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1.
JAMA Netw Open ; 3(1): e1918668, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31913492

RESUMO

Importance: Patients undergoing hematopoietic stem cell transplant (HSCT) are at risk for bloodstream infection (BSI) secondary to translocation of bacteria through the injured mucosa, termed mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI), in addition to BSI secondary to indwelling catheters and infection at other sites (BSI-other). Objective: To determine the incidence, timing, risk factors, and outcomes of patients who develop MBI-LCBI in the first 100 days after HSCT. Design, Setting, and Participants: A case-cohort retrospective analysis was performed using data from the Center for International Blood and Marrow Transplant Research database on 16 875 consecutive pediatric and adult patients receiving a first allogeneic HSCT from January 1, 2009, to December 31, 2016. Patients were classified into 4 categories: MBI-LCBI (1481 [8.8%]), MBI-LCBI and BSI-other (698 [4.1%]), BSI-other only (2928 [17.4%]), and controls with no BSI (11 768 [69.7%]). Statistical analysis was performed from April 5 to July 17, 2018. Main Outcomes and Measures: Demographic characteristics and outcomes, including overall survival, chronic graft-vs-host disease, and transplant-related mortality (only for patients with malignant disease), were compared among groups. Results: Of the 16 875 patients in the study (9737 [57.7%] male; median [range] age, 47 [0.04-82] years) 13 686 (81.1%) underwent HSCT for a malignant neoplasm, and 3189 (18.9%) underwent HSCT for a nonmalignant condition. The cumulative incidence of MBI-LCBI was 13% (99% CI, 12%-13%) by day 100, and the cumulative incidence of BSI-other was 21% (99% CI, 21%-22%) by day 100. Median (range) time from transplant to first MBI-LCBI was 8 (<1 to 98) days vs 29 (<1 to 100) days for BSI-other. Multivariable analysis revealed an increased risk of MBI-LCBI with poor Karnofsky/Lansky performance status (hazard ratio [HR], 1.21 [99% CI, 1.04-1.41]), cord blood grafts (HR, 2.89 [99% CI, 1.97-4.24]), myeloablative conditioning (HR, 1.46 [99% CI, 1.19-1.78]), and posttransplant cyclophosphamide graft-vs-host disease prophylaxis (HR, 1.85 [99% CI, 1.38-2.48]). One-year mortality was significantly higher for patients with MBI-LCBI (HR, 1.81 [99% CI, 1.56-2.12]), BSI-other (HR, 1.81 [99% CI, 1.60-2.06]), and MBI-LCBI plus BSI-other (HR, 2.65 [99% CI, 2.17-3.24]) compared with controls. Infection was more commonly reported as a cause of death for patients with MBI-LCBI (139 of 740 [18.8%]), BSI (251 of 1537 [16.3%]), and MBI-LCBI plus BSI (94 of 435 [21.6%]) than for controls (566 of 4740 [11.9%]). Conclusions and Relevance: In this cohort study, MBI-LCBI, in addition to any BSIs, were associated with significant morbidity and mortality after HSCT. Further investigation into risk reduction should be a clinical and scientific priority in this patient population.

2.
Postgrad Med ; : 1-7, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31922437

RESUMO

Background: Burnout syndrome (BOS) is characterized by emotional exhaustion, depersonalization and reduced personal accomplishment. It affects doctors, patients and their inter-relationship. There is a lack of data on BOS in Mexico. The main objective of the present study is to evaluate the prevalence of BOS in physician members of the Mexican gastroenterological association (MGA) and Mexican association for gastrointestinal endoscopy (MAGE).Materials and methods: Cross sectional, prospective study through anonymous electronic survey via e-mail, sent to members of the MGA (n = 1192) and MAGE (n = 600). The survey included questions about basic sociodemographic information, Maslach Burnout Inventory, and factors potentially associated with BOS. Continuous variables were summarized as means and ANOVA or Kruskal-Wallis test were used to compare groups. Nominal variables were summarized as proportions and Fisher's exact test or Χ2 test were used, as appropriate.Results: A total of 1792 e-mail invitations were delivered and 411 answers were received with a response rate of 22.9%. The prevalence of BOS according to the Maslach Burnout Inventory was 26.3% (108/411). The prevalence of BOS according to the single-item self-defined burnout question (SISDBOQ) was 32.6% (134/411). The Kappa coefficient for emotional exhaustion between the SISDBOQ and Maslach inventory was 0.48 (p = 0.0001). Factors associated with BOS included performing endoscopic procedures (OR 2.9 (1.2-6.6); p = 0.008), lack of support from colleagues upon complications (OR 0.2 (0.1-0.4); p = 0.0001), receiving frequent reprimands from superiors (OR 2.4 (1.5-3.8); p = 0.0001), work unrelated to medicine (OR 2.4 (1.4-3.9); p = 0.0001), work violence/harassment (OR 3.0 (1.9-4.9); p = 0.0001) and living in a big city (OR 1.9 (1.2-3); p = 0.005).Conclusion: BOS is a frequent entity in Mexican gastroenterologists and endoscopists. There are potentially modifiable factors associated with BOS.

3.
Am J Hematol ; 95(1): 28-37, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31625177

RESUMO

A total of 192 pediatric patients, median age 8.6 years, with high-risk hematological malignancies, underwent haploidentical stem cell transplantation (haplo-HSCT) using post-transplantation cyclophosphamide (PT-Cy), or ex vivo T cell-depleted (TCD) graft platforms, from January 1999 to December 2016 in 10 centers in Spain. Some 41 patients received an unmanipulated graft followed by PT-Cy for graft-vs-host disease (GvHD) prophylaxis. A total of 151 patients were transplanted with CD3-depleted peripheral blood stem cells (PBSCs) by either CD34+ selection, CD3+ CD19+ depletion, TCRαß+ CD19+ depletion or CD45RA+ depletion, added to CD34+ selection for GvHD prophylaxis. The PBSCs were the only source in patients following ex vivo TCD haplo-HSCT; bone marrow was the source in 9 of 41 patients following PT-CY haplo-HSCT. Engraftment was achieved in 91.3% of cases. A donor younger than 30 years, and the development of chronic GvHD were positive factors influencing survival, whereas positive minimal residual disease (MRD) before transplant and lymphoid disease were negative factors. The probability of relapse increased with lymphoid malignancies, a donor killer-cell immunoglobulin-like receptor (KIR) haplotype A and positive MRD pretransplant. No difference was found in overall survival, disease-free survival or relapse incidence between the two platforms. Relapse is still of concern in both platforms, and it should be the focus of future efforts. In conclusion, both platforms for haplo-HSCT were effective and could be utilized depending on the comfort level of the center.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31726205

RESUMO

Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects.

5.
Blood Adv ; 3(20): 3123-3131, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31648332

RESUMO

Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n = 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy ± Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P = .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n = 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P = .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P < .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged >30 years after HLA-matched sibling (HR, 2.74; P < .001) or unrelated donor (HR, 1.98; P = .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.

7.
Blood Adv ; 3(17): 2525-2536, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31471322

RESUMO

Presumably, reduced-intensity/nonmyeloablative conditioning (RIC/NMA) for allogeneic hematopoietic cell transplantation (alloHCT) results in reduced infections compared with myeloablative conditioning (MAC) regimens; however, published evidence is limited. In this Center for International Blood and Marrow Transplant Research study, 1755 patients (aged ≥40 years) with acute myeloid leukemia in first complete remission were evaluated for infections occurring within 100 days after T-cell replete alloHCT. Patients receiving RIC/NMA (n = 777) compared with those receiving MAC (n = 978) were older and underwent transplantation more recently; however, the groups were similar regarding Karnofsky performance score, HCT-comorbidity index, and cytogenetic risk. One or more infections occurred in 1045 (59.5%) patients (MAC, 595 [61%]; RIC/NMA, 450 [58%]; P = .21) by day 100. The median time to initial infection after MAC conditioning occurred earlier (MAC, 15 days [range, <1-99 days]; RIC/NMA, 21 days [range, <1-100 days]; P < .001). Patients receiving MAC were more likely to experience at least 1 bacterial infection by day 100 (MAC, 46% [95% confidence interval (CI), 43-49]; RIC/NMA, 37% [95% CI, 34-41]; P = .0004), whereas at least a single viral infection was more prevalent in the RIC/NMA cohort (MAC, 34% [95% CI, 31-37]; RIC/NMA, 39% [95% CI, 36-42]; P = .046). MAC remained a risk factor for bacterial infections in multivariable analysis (relative risk, 1.44; 95% CI, 1.23-1.67; P < .0001). Moreover, the rate of any infection per patient-days at risk in the first 100 days (infection density) after alloHCT was greater for the MAC cohort (1.21; 95% CI, 1.11-1.32; P < .0001). RIC/NMA was associated with reduced infections, especially bacterial infections, in the first 100 days after alloHCT.

8.
Biol Blood Marrow Transplant ; 25(12): 2398-2407, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31473319

RESUMO

Malignancy relapse is the most common cause of treatment failure among recipients of hematopoietic cell transplantation (HCT). Conditioning dose intensity can reduce disease relapse but is offset by toxicities. Improvements in radiotherapy techniques and supportive care may translate to better outcomes with higher irradiation doses in the modern era. This study compares outcomes of recipients of increasing doses of high-dose total body irradiation (TBI) divided into intermediate high dose (IH; 13-13.75 Gy) and high dose (HD; 14 Gy) with standard dose (SD; 12 Gy) with cyclophosphamide. A total of 2721 patients ages 18 to 60 years with hematologic malignancies receiving HCT from 2001 to 2013 were included. Cumulative incidences of nonrelapse mortality (NRM) at 5 years were 28% (95% confidence interval [CI], 25% to 30%), 32% (95% CI, 29% to 36%), and 34% (95% CI, 28% to 39%) for SD, IH, and HD, respectively (P = .02). Patients receiving IH-TBI had a 25% higher risk of NRM compared with those receiving SD-TBI (12 Gy) (P = .007). Corresponding cumulative incidences of relapse were 36% (95% CI, 34% to 38%), 32% (95% CI, 29% to 36%), and 26% (95% CI, 21% to 31%; P = .001). Hazard ratios for mortality compared with SD were 1.06 (95% CI, .94 to 1.19; P = .36) for IH and .89 (95% CI, .76 to 1.05; P = .17) for HD. The study demonstrates that despite improvements in supportive care, myeloablative conditioning using higher doses of TBI (with cyclophosphamide) leads to worse NRM and offers no survival benefit over SD, despite reducing disease relapse.

10.
Toxicol Mech Methods ; 29(9): 693-701, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31364914

RESUMO

Given that the cadmium (Cd) toxicity could be due to its interference with the calcium (Ca) homeostasis, the aim of this work was to study the effect of Cd over the presence, distribution and volume density (Vv) of Ca and Ca-ATPase in the secretory cells of the pars preconvoluta (PPC) and the pars convoluta (pc) in Rhinella arenarum. The severe effect of the xenobiotic (CdCl2 2.5 mg/kg) in sexually matured females was evaluated. Co-localization, as well as a marked reduction of Ca and Ca-ATPase, was observed in treated animals, in the areas analyzed, compared to control. Low calcium deposits were found in the secreting granules (SG) of the epithelial (ESC) and glandular secretory cells (GSC), while an increase in their cytoplasm and intracellular space was observed. The Ca-ATPase in treated and control animals was detected at the SG and the plasmatic membrane of the ESC and GSC. In relation to the Vv estimates, a substantial reduction of Ca deposits and Ca-ATPase activity was observed in the treated group, with respect to the control. Both amounts of Vv of Ca and Ca-ATPase activity were higher in PPC than in pc, and, higher in ESC than in GSC. These results were associated with the Cd concentration in the oviductal PC, determining that it is a bioaccumulator organ. Thus, this work demonstrated that the Cd interacted with Ca-ATPase, leading to an increase of cytosolic Ca, which is responsible for the possible disruptions in cellular metabolism.

11.
Exp Parasitol ; 204: 107729, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31348914

RESUMO

The objectives of this study are to: (1) evaluate the in vitro acaricidal effect of 54 Metarhizium anisopliae strains, six Beauveria bassiana strains and one Purpureocilium lilacinum strain, against the larvae of two populations of Rhipicephalus microplus (multi-resistant and susceptible to chemical acaricides); and (2) determine the lethal concentrations required to eliminate the 50% (LC50) and 99% (LC99) of larvae through the use of entomopathogenic fungi (EF) with high acaricidal effects. The mortality percentage was evaluated by larval immersion tests at a dose of 1 × 108 conidia/mL for each fungal strain. For calculating LC50 and LC99, four doses (1 × 108, 1 × 107, 1 × 106 and 1 × 105) were used. Nine strains of M. anisopliae and the P. lilacinum strain showed a high mortality percentage in the R. microplus larvae of both populations. The best strains that showed the lowest values of LC50 and LC99 for tick elimination were MaV50 and PlV01. In conclusion, several strains of entomopathogenic fungi showed a high acaricidal effect against the R. microplus larvae of both populations, suggesting that these fungi might be a promissory adjuvant in the control of R. microplus, including those who are resistant. Finally, the discovery of a P. lilacinum strain with a high acaricidal effect is also reported.


Assuntos
Acaricidas/farmacologia , Fungos/patogenicidade , Controle Biológico de Vetores/métodos , Rhipicephalus/microbiologia , Microbiologia do Solo , Animais , Beauveria/patogenicidade , Bioensaio/veterinária , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/parasitologia , Doenças dos Bovinos/prevenção & controle , Feminino , Hypocreales/patogenicidade , Resistência a Inseticidas , Larva/efeitos dos fármacos , Larva/microbiologia , Dose Letal Mediana , Masculino , Metarhizium/patogenicidade , México , Rhipicephalus/efeitos dos fármacos , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/parasitologia , Infestações por Carrapato/veterinária , Virulência
12.
Transpl Infect Dis ; 21(5): e13145, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31301099

RESUMO

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are associated with significant morbidity and mortality following allogeneic hematopoietic cell transplant (alloHCT). Although most PTLD is EBV-positive (EBVpos ), EBV-negative (EBVneg ) PTLD is reported, yet its incidence and clinical impact remain largely undefined. Furthermore, factors at the time of transplant impacting survival following PTLD are not well described. METHODS: Between 2002 and 2014, 432 cases of PTLD following alloHCT were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). After exclusions, 267 cases (EBVpos  = 222, 83%; EBVneg  = 45, 17%) were analyzed. RESULTS: Two hundred and eight patients (78%) received in vivo T-cell depletion (TCD) with either anti-thymocyte globulin (ATG) or alemtuzumab. Incidence of PTLD was highest using umbilical cord donors (UCB, 1.60%) and lowest using matched related donors (MRD, 0.40%). Clinical features and histology did not significantly differ among EBVpos or EBVneg PTLD cases except that absolute lymphocyte count recovery was slower, and CMV reactivation was later in EBVneg PTLD [EBVpos 32 (5-95) days versus EBVneg 47 (10-70) days, P = .016]. There was no impact on survival by EBV status in multivariable analysis [EBVneg RR 1.42, 95% CI 0.94-2.15, P = .097]. CONCLUSIONS: There is no difference in survival outcomes for patients with EBVpos or EBVneg PTLD occurring following alloHCT and 1-year survival is poor. Features of conditioning and use of serotherapy remain important.

13.
Blood Adv ; 3(12): 1826-1836, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31201170

RESUMO

HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy-based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease-donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy-based Haplo-HCT vs MSD using calcineurin inhibitor-based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.

14.
Blood Adv ; 3(9): 1441-1449, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31053571

RESUMO

We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P < .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P < .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.

15.
Biol Blood Marrow Transplant ; 25(9): 1875-1883, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31085303

RESUMO

Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3+ T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3+ T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3+ T cell dose cutoff of 14 × 107 cells/kg identified MSD/low CD3+ (n = 223) and MSD/high CD3+ (n = 1214), and a dose of 15 × 107 cells/kg identified MUD/low CD3+ (n = 197) and MUD/high CD3+ (n = 1102). On univariate analysis, the MSD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3+ group (33% versus 25%; P = .009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3+ group (49% versus 41%; P = .04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3+ T cell dose and the risk of either aGVHD grade II-IV (P = .10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4+ T cells, CD8+ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3+ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4+ and CD8+ T cell doses were not possible given our small sample size.

16.
JAMA Pediatr ; 173(5): e190081, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30882883

RESUMO

Importance: Studies demonstrating improved survival after allogeneic hematopoietic cell transplant generally exclude infants. Objective: To analyze overall survival trends and other outcomes among infants who undergo allogeneic hematopoietic cell transplant. Design, Setting, and Participants: In this cohort study, we used time-trend analysis to evaluate 3 periods: 2000 through 2004, 2005 through 2009, and 2010 through 2014. The study was conducted in a multicenter setting through the Center for International Blood and Marrow Transplant Research, which is made up of a voluntary working group of more than 450 transplant centers worldwide. Two groups of infants aged 1 year or younger in 2 cohorts were included: those with malignant conditions, such as leukemia, and those with nonmalignant disorders, including immunodeficiencies. Data analysis was conducted from July 2017 to December 2018. Exposures: Allogeneic hematopoietic cell transplant. Main Outcomes and Measures: Survival trends, disease relapse, and toxicity. Results: A total of 2498 infants with a median age of 7 months (range, <1-12 months) were included. In the nonmalignant cohort (n = 472), survival rates improved from the first to the second period (hazard ratio, 0.77 [95% CI, 0.63-0.93]; P = .007) but did not change after 2004. Compared with infants with nonmalignant diseases (n = 2026; 3-year overall survival: 2000-2004, 375/577 [65.0%]; 2005-2009, 503/699 [72.0%]; and 2010-2014, 555/750 [74.0%]), those with malignant conditions had poorer survival rates, without improvement over time (3-year overall survival: 2000-2004, 109/199 [54.8%]; 2005-2009, 104/161 [64.6%]; and 2010-2014, 66/112 [58.9%]). From 2000 through 2014, relapse rates increased in infants with malignant conditions (3-year relapse rate: 2000-2004, 19% [95% CI, 14%-25%]; 2005-2009, 23% [95% CI, 17%-30%]; 2010-2014, 36% [95% CI, 27%-46%]; P = .01). Sinusoidal obstruction syndrome was frequent, occurring with a cumulative incidence of 13% (95% CI, 11%-16%) of infants with nonmalignant diseases and 32% (95% CI, 22%-42%) of those with malignant diseases. Generally, recipients of human leukocyte antigen-identical sibling bone marrow grafts had the best outcomes. Conclusions and Relevance: Survival rates have not improved for infants with malignant diseases over the 15-year study period. Infants with nonmalignant diseases had improved survival rates in the earlier but not the later study period. Higher relapses for the malignant cohort and toxicities for all infants remain significant challenges. Strategies to reduce relapse and toxicity and optimize donor and graft selection may improve outcomes in the future.

17.
Biol Blood Marrow Transplant ; 25(6): 1099-1106, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30794931

RESUMO

The curative potential of autologous hematopoietic cell transplantation (autoHCT) for male germ cell tumors (GCTs) is well established. The optimal timing and number (single transplant [ST] versus tandem transplants [TT] versus triple transplants) of autoHCT are controversial, with wide practice variations. We examined survival trends among 2395 recipients of autoHCT for male GCTs between 1990 and 2015 reported to the Center for International Blood and Marrow Transplant Research. Trends and outcomes were analyzed by year of transplantation for intervals 1990 to 1994 (N = 288), 1995 to 1999 (N = 351), 2000 to 2004 (N = 376), 2005 to 2009 (N = 509), and 2010 to 2015 (N = 871). Multivariate analysis was restricted to the subset from 2000 to 2015 with research-level data (n = 267). The median duration of follow-up was 51 months. The median age at autoHCT was 31 years; 633 patients (26%) had primary extragonadal GCT, and 1167 (49%) underwent TT. The 3-year progression-free (PFS) and overall survival (OS) improved from 24% (95% confidence interval [CI], 18% to 31%) and 35% (95% CI, 29% to 40%), respectively, in 1990 to 1994 to 47% (95% CI, 43% to 50%) and 54% (95% CI, 50% to 57%), respectively, in 2010 to 2015 (P < .0001). TT recipients were more likely than ST recipients to undergo autoHCT as first salvage treatment. The proportion of TTs increased from 38% of all autoHCTs in 2000 to 2004 to 77% in 2010 to 2015. Nonseminoma histology, residual disease at autoHCT, >1 line of pretransplantation chemotherapy, and ST versus TT were associated with inferior PFS and OS. Post-transplantation survival has improved significantly over time for relapsed/refractory male GCT and is associated with the increased use of TTs (compared with STs) and performance of autoHCT earlier in the disease course.

18.
Blood Adv ; 3(4): 670-680, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808685

RESUMO

Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR ≥3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.

19.
Biol Blood Marrow Transplant ; 25(7): 1325-1330, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30716454

RESUMO

Bone marrow (BM) is an essential source of hematopoietic stem cell grafts for many allogeneic hematopoietic cell transplant (HCT) recipients, including adult patients (for specific diseases and transplantation strategies) and the majority of pediatric recipient. However, since the advent of granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts, there has been a significant decrease in the use of BM in HCT, thought to be due mainly to the increased logistical challenges in harvesting BM compared with PBSCs, as well as generally no significant survival advantage of BM over PBSCs. The decreased frequency of collection has the potential to impact the quality of BM harvests. In this study, we examined >15,000 BM donations collected at National Marrow Donor Program centers between 1994 and 2016 and found a significant decline in the quality of BM products, as defined by the concentration of total nucleated cells (TNCs). The mean TNC concentration in BM donations dropped from 21.8 × 106 cells/mL in the earliest era (1994 to 1996) to 18.7 × 106 cells/mL in the most recent era (2012 to 2016) (means ratio, .83; P < .001). This decline in BM quality was seen despite the selection of more donors perceived to be optimal (eg, younger and male). Multivariate regression analysis showed that higher-volume centers (performing >30 collections per era) had better-quality harvests with higher concentrations of TNCs collected. In conclusion, we have identified a significant decrease in the quality of BM collections over time, and lower-volume collection centers had poorer-quality harvests. In this analysis, we could not elucidate the direct cause for this finding, suggesting the need for further studies to investigate the key factors responsible and to explore the impact on transplant recipients.

20.
Bone Marrow Transplant ; 54(8): 1354-1360, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30696997

RESUMO

Limited data exist on characteristics of central nervous system viruses (CNS-V) in allogeneic hematopoietic stem cell transplant (HCT) recipients. Between 2007 and 2015, the Center for International Blood and Marrow Transplant Research (CIBMTR) received information on 27,532 patients undergoing HCT. Of these, centers reported 165 HCT recipients with CNS-V detected in cerebrospinal fluid within 6 months after HCT. CNS viruses predominantly included human herpes virus 6 (HHV-6) (73%), followed by Epstein-Barr Virus (10%), cytomegalovirus (3%), varicella zoster virus (3%), herpes simplex virus (3%) and Adenovirus (3%). Median time of viral detection in CNS was 31 days after HCT; and viral detection was earlier in patients with CNS HHV-6. Concurrent viremia occurred in 52% of patients. Cord blood transplant recipients (CBT) accounted for the majority (53%) of patients with CNS-V. Myeloablative conditioning (65%), use of fludarabine (63%), or use of anti-thymocyte globulin (61%) were also predominant. Overall survival from the time of detection of CNS-V was 50% at 6 months and 30% at 5 years. Infections were the leading cause of death (32%). In summary, CBT recipients predominated in the population with CNS-V. Outcomes after CNS-V were poor with significant mortality seen in the first 6 months.

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