| 1. |
- Saad, Ayman, et al.
(författare)
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Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation
- 2019
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Ingår i: Biology of blood and marrow transplantation. - : ELSEVIER SCIENCE INC. - 1083-8791 .- 1523-6536. ; 25:9, s. 1875-1883
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Tidskriftsartikel (refereegranskat)abstract
- 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 x 10(7) cells/kg identified MSD/low CD3(+) (n = 223) and MSD/high CD3(+) (n = 1214), and a dose of 15 x 107 cells/kg identified MUD/low (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. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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| 2. |
- Deol, Abhinav, et al.
(författare)
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Does FLT3 Mutation Impact Survival After Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia? : A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis
- 2016
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 122:19, s. 3005-3014
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with FMS like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT). METHODS: Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes. RESULTS: In total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild-type (WT) group (38% [95% confidence interval (CI), 30%-45%] vs 28% [95% CI, 24%-33%]; P = .04; relative risk, 1.60 [95% CI, 1.15-2.22]; P = .0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia-free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3-year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%-57%; WT group: 55%, 95% CI, 50%-60%; P = .20). CONCLUSIONS: The current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long-term survivors.
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| 3. |
- Norkin, Maxim, et al.
(författare)
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Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation
- 2019
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 25:2, s. 362-368
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P < .001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and ≥55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD.
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| 4. |
- Pasquini, Marcelo C., et al.
(författare)
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Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies
- 2016
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 22:2, s. 248-257
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Tidskriftsartikel (refereegranskat)abstract
- The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, n = 240) and in myelodysplastic syndrome (MDS) (MK+MDS, n = 221) on hematopoietic cell transplantation outcomes compared with other cytogenetically defined groups (AML, n = 3360; MDS, n = 1373) as reported to the Center for International Blood and Marrow Transplant Research from 1998 to 2011. MK+AML was associated with higher disease relapse (hazard ratio, 1.98; P < .01), similar transplantation-related mortality (TRM) (hazard ratio, 1.01; P = .90), and worse survival (hazard ratio, 1.67; P < .01) compared with those outcomes for other cytogenetically defined AML. Among patients with MDS, MK+ MDS was associated with higher disease relapse (hazard ratio, 2.39; P < .01), higher TRM (hazard ratio, 1.80; P < .01), and worse survival (HR, 2.02; P < .01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (hazard ratio, 1.72; P < .01) and MDS (hazard ratio, 1.79; P < .01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced-intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed.
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| 5. |
- Kim, Haesook T., et al.
(författare)
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Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients : Center for International Blood and Marrow Transplant Research Report
- 2019
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Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 25:16, s. 5143-5155
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT).Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research.Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or >= 5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years).Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
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| 6. |
- Sharma, Manish, et al.
(författare)
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Older Patients with Myeloma Derive Similar Benefit from Autologous Transplantation
- 2014
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:11, s. 1796-1803
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Tidskriftsartikel (refereegranskat)abstract
- Autologous hematopoietic cell transplantation (AHCT) for plasma cell myeloma is performed less often in people >70 years old than in people <= 70 years old. We analyzed 11,430 AHCT recipients for plasma cell myeloma prospectively reported to the Center for International Blood and Marrow Transplant Research between 2008 and 2011, representing the majority of US AHCT activity during this period. Survival (OS) was compared in 3 cohorts: ages 18 to 59 years (n = 5818), 60 to 69 years (n = 4666), and >70 years (n = 946). Median OS was not reached for any cohort. In multivariate analysis, increasing age was associated with mortality (P = .0006). Myeloma-specific mortality was similar among cohorts at 12%, indicating an age-related effect on nonmyeloma mortality. Analyses were performed in a representative subgroup comparing relapse rate, progression-free survival (PFS), and nonrelapse mortality (NRM). One-year NRM was 0% for age >70 years and 2% for other ages (P = not significant). The three-year relapse rate was 56% in age 18 to 59 years, 61% in age 60 to 69 years, and 63% age >70 (P = not significant). Three-year PFS was similar at 42% in age 18 to 59 years, 38% in age 60 to 69 years, and 33% in age >70 years (P = not significant). Postrelapse survival was significantly worse for the older cohort (P = .03). Older subjects selected for AHCT derived similar antimyeloma benefit without worse NRM, relapse rate, or PFS.
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| 7. |
- McClune, Brian L., et al.
(författare)
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Allotransplantation for Patients Age >= 40 Years with Non-Hodgkin Lymphoma : Encouraging Progression-Free Survival
- 2014
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:7, s. 960-968
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Tidskriftsartikel (refereegranskat)abstract
- Non-Hodgkin lymphoma (NHL) disproportionately affects older patients, who do not often undergo allogeneic hematopoietic cell transplantation (HCT). We analyzed Center for International Blood and Marrow Transplant Research data on 1248 patients age >= 40 years receiving reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT for aggressive (n = 668) or indolent (n = 580) NHL Aggressive lymphoma was more frequent in the oldest cohort 49% for age 40 to 54 versus 57% for age 55 to 64 versus 67% for age >= 65; P = .0008). Fewer patients aged >= 65 had previous autografting (26% versus 24% versus 9%; P = .002). Rates of relapse, acute and chronic GVHD, and nonrelapse mortality (NRM) at 1 year post-HCT were similar in the 3 age cohorts (22% [95% confidence interval (CI), 19% to 26%] for age 40 to 54, 27% [95% CI, 23% to 31%] for age 55 to 64, and 34% [95% CI, 24% to 44%] for age >= 65. Progression-free survival (PFS) and overall survival (OS) at 3 years was slightly lower in the older cohorts (OS: 54% [95% CI, 50% to 58%] for age 40 to 54; 40% [95% CI, 36% to 44%] for age 55 to 64, and 39% [95% CI, 28% to 50%] for age >= 65; P < .0001). Multivariate analysis revealed no significant effect of age on the incidence of acute or chronic GVHD or relapse. Age >= 55 years, Karnofsky Performance Status <80, and HLA mismatch adversely affected NRM, PFS, and OS. Disease status at HCT, but not histological subtype, was associated with worse NRM, relapse, PFS, and OS. Even for patients age >= 55 years, OS still approached 40% at 3 years, suggesting that HCT affects long-term remission and remains underused in qualified older patients with NHL.
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| 8. |
- Radivoyevitch, Tomas, et al.
(författare)
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Risk of acute myeloid leukemia and myelodysplastic syndrome after autotransplants for lymphomas and plasma cell myeloma
- 2018
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 74, s. 130-136
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).Methods: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n=916), non-Hodgkin lymphoma (NHL; n=3546) and plasma cell myeloma (PCM; n=4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS.Results: 335 MDS/ AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR=4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR=2.5 [1.1, 2.5]); (2) >= 3 versus 1 line of chemotherapy for NHL (HR=1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR=2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/ MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort.Conclusions: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.
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