Donor Types and Outcomes of Transplantation in Myelofibrosis: A CIBMTR Study.

We aim to evaluate impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using CIBMTR registry data for HCTs done between 2013 and 2019. In all 1597 undergoing HCT for myelofibrosis, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study eligible, 1032 patients who received peripheral blood grafts for chronic phase myelofibrosis, 38% recipients of haploidentical-HCT were of non-White/Caucasian ethnicity. Matched sibling donor (MSD)-HCTs were independently associated with superior overall survival (OS) in the first 3 months [reference MSD, haploidentical HR 5.80 (95% CI 2.52-13.35), matched unrelated HR 4.50 (95% CI 2.24-9.03), and mismatched unrelated HR 5.13 (95% CI 1.44-18.31), P<0.001]. This difference in OS aligns with lower graft failure with MSD [haploidentical HR 6.11 (95%CI 2.98-12.54), matched unrelated HR 2.33 (95%CI 1.20-4.51), mismatched unrelated HR 1.82 (95%CI 0.58-5.72). There was no significant difference in OS among haploidentical, matched unrelated, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months post-HCT, relapse, disease-free survival or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. While MSDs remain a superior donor option due to improved engraftment, there is no significant difference in HCT outcomes from haploidentical and matched unrelated donors. These results establish haploidentical-HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.

The Prevalence of Pretransplant Frailty and Mental Distress in Hematopoietic Cell Transplantation and Association with Clinical Outcomes.

Frailty is a phenotype of decreased physiologic reserve associated with increased risk of toxicities and nonrelapse mortality (NRM) in hematopoietic cell transplant (HCT) recipients. The incidence, predictors, and adverse effects of pre-HCT frailty are not well known. We evaluated the association of pre-HCT frailty, defined using Fried's criteria, with age and baseline characteristics in patients ≥18 years undergoing autologous (auto) or allogeneic (allo) HCT for hematological malignancies. Assessments were performed as part of routine pre-HCT evaluations and then retrospectively analyzed. We additionally investigated the association of mental health distress indicators with frailty and the association between frailty and transplant outcomes including NRM and overall survival (OS) plus healthcare utilization. Patients undergoing HCT for hematological malignancies were analyzed (total n = 300; 162 auto, 138 allo). The overall prevalence of frailty was 18%, 21.7% among alloHCT, and 14.8% among autoHCT recipients, with similar distributions of frailty domains. Logistic regression analysis of the overall cohort revealed that older age was associated with an increased risk of frailty (odds ratio [OR] 1.37, 95% confidence interval [CI] [1.02-1.82]; P = 0.04). AlloHCT (OR 2.03, CI [1.07-3.84]; P = .03), and patient health questionnaire-9 (PHQ-9) (health depression) score ≥10 (OR 6.28, CI 1.93-20.43; P < .01) were each independently associated with pre-HCT frailty. In alloHCT patients, older age (OR 1.44, CI [1.00-2.06]; P = .05) was the only significant risk factor for pre-HCT frailty, while for autoHCT patients, only a higher PHQ-9 score was associated with frailty (OR 6.43, CI [1.34-30.82]; P = .02). For the whole cohort OS at 1 year was lower in frail recipients at 83% (95% CI, 70-91%) versus 92% (95% CI, 88-95%) in nonfrail (P = .04); with multivariate analysis showing higher risk of death in the frail group (hazard ratio [HR] 2.31, CI 0.97-5.46; P = .06). In the alloHCT cohort, multivariate analysis showed greater 1-year mortality in frail recipients (HR 2.55, CI [0.99-6.56]; P = .053). In the alloHCT recipients, we observed a 1-year NRM of 20% in frail patients versus 9% in nonfrail, and multivariate analysis showed a marginally higher risk of NRM in the frail group (HR 2.70, CI 0.90-8.10; P = .08). Frailty was not associated with higher risk of relapse in alloHCT or autoHCT recipients. Frail alloHCT patients experienced a longer initial hospital stay following HCT compared to nonfrail recipients (P < .01). We observed a high prevalence of pre-HCT frailty across all age groups, and identify older age is a risk factor for frailty, particularly in alloHCT recipients. Frailty is associated with a greater risk of NRM and lower survival which needs investigation in a larger cohort. Frailty associates with greater HCT complexity suggesting a need for early assessments and targeted interventions for this vulnerable population. Our findings suggest the utility of frailty and mental distress screening along with multidisciplinary interventions in pre-HCT to limit the morbidity of HCT.

Harvest Quality, Nucleated Cell Dose and Clinical Outcomes in Bone Marrow Transplantation: A Retrospective Study.

Higher doses of infused nucleated cells (NCs) are associated with improved clinical outcomes in bone marrow transplantation (BMT) recipients. Most clinicians recommend infusing at least 2.0 × 108 NCs/kg. BMT clinicians request a target NC dose, but the harvested NC dose may be below the requested NC dose even before cell processing. We conducted this retrospective study to investigate the quality of bone marrow (BM) harvest and factors that influence infused NC doses at our institution. We also correlated infused NC doses with clinical outcomes. The study population included 347 BMT recipients (median age, 11 years; range, <1 to 75 years) at the University of Minnesota between 2009 and 2019. Underlying diagnoses mainly included 39% malignant and 61% nonmalignant diagnoses. Requested, harvested, and infused NC doses, as well as cell processing data, were obtained from the Cell Therapy Laboratory; clinical outcomes data were obtained from the University of Minnesota BMT Database. BM harvests were facilitated either by our institution (61%) or by the National Marrow Donor Program (39%). Associations of infused doses with baseline characteristics were assessed using the general Wilcoxon test/Pearson's correlation coefficient. The association of infused dose with neutrophil engraftment (absolute neutrophil count >500) by day 42, platelet engraftment (>20,000) by 6 months, acute graft-versus-host disease grade II-IV, and overall survival (OS) at 5 years were evaluated using regression and Kaplan-Meier curves. The median requested NC dose was 3.0 × 108/kg (range, 2 to 8 × 108/kg), and the median harvested and infused NC doses were 4.0 × 108/kg and 3.6 × 108/kg, respectively. Only 7% of donors had a harvested dose below the minimum requested dose. Moreover, the correlation between requested doses and harvested doses was adequate, with a harvested/requested dose ratio <.5 observed in only 5% of harvests. Additionally, the harvest volume and cell processing method were significantly correlated with the infused dose. Harvest volume exceeding the median of 948 mL was related to a significantly lower infused dose (P < .01). Moreover, hydroxyethyl starch (HES)/buffy coat processing (used to reduce RBCs with major ABO incompatibility) led to a significantly lower infused dose (P < .01). Donor age (median, 19 years; range, <1 to-70 years) and sex did not significantly influence the infused dose. Finally, the infused dose was significantly correlated with neutrophil and platelet engraftment (P < .05) but not with 5-year OS (P = .87) or aGVHD (P = .33). In our program's experience, BM harvesting is efficient and meets the requested minimum dose for 93% of recipients. Harvest volume and cell process play significant roles in determining the final infused dose. Minimizing harvest volume and cell processing could lead to increased infused dose and thus improved outcomes. Moreover, a higher infused dose leads to a better rate of neutrophil and platelet engraftment but not to improved OS, which may be linked to the sample size of our study.

Phase II Study of Myeloablative 7-8/8-Matched Allotransplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil.

Graft-versus-host disease (GVHD) is the major toxicity of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that a GVHD prophylaxis regimen of post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) would be associated with incidences of acute and chronic GVHD in patients receiving a matched or single antigen mismatched HCT. This Phase II study was conducted at the University of Minnesota using a myeloablative regimen of either total body irradiation (TBI) at a total dose of 1320 cGy, administered in 165-cGy fractions, twice daily from day -4 to day -1, or busulfan (Bu) 3.2 mg/kg daily (cumulative area under the curve, 19,000 to 21,000 µmol/min/L) plus fludarabine (Flu) 40 mg/m2 once daily on days -5 to -2, followed by a GVHD prophylaxis regimen of PTCy 50 mg/kg on days +3 and +4, Tac, and MMF beginning on day +5. The primary endpoint was the cumulative incidence of chronic GVHD necessitating systemic immunosuppression (IST) at 1 year post-transplantation. Between March 2018 and May 2022, we enrolled 125 pediatric and adult patients, with a median follow-up of 813 days. The incidence of chronic GVHD necessitating systemic IST at 1 year was 5.5%. The rate of grade II-IV acute GVHD was 17.1%, and that of grade III-IV acute GVHD was 5.5%. Two-year overall survival was 73.7%, and 2-year graft-versus-host disease-free, relapse-free survival was 52.2%. The 2-year cumulative incidence of nonrelapse mortality was 10.2%, and the rate of relapse was 39.1%. There was no statistically significant difference in survival outcomes between recipients of matched donor transplants versus recipients of 7/8 matched donor transplants. Our data show that myeloablative HCT with PTCy/Tac/MMF results in an extremely low incidence of severe acute and chronic GVHD in well-matched allogeneic HCT.

Impact of Public Reporting of Center-Specific Survival Analysis Scores on Patient Volumes at Hematopoietic Cell Transplant Centers.

The Center for International Blood and Marrow Transplant Research reports the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) at United States transplantation centers (TC) annually through its Center-Specific Survival Analysis (CSA). The CSA compares the actual 1-year overall survival (OS) and predicted 1-year OS rate after alloHCT at each TC, which is then reported as 0 (OS as expected), -1 (OS worse than expected), or 1 (OS better than expected). We evaluated the impact of public reporting of TC performance on their alloHCT patient volumes. Ninety-one TCs that serve adult or combined adult and pediatric populations and had CSA scores reported for 2012-2018 were included. We analyzed prior-calendar-year TC volume, prior-calendar-year CSA score, whether the CSA score had changed in the prior year from two years earlier, calendar year, TC type (adult only vs. combined adult and pediatric), and years of alloHCT experience for their impact on patient volumes. A CSA score of -1, as compared with 0 or 1, was associated with an 8% to 9% reduction in the mean TC volume (P < 0.001) in the subsequent year, adjusting for the prior year center volume. Additionally, being a TC neighboring an index TC with a -1 CSA score, was associated with a 3.5% increase in mean TC volume (P = 0.04). Our data show that public reporting of CSA scores is associated with changes in alloHCT volumes at TCs. Additional investigation into the causes of this shift in patient volume and the impact on outcomes is ongoing.

Inflammatory cytokines and depression symptoms following hematopoietic cell transplantation.

Increased synthesis and release of inflammatory signalling proteins is common among individuals with hematologic malignancies undergoing hematopoietic cell transplantation (HCT) due to intensive conditioning regimens and complications such as graft-versus-host-disease and infections. Prior research indicates that inflammatory responses can activate central nervous system pathways that evoke changes in mood. This study examined relationships between markers of inflammatory activity and depression symptoms following HCT. Individuals undergoing allogeneic (n = 84) and autologous (n = 155) HCT completed measures of depression symptoms pre-HCT and 1, 3, and 6 months post-HCT. Proinflammatory (IL-6, TNF-α) and regulatory (IL-10) cytokines were assessed by ELISA in peripheral blood plasma. Mixed-effects linear regression models indicated that patients with elevated IL-6 and IL-10 reported more severe depression symptoms at the post-HCT assessments. These findings were replicated when examining both allogeneic and autologous samples. Follow-up analyses clarified that relationships were strongest for neurovegetative, rather than cognitive or affective, symptoms of depression. These findings suggest that anti-inflammatory therapeutics targeting an inflammatory mediator of depression could improve quality of life of HCT recipients.

Phase II Study of Myeloablative 8/8- or 7/8-Matched Allotransplantation with Post-Transplant Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil: Marked Reduction in GVHD Risk Without Increased Relapse Risk Compared to Historical Cyclosporine/Methotrexate.

Introduction: Graft-versus host disease (GVHD) is a major limitation to the success of allogeneic hematopoietic cell transplant (HCT). We hypothesized that the GVHD prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac) and mycophenolate mofetil (MMF) would reduce the incidence of GVHD in patients receiving a matched or single antigen mismatched HCT without an increase in risk of malignant relapse. Methods: This is a phase II study conducted at the University of Minnesota using a myeloablative regimen of either: (A) total body irradiation (TBI, total dose 1320 cGy, administered in 165 cGy fractions, twice a day from days -4 to -1) or (B) Busulfan 3.2mg/kg daily (cumulative AUC 19,000 - 21,000 µmol/min/L) plus fludarabine 160mg/m2 days -5 to -2, followed by a GVHD prophylaxis regimen of PTCy (50mg/kg days +3 and +4), Tac and MMF (beginning day +5). The primary endpoint is cumulative incidence of chronic GVHD requiring systemic immunosuppression at 1-year post-transplant. We compared results to our previous myeloablative protocol for matched donors utilizing cyclosporine/methotrexate (CSA/MTX) GVHD prophylaxis. Results: From March 2018 - June 2022, we enrolled and treated 125 pediatric and adult patients with a median follow up of 472 days. Grade II-IV acute GVHD occurred in 16% (95% confidence interval (CI): 9-23%); Grade III-IV acute GVHD was 4% (CI: 0-8%). No patients experienced grade IV GVHD, and there were no deaths due to GVHD before day 100. Only 3 developed chronic GVHD requiring immune suppression, (4%, CI: 0-8%). Two-year overall survival (OS) was 80% (CI: 69-87%), and (graft-versus-host disease-free, relapse-free survival) GRFS 57% (CI: 45-67%), both higher than historical CSA/MTX. The incidence of grade II-IV aGVHD, cGVHD, and NRM were all lower with PTCy/Tac/MMF compared to historical CSA/MTX. One-quarter (25%) experienced relapse (CI: 15-36%) similar to historical CSA/MTX. There was no statistically significant difference in survival outcomes between recipients of matched versus 7/8 donors. Conclusion: Myeloablative HCT with PTCy/Tac/MMF results in extremely low incidence of severe acute or chronic GVHD, the primary endpoint of this clinical trial. Relapse risk is not increased compared to our historical CSA/MTX cohort.

How do we improve the translation of new evidence into the practice of hematopoietic cell transplantation and cellular therapy?

The field of hematopoietic cell transplantation and cell therapy (HCT/CT) is advancing rapidly to bring an ever-expanding collection of potentially curative therapies to patients with malignant and non-malignant diseases. The impact of these therapies depends on our ability to implement them as new evidence becomes available to advance the quality of care. There is often a long delay between evidence development and adoption of therapies based on that evidence into clinical practice. In this review, we describe the potential factors based on an implementation framework that could act as facilitators or barriers to adoption of therapies in the context of HCT/CT. We highlight two examples, the first to showcase the efforts to improve the efficiency of adoption of new findings and accelerate improvement in care of HCT/CT patients and the second to discuss the challenges in real world implementation of chimeric antigen receptor T cell therapy. We conclude by reviewing strategies to improve translation of evidence and ways to measure their success.

Psychological and physical function in allogeneic hematopoietic cell transplant survivors with chronic graft-versus-host disease.

PURPOSE: Chronic graft-versus-host disease (cGVHD) is a common late complication of allogeneic hematopoietic cell transplantation (HCT). This study comprehensively evaluated physical and psychological function among individuals with cGVHD. Additional aims were to investigate relationships between disease severity and psychological and physical function, and to investigate patterns of psychological and physical function by disease site. METHOD: Adults at least 6 months post allogeneic HCT were enrolled and either had cGVHD (n =59) or served as a reference sample of HCT survivors with no cGVHD history (n = 19). Participants completed self-report measures of depression, anxiety, fatigue, insomnia, pain, cognition, and sexual function and had a comprehensive clinical evaluation of cGVHD using NIH consensus scoring criteria. Participants with cGVHD were stratified by disease severity and site and compared to the reference group with no cGVHD. RESULTS: Participants with mild cGVHD had comparable psychological and physical symptoms to the reference sample, while participants with moderate cGVHD experienced more severe anxiety and problems with sexual function, and participants with severe cGVHD experienced more severe depressive symptoms and pain compared to the reference sample. Participants with cGVHD manifesting in the skin and GI tract had the most severe symptoms, including mood disturbance, fatigue, and pain. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: Results suggest that patients with more severe cGVHD and those with cGVHD manifesting in the skin, GI tract, and lungs are at risk for poorer psychological and physical outcomes and may benefit from proactive interventions to optimize function.

Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis.

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/ busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazard ratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91; P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21; 95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associated with a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P<0.001; grade 3-4 HR=2.31; 95% CI: 1.52-3.52; P<0.001) and inferior GvHD-free relapse-free survival (GRFS) (HR=1.94; 95% CI: 1.49-2.53; P<0.001) as compared to fludarabine/busulfan. Hence, our study suggests that fludarabine/busulfan is associated with better outcomes in RIC (better overall survival, lower early non-relapse mortality, lower acute GvHD) and MAC (lower acute GvHD and better GRFS) in myelofibrosis.

A Multicenter Phase 2 Clinical Trial of 10-Day Decitabine, Dose-Escalated Donor Lymphocyte Infusion, and Ruxolitinib for Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes after Allogeneic Hematopoietic Cell Transplantation.

Post-transplantation relapse of acute myeloid leukemia and myelodysplastic syndromes has a poor prognosis. Donor lymphocyte infusion (DLI) is one treatment approach. However, efficacy is limited, and toxicity, mostly in the form of acute graft-versus-host disease (GVHD), is frequent. We tested a novel approach using 10-day decitabine, dose-escalated DLI, and ruxolitinib in a multicenter phase 2 trial aimed at increasing the efficacy of DLI and reducing its toxicity. Up to four 28-day cycles were administered. The primary endpoint was 6-month overall survival (OS). Of the 14 patients who started cycle 1, 13 received 1 DLI, 6 received 2 DLIs, and 1 received 3 4 DLIs. A preplanned interim analysis after enrolling 14 patients suggested futility, and the trial was closed to accrual. The final analysis showed a 6-month OS of 36% (95% confidence interval [CI], 18 to 72), a 1-year progression-free survival of 7% (95% CI, 1% to 47%), a 6-month cumulative incidence of grade II-IV acute GVHD of 57% (95% CI, 26% to 80%), and a 1-year nonrelapse mortality of 14% (95% CI, 2% to 38%). The combined modality treatment studied in this trial was ineffective and did not reduce DLI toxicity.

Sarcopenia Predicts Inferior Progression-Free Survival in Lymphoma Patients Treated with Autologous Hematopoietic Stem Cell Transplantation.

Autologous hematopoietic stem cell transplantation (ASCT) improves survival for patients with chemotherapy-sensitive lymphoma. Validated scoring systems are used in the clinical setting to predict treatment toxicity and survival; however, complications related to disease and treatment still occur, highlighting challenges in optimal patient selection and the need for novel predictors. Analysis of body composition and muscle mass can provide an objective assessment to identify vulnerable populations, as sarcopenia and frailty have been reported to predict outcomes in other tumor types. In this retrospective cohort study of patients undergoing ASCT for lymphoma, we investigated associations of sarcopenia with clinically significant outcomes, including overall survival (OS) and progression-free survival (PFS). Computed tomography (CT) images of 78 patients obtained routinely pretransplantation were used to assess skeletal muscle mass and are reported as skeletal muscle index (SMI). OS, PFS, and clinical outcomes of interest were compared between groups. Twenty-seven patients (34.6%) in the cohort met the criteria for sarcopenia. Patients with sarcopenia had a significantly shorter 3-year PFS (59% [95% confidence interval (CI), 38% to 75%] versus 84% [95% CI, 71% to 92%]; P = .02) after 3 years of follow up, whereas there was no difference in OS between patients with and those without sarcopenia (78% [95% CI, 57% to 89%] versus 88% [95% CI, 76% to 95%]; P = .25). Interestingly, no difference in survival was found with stratification based on the Karnofsky Performance Scale or Hematopoietic Cell Transplantation-Specific Comorbidity Index. There also were no significant between-group differences in length of hospital stay and the incidences of other clinical outcomes of interest, including febrile neutropenia, mucositis, total parenteral nutrition requirement, acute kidney injury, rate of readmission, or intensive care unit admission. This is the first study to our knowledge to correlate sarcopenia with disease control and PFS after ASCT in lymphoma. Possible explanations include a higher rate of chemotherapy-related toxicity, leading to disruptions of treatment as well as dysfunction of antitumor immunity secondary to impaired regulations from myokines from the loss of muscle mass or an unknown cause that is yet to be elucidated. Physical therapy programs and personalized regimens for treatment based on the analysis of body composition indices can be further studied and implemented to mitigate treatment-related toxicity and to optimize survival in patients with sarcopenia.

A biobehavioral intervention to enhance recovery following hematopoietic cell transplantation: Protocol for a feasibility and acceptability randomized control trial.

Background: Insomnia, fatigue, and depression are among the most persistent and distressing concerns for hematologic cancer patients recovering from hematopoietic cell transplantation (HCT). This study will evaluate a novel behavioral intervention, Restoring Sleep and Energy after Transplant (ReSET), designed to alleviate insomnia, fatigue, and depression by improving rest-activity patterns. Evidence-based behavioral strategies to improve nighttime sleep and increase non-sedentary daytime activity will be combined to optimize 24-h rest-activity patterns. Methods: The protocol herein evaluates the feasibility and acceptability of ReSET by conducting a pilot randomized controlled trial to compare the intervention with usual care. Adults undergoing HCT will be randomly assigned to ReSET or usual care. The ReSET arm will receive 3 face-to-face sessions and telephone coaching delivered in an individual format tailored to each patient. Patient-reported insomnia, fatigue, and depression will be the primary outcome measures. Actigraphy will be used to objectively quantify rest-activity patterns. Semi-structured interviews will evaluate participant satisfaction with ReSET. The goals are to determine: (1) participant satisfaction with and acceptability of the behavioral techniques; (2) facilitator fidelity and participant uptake of key intervention components; (3) ability to recruit, retain, and collect complete data from participants; (4) participant willingness to be randomized and acceptability of the control condition; and (5) validity and acceptability of the assessment strategy. Conclusion: The overarching goal is to optimize recovery following HCT with a brief, non-invasive intervention that can be implemented as a part of routine clinical care.

Are We Making PROGRESS in Preventing Graft-versus-Host Disease and Improving Clinical Outcomes? Impact of BMT CTN 1301 Study Results on Clinical Practice.

The need for prospective randomized clinical trials investigating novel graft-versus-host disease (GVHD) prevention strategies that include other clinical outcomes impacted by GVHD has been highlighted as a priority for the field of hematopoietic cell transplantation. A recently completed study through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 1301) comparing CD34+ selection and post-transplantation cyclophosphamide with tacrolimus/methotrexate (Tac/MTX) for GVHD prevention demonstrated no significant differences in the primary endpoint of chronic GVHD relapse-free survival among the 3 approaches. The trial did not demonstrate a superior approach compared with Tac/MTX; however, it did highlight several challenges in determining the best and most relevant approaches to clinical trial design, particularly in the context of current and ongoing changes in real-world practices. Here we review the results of BMT CTN 1301 and their implications for clinical practice and future clinical trial design.

Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis.

Acute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007-2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60-64; 65-69; 70+). With median follow-up of nearly 3 years, patients aged 60-64 had modestly, though significantly better OS, DFS and lower TRM than those either 65-69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p = 0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥3. Conditioning intensity was not a significant predictor of OS in the 60-69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p = 0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection.

Quality Improvement in Hematopoietic Stem Cell Transplant and Cellular Therapy: Using the Model for Improvement to impact Outcomes.

Quality improvement and quality assurance form a complementary and independent relationship. Quality assurance measures compliance against industry standards using audits, whereas quality improvement is a continuous process focused on processes and systems that can improve care. The Model for Improvement is a robust quality improvement tool that transplant and cellular therapy teams can use to redesign healthcare processes. The Model for Improvement uses several components addressed in sequence to organize and critically evaluate improvement activities. Unlike other health sciences clinical research, quality improvement projects, and research are based on dynamic hypotheses that develop into observable, serial tests of change with continuous collection and feedback of performance data to stakeholders.

Predictors of posttraumatic growth among hematopoietic cell transplant recipients.

OBJECTIVE: Prior research has shown that cancer survivors often report positive psychological changes from the experience of cancer, or posttraumatic growth (PTG). However, few studies have focused on PTG in cancer patients recovering from hematopoietic cell transplantation (HCT). The present study measured PTG at specific milestones during the year following HCT and investigated psychosocial and treatment-related factors that may hinder or facilitate PTG. METHODS: Participants (N = 430) completed assessments of PTG, social support, and coping pre-transplant. Posttraumatic growth was also assessed at 1, 3, 6, and 12 months post-transplant. Information about treatment regimen and post-transplant complications was abstracted from medical records. Mixed-effects linear regression models were used to evaluate the extent to which pre-transplant social support, coping approaches, treatment intensity, and post-transplant complications predicted PTG. RESULTS: Compared to pre-transplant, PTG scores were significantly higher at 6- and 12-month post-transplant. Greater pre-transplant social support significantly predicted greater PTG across the assessment points. Use of emotional engagement coping strategies also strongly predicted post-transplant PTG. Conversely, coping styles characterized by emotional avoidance generally were not predictive of PTG. No treatment-related factors or post-transplant complications were predictive of PTG. CONCLUSIONS: Findings indicate that supportive social relationships and coping by engaging with difficult emotions may facilitate PTG following HCT. Moreover, these factors were more important than medical characteristics in explaining PTG. Findings may guide the development of interventions to enhance positive psychological outcomes after HCT.