1. |
- Jimenez, Antonio M. Jimenez, et al.
(author)
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An adapted European LeukemiaNet genetic risk stratification for acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplant. A CIBMTR analysis
- 2021
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In: Bone Marrow Transplantation. - : Springer Nature. - 0268-3369 .- 1476-5365. ; 56:12, s. 3068-3077
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Journal article (peer-reviewed)abstract
- Cytogenetic and molecular abnormalities are known to influence post-transplant outcomes in acute myeloid leukemia (AML) but data assessing the prognostic value of combined genetic models in the HCT setting are limited. We developed an adapted European LeukemiaNet (aELN) risk classification based on available genetic data reported to the Center for International Blood and Marrow Transplant Research, to predict post-transplant outcomes in 2289 adult AML patients transplanted in first remission, between 2013 and 2017. Patients were stratified according to aELN into three groups: favorable (Fav, N = 181), intermediate (IM, N = 1185), and adverse (Adv, N = 923). Univariate analysis demonstrated significant differences in 2-year overall survival (OS) (Fav: 67.7%, IM: 64.9% and Adv: 53.9%; p < 0.001); disease-free survival (DFS) (Fav: 57.8%, IM: 55.5% and Adv: 45.3; p < 0.001) and relapse (Fav: 28%, IM: 27.5% and Adv: 37.5%; p < 0.001). Multivariate analysis (MVA) revealed no differences in outcomes between the Fav and IM groups, thus they were combined. On MVA, patients in the Adv risk group had the highest risk of relapse (HR 1.47 p <= 0.001) and inferior DFS (HR 1.35 p < 0.001) and OS (HR 1.39 p < 0.001), even using myeloablative conditioning or in those without the pre-HCT measurable-residual disease. Novel approaches to mitigate relapse in this high-risk group are urgently needed.
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2. |
- Pang, Ian, et al.
(author)
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Letermovir prophylaxis for cytomegalovirus reactivation in allogeneic hematopoietic cell transplant recipients : Single center Canadian data
- 2024
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In: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 112:2, s. 301-309
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Journal article (peer-reviewed)abstract
- Background: Cytomegalovirus (CMV) is associated with morbidity and mortality following allogeneic hematopoietic cell transplantation (alloHCT). Letermovir is a novel antiviral agent that prevents CMV reactivation in alloHCT patients, with limited data regarding influence on post-alloHCT outcomes.Methods: We retrospectively examined 273 alloHCT recipients, 158 in the non-letermovir cohort (NLC), and 115 in the cohort using letermovir prophylaxis (LC). Patients that received letermovir were CMV-seropositive and met criteria for high risk of CMV reactivation.Results: Median start of letermovir was 21 days post-alloHCT, median duration of prophylaxis was 86 days. Letermovir prophylaxis demonstrated a statistically significant reduction in first CMV reactivation (at 200 days post 63.9% in the NLC vs. 35.7% in the LC; p < .001). On univariate analysis at 1 year, overall survival (OS) for NLC was 79.6% and 79.5% for LC (p = .54). Non relapse mortality (NRM) at 1 year for NLC was 12% and 12.3% for LC (p = .69). Cumulative incidence of relapse (CIR) at 1 year was 13.9% for NLC versus 17.1 for the LC (p = .27). On multivariable analysis, there was no significant difference between the two cohorts for OS, NRM, and CIR.Conclusions: Letermovir prophylaxis started at day +21 post-alloHCT reduced CMV reactivation, with no impact on posttransplant outcomes.
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3. |
- Carreira, Abel Santos, et al.
(author)
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Bloodstream Infections and Outcomes Following Allogeneic Hematopoietic Cell Transplantation : A Single-Center Study
- 2022
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In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 28:1, s. 50.e1-50.e8
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Journal article (peer-reviewed)abstract
- This study investigated the single-center incidence and risk factors for bloodstream infections (BSIs) in 651 adults who underwent allogeneic hematopoietic cell transplantation (alloHCT) between 2015 and 2019 and explored the impact of these BSIs on post-transplantation outcomes. Antibiotic prophylaxis with ciprofloxacin was given during the aplastic phase. Overall, the median patient age was 57 years, 79.7% of patients received an alternative donor graft, and 68.7% received post-transplantation cyclophosphamide (PTCy) as part of their graft-versus-host disease (GVHD) prophylaxis. Of the 651 patients, 358 (55.0%) had at least 1 episode of BSI, and the overall mortality rate secondary to this complication was 7.5% (12.6% among those diagnosed with at least 1 episode of BSI). BSI was more often diagnosed during the first 30 days (58.7%), and gram-positive bacteria were the most prevalent microorganisms isolated during the entire post-transplantation follow-up (62%). A high Disease Risk Index (hazard ratio [HR], 1.47; P < .029) and receipt of PTCy-based GVHD prophylaxis (HR, 3.33; P < .001) were identified as risk factors for BSI. Additionally, univariate analysis showed that patients diagnosed with a BSI during post-transplantation follow-up had worse overall survival (HR, 2.48; P < .001) and higher nonrelapse mortality (HR, 2.68; P < .001) than those without BSI. In conclusion, alloHCT recipients with a BSI had a higher risk of mortality compared with those who did not develop BSI. The inclusion of PTCy as part of GVHD prophylaxis was identified as an independent risk factor for BSI during early post-transplantation follow-up. Single-center analyses focused on reporting the incidence and risk factors for BSI highlight the need for active implementation of preemptive strategies to decrease BSI incidence in the alloHCT setting.
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4. |
- Carreira, Abel Santos, et al.
(author)
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Interaction Between High-Dose Intravenous Busulfan and Post-Transplantation Cyclophosphamide on Hemorrhagic Cystitis After Allogeneic Hematopoietic Cell Transplantation
- 2023
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In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 29:9, s. 581.e1-581.e8
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Journal article (peer-reviewed)abstract
- This study investigates the incidence and predictors of hemorrhagic cystitis (HC) in 960 adults undergoing allo- hematopoietic stem cell transplantation. Two hundred fifty-two (26.5%) patients received myeloablative conditioning regimens, and 81.4% received high-dose intravenous busulfan (HD Bu). Six hundred ninety-five (72.4%) patients received post-transplantation cyclophosphamide (PTCY)-based prophylaxis, and 91.4% additionally received anti-thymocyte globulin (ATG) and Cyclosporine A (CsA) (PTCY-ATG-CsA). Two hundred twenty-eight (23.8%) patients developed HC. The day 100 cumulative incidences of grades 2-4 and 3-4 HC were 11.1% and 4.9%. BK virus was isolated in 58.3% of urinary samples. Using HD BU myeloablative regimens increased the risk for grade 2-4 HC (hazard ratio [HR] = 1.97, P = .035), and HD BU combined with ATG-PTCY-CsA increased this 4 times (HR = 4.06, P < .001) for grade 2-4 HC compared to patients who received neither of these drugs. A significant correlation was documented between grade II-IV acute graft-versus-host disease and grade 2-4 HC (HR = 2.10, P < .001). Moreover, patients with BK-POS grade 2-4 HC had lower 1-year overall survival (HR = 1.51, P = .009) and higher non-relapse mortality (HR = 2.31, P < .001), and patients with BK-NEG grade 2-4 HC had comparable post-transplantation outcomes. In conclusion, intravenous HD Bu was identified as a predictor for grade 2-4 HC. Moreover, when HD Bu was combined with PTCY-ATG-CsA, the risk increased 4-fold. Based on the results provided by this study, preventing the onset of HC, especially in high-risk patients, is mandatory because its presence significantly increases the risk for mortality.
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5. |
- Garcia‐Horton, Alejandro, et al.
(author)
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Patient age and donor HLA matching can stratify allogeneic hematopoietic cell transplantation patients into prognostic groups
- 2022
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In: European Journal of Haematology. - England : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 109:6, s. 672-679
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Journal article (peer-reviewed)abstract
- Background: Mixed results surround the accuracy of commonly used prognostic risk scores to predict overall survival (OS) and non-relapse mortality (NRM) in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. We hypothesize that a simple prognostic score performs better than conventional scoring systems.Patients and methods: OS risk factors, HCT-CI, age-HCT-CI, and augmented-HCT-CI were studied in 299 patients who underwent allo-HCT for myeloid and lymphoid malignancies. A scoring system was developed based on results and validated in a different cohort of 455 patients.Results: Two-year OS was 51% (95% confidence interval (CI) 0.45–0.56); 2-year NRM was 34% (95% CI 0.29–0.39). HCT-CI and associated scores were grouped into 0–2 and ≥3. Age and HLA mismatch status were the only risk factors to affect OS in multivariate analysis (p = 0.02 and 0.05, respectively). HCT-CI and associated scores were not informative for OS prediction. The weighted scoring system assigned 0 to 2 points for age < 50, 50–64, or ≥65, respectively, and 0–1 points for no HLA mismatch versus any mismatch (except HLA-DQ). Distinct 2-year OS (62%, 53%, and 38% [p = <0.001]) and NRM (24%, 34%, and 43% [p = 0.02]) groups were characterized. The scoring system was validated in a second independent cohort with similar results on OS and NRM (p < 0.001).Conclusions: A simple scoring system based on recipient's age and mismatch status accurately predict OS and NRM in two distinct cohorts of allo-HCT patients. Its simplicity makes it a helpful tool to aid clinicians and patients in clinical decision-making.
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6. |
- Menghrajani, Kamal, et al.
(author)
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Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML
- 2022
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:3, s. 828-847
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Journal article (peer-reviewed)abstract
- Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.
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7. |
- Michelis, Fotios V., et al.
(author)
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Cytogenetic Risk Determines Outcomes After Allogeneic Transplantation in Older Patients With Acute Myeloid Leukemia in Their Second Complete Remission : A Center for International Blood and Marrow Transplant Research Cohort Analysis
- 2017
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In: Cancer. - : WILEY. - 0008-543X .- 1097-0142. ; 123:11, s. 2035-2042
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Journal article (peer-reviewed)abstract
- BACKGROUND Allogeneic hematopoietic cell transplantation (HCT) offers curative potential to a number of older patients with acute myeloid leukemia (AML) in their first complete remission. However, there are limited data in the literature concerning post-HCT outcomes for older patients in their second complete remission (CR2).METHODS The purpose of the current study was to retrospectively investigate within the Center for International Blood and Marrow Transplant Research database parameters influencing post-transplant outcomes for patients 60 years of age or older undergoing HCT for AML in CR2.RESULTS In total, 196 patients from 78 centers were identified; the median age was 64 years (range, 60-78 years). Seventy-one percent had a Karnofsky performance status >= 90 at the time of HCT. Reduced-intensity conditioning regimens were used in 159 patients (81%). A univariate analysis demonstrated a 3-year overall survival (OS) rate of 42% (95% confidence interval [CI], 35%-49%), a leukemia-free survival rate of 37% (95% CI, 30%-44%), a cumulative incidence of nonrelapse mortality of 25% (95% CI, 19%-32%), and a cumulative incidence of relapse (CIR) of 38% (95% CI, 31%-45%). A multivariate analysis demonstrated that cytogenetic risk was the only independent risk factor for OS (P=.023) with a hazard ratio (HR) of 1.14 (95% CI, 0.59-2.19) for intermediate-risk cytogenetics and an HR of 2.32 (95% CI, 1.05-5.14) for unfavorable-risk cytogenetics. For CIR, cytogenetic risk was also the only independent prognostic factor (P=.01) with an HR of 1.10 (95% CI, 0.47-2.56) for intermediate-risk cytogenetics and an HR of 2.98 (95% CI, 1.11-8.00) for unfavorable-risk cytogenetics.CONCLUSIONS Allogeneic HCT is a curative treatment option for older patients with AML in CR2, particularly for those with favorable or intermediate cytogenetic risk.
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8. |
- Novitzky‐Basso, Igor, et al.
(author)
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Anti‐thymocyte Globulin and Post‐Transplant Cyclophosphamide do not abrogate the inferior outcome risk conferred by human leukocyte antigen‐A and ‐B mismatched donors
- 2022
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 108:4, s. 288-297
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Journal article (peer-reviewed)abstract
- In donor selection for allogeneic stem cell transplant, several factors are considered for potential impact on transplant outcome. Previous publications suggested single HLA-mismatched unrelated donors (MMUD) may be equivalent to 10/10 matched unrelated donors (MUDs). We retrospectively examined factors affecting outcome in a single-center study using ATG followed by post-transplant cyclophosphamide, termed ATG-PTCy, GvHD prophylaxis. Fifty-two patients who received grafts from MMUD and 188 patients transplanted from MUD between January 2015 and December 2019, at Princess Margaret Cancer Centre, Canada, were enrolled. All patients received reduced-intensity conditioning. Overall survival for 9/10 recipients at 2 years was significantly worse, 37.2% versus 68.5% for 10/10 MUDs, p < .001, as were NRM at 1 year 39.5% versus 11.7%, p < .001, and GRFS at 2 years 29.8% versus 58.8%, p < .001, respectively, potentially due to higher incidence of infections including CMV. By multivariable analysis, factors correlating with survival negatively were DRI, and MMUD, whereas for NRM MMUD and increasing age were unfavorable. For GRFS significant unfavorable factors included donor age ≤32 years, female donor to male recipient, DRI high-very high and MMUD. These data suggest that MMUD, primarily HLA-A and HLA-B MMUD, confer significantly inferior outcome despite use of ATG-PTCy. Further development of novel conditioning regimens and GvHD prophylaxis is needed to mitigate these risks.
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9. |
- Novitzky‐Basso, Igor, et al.
(author)
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Anti‐thymocyte globulin and post‐transplant cyclophosphamide predisposes to inferior outcome when using cryopreserved stem cell grafts
- 2021
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In: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 108:1, s. 61-72
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Journal article (peer-reviewed)abstract
- During 2020, the concurrent novel COVID-19 pandemic lead to widespread cryopreservation of allogeneic hematopoietic cell transplant grafts based on National Marrow Donor Program and European Society of Blood and Marrow Transplantation recommendations, in order to secure grafts before the start of conditioning chemotherapy. We sought to examine the impact of this change in practice on patient outcomes. We analyzed the outcomes of 483 patients who received hematopoietic stem cell transplantation (HSCT) between August 2017 and August 2020, at Princess Margaret Cancer Centre, Canada, in the retrospective study, comparing the outcomes between those who received cryopreserved or fresh peripheral blood stem cell grafts. Overall compared with those who received fresh grafts (n = 348), patients who received cryopreserved grafts (n = 135) had reduced survival and GRFS, reduced incidence of chronic graft-versus-host disease (GvHD), delay in neutrophil engraftment, and higher graft failure (GF), with no significant difference in relapse incidence or acute GvHD. However, recipients of cryopreserved matched-related donor HSCT showed significantly worse OS, NRM, GRFS compared with fresh grafts. Multivariable analysis of the entire cohort showed significant impact of cryopreservation on OS, relapse, cGvHD, GF, and GRFS. We conclude that cryopreservation was associated with inferior outcomes post-HSCT, possibly due to the combination of ATG and post-transplant cyclophosphamide impacting differential tolerance to cryopreservation on components of the stem cell graft; further studies are warranted to elucidate mechanisms for this observation.
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10. |
- Pasic, Ivan, et al.
(author)
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Treosulfan- Versus Busulfan-based Conditioning in Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome : A Single-center Retrospective Propensity Score-matched Cohort Study
- 2024
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In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 30:7, s. 681.e1-681.e11
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Journal article (peer-reviewed)abstract
- Treosulfan has shown promise in allogeneic hematopoietic cell transplantation (HCT) for its myeloablative properties and low toxicity. In this single-center retrospective propensity score-matched cohort study we compared treosulfan- and busulfan-based conditioning in allogeneic HCT for patients with myelodysplastic syndrome (MDS). This study included 138 adults who underwent allogeneic HCT for MDS or chronic myelomonocytic leukemia at Princess Margaret Hospital, Toronto, from 2015 to 2022. Using propensity score matching, we compared transplant outcomes between 2 well-matched cohorts who received conditioning with either fludarabine-treosulfan (FT) (n = 46) or fludarabine-busulfan with total body irradiation (FBT200) (n = 92). A scoring system based on patient age, Karnofsky performance score, and hematopoietic cell transplant comorbidity index was used to assign patients based on fitness to low-dose (30 g/m2) or high-dose (42 g/m2) treosulfan: 32 (69.6%) received high-dose treosulfan. The racial composition of the 2 groups was similar, with 27.2% and 21.7% of FBT200 and FT recipients, respectively, identifying as non-Caucasian (P = .61). Primary outcomes were analyzed at a median follow-up of 747 days. Of all participants, 116 (84.0%) received graft-versus-host disease (GVHD) prophylaxis with posttransplant cyclophosphamide (PTCY) and antithymocyte globulin (ATG). Patients who received FT had a superior 2-year overall survival (OS) compared to those who received FBT200: 66.9% (95% confidence interval (CI): 46.1 to 81.2) versus 44.5% (95% CI: 34 to 54.4), hazard ratio (HR): 0.43, 95% CI: 0.22 to 0.84 (P = .013). In multivariate analysis (MVA), only the use of fresh grafts (P = .02) and FT (P = .01) were associated with improved OS. FT was associated with superior 2-year relapse-free survival (RFS) compared to FBT200: 63.1% (95% CI: 42.6 to 77.9) versus 39.1% (95% CI: 29.1 to 49.1), HR: 0.44 (95% CI: 0.24 to 0.81), P = .008. In MVA, the use of fresh grafts ( P = .03) and FT ( P = .009) were associated with improved RFS. Recipients of FT demonstrated superior 2-year graft-versus-host disease relapse-free survival (GRFS) compared to those who received FBT200: 57.4% (95% CI: 37.8 to 72.8) versus 35.1% (95% CI: 25.5 to 45). In MVA, only FT was associated with superior GRFS ( P = .02). FT recipients exhibited markedly superior 1-year event-free survival compared to recipients of FBT200 in univariate analysis (40.3% (95% CI: 25.9 to 54.2) versus 9.2% (95% CI: 4.4 to 16.3), HR: 0.47 (95% CI: 0.30 to 0.72), P < .001) and MVA ( P = .004). FT was associated with lower 1-year nonrelapse mortality compared to FBT200 in univariate analysis (9.9% (95% CI: 3.0 to 21.8) versus 29.7% (95% CI: 20.6 to 39.3), HR: 0.41 (95% CI: 0.17 to 0.96), P = .04) and MVA ( P = .04). Our study utilized propensity score matching to demonstrate superiority of treosulfan-over busulfan-based conditioning in stem cell transplantation of patients with MDS and is the first to evaluate the performance of treosulfanbased conditioning in combination with ATG and PTCY. As such, it contributes to the increasing body of evidence supporting the safety of treosulfan, even at the dose of 42 g/m2.
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11. |
- Pereira, Mariana Pinto, et al.
(author)
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Choosing Between Older Matched Sibling Donor and Younger Matched Unrelated Donor in Allogeneic Hematopoietic Cell Transplantation : Comparison of Clinical Outcomes in Acute Myeloid Leukemia and Myelodysplastic Syndrome
- 2023
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In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 29:11
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Journal article (peer-reviewed)abstract
- The choice between an older matched sibling donor (MSD) and a younger matched unrelated donor (MUD) in allogeneic hematopoietic cell transplantation (HCT) remains a subject of ongoing debate. In this single-center retrospective study of 377 patients who received peripheral blood stem cell (PBSC) transplants for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), we compared outcomes of 85 patients who received grafts from MSDs age >60 years and 292 patients who received grafts from MUDs age <30 years. Compared to recipients of MSD transplants, recipients of MUD transplants were younger and more likely to receive dual T cell depletion (TCD), a higher CD34(+) cell dose, and a fresh graft. Recipients of MSD transplants were maintained on immunosuppressive therapy longer than those who received MUD grafts. We found no differences in overall survival, relapse-free survival, graft-versus-host disease (GVHD)-free and relapse-free survival, nonrelapse mortality, relapse, engraftment, graft failure, and acute GVHD between recipients of MSD grafts and recipients of MUD grafts. We report a higher 30-day incidence, but not 1-year incidence, of bloodstream infections among recipients of MUD transplants compared to subjects who received their grafts from a MSD. The incidence of moderate-severe chronic GVHD was higher in MSD graft recipients compared with MUD graft recipients in univariate analysis, but not in multivariate analysis. Although this difference could reflect the greater use of dual TCD, known to be associated with very low rates of chronic GVHD in MUD transplant recipients, the incidence of moderate-severe chronic GVHD was no different between MSD and MUD transplant recipients following propensity score matching, suggesting that other variables could be responsible. Taken together, our data suggest that in patients with AML or MDS who receive PBSC transplants, such factors as convenience, ease of access, and costs should be considered when selecting an older MSD over a younger MUD.
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12. |
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13. |
- Prem, Shruti, et al.
(author)
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Relationship between certain HLA alleles and the risk of cytomegalovirus reactivation following allogeneic hematopoietic stem cell transplantation
- 2022
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In: Transplant Infectious Disease. - : John Wiley & Sons. - 1398-2273 .- 1399-3062. ; 24:4
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Journal article (peer-reviewed)abstract
- Introduction: Evidence is emerging to support an association between certain human leukocyte antigen (HLA) alleles and the risk of cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplant (allo-HSCT). The primary aim of this study was to identify HLA alleles associated with resistance or susceptibility to CMV reactivation. Methods: We studied 586 adults who underwent al lo-HSCT for high-risk hematological malignancies. High-resolution HLA typing data were available for recipients and donors. HLA class I and II alleles observed at a frequency of >5% in our population were included in the analysis. A CMV viremia level of more than 200 IU/ml on weekly monitoring was considered to be indicative of CMV reactivation. Results: The median follow-up time in surviving patients was 21 months (range 4-74 months). The cumulative incidence of CMV reactivation at 6 months in the entire cohort was 55% (95% confidence interval [CI] 50.8%-59.2%). Mismatched donors, increasing recipient age, occurrence of acute graft versus host disease and recipient CMV seropositivity were associated with an increased risk of CMV reactivation. HLA B*07:02 (hazard ratio 0.59, 95% CI 0.40-0.83) was associated with a decreased risk of CMV reactivation. Patients who developed CMV reactivation had a lower incidence of relapse, higher transplant-related mortality (TRM) and lower overall survival (OS) than those without CMV reactivation. There was an adverse correlation of OS and TRM with increasing numbers of CMV reactivations. Conclusion: We observed that HLA B*07:02 was associated with a decreased risk of CMV reactivation. CMV reactivation was associated with lower relapse post-transplant, but this did not translate into a survival benefit due to higher TRM.
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14. |
- Salas, Maria Queralt, et al.
(author)
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Improving Safety and Outcomes After Allogeneic Hematopoietic Cell Transplantation : A Single-Center Experience
- 2022
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In: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 28:5
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Journal article (peer-reviewed)abstract
- The implementation of dual T-cell depletion comprising 4.5 mg/kg of antithymocyte globulin (ATG), post-transplantation cyclophosphamide, and cyclosporine A for reduced-intensity allogeneic hematopoietic cell transplantation (HCT) independent of donor source in 2015 significantly improved graft-versus-host disease (GVHD) control at our Institution. Further advances were made between 2017 to 2020 in supportive care of allogeneic HCT recipients and were the subject of this study, with 651 adults included. Transplant outcomes were compared between patients who underwent transplantation during Period 1 (2017-2018) and Period 2 (2019-2020). Main changes implemented during the study period were reduction of ATG dose from 4.5 to 2 mg/kg in matched unrelated donor transplants, abandoning of dual T-cell depletion in matched related donor transplants, combining dual T-cell depletion with myeloablative conditioning for selected patients, and reduction of the target therapeutic cyclosporine level from 200 to 400 ng/L to 150 to 250 ng/L. Other improvements included addition of ursodiol until day 100, implementation of a double responsible physician model, and personalized patient supportive care plan focused on activity and calorie intake. The reduction in intensity of GVHD prophylaxis provided comparable acute GVHD and moderate-severe chronic GVHD between both time periods. Altogether the described improvements in transplant methodology and supportive care showed that compared to Period 1, patients transplanted in Period 2 had superior 1-year overall survival, relapse-free survival, and non-relapsemortality and showed a trend toward better GVHD- and relapse-free survival, without an increase in relapse risk. This study reports the results of outcomes-directed improvements in transplantation design, GVHD prophylaxis, and supportive care, highlighting how transplantation outcomes can be improved through careful modifications in response to meticulously monitored outcomes. (C) 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
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15. |
- Wieduwilt, Matthew J., et al.
(author)
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Haploidentical vs sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia
- 2022
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:1, s. 339-357
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Journal article (peer-reviewed)abstract
- The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLAmatched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P <_ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P <_ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (<_18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.
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