Unrelated cord blood transplantation (UCBT) and haploidentical transplantation using posttransplant cyclophosphamide (PTCy-haplo) are alternatives for patients lacking a human leukocyte antigen-matched donor. CD34(+) cell counts in cord blood affect transplantation outcomes, particularly nonrelapse mortality (NRM). The primary objective of this study was to compare the transplantation outcomes after UCBT and PTCy-haplo focusing on CD34(+) cell counts in cord blood. This retrospective study used data from 2014 to 2020 from a Japanese nationwide database. UCBT cases were divided into those with UCBT with higher (UCB-H; >=.84 x 10(5)/kg) and lower (UCB-L; <.84 x 10(5)/kg) CD34(+) cell counts, depending on the median CD34(+) cell count. The study cohort comprised cases of PTCy-haplo (n = 1142), UCB-H (n = 3185), and UCB-L (n = 3172). In the multivariate analysis, neutrophil engraftment was significantly better in the PTCy-haplo than in the UCB-H (hazard ratio [HR], .64; 95% confidence interval [CI], .57 to .70; P < .001) and UCB-L groups (HR, .45; 95% CI, .41 to .50; P < .001). The UCB-H group showed similar NRM (HR, 1.19, 95% CI, 1.00 to 1.43, P = .051) and OS (HR, 1.05, 95% CI, .94 to 1.18, P = .38) compared with PTCy-haplo, whereas UCB-L was significantly associated with poor NRM (HR, 1.35, 95% CI, 1.13 to 1.61, P = .001) and OS (HR, 1.13, 95% CI, 1.01 to 1.26, P = .038). In contrast, the UCB-H (HR, .86; 95% CI, .75 to .98; P = .027) and UCB-L groups (HR, .80; 95% CI, .70 to .92; P = .001) were associated with lower relapse rate. Regarding the graft-versus-host disease (GVHD), the UCB-H and UCB-L groups were identified as significant risk factors for the development of grade II-IV acute GVHD (UCB-H: HR, 1.73; 95% CI, 1.51 to 1.99; P < .001; UCB-L: HR, 1.55; 95% CI, 1.35 to 1.78; P < .001) and grade III-IV acute GVHD (UCB-H: HR, 2.28; 95% CI, 1.78 to 2.91; P < .001; UCB-L: HR, 1.85; 95% CI, 1.44 to 2.37; P < .001), but neither were associated with the incidence of all-grade GVHD (UCB-H: HR, 1.12; 95% CI, .95 to 1.32; P = .16; UCB-L: HR, 1.08; 95% CI, .91 to 1.27; P = .37) or extensive chronic GVHD (UCB-H: HR, .86; 95% CI, .68 to 1.09; P = .21; UCB-L: HR, .88; 95% CI, .69 to 1.12; P = .31). Furthermore, higher NRM in UCB-L was attributed to higher infection-related mortality (HR, 1.50; 95% CI, 1.15 to 1.95; P = .003) but not GVHD-related mortality (HR, 1.15; 95% CI, .82 to 1.62; P = .43), whereas UCB-H was not a significant risk factor for both infection-related mortality (HR, 1.29; 95% CI, .99 to 1.69; P = .06) and GVHD-related mortality (HR, 1.28; 95% CI, .90 to 1.80; P = .16). UCB-H offered similar NRM and OS to PTCy-haplo, whereas UCB-L had worse outcomes. Our results can provide useful information for optimal donor selection. (c) 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
The Engraft Learning Health Network (LHN) aims to improve outcomes for patients undergoing transplant and cellular therapy (TCT) through a collaborative, data-driven approach. Engraft brings together diverse stakeholders, including clinicians, patients, caregivers, and institutions, to standardize best practices and accelerate the dissemination of innovations in TCT care. By establishing a multicenter, real-world clinical registry focused on rapid-cycle quality improvement (QI) and implementation research, Engraft seeks to reduce variability in clinical practice to improve TCT outcomes across centers. Initial efforts have centered on developing QI toolkits, sharing de-identified patient data, and building consensus around best practices to reduce non-relapse mortality and improve survivorship. A distinctive feature of Engraft is its commitment to engaging patients and caregivers as equal partners in the network's direction. This manuscript outlines the network's design, early successes, and future goals.
Axicabtagene ciloleucel (axi-cel), a chimeric antigen receptor T-cell therapy, has significantly improved clinical outcomes in adult patients with relapsed/refractory large B-cell lymphoma. However, few studies have examined patient-reported outcomes (PROs) or neurocognitive performance in patients treated with axi-cel. Moreover, no longitudinal PRO study has reported on patients treated with axi-cel as standard of care in the United States, to our knowledge. This paper reports on real-world changes in PROs (i.e., quality of life [QOL] and perceived cognition) and objective neurocognitive performance before treatment with axi-cel and in the first year after. Patients scheduled to receive axi-cel as standard of care were recruited from a single cancer center between March 2020 and June 2022. QOL was assessed using the EORTC QLQ-C30 and EQ-5D-5L at baseline recruitment (ie, prior to conditioning chemotherapy before axi-cel), and at 7, 14, 30, 60, 90, 180, and 360 days after receiving axi-cel. Perceived cognition was assessed using the Patient-Reported Outcomes Measurement Information System Cognitive Function 4a scale. Objective neurocognitive performance was assessed using a battery of tests at baseline, and 30, 90, and 360 days after receiving axi-cel. Random-effects mixed models evaluated changes in QOL, perceived cognition, and neurocognitive performance using all available data. Clinically meaningful change in QOL was defined as a difference of 10 points on the EORTC QLQ-C30. Clinically meaningful change in perceived cognition or neurocognitive performance was defined as a difference of 5 points. On average, participants (N = 53) were 63 years of age (SD = 13), and predominantly male (62%), White (92%), and college graduates (60%). Participants reported statistically significant improvements from baseline to day 360 in overall QOL, physical functioning, role functioning, and social functioning (Ps < .05) after axi-cel, despite clinically significant worsening in the first 14 days. For role functioning and social functioning, improvements also met criteria for clinical significance. There were no statistically (Ps > .05) or clinically significant changes in perceived cognition over time. Despite some transient declines, neurocognitive performance generally returned to or exceeded baseline levels by day 360 (Ps < .01). However, visuospatial ability worsened by day 90 and did not recover to baseline levels by day 360 (P < .0001). These real-world data suggest that axi-cel is associated with significant improvements in overall QOL in the first year after infusion. These data are generally consistent with, or exceed, improvements in QOL reported from clinical trials of axi-cel therapy. Despite transient worsening in the acute period after treatment, neurocognitive performance in most domains also recovered to pretreatment levels by 1 year after infusion. These findings extend previous research by reporting on patients' perspectives on axi-cel therapy received as standard of care in the real-world setting and neurocognitive changes after treatment with axi-cel.
Chronic graft-versus-host disease (cGVHD) occurs in approximately 1 in 5 pediatric allogeneic HCT patients and is a leading cause of late morbidity and mortality. Late effects of hematopoietic cell transplantation (HCT) may lead to long-term chronic health conditions and shortened life expectancy. In addition to direct physiologic challenges from cGVHD and other late effects, numerous patient-important outcomes impact the quality of life (QOL) of patients and their families. The Research and Education towards Solutions for Late Effects to Innovate, Excel, and Nurture (RESILIENT) after GVHD Consensus Conference was convened to better understand the overlap of cGVHD and late effects in pediatric HCT survivors. Working Committee IV: Patient Important Outcomes identified 4 key areas for focus: (1) What are the key mental health and QOL concerns of survivors of pediatric cGVHD? (2) What is the impact of cGVHD on cognitive performance and social development? (3) What multilevel social determinants of health impact cGVHD survivors, families, and communities? (4) What is the role of racial, ethnic, and socioeconomic factors on the development of cGVHD and the risk for adverse outcomes related to survivorship? For each focus area, the Working Committee reviewed the current state of the field, developed recommendations for clinical practice, and highlighted areas to prioritize for future research. Eleven recommendations were adapted and approved. Substantial overlap exists between the role of cGVHD and late effects on the QOL and mental health of childhood HCT survivors. Recommendations based on available data and consensus opinion may be helpful to improve outcomes for these patients. However, several gaps remain that need further study.
BACKGROUND:Despite its known superior diagnostic yield for chromosomal anomalies compared with karyotype and fluorescence in situ hybridization (FISH) studies, chromosome genomic array testing (CGAT) is not used as a routine clinical test for myelofibrosis. Although many prognostic systems exist that risk stratify patients at diagnosis, limited tools are available to prognosticate transplant outcome. OBJECTIVE:The current study aimed at testing whether CGAT results obtained before transplantation improves prognosis of post-transplant outcome in patients with myelofibrosis compared with current risk categorization systems, for example, DIPSS plus (Dynamic International Prognostic Scoring System). STUDY DESIGN:We studied patients with myelofibrosis who underwent hematopoietic cell transplantation between 2000 and 2017 at our center (N = 44). We assessed the prognostic significance of CGAT, DIPSS plus, and the total count of gene mutations for post-transplant clinical outcomes, including relapse-free survival (RFS), overall survival (OS), and graft-versus-host-disease (GVHD). RESULTS:Abnormal CGAT results were seen in 24 patients (55%), including 18 with copy-neutral loss of heterozygosity (cnLOH, 41%). With a median follow-up of 91 (range 2-258) months starting from the CGAT sample date, RFS was 59% and OS was 68%. The outcome analysis showed significant prognostic implication from CGAT (normal vs. abnormal), specifically for patients with intermediate risk by DIPSS-plus scores and those with 0∼2 mutations. CGAT alone significantly stratified the patients' RFS outcome (P = .03). The addition of CGAT to DIPSS-plus improved the significance from a P value of .08 to .003, whereas the addition of CGAT to mutation count improved the P value from .02 to .01. The best stratification system for RFS was achieved when CGAT, DIPSS-plus, and mutation count were all considered (P = 1e-08). The current study also confirmed individual anomalies that are prognostically significant, including U2AF1 mutation (n = 5, P = .03) and 1q gain (n = 3, P = .01), which were associated with worse RFS. ASXL1 mutations (n = 14) appeared to associate with a later onset of chronic GVHD (P =.03). CONCLUSION:Pretransplant CGAT analysis augments the existing risk stratification tools and may be considered as routine clinical testing for myelofibrosis.
