Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct 30;36(5):530-544.
doi: 10.21147/j.issn.1000-9604.2024.05.06.

Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs. identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia

Yuewen Wang  1 , Xianli Gao  2 , Ting Wang  1 , Xiaohui Zhang  1 , Lanping Xu  1 , Yu Wang  1 , Chenhua Yan  1 , Huan Chen  1 , Yuhong Chen  1 , Wei Han  1 , Fengrong Wang  1 , Jingzhi Wang  1 , Xia Yan  1 , Xiaodong Mo  1 , Xiaojun Huang  1   3
Affiliations

Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs. identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia

Yuewen Wang et al. Chin J Cancer Res. .

Abstract

Objective: We aimed to compare the quality-adjusted time without symptoms or toxicity (Q-TWiST) in acute myeloid leukemia (AML) patients who received haploidentical-related donor (HID) and identical sibling donor (ISD) hematopoietic stem cell transplantation (HSCT).

Methods: Five clinical health states were defined: toxicity (TOX), acute graft-versus-host disease (GVHD), chronic GVHD (cGVHD), time without symptoms and toxicity (TWiST) and relapse (REL). The equation used in this study was as follows: Q-TWiST=UTOX × TOX + UTWiST × TWiST + UREL × REL + UaGVHD × aGVHD + UcGVHD × cGVHD.

Results: A total of 239 AML patients were enrolled. We established a mathematical model, i.e., Q-TWiST HID HSCT > Q-TWiST ISD HSCT, to explore the range of utility coefficients satisfying the inequality. Based on the raw data, the utility coefficient is equivalent to the following inequality: [Formula: see text][Formula: see text]. The model showed that when [Formula: see text], [Formula: see text], and [Formula: see text] were within the range of 0-1, as well as when [Formula: see text] was within the range of 0-0.569, the inequality Q-TWiST HID HSCT > Q-TWiST ISD HSCT was valid. According to the results of the ChiCTR1800016972 study, the median coefficients of TOX, acute GVHD (aGVHD), and cGVHD were 0.56 (0.41-0.76), 0.56 (0.47-0.72), and 0.54 (0.37-0.79), respectively. We selected a series of specific examples of the coefficients, i.e., [Formula: see text]=0.5, [Formula: see text]=0.05, [Formula: see text]=0.5, and [Formula: see text]=0.5. The Q-TWiST values of ISD and HID HSCT were 896 and 900 d, respectively (P=0.470).

Conclusions: We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.

Keywords: Quality-adjusted time without symptoms or toxicity; acute myeloid leukemia; allogeneic hematopoietic stem cell transplantation; haploidentical.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Three-year probability of OS (P=0.90) (A), RFS (P=0.38) (B), relapse (P=0.59) (C) and NRM (P=0.37) (D) after allo-HSCT in ISD and HID HSCT groups. OS, overall survival; RFS, relapse-free survival; NRM, non-relapse mortality; allo-HSCT, allogeneic hematopoietic stem cell transplantation; ISD, identical sibling donor; HID, haploidentical-related donor; HSCT, hematopoietic stem cell transplantation.
Figure 2
Figure 2
Details of QoL based on FACT-BMT questionnaire in AML patients. QoL of 1 month (A), 3 months (B), 6 months (C) and 12 months (D) after HSCT. QoL, quality of life; FACT-BMT, Functional Assessment of Cancer Treatment-Bone Marrow Transplant; AML, acute myeloid leukemia; ISDT, identical sibling donor transplantation; HIDT, haploidentical-related donor transplantation.
Figure 3
Figure 3
Demonstration of mathematical modeling of Q-TWiST. (A) Schematic diagram of values of parameters (UTOX, UREL), with different straight lines corresponding to different θ values. The horizontal axis represents value of UTOX, and the longitudinal axis represents value of UREL; (B) Schematic diagram of values of parameters (UaGVHD, UcGVHD). The horizontal axis represents value of UaGVHD, and the longitudinal axis represents value of UcGVHD; (C) Schematic diagram of values of parameters (UTOX, UREL) when (UaGVHD, UcGVHD) was given. The horizontal axis represents value of UTOX, and the longitudinal axis represents value of UREL; (D) Violin plot of Q-TWiST under ISD and HID HSCT. Q-TWiST, quality-adjusted time without symptoms or toxicity; TOX, toxicity; REL, relapse; aGVHD, acute graft-versus-host disease; cGVHD, chronic graft-versus-host disease; ISD, identical sibling donor; HID, haploidentical-related donor; HSCT, hematopoietic stem cell transplantation.
Figure 4
Figure 4
Survival plots for TOX, OS, RFS and GRFS under ISD HSCT (A) and HID HSCT (B) within the full data. Areas between the curves are TOX, REL, and TWiST, respectively, for ISD and HID HSCT. TOX, toxicity; OS, overall survival; RFS, relapse-free survival; GRFS, GVHD-free/relapse-free survival; ISD, identical sibling donor; HID, haploidentical-related donor; HSCT, hematopoietic stem cell transplantation; REL, relapse; TWiST, time without symptoms or toxicity.
Figure 5
Figure 5
Violin plot of TWiST and Q-TWiST in subgroup patients. Violin plot of TWiST in high-risk and intermediate-risk patients (A) and AYA and older adult patients (C) under ISD and HID HSCT. Violin plot of Q-TWiST in high-risk and intermediate-risk patients (B) and AYA and older adult patients (D) under ISD and HID HSCT. TWiST, time without symptoms or toxicity; Q-TWiST, quality-adjusted time without symptoms or toxicity; AYA, adolescents and young adults; ISD, identical sibling donor; HID, haploidentical-related donor; HSCT, hematopoietic stem cell transplantation.
Figure 6
Figure 6
Survival curves of TOX, OS, RFS and GRFS in high-risk patients in ISD HSCT (A) and HID HSCT (B), in intermediate-risk patients in ISD HSCT (C) and HID HSCT (D), in AYA patients in ISD HSCT (E) and HID HSCT (F) and in older adult patients in ISD HSCT (G) and in HID HSCT (H). TOX, toxicity; OS, overall survival; RFS, relapse-free survival; GRFS, GVHD-free/relapse-free survival; ISD, identical sibling donor; HID, haploidentical-related donor; HSCT, hematopoietic stem cell transplantation; AYA, adolescents and young adults; CR, complete remission; HLA, human leukocyte antigen; GVHD, graft-versus-host disease.
Figure S1
Figure S1
Three-year probability of OS (P=0.33) (A), RFS (P=0.38) (B), relapse (P=0.59) (C) and NRM (P=0.55) (D) after allo-HSCT in high-risk patients under ISD and HID HSCT. OS, overall survival; RFS, relapse-free survival; NRM, non-relapse mortality; allo-HSCT, allogeneic hematopoietic stem cell transplantation; ISD, identical sibling donor; HID, haploidentical-related donor; HSCT, hematopoietic stem cell transplantation.
Figure S2
Figure S2
Three-year probability of OS (P=0.41) (A), RFS (P=0.29) (B), relapse (P=0.69) (C) and NRM (P=0.01) (D) after allo-HSCT in intermediate-risk patients under ISD and HID HSCT. OS, overall survival; RFS, relapse-free survival; NRM, non-relapse mortality; allo-HSCT, allogeneic hematopoietic stem cell transplantation; ISD, identical sibling donor; HID, haploidentical-related donor; HSCT, hematopoietic stem cell transplantation.
Figure S3
Figure S3
Three-year probability of OS (P=0.61) (A), RFS (P=0.94) (B), relapse (P=0.53) (C) and NRM (P=0.22) (D) after allo-HSCT in AYA under ISD and HID HSCT. OS, overall survival; RFS, relapse-free survival; NRM, non-relapse mortality; allo-HSCT, allogeneic hematopoietic stem cell transplantation; ISD, identical sibling donor; HID, haploidentical-related donor; HSCT, hematopoietic stem cell transplantation.
Figure S4
Figure S4
Three-year probability of OS (P=0.39) (A), RFS (P=0.48) (B), relapse (P=0.38) (C) and NRM (P=0.98) (D) after allo-HSCT in older adult patients under ISD and HID HSCT. OS, overall survival; RFS, relapse-free survival; NRM, non-relapse mortality; allo-HSCT, allogeneic hematopoietic stem cell transplantation; ISD, identical sibling donor; HID, haploidentical-related donor; HSCT, hematopoietic stem cell transplantation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Lv M, Wang Y, Chang YJ, et al Myeloablative haploidentical transplantation is superior to chemotherapy for patients with intermediate-risk acute myelogenous leukemia in first complete remission. Clin Cancer Res. 2019;25:1737–48. doi: 10.1158/1078-0432.CCR-18-1637. - DOI - PubMed
    1. Wang L, Zhang C, Fan S, et al Treatment options for adult intermediate-risk AML patients in CR1: Allo-HSCT or chemotherapy. Innovation (Camb) 2023;4:100461. doi: 10.1016/j.xinn.2023.100461. - DOI - PMC - PubMed
    1. Chang YJ, Luznik L, Fuchs EJ, et al How do we choose the best donor for T-cell-replete, HLA-haploidentical transplantation. J Hematol Oncol. 2016;9:35. doi: 10.1186/s13045-016-0265-2. - DOI - PMC - PubMed
    1. Shouval R, Fein JA, Labopin M, et al Outcomes of allogeneic haematopoietic stem cell transplantation from HLA-matched and alternative donors: a European Society for Blood and Marrow Transplantation registry retrospective analysis. Lancet Haematol. 2019;6:e573–84. doi: 10.1016/S2352-3026(19)30158-9. - DOI - PubMed
    1. Wang Y, Liu DH, Liu KY, et al Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia: nine years of experience at a single center. Cancer. 2013;119:978–85. doi: 10.1002/cncr.27761. - DOI - PubMed

LinkOut - more resources