings; age ≥ 60 (HR 2.11, p=0.04) and high/very high DRI (HR 2.51, p&lt;0.001) remained predictive for OS in multivariable analysis. Conclusion: DRI and age are highly predictive of OS for patients undergoing haplo-cord transplantation. Our finding that HCT-CI is not predictive of OS when applied to haplo-cord alloHCT is supported by previous findings investigating the role of HCT-CI in cohorts with cord blood donors (Adachi Y et al BBMT 2018 and Majhail N et al BBMT 2008). To this end, our findings demonstrate that a high HCT-CI score should not preclude patients from evaluation for alternative donor transplantation using cord blood supported by Haplo-CD34+ progenitor cells. Other prognostic tools to assess specific comorbidities impacting this transplant platform are needed for accurate pre-transplant risk assessment in order to improve decision making and clinical trial assignments. Disclosures Van Besien: Miltenyi Biotec: Research Funding.

The use of comprehensive geriatric assessment in older patients before allologeneic hematopoietic stem cell transplantation: A cross-sectional study

ObjectivesTo evaluate the results of the comprehensive geriatric assessment (CGA) before allogeneic hematopoietic stem cell (HSCT) transplantation in patients aged 60 years and over. MethodsWe evaluated all consecutive patients undergoing CGA before HSCT between September 2011 and July 2018 in a private hospital in Brazil. We also evaluated the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-SCI) and the Disease Risk Index (DRI). ResultsDuring the study period, 61 patients were referred for transplant evaluation. After exclusions, we analyzed 40 patients, with a mean age of 67.6 years (60–76). The CGA detected vulnerability and frailty in 43% and 18.9% respectively according to the Fried Frailty Phenotype score; limitations across the domain of function and disability with handgrip test alterations in 65.8%. However, 36 (90%) were independent for instrumental activities of daily living (IADL). Cognitive and depression domain have shown abnormal with the clock test in 44.4%, and loss of memory complains in 37.5%. But the mini-mental test was normal in 89%. Geriatric Depression Scale (GDS) was normal in 82.5%. 30% were considered at risk for malnutrition. Half of the patients (50%) had a high Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score. 32.5% needed ICU admission. The overall survival and non-relapse mortality at 2 years were 41.8% and 38.7% respectively. ConclusionThe CGA was feasible in detecting the patients' vulnerabilities in our population. More studies, multicentric and with a larger number of patients, are needed to evaluate the role of CGA in this context of allo-HCT in our population.

Allogenic Hematopoietic Cell Transplantation (HCT) for Chronic Myelomonocytic Leukemia: Clinical, Cytogenetic, and Mutational Risk Factors Associated with Survival

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy characterized by persistent monocytosis, combined with myeloid proliferation and dysplasia. Here, we report HCT outcomes in 129 patients (pts) with CMML, 7-74 (median 55) years of age, with follow-up extending to 25 years. Patients were conditioned with various intensity regimens and transplanted from related (N=45) or unrelated donors (N= 84). The source of stem cells was marrow in 34, mobilized peripheral blood cells in 93, and cord blood in 2 patients. The HCT-CI was 0-11 (median 3). Somatic mutations present pre-HCT were analyzed with a mutation panel sequencing for 75 genes. Fig. 1A and 1B show overall survival by WHO disease criteria and the Spanish cytogenetic classification, respectively. Acute graft-versus-host disease (GVHD) grades II-IV occurred in 74% and chronic GVHD in 43%. Relapse incidence was 32%. Overall and progression-free survival at 10 years was 28% and 29%, respectively. Multivariate regression models showed the following: Blast count >20% at HCT (CMML-T: HR 1.67, CI 0.9-3.2, p=0.13, Fig. 1A), high-risk cytogenetics (HR 1.88, CI 1.2-3.0, p=0.01, Fig. 1B) and high HCT comorbidity index (HCT-CI≥4: HR 1.99, CI 1.2-3.4, p=0.01, Fig. 1 C) negatively impacted survival. There were 52% and 42% of patients who carried mutations in ASXL1 and TET2 and they were not significantly associated with inferior survival (ASXL1: HR=1.6, CI 0.3-7.6, p=0.54, TET2: HR=1.3, CI 0.4-3.9, p=0.63). Mutations in ATRX (HR=17.3, CI 4.1-73, p=0.0005) and WT1 (HR=6.3 CI 1.6-24, p=0.01), however, were associated with inferior survival. The total number of mutations (> 10 mutations, HR=3.5, CI 1.4-7.3, p=0.02) and more mutations in genes regulating epigenetic processes (HR 1.8, CI 1.1-2.8, p=0.01) were associated with relapse. The molecular CMML-specific prognostic scoring system (CPSS-Mol, Elena et al. 2016) was not correlated with relapse or survival. Unsupervised clustering of the correlation matrix revealed distinct associations between mutations and clinical features (Fig. 2), Group 1, proliferative type (mutations in mitotic signaling pathways associated with high WBC/blast counts and high risk disease by prognostic scoring systems), and Group 2, dysplastic type (mutations in genes regulating epigenetic processes including ATRX and WT), which was associated with unfavorable outcome. In summary, a proportion of patients with CMML achieve lasting remissions following HCT. However, relapse and overall mortality remain high. Molecular annotation uncovered distinct subgroups of CMML, and higher number of mutations, in particular, of epigenetic regulators, may confer unfavorable transplant outcomes. Incorporation of mutations in addition to cytogenetics and comorbidity scores should improve transplant prognostication.