Hematopoietic Cell Transplantation-specific Comorbidity Index Score Research Articles

Hospital Associated Disability Among Older Adults with Plasma Cell Disorders Receiving Autologous Stem Cell Transplant

Background: An increasing number of older adults with Plasma Cell Disorders (PCDs) are receiving autologous stem cell transplant (ASCT) in the US. Hospital associated disability (HAD) is a loss in independence in one or more activities of daily living associated with acute care hospitalization and is a common complication among older adults. The prevalence and prognostic significance of HAD among older adults with PCDs undergoing ASCT is unknown. Methods: This retrospective cohort study used consecutive adults receiving ASCT at a large U.S. comprehensive medical center between 1/2013 and 5/2023. Trained nursing staff assessed Katz Activities of Daily Living (ADL) at admission and every 3 days thereafter under our Virtual Acute Care for Elders program. The primary outcome was development of HAD defined as ≥1 point decline on the Katz ADL scale from hospital admission to discharge. We also examined the association between development of HAD and various predictors including age, Karnofsky Performance Status (KPS), and Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) using modified Poisson regression models with robust variance estimators. Using similar models, we studied the impact of HAD on unplanned 30-day readmission rates. Results: Of 870 patients undergoing ASCT during the study period, 778 had at least two Katz ADL assessments and were included. The study population was comprised of 56% Caucasian/white ethnicity and 56% male with a median age of 62y (IQR 55-68y). In the overall population, 112 (14.4%) developed HAD. The incidence of HAD was much higher among adults ≥65y compared to their younger counterparts (22% vs. 9%; p=<0.01). In multivariate analysis, age ≥65y (RR 2.22; 95% CI 1.56-3.15; p=<0.001) and baseline KPS <=70 (RR 1.83; 95% CI 1.15-2.92; p=0.011) was associated with increased risk of developing HAD; HCT-CI scores did not have a significant association with HAD. Those with HAD had a two-fold higher risk of 30-day readmission as compared to those without HAD (RR 2.18; 95% CI 1.20-3.66; p=0.003). Conclusions: Nearly 1 in 4 adults ≥65y developed HAD while undergoing ASCT, which was associated with a two-fold increased risk of 30-day readmission. Interventions to prevent HAD and its downstream consequences are critically needed.

Standard Risk Assessment Tools Fall Short to Assess Risk in Transplant Patients

Introduction: The HCT-CI (Hematopoietic Cell Transplantation-specific Comorbidity Index) predicts survival after HCT in patients with hematologic malignancies. HCT-CI ≥3 is associated with higher Non-Relapse Mortality (NRM) and lower overall survival in both allogeneic (allo) and autologous (auto)-HCT patients. The Disease Risk Index (DRI) Assessment Tool is a validated tool to categorize patients undergoing allo- transplant into risk categories based on disease status. It was developed to predict overall survival per disease status. This study was done to understand reasons for increased mortality in transplant patients at our center in 2021 compared to 2020 by comparing HCT-CI and DRI of transplant patients between the two years. Methods: The study was approved by our institution's IRB. A retrospective chart analysis of adult patients who underwent auto- or allo-HCT at Henry Ford Hospital in the years 2020 and 2021 was conducted. Relevant patient demographics, comorbidities, disease characteristics, and transplant-related data were collected. HCT-CI scores were calculated on all patients using the online calculator (https://www.mdcalc.com/calc/3980/hematopoietic-cell-transplantation-specific-comorbidity-index-hct-ci). Patients were also risk stratified based on the DRI Assessment Tool (https://cibmtr.org/CIBMTR/Resources/Research-Tools-Calculators/Disease-Risk-Index-DRI-Assignment-Tool). Data was reviewed and collected by investigators and compiled in a confidential platform. Results: A total of 166 patient records between 2020 and 2021 were reviewed. In 2020, 46 patients underwent auto-HCT and 28 underwent allo-HCT. In 2021, 58 patients underwent auto-HCT and 34 patients underwent allo-HCT. The one-year post transplant survival rates for patients are elucidated in Table 1. The median HCT-CI scores amongst the patients who underwent transplant was 3 in 2020 and 4 in 2021(refer Table 2). When assessing the Disease Risk Index, overall, more patients with higher disease risk were transplanted in 2021 compared to 2020 (refer Table 3). 16 patients (12 in 2021 and 4 in 2020) underwent transplant for diseases that are not included in the DRI assessment tool. Of these, 8 patients in 2021 underwent allo-HCT. These included aplastic anemia (AA), inherited bone marrow failure syndromes (BMF), solid tumors, primary CNS lymphomas, mycosis fungoides and hemophagocytic lymphohistiocytosis (HLH). Conclusion: The HCT-CI and the DRI are both tools used in transplant centers to risk stratify patients pre-transplant. The use of both tools can give a good sense of post-transplant outcomes, combining both individual patient characteristics as well as diseases specific variations. These data are also important for monitoring outcomes at transplant centers. In this study, patients who had an HCT-CI >/3 were similar in both years. The DRI however could not be ascertained in 16 patients, as these diseases are not currently included in the DRI. This makes outcome prediction for these particular patients suboptimal especially if they do not have as many comorbidities but still higher risk diseases. Furthermore, this precludes effective outcome monitoring in and amongst transplant centers. The combination of both the HCT-CI and the DRI would perform better if the DRI tool is revised to become more comprehensive or by creating a DRI that is specific for non-malignant disorders like AA, HLA and BMF. We intend to propose this to CIBMTR for further consideration.

Frailty Impact on Outcomes of Patients Undergoing Chimeric Antigen Receptor T-Cell (CAR T) Therapy at Princess Margaret Cancer Centre: A Prospective Pilot Study

Introduction Princess Margaret Cancer Centre is 1 of 3 adult centres in Ontario, Canada providing Chimeric Antigen Receptor T-Cell (CAR T) therapy as a standard of care treatment for adult patients with relapsed and refractory B-cell lymphomas. There is no upper age limit for treatment consideration, and frailty may be an important factor in assessing fitness for treatment. This study aims to determine if frailty assessments pre-CAR T can predict those at higher risk for acute toxicities, PFS, and OS, as well as evaluate changes in frailty over time. Methods We performed a cohort study of consecutive patients with lymphoma undergoing CAR T cell therapy at our institution, from April 2021 to date. Frailty was evaluated using the Clinical Frailty Scale (CFS), Grip Strength, Gait Speed, Mini-Cog, Edmonton Symptom Assessment System (ESAS) and Patient Health Questionnaire (PHQ-2 and PHQ-9) at 5 time points: baseline (clearance visit), and 1, 3, 6 and 12 months post-CAR T. At baseline, additional assessments were completed to further characterize frailty including the Vulnerable Elders Survey (VES-13), Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) and Cumulative Illness Rating Scale (CIRS). We present data on patients enrolled to date. Results Fifty-two patients have had their data analyzed thus far. Mean age is 57.9 ± 12.7 years and 54% are male. 50% have de novo diffuse large B-cell lymphoma, 24% transformation from follicular lymphoma,14% HGBCL, 6% PMBCL and 6% FL. Most patients (83%) received axi-cel. Median follow-up is 3.80 months (IQR 0.56-24.7 mo). All 52 patients completed assessments at baseline, 44 completed 1 month, 25 completed 3 month, 12 completed 6 month and 11 completed 12 month assessments. Median scores (and IQR) for the HCT-CI, CIRS, VES-13 and CFS at baseline were 1.5 (0-5), 3.0 (0-13), 1.0 (0-7), and 3.0 (1-7) respectively. There were clinically significant changes observed in CFS over time ( p=<0.001), with mean scores of 3.3 at baseline, 3.7 at 1 month, 2.8 at 3 months and 2.1 at 12 months. There were no significant changes ( p=0.051; p=0.078) between timepoints for either of the physical assessments of grip strength or gait speed. Sixteen patients (31%) experienced immune effector cell neurotoxicity syndrome (ICANS) (4% Grade 4, 4% Grade 3, 8% Grade 2, 15% Grade 1) and forty-nine patients (94%) experienced cytokine release syndrome (CRS) (2% Grade 3, 65% Grade 2, 27% Grade 1), during the 30 days following cell re-infusion. Seven patients (13%) were admitted to the ICU, with a median in-hospital length of stay for all 52 patients of 12.5 days (IQR 7.0, 99.0). None of the variables tested (age, sex, bridging therapy, LDH, CRP and frailty assessments) were significantly associated with the development or grade of CRS or ICANS. There have been 21 progression events and 18 deaths (6 without progression); 9 pts remain alive post-progression (Figure 1). On univariable analysis of baseline data, ECOG performance status, LDH level, and the VES-13 score were predictive of PFS, while ECOG, LDH, CRP, VES-13 score, CFS and the time to walk 4m were predictive of OS. The HCT-CI and CIRS score were not significantly associated with outcomes. On multivariable analysis of PFS, baseline VES-13 score (HR 1.17, p=0.04) and LDH (HR 1.002, p=0.05) remained significant. Multivariable analysis for OS was not performed due to insufficient number of events. Analyses incorporating repeated measures were performed, and on univariable analysis, the CFS, 4m walk test (s), LDH, VES-13 were significantly associated with PFS and the same variables and CRP were associated with OS (Table 1). On multivariable repeated measurements analyses, only the CFS was still associated with PFS, and CFS and LDH with OS (Table 1). Conclusions Conducting serial frailty assessments in patients undergoing CAR T therapy is feasible. The only longitudinal measurement of frailty found to have clinically significant changes between timepoints was the CFS, suggesting an element of reversible functional impairment related to patients' lymphoma. Within the limits of our sample size, baseline measures of frailty were not predictive of CRS or ICANS; the relationship of CFS change over time with PFS and OS may be indicative of lymphoma response. Enrollment is ongoing and data on larger number of patients with longer term follow-up are needed.

Comparison of Two Reduced Intensity Conditioning Regimens (Baltimore with Clofarabine vs Thiotepa-Busulfan-Fludarabine) in Adults Receiving Peripheral Blood Stem Cell Haploidentical Transplantation for Myeloid Malignancies: A Retrospective Study of the SFGM-TC

Background: Haploidentical transplantation (haploT) has become a routine practice in many centers but the optimal conditioning regimen has yet to be determined. Indeed, the historic Baltimore reduced intensity conditioning (RIC) regimen has been associated with poor outcomes in myeloid malignancies. Two alternative RIC regimens have recently demonstrated promising results in this setting. One of them replaces fludarabine with second-generation nucleoside analogue clofarabine (Clo-Baltimore regimen [CloB], Chevallier et al., Oncotarget 2018) and the other combines thiotepa-busulfan-fludarabine (TBF, Duléry et al., BBMT 2019). Here we compared outcomes in order to determine if one of these two regimens was superior for the treatment of myeloid malignancies. Methods: This was a multicenter retrospective study conducted by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). All consecutive adults having received a haploT after a CloB or a TBF RIC regimen for a myeloid malignancy between September 2013 and May 2023 were eligible. Patients data were extracted from the PROMISE database. CloB consisted of clofarabine 30 mg/m²/day (d) 5 d, cyclophosphamide (Cy) 14.5mg/kg/d 2 d, and 2-Gy TBI on d-2. TBF consisted of thiotepa 5mg/kg 1 d, busulfan 3.2 mg/kg 2 d, a fludarabine total dose of 120 to 150 mg/m². Graft-versus-host disease (GVHD) prophylaxis consisted of post-transplant Cy (2 doses of 50mg/kg), followed by cyclosporine A and mycophenolate mofetil starting on d+5. Some patients received antithymocyte globulin (ATG) 2.5mg/kg/d on d-2. Graft source was exclusively peripheral blood stem cells (PBSC). To minimize bias between the CloB and the TBF groups, a propensity score matching (PSM) was constructed using a logistic regression model that included age, donor and recipient sex, hematopoietic cell transplantation-specific comorbidity index (HCT-CI), disease, cytogenetic risk (European LeukemiaNet [ELN] 2022), previous transplant, use of ATG, and cytomegalovirus (CMV) status, with the nearest-neighbor algorithm, and strict matching of key factors. Matched groups were then compared for time to engraftment (absolute neutrophil count > 0.5 x 10 9/L) and platelet (PLT) recuperation (>50 x 10 9/L), overall survival (OS), progression-free survival (PFS), GVHD-free, progression-free survival (GRFS), non-relapse mortality (NRM), and incidences of relapse as well as acute and chronic GVHD. Results: A total of 329 patients from 25 centers were included, 267 (81%) receiving TBF and 62 (19%) CloB. After PSM, 51 patients remained in each group, with comparable baseline characteristics except for the proportion of previous allotransplants ( Table). Median age was 60 years, and median HCT-CI score was 2. Main diagnoses comprised acute myeloblastic leukemia (AML, n=72 [71%]), including 42% with adverse genetic risk, and myelodysplastic syndrome (MDS, n=22 [22%]), including 25% with high or very high Revised International Prognostic Scoring System (R-IPSS). Thirty-eight (37%) patients received ATG. Time to engraftment was equivalent after both TBF and CloB (19 d vs 19.5 d, respectively, p=0.70), but TBF patients achieved PLT recuperation faster (27 d vs 31 d, p=0.03). Median follow-up was 24 months. Two-year OS, PFS and GRFS were 55% vs 60% (p=0.19), 52% vs 60% (p=0.25), and 37% vs 50% (p=0.15) for TBF and CloB patients, respectively. No differences were observed in terms of grade 3-4 acute GVHD at 3 months (18 vs 20%, p=0.86) nor two-year extensive chronic GVHD (16% vs 8.3%, p=0.25). However, two-year NRM was significantly higher after TBF (41% vs 16%, p=0.003), while relapse incidence was lower (7.1% vs 24%, p=0.02, Figure). In multivariate analysis, CloB was associated with a lower risk of NRM (hazard ratio [HR] 0.31, 95%CI: 0.1-0.7, p=0.008) and a higher risk of relapse (HR 4.03, 95%CI: 1.2-13.9, p=0.03). Finally, in patients aged >60y, two-year OS was significantly lower for those receiving TBF conditioning (39% vs 61%, p=0.02, Figure) due to higher NRM (56% vs 23%, p=0.005). Conclusions: In this retrospective study, a TBF RIC regimen used for PBSC haploT in adults with myeloid malignancies appeared substantially more toxic than a CloB RIC regimen. However, its enhanced anti-leukemic effect suggests that it should be offered to younger patients with no comorbidities or to those with high-risk disease. Conversely, CloB should be proposed for older or frail patients.

Myeloablative fractionated busulfan for allogeneic stem cell transplant in older patients or patients with comorbidities

AbstractTraditional conditioning regimens for patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) provide suboptimal outcomes, especially for older patients and those with comorbidities. We hypothesized that a fractionated myeloablative busulfan dose delivered over an extended period would reduce nonrelapse mortality (NRM) while retaining antileukemic effects. Here, we performed a phase 2 trial for adults with hematological malignancies receiving matched related or unrelated allo-HCT. Participants received busulfan 80 mg/m2 as outpatients on days −20 and −13 before transplant. Fludarabine 40 mg/m2 was administered on days −6 to −3, followed by busulfan dosed to achieve a target area under the curve of 20 000 mol/min for the whole course. The primary end point was day-100 NRM. Seventy-eight patients were included, with a median age of 61 years (range, 39-70 years), who received transplantation for acute leukemia (24%), myelodysplastic syndrome (27%), or myeloproliferative disease/chronic myeloid leukemia (44%). HCT-specific comorbidity index (HCT-CI) was ≥3 in 34 (44%). With a median follow-up of 36.4 months (range, 2.9-51.5), the 100-day, 1-year, and 3-year NRM rates were 3.8%, 8%, and 9.3%, respectively, without a significant difference in age or HCT-CI score. The 1-year and 3-year relapse incidence was 10% and 18%, respectively. The 3-year overall survival was 80%, without a significant difference in age or HCT-CI score and was similar for patients aged >60 years and those aged <60 years as well as for those with HCT-CI ≥3 and HCT-CI <3. Overall, a myeloablative fractionated busulfan regimen has low NRM without an increase in relapse rate, resulting in promising survival, even in older patients or in patients with comorbidities. This trial was registered at www.clinicaltrials.gov as #NCT02861417.

Reduced Post-Transplant Cyclophosphamide Dose Associated with Antithymocyte Globulin in Peripheral Blood Stem Cell Haploidentical Transplantation

INTRODUCTION Post-transplant cyclophosphamide (PT-Cy) has become the standard graft-versus-host disease (GVHD) prophylaxis for haploidentical hematopoietic cell transplantation (HCT) and has been increasingly used in allogeneic HCT with HLA-matched donors. However, PT-Cy is associated with significant toxicities and organ damage, especially in elderly patients. While toxicities may be correlated with the total cyclophosphamide dose, few studies have evaluated the safety and efficacy of different PT-Cy doses. We aimed to compare the outcomes with a reduced PT-Cy total dose of 70 mg/kg to those with PT-Cy at 100 mg/kg in elderly patients and patients with cardiac comorbidities undergoing haploidentical HCT. PATIENTS AND METHODS Inclusion criteria included: (1) age ≥ 65 years, or patients of any age with a history of cardiac events, (2) hematological malignancy, (3) haploidentical HCT, (4) peripheral blood stem cells, and (5) thiotepa-based conditioning regimen with antithymocyte globulin (ATG). Since 2015, our center policy has been PT-Cy at 100 mg/kg divided in 2 doses, to all patients. Starting from 2020, 40 patients have received PT-Cy at 35 mg/kg/day on day+3 and day+4 either because of older age or cardiac comorbidities. RESULTS Fifty-eight patients met the inclusion criteria. Median age was 68 years (range, 15-76) and 60% of patients were male. Median HCT-specific comorbidity index (HCT-CI) score was 2 (range, 0-5). Patients were transplanted for acute myeloid leukemia (n=37, 64%), myelodysplastic syndrome (n=11, 19%), lymphoma (n=8, 14%), or myeloproliferative neoplasm (n=2, 3%). Disease risk index was intermediate in 22 (38%) patients and high or very high in 36 (62%). Disease status at transplantation was complete remission in 18 patients (31%). Conditioning regimens were reduced intensity thiotepa-based (thiotepa - busulfan - fludarabine) in 25 (43%) patients or Flamsa-like sequential (thiotepa - etoposide - cyclophosphamide, followed by fludarabine - busulfan) in 33 (57%). GVHD prophylaxis included cyclosporin, mycophenolate mofetil, and ATG in all patients. Thirty-three patients received PT-Cy at 70 mg/kg and 25 at 100 mg/kg. There was no significant difference between the 2 groups (PT-Cy at 70 mg/kg versus 100 mg/kg) in terms of age, gender, HCT-CI score, cardiovascular risk factors, type of hematological disease, disease risk index, disease status, and type of conditioning regimen. The median follow-up was 17 months (interquartile range [IQR], 13-20) and 59 months (IQR, 51-66) in patients receiving PT-Cy at 70 mg/kg and 100 mg/kg, respectively. The cumulative incidences (CIs) of acute grade II-IV and grade III-IV GVHD were 18% and 0% with PT-Cy at 70 mg/kg compared to 17% and 5% with 100 mg/kg, respectively (p=0.94 for grade II-IV and p=0.87 for grade III-IV acute GVHD). The CI of chronic GVHD was 27% and 29% with PT-Cy at 70 mg/kg and 100 mg/kg, respectively (p=0.95). No significant difference was observed for moderate to severe chronic GVHD. Neutrophil recovery was significantly improved with 70 mg/kg compared to 100 mg/kg (median time of 16 versus 19 days, respectively, p=0.006). At days +30, +60, and +90 after HCT, 75%, 88% and 91% patients had a platelet count > 50 x 109/L with 70 mg/kg of PT-Cy, respectively, compared to 36%, 64%, and 64% with 100 mg/kg of PT-Cy, respectively (p=0.011). The CI of post-HCT bacteremia was 38% with PT-Cy at 70 mg/kg and 72% with 100 mg/kg (p=0.004). Other complications commonly associated with PT-Cy were also reduced with 70 mg/kg compared to 100 mg/kg of PT-Cy, such as BK-virus associated hemorrhagic cystitis (12% versus 28%) and left ventricular systolic dysfunction (9% versus 24%). At 2 years, CIs of non-relapse mortality were 18% and 33% (p=0.13), progression free-survival 65% and 46% (p=0.09), overall survival 68% and 52% (p=0.31), and GVHD-free, relapse-free survival 60% and 33% (p=0.04) with 70 mg/kg and 100 mg/kg of PT-Cy, respectively. CONCLUSIONS Reducing PT-Cy dose to 70 mg/kg is a safe and valid approach in elderly patients and patients with cardiac comorbidities underdoing haploidentical HCT with peripheral blood stem cells and low-dose ATG. Compared to 100 mg/kg, neutrophil and platelet recovery were improved, CIs of bacteremia, BK-virus associated hemorrhagic cystitis, and cardiac complications were reduced, the risk of acute and chronic GVHD was not increased, and GVHD-free, relapse-free survival was higher with PT-Cy at 70 mg/kg. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Axicabtagene Ciloleucel As Second-Line Therapy for Large B-Cell Lymphoma in Transplant-Ineligible Patients: Primary Analysis of Alycante, a Phase 2 Lysa Study

Background Patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after first-line treatment who are unable to undergo high-dose chemotherapy (HDCT) and hematopoietic stem cell transplantation (HSCT) have poor outcomes and limited treatment options. Axicabtagene ciloleucel (axi-cel) has recently demonstrated superiority over standard of care (SOC; salvage chemotherapy followed by HDCT/HSCT in responders) as second-line therapy in patients intended for transplant in the phase 3, ZUMA-7 study (Locke et al, NEJM 2022). The objective of the open-label, phase 2, ALYCANTE study (NCT04531046) was to evaluate the efficacy and safety of axi-cel in patients with R/R LBCL after 1 prior line of therapy not intended for HDCT/HSCT owing to age and/or comorbidities. Methods Eligible patients were adults with R/R LBCL that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy and who were not deemed candidates for HDCT/HSCT based on physician's assessment and at least one of the following criteria: age ≥ 65 years; age ≥ 18 years and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) score ≥3; or age ≥ 18 years and prior ASCT (as 1st line consolidation). Patients received lymphodepletion with cyclophosphamide and fludarabine, followed 2 days later by axi-cel infusion at a target dose of 2 × 10^6 CAR T-cells/kg. Cytokine release syndrome (CRS) and neurological events (ICANS) were graded using the ASTCT grading system. The primary endpoint was the complete metabolic response (CMR) at 3 months from axi-cel infusion based on investigator disease assessment. Results Of 43 patients who underwent leukapheresis, 40 received axi-cel. Median age was 68 years (range, 49-81; 45% ≥ 70 years), 30% had HCT-CI score ≥ 3, and 52.5% were refractory to first-line treatment. Overall, 37 patients (92.5%) received bridging chemotherapy (R-GEMOX for all patients but one). Twenty-seven patients (67.5%) were refractory to bridging therapy, including 15 patients (37.5%) who experienced disease progression upon bridging therapy. Median on-study follow-up was 6.7 months. The study met its primary endpoint with a CMR at 3 months of 67.5% versus 12% expected with SOC based on historical controls (Cazelles et al, Leukemia & Lymphoma 2021). Objective response (OR) rate at 3 months was 75%. Best OR and CR rates were 92.5% and 77.5%, respectively. CRS were seen in 90% of patients, including 10% of grade 3-4. ICANS were seen in 55% of patients, including 17.5% of grade 3-4. Twelve patients (30%) patients were admitted to ICU. Six patients died: 2 due to lymphoma and 4 due to fatal adverse events (COVID-19, mucormycosis, perineal infection, and sepsis). Grade ≥ 3 prolonged cytopenias (i.e. not resolved on Day 29 after axi-cel infusion) occurred in 14 patients (35%). Conclusions In the ALYCANTE study, axi-cel as second-line treatment in patients with LBCL who were not deemed candidates for HDCT/HSCT appears feasible and induces high response rates. Additional exploratory analyses are ongoing, including early PET-CT at Day 14 post-infusion and ctDNA monitoring, which will be presented at the meeting. Finally, the protocol was amended to allow an expansion of 20 additional patients (for a total of 60 patients) to achieve sufficient power to compare 2 subgroups of patients based on age (≥ 70 vs < 70 years).

Comorbidities Associated with Early Mortality after CD19 CAR-T Cell Therapy

Objective: CD19 chimeric antigen receptor (CAR) T-cell therapy has changed the standard for treatment of relapsed and/or refractory (r/r) large b-cell lymphoma (LBCL). Currently, pre-treatment evaluation of patients and disease factors do not accurately predict outcomes. This study aims to identify risk factors associated with early mortality prior to day 100 after CAR-T infusion. Methods: We performed a single-centered retrospective adult patients (pts) with r/r LBCL who received CAR-T cell therapy between 2018-2021. CAR-T cell toxicities graded according to either CAR T-Cell Therapy-Associated Toxicity (CARTOX) grading system prior to May, 2019 or American Society of Transplantation and Cellular Therapy (ASTCT) consensus grading thereafter for cytokine release syndrome (CRS) and immune cell associated neurotoxicity syndrome (ICANS). Comorbidities defined as per Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). (Sorror et al., 2009). Hepatic dysfunction defined as infection with hepatitis B or C or history of liver cirrhosis or elevated total bilirubin, AST, or ALT on at least two values on two different days from day -24 till day -10 prior to CAR-T. Cardiovascular (CV) comorbidity determined by presence of coronary heart disease, congestive heart failure or reduced ejection fraction detected by echocardiogram. Psychiatric disturbance defined as presence of depression and/or anxiety requiring treatment or consultation. Patient demographics, disease characteristics and clinical outcomes summarized through descriptive statistics. Wilcoxon rank sum test used to evaluate difference in a continuous variable between patient groups. Kaplan-Meier method used to estimate time-to-event endpoints including progression free survival (PFS), and overall survival (OS). Results: Two hundred and fifty patients included in analysis. Median age of 61years (range: 18-89) and 30.8% of patients were female (n=77). Histology was categorized as LBCL (65.9%) and included diffuse LBCL or high grade LBCL, transformed follicular lymphoma (26.9%), primary mediastinal b-cell lymphoma (6.4%) or follicular lymphoma (0.8%). Majority of pts received axicabtagene ciloleucel 95.6% (n=239) while 4.4% (n=11) received tisagenlecleucel and 52% (n=130) of pts received bridging therapy. CRS of any grade was 90.4% ; ICANS any grade was 57.2% while grade 3 CRS/ICANS occurred 6.4% and 38.4% respectively. Median follow-up 24.7 months (mo) (95% CI: 20.7 ~ 26.4 mo). One-hundred twenty-eight pts died during follow-up, 48 pts died within 100 days, and most common cause of death was progression of lymphoma (29.2%; n=73). Early 30-day mortality occurred in 4.8% pts and causes of death due to CAR-T related toxicity in 6 pts, disease progression in 3 pts, and infection in 1 pts. 100-day mortality rate was 24.6% (n=32) for pts >60 years old vs 13.3% (n=16) for <60 (p-value=0.02). 100-day mortality rate was 36.5% for ECOG 2-4 vs 14.9% for ECOG 0-1 (p-value=0.0005). In terms of non-relapsed mortality (NRM), risk stratification according to cumulative HCT-CI score was not associated with higher 100-day NRM (p=0.24). Pts with cardiac score of 1 had a higher NRM (26.9% vs. 8.1%; p-value=0.005). The 100-day NRM rates for hepatic score of 0, 1, and 3 were 8.9%, 14.3%, and 50% (p-value=0.04). Pts with psychiatric disturbance score of 1 had higher 100-day NRM (19.6% vs. 7.8%; p-value=0.03). Conclusion: This single center retrospective study observed an increase in 100-day mortality in correlation with pre-treatment performance status, and older age. Pts with cardiac comorbidity, hepatic dysfunction or psychiatric disturbance had a higher 100-day NRM. Similar to other studies, the combined HCT-CI score was not predictive of NRM, but individual variables were associated with higher non-CART related toxicity. These findings require validation with further studies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Conditioning Regimen Intensity and Donor Choice Do Not Impact Outcomes of Patients (pts) with Acute Myeloid Leukemia (AML) after Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) in First Complete Remission (CR1): An EBMT Analysis

Allo-HCT is a curative treatment for fit pts with intermediate and adverse risk AML who achieve CR1. The presence of minimal residual disease (MRD) before allo-HCT has been shown to increase risk of relapse and decrease survival. Here, we describe outcomes of pts with AML who received allo-HCT in CR1 and the impact of MRD before allo-HCT on outcomes. We identified 1032 pts with AML who received allo-HCT in CR1 between 2015 and 2020 from the EBMT registry. The median age was 53.6 (range, 18.1-82.5) years and 526 (51%) were male. Most (94%) pts had de novo AML. FLT3-ITD and NPM1 mutations were detected in 46% and 44% of pts, respectively and high-risk cytogenetics were present in 20%. >1 course of induction therapy was required by 18% of pts to achieve CR1 and 39% were MRD positive at time of allo-HCT. The median time from diagnosis to allo-HCT was 4.9 months. Of pts with FTL3-wild type (FLT3-wt) disease, 33% were MRD negative and 22% were MRD positive at time of allo-HCT. In pts with FTL3-ITD mutation, 29% were MRD negative and 17% were MRD positive at time of allo-HCT. Donor type was matched sibling donor (MSD) in 29% of pts (n=297), matched unrelated donor (MUD) in 47% (n=481), mismatched unrelated donor (MMUD 9/10) in 8% (n=88), or haploidentical donor (haplo) in 16% (n=166). HCT-specific comorbidity index (HCT-CI) was >3 in 22% of pts (n=190). Myeloablative conditioning (MAC) was administered to 45% of pts (n=470), while reduced intensity conditioning (RIC) was used in 55% (n=562). The most common conditioning regimen was fludarabine/busulfan in MSD (n=148, 50%), MUD (n=272, 57%) and MMUD (n=38, 43%) recipients, while thiotepa/fludarabine/busulfan was the most used in haplo-HCT (n=99, 60%). Total body irradiation (TBI) was given to only 8% of pts (n=84), mainly in haplo-HCT (n=29). Most (n=1002, 98%) pts received calcineurin inhibitors (CNI), tacrolimus or cyclosporine A, for graft-versus-host disease (GVHD) prophylaxis in addition to mycophenolate mofetil (43%) or methotrexate (38%). Post-transplant cyclophosphamide was used in 18% (n=191) of pts, with 71% (n=136) having received haplo-HCT, and anti-thymocyte globulin was given to 67% (n=689). The median follow-up was 24 months. At day 60, the cumulative incidence of neutrophil engraftment was 99%. The cumulative incidence of grade III-IV acute GVHD (aGVHD) was 9% at day 180. At 2 years, the cumulative incidence of extensive chronic GVHD (cGVHD) was 17%. At 2 years, relapse incidence (RI), NRM, overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) were 26%, 13%, 69%, 61%, and 48%, respectively. The main cause of death was primary disease in 55% of pts (n=157). Other causes of NRM were infections in 16% (n=45), and GVHD in 17% (n=47). In the multivariate analysis, compared to MSD, the use of MUD increased NRM (hazard ratio (HR) 1.86, p=0.02), GRFS (HR 1.28, p=0.039), aGVHD (HR 2.17, p<0.0001), and cGVHD (HR 1.36, p=0.044). The use of MMUD was associated with worse OS (HR 1.6, p=0.042) and higher risk of aGVHD (HR 2.11, p=0.003). Haplo-HCT was associated with higher incidence of aGVHD (HR 1.69, p=0.021) but lower risk of cGHVD (HR 0.63, p=0.033). Older age, lower performance status (PS), requiring >1 induction to achieve CR1, and FLT3-MRD positivity before allo-HCT were associated with worse LFS. Factors associated with lower OS were MMUD 9/10, older age, poor PS, >1 induction to achieve CR1, adverse cytogenetics, and FLT3-MRD positivity before transplant. In vivo TCD was associated with improved GRFS and lower risk of acute and cGVHD without increase of relapse. The use of RIC compared with MAC did not affect relapse, NRM or any other outcome. In conclusion, in pts with AML transplanted in CR1, those requiring >1 induction or with persistent FLT3-MRD positivity at time of allo-HCT had lower OS. Strategies to improve induction therapy, possibly through the addition of targeted agents, aiming to improve CR rates and deepening responses could potentially improve OS after allo-HCT. The use of RIC was associated with similar outcomes compared to MAC. This finding is particularly important for older pts or those with high HCT-CI scores unlikely to tolerate MAC. Survival after MSD allo-HCT is comparable to MUD and haplo, a finding that is in accordance with previous results for haplo and MUD as valid alternative donors in the absence of MSD. The use of MMUD was associated with lower OS compared to MSD and should be used as a last resort donor in this setting.

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.

Assessment Of The Hematopoietic Cell Transplantation Comorbidity Index In Older Patients Receiving Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation

BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is an established therapy for malignant and nonmalignant hematologic disorders. Reduced-intensity conditioning (RIC) regimens have expanded the use of HSCT to elderly and higher risk patients. However, HSCT still remains associated with a significant mortality and morbidity and the careful assessment of risks and benefits before transplantation is essential. Major factors which influence non-relapse mortality (NRM) and overall survival (OS) after HSCT are diagnosis, type of transplant, remission status and the patient's risk profile, which includes age and presence of comorbidities. The use of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) has been proposed to predict the probability of NRM and OS following HSCT. However, the HCT-CI usefulness for older patients receiving a reduced intensity allogeneic HSCT remains unclear. MethodsA retrospective medical record review was performed to collect data from patients who underwent an allogeneic HSCT at a large, urban, NCI Comprehensive Cancer Center during a five year period (January 2005 to December 2010). Patients 55 years and older who were transplanted using RIC for a hematologic malignancy were selected to be analyzed. Comorbidities and test results were collected to determine the HCT-CI score and other clinical data collected included disease and remission status at time of transplant. Results85 patients aged >55 years old who received a RIC HSCT for hematologic malignancies between January 2005 to December 2010 were analyzed. The median patient age at the time of transplantation was 63 years (range: 55-75 years). The patient diagnoses included AML (39%), NHL (29%), MM (9%), MDS (11%), CLL (8%), ALL (4%). The median pre-transplantation HSCT-CI score was 2 (range: 0-9). Among 85 patients, OS at 2 years was 44%. The 2 yr OS was 31%, 37% and 44% in the low-, intermediate-, and high-risk HSCT-CI groups (p = 0.61), respectively. The corresponding NRM at 2 years was 25%, 17% and 18% (p = 0.91). We found no predictive value of HSCT-CI for either OS or NRM in older patients having an allogeneic HSCT with reduced-intensity condition. Stratification of age (55-59, 60-64, and 65+) showed no significant impact on 2 yr OS or NRM. However, there was a trend towards a better 2 yr OS for patients who had achieved a CR versus no CR at time of transplant (48% vs 41%). ConclusionOlder patients with hematologic malignancies represent a highly selected cohort, with the prospect of an allogeneic HSCT often considered too high-risk. A method to reliably stratify these older HSCT candidates is greatly needed. However, the HCT-CI score in this retrospective analysis did not help predict their NRM or 2 year OS for patients 55 years and older with hematologic malignancies receiving a reduced intensity HSCT. Further research is warranted into what combination of factors may provide a reliable predictive score for older patients with hematologic malignancies. Disclosures:Mehta:Millennium: Speakers Bureau; Celgene: Speakers Bureau.

Comparison of Dinakara and Cotes Method on Correction of Diffusion Limit of Carbon Monoxide and the Impact on Outcomes of Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI)

AIMHaematopoietic stem cell transplantation poses significant physiological stresses on the recipient. Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) described by Sorror in 2005 aims to provide risk stratification to these patients.Respiratory comorbidity, which takes into account diffusion limit of carbon monoxide (DLCO) and forced expiratory volume in 1 second (FEV1), is the most common comorbidity scored on the HCT-CI. The original publication utilised Dinakara method for correction of DLCO to haemoglobin concentration (Hb). Recommendation of the American Thoracic Society (ATS) and European Respiratory Society (ERS) and therefore, our institution utilises the Cotes method for correction.We compared the effect of Dinakara and Cotes method on correction of DLCO, HCT-CI scoring and non-relapse mortality (NRM). MethodWe retrospectively collected HCT-CI scores, relapse, deaths from 195 consecutive allogeneic stem cell transplants at the Royal Brisbane and Women's Hospital between May 2014 and May 2016 with median follow up of 394 Days. Non-relapse mortality defined as any death in the absence of relapsed disease. ResultsDuring our follow up period, 44 patients relapsed and 50 deaths occurred with median survival not reached. When utilising Dinakara method for scoring respiratory co-morbidity, number of patients who scored 2(moderate) or 3(severe) was 22.1% and 8.7% respective. However, by utilising the Cotes method, this increased the moderate and severe respiratory co-morbidity to 43.1% and 23.1% respectively, thereby pushing the total HCT-CI score higher Figure 1 . By utilising the Cotes instead of Dinakara method, number of patients classified as high risk HCT-CI increased from 32.3% to 49.7%.There were no significant difference in non-relapse mortality between the two methods at Day 100 or 2 years. The high risk patients had NRM using Dinakara vs Cotes of 9.2 % vs 10.1% at day 100 and 16.9% vs 22.8% at 2 years Figure 2 and Figure 3 . ConclusionUtilising Cotes method rather than Dinakara method for the correction of DLCO significantly increased the number of high risk patient on HCT-CI, however, there was no significant impact on non-relapse mortality. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Validation of Scores Predicting Non-Relapse Mortality in Patients with Myelodysplastic Syndrome: A Study on 1276 Patients on Behalf the Chronic Malignancies Working Party of the EBMT

Allogeneic stem cell transplantation (HSCT) is the only potential curative treatment for myelodysplastic syndromes (MDS). Non-relapse mortality (NRM) remains a matter of concern despite the introduction of reduced-intensity conditioning in this disease, occurring mainly in an elderly population. Disease features and status at transplant are cornerstones for the risk of relapse. Different pre-transplant parameters have been analysed in various population without resulting in consensus.Here, we aim to evaluate the predictive role of different pre-transplant parameters including comorbidities on NRM, in 1276 patients who were transplanted for MDS between 2003 and 2014 in centers who participated to the EBMT Data Quality Initiative. The performance of the HCT-CI (Hematopoietic cell transplantation-specific comorbidity index) and PAM (Pretransplant Assessment of Mortality) scores1,2,3 in predicting NRM and overall survival (OS) was investigated according to principles and methods that have been described for external validation of prediction models4. Besides, model discrimination was assessed by the concordance (c) index and its adaptation for competing risks analyses5,6.Median age was 59 (18-79) and the median follow-up was 73 months. The different scores were categorized as initially published. According to the IPSS classification, two-thirds of the patients were classified within the low or intermediate groups of risk (score ≤1) and one-third within the higher-risk's categories (score ≥1.5). Donors were mostly matched related (34.3%) or unrelated (62.1%), use of peripheral blood stem cells was predominant (89.8%) and conditioning was non-myeloablative in 60% of the transplants. Overall, 731 patients died during the study period, including 445 non-relapse deaths. At 48 months, OS was 46.7% (95%CI 44.0 to 49.6) and NRM was 32.5% (95%CI 29.8 to 35.0).The c-index for HCT-CI score, HCT-CI/Age score and PAM were lower than for Karnofsky score meaning that the scores did not predict better the NRM and the OS than Karnofsky score. Furthermore, PAM score did not predict NRM but was able to predict OS (See Figure 1).In multivariate analysis including age, disease risk, conditioning, HCT-CI and KS, age ≥ 70 (HR 1.89, 95%CI 1.14-3.12, p=0.013; HR 1.63, 95%CI 1.09-2.45, p=0.018), HCT-CI ≥3 (HR 1.31, 95%CI 1.02-1.68, p=0.033; HR 1.31, 95%CI 1.08-1.59, p=0.006) and KS ≤ 80 (HR 2.08, 95%CI 1.57-2.76, p<0.0001; HR 1.75, 95%CI 1.41-2.17, p<0.0001) were statistically significantly associated with respectively increased risks for NRM and with a decreased OS. Disease risk and intensity of conditioning regimens had no significant influence on outcomes (Table 1).In conclusion, our study demonstrated on a large homogeneous population of MDS patients the ability of the different comorbidities scoring system to predict toxicity and survival outcomes after HSCT. Among them, Karnofsky score was the most powerful predictive tool. Patient's risk profile assessment is crucial to refine predictive models assessing disease features and transplant procedures.

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.

Values of Hematopoietic Cell Transplantation-Specific Comorbidity Index, Comorbidity/Age Index and Augmented Comorbidity/Age Index in Recipients of Haploidentical Stem Cell Transplantation Using Ptcy As Gvhd Prophylaxis: A Retrospective Study of 223 Cases

Introduction: Pre-transplant comorbidities, which may impact the success of allogeneic stem cell transplantation (AlloSCT) can be appreciated through 3 different scoring systems. The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) allows to predict non-relapse mortality (NRM) and survival (Sorror, Blood 2005). Its prognostic value was further augmented by the addition of donor age (&amp;lt; vs ≥40 yo) (Comorbidity/Age index, C/AI, Sorror, JCO 2014) then of pre-transplant ferritin (&amp;lt; or &amp;gt;2500 µg/L) and albumin (&amp;lt;3 g/dL vs 3-3.5 g/dL vs &amp;gt;3.5g/dL) serum levels as well as platelet count (&amp;lt; vs &amp;gt;100 109/L) (Augmented Comorbidity/Age index, AC/AI, Elsawy, BBMT 2019). The performance of these 3 scores has not been evaluated in haploASCT using post-transplant cyclophosphamide (PTCY), a procedure in constant expansion worldwide. Material and Methods: We studied retrospectively the impact on non-relapse mortality (NRM), overall (OS) and disease-free (DFS) survival of the 3 comorbidity scores on a cohort of 223 patients (pts) having received a haploSCT with PTCY. All pts had pre-transplant ferritin and albumin levels and platelet counts available. These parameters were evaluated at the time of the pre-transplant check-up or just before conditioning (median from transplant: 20 days, range: 4-49). Results: Pts were recruited in 4 French centers (Nantes n=127; Angers n=45; Besançon n=29, Brest n=22). They had received haploSCT between October 2013 and January 2020. There were 136 males and 87 females with a median age of 55 yo (16-71, &amp;gt;40 years n=172). The majority of pts had a myeloid disease (n=157) and received a reduced intensity regimen (n=161, myeloablative n=30; sequential n=32). Respectively, 132 and 91 pts had low/intermediate and high/very-high Disease-Risk Index (DRI). All pts received PTCY, cyclosporine and mycophenolate mofetyl as graft versus host disease (GVHD) prophylaxis. Donors had a median age of 40.8 years (19.4-71.7). Median HCT-CI, C/AI and AC/AI scores were 2 (0-8), 3 (0-9) and 3 (0-11), respectively. The HCT-CI score was &amp;lt;2 in 139 patients, CA/I was &amp;lt;3, 3-4 and &amp;gt;5 in 110, 83 and 30 pts, respectively, while the AC/AI score was &amp;lt;4 in 112 cases. With a median follow-up for alive patients of 35.6 months (6-77), 3-year OS, DFS and NRM were 47.8+3%, 46+3% and 29.4+6%, respectively. In univariate analysis, better 3-year OS and DFS were associated with lymphoid diseases (OS: 60.4+6% vs 42.3+4%, p=0.02; DFS: 56.2+6% vs 41.6+4%, p=0.04), low/intermediate DRI (OS: 59.1+4% vs 30.1+7%, p&amp;lt;0.001; DFS: 56.3+4% vs 31.1+5% p&amp;lt;0.001), donor age &amp;lt;40 years (OS: 58.1+4% vs 36.2+5% p=0.004; DFS: 55.4+4% vs 35.7+4% p=0.01), and albumin level (&amp;lt;3g/dL OS: 33.3+12% vs 3-3.5g/dL 46.1+8% vs &amp;gt;3.5g/dL 50.1+4%, p=0.03; &amp;lt;3g/dL DFS: 30+12% vs 3-3.5g/dL 44.5+8% vs &amp;gt;3.5g/dL 47.4+3%, p=0.05). OS and DFS were not impacted by ferritin levels, platelet count, recipient age, gender, nor any of the 3 comorbidity scores. A lower 3-year NRM was observed in younger pts (&amp;lt;55 yo) (21.8% vs 36.8%, p=0.02) and in those with a younger donor (&amp;lt;40 yo) (20.5% vs 39.2%, p=0.003). NRM was not associated with gender, type of disease, DRI, ferritin, albumin, platelet counts nor any of the 3 comorbidity scores. In multivariate analysis, each comorbidity score was compared to DRI, donor and patient age, type of disease and pre-transplant albumin levels. DRI and donor age remained associated with OS and DFS. This was also the case for recipient age, except when considering a high C/AI index score. Finally, an older age of recipients and donors remained associated with higher NRM. Conclusion: HCT-CI, C/AI and AC/AI do not to predict survivals nor NRM in haploSCT with PTCY, suggesting that pre-transplant comorbidities should not be a contra-indication to this procedure. As donor age is the only factor predicting survivals and NRM in this series, while multiple donors are generally available in the haploSCT setting, the selection of a younger donor should be the rule whenever possible for all patients. Disclosures Hunault: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Diachi: Membership on an entity's Board of Directors or advisory committees; Jansen: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Deconinck:ImmunoGen: Consultancy, Research Funding; Stemline: Consultancy. Thepot:astellas: Honoraria; novartis: Honoraria; sanofi: Honoraria; celgene: Honoraria. Le Gouill:Loxo Oncology at Lilly: Consultancy; Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria. Chevallier:Incyte Corporation: Honoraria.

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.

Comorbidities Predict Inferior Survival in Patients Receiving CAR T-Cell Therapy for Relapsed/Refractory DLBCL: A Multicenter Retrospective Analysis

Comorbidities Predict Inferior Survival in Patients Receiving CAR T-Cell Therapy for Relapsed/Refractory DLBCL: A Multicenter Retrospective Analysis

Increased Early Mortality after Fludarabine and Melphalan Conditioning with Peripheral Blood Grafts in Haploidentical SCT with Post-Transplant Cyclophosphamide

The use of post-transplant cyclophosphamide (PTCy) in the context of haploidentical stem cell transplant (haplo-SCT) has led to drastically reduced rates of Graft-vs-Host (GvH) disease through selective depletion of highly allo-reactive donor T-cells. Early trials utilized a reduced-intensity Flu/Cy/TBI preparative regimen and bone marrow grafts; however, relapse rates remained relatively high (Luznik et al. BBMT. 2008). This led to the increased use of myeloablative (MA) regimens for haplo-SCT, which have been associated with decreased relapse rates (Bashey et al. J Clin Oncol. 2013). Most studies have used a MA total body irradiation (TBI) based regimen for haplo-SCT. Preparative regimens using fludarabine and melphalan (FluMel), with or without thiotepa, ATG, and/or low dose TBI have also been reported using bone marrow grafts. Reports on the safety and toxicity of FluMel in the haplo-SCT setting with PTCy and peripheral blood stem cell (PBSC) grafts are lacking. In this two-center retrospective analysis, the safety/toxicity of FluMel as conditioning for haplo-SCT was evaluated. We report increased early mortality and toxicity using standard FluMel conditioning and PBSC grafts for patients undergoing haplo-SCT with PTCy. 38 patients at the University of Rochester Medical Center and the Washington University School of Medicine underwent haplo-SCT with FluMel conditioning and PBSC grafts between 2015-2019. Outcomes were measured by retrospective chart review through July 2019. 34 patients (89.5%) received FluMel(140 mg/m2). Two patients received FluMel(100 mg/m2) and two patients received FluMel(140 mg/m2) + ATG. The median age at time of haplo-SCT was 60 years (range 21-73). 20 patients were transplanted for AML, eight for MDS, two for PMF, two for NHL, and five for other malignancies. The median Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) score was 4 (≥3 indicates high risk). 11 patients had a history of prior stem cell transplant, and 16 patients had active disease prior to their haplo-SCT. Seven patients had sex mismatch with their stem cell donor. Median donor age was 42 (range 21-71). 20 patient deaths occurred by July 2019 with a median follow up of 244 days for surviving patients. Nine patients died before day +100 (D100, "early mortality"), with a D100 non-relapse mortality (NRM) rate of 24%. Median overall and relapse free survival (OS and RFS, respectively) were 197 days (95% CI 142-not reached) and 180 days (95% CI 141-not reached), respectively, for the entire cohort. The 1 year OS and NRM were 29% and 50%. The incidence of grades 2-4cytokine release syndrome (CRS) was 66%, and 52% of these patients were treated with tocilizumab. CRS was strongly associated with early mortality, with D100 NRM of 36% in patients with grade 2-4 CRS compared to 0% in those with grade 0-1. The incidence of acute kidney injury (AKI) was 64% in patients with grade 2-4 CRS, and 8% in those without (p &lt; 0.001). 28% of patients with AKI required dialysis. Grade 2-4 CRS was seen in 54% of patients in remission prior to haplo-SCT and in 92% of those with active disease (p = 0.02). Of the 9 patients with early mortality, 89% had AKI, 44% needed dialysis, and 100% had grade 2-4 CRS, compared to 31%, 10%, and 55% in those without early mortality (p = 0.002, p = 0.02, p = 0.01). Early mortality was not significantly associated with age, HCT-CI score, second transplant, disease status at transplant, total dose of melphalan, volume overload/diuretic use, or post-transplant infection. In conclusion, we observed a very high rate of NRM with FluMel conditioning and PBSC grafts for haplo-SCT with PTCy. The pattern of toxicity was strongly associated with grade 2-4 CRS, AKI, and need for dialysis. These complications may be mediated by excessive inflammation in the context of allo-reactive donor T-cell over-activation. Consistent with this, multiple groups have shown that FluMel conditioning in haplo-SCT is safe when using bone marrow or T-cell depleted grafts. Based on our institutional experiences, we would discourage the use of FluMel as conditioning for haplo-SCT with PTCy with T-cell replete PBSC grafts. Alternative regimens or variations on melphalan-based regimens, such as fractionated melphalan dosing or inclusion of TBI may improve outcomes but further study and randomized controlled trials are needed. This study is limited in its retrospective design and sample size. Figure Disclosures DiPersio: WUGEN: Equity Ownership, Patents &amp; Royalties, Research Funding; Karyopharm Therapeutics: Consultancy; Magenta Therapeutics: Equity Ownership; Celgene: Consultancy; Cellworks Group, Inc.: Membership on an entity's Board of Directors or advisory committees; NeoImmune Tech: Research Funding; Amphivena Therapeutics: Consultancy, Research Funding; Bioline Rx: Research Funding, Speakers Bureau; Macrogenics: Research Funding, Speakers Bureau; Incyte: Consultancy, Research Funding; RiverVest Venture Partners Arch Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees. Liesveld:Onconova: Other: Data safety monitoring board; Abbvie: Membership on an entity's Board of Directors or advisory committees.

Outcomes and Factors Impacting Use of Axicabtagene Ciloleucel in Refractory and Relapsed Large B-Cell Lymphoma: An Intent-to-Treat Analysis

Outcomes and Factors Impacting Use of Axicabtagene Ciloleucel in Refractory and Relapsed Large B-Cell Lymphoma: An Intent-to-Treat Analysis

Role of Age and Hematopoietic Cell Transplantation-Specific Comorbidity Index in Myelodysplastic Patients Undergoing an Allotransplant: A Retrospective Study from the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option for myelodysplastic syndromes (MDSs) but is severely limited by nonrelapse mortality (NRM), especially in this mostly older population. Comorbidity assessment is crucial to predict NRM and often assessed with the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). Moreover, the impact of age on NRM still remains a matter of debate. In recent years, the age at which transplants are made has been progressively increasing, and patients with comorbidities have become more common. Extricating the respective roles of age and comorbidities in toxic mortality is all the more important. This study by the European Group for Blood and Marrow Transplantation registry included 1245 adult patients who underwent a first allogeneic stem cell transplantation for MDSs between 2003 and 2014. Overall, 4-year NRM and overall survival were 32% and 47%, respectively. When considered as continuous predictors, HCT-CI score and age were associated with an increased hazard ratio (HR) for NRM. In multivariate analysis, age band (HR, 1.13; 95% CI, 1.02 to 1.25; P= .016), HCT-CI ≥3 (HR, 1.34; 95% CI, 1.04 to 1.73; P = .022), and Karnofsky Performance Status ≤80 (HR, 2.03; 95% CI, 1.52 to 2.73; P< .0001) were significantly predictive of a worse NRM. In our large cohort, both comorbidities, evaluated by the original HCT-CI score, and chronological age significantly affected NRM. Thus, age should be part of the transplant decision-making process and should be integrated in future scoring systems predicting outcomes of HSCT in MDSs.