Multidisciplinary Care for Refractory Pediatric Functional Abdominal Pain Decreases Emergency and Inpatient Utilization.

ABSTRACT: Children with refractory functional abdominal pain (FAP) experience functional disability and may utilize emergency department (ED) and/or inpatient services. Whether multidisciplinary programs which help care for children with refractory FAP affect acute healthcare utilization is unknown. A retrospective chart review of children initially evaluated by the outpatient Multidisciplinary Abdominal Pain Program (MAPP) from October 2016 to May 2019 was completed. Patient characteristics and number of ED visits and hospitalizations for abdominal pain in the year prior to versus year after MAPP evaluation were captured. Thirty-eight children (ages 9-17 years [median 13 years]) were included. The median number of ED visits/patient/year decreased from 1 (range: 0-7) to 0 (range: 0-3) (P < 0.0001). Seven (18%) children had been hospitalized and, in these children, the median number of hospitalizations/patient/year decreased from 1 (range: 1-5) to 0 (range: 0-1) (P < 0.05). These data suggest multidisciplinary outpatient intervention for refractory FAP is associated with significant decreases in acute healthcare utilization.

Can greater reliance on test scores ameliorate the association between family background and access to post-collegiate education? Survey evidence from the Beijing College Students Panel survey.

We evaluate whether greater reliance on test scores may reduce the extent of educational inequality by family origin as college graduates seek entrance to graduate school. In this article, we present a case study using survey data of colleges in Beijing, China, where students' performance in standardized graduate school entrance examination (the GSEE) is the primary determinant for the entrance to graduate school. Using multiple waves of the Beijing College Students Panel Survey (BCSPS), we fit a series of models to capture the correlations of family socio-economic status (SES) with the probabilities of seeking entrance to post-collegiate education, registering for and taking the GSEE, and finally obtaining admission to graduate school. After balancing the differential probabilities of seeking graduate level education, we find that family SES is not significantly associated with the likelihood of taking the GSEE, but significantly predicts the probability of applying a foreign graduate program. Although family SES can be marginally correlated with the odds of being admitted by a domestic graduate program, the strength of such an association is significantly weaker than for overseas programs. It is also shown that, for the elite graduate programs, family origin is independent from both GSEE registration and subsequent admission. These findings suggest that the test-oriented evaluations could ameliorate the extent of inequality at the post-collegiate level.

Arts and crafts as an educational strategy and coping mechanism for Republic of Korea and United States parents during the COVID-19 pandemic.

The COVID-19 pandemic and ensuing stay-at-home orders have shifted family lives worldwide. Government regulations about social distancing and isolation have resulted in parents/carers and children spending most of their time together in private spaces. During the northern hemisphere spring 2020 semester, most childcare and school systems closed and parents had to dramatically modify their balance between work and home life. Using data from consumer reports, online parenting forums and blog posts, and Google Trends, the authors of this article explored how some parents have shifted towards cultural and creative enrichment as a resource to occupy their children during governmental stay-at-home directives in both the United States and the Republic of Korea. The authors found that arts and crafts and educational toy sales have increased, parents are sharing advice and resources for at-home creative activities, and arts and cultural institutions have expanded their free online content. Finally, this article discusses whether the short-term stressors from COVID-19 might lead to long-term changes in parenting and sustained interest in these resources. The authors' findings provide additional support for the importance of arts and humanities in the educational experience of children.

Les activités artistiques et artisanales, une stratégie éducative et d'adaptation pour les parents en République de Corée et aux États-Unis pendant la pandémie de COVID-19 ­ La pandémie de COVID-19 et les ordres de confinement qu'elle a entraînés ont bouleversé la vie des familles dans le monde entier. Du fait des mesures de distanciation physique et d'isolement prises par les gouvernements, les enfants et les parents/les personnes chargées de s'occuper d'eux ont passé la majeure partie du temps ensemble, dans des espaces privés. Pendant le printemps 2020 de l'hémisphère nord, la plupart des services de garde d'enfants et des établissements scolaires ont fermé, et les parents ont dû modifier considérablement l'équilibre travail-famille. En s'appuyant sur des informations recueillies dans des rapports sur les consommateurs, dans des forums en ligne et des billets publiés dans des blogs sur la parentalité, et sur une analyse des tendances de Google Trends, les auteures de cet article ont examiné comment certains parents ont fait de l'enrichissement culturel et créatif une ressource pour occuper leurs enfants durant le confinement ordonné par les gouvernements aux États-Unis et en Corée. Elles ont constaté que les ventes de jouets créatifs et éducatifs avaient augmenté, que les parents partageaient des conseils et des ressources pour faire des activités d'art et d'artisanat à la maison, et que les établissements artistiques et culturels proposaient davantage de contenus gratuits. Enfin, l'article se demande si les facteurs de stress à court terme dus à la COVID-19 pourraient provoquer des changements à long terme en ce qui concerne la parentalité et créer un intérêt durable pour ces ressources. Les résultats des recherches menées par les auteures sont des éléments de plus qui étayent l'importance des arts et des sciences humaines dans l'éducation des enfants.

Pain Acceptance as a Predictor of Medical Utilization and School Absenteeism in Adolescents With Chronic Pain.

Objective: Identifying factors contributing to high medical utilization and productivity loss is important, given the high cost of pediatric chronic pain. The current study examined chronic pain acceptance as a predictor of medical utilization and school absenteeism in adolescents with chronic pain. Methods: In all, 122 adolescents (aged 12-21 years) with chronic pain and their parents/guardians completed questionnaires assessing medical visits (past 6 months), medication usage, and number of school absences (past month). Homebound school status was also reported. Adolescents completed the Chronic Pain Acceptance Questionnaire and pain intensity ratings, and underwent a diagnostic psychological evaluation. Results: Multivariate generalized linear model analyses indicated lower pain acceptance predicted increased inpatient hospitalizations and higher number of opioid and nonopioid prescription medications, controlling for pain intensity, age, and sex. Pain acceptance was not associated with outpatient consultations or number of nonprescription medications. Exploratory moderation analyses indicated lower pain acceptance significantly predicted increased emergency department visits and inpatient hospitalizations for patients diagnosed with an internalizing psychological disorder. Patients in homebound schooling reported low pain acceptance and for those in school full-time, linear regression indicated lower pain acceptance significantly predicted higher number of school absences. Conclusions: Findings suggest that lower pain acceptance contributes to the use of higher-level medical care (especially for adolescents with internalizing disorders) and increased productivity loss owing to school absences or homebound school status. Clinical implications exist for recommending acceptance-based interventions for pain acceptance promotion and continued development of cost-effective, easily disseminated acceptance-based therapy modules to curb the economic burden of chronic pain.

Intraoperative Administration of 4-Factor Prothrombin Complex Concentrate Reduces Blood Requirements in Cardiac Transplantation.

OBJECTIVE: Assessing the efficacy of intraoperative 4-factor prothrombin complex concentrate (4F-PCC) use in blood product utilization, time to chest closure, intensive care unit (ICU) and hospital length of stay (LOS), thromboembolic complications, renal injury and mortality in left ventricular assist device (LVAD) patients on home anticoagulation therapy with warfarin, undergoing orthotopic heart transplantation (OHT). DESIGN: Retrospective analysis of OHT patients at Tufts Medical Center from May 2013 to October 2016. SETTING: Single-institution, university hospital setting. PARTICIPANTS: Patients with preexisting LVADs who received orthotopic heart transplants (n = 74; 32 patients 4F-PCC, 42 patients no 4F-PCC). INTERVENTIONS: Warfarin reversal using 4F-PCC in patients with LVADs undergoing orthotopic heart transplantation with the 4F-PCC dosing partitioned such that one-third was given pre-CPB and two-thirds were given post-CPB. MEASUREMENTS AND MAIN RESULTS: The 4F-PCC group required less plasma (6 [IQR 4] v 1.31 [IQR 2] U, p < 0.001), cryoprecipitate (10 [IQR 10] v 7.50 [IQR 5] U, p < 0.001), and packed red blood cells (5 [IQR 4] v 2 [IQR 1.5] U, p < 0.001) and had a shorter time to chest closure (618.8 ± 111.4 v 547.9 ± 110.1 minutes, p = 0.008). There was no difference in platelet transfusion (2 [IQR 1] v 2 [IQR 1] U, p = 0.16), ICU or hospital LOS, acute kidney injury, or mortality. No thrombotic complications occurred. CONCLUSIONS: Replacing plasma with 4F-PCC to reverse preoperative warfarin anticoagulation during OHT was associated with a shorter time to chest closure and less blood product utilization, without an increase in acute kidney injury, thromboembolic complications, or death.

Hit, Robbed, and Put Down (but not Bullied): Underreporting of Bullying by Minority and Male Students.

To tackle adolescent bullying and identify students most vulnerable to being bullied, it is essential to examine both occurrences of bullying behaviors and students' own likelihoods of reporting bullying. This study examines ethnic and gender differences in students' odds of reporting bullying using the Education Longitudinal Study of 2002, a nationally representative study of United States high school sophomores (N = 15,362; ages 15-19; 50.2% female). Compared to White and female students, minority (particularly Black and Hispanic) and male students report comparable or greater experiences of bullying behaviors (such as being threatened, hit, put down by peers, or having belongings forced from them, stolen or damaged), but are less likely to report that they have been "bullied." These findings point to racialized and gendered differences in reporting bullying experiences such that indicators of "weakness" in peer relations may carry a greater stigma for minority and male students.

Lack of impact of umbilical cord blood unit processing techniques on clinical outcomes in adult double cord blood transplant recipients.

BACKGROUND AIMS: Despite widespread use of umbilical cord blood (UCB) transplantation and distinct practice preferences displayed by individual UCB banks and transplant centers, little information exists on how processing variations affect patient outcomes. METHODS: We reviewed 133 adult double UCB transplants performed at a single center: 98 after reduced-intensity and 35 after myeloablative conditioning. Processing associated with contributing UCB banks and units was surveyed to identify differences in practice. We analyzed effect of selected variables on clinical outcomes of engraftment, dominance, transplant-related mortality, and survival. RESULTS: Eighty-eight percent of banks queried currently practice red blood cell (RBC) depletion before cryopreservation. This reflects a shift in practice because previously 65% of banks employed RBC-replete processing methods (i.e., cryopreservation or plasma/volume reduction). Neither neutrophil nor platelet engraftment was affected by processing conditions analyzed. RBC depletion was not associated with clinical outcomes, except in 17 recipients of 2 RBC-replete units, where survival was better than that observed in 116 recipients of ≥1 RBC-depleted units (hazard ratio 3.26, P = 0.004). When analyzed by attributes of the dominant unit, RBC depletion, time in storage, bank years in existence, and inventory size did not affect clinical outcomes. Postthaw viability and CD34 dose were factors impacting engraftment. Notably, all RBC-replete units in this cohort were washed in dextran-human serum albumin before infusion. DISCUSSION: These findings support continued utilization of the entire existing pool of cord blood units, despite recent trends in processing, and have important implications for banking resources and UCB selection practices.

Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.

Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) for use in allogeneic transplantation. Key advantages of UCB are rapid availability and less stringent requirements for HLA matching. However, UCB contains an inherently limited HSC count, which is associated with delayed time to engraftment, high graft failure rates, and early mortality. 16,16-Dimethyl prostaglandin E2 (dmPGE2) was previously identified to be a critical regulator of HSC homeostasis, and we hypothesized that brief ex vivo modulation with dmPGE2 could improve patient outcomes by increasing the "effective dose" of HSCs. Molecular profiling approaches were used to determine the optimal ex vivo modulation conditions (temperature, time, concentration, and media) for use in the clinical setting. A phase 1 trial was performed to evaluate the safety and therapeutic potential of ex vivo modulation of a single UCB unit using dmPGE2 before reduced-intensity, double UCB transplantation. Results from this study demonstrated clear safety with durable, multilineage engraftment of dmPGE2-treated UCB units. We observed encouraging trends in efficacy, with accelerated neutrophil recovery (17.5 vs 21 days, P = .045), coupled with preferential, long-term engraftment of the dmPGE2-treated UCB unit in 10 of 12 treated participants.

White blood cell recovery after allogeneic hematopoietic cell transplantation predicts clinical outcome.

To determine whether outcome after allogeneic hematopoietic cell transplantation (HCT) could be estimated by using peripheral white blood cell count (WBC) as a metric that integrates several aspects of HCT recovery, we conducted a retrospective study of 1,109 adult patients who underwent first allogeneic HCT from 2003 through 2009. WBC at 1-3 months after HCT was categorized as low (<2), normal (2-10), and high (>10 × 10(9) cells/L). Overall survival (OS) and progression-free survival (PFS) were lower for patients with low or high WBC at 1-3 months after HCT (P < 0.0001). We developed a predictive three-group risk model based on the pattern of WBC recovery early after HCT. Five-year OS was 47, 30, and 15% (P < 0.0001) and 5-year PFS was 39, 22, and 14% for patients in the three different risk groups (P < 0.0001). The pattern of WBC recovery early after HCT provides prognostic information for relapse, nonrelapse mortality, progression-free survival, and overall survival. A scoring system based on the trajectory of the WBC in the first 3 months after HCT can effectively stratify patients into three groups with different PFS and OS. If validated, this system could be useful in the clinical management of patients after HCT, and to stratify patients enrolled on HCT clinical trials.

Sequential infusion of donor-derived dendritic cells with donor lymphocyte infusion for relapsed hematologic cancers after allogeneic hematopoietic stem cell transplantation.

Donor lymphocyte infusion (DLI) is often given to induce a graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation (HSCT). However, efficacy of DLI is limited in most hematologic cancers. As antigen presenting cells, dendritic cells (DC) bolster immune responses. We conducted a Phase I trial testing the coinfusion of DC followed by DLI. DC were generated by culturing peripheral blood mononuclear cells from HLA matched-related donors in GM-CSF and IL-4 for 7 days, followed by TNF-α for 3 days. DC were administered intravenously on 3 dose levels (5 × 10(6) ; 1 × 10(7) ; 5 × 10(7) cells). DLI (3 × 10(7) CD3+ cells/kg) was administered intravenously 1 day after the DC. Sixteen patients with hematologic cancers relapsed after HSCT were treated. A maximum tolerated dose for DC was not reached. Two of 16 patients met criteria for DLT within 10 weeks of the infusion: 1 idiopathic respiratory failure, 1 ventricular cardiac arrest. None developed grade III/IV GVHD. One patient developed grade II acute intestinal graft-vs.-host disease (GVHD) and 1 chronic GVHD within 6 months of the infusion. Both resolved with corticosteroids. Four of 14 patients evaluable for disease response achieved durable remissions and are alive and cancer free 6.7, 8.4, 8.8, and 10.1 years from infusion. Sequential infusion of donor-derived DC with DLI is feasible in patients with relapsed hematologic cancers after allogeneic HSCT. Future studies may consider donor DC preloaded with tumor antigens to investigate whether DC infusion could augment the GVL effect.

Bacillus cereus septicemia attributed to a matched unrelated bone marrow transplant.

BACKGROUND: Hematopoietic cell transplantation (HCT) is performed in more than 25,000 patients annually. Clinically significant bacterial transmission from HCT products is rare. CASE REPORT: A 36-year-old male of Asian descent with chronic myelogenous leukemia developed sepsis leading to acute renal failure and disseminated intravascular coagulation during infusion of matched unrelated donor bone marrow. This product later tested positive for Bacillus cereus. DISCUSSION: This HCT product traveled 31 hours at room temperature before arriving at the transplant center. Reducing transport times, transporting at 4 °C, and enhancing bacterial surveillance of HCT products may increase the ability to detect bacterial proliferation from transport. CONCLUSION: To prevent a similar case in the future, we will begin Gram staining all HCT products in transit more than 24 hours to alert physicians of the need for prophylactic antibiotic therapy.

SALL4 is a key transcription regulator in normal human hematopoiesis.

BACKGROUND: Stem cell factor SALL4 is a zinc finger transcription factor. It plays vital roles in the maintenance of embryonic stem cell properties, functions as an oncogene in leukemia, and has been recently proposed to use for cord blood expansion. The mechanism(s) by which SALL4 functions in normal human hematopoiesis, including identification of its target genes, still need to be explored. STUDY DESIGN AND METHODS: Chromatin immunoprecipitation followed by microarray hybridization (ChIP-chip) was used for mapping SALL4 global gene targets in normal primary CD34+ cells. The results were then correlated with SALL4 functional studies in the CD34+ cells. RESULTS: More than 1000 potential SALL4 downstream target genes have been identified, and validation of binding by ChIP-quantitative polymerase chain reaction was performed for 5% of potential targets. These include genes that are involving in hematopoietic differentiation and self-renewal, such as HOXA9, RUNX1, CD34, and PTEN. Down regulation of SALL4 expression using small-hairpin RNA in these cells led to decreased in vitro myeloid colony-forming abilities and impaired in vivo engraftment. Furthermore, HOXA9 was identified to be a major SALL4 target in normal human hematopoiesis and the loss of either SALL4 or HOXA9 expression in CD34+ cells shared a similar phenotype. CONCLUSION: Taken together, SALL4 is a key regulator in normal human hematopoiesis and the mechanism of its function is at least in part through the HOXA9. Future study will determine whether modulating the SALL4/HOXA9 pathway can be used in cellular therapy such as cord blood expansion and/or myeloid engraftment.

Merkel cell polyomavirus detection in a patient with familial epidermodysplasia verruciformis.

We report a case of Merkel cell polyomavirus detection in the skin of a patient with epidermodysplasia verruciformis (EDV) and a family history remarkable for an unusual inheritance pattern for EDV.

Reduced-intensity conditioning stem cell transplantation: comparison of double umbilical cord blood and unrelated donor grafts.

There are little data comparing umbilical cord blood (UBC) and conventional stem cell sources for reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT). We performed a retrospective analysis of RIC HCST using double UCB (dUCB) grafts and RIC HSCT using unrelated donor (URD) grafts. The study included 64 dUCB transplantations and 221 URD transplantations performed at Dana-Farber Cancer Institute and Massachusetts General Hospital between 2004 and 2008. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 14.1% for dUCB and 20.3% for URD (P = .32). The 2-year cumulative incidence of chronic GVHD was significantly lower in dUCB compared with URD (21.9% versus 53.9%; P < .0001). The 2-year cumulative incidence of nonrelapse mortality was significantly higher in dUCB (26.9% versus 10.4%; P = .0009). In our analysis, dUCB HSCT and URD HSCT had comparable 3-year overall survival (46% in dUCB and 50% in URD; P = .49) and progression-free survival (30% in dUCB and 40% in URD; P = .47). dUCBT was associated with greater nonrelapse mortality despite less chronic GVHD. Our findings suggest that the use of 2 partially matched UCB units appears to be a suitable alternative for patients undergoing RIC HSCT without an HLA-matched donor.

Immune reconstitution after double umbilical cord blood stem cell transplantation: comparison with unrelated peripheral blood stem cell transplantation.

Double umbilical cord blood (DUCB) transplantation is an accepted transplantation strategy for patients without suitable human leukocyte antigen (HLA) matched donors. However, DUCB transplantation is associated with increased morbidity and mortality because of slow recovery of immunity and a high risk of infection. To define the differences in immune reconstitution between DUCB transplantation and HLA matched unrelated donor (MUD) transplantation, we performed a detailed, prospective analysis of immune reconstitution in 42 DUCB recipients and 102 filgrastim-mobilized unrelated peripheral blood stem cell recipients. Reconstitution of CD3 T cells was significantly delayed in the DUCB cohort compared with the MUD cohort for 1 to 6 months posttransplantation (P < .001), including naive (CD45RO-) and memory (CD45RO+) CD4 T cells, regulatory (CD4CD25) T cells, and CD8 T cells. In contrast, CD19 B cells recovered more rapidly in the DUCB cohort and numbers remained significantly greater from 3 to 24 months after transplantation (P = .001). CD56CD16 natural killer (NK) cells also recovered more rapidly in DUCB recipients and remained significantly greater from 1 to 24 months after transplantation. B cell activating factor (BAFF) levels were higher in the DUCB cohort at 1 month (P < .001), were similar in both cohorts at 3 and 6 months, and were lower in the DUCB cohort at 12 months (P = .002). BAFF/CD19 B cell ratios were lower in the DUCB cohort at 3 (P = .045), 6 (P = .02), and 12 months (P = .002) after transplantation. DUCB recipients had more infections within the first 100 days after transplantation (P < .001), and there was less chronic graft-versus-host disease (P < .001), but there were no differences in cumulative incidence of relapse, nonrelapse death, progression-free survival, or overall survival between the 2 groups. These results suggest that increased risk of infections is specifically associated with delayed reconstitution of all major T cell subsets, but the increased risk is limited to the first 3 months after DUCB transplantation. There is no increased risk of relapse, suggesting that graft-versus-leukemia activity is maintained. Early reconstitution of B cells and NK cells may, in part, account for these findings.

Clearance of CMV viremia and survival after double umbilical cord blood transplantation in adults depends on reconstitution of thymopoiesis.

Umbilical cord blood grafts are increasingly used as sources of hematopoietic stem cells in adults. Data regarding the outcome of this approach in adults are consistent with delayed and insufficient immune reconstitution resulting in high infection-related morbidity and mortality. Using cytomegalovirus (CMV)-specific immunity as a paradigm, we evaluated the status, mechanism, and clinical implications of immune reconstitution in adults with hematologic malignancies undergoing unrelated double unit cord blood transplantation. Our data indicate that CD8(+) T cells capable of secreting interferon-gamma (IFN-gamma) in a CMV-specific enzyme-linked immunosorbent spot (ELISpot) assay are detectable at 8 weeks after transplantation, before reconstitution of thymopoiesis, but fail to clear CMV viremia. Clearance of CMV viremia occurs later and depends on the recovery of CD4(+)CD45RA(+) T cells, reconstitution of thymopoiesis, and attainment of T-cell receptor rearrangement excision circle (TREC) levels of 2000 or more copies/mug DNA. In addition, overall survival was significantly higher in patients who displayed thymic regeneration and attainment of TREC levels of 2000 or more copies/mug DNA (P = .005). These results indicate that reconstitution of thymopoiesis is critical for long-term clinical outcome in adult recipients of umbilical cord blood transplant. The trial was prospectively registered at http://www.clinicaltrials.gov (NCT00133367).

Generalized verrucosis: a review of the associated diseases, evaluation, and treatments.

Generalized verrucosis has been described in the past as synonymous with epidermodysplasia verruciformis. It has been shown, however, that epidermodysplasia verruciformis and other genetic or immunodeficiency diseases are just a subset of diffuse infections with human papillomavirus termed "generalized verrucosis." This article defines generalized verrucosis and distinct diseases associated with generalized warts. The indications for histopathologic testing, human papillomavirus typing, and other laboratory analyses and potential treatment options are discussed.

Educational achievement of immigrant adolescents in Spain: do gender and region of origin matter?

This study explores the educational achievement of immigrant youth in Spain employing data from 3 waves of the Longitudinal Study of Families and Childhood (Pànel de Famílies i Infància), a representative sample of children in Catalonia first interviewed at ages 13-16 in 2006 (N = 2,710). Results suggest consistent disadvantage in achievement among first-generation students. Differences in achievement between the second and third generations are apparent in bivariate analyses, but are explained by observable characteristics in multivariate analyses. Gender-specific analyses uncover a large achievement gap between first-generation girls and their third-generation counterparts, but no equivalent gap for boys. Region-of-origin differences are modest, with the exception of Latin American adolescents who exhibit the lowest educational outcomes. The significance of perceptions about school on achievement are discussed.

Use of matched unrelated donors compared with matched related donors is associated with lower relapse and superior progression-free survival after reduced-intensity conditioning hematopoietic stem cell transplantation.

As success of reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) relies primarily on graft-versus-leukemia (GVL) activity, increased minor HLA disparity in unrelated compared to related donors could have a significant impact on transplant outcomes. To assess whether use of unrelated donors (URD) engenders more potent GVL in RIC HSCT compared to matched related donors (MRD), we retrospectively studied 433 consecutive T-replete 6/6 HLA matched URD (n = 246) and MRD (n = 187) RIC HSCT for hematologic malignancies at our institution. Diseases included: acute myelogenous leukemia (AML) (127), non-Hodgkin lymphoma (NHL) (71), chronic lymphocytic leukemia (CLL) (68), myelodysplastic syndrome (MDS) (64), Hodgkin disease (HD) (40), chronic myeloid leukemia (CML) (25), multiple myeloma (MM) (23), myeloproliferative disorder (MPD) (12), acute lymphoblastic leukemia (ALL) (7), and other leukemia (1). All received uniform fludarabine and intravenous busulfan conditioning, and GVHD prophylaxis with tacrolimus/mini-methroxate (mini-MTX) or tacrolimus/sirolimus ± mini-MTX. Unrelated donors were younger compared to MRD (median donor age: 33 years versus 52 years, P < .0001), and provided larger CD34(+) products (median CD34(+) cells infused: 8.7 × 10(6)/kg versus 7.5 × 10(6)/kg, P = .002). Distribution of diseases, disease risk, prior transplant, and cytomegalovirus (CMV) status was similar in both cohorts. Cumulative incidence of grade II-IV acute GVHD (at day +180), 2-year chronic GVHD, and 2-year nonrelapse mortality (NRM) were 20% versus 16%, 55% versus 50%, and 8% versus 6% in URD and MRD, respectively (P = NS). Cumulative incidence of relapse at 2 years was lower in URD, 52% versus 65% (P = .005). With median follow-up of 26.5 and 35.8 months, 2-year progression-free survival (PFS) was significantly better in unrelated donor transplants, 39.5% for URD, and 29% for MRD (P = .01). Overall survival (OS) at 2 years were 56% for URD versus 50% for MRD (P = .53). In multivariable analysis, URD was associated with a lower risk of relapse (hazard ratio [HR] 0.67, P = .002) and superior PFS (HR 0.69, P = .002). These results suggest that URD is associated with greater GVL activity than MRD, and could have practice changing impact on future donor selection in RIC HSCT.

Validation of short-term handling and storage conditions for marrow and peripheral blood stem cell products.

BACKGROUND: Allogeneic hematopoietic stem cell transplants from unrelated donors are routinely used in the treatment of patients with hematologic malignancies. These cellular products are often collected off-site and require transport from the collection site to transplantation centers. However, the effects of transport conditions and media on stem cell graft composition during short-term storage have not been well described. STUDY DESIGN AND METHODS: Five bone marrow (BM), four filgrastim-mobilized peripheral blood stem cell (PBSC), and four nonmobilized peripheral blood mononuclear cell (PBMNC) products were collected from healthy volunteer donors and stored at 4 or 20°C for up to 72 hours in 10% PlasmaLyte A plus anticoagulants such as 10% acid citrate dextran-A (ACD-A) and/or 10 IU/mL heparin. Products were evaluated at 0, 24, 48, and 72 hours for cellular content, viability, and metabolic activities. RESULTS: BM products maintained equivalent cell viability when stored at either 4 or 20°C over 72 hours, but cell viability was better maintained for PBSC products stored at 4°C. The mean viable CD34+ cell recovery for PBSC and BM products stored over 72 hours at 4°C was higher than 75%. Significantly lower CD34+ cell and colony-forming unit recoveries were seen in PBSC products but not BM products stored at room temperature. Faster lactic acid accumulation was observed in PBMNC and PBSC products stored without ACD-A. CONCLUSIONS: Seventy-two-hour storage of BM, PBSC, and PBMNC products at refrigerated temperature maintains optimal cell viability and recovery. Anticoagulation with ACD-A is preferred over heparin to reduce lactic acid accumulation in the product media.