Allogeneic Transplantation for Patients With Advanced Myelofibrosis: Splenomegaly and High Serum LDH are Adverse Risk Factors for Successful Engraftment

Gergis, Usama; Kuriakose, Emil; Shore, Tsiporah B.; Mayer, Sebastian; Mark, Tomer M.; Pearse, Roger; Schuster, Michael; Feldman, Eric J.; Roboz, Gail J.; Ritchie, Ellen K.; Scandura, Joseph M.; Wang, Hanhan; Zhou, Xi Kathy; Silver, Richard T.; Besien, Koen van

doi:10.1016/j.clml.2016.02.004

Cited by 16 publications

(5 citation statements)

References 23 publications

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“…We observed comparable survival outcomes (3-year OS of 85.4% versus 92.9% and FFS of 82.7% versus 92.9%) in the PR/SD and CR groups, with poor performance (ECOG scores = 3) being an adverse factor. Previous reports also observed that poor performance affected outcomes after transplantation [23,[32][33][34]. These results suggest that reducing the pretransplantation delay may be beneficial for transplant patients because of better performance status and milder infections, although the small number of cases was a limitation.…”

Section: Discussionmentioning

confidence: 54%

Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Severe Aplastic Anemia Patients with Infection: A Single-Center Retrospective Study

Zhang

et al. 2018

Biology of Blood and Marrow Transplantation

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To assess the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (SAA) patients with infection, we conducted a retrospective study on 65 SAA patients with infection who received allo-HSCT from August 2012 to December 2016. All patients received antibacterial and/or antifungal therapy before transplantation. The infection status after initial anti-infection therapy was classified as complete response (CR) (n = 14) or partial response/stable disease (PR/SD) (n = 51) before transplantation. The median times for myeloid engraftment in the PR/SD and CR groups were 10.5 days (range, 7 to 22) and 10 days (range, 8 to 11), with cumulative incidences of 98% and 100%, respectively. With a median follow-up of 788 days (range, 181 to 1758), patients with PR/SD had comparable results for 3-year estimated overall survival (85.4% versus 92.9%, P = .530) and 3-year failure-free survival (82.7% versus 92.9%, P = .458) with 14 patients with CR who received contemporaneous transplantation. In multivariate analysis, poor survival outcomes for the entire cohort was significantly associated with poor pretransplantation performance status. This retrospective study indicated that allo-HSCT may be a feasible therapeutic option for SAA patients with infection.

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Section: Discussionmentioning

confidence: 54%

Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Severe Aplastic Anemia Patients with Infection: A Single-Center Retrospective Study

Zhang

et al. 2018

Biology of Blood and Marrow Transplantation

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“…The significance of splenomegaly may vary among different indications for stem cell transplantation. Most of the evidence linking splenomegaly and rejection in stem cell transplant comes from myelofibrosis [33][34][35][36]. It also has been described in other conditions such as acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia [22,25].…”

Section: Discussionmentioning

confidence: 99%

Splenomegaly May Increase the Risk of Rejection in Low-Risk Matched Related Donor Transplant for Thalassemia, This Risk Can Be Partially Overcome by Additional Immunosuppression during Conditioning

Ramprakash¹,

Raghuram²,

Marwah

et al. 2020

Biology of Blood and Marrow Transplantation

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Severe thalassemia syndromes (ST) are highly curable by bone marrow transplant (BMT), but rejection may still occur. We retrospectively analyzed our fully matched related donor transplants to establish if isolated splenomegaly is an independent risk factor for rejection and if this risk can be reduced by modifying the conditioning protocol. In this study, we compared rejection rates between patients with and without splenomegaly in 189 consecutive low-risk ST transplants across 2 sequential conditioning regimens: regimen A (August 2013 to December 2016): busulfan (14 mg/kg oral, not adjusted to serum levels), cyclophosphamide (200 mg/kg), and anti-thymocyte globulin (ATG) (Genzyme (Sanofi, Paris, France) 4 mg/kg or Fresenius (Grafalon, Neovii Biotech GmbH, Gr€ afelfing Germany) 16 mg/kg on days À12 to À10), and regimen B: same backbone as regimen A except fludarabine total dose of 150 mg was added upfront and ATG dose was increased to 7 mg/kg in case of splenomegaly and/or sex-mismatched transplants (January 2017 to September 2018). Compared with regimen A, in regimen B, both overall rejection rates (RRs) (16% versus 6.5%, P = .023) and treatment-related mortality (TRM) (9.9% versus 2.8%, P = .038) improved significantly. By Cox regression analysis, the improvement in RR between the 2 protocols was particularly significant in patients with splenomegaly (RR 54.5% versus 6.5%, P = .00015; TRM 18.2% versus 6.5%, P = .25) (hazard ratio, 4.13; confidence interval, 1.61 to 10.6; P = .003). The increased risk of rejection related to splenomegaly can be overcome by adding fludarabine to the standard ATG-Busulfan-Cyclophosphamide (ATG-Bu-Cy) protocol without significantly increasing transplant-related morbidity and mortality or resorting to splenectomy pre-BMT.

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“…Our findings were reflected in a separate retrospective analysis of 156 patients receiving all-HSCT in which no significant correlation between pretransplant sLDH levels and time to engraftment of PLT and/or WBC was found (19). Conversely, Gergis et al reported that pretransplant sLDH levels above 487 IU/L were negatively associated with PLT engraftment (p= 0.04) in patients with advanced myelofibrosis undergoing allo-HSCT (23). We believe that the inconsistencies described among studies regarding the effect of pre-transplant sLDH levels and engraftment may be a result of varying definitions of what constitutes PLT and WBC engraftment, population heterogeneity, disease diagnosis, and cut-off points for what is considered low or high sLDH.…”

Section: Discussionmentioning

confidence: 54%

Pre-and Post-Transplant Serum Lactate Dehydrogenase Levels as a Predictive Marker for Patient Survival and Engraftment in Allogeneic Hematopoietic Stem Cell Transplant Recipients

et al. 2021

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Background:The discovery of biomarkers to predict the development of complications associated with hematopoietic stem cell transplantation (HSCT) offers a potential avenue for the early identification and treatment of these life-threatening consequences. Serum lactate dehydrogenase (sLDH) has been identified as a potential biomarker for determining the outcome of allogenic HSCT (allo-HSCT). Methods: A retrospective study was performed using data collected from 204 allo-HSCT recipient patients to examine the predictive value of sLDH levels pre-and post-allo-HSCT on patient survival, graft-versushost-disease (GVHD) incidence, and time to platelet/white blood cells (WBC) engraftment. Results: Our findings show that neither pre-(p= 0.61) nor post-transplantation (p= 0.55) sLDH levels were associated with GVHD incidence. However, elevated sLDH levels pre-and post-transplantation (≥ 386 and ≥ 409 IU/mL, respectively) were found to be adverse risk factors for patient survival (p= 0.16, p= 0.20, respectively). Furthermore, a median sLDH level≥ 400 IU/mL from day +5 to day +15 post-transplantation had a significant positive association with enhanced time to platelet and white blood cell (WBC) engraftment, compared to patients with sLDH levels < 400 IU/mL (p< 0.001). Conclusions: Our data suggests that high sLDH levels pre-and post-allo-HSCT could be considered a predictor of poor patient survival. Furthermore, high levels of sLDH days 5-15 post-allo-HSCT could be associated with improved time to platelet and WBC engraftment; however, this appears to come at the cost of increased mortality risk.

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Allogeneic Transplantation for Patients With Advanced Myelofibrosis: Splenomegaly and High Serum LDH are Adverse Risk Factors for Successful Engraftment

Cited by 16 publications

References 23 publications

Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Severe Aplastic Anemia Patients with Infection: A Single-Center Retrospective Study

Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Severe Aplastic Anemia Patients with Infection: A Single-Center Retrospective Study

Splenomegaly May Increase the Risk of Rejection in Low-Risk Matched Related Donor Transplant for Thalassemia, This Risk Can Be Partially Overcome by Additional Immunosuppression during Conditioning

Pre-and Post-Transplant Serum Lactate Dehydrogenase Levels as a Predictive Marker for Patient Survival and Engraftment in Allogeneic Hematopoietic Stem Cell Transplant Recipients

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