| 1. |
- Aplenc, Richard, et al.
(författare)
-
Effect of body mass in children with hematologic malignancies undergoing allogeneic bone marrow transplantation.
- 2014
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 123:22, s. 3504-11
-
Tidskriftsartikel (refereegranskat)abstract
- The rising incidence of pediatric obesity may significantly affect bone marrow transplantation (BMT) outcomes. We analyzed outcomes in 3687 children worldwide who received cyclophosphamide-based BMT regimens for leukemias between 1990 and 2007. Recipients were classified according to age-adjusted body mass index (BMI) percentiles as underweight (UW), at risk of UW (RUW), normal, overweight (OW), or obese (OB). Median age and race were similar in all groups. Sixty-one percent of OB children were from the United States/Canada. Three-year relapse-free and overall survival ranged from 48% to 52% (P = .54) and 55% to 58% (P = .81) across BMI groups. Three-year leukemia relapses were 33%, 33%, 29%, 25%, and 21% in the UW, RUW, normal, OW, and OB groups, respectively (P < .001). Corresponding cumulative incidences for transplant-related mortality (TRM) were 18%, 19%, 21%, 22%, and 28% (P < .01). Multivariate analysis demonstrated a decreased risk of relapse compared with normal BMI (relative risk [RR] = 0.73; P < .01) and a trend toward higher TRM (RR = 1.28; P = .014). BMI in children is not significantly associated with different survival after BMT for hematologic malignancies. Obese children experience less relapse posttransplant compared with children with normal BMI; however, this benefit is offset by excess in TRM.
|
|
| 2. |
- Ayas, Mouhab, et al.
(författare)
-
Allogeneic hematopoietic cell transplantation for fanconi anemia in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome, or acute leukemia.
- 2013
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 31:13, s. 1669-76
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi anemia (FA). Data on outcomes in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome (MDS), or acute leukemia have not been separately analyzed. PATIENTS AND METHODS We analyzed data on 113 patients with FA with cytogenetic abnormalities (n = 54), MDS (n = 45), or acute leukemia (n = 14) who were reported to the Center for International Blood and Marrow Transplant Research from 1985 to 2007. Results Neutrophil recovery occurred in 78% and 85% of patients at days 28 and 100, respectively. Day 100 cumulative incidences of acute graft-versus-host disease grades B to D and C to D were 26% (95% CI, 19% to 35%) and 12% (95% CI, 7% to 19%), respectively. Survival probabilities at 1, 3, and 5 years were 64% (95% CI, 55% to 73%), 58% (95% CI, 48% to 67%), and 55% (95% CI, 45% to 64%), respectively. In univariate analysis, younger age was associated with superior 5-year survival (≤ v > 14 years: 69% [95% CI, 57% to 80%] v 39% [95% CI, 26% to 53%], respectively; P = .001). In transplantations from HLA-matched related donors (n = 82), younger patients (≤ v > 14 years: 78% [95% CI, 64% to 90%] v 34% [95% CI, 20% to 50%], respectively; P < .001) and patients with cytogenetic abnormalities only versus MDS/acute leukemia (67% [95% CI, 52% to 81%] v 43% [95% CI, 27% to 59%], respectively; P = .03) had superior 5-year survival. CONCLUSION Our analysis indicates that long-term survival for patients with FA with cytogenetic abnormalities, MDS, or acute leukemia is achievable. Younger patients and recipients of HLA-matched related donor transplantations who have cytogenetic abnormalities only have the best survival.
|
|
| 3. |
- Bejanyan, Nelli, et al.
(författare)
-
Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myelogenous Leukemia and Myelodysplastic Syndromes with Low/Intermediate but not High Disease Risk Index : A Center for International Blood and Marrow Transplant Research Study
- 2021
-
Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:1, s. 68.e1-68.e9
-
Tidskriftsartikel (refereegranskat)abstract
- Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/ intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR],.74; 95% confidence interval [CI],.62 to.88; P <.001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P <.001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P =.001). In the high/ very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR,.83; 95% CI,.68 to 1.00; P =.051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P =.002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/ very-high risk DRI group.
|
|
| 4. |
- Buchbinder, David, et al.
(författare)
-
Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors : A Report from the Center for International Blood and Marrow Transplant Research
- 2020
-
Ingår i: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 26:3, s. 553-561
-
Tidskriftsartikel (refereegranskat)abstract
- 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. |
- Chaudhury, Sonali, et al.
(författare)
-
Outcomes of Allogeneic Hematopoietic Cell Transplantation in Children and Young Adults with Chronic Myeloid Leukemia : A CIBMTR Cohort Analysis
- 2016
-
Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 22:6, s. 1056-1064
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic myeloid leukemia (CML) in children and young adults is uncommon. Young patients have long life expectancies and low morbidity with hematopoietic cell transplantation (HCT). Prolonged tyrosine kinase inhibitor (TKI) use may cause significant morbidity. In addition, indication for HCT in patients in the first chronic phase is not established. We hence retrospectively evaluated outcomes in 449 CML patients with early disease receiving myeloablative HCT reported to the CIBMTR. We analyzed various factors affecting outcome, specifically the effect of age and pre-HCT TKI in pediatric patients (age < 18 years, n = 177) and young adults (age 18 to 29 years, n = 272) with the goal of identifying prognostic factors. Post-HCT probability rates of 5-year overall survival (OS) and leukemia-free survival (LFS) were 75% and 59%, respectively. Rates of OS and LFS were 76% and 57% in <18-year and 74% and 60% in 18- to 29-year group, respectively, by univariate analysis (P = .1 and = .6). Five-year rates of OS for HLA matched sibling donor (MSD) and bone marrow (BM) stem cell source were 83% and 80%, respectively. In multivariate analysis there was no effect of age (<18 versus 18 to 29) or pre-HCT TKI therapy on OS, LFS, transplant related mortality, or relapse. Favorable factors for OS were MSD (P < .001) and recent HCT (2003 to 2010; P = .04). LFS was superior with MSD (P < .001), BM as graft source (P = .001), and performance scores > 90 (P = .03) compared with unrelated or mismatched peripheral blood stem cells donors and recipients with lower performance scores. Older age was associated with increased incidence of chronic graft-versus-host disease (P = .0002). In the current era, HCT outcomes are similar in young patients and children with early CML, and best outcomes are achieved with BM grafts and MSD.
|
|
| 6. |
- Dandoy, Christopher E., et al.
(författare)
-
Incidence, Risk Factors, and Outcomes of Patients Who Develop Mucosal Barrier Injury-Laboratory Confirmed Bloodstream Infections in the First 100 Days After Allogeneic Hematopoietic Stem Cell Transplant
- 2020
-
Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- 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 16875 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 (11768 [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 16875 patients in the study (9737 [57.7%] male; median [range] age, 47 [0.04-82] years) 13686 (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. This cohort study examines the incidence, timing, risk factors, and outcomes of patients who develop mucosal barrier injury-laboratory confirmed bloodstream infection (MBI-LCBI) in the first 100 days after hematopoietic stem cell transplant (HSCT).
|
|
| 7. |
- Flannick, Jason, et al.
(författare)
-
Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
-
Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
|
|
| 8. |
- Fuchsberger, Christian, et al.
(författare)
-
The genetic architecture of type 2 diabetes
- 2016
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
-
Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
|
|
| 9. |
- Gerds, Aaron T., et al.
(författare)
-
Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes
- 2017
-
Ingår i: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 23:6, s. 971-979
-
Tidskriftsartikel (refereegranskat)abstract
- For patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation, umbilical cord blood transplantation (UCBT) has become an acceptable alternative donor source in the absence of a matched sibling or unrelated donor. To date, however, there have been few published series dedicated solely to describing the outcomes of adult patients with myelodysplastic syndrome (MDS) who have undergone UCBT. Between 2004 and 2013, 176 adults with MDS underwent UCBT as reported to the Center for International Blood and Marrow Transplant Research. Median age at the time of transplantation was 56 years (range, 18-73 years). The study group included 10% with very low, 23% with low, 19% with intermediate, 19% with high, and 13% with very high-risk Revised International Prognostic Scoring System (IPSS-R) scores. The 100-day probability of grade II-IV acute graft-versus-host disease (GVHD) was 38%, and the 3-year probability of chronic GVHD was 28%. The probabilities of relapse and transplantation-related mortality (TRM) at 3 years were 32% and 40%, respectively, leading to a 3-year disease-free survival (DFS) of 28% and an overall survival (OS) of 31%. In multivariate analysis, increasing IPSS-R score at the time of HCT was associated with inferior TRM (P = .0056), DFS (P = .018), and OS (P = .0082), but not with GVHD or relapse. The presence of pretransplantation comorbidities was associated with TRM (P = .001), DFS (P = .02), and OS (P = .001). Reduced intensity conditioning was associated with increased risk of relapse (relative risk, 3.95; 95% confidence interval, 1.78-8.75; P < .001), and although a higher proportion of myeloablative UCBTs were performed in patients with high-risk disease, the effect of conditioning regimen intensity was the same regardless of IPSS-R score. For some individuals who lack a matched sibling or unrelated donor, UCBT can result in long-term DFS; however, the success of UCBT in this population is hampered by a high rate of TRM. (C) 2017 American Society for Blood and Marrow Transplantation.
|
|
| 10. |
- Hsu, Jack W., et al.
(författare)
-
Collection of Peripheral Blood Progenitor Cells in 1 Day Is Associated with Decreased Donor Toxicity Compared to 2 Days in Unrelated Donors
- 2020
-
Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 26:6, s. 1210-1217
-
Tidskriftsartikel (refereegranskat)abstract
- Peripheral blood stem cells (PBSCs) have been increasingly used for allogeneic hematopoietic cell transplantation instead of bone marrow stem cells. Current National Marrow Donor Program policy recommends 5 days of daily filgrastim, followed by either 1 or 2 days of apheresis for unrelated donors, depending on collection center choice. To date, there are no published studies comparing the differences in donor experience between 1 day and 2 days of apheresis. We examined 22,348 adult unrelated donor collections in 184 centers between 2006 and 2016. Of these 22,348 donors, 20,004 (89.5%) had collection on 1 day, and the other 2344 (9.5%) had collection over 2 days. Information on why donors underwent apheresis in 1 day or 2 days was not available. Donors who underwent apheresis in 1 day were more likely to be male (67% versus 46%; P < .001), younger (age <30 years, 48% versus 36%; P < .001), and have a higher body weight (83.0 kg versus 75.9 kg; P< .001) and body mass index (BMI; >30, 30% versus 22%; P < .001). Successful collection of the requested CD34(+) cell count was achieved on the first day in 82% of 1-day collections and in 16% of 2-day collections. Despite not administering filgrastim the evening after the first day of collection in patients who underwent 2 days of apheresis, the median concentration of CD34' cells/I, in the product was higher on the second day of apheresis compared with the first day (23.8 x 10(6) CD34(+)/L. on day 1 versus 28.7 x 10(6) CD34(+)/L. on day 2; P< .001). Donors who underwent collection in 1 day were less likely to experience citrate toxicity (36% versus 52%; P< .001), hospitalization (1% versus 6%; P< .001), and other side effects related to apheresis (Modified Toxicity Criteria incidence: 20% versus 26%; P < .001). Female sex, older age, collection via central lines, and higher BMI were factors associated with greater likelihood for the development of toxicity, whereas less toxicity was noted in those with higher CD34(+) counts and more blood processed on the first day of collection. We conclude that although unrelated donors can be successfully collected in 1 day or 2 days, 1-day apheresis procedures were associated with less overall toxicity, and thus we recommend single-day collections, especially if the requested number of cells have been collected in 1 day.
|
|
