Umbilical cord blood: an undervalued and underutilized resource in allogeneic hematopoietic stem cell transplant and novel cell therapy applications.

PURPOSE OF REVIEW: The purpose of this review is to primarily discuss the unwarranted decline in the use of umbilical cord blood (UCB) as a source of donor hematopoietic stem cells (HSC) for hematopoietic cell transplantation (HCT) and the resulting important implications in addressing healthcare inequities, and secondly to highlight the incredible potential of UCB and related birthing tissues for the development of a broad range of therapies to treat human disease including but not limited to oncology, neurologic, cardiac, orthopedic and immunologic conditions. RECENT FINDINGS: When current best practices are followed, unrelated donor umbilical cord blood transplant (CBT) can provide superior quality of life-related survival compared to other allogeneic HSC donor sources (sibling, matched or mismatched unrelated, and haploidentical) through decreased risks of relapse and chronic graft vs. host disease. Current best practices include improved UCB donor selection criteria with consideration of higher resolution human leukocyte antigen (HLA) typing and CD34+ cell dose, availability of newer myeloablative but reduced toxicity conditioning regimens, and rigorous supportive care in the early posttransplant period with monitoring for known complications, especially related to viral and other infections that may require intervention. Emerging best practice may include the use of ex vivo expanded single-unit CBT rather than double-unit CBT (dCBT) or 'haplo-cord' transplant, and the incorporation of posttransplant cyclophosphamide as with haploidentical transplant and/or incorporation of novel posttransplant therapies to reduce the risk of relapse, such as NK cell adoptive transfer. Novel, non-HCT uses of UCB and birthing tissue include the production of UCB-derived immune effector cell therapies such as unmodified NK cells, chimeric antigen receptor-natural killer cells and immune T-cell populations, the isolation of mesenchymal stem cells for immune modulatory treatments and derivation of induced pluripotent stem cells haplobanks for regenerative medicine development and population studies to facilitate exploration of drug development through functional genomics. SUMMARY: The potential of allogeneic UCB for HCT and novel cell-based therapies is undervalued and underutilized. The inventory of high-quality UCB units available from public cord blood banks (CBB) should be expanding rather than contracting in order to address ongoing healthcare inequities and to maintain a valuable source of cellular starting material for cell and gene therapies and regenerative medicine approaches. The expertise in Good Manufacturing Practice-grade manufacturing provided by CBB should be supported to effectively partner with groups developing UCB for novel cell-based therapies.

Group Coaching Using Energy-Based Practices for Health, Healing, and Personal Growth: Program Design and Training Outcomes.

An innovative training curriculum on energy-based practices for group coaching was developed and disseminated to 16 coaching students. This article describes phase 1 curriculum design and initial evaluation of the coaching program. Findings demonstrated the benefits of this course, highlighted areas for refinement, and support progression to phase 2 for wider dissemination.

High Incidence of Herpes Zoster After Cord Blood Hematopoietic Cell Transplant Despite Longer Duration of Antiviral Prophylaxis.

BACKGROUND: Cord blood transplant (CBT) recipients have a high incidence of herpes zoster (HZ) in the context of short-term peritransplant antiviral prophylaxis. In 2009, international guidelines recommended HZ prophylaxis for at least 1 year after hematopoietic cell transplant. The impact of longer-term antiviral prophylaxis on HZ incidence after CBT is unknown. METHODS: We retrospectively analyzed varicella zoster virus (VZV)-seropositive CBT recipients who were transplanted between 2006 and 2016. We abstracted HZ events and other variables for up to 5 years post-CBT. We calculated the cumulative incidence of HZ and used Cox proportional hazards regression to identify variables associated with HZ. RESULTS: The study cohort consisted of 227 patients. Among 1-year survivors, 91% were still receiving prophylaxis, for a median duration of 20.6 months. HZ occurred in 44 patients (19%) at a median of 23.6 months. The cumulative incidence of HZ by 1 year after CBT was 1.8% (95% confidence interval [CI], .1%-4%), but increased to 26% (95% CI, 19%-33%) by 5 years. In a multivariable analysis, acute graft-vs-host disease was associated with increased risk, whereas antiviral prophylaxis was associated with reduced risk for HZ (adjusted hazard ratio, 0.19 [95% CI, .09-.4]). There was no association between CD4+ T-cell counts at 1 year post-CBT and subsequent risk for HZ. CONCLUSIONS: We found a high incidence of HZ after CBT despite antiviral prophylaxis for > 1 year. Based on these findings, we suggest longer duration of prophylaxis for HZ after CBT. Compliance with antiviral prophylaxis, VZV-specific immune monitoring, and vaccination to mitigate HZ after CBT also require further study.

Needs Assessment to Inform and Improve Educational Practices Surrounding Omega-3 Consumption during Pregnancy.

OBJECTIVES: Adequate dietary consumption of long chain omega-3 fatty acids (n-3 LCPUFA) during pregnancy has been associated with better maternal and infant health outcomes. Given that the primary source of n-3 LCPUFA is fish and fish oils, concerns surrounding contamination and uncertainty of safe fish intake guidelines have negatively affected consumption of fish during pregnancy. Although obstetric healthcare providers are in a unique position to influence dietary intake patterns, a gap exists in their understanding the knowledge and practices surrounding n-3 LCPUFA. This needs assessment investigation evaluated knowledge, attitudes and prescribing/recommending practices of obstetric practitioners surrounding n-3 LCPUFA consumption and/or supplementation to generate evidence supporting the development of targeted educational initiatives. METHODS: A cross-sectional, needs assessment was conducted using anonymous online-survey of affiliate members of the American College of Nurse Midwives (N = 105). A 24-item, previously validated (α = 0.86) needs assessment survey (Obstetric Clinicians Omega-3 Survey, OCOS) was used to assess attitudes, knowledge, and prescribing practices surrounding n-3 LCPUFA. RESULTS: The total OCOS score representing attitudes, knowledge and prescribing patterns collectively was 69.48% (Mean = 79.90(± 12.44), score range = 24-115). Scores for the sub-domains included attitude 68.33% (Mean = 20.50(± 3.64), score range = 6-30); knowledge 71.40% (Mean = 30.70(± 5.43), score range = 9-43); and prescribing patterns 68.31% (Mean = 28.69(± 5.39), score range = 9-42). CONCLUSIONS FOR PRACTICE: Although the majority of respondents had fair-moderate n-3 LCPUFA knowledge, attitudes and prescribing/recommending, our results highlight an opportunity for additional research and educational outreach targeting improved n-3 LCPUFA knowledge and practices. Specific areas of educational interest included associated health outcomes, dosing and safe consumption guidelines.

Unlicensed Umbilical Cord Blood Units Provide a Safe and Effective Graft Source for a Diverse Population: A Study of 2456 Umbilical Cord Blood Recipients.

Umbilical cord blood (UCB) transplantation (UCBT) is a curative procedure for patients with hematologic malignancies and genetic disorders and expands access to transplantation for non-Caucasian patients unable to find a fully matched unrelated donor. In 2011, the US Food and Drug Administration required that unrelated UCBT be performed using either licensed UCB or unlicensed UCB under the Investigational New Drug (IND) program. The National Marrow Donor Program manages an IND under which 2456 patients (1499 adults and 957 children, 564 with malignant diseases and 393 with nonmalignant diseases) underwent single or double UCBT between October 2011 and December 2016. The median patient age was 31 years (range, <1 to 81 years), and 50% of children and 36% of adults were non-Caucasian. The median time to neutrophil engraftment (ie, absolute neutrophil count ≥500/mm3) was 22 days for adults, 20 days for pediatric patients with malignant diseases, and 19 days for pediatric patients with nonmalignant diseases, with corresponding rates of engraftment at 42 days of 89%, 88%, and 90%. In these 3 groups of patients, the incidence of acute graft-versus-host disease (GVHD) grade II-IV was 35%, 32%, and 24%; the incidence of chronic GVHD was 24%, 26%, and 24%; and 1-year overall survival (OS) was 57%, 71%, and 79%, respectively. In multivariate analysis, younger age, lower Hematopoietic Cell Transplantation-Specific Comorbidity Index, early-stage chemotherapy-sensitive disease, and higher performance score were predictive of improved OS for adults. In a subset analysis of children with malignancies undergoing single UCBT, the use of either licensed UCB (n = 48) or unlicensed UCB (n = 382) was associated with similar engraftment and survival. The use of unlicensed UCB units is safe and effective and provides an important graft source for a diverse population.

Pain Management in Patients with Heart Failure: A Survey of Nurses' Perception.

BACKGROUND: Over 50% of patients with heart failure (HF) report suffering from pain and pain-related burdens; however, pain in HF patients has not been recognized or well treated. Few studies have comprehensively examined pain management in patients with HF from nurses' perception. AIMS: To investigate nurses' perception of pain management in HF patients. METHODS: Members of American Association of Heart Failure Nurses (AAHFN) were invited to participate in a cross-sectional online survey. RESULTS: A total of 147 nurses responded and completed the survey. The majority agreed that pain in HF patients was related to anxiety, depression, fatigue, and unplanned hospitalization, and that pain should be individually assessed and managed. More than 80% thought pain management practice in HF patients should be improved, and 78.1% were interested in getting more information and believed an online education module was the most preferable approach. Lack of pain assessment tools, drug addiction, side effect, overuse, underuse, and contraindication with other medications were the main concerns regarding opioid use in pain management in HF. The gaps in pain management in HF patients included lack of knowledge of opioid use, lack of consideration and awareness of pain, no clinical guidelines for pain assessment and treatment, and complicated pain management with multiple chronic conditions. CONCLUSIONS: The impact of pain and need for individual assessment and management of pain in HF patients were perceived by nurses; improvement in pain management practice in HF patients is needed. Concerns regarding opioid use and gaps in pain management of HF patients should be addressed.

A Metaphor Analysis of Patients' With Chronic Conditions Experiences With Holistic Nurse Coaching.

The purpose of this study was to examine metaphors used by patients with chronic conditions to describe their experience with holistic nurse coaching. A secondary analysis was conducted using Metaphor Identification Procedure to analyze the corpus of 112 pages of typed transcription. Five metaphors emerged: (1) taking personal power back like acquiring a new toolbox; (2) seeing health challenges from different angles like a duck pond race; (3) shifting perception of a chronic condition like a spider turned into a friend; (4) engaging in self-care like caring for a favorite plant; and (5) choosing to focus on the positive like a collage that changed from dark to light. Specific interventions can be developed to address each of these metaphors to help patients live well with chronic conditions.

Prognostic Performance of the Augmented Hematopoietic Cell Transplantation-Specific Comorbidity/Age Index in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation from Alternative Graft Sources.

The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) was developed and validated to weigh the burden of pretransplantation comorbidities and estimate their impact on post-transplantation risks of nonrelapse mortality (NRM). Recently, the HCT-CI was augmented by the addition of both age and the values of 3 markers: ferritin, albumin, and platelet count. So far, research involving The HCT-CI has been limited almost exclusively to recipients of allogeneic hematopoietic cell transplantation (HCT) from HLA-matched grafts. To this end, we sought to investigate the discriminative capacity of an augmented comorbidity/age index among 724 recipients of allogeneic HCT from HLA-mismatched (n = 345), haploidentical (n = 117), and umbilical cord blood (UCB; n = 262) grafts between 2000 and 2013. In the overall cohort, the augmented comorbidity/age index had a higher c-statistic estimate for prediction of NRM compared with the original HCT-CI (.63 versus .59). Findings were similar for recipients of HLA-mismatched (.62 versus .59), haploidentical (.60 versus .54), or UCB grafts (.65 versus .61). Compared with patients with an HCT-CI score ≥4, those with a score <4 had a higher survival rate among recipients of HLA-mismatched (55% versus 39%; P < .0008), HLA-haploidentical (58% versus 38%; P = .01), or UCB (67% versus 48%; P = .004) grafts. Our results demonstrate the utility of the augmented comorbidity/age index as a valid prognostic tool among recipients of allogeneic HCT from alternative graft sources.

Cord-Blood Transplantation in Patients with Minimal Residual Disease.

BACKGROUND: The majority of patients in need of a hematopoietic-cell transplant do not have a matched related donor. Data are needed to inform the choice among various alternative donor-cell sources. METHODS: In this retrospective analysis, we compared outcomes in 582 consecutive patients with acute leukemia or the myelodysplastic syndrome who received a first myeloablative hematopoietic-cell transplant from an unrelated cord-blood donor (140 patients), an HLA-matched unrelated donor (344), or an HLA-mismatched unrelated donor (98). RESULTS: The relative risks of death and relapse between the cord-blood group and the two other unrelated-donor groups appeared to vary according to the presence of minimal residual disease status before transplantation. Among patients with minimal residual disease, the risk of death was higher in the HLA-mismatched group than in the cord-blood group (hazard ratio, 2.92; 95% confidence interval [CI], 1.52 to 5.63; P=0.001); the risk was also higher in the HLA-matched group than in the cord-blood group but not significantly so (hazard ratio, 1.69; 95% CI, 0.94 to 3.02; P=0.08). Among patients without minimal residual disease, the hazard ratios were lower (hazard ratio in the HLA-mismatched group, 1.36; 95% CI, 0.76 to 2.46; P=0.30; hazard ratio in the HLA-matched group, 0.78; 95% CI, 0.48 to 1.28; P=0.33). The risk of relapse among patients with minimal residual disease was significantly higher in the two unrelated-donor groups than in the cord-blood group (hazard ratio in the HLA-mismatched group, 3.01; 95% CI, 1.22 to 7.38; P=0.02; hazard ratio in the HLA-matched group, 2.92; 95% CI, 1.34 to 6.35; P=0.007). Among patients without minimal residual disease, the magnitude of these associations was lower (hazard ratio in the HLA-mismatched group, 1.28; 95% CI, 0.51 to 3.25; P=0.60; hazard ratio in the HLA-matched group, 1.30; 95% CI, 0.65 to 2.58; P=0.46). CONCLUSIONS: Our data suggest that among patients with pretransplantation minimal residual disease, the probability of overall survival after receipt of a transplant from a cord-blood donor was at least as favorable as that after receipt of a transplant from an HLA-matched unrelated donor and was significantly higher than the probability after receipt of a transplant from an HLA-mismatched unrelated donor. Furthermore, the probability of relapse was lower in the cord-blood group than in either of the other groups.

The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality.

Strategies to prevent active infection with certain double-stranded DNA (dsDNA) viruses after allogeneic hematopoietic cell transplantation (HCT) are limited by incomplete understanding of their epidemiology and clinical impact. We retrospectively tested weekly plasma samples from allogeneic HCT recipients at our center from 2007 to 2014. We used quantitative PCR to test for cytomegalovirus, BK polyomavirus, human herpesvirus 6B, HHV-6A, adenovirus, and Epstein-Barr virus between days 0 and 100 post-HCT. We evaluated risk factors for detection of multiple viruses and association of viruses with mortality through day 365 post-HCT with Cox models. Among 404 allogeneic HCT recipients, including 125 cord blood, 125 HLA-mismatched, and 154 HLA-matched HCTs, detection of multiple viruses was common through day 100: 90% had ≥1, 62% had ≥2, 28% had ≥3, and 5% had 4 or 5 viruses. Risk factors for detection of multiple viruses included cord blood or HLA-mismatched HCT, myeloablative conditioning, and acute graft-versus-host disease (P values < .01). Absolute lymphocyte count of <200 cells/mm3 was associated with greater virus exposure on the basis of the maximum cumulative viral load area under the curve (AUC) (P = .054). The maximum cumulative viral load AUC was the best predictor of early (days 0-100) and late (days 101-365) overall mortality (adjusted hazard ratio [aHR] = 1.36, 95% confidence interval [CI] [1.25, 1.49], and aHR = 1.04, 95% CI [1.0, 1.08], respectively) after accounting for immune reconstitution and graft-versus-host disease. In conclusion, detection of multiple dsDNA viruses was frequent after allogeneic HCT and had a dose-dependent association with increased mortality. These data suggest opportunities to improve outcomes with better antiviral strategies.

Disability related to chronic graft -versus-host disease after alternative donor hematopoietic cell transplantation.

We determined the incidence of disability related to chronic graft-versus-host disease (bronchiolitis obliterans, grade ≥2 keratoconjunctivitis sicca, sclerotic features or esophageal stricture) for three categories of alternative donor: cord blood, haplorelated marrow or peripheral blood with post-transplant cyclophosphamide, and unrelated single HLA-allele mismatched peripheral blood. Among 396 consecutive hematopoietic cell transplant recipients, 129 developed chronic graft-versus-host disease with 3-year cumulative incidences of 8% for cord blood, 24% for haplorelated grafts, and 55% for unrelated single HLA-allele mismatched peripheral blood. Disability rates were significantly lower for cord blood [hazard ratio (HR) 0.13; 95% confidence interval (CI): 0.1-0.4] and for the haplorelated group (HR 0.31; 95% CI: 0.1-0.7) compared to the rate in the group transplanted with unrelated single HLA-allele mismatched peripheral blood. Cord blood recipients were also >2-fold more likely to return to work/school within 3 years from the onset of chronic graft-versus-host disease (HR 2.54; 95% CI: 1.1-5.7, P=0.02), and the haplorelated group trended similarly (HR 2.38; 95% CI: 1.0-5.9, P=0.06). Cord blood recipients were more likely to discontinue immunosuppression than were recipients of unrelated single HLA-allele mismatched peripheral blood (HR 3.96; 95% CI: 1.9-8.4, P=0.0003), similarly to the haplorelated group (HR 4.93; 95% CI: 2.2-11.1, P=0.0001). Progression-free survival and non-relapse mortality did not differ between groups grafted from different types of donors. Our observations that, compared to recipients of unrelated single HLA-allele mismatched peripheral blood, recipients of cord blood and haplorelated grafts less often developed disability related to chronic graft-versus-host disease, and were more likely to resume work/school, should help better counseling of pre-hematopoietic cell transplant candidates.

Kinetics of Double-Stranded DNA Viremia After Allogeneic Hematopoietic Cell Transplantation.

Background: Improved understanding of double-stranded DNA (dsDNA) virus kinetics after hematopoietic cell transplantation (HCT) would facilitate development of therapeutic strategies. Methods: We tested weekly plasma samples from 404 patients through day 100 after allogeneic HCT for cytomegalovirus (CMV), human herpesvirus (HHV) 6A and 6B, BK polyomavirus (BKV), adenovirus (AdV), and Epstein-Barr virus (EBV) using quantitative polymerase chain reaction. Episodes lasting ≤1 week were defined as blips and >1 week as persistent. We described virus-specific kinetics, analyzed the association of virus area under the curve (AUC) with overall mortality, and identified risk factors for persistent episodes. Results: We identified 428 episodes of CMV, 292 of BKV, 224 of HHV-6B, 46 of AdV, and 53 of EBV. CMV and BKV had the highest proportions of persistent episodes (68% and 80%, respectively). Detection and kinetics varied by virus. HHV-6B episodes reached maximum levels fastest and had the shortest intervals between detection and end-organ disease. End-organ disease occurred within 14 days of viremia in 68% of cases, generally during persistent episodes. For all viruses, higher viral load AUC increased risk for overall mortality through day 365, persistent episodes had higher viral load than blips, and higher first positive viral load significantly increased risk for persistent episodes. First viral load >2 log10 copies/mL (range, 2.04-3.06 per virus) had high specificity for persistent episodes. Conclusions: Persistent high viral load dsDNA viremia episodes after allogeneic HCT predict mortality. Virus-specific kinetics can guide timing and thresholds for early intervention in studies of novel agents.

A Modified Intensive Strategy to Prevent Cytomegalovirus Disease in Seropositive Umbilical Cord Blood Transplantation Recipients.

We previously demonstrated a lower rate of cytomegalovirus (CMV) reactivation and disease among seropositive umbilical cord blood transplantation (CBT) recipients receiving an intensive prophylaxis strategy consisting of ganciclovir on days -8 to -2 pretransplantation, high-dose valacyclovir post-transplantation, and twice-weekly serum CMV polymerase chain reaction testing. We hypothesized that a modified intensive strategy excluding pretransplantation ganciclovir would be similarly effective. We compared the risk of CMV reactivation, occurrence of CMV disease, and duration of anti-CMV therapy by day 100 post-CBT in patients receiving the modified intensive and intensive strategies. Forty patients received the modified intensive strategy, and 43 received the intensive strategy. There was no difference in the hazard for CMV reactivation (hazard ratio, 1.1; P = .77). No patients in the modified intensive cohort, but 2 patients in the intensive cohort, developed CMV disease (P = .53). There was no difference in the hazard for early (≤30 days post-CBT; P = .76) or high-level (>1000 IU/mL; P = .37) CMV reactivation. Patients in the modified intensive cohort had marginally higher CMV viral loads and percentage of days of CMV detection and treatment, although the contribution of pretransplantation ganciclovir to these differences is unclear. The overall percentage of treatment days was 32% in both cohorts after accounting for pretransplantation ganciclovir. In conclusion, exclusion of prophylactic ganciclovir before CBT did not impact the risk of CMV reactivation or disease, although CMV kinetics appeared to differ by prevention strategy. Best practices for CMV prevention will need further study as new prophylactic strategies become available.

Treosulfan, Fludarabine, and Low-Dose Total Body Irradiation for Children and Young Adults with Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation: Prospective Phase II Trial of the Pediatric Blood and Marrow Transplant Consortium.

This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (range, 1 to 19) underwent allogeneic HCT for AML in first (n = 18), second (n = 11), and third or greater remission (n = 3) or MDS (n = 8) using bone marrow (n = 25), peripheral blood stem cells (n = 5), or cord blood (n = 9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m2/day (BSA ≤ .5 m2), 12 g/m2/day (BSA > .5 to 1.0 m2), or 14 g/m2/day (BSA > 1.0 m2) on days -6 to -4; fludarabine 30 mg/m2/day on days -6 to -2; and a single fraction of 200 cGy total body irradiation on day -1. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and methotrexate for marrow and peripheral blood stem cell and cyclosporine/mycophenolate mofetil for cord blood. One-year overall survival, disease-free survival, and nonrelapse mortality were 80%, 73%, and 3%, respectively. One-year relapse was 38% for AML and 13% for MDS. No serious organ toxicities were observed. All 37 assessable patients engrafted. Cumulative incidences of grades II to IV acute GVHD and chronic GVHD were 22% and 40%, respectively. BSA-based treosulfan dosing resulted in predictable area under the curve and maximum concentration, which is required for dosing without measuring individual pharmacokinetic parameters. Observed differences in pharmacokinetics did not impact disease control or regimen toxicity. This BSA-based treosulfan regimen resulted in excellent engraftment and disease-free survival and minimal toxicity and transplant-related mortality (3%) in children and young adults with AML and MDS.

Transplant Conditioning with Treosulfan/Fludarabine with or without Total Body Irradiation: A Randomized Phase II Trial in Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia.

In this prospective, randomized, phase II "pick the winner" trial we assessed the efficacy of transplant conditioning with treosulfan/fludarabine ± 2 Gy total body irradiation (TBI) in reducing post-transplant relapse in 100 patients, aged 2 to 70 years (median, 57), with myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (n = 51) or acute myeloid leukemia (AML; n = 49). Patients received i.v. treosulfan, 14 g/m2/day on days -6 to -4 and i.v. fludarabine, 30 mg/m2/day on days -6 to -2, alone or combined with 2 Gy TBI (day 0). Donors were related (n = 43) or unrelated (n = 57). When a planned interim analysis showed superior progression-free survival in the TBI arm (P = .04), all subsequent patients received TBI. With a follow-up of 12 to 40 months (median, 20), the 1-year overall survival was 80% for the TBI arm and 69% for the non-TBI arm. The 1-year cumulative incidence of relapse was 22% and 34%, respectively (P = .06). Among patients with low-risk disease the 1-year relapse incidence was 15% and 31% (P = .20) and for patients with high-risk disease, 26% and 36% (P = .18), respectively. Among MDS patients the 1-year relapse incidence was 27% versus 33% (P = .49) and among AML patients 16% versus 35% (P = .05), respectively. The largest difference was among patients with unfavorable cytogenetics, with 1-year relapse incidences of 31% and 63% (P = .18), respectively. Nonrelapse mortality in this high-risk patient population was 9% at 6 months and did not differ between arms. Thus, treosulfan/fludarabine/low-dose TBI provided effective conditioning for allogeneic hematopoietic cell transplantation in high-risk patients up to 70 years of age. The addition of TBI had a more profound effect in patients with AML than in those with MDS. High-risk disease features were associated with a lower overall success rate. Further studies are warranted.

Quality indicator survey versus traditional survey in New York State: a comparison of results from annual nursing home surveys.

Despite the passage of OBRA'87 for nursing home reform, concerns about care in facilities continue. The Centers for Medicare and Medicaid developed new regulations and the Traditional Survey (TS) process for annual nursing home survey. The survey is conducted by state regional offices to determine facility compliance with federal regulations. Despite the regulations and new survey process, the TS inconsistently identified problems. A computerized process called the Quality Indicator Survey (QIS) was subsequently developed. This study was designed to compare results from TS and QIS on overall deficiencies, select quality indicators, high-severity deficiencies, and severity differences of seven quality indicators in New York State over a 6-year period from 2010 through 2015. Results of t-tests determined a significant difference in the overall mean number of deficiencies (p < .001), and on four indicators: choices (p < .001), nursing staff (p < .001), dental (p < .001), and dignity (p < .05). Facilities using the TS showed a higher mean number of harm level or higher deficiencies (p < .001). Chi-square tests for severity levels showed significantly more higher severity deficiencies on two quality indicators: nutrition (p < 0.001) and hydration (p < 0.05). Thus, the QIS produced a greater mean number of deficiencies, while TS produced more higher severity deficiencies in New York State.

Prognostic Value of the Hematopoietic Cell Transplantation Comorbidity Index for Patients Undergoing Reduced-Intensity Conditioning Cord Blood Transplantation.

The Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) has been validated as a tool for evaluating the risk of treatment-related mortality (TRM) in HLA-matched sibling and matched unrelated donor bone marrow and peripheral blood stem cell transplantation patients. However, the role of the HCT-CI after cord blood transplantation (CBT) has not been fully investigated. In this analysis, we sought to evaluate the predictive value of the HCT-CI in patients undergoing reduced-intensity conditioning (RIC) CBT. Between 2006 and 2013, HCT-CI scores were prospectively tabulated for patients with hematologic malignancies sequentially enrolled on multicenter RIC CBT studies coordinated by the Fred Hutchinson Cancer Research Center: 151 patients with acute myeloid leukemia/myelodysplastic syndrome (n = 101), chronic myeloid leukemia (n = 3), acute lymphocytic leukemia (n = 24), non-Hodgkin lymphoma (n = 8), Hodgkin lymphoma (n = 3), and other hematologic malignancies (n = 12) underwent RIC CBT and were included. Two patients received a single CBT and the remaining 149 received a double CBT. All patients received cyclosporine and mycophenolate mofetil for graft-versus-host disease prophylaxis. Median HCT-CI for the whole group was 3 (range, 0 to 8). Using the HCT-CI categories of low (0), intermediate (1 or 2), and high risk (>3), there was no significant difference in TRM between the 3 groups. However, when the patients were divided into 2 groups, HCT-CI ≤ 3 or > 3, the incidence of TRM at 3 years after transplantation was 26% (95% confidence interval [CI], 17 to 36) in the HCT-CI ≤ 3 group versus 50% (95% CI, 30 to 67) in the HCT-CI > 3 group (P = .01). Overall survival for patients with HCT-CI ≤ 3 was 40% (95% CI, 27 to 51) versus 29% in patients with HCT-CI >3 (95% CI, 12 to 48) (P = .08). Our study demonstrates that HCT-CI score > 3 is associated with an increased risk of TRM at 3 years after transplantation in patients undergoing RIC CBT. Because of the significant risk of TRM in patients with HCT-CI > 3 compared with risk for those with HCT-CI ≤ 3, patients with an HCT-CI score >3 should be counseled before undergoing RIC CBT.

Real Time Immunophenotyping of Leukocyte Subsets Early after Double Cord Blood Transplantation Predicts Graft Function.

Cord blood transplantation (CBT) recipients are at increased risk for delayed engraftment and primary graft failure, complications that are often indistinguishable early post-transplantation. Current assays fail to accurately identify recipients with slow hematopoietic recovery and distinguish them from those with pending graft failure. To address this, we prospectively examined the kinetics of immune cell subset recovery in the peripheral blood of 39 patients on days +7 and +14 after double-unit CBT (dCBT) by multiparametric flow cytometry analysis, which we term real-time immunophenotyping (RTIP). RTIP analysis at day +14 revealed distinctive patterns of reconstitution and, importantly, identified patients with slow hematopoietic recovery who went on to engraft. Strikingly, higher absolute numbers of circulating monocytes and natural killer cells at day +14 were predictive of engraftment, but only the absolute number of circulating monocytes was significantly correlated with time to engraftment. This is the first evidence that RTIP on patient peripheral blood mononuclear cells early after dCBT is technically feasible and can be used as a "signature" for predicting the kinetics of hematopoietic recovery. Furthermore, RTIP is a time- and cost-efficient methodology that has the potential to become a clinically feasible diagnostic tool to guide therapeutic interventions in high-risk patients; therefore, its utility should be evaluated in a large cohort of patients.

Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies.

Unrelated donor cord blood transplantation (CBT) results in disease-free survival comparable to that of unrelated adult donor transplantation in patients with hematologic malignancies. Extension of allograft access to racial and ethnic minorities, rapid graft availability, flexibility of transplantation date, and low risks of disabling chronic graft-versus-host disease (GVHD) and relapse are significant advantages of CBT, and multiple series have reported a low risk of late transplantation-related mortality (TRM) post-transplantation. Nonetheless, early post-transplantation morbidity and TRM and the requirement for intensive early post-transplantation management have slowed the adoption of CBT. Targeted care strategies in CBT recipients can mitigate early transplantation complications and reduce transplantation costs. Herein we provide a practical "how to" guide to CBT for hematologic malignancies on behalf of the National Marrow Donor Program and the American Society of Blood and Marrow Transplantation's Cord Blood Special Interest Group. It shares the best practices of 6 experienced US transplantation centers with a special interest in the use of cord blood as a hematopoietic stem cell source. We address donor search and unit selection, unit thaw and infusion, conditioning regimens, immune suppression, management of GVHD, opportunistic infections, and other factors in supportive care appropriate for CBT. Meticulous attention to such details has improved CBT outcomes and will facilitate the success of CBT as a platform for future graft manipulations.

Allogeneic Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for Treatment of Marrow Failure Disorders.

Hematopoietic cell transplantation (HCT) is effective in the treatment of inherited marrow failure disorders and other nonmalignant diseases. Conventional myeloablative conditioning regimens have been associated with high transplant-related mortality, particularly in patients with comorbid conditions. Here we report on 14 patients with marrow failure disorders (Shwachman-Diamond syndrome, n = 3; Diamond Blackfan anemia, n = 4; GATA2 deficiency, n = 2; paroxysmal nocturnal hemoglobinuria, n = 4; and an undefined marrow failure disorder, n = 1) who underwent HCT on a prospective, phase II, multicenter clinical trial. Patients were given HLA-matched related (n = 2) or unrelated (n = 12) grafts after conditioning with treosulfan (42 g/m2), fludarabine (150 mg/m2), ± thymoglobulin (n = 11; 6 mg/kg). All patients engrafted. At a median follow-up of 3 years, 13 patients are alive with complete correction of their underlying disease. These results indicate that the combination of treosulfan, fludarabine, and thymoglobulin is effective at establishing donor engraftment with a low toxicity profile and excellent disease-free survival in patients with marrow failure disorders.