Haploidentical stem cell transplantation in patients with chronic myelomonocytic leukemia

Sun, Yu‐Qian; Zhao, Chen; Wang, Yu; Yan, Chen‐Hua; Zhang, Xiao-Hui; Xu, Lei; Liu, Kai-Yan; Huang, Xiao‐Jun

doi:10.1007/s11427-019-1606-3

Cited by 8 publications

(7 citation statements)

References 11 publications

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“…The treatment options for CMML were various given the fact of disease heterogeneity. The strategies included: best supportive treatment, HMAs, chemotherapy, and allo-HSCT [ 46 , 47 ]. In our study, the Cox model showed that treatment modalities (HMAs ± chemotherapy/allo-HSCT) was closely correlated with a better OS.…”

Section: Discussionmentioning

confidence: 99%

“…A retrospective study showed that HMAs monotherapy group had a prolonged OS and achieved high response, but could not significantly modify the disease process [ 48 ]. In addition, the universal applicability of this treatment option was limited by the complication of allo-HSCT, such as non-recurrent mortality (NRM) and acute and chronic graft-versus-host disease (GVHD) [ 5 , 47 ]. An open-label, non-randomized phase 2 clinical trial is undergoing to evaluate the efficacy of cobimetinib, a selective a reversible ATP-noncompetitive MEK inhibitor, in CMML patients with activated RAS pathway (mutations in NRAS , KRAS , PTPN11 , FLT3 , CBL , JAK2 , BRAF, and NF1 at VAF ≥ 5%) (NCT04409639) [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

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Mutational landscape of chronic myelomonocytic leukemia in Chinese patients

Nie¹,

Shao

Zhang³

et al. 2022

Exp Hematol Oncol

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Background Chronic myelomonocytic leukemia (CMML) is a rare and heterogeneous hematological malignancy. It has been shown that the molecular abnormalities such as ASXL1, TET2, SETBP1, and SRSF2 mutations are common in Caucasian population. Methods We retrospectively analyzed 178 Chinese CMML patients. The targeted next generation sequencing (NGS) was used to evaluate 114 gene variations, and the prognostic factors for OS were determined by COX regression analysis. Results The CMML patients showed a unique mutational spectrum, including TET2 (36.5%), NRAS (31.5%), ASXL1 (28.7%), SRSF2 (24.7%), and RUNX1 (21.9%). Of the 102 patients with clonal analysis, the ancestral events preferentially occurred in TET2 (18.5%), splicing factors (16.5%), RAS (14.0%), and ASXL1 (7.8%), and the subclonal genes were mainly ASXL1, TET2, and RAS. In addition, the secondary acute myeloid leukemia (sAML) transformed from CMML often had mutations in DNMT3A, ETV6, FLT3, and NPM1, while the primary AML (pAML) demonstrated more mutations in CEBPA, DNMT3A, FLT3, IDH1/2, NPM1, and WT1. It was of note that a series of clones were emerged during the progression from CMML to AML, including DNMT3A, FLT3, and NPM1. By univariate analysis, ASXL1 mutation, intermediate- and high-risk cytogenetic abnormality, CMML-specific prognostic scoring system (CPSS) stratifications (intermediate-2 and high group), and treatment options (best supportive care) predicted for worse OS. Multivariate analysis revealed a similar outcome. Conclusions The common mutations in Chinese CMML patients included epigenetic modifiers (TET2 and ASXL1), signaling transduction pathway components (NRAS), and splicing factor (SRSF2). The CMML patients with DNMT3A, ETV6, FLT3, and NPM1 mutations tended to progress to sAML. ASXL1 mutation and therapeutic modalities were independent prognostic factors for CMML.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mutational landscape of chronic myelomonocytic leukemia in Chinese patients

Nie¹,

Shao

Zhang³

et al. 2022

Exp Hematol Oncol

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“…The follow‐up period lasted until October 23, 2021. Nineteen of the 59 patients included in this study were previously reported in 2020 3 and further followed up in this study. The study design adhered to the principles of the Declaration of Helsinki and was approved by the ethics committees of Peking University People's Hospital.…”

Section: Methodsmentioning

confidence: 99%

“…Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is currently the only curative treatment strategy for numerous hematological malignancies, including CMML. Studies have shown that the outcomes of patients with CMML who underwent allo‐HSCT were gradually improved; the rates of 3‐year OS and EFS after HSCT were 64% and 57%, respectively 3 . Disease recurrence after transplantation remains the main cause of transplantation failure 4,5 .…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that the outcomes of patients with CMML who underwent allo-HSCT were gradually improved; the rates of 3-year OS and EFS after HSCT were 64% and 57%, respectively. 3 Disease recurrence after transplantation remains the main cause of transplantation failure. 4,5 Since CMML is a rare hematologic malignancy, few studies have focused thus far on the prediction of relapse in this setting.…”

Section: Introductionmentioning

confidence: 99%

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Significance of WT1 and multiparameter flow cytometry assessment in patients with chronic myelomonocytic leukemia receiving allogeneic hematopoietic stem cell transplantation

Pan

Gao

Sun

et al. 2022

Int J Lab Hematology

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Introduction:The objective of this study was to investigate the clinical significance of minimal residual disease (MRD) monitoring through Wilms tumor 1 (WT1) gene expression and multicolor flow cytometry (FCM) in patients with chronic myelomonocytic leukemia (CMML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods: For this purpose, WT1 gene expression and the CMML-related abnormal immunophenotype were examined using real-time quantitative polymerase chain reaction and FCM, respectively. Results:In total, 59 patients with CMML who underwent allo-HSCT were enrolled in this study. Thirteen cases (22.0%) developed hematological relapse, and 15 patients (25.4%) expired during the follow-up period. Thirty-four patients (37.6%) were positive for WT1 (WT1+), and 44 patients (74.6%) were positive for FCM prior to allo-HSCT. After allo-HSCT, there were 21 WT1+ patients (35.6%) and 10 patients (16.9%) who were positive in FCM (FCM+). Post-transplant WT1+ (post-WT1 0.6+; 50.7% vs. 7.6%, p < .001) and post-transplant FCM+ (post-FCM+; 90.0% vs. 8.8%, p < .001) indicated a higher 3-year cumulative incidence of relapse (CIR) compared with the WT1− or FCM−patients. Multivariate analysis of event-free survival (EFS), overall survival (OS), and CIR showed that the FCM status after transplantation was an independent prognostic factor for relapse (p < .05). Conclusion:Both FCM and WT1 after HSCT were identified as important predictors of recurrence of CMML following transplantation and may be useful in guiding interventions against disease relapse.

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Advances in hematopoietic stem cells ex vivo expansion associated with bone marrow niche

Deng,

Tan,

et al. 2024

Ann Hematol

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Haploidentical stem cell transplantation in patients with chronic myelomonocytic leukemia

Cited by 8 publications

References 11 publications

Mutational landscape of chronic myelomonocytic leukemia in Chinese patients

Mutational landscape of chronic myelomonocytic leukemia in Chinese patients

Significance of WT1 and multiparameter flow cytometry assessment in patients with chronic myelomonocytic leukemia receiving allogeneic hematopoietic stem cell transplantation

Advances in hematopoietic stem cells ex vivo expansion associated with bone marrow niche

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