Incidence, risk factors and outcome of extramedullary relapse after allogeneic hematopoietic stem cell transplantation in patients with adult acute lymphoblastic leukemia

Yu, Jian; Ge, Xiaolong; Luo, Yi; Shi, Jimin; Tan, Yamin; Lai, Xiaoyu; Zhao, Yanmin; Ye, Yishan; Zhu, Yuanyuan; Zheng, Weiyan; Huang, He

doi:10.1007/s00277-020-04199-9

Cited by 9 publications

(5 citation statements)

References 37 publications

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“…It is still critical to understand the mechanisms of leukemia cell trafficking and homing, not only to devise means to prevent further bone marrow homing of the leukemia, but also to provide potential strategies based on mobilizing leukemia cells from the marrow into the peripheral blood where they are more susceptible to other therapies to overcome drug resistance (61,62). In addition, extramedullary infiltration leads to the development of leukemic tumors in non-marrow sites and plays critical roles in leukemia progression and chemoresistance, as well as extramedullary relapse in ALL patients (63,64). (58,65).…”

Section: Discussionmentioning

confidence: 99%

Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia

Gao¹,

Qin²,

Wu³

et al. 2021

Journal of Clinical Investigation

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PFKP (phosphofructokinase, platelet), the major isoform of PFK1 expressed in T cell acute lymphoblastic leukemia (T-ALL), is predominantly expressed in the cytoplasm to carry out its glycolytic function. Our study showed PFKP was a cyto-nuclear shuttling protein with functional nuclear export and nuclear localization sequences. Cyclin D3/CDK6 facilitated PFKP nuclear translocation by dimerization and by exposing the NLS of PFKP to induce the interaction between PFKP and importin 9. Nuclear PFKP stimulated the expression of C-X-C chemokine receptor type 4 (CXCR4), a chemokine receptor regulating leukemia homing/infiltration, to promote T-ALL cell invasion, which depended on the activity of c-Myc. In vivo experiments showed that nuclear PFKP promoted leukemia homing/infiltration into the bone marrow, spleen and liver, which could be blocked with CXCR4 antagonists. Immunohistochemistry staining of tissues from a clinically well-annotated cohort of T cell lymphoma/leukemia patients showed nuclear PFKP localization only in invasive cancers, but not in nonmalignant T lymph node or reactive hyperplasia. The presence of nuclear PFKP in these specimens correlated with poor survival in patients with T cell malignancy, suggesting the potential utility of nuclear PFKP as a diagnostic marker.

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Section: Discussionmentioning

confidence: 99%

Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia

Gao¹,

Qin²,

Wu³

et al. 2021

Journal of Clinical Investigation

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“…Notably, extramedullary disease before transplantation can predict higher relapse and a worse prognosis. Recently, Yu J et al 34 reported retrospective research on 268 patients with ALL experiencing allo-HSCT. The results suggested that extramedullary relapse was signi cantly associated with MSD-HSCT, a history of extramedullary disease pre-HSCT and the T-lineage phenotype.…”

Section: Discussionmentioning

confidence: 99%

Busulfan plus cyclophosphamide vs. total body irradiation plus cyclophosphamide for allogeneic hematopoietic stem cell transplantation in patients with acute T lymphoblastic leukemia: a large-scale propensity score matching-based study

Shen,

Liu,

Shen

et al. 2024

Bone Marrow Transplant

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as a promising treatment option for T-cell acute lymphoblastic leukemia (T-ALL). However, the clinical prognosis outcomes of allo-HSCT in T-ALL patients following the two myeloablative conditioning regimens, total body irradiation plus cyclophosphamide (TBI-Cy) and busulfan plus cyclophosphamide (BuCy), have not yet been determined. We conducted a retrospective analysis on 222 patients with T-ALL. Of these, 83 received TBI-Cy and 139 received BuCy as conditioning regimens. The analysis was conducted after propensity score matching based on a large-scale data between 2012 and 2022. The TBI-Cy conditioning regimen resulted in signi cantly higher 2-year overall survival (OS) and progression-free survival (PFS) compared to the BuCy conditioning regimen (OS: 73.9% vs. 53.7%, p = 0.003; PFS: 58.6% vs.46.0%, p = 0.020). The improved survival outcomes may be attributed to the reduced cumulative incidence of relapse (CIR). The 2-year CIR was 35.7% in the TBI-Cy group, and 46.4% in the BuCy group (p = 0.036). Additionally, there was no signi cant difference in non-relapse mortality (NRM) between the two groups, with a 2-year NRM of 8.0% in the TBI-Cy group and 12.6% following the BuCy group (p = 0.315). Patients with extramedullary disease prior to allo-HSCT or were in no remission (NR) at allo-HSCT who received the TBI-Cy conditioning regimen showed improved survival outcomes compared to those who received the BuCy conditioning regimen.Multivariate analysis con rmed that the TBI-Cy conditioning regimen was an independent predictive factor for improved OS and PFS and reduced CIR. In conclusion, TBI-Cy conditioning regimen appears to be a safe and effective choice for allo-HSCT in T-ALL patients.

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“…Secondary, the independent variables applied do not allow the model to be used to predict isolated extramedullary relapses (which accounts for 7% in our cohort). At the same time, according to the literature data the incidence of posttransplant isolated extramedullary relapses is relatively high and varies from 5 to 15% in ALL patients [46, [55][56][57][58], which poses a signi cant challenge for physicians because of limited treatment options and low response rates in this refractory subgroup. For these it is necessary to apply other variables based on the data of lumbar punctures, instrumental methods of research (magnetic resonance imaging, ultrasound, PET-CT and others) to predict extramedullary relapses.…”

Section: Discussionmentioning

confidence: 99%

Implication of machine learning for relapse prediction after allogeneic stem cell transplantation in adults with Ph-positive acute lymphoblastic leukemia

Афанасьева

Bakin

Smirnova

et al. 2023

Preprint

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The posttransplant relapse in Ph-positive ALL increases the risk of death. There is an unmet need for instruments to predict the risk of relapse and plan prophylaxis treatments. In this study we analyzed posttransplant data by machine learning algorithms. Seventy-four Ph-positive ALL patients with median age of 30 (range, 18–55) years, who previously underwent allo-HSCT were retrospectively enrolled. Ninety-three percent of patients received prophylactic/preemptive TKIs after allo-HSCT. The values of the BCR::ABL1 level at serial assessments and over variables were collected in specified intervals after allo-HSCT and were used to model relapse risk with several machine learning approaches. GBM proved superior to the other algorithms utilized and provided maximal AUC score of 0.91. BCR::ABL1 level before and after allo-HSCT, prediction moment and chronic GvHD had the highest value in the model. It was shown that after Day + 100 both error rates don’t exceed 22%, while before D + 100 the model fails to make accurate prediction. After day + 100 patients with chronic GVHD, BCR::ABL1 level more than 0.11% post-transplant and current BCR::ABL1 above 0.06% can be classified as high risk group of relapse. At the same time, if the patient had no chronic GVHD after allo-HSCT till the prediction moment, he should be classified to a high risk group already with a BCR::ABL1 level more than 0,05% at any time point. GBM model with posttransplant laboratory values of BCR::ABL1 provides high prediction of relapse in the era of TKIs prophylaxis. Validation of this approach is warranted.

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Incidence, risk factors and outcome of extramedullary relapse after allogeneic hematopoietic stem cell transplantation in patients with adult acute lymphoblastic leukemia

Cited by 9 publications

References 37 publications

Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia

Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia

Busulfan plus cyclophosphamide vs. total body irradiation plus cyclophosphamide for allogeneic hematopoietic stem cell transplantation in patients with acute T lymphoblastic leukemia: a large-scale propensity score matching-based study

Implication of machine learning for relapse prediction after allogeneic stem cell transplantation in adults with Ph-positive acute lymphoblastic leukemia

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