Hypomethylating agents are associated with high rates of hematologic toxicity in patients with secondary myeloid neoplasms developing after acquired aplastic anemia.

Not available.

Patient-Reported Outcomes and Mortality in Cutaneous Chronic Graft-vs-Host Disease.

Importance: Chronic graft-vs-host disease (GVHD) is associated with impaired quality of life and symptom burden. The independent association of skin involvement with patient-reported outcomes (PROs) and their utility as a clinical prognostic marker remain unknown. Identification of patients with cutaneous chronic GVHD and impaired PROs could assist in initial risk stratification and treatment selection. Objective: To compare the association of sclerotic and epidermal-type chronic GVHD with longitudinal PROs and to evaluate whether PROs can identify patients with cutaneous chronic GVHD at high risk for death. Design, Setting, and Participants: This multicenter prospective cohort study involved patients from the Chronic GVHD Consortium of 9 US medical centers, enrolled between August 2007 and April 2012, and followed up until December 2020. Participants included adults 18 years and older with a diagnosis of chronic GVHD requiring systemic immunosuppression and with skin involvement during the study period. Main Outcomes and Measures: Patient-reported symptom burden was assessed using the Lee Symptom Scale (LSS) skin subscale with higher scores indicating worse outcomes. Quality of life was measured using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) instrument with lower scores indicating worse outcomes. Nonrelapse mortality, overall survival, and their association with PROs at diagnosis were also assessed. Results: Among 436 patients with cutaneous chronic GVHD (median [IQR] age at transplant, 51 [41.5-56.6] years; 261 [59.9%] male), 229 patients had epidermal-type chronic GVHD (52.5%), followed by 131 with sclerotic chronic GVHD (30.0%), and 76 with combination disease (17.4%). After adjusting for confounders, patients with sclerotic chronic GVHD had mean FACT-BMT scores 6.1 points worse than those with epidermal disease (95% CI, 11.7-0.4; P = .04). Patients with combination disease had mean LSS skin subscale scores 9.0 points worse than those with epidermal disease (95% CI, 4.2-13.8; P < .001). Clinically meaningful differences were defined as at least 7 points lower for FACT-BMT and 11 points higher for LSS skin subscale. At diagnosis, clinically meaningful worsening in FACT-BMT score was associated with an adjusted odds of nonrelapse mortality increased by 9.1% (95% CI, 2.0%-16.7%; P = .01). Similarly, for clinically meaningful worsening in LSS skin subscale score, adjusted odds of nonrelapse mortality increased by 16.4% (95% CI, 5.4%-28.5%; P = .003). These associations held true after adjusting for clinical severity by the National Institutes of Health Skin Score. Conclusions and Relevance: The results of this cohort study demonstrated that skin chronic GVHD was independently associated with long-term PRO impairment, with sclerotic and combination disease carrying the highest morbidity. The degree of impairment at skin chronic GVHD diagnosis was a prognostic marker for mortality. Therefore, PROs could be useful for risk stratification and treatment selection in clinical practice and clinical trials.

Preconditioning Frailty Phenotype Influences Survival and Relapse for Older Allogeneic Transplantation Recipients.

Hematologic malignancies disproportionately affect older adults. Hematopoietic cell transplantation (HCT) is potentially curative, but poor overall survival (OS) has limited its use in older adults. Fried's frailty phenotype (FFP) is a geriatric assessment tool that combines objective and subjective performance measures: gait speed, grip strength, activity level, exhaustion, and weight loss. People meeting ≥3 criteria are classified as frail; 1 or 2 criteria, as pre-frail; and 0 criteria, as fit. To evaluate the association of pre-HCT FFP with post-HCT outcomes, we assessed FFP prior to conditioning for 280 HCT recipients age ≥60 years with acute leukemia or a myeloid neoplasm at 3 institutions. When analyzing survival by age group, patients age ≥70 years had inferior OS compared to patients age 60 to 69 years (P = .002), with corresponding OS estimates of 38.9% (95% confidence interval [CI], 27.8% to 49.9%) and 59.3% (95% CI, 51.9% to 65.9%). Nonrelapse mortality (NRM) also was significantly higher in the older patients (P = .0005); the 2-year cumulative incidences of NRM were 38.5% (95% CI, 27.5% to 49.2%) and 17.2% (95% CI, 12.3% to 22.8%), for older and younger recipients, respectively. The cumulative incidences of relapse did not differ by age group (P = .3435). Roughly one-third (35.5%) of the patients were fit, 57.5% were pre-frail, and 7.5% were frail, with corresponding 2-year OS estimates of 68.4% (95% CI, 57.9% to 76.8%), 45.5% (95% CI, 37.4% to 53.2%), and 45.8% (95% CI, 23.4% to 65.8%) (P = .013). FFP was not significantly associated with NRM, but being frail or pre-frail was associated with a higher rate of disease-related deaths (33.3% and 27.3%, respectively, compared with 17.4% for fit patients; P = .043). In univariate modeling of restricted mean survival time with a 3-year horizon (RMST_3y), the factors that were significantly associated were FFP, age, Karnofsky Performance Status (KPS), Disease Risk Index (DRI), and HCT-specific Comorbidity Index (HCT-CI). Of those factors, only FFP (P = .006), age (P = .006), KPS (P = .004), and DRI (P = .005) were significantly associated in multivariate modeling of RMST_3y. Estimates of RMST_3y were computed and 5 risk-groups were created with survival ranging from 31.4 months for those who were age 60 to 69 years, fit, had KPS 90 to 100, and low/intermediate-risk DRI compared to 10.5 months for those who had high-risk features for all the evaluated factors. In univariate and multivariate analyses for restricted mean time to relapse with a 3-year horizon (RMRT_3y), FFP (pre-frail versus fit, P = .007; frail versus fit, P = .061) and DRI (P = .001) were the only significant factors. Predicted RMRT_3y was longest (30.6 months) for those who were fit and had low/intermediate-risk DRI scores and shortest (19.1 months) for those who were frail and had high-risk or very high-risk DRI scores. Both age and FFP impact survival after HCT. Incorporation of FFP into pre-HCT evaluations may improve decision-making and counseling regarding HCT risk for older adults. Our findings support future trials designed to reverse frailty, such as pre-HCT supervised exercise programs, and correlative analyses to unravel the connection of frailty and relapse to generate future targets for intervention. Finally, exploration of novel HCT platforms to reduce relapse in pre-frail and frail patients, as well as reduce NRM in adults age >70 years, are warranted.

Characterization of the calcineurin inhibitor pain syndrome in patients undergoing allogeneic hematopoietic cell transplantation.

Calcineurin inhibitor pain syndrome (CIPS) is a rare complication of graft-vs-host disease prophylaxis following allogeneic hematopoietic cell transplant (alloHCT). CIPS presents as severe bilateral lower extremity pain, and the incidence, risk factors, and management of CIPS are poorly characterized.This is a single center retrospective study of patients who received tacrolimus (TAC) following alloHCT to describe the characteristics and management of CIPS and compare to a cohort who did not develop CIPS.Fifteen of 585 alloHCT patients (2.6%) developed CIPS at a median of 5 days following TAC initiation and a median level of 10.5 ng/mL. Severe bilateral foot, ankle, or leg pain were the primary symptoms. Patients with CIPS were younger and more frequently received myeloablative conditioning and total body irradiation compared to patients without CIPS. Analgesic regimens included dihydropyridine calcium channel blockers, gabapentinoids, topical diclofenac, and opioids.Clinicians should be aware of this uncommon but severe adverse effect.

Chronic Graft-versus-Host Disease-Associated Muscle Cramps: Severity and Response to Immunomodulatory Therapies.

Muscle cramps in patients with chronic graft-versus-host disease (cGVHD) are common and associated with impaired quality of life and symptom burden. Muscle cramps are not currently captured in the 2014 National Institutes of Health (NIH) response criteria, and thus characterization and response to immunomodulatory therapies are lacking. The objective of this study was to characterize muscle cramp frequency, duration, and pain level in patients with steroid-refractory cGVHD undergoing extracorporeal photopheresis (ECP). A single-center cohort of patients who underwent ECP for the indication of steroid-refractory cGVHD with muscle cramps at treatment initiation were followed from April 2021 to April 2023. Of 22 patients receiving ECP for cGVHD during the study period, 9 (41%) had muscle cramps at ECP initiation (6 males [66%]; median age, 59 years; range, 25 to 66 years). Seven of these 9 patients (78%) had multiple organs involved, and 7 (78%) had severe disease by the NIH Global Severity scale. Over a median treatment duration of 28 weeks (range, 10 to 48 weeks), 8 patients (89%) had decreased frequency of muscle cramps from a median of 5 episodes per week (range, 3 per day to 2 per week) to a median of <1 episode per week (range, 1 per month to 3 per week). The pain and duration of muscle cramps were not changed meaningfully. The NIH Global Severity score remained unchanged in 6 patients (67%) and was improved in 3 patients (33%). Muscle cramping is a morbid feature of cGVHD that may be sensitive to change with standard immunomodulatory therapies. Muscle cramp frequency should be further validated as a response measure in cGVHD.

Fertility Preservation in Adolescents and Young Adults With Cancer: A Case-Based Review.

Adolescent and young adult (AYA) oncology patients are unique in many aspects of their care; fertility preservation (FP) is one of the most complex to address. In addition to the newly diagnosed AYA patient, there are growing numbers of AYA survivors of childhood cancer who present with concerns about their fertility. Emerging independence, emotional and intellectual growth, and development of an adult mindset are hallmarks of the AYA population; these transitions heighten the intrinsic medical, social, and financial challenges of a cancer diagnosis. FP is extraordinarily important in AYA oncology and can be addressed in many ways: experimental options as well as standard of care, with key differences on the basis of pubertal development, cancer diagnosis, and urgency of cancer-directed therapy. Options exist both at diagnosis and throughout the survivorship journey. It is imperative that oncologists recognize the challenges in this age group, as well as opportunities to pursue FP. The field has evolved significantly in the past 25 years and will continue to evolve as we incorporate more immune-based and targeted therapies into our treatment regimens. This case-based review will explore opportunities to preserve fertility in this unique patient population.

Chronic graft-versus-host disease. Part I: Epidemiology, pathogenesis, and clinical manifestations.

Chronic graft-versus-host disease is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 U.S. Food and Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of chronic graft-versus-host disease. Part II discusses disease grading and therapeutic management.

Chronic graft-versus-host disease. Part II: Disease activity grading and therapeutic management.

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation and a leading cause of long-term morbidity, nonrelapse mortality, and impaired health-related quality of life. The skin is commonly affected and presents heterogeneously, making the role of dermatologists critical in both diagnosis and treatment. In addition, new clinical classification and grading schemes inform treatment algorithms, which now include 3 Federal Drug Administration-approved therapies, and evolving transplant techniques are changing disease epidemiology. Part I reviews the epidemiology, pathogenesis, clinical manifestations, and diagnosis of cGVHD. Part II discusses disease grading and therapeutic management.

One versus two sets of busulfan therapeutic drug monitoring in myeloablative allogeneic hematopoietic cell transplant.

INTRODUCTION: Busulfan is a common component of allogeneic hematopoietic cell transplant (alloHCT) conditioning, however interpatient pharmacokinetic variability can result in enhanced toxicity or increased relapse risk. Therapeutic drug monitoring (TDM) can minimize variability, yet the optimal frequency of TDM is unknown. We compared outcomes for patients with one versus two sets of busulfan TDM during myeloablative conditioning (MAC) prior to alloHCT. METHODS: We analyzed the impact of busulfan TDM frequency and dose adjustments, with the primary outcome being relapse-free survival (RFS). Other outcomes included the incidence of acute and chronic graft versus host disease (GVHD), oral mucositis, pulmonary toxicity, sinusoidal obstruction syndrome (SOS), the cumulative incidence of relapse (CIR), and overall survival (OS). RESULTS: Twenty-two patients underwent one set of sampling while 53 patients underwent two sets. Similar baseline characteristics were observed between the groups. There were no significant differences observed in RFS by day +180 (77.3% vs. 79.2%, p = 1.0), CIR by day +180 (18.2% vs. 17.8%, p = 0.74), or OS (p = 0.73). The incidences of acute GVHD, chronic GVHD, SOS, and severe mucositis were also similar. In each group, 63% received busulfan dose adjustments after one set, with 52.8% receiving further dose adjustments following the second set. CONCLUSION: We observed no significant difference in alloHCT outcomes between patients who underwent one versus two sets of busulfan TDM sampling, suggesting that a single-time TDM and dose adjustment may be adequate to maximize outcomes after MAC alloHCT.

Real-world effectiveness of intensive chemotherapy with 7&3 versus venetoclax and hypomethylating agent in acute myeloid leukemia.

Intensive chemotherapy with cytarabine and anthracycline (7&3) remains the standard therapy for patients medically fit for induction, but the assessment of fitness remains controversial. Venetoclax and hypomethylating agent (ven/HMA) combination therapy has improved outcomes in unfit patients but no prospective study has assessed ven/HMA versus 7&3 as initial therapy in older, fit patients. Given no studies and expectation of ven/HMA use in patients outside of trial criteria, we evaluated retrospective outcomes among newly diagnosed patients. A nationwide electronic health record (EHR)-derived database and the University of Pennsylvania EHR identified 312 patients receiving 7&3 and 488 receiving ven/HMA who were 60-75 years old without history of organ failure. Ven/HMA patients were older and more likely to have secondary AML, adverse cytogenetics, and adverse mutations. Median overall survival (OS) for patients receiving intensive chemotherapy was 22 versus 10 months for ven/HMA (HR 0.53, 95% CI 0.40-0.60). Controlling for measured baseline characteristic imbalances reduced survival advantage by half (HR 0.71, 95% CI 0.53-0.94). A sub-group of patients with equipoise, likelihood at least 30%-70% of receiving either treatment, had similar OS outcomes (HR 1.10, 95% CI 0.75-1.6). Regarding safety outcomes, 60-day mortality was higher for ven/HMA (15% vs. 6% at 60 days) despite higher documented infections and febrile neutropenia for 7&3. In this multicenter real-word dataset, patients selected for intensive chemotherapy had superior OS but a large group had similar outcomes with ven/HMA. Prospective randomized studies, controlling for both measured and unmeasured confounders, must confirm this outcome.

Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis.

BACKGROUND: In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against graft-versus-host disease (GVHD). A phase 2 study indicated the potential superiority of a post-transplantation regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil. METHODS: In a phase 3 trial, we randomly assigned adults with hematologic cancers in a 1:1 ratio to receive cyclophosphamide-tacrolimus-mycophenolate mofetil (experimental prophylaxis) or tacrolimus-methotrexate (standard prophylaxis). The patients underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched (i.e., mismatched at only one of the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci) unrelated donor, after reduced-intensity conditioning. The primary end point was GVHD-free, relapse-free survival at 1 year, assessed in a time-to-event analysis, with events defined as grade III or IV acute GVHD, chronic GVHD warranting systemic immunosuppression, disease relapse or progression, and death from any cause. RESULTS: In a multivariate Cox regression analysis, GVHD-free, relapse-free survival was significantly more common among the 214 patients in the experimental-prophylaxis group than among the 217 patients in the standard-prophylaxis group (hazard ratio for grade III or IV acute GVHD, chronic GVHD, disease relapse or progression, or death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P = 0.001). At 1 year, the adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) with experimental prophylaxis and 34.9% (95% CI, 28.6 to 41.3) with standard prophylaxis. Patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall and disease-free survival, relapse, transplantation-related death, and engraftment did not differ substantially between the groups. CONCLUSIONS: Among patients undergoing allogeneic HLA-matched HSCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common among those who received cyclophosphamide-tacrolimus-mycophenolate mofetil than among those who received tacrolimus-methotrexate. (Funded by the National Heart, Lung, and Blood Institute and others; BMT CTN 1703 ClinicalTrials.gov number, NCT03959241.).

Patient-Centered Care in the Management of Cancer During Pregnancy.

The management of cancer during pregnancy requires a patient-centered, multidisciplinary approach to balance maternal and fetal well-being given the rarity of this clinical scenario and lack of substantial data. Involvement of oncology and nononcology medical specialists and ethical, legal, and psychosocial supports, as needed, is instrumental in navigating the complexities of care for this patient population. Critical periods of fetal development and physiological changes in pregnancy must be considered when planning diagnostic and therapeutic approaches during pregnancy. The complexity of symptom recognition and interventional approaches contributes to diagnostic delays of cancers during pregnancy. Ultrasound and whole-body diffusion-weighted magnetic resonance imaging are safe throughout pregnancy. Surgery can be safely performed throughout pregnancy, with the early second trimester preferred for intra-abdominal surgery. Chemotherapy can be safely administered after 12-14 weeks of gestation until 1-3 weeks before the anticipated delivery. Most targeted and immunotherapeutic agents are contraindicated during pregnancy because of limited data. Pelvic radiation during pregnancy is absolutely contraindicated, while if radiation to the upper body is needed, administration should only be considered early in pregnancy. To ensure that the total cumulative fetal exposure to ionizing radiation does not exceed 100 mGy, early inclusion of the radiology team in the care plan is required. Closer prenatal monitoring is recommended for maternal and fetal treatment-related toxicities. Delivery before 37 weeks of gestation should be avoided if possible, and vaginal delivery is preferred unless obstetrically indicated or specific clinical scenarios. Postpartum, breastfeeding should be discussed, and the neonate should receive blood work to assess for acute toxicities with follow-up arranged for long-term monitoring.

Health-Related Quality of Life Outcomes in Older Hematopoietic Cell Transplantation Survivors.

The use of hematopoietic cell transplantation (HCT) has been increasing in older patients. However, the levels if distress, psychosocial functioning, and health-related quality of life (HRQOL) among older HCT survivors remains largely unknown. In this secondary analysis using data from 2 randomized controlled trials, we analyzed baseline Cancer and Treatment Distress (CTXD) and Confidence In Survivorship Information (CSI) surveys of HCT survivors who were age ≥60 years at the time of transplantation and alive and disease-free ≥1 year post-autologous or -allogeneic HCT. We analyzed associations of these parameters with the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the 12-Item Short Form Survey (SF-12) and a healthcare adherence (HCA) scale, after adjusting for transplantation and patient demographic factors. A total of 567 patients were included. The median patient age at HCT was 65 years, and 68% of the patients underwent autologous HCT. The median CTXD score was .7 (mild), and the greatest distress was reported in the "health burden" subscale. The median CSI score was 1.4 (moderate-high), with the lowest confidence reported in the "late effects" subscale. We found negative Spearman correlations between CTXD score and SF-12 PCS (P = -.59) and MCS (P = -.54) and positive Spearman correlations between CSI score and SF-12 PCS (P = .23) and MCS (P = .30). The median HCA scale score was high at .8. Male sex, autologous HCT, increased distress level, and worse CSI score were associated with lower use of preventive care. Older survivors experienced a low level of distress and moderate-high level of CSI at ≥1 year post-HCT. As lower distress and higher CSI were associated with improved HRQOL and optimized preventive HCA, CTXD/CSI measures can be used to individualize the care of older adult HCT survivors.

Clofarabine and Busulfan Myeloablative Conditioning in Allogeneic Hematopoietic Cell Transplantation for Patients With Active Myeloid Malignancies.

Patients with refractory or relapsed and refractory myeloid malignancies have a poor prognosis. Allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning (MAC) in patients with active, chemotherapy-refractory myeloid disease is historically associated with high rates of relapse and nonrelapse mortality (NRM). A MAC regimen combining clofarabine with busulfan (Clo/Bu4) has been reported to exhibit antileukemic activity with acceptable toxicity in patients age ≤70 years. Here we describe the clinical outcomes of a real-world population of patients with active myeloid malignancies undergoing allogeneic HCT with Clo/Bu4 MAC. In a single-center retrospective descriptive analysis, we identified patients who underwent HCT for myeloid malignancies not in remission using Clo/Bu4 MAC between 2012 and 2020. We report event-free survival (EFS) and overall survival (OS), cumulative incidences of relapse and NRM, and the incidence and severity of acute and chronic graft-versus-host disease (GVHD). We identified 69 patients with a median age of 60 years (range, 22 to 70 years). Most patients had relapsed/refractory or primary refractory acute myelogenous leukemia (AML; n = 55) or refractory myelodysplastic syndrome (MDS; n = 12); 1 patient had chronic myelogenous leukemia, and 1 patient had a blastic plasmacytoid dendritic cell neoplasm. Fifty patients (72.5%) had complete remission at day 100 post-transplantation. Two-year EFS and OS were 30% (95% confidence interval [CI], 20% to 44%) and 40% (95% CI, 29% to 54%), respectively. Patients with AML had a 2-year EFS and OS of 28% (95% CI, 18% to 44%) and 38% (95% CI, 27% to 54%), respectively; those with MDS had a 2-year EFS and OS of 47% (95% CI, 25% to 88%) and 56% (95% CI, 33% to 94%), respectively. The cumulative incidence of relapse at 2 years was 39% (95% CI, 27% to 51%) for all patients, including 45% (95% CI, 31% to 58%) in the patients with AML and 18% (95% CI, 2% to 45%) in those with MDS. NRM at 2 years was 31% (95% CI, 20% to 42%), including 27% (95% CI, 15% to 39%) in patients with AML and 35% (95% CI, 10% to 63%) in those with MDS. The total incidence of acute GVHD (aGVHD) of any severity was 80%, and the incidence of grade III-IV aGVHD was 22%. In patients who achieved remission, those who required systemic immunosuppression for aGVHD (58%) had poorer 2-year EFS (29% versus 54%; P = .05) and 2-year OS (39% versus 70%; P = .04) compared to those who did not. The 2-year cumulative incidence of chronic GVHD was 44% (95% CI, 28% to 58%). Clo/Bu4 MAC followed by allogeneic HCT for patients with active myeloid malignancies is an effective transplantation strategy for patients up to age 70, particularly those with advanced MDS. The high incidence of and poor outcomes associated with aGVHD highlight the importance of optimizing preventative strategies.

Health-Related Quality of Life in Young Adult Survivors of Hematopoietic Cell Transplantation.

Young adults (YA), age 18 to 39 years, are at a stage of life that may make them more vulnerable than older adults to impairments in health-related quality of life (HRQOL) during and after hematopoietic cell transplantation (HCT). Health self-efficacy (HSE), the belief that one can implement strategies to produce a desired health outcome, has been associated with health outcomes in oncology research. Little is known about HRQOL or HSE in YA HCT survivors compared with older HCT survivors. Given the age-specific psychosocial challenges facing YA HCT recipients and research on non-transplant YA cancer survivors, we hypothesized that YA survivors would have worse post-HCT HRQOL compared with older adults, and that among YA HCT survivors, higher levels of HSE would be associated with higher levels of HRQOL and lower levels of cancer-related distress. This was a cross-sectional secondary analysis of 2 combined baseline datasets from multicenter studies of HCT survivors approached for participation in clinical trials of survivorship interventions. Participants from 20 transplantation centers in the United States were at 1 to 10 years post-HCT and age ≥18 years at the time of study enrollment, had no evidence of disease relapse/progression or subsequent malignancies, and could read English adequately to consent for and complete assessments. Medical record and patient-reported data were obtained for demographics and HCT-related clinical factors and complications (eg, total body irradiation, chronic graft-versus-host disease [cGVHD]). Participants completed surveys on HRQOL, including the Short-Form [SF]-12, HSE, and Cancer and Treatment Distress (CTXD), which includes 6 subscales and reports an overall mean score. On the SF-12, both the Mental Component Score (MCS) and Physical Component Score (PCS) were calculated. Two cohorts were compared: YAs (age 18 to 39 years at transplantation) and older adults (age ≥40 years at transplantation). Multiple linear regression analyses identified factors associated with HSE, PCS, MCS, and CTXD in YAs. In this analysis of 979 survivors, compared with the older adults, the YA participants had lower median mental health scores (SF-12 MCS: 48.40 versus 50.23; P = .04) and higher cancer-related distress (CTXD: .96 versus .85; P = .04), but better physical health (SF-12 PCS: 48.99 versus 47.18; P = .049). Greater overall cancer-related distress was driven by higher levels of uncertainty, financial concern, and medical demand subscales for YAs compared with older adults. Young adults also had lower HSE (2.93 versus 3.08; P = .0004). In a multivariate model, HSE was strongly associated with age group (P = .0005) after adjusting for multiple other transplantation-related factors. Among YAs, HSE was associated with the SF-12 MCS and PCS and the CTXD, and HSE remained significant after adjusting for other transplantation-related factors. Overall, the YA HCT survivors had lower mental health, increased cancer-related distress, and lower levels of HSE compared with the older adults. Although the direction of these effects cannot be determined with these data, the strong association between HSE and HRQOL among YAs suggests that targeting interventions to improve HSE may have broad impact on health outcomes.

Self-Efficacy for Symptom Management in Long-Term Adult Hematopoietic Stem Cell Survivors.

Hematopoietic cell transplantation (HCT) survivors have a complex and multiphase recovery period. Health care delivery and psychosocial interventions for HCT survivors are challenging because many HCT recipients live great distances from the facility where they had their HCT. Therefore identifying factors associated with a patient's capability to self-manage symptoms is a significant focus of survivorship research. A patient's self-efficacy may be important for the successful management of major stressors associated with treatments and recovery. Here, we aimed to evaluate the impact of perceived self-efficacy on distress, quality of life (QoL), depression, and fatigue and identify the factors associated with lower self-efficacy. This cross-sectional study analyzed baseline data from a randomized controlled trial INSPIRE (NCT01602211) in adult (age 18 and older) survivors 2 to 10 years after HCT. Patients with recurrence or subsequent malignancy requiring cancer treatment during the 2 years before enrollment, inability to read and understand English, and lack of access to email and the Internet were excluded. Data included medical records and patient-reported outcomes including Cancer and Treatment Distress (CTXD) with 6 subscales, Patient Health Questionnaire depression scale (PHQ-8), Short Form 12 Health Survey (SF-12) physical function and mental function scores, Brief Fatigue Inventory (BFI) and Self-Efficacy. Pearson correlations were used to test bivariate associations for self-efficacy of CTXD, SF-12, BFI, and PHQ-8. General linear models were used to test the independent associations for CTXD and SF-12 outcomes with self-efficacy, controlling for selected sociodemographic and treatment covariates. Tenability of statistical model assumptions were examined, and no remediation was necessary. A total of 1078 HCT survivors were included in the analysis. Participants were 19 to 85 years (mean age 58), 53% male, and over 90% White and non-Hispanic. Only 16% reported living in a rural area. A majority received an autologous HCT (55%) and were less than 5 years from their first HCT (54%). Among the allogeneic HCT recipients, more than half (55%) had active chronic Graft-versus-Host (cGVHD) and nearly 40% were on active systemic treatment. The mean self-efficacy score was 3.01 (SD = 0.49). Female sex (P = .014), younger age at HCT, younger age at cGVHD presentation (P = .031), moderate to severe currently active cGVHD (P = .003) and household income less than $40,000 (P< .001) were associated with lower self-efficacy. In bivariate analyses, self-efficacy was negatively correlated with mean total distress (CTXD, r = -.5, P< .001) and each of the CTXD subscales. HCT survivors with higher self-efficacy also reported better physical (r 0.48, P< .001) and mental function on the SF-12 (r = 0.57, P< .001). Moreover, self-efficacy was negatively correlated with symptoms such as fatigue (r = -.44, P< .001) and depression (r = -.48, P< .001). In a regression model investigating the impact of self-efficacy on CTXD controlled for demographics and disease characteristics, lower self-efficacy was independently associated with higher distress (CTXD, ß = -.232; 95% CI [-.294, -.169], P< .001). Moreover, there was a significant positive relationship between self-efficacy and both mental (ß = 4.68; 95% CI [3.82, 5.54]; P< .001) and physical (ß = 2.69; 95% CI [1.74, 3.64]; P< .001) components of QoL. Our study demonstrates that lower levels of self-efficacy reported by HCT survivors were independently associated with higher levels of symptoms such as fatigue and depression, lower QoL, and more cancer-related distress. Furthermore, self-efficacy was more likely to be impaired in females, younger adults, those with lower incomes, and survivors with active cGVHD. These findings support the value of self-management interventions focused on improving self-efficacy as having the potential to improve multiple symptoms and QoL in HCT survivors.

Pentosan polysulfate for the treatment of hemorrhagic cystitis after allogeneic hematopoietic cell transplant.

INTRODUCTION: Hemorrhagic cystitis can commonly occur following an allogeneic hematopoietic cell transplant and treatment options are currently limited. Pentosan polysulfate, a heparin-like, sulfated polysaccharide, is used to relieve bladder pain and discomfort associated with interstitial cystitis. Initial reports in patients with hemorrhagic cystitis demonstrate that pentosan polysulfate may hasten hemorrhagic cystitis resolution and control symptoms. METHODS AND RESULTS: This report includes a retrospective case series of six patients who received pentosan polysulfate for the treatment of hemorrhagic cystitis following an allogeneic hematopoietic cell transplant. Pentosan polysulfate was initiated at a median of 4.5 days (range: 3-18) following hemorrhagic cystitis onset and continued for a median duration of 17.5 days (range: 7-64). Four patients were tested for BK virus and all were found to have BK viremia and viruria around the time of pentosan polysulfate initiation. The median number of red blood cell transfusions seemed to decrease in the patients initiated on pentosan polysulfate. All patients received a multi-agent treatment regimen, which included pentosan polysulfate, and half the patients had symptom resolution. The median time to symptom resolution from pentosan polysulfate initiation was 9 days (range: 7-10). CONCLUSION: Pentosan polysulfate was well-tolerated and seemed to assist with symptom resolution. Future studies are needed to confirm the impact of pentosan polysulfate on the treatment of hemorrhagic cystitis.

Low-Dose Total Body Irradiation Added to Fludarabine and Busulfan Reduced-Intensity Conditioning Reduces Graft Failure in Patients with Myelofibrosis.

Allogeneic hematopoietic cell transplantation (alloHCT) is indicated for patients with intermediate-risk or high-risk myelofibrosis (MF) and remains the sole potential cure. Reduced-intensity conditioning (RIC) is commonly used because of older patient age, comorbidities, and a high incidence of transplantation-related mortality. Patients with MF are at increased risk of graft failure (GF), which is more common with RIC regimens, and is associated with shortened overall survival (OS). Owing to the high rate of GF with conventional fludarabine (Flu) and busulfan (Bu) RIC, we added low-dose total body irradiation (TBI; 200 cGy) for patients with MF. We retrospectively compared alloHCT outcomes in adult patients with MF who received RIC with Flu/Bu/TBI and those who received RIC with Flu/Bu. The primary endpoint was the incidence of GF. Secondary endpoints included time to engraftment, acute and chronic graft-versus-host disease (GVHD), hepatic sinusoidal obstruction syndrome (SOS), nonrelapse mortality, overall response rate, progression-free survival, and OS. Of 33 patients who underwent alloHCT, 8 received Flu/Bu RIC and 25 received Flu/Bu/TBI RIC. GF occurred in 50% of the Flu/Bu recipients (all secondary GF) and in 4% of the Flu/Bu/TBI recipients (1 case of primary GF; relative risk, .08; 95% confidence interval [CI], .01 to .62; P = .0016). GF incidence was similar with related or unrelated donors and in patients who did and did not receive Janus-associated kinase inhibitors prior to alloHCT. Molecular remission and donor chimerism ≥99% were significantly more common with Flu/Bu/TBI. No significant differences in acute GVHD, chronic GVHD, or time to engraftment were observed. SOS occurred in none of the 8 patients who received Flu/Bu and in 6 of the 25 patients who received Flu/Bu/TBI, but this difference did not reach statistical significance. Progression or relapse at 1 year was less common with Flu/Bu/TBI (0% versus 63%; P < .001). The median OS was 49 months for Flu/Bu/TBI recipients and 30.8 months for Flu/Bu recipients (hazard ratio, .98; 95% CI, .33 to 2.88; P = .97). Flu/Bu/TBI resulted in a significant reduction in GF and a significant improvement in the frequency of molecular remission and full donor chimerism compared with Flu/Bu. The addition of low-dose TBI to Flu/Bu successfully mitigates against GF in patients with MF without increased rates of complications.

Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia.

CPX-351 and venetoclax and azacitidine (ven/aza) are both indicated as initial therapy for acute myeloid leukemia (AML) in older adults. In the absence of prospective randomized comparisons of these regimens, we used retrospective observational data to evaluate various outcomes for patients with newly diagnosed AML receiving either CPX-351 (n = 217) or ven/aza (n = 439). This study used both a nationwide electronic health record (EHR)-derived de-identified database and the University of Pennsylvania EHR. Our study includes 217 patients who received CPX-351 and 439 who received ven/aza. Paitents receiving ven/aza were older, more likely to be treated in the community, and more likely to have a diagnosis of de novo acute myeloid leukemia. Other baseline covariates were not statistically significantly different between the groups. Median overall survival (OS) for all patients was 12 months and did not differ based on therapy (13 months for CPX-351 vs 11 months for ven/aza; hazard ratio, 0.88; 95% confidence interval, 0.71-1.08; P = .22). OS was similar across multiple sensitivity analyses. Regarding safety outcomes, early mortality was similar (10% vs 13% at 60 days). However, documented infections were higher with CPX-351 as were rates of febrile neutropenia. Hospital length of stay, including any admission before the next cycle of therapy, was more than twice as long for CPX-351. In this large multicenter real-world dataset, there was no statistically significant difference in OS. Prospective randomized studies with careful attention to side effects, quality of life, and impact on transplant outcomes are needed in these populations.