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Companiens as well as boundaries for making use of patient-reported end result steps in clinical treatment: An academic center's first encounter.
The addition of palifermin limits severe regimen-related toxicities and decreases readmissions and duration of hospital stay. V-9302 Amino acid transporter antagonist This and other measures are needed to identify comprehensive and cost-effective approaches, possibly including palifermin, to prevent severe regimen-related toxicities and decrease health care resource utilization.Clostridioides difficile infection (CDI) is a major cause of infectious diarrhea among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. The relationship between CDI and acute graft-versus-host disease (aGVHD) has been a topic of interest, as these 2 conditions may influence each other. We studied the temporal relationship of CDI to aGVHD in the first 100 days post-transplantation in a large cohort of allo-HSCT recipients. We performed a retrospective cohort study of adult patients undergoing their first allo-HSCT at our tertiary care medical center between January 1, 2010, and December 31, 2016. Patients were followed for CDI diagnosis, development of aGVHD, and vital status up to day +100 post-transplantation. Descriptive statistics and multivariate Cox models with CDI as a time-varying covariate and aGVHD and high-grade aGVHD as outcomes were used for data analyses. A total of 656 allo-HSCT recipients were included in the analysis. Of these, 419 (64%) developed aGVHD, and 111 (17%)ting for age, sex, race, underlying disease, cytomegalovirus CMV serostatus, transplant source, and receipt of antithymocyte globulin (ATG). There was no association between CDI and high-grade aGVHD after adjustment for age, underlying disease, transplant type, intensity of conditioning, and receipt of ATG (aHR, 1.59; 95% CI, 0.95 to 2.66; P = .0755). CDI after allo-HSCT is associated with increased risk of GVHD when no CDI prophylaxis was used. Further studies examining CDI preventive measures, including prophylaxis, as well as the preservation or reconstitution of the gastrointestinal microbiome in the setting of HSCT are warranted.The majority of adults are seropositive for human herpesvirus 6 (HHV-6). HHV-6 reactivation can occur after allogeneic hematopoietic stem cell transplantation (HSCT) and lead to life-threatening central nervous system disorders. In this prospective study, we evaluated the relationship between HHV-6 reactivation and anti-HHV-6 IgG antibody levels in recipients of allogeneic HSCT. The HHV-6 viral load in the plasma was quantitatively measured weekly after allogeneic HSCT by real-time polymerase chain reaction. The level of anti-HHV-6 IgG antibody was measured by enzyme-linked immunosorbent assay before and serially after transplantation. In 28 of the 56 evaluated patients (50%), HHV-6 reactivation was detected after transplantation. In a multivariate analysis, cord blood as the stem cell source was the only significant factor associated with HHV-6 reactivation (odds ratio, 8.6; 95% confidence interval, 2.3 to 32.6; P less then .01). When evaluated in the recipients of cord blood transplantation (CBT), the anti-HHV-6 antibody level before transplantation was significantly lower in the patients with HHV-6 reactivation compared with those without (sample positivity index median, 2.04 [range, 0.95 to 5.98] versus 4.15 [range, 3.93 to 5.65]; P less then .05). The anti-HHV-6 antibody level was significantly decreased at 3 months post-transplantation compared with before transplantation (P less then .01). Such differences were not observed in other stem cell sources. Our results demonstrate that the low anti-HHV-6 antibody level before transplantation was associated with the reactivation of HHV-6 after CBT, and that the anti-HHV-6 antibody level was significantly decreased specifically after CBT. These results suggest that HHV-6-specific humoral immunity plays a role in HHV-6 reactivation after CBT.The use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for consolidation therapy in patients with core binding factor (CBF) acute myelogenous leukemia (AML) with intermediate- and adverse-risk genetics remains controversial. We retrospectively analyzed the clinical outcomes of 286 CBF-AML patients with intermediate- and adverse-risk genetics in first complete remission following consolidation with chemotherapy (n = 122), auto-HSCT (n = 27), or allo-HSCT (n = 137) between January 2009 and December 2018 at our center. Patients with allo-HSCT showed superior 5-year overall survival (OS; 74% versus 38% or 49%; P less then .001) and progression-free survival (PFS; 74% versus 26% or 49%; P less then .001) and lower cumulative incidence of relapse (CIR; 9% versus 69% or 31%; P less then .001) compared with chemotherapy alone or auto-HSCT. In the allo-HSCT group, minimal residual disease (MRD) at the second and third months after allo-HSCT could predict relapse in t(8;21) patients (2 months PCIR = .002; 3 months PCIR less then .001) but not in inv(16) patients. Moreover, positive MRD after 2 courses of consolidation chemotherapy before allo-HSCT was an independent risk factor for survival in CBF-AML patients with intermediate- and adverse-risk genetics, whereas haploidentical donor (haplo-) HSCT could overcome the adverse prognosis (5-year OS, 87%; 5-year PFS, 81%; 5-year CIR, 7%). Allo-HSCT could be the optimal first-line consolidation therapy for patients with intermediate- and adverse-risk genetics, and haplo-HSCT could improve survival for patients with positive MRD after 2 courses of consolidation chemotherapy.The optimal myeloablative conditioning (MAC) for patients undergoing haploidentical hematopoietic cell transplantation (haplo-HCT) is unknown. We studied the outcomes of total body irradiation (TBI)-based versus chemotherapy (CT)-based MAC regimens in patients with acute lymphoblastic leukemia (ALL). The study included 427 patients who underwent first haplo-HCT with post-transplantation cyclophosphamide (PTCy), following TBI-based (n = 188; 44%) or CT-based (n = 239; 56%) MAC. The median patient age was 32 years. Fludarabine-TBI (72%) and thiotepa-busulfan-fludarabine (65%) were the most frequently used TBI- and CT-based regimens, respectively. In the TBI and CT cohorts, 2-year leukemia-free survival (LFS) was 45% versus 37% (P = .05), overall survival (OS) was 51% versus 47% (P = .18), relapse incidence (RI) was 34% versus 32% (P = .44), and nonrelapse mortality (NRM) was 21% versus 31% (P less then .01). In the multivariate analysis, TBI was associated with lower NRM (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.33 to 0.86; P = .01), better LFS (HR, 0.71; 95% CI, 0.52 to 0.98; P =.04), and increased risk for grade II-IV acute graft-versus-host disease (GVHD) (HR, 1.59; 95% CI, 1.08 to 2.34; P = .02) compared with CT-based MAC. The type of conditioning regimen did not impact RI, chronic GVHD, OS, or GVHD-free, relapse-free survival after adjusting for transplantation-related variables. TBI-based MAC was associated with lower NRM and better LFS compared with CT-based MAC in patients with ALL after haplo-HCT/PTCy.TCRαβ/CD19-depleted HCT has been used with excellent outcomes in pediatric patients with hematologic malignancies, and several studies have demonstrated rapid immune reconstitution in the nonmalignant setting. However, immune recovery following TCRαβ/CD19-depleted hematopoietic cell transplantation (HCT) for malignancy remains incompletely elucidated. Furthermore, the majority of studies to date have used haploidentical and matched unrelated donors. Here we report results of immune reconstitution following TCRαβ/CD19-depleted HCT for hematologic malignancy in 51 pediatric patients with hematologic malignancies, the majority of whom received grafts from unrelated donors. Grafts were from matched unrelated (n = 20), mismatched unrelated (n = 20), and haploidentical (n = 11) donors. The median CD34+ cell dose was 10.2 × 106/kg (range, 4.54 to 20 × 106/kg), and the median TCRαβ+ cell dose was 2.53 × 104/kg (range, 0 to 44.9 × 104/kg). Conditioning was myeloablative with either busulfan or total body irradiation, iagnosis, donor source, TCRαβ+ T cell dose, conditioning regimen, or use of antithymocyte globulin. B cell recovery mirrored T cell recovery, and i.v. Ig was discontinued at a median of 8 months (range, 4 to 22 months) post-HCT in patients alive and relapse-free at last follow-up. Immune reconstitution is rapid following TCRαβ/CD19-depleted HCT in pediatric patients with hematologic malignancies. Donor graft source, haploidentical or unrelated, did not affect immune reconstitution. Viral reactivation is common in the first 100 days post-HCT, indicating that improved T cell defense is needed in the early post-HCT period.Sickle cell disease (SCD) affects more than 300,000 children annually worldwide. Despite improved supportive care, long-term prognosis remains poor. Allogeneic hematopoietic cell transplantation (allo-HCT) is the sole validated curative option, resulting in sustained resolution of the clinical phenotype. The medical literature on allo-HCT for SCD is largely limited to children. Recent studies have evaluated allo-HCT efficacy in adults. Here, we conducted a systematic review/meta-analysis to assess the totality of evidence on the efficacy, or lack thereof, of allo-HCT in treating SCD. We performed a comprehensive literature search using PubMed/Medline, Embase, and Cochrane library databases on November 13, 2019. Four authors independently extracted data on clinical outcomes related to benefits (overall survival [OS] and disease-free survival [DFS]) and harms (acute graft-versus-host disease [aGVHD], chronic graft-versus-host disease [cGVHD], nonrelapse mortality [NRM], and graft failure [GF]). Our search identified a total of 1906 references. Only 33 studies (n= 2853 patients) met our inclusion criteria. We also performed a subset analysis by age. Analyses of all-age groups showed pooled rates of 96% for OS, 90% for DFS, 20% for aGVHD, 10% for cGVHD, 4% for NRM, and 5% for GF. In the pediatric population, pooled rates for OS, DFS, aGVHD, cGVHD, NRM, and GF were 97%, 91%, 26%, 11%, 5%, and 3%, respectively. In adults, pooled rates for OS, DFS, aGVHD, cGVHD, NRM, and GF were 98%, 90%, 7%, 1%, 0%, and 14%, respectively. Our data show that allo-HCT is safe and effective, yielding pooled OS rates exceeding 90%. The high GF rate of 14% in adults is concerning and emphasizes the need to evaluate new strategies.Novel high-risk groups have recently been identified in adult acute lymphoblastic leukemia (ALL), including Philadelphia-like, therapy-related, and measurable residual disease after induction therapy. Furthermore, modern targeted therapies have recently been incorporated into ALL management; rituximab for CD20-positive and blinatumomab for measurable residual disease after induction therapy or relapsed or refractory disease. Allogeneic hematopoietic cell transplantation (allo-HCT) is recommended as consolidation therapy for high-risk ALL; however, its relative benefit for these high-risk groups and after novel therapies is unclear. We performed an analysis of posttransplantation outcomes in a cohort of 261 consecutive patients who underwent allo-HCT for ALL at the 3-site Mayo Clinic Cancer Center (January 1, 2008-December 31, 2018). With a median (range) follow-up of 22.4 months (0.5-135.0), the 100-day and 5-year cumulative incidences of nonrelapse mortality rates were 6.5% and 26.7%, respectively. The 5-year cumulative incidences of relapse and death were 22.
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