Idarubicin-Intensified Hematopoietic Cell Transplantation Improves Relapse and Survival of High-Risk Acute Leukemia Patients with Minimal Residual Disease

Zhang, Ran; Lu, Xuan; Wang, Huafang; You, Yong; Zhong, Zhaodong; Zang, Sibin; Zhang, Chun; Shi, Wei; Li, J.; Wu, Qirui; Fang, Jun; Xia, Linghui

doi:10.1016/j.bbmt.2018.07.021

Cited by 8 publications

(16 citation statements)

References 36 publications

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“…Generally, patients who were diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) used IDA-BUCY2 regimen or traditional BUCY2 regimen, while patients with acute lymphoblastic leukemia (ALL) received regimens of IDA-intensified total body irradiation (TBI)-CY or traditional TBI-CY, which were consistent with our previous reports ( 4 , 12 – 14 ). ATG (Sanofi Aventis, Paris, France) was given to all patients as part of the conditioning regimen.…”

Section: Methodssupporting

confidence: 87%

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Influence of graft composition in patients with hematological malignancies undergoing ATG-based haploidentical stem cell transplantation

Zhang

Lu²,

Tang³

et al. 2022

Front. Immunol.

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To determine the influence of graft composition in haplo-HSCT, we summarized the long-term consequences of 251 consecutive transplantations from haploidentical donors. For donor-recipient HLA3/6matched setting, 125 cases used G-CSF-mobilized BM and PBSCs mixtures, while 126 cases only used G-CSF-mobilized PBSCs in HLA4/6-matched transplantation. On the one hand, we wanted to explore the effect of harvests (CD34+ cells and TNCs dosages) on transplantation outcome in the context of haplo-HSCT no matter HLA4/6 or HLA3/6-matched setting. On the other hand, for patients using G-CSF-mobilized BM and PBSCs combination in HLA3/6-matched setting, we attempted to analyze whether TNCs or CD34+ cells from G-CSF-mobilized BM or G-CSF-mobilized PBSCs play the most paramount role on transplantation prognosis. Collectively, patients with hematologic malignancies receiving G-CSF-primed BM and PBSCs harvests had comparable consequences with patients only receiving G-CSF-mobilized PBSCs. Moreover, when divided all patients averagely according to the total amount of transfused nucleated cells, 3-year TRM of the intermediate group (13.06-18.05×10 8 /kg) was only 4.9%, which was remarkably reduced when compared to lower and higher groups with corresponding values 18.3%, 19.6% (P=0.026). The 3-year probabilities of OS and DFS of this intermediate group were 72.6% and 66.5%, which were slightly improved than the lower and higher groups. Most importantly, these data suggest that the transfused nucleated cells from G-CSF-primed BM above than 5.20×10 8 /kg could achieve remarkably lower TRM in haplo-HSCT receiving G-CSF-mobilized BM and PBSCs harvests. These encouraging results suggested that we could improve the efficacy of haplo-HSCT by adjusting the component and relative ratio of transfused graft cells. Nevertheless, the above findings should be confirmed in a randomized prospective comparative research with adequate follow-up.

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Section: Methodssupporting

confidence: 87%

“…Supportive care after allo-HSCT, including the usage of empirical antibiotics, prophylaxis and therapy for cytomegalovirus (CMV), and hepatic veno-occlusive disease (HVOD) prevention were executed as our previous reports ( 4 , 12 – 14 ).…”

Section: Methodsmentioning

confidence: 99%

Influence of graft composition in patients with hematological malignancies undergoing ATG-based haploidentical stem cell transplantation

Zhang

Lu²,

Tang³

et al. 2022

Front. Immunol.

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“…Among them, 58 patients had received Dec in combination with mBuCy as the conditioning regimen (Dec group), and 98 who received the mBuCy regimen were selected as the control group (mBuCy group). High-risk AML included the following: hyperleukocytosis at diagnosis, no response to induction chemotherapy, ≥complete response 2 (CR2) or not in remission, extramedullary leukemia, relapse within 6 months from induction or consolidation therapy, ≥two relapses or relapse after auto-HSCT, and high-risk cytogenetics according to the National Comprehensive Cancer Network 2018 guidelines ( ) ( 20 , 21 ). Patients who had ≥5% BM blasts in pretransplantation were classified as having active disease (NR).…”

Section: Methodsmentioning

confidence: 99%

“…Antithymocyte globulin (Thymoglobulin; Sanofi Aventis, Paris, France) was used as part of conditioning in HID-HSCT as previously reported ( 22 ). Supportive care was administered as described previously ( 21 ).…”

Section: Methodsmentioning

confidence: 99%

Decitabine-Intensified Modified Busulfan/Cyclophosphamide Conditioning Regimen Improves Survival in Acute Myeloid Leukemia Patients Undergoing Related Donor Hematopoietic Stem Cell Transplantation: A Propensity Score Matched Analysis

Shi

et al. 2022

Front. Oncol.

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To identify the benefit of decitabine (Dec)-intensified myeloablative conditioning on the outcomes of patients with acute myeloid leukemia (AML) after related donor hematopoietic stem cell transplantation (HSCT), we performed a retrospective matched‐pair study from a pool of 156 patients to evaluate Dec [20 mg/m2/day intravenously (i.v.) on days −11 to −7]-intensified modified busulfan/cyclophosphamide (mBuCy) conditioning regimen vs. mBuCy regimen in 92 AML patients, with 46 patients in each cohort. The cumulative incidence of grade II–IV acute graft-versus-host disease (aGVHD) was lower in the Dec group (15.2% ± 0.3% vs. 32.6% ± 0.5%, P = 0.033). Compared with mBuCy group (15.5% ± 0.3%), a significantly higher proportion of limited chronic GVHD (cGVHD) in Dec group (35% ± 0.6%) was observed (P = 0.025). Dec-intensified mBuCy conditioning was associated with better 2-year overall survival (OS) and GVHD-free relapse-free survival (GRFS) (81% ± 6.2% vs. 59.4% ± 7.5%, P = 0.03; 58.7% ± 8.1% vs. 40.9% ± 7.3%, P = 0.042; respectively). Our results also elucidated that the Dec group had better 2-year OS and lower 2-year cumulative incidence of relapse (CIR) in patients acquiring haploidentical HSCT than that of the mBuCy group (84.8% ± 7.1% vs. 58.2% ± 10.3%, P = 0.047; 17.9% ± 0.8% vs. 40.0% ± 1.0%, P = 0.036; respectively), which did not increase the treatment-related mortality and regimen-associated toxicities. Dec-intensified myeloablative regimen and high-risk stratification were the variables associated with OS, leukemia-free survival (LFS), and GRFS in multivariate analysis. In high-risk patients, no differences were found in CIR, OS, LFS, and GRFS between the two groups. These data indicated that Dec-intensified mBuCy conditioning regimen was associated with better survival than mBuCy regimen in AML patients, especially in patients undergoing haploidentical HSCT.

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“…For instance, idarubicin administration (for 3 days) just prior to busulfan/cyclophosphamide conditioning has been reported to improve post-SCT survival in MRD-positive patients. 84…”

Section: Treatment Of Philadelphia Chromosome-like Acute Lymphoblastimentioning

confidence: 99%

How I diagnose and manage Philadelphia chromosome-like acute lymphoblastic leukemia

Frisch

Ofran

2019

Haematologica

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Advances in our understanding of mechanisms of leukemogenesis and driver mutations in acute lymphoblastic leukemia (ALL) lead to a more precise and informative sub-classification, mainly of B-cell ALL. In parallel, in recent years, novel agents have been approved for the therapy of B-cell ALL, and many others are in active clinical research. Among the newly recognized disease subtypes, Philadelphia-chromosome-like ALL is the most heterogeneous and thus, diagnostically challenging. Given that this subtype of B-cell ALL is associated with a poorer prognosis, improvement of available therapeutic approaches and protocols is a burning issue. Herein, we summarize, in a clinically relevant manner, up-to-date information regarding diagnostic strategies developed for the identification of patients with Philadelphia-chromosome-like ALL. Common therapeutic dilemmas, presented as several case scenarios, are also discussed. It is currently acceptable that patients with B-cell ALL, treated with an aim of cure, irrespective of their age, be evaluated for a Philadelphia-chromosome-like signature as early as possible. Following Philadelphia-chromosome-like recognition, a higher risk of resistance or relapse must be realized and treatment should be modified based on the patient’s specific genetic driver and clinical features. However, while active targeted therapeutic options are limited, there is much more to do than just prescribe a matched inhibitor to the identified mutated driver genes. In this review, we present a comprehensive evidence-based approach to the diagnosis and management of Philadelphia-chromosome-like ALL at different time-points during the disease course.

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Idarubicin-Intensified Hematopoietic Cell Transplantation Improves Relapse and Survival of High-Risk Acute Leukemia Patients with Minimal Residual Disease

Cited by 8 publications

References 36 publications

Influence of graft composition in patients with hematological malignancies undergoing ATG-based haploidentical stem cell transplantation

Influence of graft composition in patients with hematological malignancies undergoing ATG-based haploidentical stem cell transplantation

Decitabine-Intensified Modified Busulfan/Cyclophosphamide Conditioning Regimen Improves Survival in Acute Myeloid Leukemia Patients Undergoing Related Donor Hematopoietic Stem Cell Transplantation: A Propensity Score Matched Analysis

How I diagnose and manage Philadelphia chromosome-like acute lymphoblastic leukemia

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