Heather R. Millard

Allogeneic transplantation for advanced acute myeloid leukemia: The value of complete remission

Patients with acute myeloid leukemia (AML) without complete remission (CR) or in first relapse (Rel1) can have extended leukemia control and survival after allogeneic hematopoietic cell transplantation (HCT). For patients in Rel1 or primary induction failure (PIF), transplantation versus treatment to achieve a second CR (CR2) and subsequent HCT might yield similar outcomes, but available comparative data are scarce.

Hematopoietic Stem Cell Transplantation Activity in Pediatric Cancer between 2008 and 2014 in the United States: A Center for International Blood and Marrow Transplant Research Report

This Center for International Blood and Marrow Transplant Research report describes the use of hematopoietic stem cell transplantation (HSCT) in pediatric patients with cancer, 4408 undergoing allogeneic (allo) and3076 undergoing autologous (auto) HSCT in the United States between 2008 and 2014. In both settings, there was a greater proportion of boys (n = 4327; 57%), children < 10 years of age (n = 4412; 59%), whites (n = 5787; 77%), and children with a performance score ≥ 90% at HSCT (n = 6187; 83%). Leukemia was the most common indication for an allo-transplant (n = 4170; 94%), and among these, acute lymphoblastic leukemia in second complete remission (n = 829; 20%) and acute myeloid leukemia in first complete remission (n = 800; 19%) werethe most common. The most frequently used donor relation, stem cell sources, and HLA match were unrelated donor (n = 2933; 67%), bone marrow (n = 2378; 54%), and matched at 8/8 HLA antigens (n = 1098; 37%) respectively. Most allo-transplants used myeloablative conditioning (n = 4070; 92%) and calcineurin inhibitors and methotrexate (n = 2245; 51%) for acute graft-versus-host disease prophylaxis. Neuroblastoma was the most common primary neoplasm for an auto-transplant (n = 1338; 44%). Tandem auto-transplants for neuroblastoma declined after 2012 (40% in 2011, 25% in 2012, and 8% in 2014), whereas tandem auto-transplants increased for brain tumors (57% in 2008 and 77% in 2014). Allo-transplants from relatives other than HLA-identical siblings doubled between 2008 and 2014 (3% in 2008 and 6% in 2014). These trends will be monitored in future reports of transplant practices in the United States.

Personalized Prognostic Risk Score for Long-Term Survival for Children with Acute Leukemia after Allogeneic Transplantation

We studied leukemia-free (LFS) and overall survival (OS) in children with acute myeloid (AML, n = 790) and acute lymphoblastic leukemia (ALL, n = 1096) who underwent transplantation between 2000 and 2010 and who survived for at least 1 year in remission after related or unrelated donor transplantation. Analysis of patient-, disease-, and transplantation characteristics and acute and chronic graft-versus-host disease (GVHD) was performed to identify factors with adverse effects on LFS and OS. These data were used to develop risk scores for survival. We did not identify any prognostic factors beyond 4 years after transplantation for AML and beyond 3 years for ALL. Risk score for survival for AML includes age, disease status at transplantation, cytogenetic risk group, and chronic GVHD. For ALL, the risk score includes age at transplantation and chronic GVHD. The 10-year probabilities of OS for AML with good (score 0, 1, or 2), intermediate (score 3), and poor risk (score 4, 5, 6, or 7) were 94%, 87%, and 68%, respectively. The 10-year probabilities of OS for ALL were 89% and 80% for good (score 0 or 1) and poor risk (score 2), respectively. Identifying children at risk for late mortality with early intervention may mitigate some excess late mortality.

Survival and Late Effects after Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancy at Less than Three Years of Age

Very young children undergoing hematopoietic cell transplantation (HCT) are a unique and vulnerable population. We analyzed outcomes of 717 patients from 117 centers who survived relapse free for ≥1 year after allogeneic myeloablative HCT for hematologic malignancy at <3 years of age, between 1987 and 2012. The median follow-up was 8.3 years (range, 1.0 to 26.4 years); median age at follow-up was 9 years (range, 2 to 29 years). Ten-year overall and relapse-free survival were 87% (95% confidence interval [CI], 85% to 90%) and 84% (95% CI, 81% to 87%). Ten-year cumulative incidence of relapse was 11% (95% CI, 9% to 13%). Of 84 deaths, relapse was the leading cause (43%). Chronic graft-versus-host-disease 1 year after HCT was associated with increased risk of mortality (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.3; P = .0018). Thirty percent of patients experienced ≥1 organ toxicity/late effect >1 year after HCT. The most frequent late effects included growth hormone deficiency/growth disturbance (10-year cumulative incidence, 23%; 95% CI, 19% to 28%), cataracts (18%; 95% CI, 15% to 22%), hypothyroidism (13%; 95% CI, 10% to 16%), gonadal dysfunction/infertility requiring hormone replacement (3%; 95% CI, 2% to 5%), and stroke/seizure (3%; 95% CI, 2% to 5%). Subsequent malignancy was reported in 3.6%. In multivariable analysis, total body irradiation (TBI) was predictive of increased risk of cataracts (HR, 17.2; 95% CI, 7.4 to 39.8; P < .001), growth deficiency (HR, 3.5; 95% CI, 2.2 to 5.5; P < .001), and hypothyroidism (HR, 5.3; 95% CI, 3.0 to 9.4; P < .001). In summary, those who survived relapse free ≥1 year after HCT for hematologic malignancy at <3 years of age had favorable overall survival. Chronic graft-versus-host-disease and TBI were associated with adverse outcomes. Future efforts should focus on reducing the risk of relapse and late effects after HCT at early age.

Long-term outcomes among 2-year survivors of autologous hematopoietic cell transplantation for Hodgkin and diffuse large b-cell lymphoma: Long-Term Outcomes After Auto-HCT

Autologous hematopoietic cell transplantation (auto‐HCT) is a standard therapy for relapsed classic Hodgkin lymphoma (cHL) and diffuse large B‐cell lymphoma (DLBCL); however, long‐term outcomes are not well described.

Centralized patient-reported outcome data collection in transplantation is feasible and clinically meaningful

Allogeneic hematopoietic cell transplantation (HCT) cures many patients, but often with the risk of late effects and impaired quality of life. The value of quantifying patient‐reported outcomes (PROs) is increasingly being recognized, but the routine collection of PROs is uncommon. This study evaluated the feasibility of prospective PRO collection by an outcome registry at multiple time points from unselected HCT patients undergoing transplantation at centers contributing clinical data to the Center for International Blood and Marrow Transplant Research (CIBMTR), and then it correlated the PRO data with clinical and demographic data.

Effect of β-blocker Therapy on Hospital Readmission and Mortality in Heart Failure Patients With Concurrent Cocaine Use:

Background: β-Blockers are first-line agents for reduction in symptoms, hospitalization, and mortality in patients with heart failure having reduced ejection fraction (HFrEF). However, the safety and efficacy of continuous β-blocker therapy (BBT) in patients who actively use cocaine remain controversial, and available literature is limited. We aimed to evaluate the effect of BBT on hospital readmission and mortality in patients having HFrEF with concurrent cocaine use. Methods: We conducted a retrospective study of patients with a diagnosis of HFrEF between 2011 and 2014 based on International Classification of Diseases 9-Clinical Modification codes. We included patients aged 18 and older who tested positive for cocaine on a urine toxicology test obtained at the time of index admission. Patients were followed for 1 year. Multivariate logistic regression was used to assess the effect of BBT on the 30-day, all-cause and heart failure–related readmissions. Results: The 30-day readmission rates for BBT versus no BBT groups were 20% versus 41% (odds ratio [OR]: 0.17, 95% confidence interval [CI] = 0.05-0.56, P = .004) for heart failure-related readmissions and 25% versus 46% (OR: 0.19, 95% CI = 0.06-0.64, P = .007) for all-cause readmissions. Conclusion: The BBT reduced 30-day, all-cause and heart failure–related readmission rate but not 1-year mortality in patients having HFrEF with concurrent cocaine use.

Prevalence of self-reported sleep dysfunction before allogeneic hematopoietic cell transplantation

To the Editor, Allogeneic hematopoietic cell transplantation (alloHCT) is an increasingly utilized high-risk therapy used to treat various malignant and nonmalignant diseases [1]. The numbers of alloHCT performed each year continue to increase for all age groups, particularly those aged 60 and older [1], and it remains a physically and psychologically arduous treatment approach [2, 3]. Nearly 75–80% of hospitalized HCT patients experience sleep disruption in the early post-transplant setting [4, 5]; this can exacerbate impaired quality of life, depression, and fatigue in HCT recipients [6]. Sleep is a restorative biologic process essential for maintaining health [7]. There is epidemiologic evidence that sleep disturbance independently contributes to inflammation and that improving sleep quality in older adults with insomnia can reduce biomarkers of multisystem biological risk, including C-reactive protein, hemoglobin A1C, insulin, lipoproteins, and triglycerides among others, in a randomized clinical trial setting [8, 9]. Sleep dysfunction may adversely impact alloHCT outcomes through increased pro-inflammatory pathways as shown in HCT and other populations and may lead to adverse post-alloHCT outcomes [5, 10]. Based on this intriguing background, we hypothesized that patient-reported sleep disturbance before alloHCT would correlate with early post-alloHCT outcomes. We used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to conduct this research. From 2011 to 2013, the CIBMTR prospectively enrolled 390 patients from 7 transplant centers to assess the feasibility of collecting patient-reported outcomes [11]. Of these, 340 patients completed the baseline survey including 84 pediatric patients. Adult patients completed the 36-item short form health survey (SF-36) and Functional Assessment of Cancer Therapy-Bone Marrow Transplantation subscale (FACT-BMT) questionnaires before HCT and at day 100, 6 months, and 1 year after HCT. Herein, we focus on responses to the sleep-specific question from FACTBMT in all adult patients included in this pilot who underwent alloHCT for acute and chronic leukemias, myelodysplastic syndromes, and myeloproliferative neoplasms (N= 198). We excluded small numbers of patients with non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, and variety of nonmalignant diseases owing to a wide heterogeneity in pre-transplant treatments, as well as duration of disease. The sleep question in FACT-BMT is a single question applied to the past 7 days, “I am sleeping well,” with five response options: (0—not at all, 1—a little bit, 2—somewhat, 3—quite a bit, 4—very much). We analyzed 0/1/2 as “poor sleep” and 3/4 as “good sleep” groups as reported on the before HCT questionnaire. Descriptive statistics were used to summarize the characteristics of the groups and the Kaplan–Meier estimator was used to evaluate survival. The primary outcome of interest was 1-year overall survival (OS). Other outcomes included transplant-related mortality, relapse, and graftversus-host disease, acute (aGVHD) and chronic (cGVHD); GVHD was analyzed as a time-dependent variable. All outcomes were assessed at 1 year, except aGVHD, which was assessed at day 100. Multivariate analysis was conducted using a Cox proportional hazards model. Factors assessed in multivariate analysis included baseline sleep group (main effect), age at transplant, gender, Karnofsky Performance Score (KPS), disease, disease risk, * Anita D’Souza andsouza@mcw.edu