Hematopoietic Cell Transplantation Comorbidity Index Score Research Articles

Prognostic impact of the conditioning intensity on outcomes after allogeneic transplantation for MDS with low blasts: a nationwide retrospective study by the adult MDS working group of the Japan Society for Transplantation and Cellular Therapy.

Poor prognostic factors, such as transfusion dependency and chromosomal risk, need to be considered in the indication of allogeneic hematopoietic cell transplantation (allo-HCT) for patients harboring myelodysplastic syndromes with less than 5% marrow blasts (MDS-Lo). We analyzed the post-transplant outcomes of 1229 MDS-Lo patients who received myeloablative (MAC)(n = 651), reduced-intensity (RIC)(n = 397), and non-myeloablative conditioning (NMAC) regimens (n = 181). The multivariate analysis revealed that the RIC group had better chronic graft-versus-host disease (GVHD)- and relapse-free survival (CRFS) (P = 0.021), and GVHD- and relapse-free survival (GRFS) than the MAC group (P = 0.001), while no significant differences were observed between the NMAC and MAC groups. In the subgroup analysis, the MAC group has better overall survival (P = 0.008) than the RIC group among patients with an HCT-comorbidity index (HCT-CI) score of 0, while the RIC group had better overall survival (P = 0.029) than the MAC group among those with an HCT-CI score ≥3. According to the type of conditioning regimen, total body irradiation 12 Gy-based MAC regimen showed better OS and CRFS than the other MAC regimen, and comparable outcomes to the RIC regimen. In conclusion, the RIC and NMAC regimens are promising options for MDS-Lo patients in addition to the MAC regimen.

The impact of pre-transplant respiratory virus detection on post-transplant outcomes in children undergoing hematopoietic cell transplantation.

Pre-transplant respiratory virus (RV) infections have been associated with negative transplant outcomes in adult hematopoietic cell transplantation (HCT) recipients. In the era of HCT delay due to high-risk RVs, we examined the impact of pre-transplant RV detection on transplant outcomes in a pediatric HCT recipients. This retrospective cohort study included myeloablative allogeneic HCT recipients from 2010 to 2019. All patients were screened for RV at least once within 90 days before HCT using RT-PCR, regardless of symptoms. Post-transplant outcomes included days alive and out of hospital (DAOH) and progression to lower respiratory tract infection (LRTI). Among 310 patients, 134 had a RV detected in the 90 days prior to HCT. In univariable analysis, transplant factors including younger age, total body irradiation, umbilical cord blood transplantation, lymphocyte count less than 100/mm3, and HCT comorbidity index score ≥3, and viral factors including symptomatic infection, human rhinovirus (HRV) as a virus type, and symptomatic pre-transplant upper respiratory tract infection (URTI) were associated with fewer DAOH. In multivariable analysis, transplant factors remained significant, but not viral factors. There was a higher incidence of progression to post-transplant LRTI with the same pre-transplant RV if the last positive PCR before HCT was ≤30 days compared to >30 days (p=0.007). In the setting of recommending HCT delay for high-risk RVs, symptomatic URTI, including HRV infections, may lead to increased duration of hospitalization and early progression to LRTI when transplantation is performed within 30 days of the last positive PCR test.

Treosulfan (Trecondyv)


 CADTH recommends that Trecondyv in combination with fludarabine should be reimbursed by public drug plans as part of conditioning treatment before allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) at increased risk for standard conditioning therapies if certain conditions are met.
 Trecondyv in combination with fludarabine should only be covered to treat adult patients with AML or MDS who are eligible for alloHSCT, are at least 50 years old at transplant, and/or have a Hematopoietic Cell Transplantation-Comorbidity Index score greater than 2. Patients should have good performance status.
 Trecondyv should only be reimbursed in combination with fludarabine if prescribed by clinicians with appropriate training and experience in transplant centres with alloHSCT programs and if the cost of Trecondyv is not more than the least costly alternative conditioning treatment.

Evaluation of Atrial Fibrillation Risk and Outcome after Allogeneic Transplantation Using an Artificial Intelligence ECG Algorithm and Echocardiographic Parameters in an MDS Cohort

Introduction Atrial fibrillation/flutter (Afib) contributes independently to the hematopoietic cell transplant comorbidity index (HCTCI) and is a known complication of allogeneic hematopoietic transplantation (AlloHCT) which has been linked to inferior outcomes, particularly in older patients. An electrocardiogram (ECG)-based artificial intelligence (AI) algorithm to predict Afib and cardiac contractile dysfunction risk has been validated (Lancet 394:861, 2019). We hypothesized that assessment of pre-transplant Afib risk using the AI algorithm may predict future development of Afib and help identify patients at higher risk for this complication. Methods 191 consecutive MDS patients undergoing AlloHCT with curative intent using myeloablative (28.3%) or reduced intensity conditioning (62.3%) in the Mayo Clinic Comprehensive Cancer Center (Rochester, Jacksonville, Phoenix) between November 2015 and January 2022 were included in this retrospective analysis. Primary outcome was Afib within 100 days and 365 days of transplantation, and we also assessed the outcomes of Death and Relapse. Revised IPSS (IPSS-R) and HCTCI scores were included for all patients. Elevated Afib risk score using the AI algorithm was calculated from pre-transplant ECG, performed during vital organ testing at AlloHCT clearance. In addition to left ventricular (LV) ejection fraction (EF) we evaluated detailed echocardiographic (Echo) parameters including LV volume and mass indices, left atrial volume index (LAVI), maximum trans mitral flow velocities during LV filling (E velocity) and during the diastolic phase due to atrial contraction (A velocity), the velocity of the annulus away from the apex during the protodiastolic phase (e' velocity), E/A and E/e' ratios, the presence of valvular disease, and right ventricular systolic pressure (RVSP). We performed an analysis using a Cox proportional hazards regression models (adjusting for age and sex) to evaluate associations with Afib risk, Relapse, and Overall Survival. Results The median age was 64 years (18-75), 58.6% were male, 6.9% non-white race, and 3.7% Hispanic/Latino ethnicity. Most patients had an HCTCI score of 0-3 (76.3%). GVHD prophylaxis was predominantly with calcineurin inhibitor-based regimes plus/minus methotrexate or mycophenolate mofetil (83.8%). 5.2% of patients had a history of Afib before transplant. Non-relapse mortality was 7.9% at 100 days, and 18.3% at 365 days. N=25 patients (13.1%) developed Afib within 100 days, and n=28 (14.7%) within 1-year after AlloHCT. On multivariable analysis, Age [Hazard Ratio (HR) 2.83, 95% Confidence Interval (CI) 1.36-5.89, p=0.0055] and Echo parameters [including LAVI (HR 2.10, CI 1.23-3.58, p=0.0067), E velocity (HR 3.28, CI 1.29-8.80, p=0.013), E/A ratio (HR 3.74, CI 1.75-7.97, p=0.0006), E/e ' ratio (HR 1.81, CI 1.07-3.07, p=0.026) and RVSP (HR 1.68, CI 1.04-2.70, p=0.032)] were significantly associated with Afib risk; elevated AI risk score was significant in the univariate model (HR 2.74, CI 1.15-6.53, p=0.023) but was borderline in the multivariate model (HR 2.34, CI 0.98-5.60, p=0.056) ( Table 1). Based on previous observations we evaluated the association of AI and Echo parameters with Relapse and Death after AlloHCT ( Table 1). Age (HR 1.32, CI 1.01-1.71, p=0.041) and IPSS-R (HR 1.20, CI 1.08-1.33, p=0.0009) were significantly associated with Death after AlloHCT, while HCTCI (HR 1.10, CI 1.00-1.22, p=0.052) and higher LV EF (HR 0.63, CI 0.38-1.06, p=0.084) were borderline. For Relapse, only IPSS-R (HR 1.52, CI 1.31-1.75, p=1.22E-08) was significant, while increase Echo E velocity was of borderline significance (HR 0.45, CI 0.20-1.02, p=0.057). Conclusions Afib is a common post-AlloHCT complication and is more frequent with increasing Age. Echo parameters (specifically E/A ratio) predict significantly higher Afib risk, while the baseline ECG AI algorithm was of borderline significance. The selection of patients with lower HCTCI scores, and the low background prevalence of Afib in this cohort (i.e., selection of patients with lower baseline cardiac morbidity) are possible explanations for non-significance of the AI algorithm. As anticipated Age and IPSS-R are the greatest predictors of Death after AlloHCT, although the suggestion of an association with baseline Echo parameters highlights the importance of identifying those who may benefit from preemptive Cardiology intervention.

Phase II Trial of Reduced-Intensity Fludarabine, Melphalan, and Total Body Irradiation Conditioning Results in Favorable Outcomes with Haploidentical Donor Peripheral Blood Stem Cell Transplant

Introduction High risk hematologic malignancies are curable with allogeneic hematopoietic cell transplant (HCT). Haploidentical (haplo) HCT with post-transplant cyclophosphamide (PTCy) has improved access to transplant in patients lacking an HLA matched donor. However, traditional reduced-intensity conditioning (RIC) with fludarabine/cyclophosphamide/total body irradiation (TBI) for haplo HCT with PTCy is marred by high rates of relapse. This study seeks to optimize the RIC haplo HCT with PTCy platform in older adults with a slight intensification in conditioning and the use of peripheral blood stem cell (PBSCT) grafts in lieu of bone marrow grafts (BMT). Additionally, tacrolimus was substituted by sirolimus based on prior phase II data suggesting favorable rates of graft-versus-host disease (GVHD) after haplo PBSCT with PTCy (Bejanyan, Blood Adv. 2021). We hypothesized that this approach could successfully reduce the risk of relapse and improve disease-free survival (DFS) without substantially increasing non-relapse mortality (NRM). Methods: This single arm, single center phase II trial of haplo PBSCT used a RIC regimen consisting of Melphalan 70 mg/m 2 IV on day -6, fludarabine 30mg/m 2 IV daily on days -6 to -2, and TBI 200 cGy on day -1 (NCT04191187). Subjects received haplo PBSCT with a target dose of 5 x 10 6 CD34+ cells/kg and capped at 7 x 10 6 CD34+ cells/kg. GVHD prophylaxis consisted of PTCy 50 mg/kg on days +3 and +4, mycophenolate mofetfil (MMF) 1 gram three times daily from days +5 to +35, and sirolimus initiated at a target trough of 8-14 ng/mL on day +5 and tapered off between days +100 and +180. Eligibility criteria required a hematologic malignancy as the indication for allogeneic HCT and either age >55 years or a hematopoietic cell transplant comorbidity index (HCT-CI) > 3. The primary endpoint of this study is DFS with a hypothesis that the experimental regimen would have an 18 month DFS of 60% compared to a historic DFS of 40% and 90% power to reject the null hypothesis. Results: A total of 34 subjects were treated on the trial. The median age was 66 years (range: 31-74 years). The HCT-CI score was > 3 in 41%. Acute myeloid leukemia (AML, 44%) was the predominant indication for transplant followed by myelodysplastic syndromes (MDS, 29%). Nine patients (26%) were from underrepresented racial/ethnic minorities (those other than non-Hispanic white). Five patients (15%) received tacrolimus for GVHD prophylaxis before a protocol amendment changed the regimen to sirolimus for the remaining 29 patients (85%). The median follow-up time for 25 surviving patients was 28.5 months . The trial met the primary endpoint with 18-month DFS of 70.5% (90% CI > 59.1%, p=0.002). We observed no primary graft failure events. Neutrophil engraftment by day 30 was achieved in 30 patients (88%), and platelet engraftment by day 60 was achieved in 28 patients (82%). The cumulative incidence of grade II-IV acute GVHD at day 100 was 11.8% (95% CI: 3.6-25.1%). The cumulative incidence of moderate to severe chronic GVHD at 18 months was 9.1% (95% CI: 2.2-22.0%). At 18 months, the cumulative incidence of NRM was 17.7% (95% CI: 7.0-32.2%) and of relapse was 11.9% (3.7-25.4%). GVHD-free relapse-free survival at 18 months was 61.4% (95% CI: 42.9-75.5%) and the overall survival at 18 months was 73.3% (95% CI: 54.9-85.1%). Conclusion: In this completed phase II trial of fludarabine, melphalan 70 mg/m 2, TBI with haplo PBSCT and PTCy/sirolimus/MMF, the primary endpoint was met with an 18-month DFS that was superior to historical control. This was attributable to low rates of relapse without excessive NRM. Acute and chronic GVHD rates were favorable. Pharmacogenomic and pharmacokinetic correlative data is pending and will be included in the final presentation. These promising results merit further investigation to potentially establish this platform as a new standard approach to RIC haplo PBSCT.

Stratification Using ECOG, ADL and HCT-CI Scales, but Not CGA Enables Identifying Elderly AML Patients Fit for Intensive Chemotherapy - a Multicenter Study from Polish Adult Leukemia Group

Introduction: A key part of decision-making in older AML patients is an insightful clinical assessment before qualification for treatment with intensive chemotherapy (IC). It was demonstrated that among the patients initially deemed “fit” for IC, there are vulnerable patients who experience greater treatment toxicity and have poorer outcomes. Comprehensive geriatric assessment (CGA) is a well-recognized tool for identifying such patients. However, due to its time-consuming nature, it is not commonly used. A number of other prognostic models exist, but none of them enable fast and optimal identification of patients eligible for IC. Aim: In this prospective observational study our group aimed to I) assess clinical outcomes of elderly AML patients who were stratified by Eastern Cooperative Oncology Group Performance Status (ECOG PS), Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), Activity of Daily Living (ADL) scales and received IC and II) evaluate the predictive and prognostic value of CGA components. Material and methods: AML patients aged between 60 and 75 were considered fit for IC if they met all 3 stratification criteria: ECOG PS<2 and HCT-CI<3 and ADL=6. IC regimens included daunorubicin and cytarabine (DA) or daunorubicin, cytarabine and cladribine (DAC) followed by 2 consolidation cycles according to local references. CGA was performed by a qualified medical professional before treatment initiation. CGA included Instrumental Activities of Daily Living Score (iADL), timed up and go test (TUG), geriatric depression scale (GDS), Mini-mental scale Examination (MMSE) and Mini Nutritional Assessment (MNA). The correlations between CGA and complete response (CR) rate were determined by Chi-square test or Fisher's exact test. The Kaplan-Meier analysis and log-rank test were used to compare relapse-free survival (RFS) and overall survival (OS) Results: In total, 85 patients with a median age of 65 years [IQR:63.5-69.0] and slight male predominance (53%) were included in the study. Most patients had HCT-CI score <2 (71.8%). Secondary AML was diagnosed in 23.5% of patients, and most patients had intermediate (32.9%) or adverse (37.6%) ELN cytogenetic risk. Fifty-five (58.8%) patients achieved CR after induction. Median OS reached 16.0 months [95% CI: 11.0-21.00] with median RFS 15.3 months [95% CI: 12.1-18.4]. No significant difference in CR rate (p=0.451), OS (p=0.484) or RFS (p=0.529) was demonstrated between DA or DAC groups. Regardless of induction regimen, patients with CR presented significantly improved OS (p=0.015 for DA, p=0.029 for DAC) compared with non-CR patients. None of the CGA components was shown to influence the CR rate, OS or RFS. Conclusions: In patients aged 60-70 years with AML, stratification by ECOG, ADL, and HCT-CI is an effective tool for qualifying patients for intensive chemotherapy. Comprehensive geriatric assessment does not improve identification of vulnerable patients in this group.

Favorable Survival Outcomes in AML Patients Undergoing Allogeneic Hematopoietic Cell Transplant with Fludarabine/Melphalan-Conditioning with Tacrolimus/Sirolimus-Based Gvhd Prophylaxis

Introduction: Fludarabine/melphalan (F/M) conditioning is associated with superior disease-free survival (DFS) compared to busulfan-based reduced-intensity conditioning (RIC) regimens in patients with AML/MDS undergoing allogeneic hematopoietic cell transplantation (alloHCT). A recent CIBMTR analysis in AML patients reported 5-year OS, cumulative incidence of Relapse (CIR) and NRM of 29%, 36% and 36% respectively after F/M conditioning when Tac/MTX was used for graft-vs-host disease (GVHD) prophylaxis (Blood Adv 2020). At City of Hope (COH), tacrolimus and sirolimus (T/S)-based GVHD prophylaxis has been used in patients undergoing HLA-matched sibling and unrelated donor alloHCT, based on the results of a phase 2 study by Rodriguez et al (Blood 2010). Here, we retrospectively reviewed clinical outcomes of 409 consecutive AML patients who underwent RIC alloHCT at COH from 2008-2019 with F/M conditioning and T/S-based GVHD prophylaxis. The primary objective was to assess long term survival outcomes and associated risk factors adjusted for secular trends in patient demographics undergoing alloHCT over time. Methods: Descriptive statistics were used to summarize patient demographics, and disease characteristics. Kaplan-Meier curves and log-rank test were used to evaluate OS and LFS. Cumulative incidence curves and Gray test were used to examine differences in relapse and NRM. The assumptions of proportionality for Cox regression and Fine-Gray models were checked by corresponding tests and plots of the scaled Schoenfeld residuals. To study changes in patient demographics, we divided patients into early era of 2008-2012 (n=140; 34%) and late era of 2013-2019 (n=269; 66%). Results: Patient and HCT characteristics are shown in Table 1. Briefly, the median age was 63 years (range: 19-78) and 70% of patients underwent alloHCT in CR-1. Cytogenetics (ELN 2017) were classified as adverse risk in 25% (n=104) and intermediate risk in 65% (n=265) patients. By disease risk index (DRI), patients were categorized as low (32%; n=131), intermediate (47%; n=193), or high/very high risk (20%; n=84). KPS of 80-100 was recorded in 93% of patients and HCT comorbidity index score of ≥3 was seen in 41%. AML-from prior hematologic disorder (secondary AML) or therapy related was documented in 32% (n=133) and data on somatic mutations and measurable residual disease (MRD) were available only in the recent era. Compared to the early era, HCT recipients of the recent era were significantly older(64 vs 60 years; p=0.0001), had higher HCT-CI (median score of 3 vs 1; p<0.0001), and more patients with KPS < 80 (9% vs 2 %; p=0.0024). With the median follow-up duration of 4 years (range: 0.3-12.5) for the whole cohort, the 5-year OS and DFS were 53% (95% CI: 0.48-0.58) and 51% (95% CI: 0.46-0.56), respectively. The cumulative incidence of relapse (CIR) at 5 years was 23% (95% CI: 0.19-0.28). The non-relapse mortality (NRM) at day+100 and 5 years were 5% (95% CI: 0.03-0.08) and 25% (95% CI:0.20-0.29), respectively. Day +100 grade 2-4 acute GVHD was 37% (95% CI: 0.32-0.42) and 2-year chronic GVHD was 70% (95% CI: 0.65-0.74). Overall survival (OS) and disease-free survival (DFS) were not significantly different in the two eras (Figure 1). Despite high incidence of cGVHD, only 21% (n=86) required prednisone at one year with median dose of 10 mg/day (range: 2-60mg/day). In key subgroups of interest, the 5-year OS were: 70% for FLT3-ITD mutation (n=50), 70% for NPM1 mutation (n=47), 83% for IDH 1/2 mutation (n=30), 65% for patients older than ≥70 (n=55), and 55% (95%CI :43-63) for secondary AML (n=102). MRD by multi-color flow cytometry was available in 58 patients in CR of whom 18 were MRD-positive; this was associated with worse 5-year OS (26%: 95% CI: 5.5-53%). Multivariate analyses (MVA) identified DRI high/very high-risk as the only independent variable associated with worse OS (HR=1.62, [95%CI: 1.16-2.27]) and DFS (HR=1.76, [95%CI: 1.28-2.41]), primarily due to increased NRM (HR 1.86, 95%CI [1.21-2.87]), while its impact on relapse was insignificant. Conclusion: Fludarabine-melphalan with T/S associated with favorable long-term OS with good disease control without excessive NRM, even in high-risk patient subgroups and changing demographics of older adults with higher comorbidity. However, cGVHD rates remain high and novel strategies are being explored to realize the OS benefits of the FM backbone while attenuating chronic GVHD and NRM.

Myeloablative Dose of Busulfan and Fludarabine Combined with In Vivo T Cell Depletion Is Safe and Effective Conditioning for Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative strategy for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The prediction of transplantation-related mortality (TRM) using the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score and an arbitrary upper age limit of 55 years for administering myeloablative conditioning (MAC) are common strategies to ensure a safe procedure. The use of reduced-toxicity conditioning regimens is an additional approach to providing safe and effective myeloablation. Herein we report the outcome of AML and MDS patients conditioned with fludarabine and a myeloablative dose of busulfan (FB4) stratified by age and HCT-CI score. The primary objective was overall survival (OS) for patients age ≥55 years. Secondary objectives were total OS, TRM, graft-versus-host disease (GVHD), and GVHD, relapse-free survival (GRFS). The 2 year OS was 72% in patients age <55 and 51% in patients age ≥55. In patients age ≥55 with an HCT-CI <2, the estimated 2 year OS was 64%, with median OS not reached. In those with HCT-CI ≥2, the 2-year OS was 43%, with a median OS of 14 months. The total cumulative incidence of relapse was 30% regardless of age or HCT-CI score. FB4 conditioning regimen offers a high rate of prolonged remission with a relapse rate similar to that reported in previous studies. These positive outcomes suggest that this conditioning platform can be offered to patients age ≥55 years in the absence of comorbidities, and that age should not be the sole determinant of conditioning intensity.

The prognostic value of patient-reported outcomes in allogeneic hematopoietic stem cell transplantation: exploratory analysis of a randomized nutrition intervention trial

Whether patient-reported outcomes (PROs) can predict overall survival (OS) and non-relapse mortality (NRM) among recipients of allogeneic stem cell transplantation (allo-HSCT), is unclear. We performed an exploratory analysis of the prognostic value of patient-reported outcomes (PROs) among 117 recipients of allogeneic stem cell transplantation (allo-HSCT) who participated in a randomized nutrition intervention trial. Cox proportional hazards models were used to investigate possible associations between PROs collected pre-allo-HSCT (baseline) using scores from the EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) and 1-year overall survival (OS), whereas logistic regression was used to study associations between these PROs and 1-year non-relapse mortality (NRM). Multivariable analyses indicated that only the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) and the European Bone Marrow Transplantation (EBMT) risk score were associated with 1-year OS. In the multivariable model including clinical-sociodemographic factors for 1-year NRM, our analysis showed that living alone (p=0.009), HCT-CI (p=0.016), EBMT risk score (p=0.002), and stem cell source (p=0.046) could be associated with 1-year NRM. Moreover, in the multivariable model, our analysis showed that only appetite loss from the QLQ-C30 was associated with 1-year NRM (p=0.026). In conclusion, in this specific setting, our analysis suggests that the commonly used HCT-CI and EBMT risk scores could be predictive for both 1-year OS and 1-year NRM, whereas baseline PROs in general were not.

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

Assessment of Comorbidities and Their Association with Outcomes in Adults with Acute Lymphoblastic Leukemia (ALL)Using Various Comorbidity-Based Scoring Systems

Background: Outcomes of adults with ALL has remained poor as compared to pediatric ALL. While biological characteristics of the disease can increase the risk of poor treatment responses and resistance, age and concurrent comorbidities limit patient's tolerability to aggressive therapies and predispose to treatment related adverse effects, ultimately affecting survival. Despite similar chronological age, patients vary widely with respect to comorbidities and other aspects of health such that routine performance assessment scales such as Eastern Cooperative Oncology Group (ECOG) or Karnofsky Performance Scale (KPS) may not be accurate in assessing their fitness for therapy. Several measures such as Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), Charlson Comorbidity Index (CCI), Cumulative Illness Rating Scale-Geriatric (CIRS-G) and Adult Comorbidity Evaluation-27 (ACE-27) have been reported in the literature to assess comorbidities in patients receiving intensive treatments, but their utility when it comes specifically to ALL patients is unknown, given the lack of studies assessing role comorbidities in ALL. Methods: We conducted a retrospective single center analysis of adults (age >=18) with ALL to assess the effect of comorbid conditions using available scales and determined their association with outcomes. Patients with a diagnosis of ALL (B/T-cell) who received first line therapy between 2009-2021 were included. Key exclusion criteria were patients with relapsed/refractory ALL and with incomplete follow-up. Comorbid conditions prior to first line therapy were calculated using four scales - HCT-CI, CCI, CIRS-G and ACE-27. Baseline demographic and disease characteristics, first line treatment, response, outcomes were collected using chart review. Descriptive statistics, logistic regression, Cox Proportional Hazards regression method was used for analysis. Concordance (C-statistic) and 95% confidence interval was reported for each model for comparison. A receiver operating characteristic (ROC) curve was also created for each outcome to compare the performance of base and comorbidity score models. Results: A total of 201 patients were included for analysis. Median age was 54(range 39-65), 53% were males, 82% were Caucasians, 8.5% Hispanics. 86% had B-ALL (32% were Philadelphia chromosome positive), 83% received intensive therapy. Median OS was 3.8 years (3.7-not reached) and Event free survival was 2.0(1.5,3.3) for the entire patient population. Patients were categorized in 0(22%), 1 (19%),2(13%) and 3+(46%) per HCT-CI, 0(32%), 1(23%),2(12%) and 3+(33%) per CCI. In CIRS-G scale patients were categorized in to 2 groups of <6 and >=6(51.5% vs 48.5%). In ACE-27 scale there were 4 categories (none(0),mild(1) moderate(2) and severe(3)) with 19%, 41%, 21% and 18% in each group consecutively. All four comorbidity scales were able to predict overall and event-free survival with statistical significance. Patients with HCT-CI category of <=1 had statistically significant OS and EFS advantage when compared to patients with a score of >=2 (Not reached vs 3.1-3.7 yrs for OS, 2.4-5.2 vs 1.4-1.6 yrs for EFS). Patients with CCI category 0 (not reached, 3.4) had better median OS and PFS than categories 1,2 (3.7 years OS, 1.8-3.1 yrs PFS) and 3+ (3.4, 1.4 yrs). CIRS-G category of <6 score had better median OS and PFS (not reached) than 6+ category (3.0 yrs). In ACE-27 scale, 0 and 1 categories had better OS and PFS (not reached and 3.4 yrs, not reached and 2.3 yrs vs 3.0-3.2 and 1.4 yrs) than moderate and severe (2,3) categories. Though all scales could predict OS and EFS, the overall survival model with CIRS-G scale had a significantly higher C-statistic compared to the base model than other scales. The HCT-CI and CIRS scores were each significant in their models for complete remission, but there were no significant differences between c-statistics among any of the CR models. None of the comorbidity scores were significant in predicting 90-day readmission or ED visit. Conclusions: Comorbidities as assessed by HCT-CI, CCI, ACE-27 or CIRS-G were significantly associated with survival in adults with ALL. Incorporation of these formal methods of comorbidity assessment in clinical practice is needed to assess ALL patients at baseline and tailor therapy accordingly. Prospective studies to validate and identify the optimal comorbidity determination scale in ALL is needed. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Utility and Validity of Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) in Predicting Overall Survival and Non-Relapse Mortality in Adolescent and Young Adult Population

Introduction: Hematopoietic cell transplantation-comorbidity index (HCT-CI) is a scoring tool of pretransplant comorbidities that is widely used to predict posttransplant overall survival (OS) and non-relapse mortality (NRM). It was initially studied and validated on cohorts of patients from two institutions with higher HCT-CI score predicting higher NRM and lower OS. Median age of patients in those cohorts was 44.8 (0.8-72.2). Further studies from multiple centers showed similar results however, most of these studies included patients older than 40 years. One study looked at the usefulness of HCT-CI in adolescent and young adult (AYA) population and found that HCT-CI might be useful in predicting OS but not NRM, although the sample size was only 56 patients. We aim in this study to test the utility and validity of HCT-CI for predicting OS and NRM in a larger cohort of AYA patients undergoing allogenic stem cell transplant in our center. Methods: We conducted a retrospective cohort, single center study. Only patients between the ages of 14 and 40 years were included. Patients were divided into 3 groups according to HCT-CI: 0, 1-2, or more than 2. Causes of death were assigned as either relapse related versus non-relapse related mortality. Patients have to be seen in clinic at least once after discharge to be included. Results: 499 patients were included in the study. Median age was 24 years. 292 (58.5%) male and 207 (41.5%) female (P = 0.4). Among those patients, 184, 162 and 153 were having HCT-CI of 0, 1-2 and more than 2 respectively (P = 0.4). 361 (73%) patients were having malignant disease while 138 (27%) were having non-malignant disease (P = 0.18). 2-year and 4-year NRM were 8.6% and 16.1% for HCT-CI 0, 9.8% and 20.4% for HCT-CI 1-2, 10% and 16.18 for HCT-CI more than 2 (P = 0.9). 2-year and 4-year OS were 75.7% and 62% for HCT-CI 0, 69.7% and 58.5% for HCT-CI 1-2, 63.5% and 53.7 for HCT-CI more than 2 (P = 0.06). There was no statistically significant difference among all 3 groups in terms of OS or NRM. Conclusion: HCI-CI was not predictive of neither OS nor NRM in our cohort of patients aged between 14 and 40 years. Limitations of our study include the retrospective nature of data collection as well as being a single center-based study. Larger prospective studies in this particular age group would help to more accurately risk stratify patients and predict their post-transplant course. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

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

Social Vulnerability and Risk of Nonrelapse Mortality After Allogeneic Hematopoietic Cell Transplantation.

Risk of nonrelapse mortality (NRM) after hematopoietic cell transplantation (HCT) is high. Patient-level clinical prediction models such as the HCT-comorbidity index (HCT-CI) help identify those at increased risk for NRM, but the independent contribution of social determinants of health on HCT outcomes is not well characterized. This study included 1602 patients who underwent allogeneic HCT between 2013 and 2019 at City of Hope. Census tract-level social vulnerability was measured using the social vulnerability index (SVI). Fine-Gray multivariable regression evaluated the association between SVI and 1-year NRM. Subgroup analysis examined risk of NRM across combined SVI and HCT-CI categories and by race and ethnicity. Cumulative incidence of 1-year NRM after HCT was 15.3% (95% confidence interval [CI] = 13.6% to 17.1%). In multivariable analysis, patients in the highest SVI tertile (highest social vulnerability) had a 1.4-fold risk (subdistribution hazard ratio [sHR] = 1.36, 95% CI = 1.04 to 1.78) of NRM compared with individuals in the lower tertiles; patients in the highest SVI tertile who also had elevated (≥3) HCT-CI scores had the highest risk (sHR = 1.81, 95% CI = 1.26 to 2.58) of 1-year NRM (reference: lower SVI tertiles and HCT-CI < 3). High social vulnerability was associated with risk of 1-year NRM in Asian (sHR = 2.03, 95% CI = 1.09 to 3.78) and Hispanic (sHR = 1.63, 95% CI = 1.04 to 2.55) but not non-Hispanic White patients. High social vulnerability independently associated with 1-year NRM after HCT, specifically among minority populations and those with a high comorbidity burden at HCT. These findings may inform targeted approaches for needs assessment during and after HCT, allowing for timely interventions to improve health outcomes in at-risk patients.

P1444: IMPACT OF CO-MORBIDITIES ON NON-RELAPSE MORTALITY AND CYTOKINE-RELEASE SYNDROME AFTER CD19 CAR-T CELL THERAPY - A RETROSPECTIVE STUDY FROM THE TCWP OF THE EBMT AND GOCART COALITION

Background: CAR T-cell therapies have been associated with a profile of significant toxicities and previously unknown side effects. For that reason, the registration of clinical trials with commercial and non-commercial products included very strict inclusion and exclusion criteria, to minimize severe adverse events and maximize therapeutic effect. The real-life analyses revealed that a proportion of patients are treated outside of these specifications, with variable outcomes. Aims: The goal of this study was to determine the cumulative incidence of non-relapse mortality (NRM) and cytokine-release syndrome (CRS) after anti-CD19 CAR T-cell therapy, and impact of patients’ co-morbidities expressed as the hematopoietic cell transplantation-co-morbidity index (HCT-CI) scores, on the major outcome measures. Methods: This is a retrospective multicentre analysis from the Transplant Complications Working Party (TCWP) of the EBMT using the data of the GoCART coalition. Eligibility criteria for this analysis include diffuse large B-cell lymphoma (DLBCL) and acute lymphocytic leukemia (ALL) patients that underwent CD19 CAR T-cell therapy in an EBMT member centre before 31 January 2021. Exclusion criteria were lack of information on comorbidities, survival or relapse status, or age <18 years. Outcomes were measured from the date of CAR T-cell infusion for all endpoints. NRM was defined as death without relapse/progression. Cumulative incidence functions were used to estimate the incidence of complications. Multivariate analyses were performed using the Cox cause-specific model for all endpoints. The primary endpoint was NRM at 3 and at 12 months post CAR T-cell therapy, while secondary endpoints included cumulative incidence of CRS as well as NRM and CRS incidence in subgroups based on HCT-CI. Statistical analyses were performed with R 3.4.2 software packages. Results: The study identified 586 patients treated with CAR T-cells in the years 2018-2021 for DLBCL (96.4%) or ALL (3.6%). The median age was 60 (range, 18-84). 166/437 (38%) patients had a Karnofsky performance status <90%, while the HCT-CI was available for 483 (82%) patients and was intermediate (1-2) in 17.6% and high (≥3) in 13.9% of these patients. The most common co-morbidities were pulmonary (16.1%), cardiac (6.8%), obesity (6.8%), diabetes (6.4%), arrythmia (5.5%), history of solid tumor (5.3%), and active infection before treatment (4.3%). The median follow up was 12.5 months. The NRM was reported to be very low: 1.7% (95%CI 0.9-3) at 3 months and 2.9% (95%CI 1.7-4.5) at 12 months. The cumulative incidence of CRS (all grades) was 35.3% (95%CI 30.6-40.1) at 3 days and 82.7% (95%CI 78.5-86.1) at 12 days. Unexpectedly, no significant impact of HCT-CI on NRM, CRS incidence, or overall survival was observed (Fig. 1) both in univariate and multivariate analyses. Most deaths were caused by the original disease (75.4%) with concomitant infection (5.9%) or with multiorgan failure (4.3%). Image:Summary/Conclusion: Our real-life data from the GoCART registry revealed the profile and frequency of co-morbidities of patients undergoing CAR T-cell treatments at EBMT centers. While the HCT-CI score was high in a substantial proportion of patients, it did not influence any major outcome. The incidence of CRS was also high and not influenced by the HCT-CI. Our preliminary results might support application of more liberal criteria for patient qualification for CAR T-cell therapies based on co-morbidities, but this needs to be confirmed in further studies.

Impact of risk scores in outcome of patients with myeloid neoplasms after allogeneic stem cell transplant

BackgroundThe main causes of failure of allogeneic hematopoietic stem cell transplantation (allo-transplant) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are relapse and transplant-related mortality. Different scores have been designed to predict the prognosis of these patients. The objective of this study was to assess which score or combination has better outcome predictive capacity. MethodsRetrospective analysis of patients with AML and MDS who received a first peripheral blood allo-transplant in a single center, between December 2001 and October 2019. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) and Disease Risk Index (DRI) scores were calculated. For each score and for the HCT-CI/DRI and HCT-CI/EBMT combinations, overall survival (OS), cumulative incidence of relapse (CIR), non-relapse-related mortality (NRM), and graft versus host disease-free relapse-free survival (GRFS) were analyzed. Results175 patients were evaluated. With a median (range) follow-up of 3.96 (0.32–17.22) years, the 5-year probabilities (95% CI) of OS, CIR, NRM, and GRFS were 36% (28%–44%), 28% (21%–35%), 38% (30%–46%) and 24% (17%–31%), respectively. For OS, only the DRI score selected two groups with statistically significant differences (DRI 0–1: 41% vs. DRI ≥2: 24%; p=0.011). The combination of DRI 0–1 and HCT-CI 0–2 showed OS probabilities of 45% vs. 26% for those with DRI 0–1 and HCT-CI ≥3; p=0.041. ConclusionsIn patients with AML and MDS submitted to allo-transplant, the combination of HCT-CI and DRI scores provided the best stratification for OS.

Noninfectious Pulmonary Toxicity after Allogeneic Hematopoietic Cell Transplantation

Noninfectious pulmonary toxicity (NPT), a significant complication of allogeneic hematopoietic cell transplantation (alloHCT), includes idiopathic pneumonia syndrome (IPS), diffuse alveolar hemorrhage (DAH), and cryptogenic organizing pneumonia (COP), with an overall incidence ranging from 1% to 15% in different case series and a variable mortality rate. A registry study of the epidemiology and outcomes of NPT after alloHCT has not been conducted to date. The primary objective of the present study was to assess the incidence of and risk factors for IPS, DAH, and COP; the secondary objective was to assess overall survival (OS) in patients developing NPT. This retrospective study included adult patients who underwent alloHCT between 2008 and 2017 and reported to the Center for International Blood and Marrow Transplant Research. Multivariable Cox proportional hazards regression models were developed to identify the risk factors for development of NPT and for OS, by including pretransplantation clinical variables and time-dependent variables of neutrophil and platelet recovery, and acute graft-versus-host disease (GVHD) post-transplantation. This study included 21,574 adult patients, with a median age of 55 years. According to the HCT Comorbidity Index (HCT-CI), 24% of the patients had moderate pulmonary comorbidity and 15% had severe pulmonary comorbidity. The cumulative incidence of NPT at 1 year was 8.1% (95% confidence interval [CI], 7.7% to 8.5%). Individually, the 1-year cumulative incidences of IPS, DAH, and COP were 4.9% (95% CI, 4.7% to 5.2%), 2.1% (95% CI, 1.9% to 2.3%), and .7% (95% CI, .6% to .8%), respectively. Multivariable analysis showed that severe pulmonary comorbidity, grade II-IV acute GVHD, mismatched unrelated donor and cord blood transplantation, and HCT-CI score ≥1 significantly increased the risk of NPT. In contrast, alloHCT performed in 2014 or later, non-total body irradiation (TBI)- and TBI-based nonmyeloablative conditioning and platelet recovery were associated with a decreased risk. In a landmark analysis at day+100 post-transplantation, the risk of DAH was significantly lower in patients who had platelet recovery by day +100. Multivariable analysis for OS demonstrated that NPT significantly increased the mortality risk (hazard ratio, 4.2; P < .0001).

Hematopoietic Cell Transplantation-Comorbidity Index Score Is Correlated with Treatment-Related Mortality and Overall Survival following Second Allogeneic Hematopoietic Cell Transplantation in Children

Allogeneic hematopoietic cell transplantation (HCT) can lead to considerable complications and treatment-related mortality (TRM); therefore, a detailed assessment of risks is essential. The Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) can predict both TRM and overall survival (OS). Although the HCT-CI has been validated as a useful tool for first HCT, its potential utility for second HCT has not yet been investigated. Here we aimed to evaluate the utility of the HCT-CI score in assessing the risk of TRM and OS in the setting of a second allogeneic HCT. This was a retrospective analysis of all pediatric patients (age <21 years) who underwent a second allogeneic HCT at UCSF Benioff Children's Hospital San Francisco between 2008 and 2019. According to their HCT-CI, patients were classified as "low risk" with an HCT-CI of 0 or "intermediate-high risk" with an HCT-CI ≥1. A total of 59 patients were included in the study. Our primary endpoint was TRM, observed at 100 days, 180 days, 1 year, and last follow-up following HCT, and our secondary endpoint was OS at 1 year and at 5 years or last follow-up. We also evaluated outcomes of patients admitted to the pediatric intensive care unit based on the HCT-CI score. Seventy-six percent of patients had an HCT-CI of 0. The most frequent comorbidities were pulmonary, seen in 7 patients (12%; 95% CI, 5% to 23%), including 5 (71%) with moderate and 2 (29%) with severe comorbidities. The OS and the cumulative incidence of TRM at 1 year for the entire cohort were 81% (95% CI, 69% to 90%) and 12% (95% CI, 5% to 22%), respectively. The cumulative incidence of TRM and OS at 1 year showed a significant correlation with HCT-CI score; TRM was 4% (95% CI, 1% to 13%) for an HCT-CI of 0 versus 36% (95% CI, 13% to 60%) for an HCT-CI ≥1 (P < .001), and OS was 89% (95% CI, 75% to 99%) for an HCT-CI of 0 versus 57% (95% CI, 28% to 78%) for an HCT-CI ≥1 (P=.003). After adjusting for covariates, HCT-CI continued to be associated with both TRM (P=.004) and OS (P=.003). In addition, comparing patients with malignancies and nonmalignant disorders, disease-free-survival at last follow-up was higher in the nonmalignant disorder group and also was influenced by the HCT-CI score in each group (P=.0035). There also was a significant difference in outcomes of patients admitted to the pediatric intensive care unit; 15 patients (68%) with an HCT-CI of 0 were alive at last follow-up, compared with only two (22%) with an HCT-CI ≥1 (P=.016). HCT-CI has an impact on TRM and OS and may serve as a predictor of outcomes of second allogeneic transplantation. Although this study was conducted in a relatively small sample, it is the first to investigate the utility of the HCT-CI score in predicting outcomes after a second allogeneic HCT in pediatric recipients. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

GITMO Registry Study on Allogeneic Transplantation in Patients Aged ≥60 Years from 2000 to 2017: Improvements and Criticisms

Today, allogeneic stem cell transplantation (allo-SCT) can be offered to patients up to age 70 to 72 years and represents one of the most effective curative treatments for many hematologic malignancies. The primary objective of the study was to collect data from the allo-SCTs performed in Italy between 2000 and 2017 in patients aged ≥60 years to evaluate the changes in safety and efficacy outcomes, as well as their distribution and characteristics over time. The Italian Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) AlloEld study (ClinicalTrials.gov identifier NCT04469985) is a retrospective analysis of allo-SCTs performed at 30 Italian transplantation centers in older patients (age ≥60 years) between 2000 and 2017 (n=1996). For the purpose of this analysis, patients were grouped into 3 time periods: time A, 2000 to 2005 (n=256; 12%); time B, 2006 to 2011 (n=584; 29%); and time C, 2012 to 2017 (n=1156; 59%). After a median follow-up of 5.6 years, the 5-year nonrelapse mortality (NRM) remained stable (time A, 32.8%; time B, 36.2%; and time C, 35.0%; P=.5), overall survival improved (time A, 28.4%; time B, 31.8%; and time C, 37.3%; P=.012), and the cumulative incidence of relapse was reduced (time A, 45.3%; time B, 38.2%; time C, 30.0%; P < .0001). The 2-year incidence of extensive chronic graft-versus-host disease was reduced significantly (time A, 17.2%; time B, 15.8%; time C, 12.2%; P=.004). Considering times A and B together (2000 to 2011), the 2-year NRM was positively correlated with the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score; NRM was 25.2% in patients with an HCT-CI score of 0, 33.9% in those with a score of 1 or 2, and 36.1% in those with a score of 3 (P < .001). However, after 2012, the HCT-CI score was not significantly predictive of NRM. This study shows that the transplantation procedure in elderly patients became more effective over time. Relapse incidence remains the major problem, and strategies to prevent it are currently under investigation (eg, post-transplantation maintenance). The selection of patients aged ≥60 could be improved by combining HCT-CI and frailty assessment to better predict NRM.

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.