Treatment of acute myeloid leukaemia in older patients - scope of intensive therapy? - A retrospective analysis.

PURPOSE: Therapeutic regimens and outcome of acute myeloid leukaemia (AML) patients substantially improved over the past decades. However, AML in older patients is still widely understudied and therapeutic standards are far less well defined. This study provides a retrospective analysis of a cohort of AML patients above 65 years of age treated at a single university centre in Germany. METHODS: Treatment regimens including intensive chemotherapy with or without subsequent allogenic stem cell transplantation (allo-SCT), hypomethylating agent (HMA) or low-dose cytarabine (LD-AraC) based therapy or best supportive care (BSC) were evaluated and compared to patient-specific variables, comorbidities indices such as Haematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) or Charlson Comorbidity Index (CCI), or Eastern Cooperative Oncology Group (ECOG) performance status to assess their potential impact on outcome. RESULTS: 229 patients ≥ 65 years with newly diagnosed AML were included in this study. Patients received either intensive chemotherapy (IT) without (n = 101, 44%), or followed by allo-SCT (n = 27, 12%), HMA (n = 29, 13%), LD-Ara-C (n = 16, 7%) or best supportive care (BSC) only (n = 56, 24%). Of interest, ECOG performance status predicted overall survival in patients treated with IT, and combinatorial assessment of ECOG and HCT-CI was particularly useful to predict outcome in this subgroup of patients. CONCLUSION: Subsets of AML patients above 65 years of age benefit from intensive chemotherapy and allogenic stem cell transplantation. Combined assessment of ECOG scores and HCT-CI might help to objectively identify suitable patients, and this concept should be further investigated in a prospective manner in future studies.

Selected subsets of AML patients may profit from intensive chemotherapy and allogenic stem cell transplantation.Combined analysis of ECOG performance status and HCT-CI might help to predict outcome in elderly AML patients.

Combining the HCT-CI, G8, and AML-Score for Fitness Evaluation of Elderly Patients with Acute Myeloid Leukemia: A Single Center Analysis.

BACKGROUND: Accurate assessment of elderly acute myeloid leukemia (AML) patients is essential before intensive induction chemotherapy and subsequent allogeneic hematopoietic stem cell transplantation. In this context, we investigated the capacity of three scores for frailty prediction. METHODS: At diagnosis, 197 patients were clinically evaluated for appropriate treatment intensity. In parallel and independently, the G8-score, the Hematopoietic Stem Cell Index (HCT-CI) and the AML-score for CR were determined for each patient and analyzed with respect to overall survival (OS). RESULTS: The G8-score and the HCT-CI were able to significantly separate "fit" from "unfit" patients, <0.001 and p = 0.008. In univariate Cox models, the predictive role for OS was confirmed: for the G8-score (HR: 2.35, 95% CI 1.53-3.60, p < 0.001), the HCT-CI (HR: 1.91, 95% CI 1.17-3.11, p = 0.009) and the AML-score (HR: 5.59, 95% CI 2.04-15.31, p = 0.001), the latter was subsequently used to verify the cohort. In the multivariate Cox model, the results were confirmed for the G8- (HR: 2.03, p < 0.001) and AML-score (HR: 3.27, p = 0.001). Of interest, when combining the scores, their prediction capacity was significantly enhanced, p < 0.001. CONCLUSIONS: The G8-, the HCTCI and the AML-score represent valid tools in the frailty assessment of elderly AML patients at diagnosis.

Expanded HCT-CI Definitions Capture Comorbidity Better for Younger Patients of Allogeneic HCT for Nonmalignant Diseases.

Allogeneic hematopoietic cell transplantation (HCT) can cure many nonmalignant conditions, but concern for morbidity and mortality remains. To help physicians estimate patient-specific transplant mortality risk, the HCT comorbidity index (HCT-CI) is used. However, pediatric physicians use the HCT-CI less frequently than adult counterparts. We used the Center for International Blood and Marrow Transplant Research database to expand the HCT-CI comorbidity definitions to be more inclusive of children and adolescent and young adult (AYA) patients, adding history of mechanical ventilation, history of invasive fungal infection, assessment of chronic kidney disease (CKD) by estimated glomerular filtration rate, expanding the definition of obesity, and adding an underweight category. A total of 2815 children and AYAs (<40 years old) who received first allogeneic HCT for nonmalignant diseases from 2008 to 2017 were included to create an expanded youth nonmalignant HCT-CI (expanded ynHCT-CI) and a simplified non-malignant (simplified ynHCT-CI) HCT-CI. The expanded comorbidities occurred frequently-history of mechanical ventilation (9.6%), history of invasive fungal infection (5.9%), mild CKD (12.2%), moderate/severe CKD (2.1%), obesity (10.9%), and underweight (14.5%). Thirty-nine percent of patients had an increase in their comorbidity score using the expanded ynHCT-CI, leading to a redistribution of scores: ynHCT-CI score 0 (35%), 1-2 (36.4%), and ≥3 (28.6%). Patients with an increase in their comorbidity score had an increased hazard of mortality compared to those whose score remained the same (hazard ratio = 1.41; 95% confidence interval, 1.01-1.98). Modifications to the HCT-CI can benefit children and AYA patients with nonmalignant diseases, creating a risk assessment tool that is clinically relevant and better captures comorbidity in this younger population.

Adapting the HCT-CI Definitions for Children, Adolescents, and Young Adults with Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation.

Allogeneic hematopoietic cell transplantation is a curative procedure for hematologic malignancies but is associated with a significant risk of non-relapse mortality (NRM). The Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) is a prognostic tool that discriminates this risk in all age groups. A recent survey of transplant physicians demonstrated that 79% of pediatric providers used the HCT-CI infrequently, and most reported concerns about its applicability in the younger population. We conducted a retrospective study using the Center for International Blood and Marrow Transplant Research database to examine the impact of expanded HCT-CI definitions on NRM in pediatric and young adult patients with hematologic malignancies. We included 5790 patients <40 years old receiving allogeneic transplants between 2008 and 2017 to examine broader definitions of comorbidities in the HCT-CI, including history of mechanical ventilation and fungal infection, estimated glomerular filtration rate, and body mass index (BMI) percentiles. Multivariable Fine-Gray models were created to determine the effect of each HCT-CI defining comorbidity and its modification on NRM and were used to develop 2 novel risk scores. We next developed the expanded HCT-CI for children and young adults (youth with malignancies; expanded ymHCT-CI), where 23% patients had an increased comorbidity score, compared to the HCT-CI. Comorbidities with hazard ratio < 1.2 were then removed to create the simplified HCT-CI for children and young adults (youth with malignancies; simplified ymHCT-CI), which demonstrated higher scores corresponded to a greater risk of NRM (P < .001). These novel comorbidity indexes with broader definitions are more relevant to pediatric and young adult patients, and prospective studies are needed to validate these in the younger patient population. It remains to be seen whether the development of these pediatric-specific and practical risk indexes increases their use by the pediatric transplant community.

Autologous stem cell transplant for multiple myeloma: Impact of melphalan dose on the transplant outcome.

We evaluated impact of melphalan dose on transplant outcomes for multiple myeloma. Between 1995 and 2019 459 consecutive patients received a transplant; 69(15%) received melphalan ≤150 mg/m2 (Mel 150 cohort) and 390 (85%) melphalan 200 mg/m2 (MEL 200 cohort). The primary outcome was overall survival (OS) from the date of transplant. Progression-free survival (PFS), engraftment, transplant response, and cumulative relapse at 2 years were secondary outcome measures. Patients in Mel 150 cohort had adverse clinical and laboratory parameters at base line. Transplant response was better for Mel 200 cohort (p < 0.024). Median OS at a median follow-up of 88 months was similar in the two cohorts; 100 Vs 102 months (Mel 200), p = 0.817. Median PFS (60.0 Vs 53 months, p = 0.746), relapse at two years (32.4% Vs 30.9%, p = 0.745) and grade 3-4 mucositis (p = 0.823) were similar. Initial treatment prepares patients better for subsequent similar transplant outcomes despite differences in baseline characteristics.

Risk factors for fatal cardiac complications after allogeneic hematopoietic cell transplantation: Japanese Society for Transplantation and Cellular Therapy transplant complications working group.

Fatal cardiac complications can occur from the early to late phases after hematopoietic cell transplantation (HCT). Herein, the Japanese transplant registry database was used to retrospectively analyze health records of 33,791 allogeneic HCT recipients to elucidate the pathogenesis and risk factors involved. Overall, 527 patients died of cardiac complications at a median of 130 (range 0-3924) days after HCT. The cumulative incidence of fatal cardiac complications was 1.2% (95% confidence interval [CI]: 1.0-1.3) and 1.6% (95% CI: 1.5-1.8) at 1 and 5 years after HCT, respectively. Fatal cardiovascular events were significantly associated with an HCT-specific comorbidity index (HCT-CI) score of ≥1 specific to the three cardiovascular items, lower performance status, conditioning regimen cyclophosphamide dose of >120 mg/kg, and female sex. Cardiovascular death risk within 60 days after HCT was associated with the type of conditioning regimen, presence of bacterial or fungal infections at HCT, and number of blood transfusions. Contrastingly, late cardiovascular death beyond 1 year after HCT was associated with female sex and older age. Lower performance status and positive cardiovascular disease-related HCT-CI were risk factors for cardiac complications in all phases after HCT. Systematic follow-up may be necessary according to the patients' risk factors and conditions.

Development and Validation of a Novel Prognostic Model for Overall Survival in Newly Diagnosed Multiple Myeloma Integrating Tumor Burden and Comorbidities.

Background: Multiple myeloma (MM) is a highly heterogeneous disease with enormously variable outcomes. It remains to be a major challenge to conduct a more precise estimation of the survival of MM patients. The existing stratifications attached less importance to the prognostic significance of comorbidities. In the present study, we aimed to develop and validate a novel and simple prognostic stratification integrating tumor burden and comorbidities measured by HCT-CI. Method: We retrospectively enrolled 385 consecutive newly diagnosed multiple myeloma (NDMM) patients in Xijing Hospital from January 2013 to December 2020. The cohort between January 2016 and December 2020 was selected as development cohort (N = 233), and the cohort between January 2013 and December 2015 was determined as validation cohort (N = 152). By using LASSO analysis and univariate and multivariable Cox regression analyses, we developed the MM-BHAP model in the way of nomogram composed of ß2-MG, HCT-CI, ALB, and PBPC. We internally and externally validated the MM-BHAP model and compared it with ISS stage and R-ISS stage. Results: The MM-BHAP model was superior to the ISS stage and partially better than the R-ISS stage according to time-dependent AUC, time-dependent C-index, DCA, IDI, and continuous NRI analyses. In predicting OS, only the MM-BHAP stratification clearly divided patients into three groups while both the ISS stage and R-ISS stage had poor classifications in patients with stage I and stage II. Moreover, the MM-BHAP stratification and the R-ISS stage performed well in predicting PFS, but not for the ISS stage. Besides, the MM-BHAP model was also applied to the patients with age ≤65 or age >65 and with or without HRCA and could enhance R-ISS or ISS classifications. Conclusions: Our study offered a novel simple MM-BHAP stratification containing tumor burden and comorbidities to predict outcomes in the real-world unselected NDMM population.

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.

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

Abstract Introduction: To 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. Methods: One 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. Results: The 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. Conclusions: This 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.

Discharge Disposition Following Hematopoietic Cell Transplantation: Predicting the Need for Rehabilitation and Association with Survival.

Many hematopoietic cell transplantation (HCT) recipients require rehabilitation due to deconditioning following intensive conditioning regimens and immune reconstitution. HCT recipients are preferentially discharged to home to avoid the risk of exposure to healthcare-associated infection in a rehabilitation facility (RF), with a caregiver who has been provided specific education about the complexity of post-HCT care. This study was conducted to determine the incidence of discharge to an RF following HCT, identify pre-HCT and peri-HCT risk factors for discharge to an RF, and estimate the effect of discharge disposition on overall survival (OS). This retrospective, matched 1:4 case-control study included 56 cases over a 10-year period from a single institution. Controls were matched by transplantation type (autologous versus allogeneic) and date of transplantation. The incidence of discharge to an RF was 2.2%. Controlling for disease, increasing age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.04 to 1.15; P < .001), female sex (OR, 3.11; 95% CI, 1.32 to 7.32; P = .01), high-risk HCT Comorbidity Index (HCT-CI) score (≥3) (OR, 3.44; 95% CI, 1.39 to 8.52; P = .008), decreasing pre-HCT serum albumin (OR, 2.60; 95% CI, 1.07 to 6.38; P = .037), and development of acute kidney injury during HCT (OR, 4.10; 95% CI, 1.36 to 12.40; P = .012) were associated with discharge to an RF. Discharge to an RF was associated with worse OS and higher nonrelapse mortality (NRM) compared with discharge to home (1-year OS, 70.5% [95% CI, 55.8% to 81.1%] versus 88.8% [95% CI, 83.6% to 92.4%], P < .001; 100-day NRM: 9.5% [95% CI, 3.5% to 19.2%] versus 1.8% [95% CI, 0.6% to 4.3%]; P = .03). Discharge to an RF following HCT is a rare event but associated with poor OS. Modifiable risk factors for discharge to an RF, including serum albumin as a measure of nutrition and reversible HCT-CI components, should be prospectively studied to determine the effect of mitigation on discharge disposition and survival.

Impact of Pretransplantation Renal Dysfunction on Outcomes after Allogeneic Hematopoietic Cell Transplantation.

Renal dysfunction is a recognized risk factor for mortality after allogeneic hematopoietic cell transplantation (alloHCT), yet our understanding of the effect of different levels of renal dysfunction at time of transplantation on outcomes remains limited. This study explores the impact of different degrees of renal dysfunction on HCT outcomes and examines whether the utilization of incremental degrees of renal dysfunction based on estimated glomerular filtration rate (eGFR) improve the predictability of the hematopoietic cell transplantation comorbidity index (HCT-CI). The study population included 2 cohorts: cohort 1, comprising patients age ≥40 years who underwent alloHCT for treatment of hematologic malignancies between 2008 and 2016 (n = 13,505; cohort selected given a very low incidence of renal dysfunction in individuals age <40 years), and cohort 2, comprising patients on dialysis at the time of HCT (n = 46). eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. The patients in cohort 1 were assigned into 4 categories-eGFR ≥90 mL/min (n = 7062), eGFR 60 to 89 mL/min (n = 5264), eGFR 45 to 59 mL/min (n = 897), and eGFR <45 mL/min (n=282)-to assess the impact of degree of renal dysfunction on transplantation outcomes. Transplantation outcomes in patients on dialysis at the time of alloHCT were analyzed separately. eGFR <60 mL/min was associated with an increased risk for nonrelapse mortality (NRM) and requirement for dialysis post-HCT. Compared with the eGFR ≥90 group, the hazard ratio (HR) for NRM was 1.46 (P = .0001) for the eGFR 45 to 59 mL/min group and 1.74 (P = .004) for the eGFR <45 mL/min group. Compared with the eGFR ≥90 mL/min group, the eGFR 45 to 59 mL/min group (HR, 2.45; P < .0001) and the eGFR <45 mL/min group (HR, 3.09; P < .0001) had a higher risk of renal failure necessitating dialysis after alloHCT. In addition, eGFR <45 mL/min was associated with an increased overall mortality (HR, 1.63; P < .0001). An eGFR-based revised HCT-CI was also developed and shown to be predictive of overall survival (OS) and NRM, with predictive performance similar to the original HCT-CI. Among 46 patients on dialysis at alloHCT, the 1-year probability of OS was 20%, and that of NRM was 67%. The degree of pretransplantation renal dysfunction is an independent predictor of OS, NRM, and probability of needing dialysis after alloHCT. An eGFR-based HCT-CI is a validated index for predicting outcomes in adults with hematologic malignancies undergoing alloHCT. The outcomes of alloHCT recipients on dialysis are dismal; therefore, one should strongly weigh the significant risks of being on hemodialysis as a factor in determining alloHCT candidacy.

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

INTRODUCTION: To 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. METHODS: One 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. RESULTS: The 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. CONCLUSIONS: This 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 Chimeric Antigen Receptor T Cell Therapy for Diffuse Large B Cell Lymphoma: A Multicenter Analysis.

Chimeric antigen receptor T cell (CAR-T) therapy is approved for treatment of relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). Here we evaluate whether comorbidities, calculated using the Cumulative Illness Rating Scale (CIRS), predict survival for these patients. A retrospective chart review was performed at 4 academic institutions. All patients who underwent leukapheresis for commercial CAR-T therapy for R/R DLBCL were included. CIRS scores were calculated at the time of leukapheresis. High comorbidity was defined as either CIRS ≥7 or the presence of severe impairment (CIRS 3/4 in ≥1 system; CIRS-3+). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and differences in curves were detected by the log-rank test. A total of 130 patients were analyzed, 56.9% with CIRS ≥7 and 56.2% with CIRS-3+. After a median follow-up of 13 months, the median PFS was 6.7 months, and the median OS was not reached. On univariable analysis, Eastern Cooperative Oncology Group (ECOG) performance status (PS) was associated with inferior PFS (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.03-2.05; P = .03) and OS (HR, 1.76; 95% CI, 1.17-2.64; P = .007). Higher CIRS (CIRS ≥7 or CIRS-3+) was associated with inferior OS (HR, 2.12; 95%, CI, 1.06-4.22; P = .03) and a nonsignificant trend in worse PFS (HR, 1.45; 95% CI, .87-2.44; P = .16). In multivariable analyses, CIRS ≥7 or CIRS-3+ and ECOG PS maintained independent prognostic significance. Comorbidities as determined by CIRS and ECOG PS predict inferior survival in patients receiving CAR-T therapy for R/R DLBCL.

Limitations of Applying the Hematopoietic Cell Transplantation Comorbidity Index in Pediatric Patients Receiving Allogeneic Hematopoietic Cell Transplantation.

Identifying which patients are at high risk for transplant-related mortality, prior to allogeneic hematopoietic cell transplantation (alloHCT), is crucial both to guide decision making with patients and families and to inform the alloHCT approach. There is a paucity of data evaluating the utility of the HCT comorbidity index (HCT-CI) in pediatric patients. We performed a retrospective cohort study of 188 patients who underwent alloHCT between January 2008 and October 2016 and assessed pretransplant comorbidities defined and weighted by the HCT-CI. The primary endpoint of our study was overall survival (OS). Kaplan-Meier method was used to assess survival estimates at 1-year post-transplant and did not differ based on HCT-CI scores: 78.7% (SE 6.69%) for HCT-CI = 0, 74.7% (SE 6.33%) for HCT-CI = 1 to 2, and 77.3% (SE 4.17%) for HCT-CI ≥3. Multivariable Cox proportional hazards analysis did not show HCT-CI having an effect on OS: hazard ratio (HR) of 0.633 (95% confidence interval [CI], 0.297 to 1.347) for HCT-CI scores 1 to 2 and HR of 0.935 (95% CI, 0.456 to 1.918) for HCT-CI scores ≥3 compared to scores of 0. The most frequent comorbidities observed were hepatic disease (mild in 29%, severe in 23%) and pulmonary disease (moderate in 15% and severe in 29%). However, only 55% were able to complete pulmonary function testing. Hepatic disease was based on transaminitis in 48% and by bilirubin alone in 26% of patients; 46% of patients with hepatic dysfunction had an underlying hemoglobinopathy and hyperbilirubinemia related to ongoing hemolysis. This study evaluates HCT-CI comorbidities in greater detail than has been performed previously in children undergoing alloHCT. We identify challenges with the HCT-CI in the pediatric population and highlight the comorbidities that may benefit from adjustments to their definition to create an improved risk assessment tool for children.

The Prognostic Impact of Comorbidities in Patients with De-Novo Diffuse Large B-Cell Lymphoma Treated with R-CHOP Immunochemotherapy in Curative Intent.

BACKGROUND: Patient-related factors, namely comorbidities, impact the clinical outcome of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The prevalence and prognostic impact of comorbidities were examined using the validated scores Charlson Comorbidity Index (CCI) and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) in 181 patients with DLBCL at initial diagnosis before treatment with rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone (R-CHOP). RESULTS: Pronounced comorbidities as defined by CCI and HCT-CI scoring of ≥2 were detected in 9.9% and 28.2% of patients, respectively, and occurred more frequently at advanced age (p < 0.001). Higher CCI scoring was associated with lower complete response rate (p = 0.020). Both advanced CCI and HCT-CI were significantly associated with shortened overall survival (3-year OS: CCI ≥2 vs. 0-1, 38.9% vs. 81.3%, p < 0.001; HCT-CI ≥2 vs. 0-1, 56.9% vs. 84.9%, p < 0.001). Both comorbidity scores remained independent risk factors in the multivariate analysis (HCT-CI ≥2 HR: 2.6, p = 0.004; CCI ≥2 HR: 3.6, p = 0.001). CONCLUSION: This study demonstrates the prognostic relevance of comorbidities classified by CCI and HCT-CI in patients with DLBCL undergoing curative treatment with R-CHOP. A structured evaluation of comorbidities might refine prognostication alongside currently used prognostic parameters, namely age, and should be evaluated in prospective trials.

Assessment of older adult candidates for allogeneic hematopoietic cell transplantation: updates and remaining questions.

INTRODUCTION: Allogeneic hematopoietic cell transplantation (allo-HCT) has seen marked growth among older adults, where chronological age is no longer a barrier to transplant. As allo-HCT expands to older and potentially less fit individuals, prognosticating transplant outcomes in this population remains an ongoing need. Areas covered: This review summarizes pre-transplant assessment tools in optimizing patient selection and predicting transplant outcomes in older adults, including comorbidity indices, psychosocial assessment, geriatric assessment, serum biomarkers, and disease risk. This review also discusses the impact of donor age and clonal hematopoiesis of indeterminate significance on transplant outcomes. Expert commentary: Determining which patients should be referred for transplant remains challenging, especially in older adults. Chronological age is an insufficient prognostic metric, and refining, validating, and developing novel pre-transplant risk assessment tools for geriatric patients offers great potential benefit to the field.

Comorbidities, age, and other patient-related predictors of allogeneic hematopoietic cell transplantation outcomes.

INTRODUCTION: Allogeneic hematopoietic cell transplantation (HCT) provides potential cure to a large number of malignant and nonmalignant hematological disorders. With the development of non-myeloablative and reduced-intensity conditioning regimens, allogeneic HCT can nowadays be offered to a number of older or medically unfit patients. Up until the twenty-first century, chronological age was considered a hypothetical barrier. Recent reports, however, have shown that comorbidities, function, and other patient-related factors influence HCT outcomes at a higher magnitude than age alone. Areas covered: To define the eligibility of older or medically unfit patients for allogeneic HCT, a range of factors have to be considered. To solve this considerable issue, we need to further understand the mechanism and consequences of aging, such as chronic inflammation, sarcopenia, and especially the structure of frailty. Domains covering functional, physical, mental, social, nutritional, bone, and other health statuses should be evaluated and considered. Expert commentary: In this review we merge the current assessment tools with the potential approaches to objectify functional resources, as well as with possible methods to improve these resources in older or otherwise medically unfit patients prior to allogeneic HCT.

Age adjusted hematopoietic stem cell transplant comorbidity index predicts survival in a T-cell depleted cohort.

OBJECTIVES: Allogeneic hematopoietic stem cell transplant (HCT) continues to evolve with the treatment in higher risk patient population. This practice mandates stringent update and validation of risk stratification prior to undergoing such a complex and potentially fatal procedure. We examined the adoption of the new comorbidity index (HCT-CI/Age) proposed by the Seattle group after the addition of age variable and compared it to the pre-transplant assessment of mortality (PAM) that already incorporates age as part of its evaluation criteria. METHODS: A retrospective analysis of adult patients who underwent HCT at our institution from January 2010 through August 2014 was performed. Kaplan-Meier's curve, log-rank tests, Cox model and Pearson correlation was used in the analysis. RESULTS: Of the 114 patients that underwent allogeneic transplant in our institution, 75.4% were ≥40 years old. More than 58% had a DLCO ≤80%. Although scores were positively correlated (correlation coefficient 0.43, p < 0.001), HCT-CI/Age more accurately predicted 2-year overall survival (OS) and non-relapse mortality (NRM) in patients with lower (0-4) and higher (5-7) scores (52% and 36% versus 24% and 76%, p = 0.004, 0.003 respectively). PAM score did not reach statistical significance for difference in OS nor NRM between the low (<24) and high-risk (≥24) groups (p = 0.19 for both). CONCLUSIONS: Despite our small sample population, HCT-CI/Age was more discriminative to identify patients with poor outcome that might benefit from intensified management strategies or other therapeutic approaches rather than allogeneic HCT.

Distribution and Impact of Comorbidities on Survival and Leukemic Transformation in Myeloproliferative Neoplasm-Associated Myelofibrosis: A Retrospective Cohort Study.

BACKGROUND: We sought to describe the distribution and impact of comorbidities on outcomes in patients with myelofibrosis, a disease characterized by aberrant bone marrow function with eventual fibrosis. Comorbidities were scored using the Adult Comorbidity Evaluation-27 (ACE-27) and the Hematopoietic Cell Transplant Comorbidity Index (HCT-CI), in which a score ≥ 3 indicates severe comorbidities. PATIENTS AND METHODS: We conducted a retrospective study of 306 patients with a confirmed diagnosis of myelofibrosis. Patients were seen from 1999 to 2014 with a median follow-up of 2 years. Multivariable Cox proportional hazards models were constructed to assess the impact of comorbidities on overall survival and leukemic transformation from the date of presentation to our center. A series of descriptive analyses were performed examining the distribution of comorbidities captured by the scales. RESULTS: On multivariable survival analysis, an ACE-27 score of 3 was associated with an almost twofold increase in the risk of all-cause death (hazard ratio [HR] 1.95; 95% confidence interval [CI], 1.06-3.58; P = .03) compared with a lower score of 0 to 1. An HCT-CI score ≥ 3 was marginally significantly associated with an increased risk of all-cause death (HR 1.60; 95% CI 0.96-2.68; P = .07). ACE-27 captured a greater spectrum of cardiovascular and venous thrombotic disease. No impact of comorbidities on leukemic transformation was observed. CONCLUSIONS: Although the presence of severe comorbidities was lower when assessed by ACE-27 (13%) compared with HCT-CI (23%), and the spectrums of comorbidities captured were different, the overall impact of severe comorbidities as assessed by both scales appears to be similar and associated with a survival disadvantage.