Impact of Additional Cytogenetic Aberrations at Diagnosis on Prognosis of Adults Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation：A Retrospective Analysis

Impact of Additional Cytogenetic Aberrations at Diagnosis on Prognosis of Adults Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation：A Retrospective Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Additional Cytogenetic Aberrations at Diagnosis on Prognosis of Adults Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation：A Retrospective Analysis Jing zheng, Yanmin Zhao, Yi Luo, Jian Yu, Xiaoyu Lai, Jinuo Wang, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4223756/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Jul, 2024 Read the published version in Annals of Hematology → Version 1 posted 7 You are reading this latest preprint version Abstract Additional chromosomal abnormalities(ACAs) at diagnosis are associated with inferior prognosis in chronic myelogenous leukemia. However, the prognostic significance of ACAs in adult patients with Philadelphia Chromosome Positive acute lymphoblastic leukemia (Ph + ALL) receiving TKI-targeted drugs and allogeneic hematopoietic stem cell transplantation(HSCT) is unknown. One hundred eighty-eight adult patients with Ph + ALL were retrospectively analysed, evaluating the effect of ACAs on outcomes of transplantation. One hundred thirty-six patients were included in the study. ACAs are observed in 60 cases (44%). The major-route ACAs are detected in more than 5% are as follows: +der(22), +der(9), + 8, -7 and complex karyotype. The median follow-up was 26.4 months. In the subgroup analyses of major route ACAs, three-year cumulative incidence of relapse (CIR) and progression-free survival(PFS) are statistically significant in + 8[66.7% vs.23.7%, P = 0.024; 77.8% vs. 23.7%, P = 0.0087], -7[53.8% vs. 23.7%, P = 0.035%; 61.5% vs. 32.9%, P = 0.033], and complex karyotypes[42.9% vs. 23.7%, P = 0.027; 47.6% vs. 23.7%] compared with isolated t(9;22). Additionally, the 3-year CIR for Ph + ALL with + der(22) is 44% vs. 23.7% for standard Ph + ALL(P = 0.045). The 3-year overall survival (OS) in the − 7 group is 46.5%, which is statistically significant compared with the other groups(P = 0.001). In multivariate analyses, three years CIR and PFS are statistically significant in + der(22), + 8, -7 and complex karyotype compared with standard Ph + ALL(P < 0.05). More importantly, Ph + ALL with − 7 was negatively associated with the rate of 3-year OS(P = 0.012). Partial ACAs at diagnosis appear to have a significant prognostic impact on transplantation outcomes in patients with Ph + ALL. Philadelphia chromosome Acute lymphoblastic leukaemia Additional chromosomal abnormalities Hematopoietic stem cell transplantation Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph + ALL) accounts for approximately 25–30% of young patients with ALL and 40–50% of elderly patients with ALL. It is characterised by the translocation of chromosomes 9 and 22 and the formation of BCR/ABL1 fusion genes[ 1 – 2 ]. In the last 20 years, tyrosine kinase inhibitors (TKIs) and allogeneic haematopoietic stem-cell transplantation(HSCT) have significantly improved outcomes of Ph + ALL[ 3 – 4 ]. With the continuous improvement of polymerase chain reaction (RT-PCR) and next-generation sequencing technology, the BCR/ABL1 gene as the primary monitoring indicator of minimal residual disease (MRD) plays an essential role in diagnosis, prognosis and treatment of Ph + ALL[ 5 – 6 ]. Nonetheless, the role of cytogenetics is irreplaceable in adults with Ph + ALL[ 7 – 8 ]. The presence of additional cytogenetic aberrations (ACAs) has been reported in approximately 40–80% of patients with Ph + ALL[ 9 – 12 ]. Several previous studies have investigated the prognostic role of ACA in Ph + ALL, but there was no uniform conclusion[ 10 , 12 – 13 ]. The study aims to investigate the prognosis significance of common ACAs for Ph + ALL patients who had received HSCT in the TKI era. Methods Data Source and Patient Selection Clinical and cytogenetic data of 136 of 188 patients with Ph + ALL undergoing allogeneic hematopoietic cell transplantation were(HSCT) obtained from Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine. This study includes consecutive adult patients with Ph + ALL who had received allogenic HSCT between January 2015 and May 2023. Written informed consent was obtained from all patients before they enrolled in the study. Patient characteristics and Cytogenetic analyses Baseline characteristics are shown in Table 1 . Chromosomal analyses of G-banded bone marrow (136 samples) were performed in cytogenetics laboratories of the First Affiliated Hospital of Zhejiang University School of Medicine according to the International System for Human Cytogenetic Nomenclature (ISCN)[ 14 ]. Specimens were obtained at diagnosis from all patients. Major-route of ACAs is defined as having an extra chromosome frequency of more than 5%, including + der(22), +der(9), + 8, -7, hyperdiploid and complex karyotype. ACAs that were rarely observed in Ph + ALL, such as t(1;5), t(8;9), t(v;22), +der(1), +der(2), +der(5), +der(14), +der(16), +X, + 5 and hypodiploid, were designated minor-route ACAs. Treatment Of the 136 participants, all patients received induction therapy, consolidation therapy and allogeneic HSCT. In addition, all were treated with Tyrosine kinase inhibitors (TKI) prior to transplantation (see Table 1 ). Most patients received TKI maintenance treatment after HSCT. Patients who relapse after transplantation primarily received the following treatments: higher level TKI targeted therapy, donor lymphocyte infusion, secondary transplantation, chimeric antigen receptor T-Cell immunotherapy, chemotherapy, blinatumomab and inotuzumab ozogamicin. Most of the patients with central nervous system leukemia after transplantation received intrathecal injections and whole-brain radiotherapy. Table 1 Patient and Disease Characteristics Patient and disease characteristics Single Ph+ALL （ n=76) Ph+ALL plus ACA(n=60) P Age(y) median(range) 36.6±12.1 40.7±12.1 >0.05 Male,n(%) 42(55%) 35(58%) >0.05 BCR-ABL p190 transcript,n(%) 53(70%) 46(77%) >0.05 BCR-ABL p210 transcript,n(%) 23(30%) 14(23%) >0.05 IKZF1 Mutation 11(14%) 8(13%) >0.05 TKI induction Imatinib Dasatinib/Flumatinib Ponatinib/Overembatinib 31(41%) 31(41%) 11(14%) 27(25%) 29(48%) 2(3%) >0.05 MRD Status Pre-HCT MRD positive MRD negative CR1 CR2 or beyond Non-remission 30(39%) 46(61%) 66(87%) 8(11%) 2(3%) 26(43%) 33(55%) 54(90%) 6(10%) 0(0%) >0.05 Allo-HCT MA-HCT RIC-HCT 73(96%) 3(4%) 52(87%) 8(13%) >0.05 Statistical analysis The primary endpoints for outcome analyses were 3-year cumulative incidence of relapse (CIR), progression-free survival(PFS), overall survival (OS) and non-relapse mortality(NRM). OS is defined as the time from the date of transplant to death. CIR is measured from the date of transplant until the beginning of relapse. PFS is defined as the time from transplant until the beginning of relapse or death from any cause, whichever occurs first. Probabilities of PFS and OS were calculated using the Kaplan-Meier method and compared with the log-rank test. CIR is calculated by using Gray's method and the competing-risk cumulative function considering NRM as a competing risk. Baseline characteristics were summarised by using the median for continuous variables and percentages for categorical variables, which were compared using a two-sided t-test. To evaluate the influence of chromosome subsets on relapse, the Fine and Gray model was used for multivariate analysis. All analyses were performed using R(version 4.3.2). P-values < 0.05 are considered significant. Results Chromosome distribution The following conditions are excluded: 1. Thirteen patients are under the age of 18 2. Thirty-four patients had no cytogenetic information at diagnosis 3. One patient had a history of chronic granulocytic leukemia 4. Four patients were followed for less than 90 days. Finally, 136 patients were eligible for the study, with 76(56%) having the standard translocation t(9;22)(q34;q11) only, and 60 (44%) showing ACAs. Fifty patients (37%) were found to have major ACAs, and ten patients(7%) had minor ACAs. In patients with major-route ACAs, 25 patients(18%) were found to have + der(22), with 24 patients(96%) exhibiting complex karyotypes. Concurrent chromosomal abnormalities included + der(9), + 8 and − 7. +der(9) is observed in 9 patients(6.6%) and all were complex karyotype. Chromosomal abnormalities that can co-exist with + der(9) included + der(22) and − 7. Moreover, while + der(9) and + 8 were not found together. +8 is observed in 9 patients(6.6%) and all were complex karyotype. Chromosomal abnormalities that can co-exist with + 8 included + der(22) and − 7. -7 is observed in 13 patients(9.6%), of which 8 patients(62%) were complex karyotypes. Other ACAs, such as + der(22), +der(9) and + 8, were also detected. In addition, -7 is the only ACA in 5 cases. A complex karyotype is defined as having at least two abnormalities other than t(9;22)(q34;q11). In the current study, complex karyotypes were observed in 42 patients (31%) and consisted primarily of + der(22), +der(9), + 8, and − 7. Minor-route ACAs are defined as having an extra chromosome frequency of less than 5% and were found in 19 patients(14%). Prognostic significance of ACAs The median follow-up was 26.4 months. The three-year OS proportion and PFS of patients with isolated t(9;22) and those with ACAs are not significant (76.3% VS 81.7%, P = 0.79;32.9% VS 38.3%, P = 0.19). The three-year NRM of patients with isolated t(9;22) and those with ACAs is also not significant (9.2% VS 3.3%, P = 0.22). The three-year CIR is higher in patients with ACAs compared with patients with standard t(9;22)(q34;q11) (36.7% VS 19.7%, P = 0.04). The three-year OS proportion and CIR of patients with major ACAs are 78% and 32%, respectively. The three-year OS proportion and CIR of patients with minor ACAs are 100% and 10%, respectively. Subsequently, the three-year OS proportion and CIR are not statistically different in patients with major ACAs compared with patients with minor ACAs(P = 0.1; P = 0.07). At the same time, the three-year NRM proportion and PFS of patients with major ACAs and those with minor ACAs are not significantly different (3.3% VS 0%, P = 0.52;38.3% VS 10%, P = 0.054). To further understand the prognostic value of ACAs for ph + ALL undergoing HSCT, the influence of some chromosome subsets was analysed, such as + der(22), +der(9), + 8, -7 and complex karyotype. In the predictive analysis of + der(22) on HSCT outcomes, the group was divided into three subgroups: isolated Ph chromosome(Ph + ALL,n = 76), Ph + ALL plus + der(22)(n = 25), and Ph + ALL plus other ACAs(no + der(22))(n = 35). There is no significant difference between Ph + ALL plus + der(22), Ph + ALL and Ph + ALL plus other ACAs(no + der(22) regarding the 3-year probability of survival (80% vs. 77.6% vs.82.9%; P = 0.78), PFS(48% vs. 32.9% vs.28.6%;P = 0.083), NRM(4% vs. 9.2% vs.2.9%; P = 0.469). Nevertheless, the 3-year CIR for Ph + ALL plus + der(22) is 44% vs. 23.7% for Ph + ALL vs. 31.4% for Ph + ALL plus other ACAs(no + der(22))(P = 0.045)(Fig. 1 ). The chromosomal abnormality − 7 is the common ACA examined regarding its prognostic significance on HSCT outcomes by splitting the Philadelphia chromosome-positive acute lymphoblastic leukemia into three subgroups: isolated Ph chromosome(Ph + ALL,n = 76), Ph + ALL plus − 7(n = 13), and Ph + ALL plus other ACAs(no -7)(n = 47). Both the three-year OS and PFS were inferior in patients with Ph + ALL plus − 7 compared to Ph + ALL and Ph + ALL plus other ACAs(no -7)(Fig. 2 ). At the same time, the three-year CIR of patients with Ph + ALL plus − 7 and the other two groups were also statistically significant(Figure 2 ). However, the three-year NRM of patients with these three groups is not significantly different (Fig. 2 ). Subsequently, the 3-year proportion of OS for Ph + ALL plus − 7 is 46.5% vs 77.6% for Ph + ALL vs. 91.5% for Ph + ALL plus other ACAs (no -7)(P = 0.001). The 3-year PFS for Ph + ALL plus − 7 is 61.5% vs. 32.9% for Ph + ALL vs. 31.9% for Ph + ALL plus other ACAs(no -7)(P = 0.033). In addition, the 3-year CIR for Ph + ALL plus − 7 is 53.8% vs. 23.7% for Ph + ALL vs. 31.9% for Ph + ALL plus other ACAs(no -7)(P = 0.035). Complex karyotype is the most frequent ACA, mainly composed of + der(22), +der(9), + 8 and − 7. In a prognostic analysis of complex karyotype on HSCT outcomes, the group was divided into three subgroups: isolated Ph chromosome(Ph + ALL,n = 76), Ph + ALL plus ≧ 2 ACAs(n = 42), and Ph + ALL plus 1 ACA(n = 18). There is no statistical difference between Ph + ALL plus ≧ 2 ACAs, Ph + ALL and Ph + ALL plus 1 ACA regarding the 3-year probability of survival (78.6% vs. 77.6% vs. 94.4%; P = 0.28) and NRM(4.8% vs. 9.2% vs. 0%; P = 0.368). However, the 3-year PFS for Ph + ALL plus ≧ 2 ACAs is 47.6% vs. 23.7% for Ph + ALL vs. 22.2% for Ph + ALL plus 1 ACA(P = 0.033) and the 3-year CIR for Ph + ALL plus ≧ 2 ACAs is 42.9% vs. 23.7% for Ph + ALL vs. 22.2% for Ph + ALL plus 1 ACA(P = 0.027(Fig. 3 ). + 8 is also the common ACA. For prognostic analysis of + 8, the group was divided into three subgroups: isolated Ph chromosome(Ph + ALL,n = 76), Ph + ALL plus + 8(n = 9), and Ph + ALL plus other ACAs(no + 8)(n = 51). Although the OS and NRM of Ph + ALL plus + 8 are worse than the other two groups, there is no statistical difference among Ph + ALL plus + der(+ 8), Ph + ALL and Ph + ALL plus other ACAs(no + 8) regarding the 3-year proportion of OS (55.5% vs. 77.6% vs. 86.3%; P = 0.17) and NRM(11.1% vs. 9.2% vs. 2%; P = 0.3). However, the 3-year PFS for Ph + ALL plus + der(+ 8) is 77.8% vs. 23.7% for Ph + ALL vs. 33.3% for Ph + ALL plus other ACAs(no + 8)(P = 0.0087) and the 3-year CIR for Ph + ALL plus + der(+ 8) is 66.7% vs. 23.7% for Ph + ALL vs. 31.4% for Ph + ALL plus other ACAs(no + 8)(P = 0.024) (Fig. 4 ) . The prognostic analysis of + der(9) on HSCT outcomes shows no significant difference between Ph + ALL plus + der(9), Ph + ALL and Ph + ALL plus other ACAs(no + der(9)) regarding the 3-year rate of OS(100% vs. 77.6% vs.78.4%; P = 0.35), CIR(33.3% vs. 23.7% vs. 37.3%; P = 0.35), PFS(33.3% vs. 32.9% vs. 41.2%;P = 0.3), and NRM(0% vs. 9.2% vs. 3.9%; P = 0.123). These statistically significant subgroups were included in a multivariate analysis to explore the effect of ACAs on HSCT outcomes. In the multivariate analysis for IR, regarding + der(22), + 8, -7, and complex ACAs, the factors that had a negative impact are + der(22) (P = 0.014), + 8(P = 0.005), -7(P = 0.009), and complex ACAs( ≧ 2 ACAs) (P = 0.016)(Table 3). The factors with a poor prognosis are + der(22) (P = 0.035), + 8(P = 0.005), -7(P = 0.011) and complex ACAs( ≧ 2 ACAs)(P = 0.022) in multivariate analysis for PFS(Table 3). The presence of ACAs at diagnosis is not associated with the risk of NRM in the multivariate analyses(P > 0.05)(Table 3). In multivariate analysis for OS, considering + der(22), + 8, -7 and complex ACAs as variables, the only factor that retains statistical significance is -7(P = 0.012)(Table 2 ). Table 2 Influence of additional chromosome abnormalities on Transplantation Outcomes in Multivariate Analyses Group n CIR PFS NRM OS SHR(95% CI) P HR(95% CI) P SHR(95% CI) P HR(95% CI) P ph alone* 76 +der(22) +der(22) ACAs(no + der(22) 25 35 2.54(1.21–5.32) 1.53(0.72–3.22) 0.014 0.270 2.12(1.05–4.27) 1.04(0.49–2.18) 0.035 0.930 0.48(0.06–3.89) 0.32(0.04–2.63) 0.490 0.290 1.17(0.44–3.12) 0.76(0.30–1.92) 0.750 0.560 + 8 +8 ACAs(no + 8) 9 51 3.64(1.48-9.00) 1.60(0.83–3.11) 0.005 0.160 3.59(1.49–8.70) 1.23(0.67–2.28) 0.005 0.500 1.22(0.14–10.7) 0.23(0.03–1.84) 0.860 0.160 2.11(0.71–6.24) 0.69(0.29–1.62) 0.180 0.380 -7 -7 ACAs(no -7) 13 47 3.15(1.34–7.43) 1.62(0.83–3.20) 0.009 0.160 2.89(1.27–6.56) 1.18(0.62–2.25) 0.011 0.610 0.87(0.10–7.40) 0.25(0.03–1.99) 0.900 0.190 3.02(1.28–7.13) 0.41(0.14–1.21) 0.012 0.110 Complex ACAs $ 1 ACA ≧ 2 ACAs 18 42 1.04(0.35–3.15) 2.37(1.24–4.51) 0.940 0.009 0.72(0.24–2.15) 1.99(1.10–3.58) 0.560 0.022 0.87(0.10–7.40) 0.53(0.15–2.45) 0.900 0.480 0.24(0.03–1.74) 1.12(0.50–2.50) 0.160 0.780 *: Ph alone was used as a control group. $: Complex karyotype is defined as the presence of at least two chromosome abnormalities other than t(9;22)(q34;q11). Discussion Cytogenetic studies have shown that some haematologic malignancies with ACAs at diagnosis had a poor prognosis[ 8 , 15 ]. At present, the prognostic value of ACAs in Ph + ALL has not been determined in the era of TKI and HSCT, which may be attributed to the differences in the number of patients, racial population, and antineoplastic protocols. In view of this, this study details the prognosis effect of different ACAs subgroups on Ph + ALL patients receiving TKI-targeted drugs and HSCT. The analysis shows that the incidence of ACA in Ph + ALL is 44%, and the common ACAs include complex karyotypes, +der(22), -7, + 8 and + der(9), consistent with previous studies[ 9 – 10 , 12 , 16 ]. Johansson defines ACAs that occur more than 5% as major-route ACAs[ 17 ]. Other ACAs that are rare, such as t(1;5), t(8;9), +der(1), and + der(5), were designated minor-route ACAs. In the pre-TKI era, a prospective study analysed the prognoses of ACAs in adults with Ph + ALL and included cytogenetic data from 111 newly diagnosed adults with Ph + ALL[ 10 ]. Seventy-five patients (68%) had ACAs. The results showed that − 7 is related to the lower CR rate, and the complex ACAs are related to higher CR rates. At the same time, +der (22) was associated with the high accumulation of recurrence rate. To further understand the prognosis of ACA in the TKI era on adult Ph + ALL, a retrospective study evaluated 152 patients with Ph + ALL patients who received TKI combined chemotherapy[ 12 ]. The research showed that a 5-year survival rate and non-recurrence survival probability were lower in Ph + ALL patients who had + der (22) with or without − 9/9p. The current study analysed the effects of major ACAs and minor ACAs on the prognosis of Ph + ALL. Patients with major ACAs or minor ACs have a prognosis not significantly different from those with standard t(9,22), consistent with the outcomes reported by Mitelman[ 18 ]. To further explore the prognostic value of ACAs for Ph + ALL undergoing TKI-targeted drugs and HSCT, the influence of major ACAs, such as + der(22), +der(9), + 8, -7, hyperdiploid, and complex karyotypes were analysed. A complex karyotype is the most frequent ACA in this cohort, which mainly consisted of + der(22), +der(9), + 8, and − 7. Previous studies have shown that chronic myelogenous leukemia with complex karyotypes has poorer survival and higher rates of disease progression[ 19 – 20 ]. Additionally, the complex karyotype is associated with a poor prognosis in Ph-negative ALL[ 21 – 22 ]. However, Akahoshi et al. emphasised that complex karyotypes had no prognostic significance in Ph + ALL[ 23 ]. The current study shows inferior PFS and higher CIR in patients with Ph + ALL with complex karyotypes compared to those with isolated t(9;22) and Ph + ALL with a secondary ACA, while patients with Ph + ALL with complex karyotypes did not have a positive prognostic effect on OS and NRM. Such results may be due to more aggressive treatments in patients with progressive or recurrent disease following HSCT. Patients in the current study with + der(22) have a significantly higher CIR and shorter PFS compared to the other groups. Nevertheless, there is no difference in their survival and NRM. Some previous studies have confirmed that + der(22) is associated with an unfavourable prognosis and shorter OS[ 12 , 24 ]. Gorre et al. and Hochhaus et al. showed in their studies of chronic myelogenous leukemia that + der(22) may be resistant to imatinib[ 25 – 26 ]. Therefore, targeting drugs of the second-generation and third-generation TKI may overcome the poor prognosis caused by + der(22), which is consistent with results in the current study. The chromosomal abnormality − 7 is the common ACA in the current cohort, as previously reported[ 10 , 12 , 13 , 24 ]. The analysis shows higher CIR and inferior PFS and OS in patients with Ph + ALL with − 7 compared to the sole t(9;22) group and the ACA group without monosomy 7. The prognostic value of monosomy 7 in haematological malignancy has been widely discussed. Several studies on CML have concluded that − 7 or 7q-, particularly in Philadelphia chromosome-negative myeloid neoplasms, is strongly associated with poor prognosis[ 27 – 28 ]. In addition, some studies have demonstrated that − 7 or 7q- is inextricably linked to an inferior survival and prognosis in Ph + ALL, consistent with the main findings of the current study[ 29 – 30 ]. However, several other studies did not show an association between − 7 and poor outcomes[ 13 , 23 ]. Such a different conclusion may be due to the number of enrolled cases, study methods and treatment regimen. Therefore, a further large-scale study was undertaken to analyse the correlation between − 7 and prognosis in Ph + ALL and to explore the effects of TKI targeting drugs and HSCT on -7. The + 8 abnormal chromosome is also a common ACA. The current study shows that patients with + 8 have a higher CIR and shorter PFS compared to the other groups. Although Hehlmann et al. have demonstrated that + 8 is associated with an inferior OS in CML [19] , another study did not[ 27 ]. In Ph + ALL, Akahoshi et al. concluded that + 8 was closely associated with a high CIR, which concurs with the results of the current study. Conclusion In conclusion, ACAs at diagnosis, especially in patients with − 7, + 8, +der(22) and complex karyotype, appear to have a significant prognostic impact on transplantation outcomes in patients with Ph + ALL undergoing HSCT and TKI. Therefore, we may take more aggressive treatment such as second or third-generation TKI drug maintenance after transplantation and earlier donor lymphocyte infusion to improve the prognosis of patients with Ph + ALL with these high-risk chromosome subsets. Finally, more research is needed to explore further the effects of different TKI drugs on the prognosis of Ph + ALL with ACAs at diagnosis or treatment process. Declarations Acknowledgements Not applicable. Author contributions JZ writed the manuscript; JY and JS have made great contribution to date collection; YZ, YZ, WW, ZC and YL supported the project design and literature review; HH and JS are corresponding authors and they have made significant contribution to the manuscript. Funding This study was supported by the National Natural Science Foundation of China (grant number:82070179) and Yichang City Medical Health Project(A23-1-028). Data availability statement The datesets will be maded available by the first author. Ethics statements Patient consent for publication. Not applicable. Competing interests The authors declare no competing interests. Authors and Affiliations Jing Zheng 1,2 · Yanmin Zhao 1 · Yi Luo 1 · Jian Yu 1 · Xiaoyu Lai 1 · Jinuo Wang 1 · Yishan Ye 1 · Li zhen Liu 1 · Huarui Fu 1 · Luxin Yang 1 · Yibo Wu 1 · Jie Sun 1 · Weiyan Zheng 1 · Hejing Song 1 · Yi Zhao 1 · Wenjun Wu 1 · Zhen Cai 1 · Guoqing Wei 1 · He Huang 1,* · Jimin Shi 1,* 1Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China. 2Departments of Hematology, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People’s Hospital, Yichang 443000, China. * Corresponding to. Professor Jimin Shi, Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, China, [email protected] . Professor He Huang, Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, China, [email protected] . JZ contributed as first author to this study. References Chiaretti S, Vitale A, Cazzaniga G et al（2013）Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts. Haematologica 98: 1702-1710. Jabbour E, Pui C-H, Kantarjian H（2018）Progress and innovations in the management of adult acute lymphoblastic leukemia. JAMA Oncol 4:1413-1420. Soverini S, Bassan R, Lion T（2019）Treatment and monitoring of Philadelphia chromosome-positive leukemia patients: recent advances and remaining challenges. J Hematol Oncol 12:39. Short NJ, Kantarjian H, Jabbour E（2012）Optimizing the treatment of acute lymphoblastic leukemia in younger and older adults: new drugs and evolving paradigms. Leukemia 35:3044–58. Soverini S, Albano F, Bassan R et al（2020）Next-generation sequencing for BCR-ABL1 kinase domain mutations in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A position paper. Cancer Med 9:2960-2970. Nishiwaki S, Kim JH, Ito M et al（2020）Multi-Lineage BCR-ABL Expression in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Is Associated With Improved Prognosis but No Specific Molecular Features. Front Oncol 10:586567. Arana Trejo R M, Del C M A, Alcalá Carmona L G et al（2016）Chromosomal abnormalities in patients with haematologic malignancies in the general hospital of Mexico. Revista Médica Del Hospital General De México 80:87-91. Awan UA, Farooq N, Sarwar A et al（2021）Cytogenetic abnormalities in patients with hematological malignancies in Lahore city, Pakistan. Braz J Biol 83: e249911. Dombret H, Gabert J, Boiron JM et al（2002）Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia--results of the prospective multicenter LALA-94 trial. Blood 100:2357–2366. Wetzler M, Dodge RK, Mrozek K et al（2004）Additional cytogenetic abnormalities in adults with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a study of the Cancer and Leukaemia Group B. Br J Haematol 124:275–288. Schultz KR, Carroll A, Heerema NA et al（2014）Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children’s Oncology Group study AALL0031. Leukemia 28:1467–1471. Short NJ, Kantarjian HM, Sasaki K et al（2017）Poor outcomes associated with +der(22)t(9;22) and -9/9p in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia receiving chemotherapy plus a tyrosine kinase inhibitor. Am J Hematol 92:238-243. Aldoss I, Stiller T, Cao TM et al（2015）Impact of Additional Cytogenetic Abnormalities in Adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 21:1326-9. Gonzalez Garcia JR, Meza-Espinoza JP（2006）Use of the International System for Human Cytogenetic Nomenclature (ISCN). Blood 108:3952-3. Malakzai HA, Rahmani S, Haidary AM et al（2020）Complex cytogenetic abnormalities in chronic myeloid leukemia resulting in early progression to blast crisis: a case report. J Med Case Rep 14:231. Ansari S, Verma M（2023）Control of Ph+ and additional chromosomal abnormalities in chronic myeloid leukemia by tyrosine kinase inhibitors. Med Oncol 40: 237. Johansson B, Fioretos T, Mitelman F（2002）Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol 107 :76-94. Mitelman F, Levan G, Nilsson PG et al(1976)Non-random karyotypic evolution in chronic myeloid leukemia. Int J Cancer 18:24-30. Hehlmann R, Voskanyan A, Lauseker M et al(2020)High-risk additional chromosomal abnormalities at low blast counts herald death by CML. Leukemia 34(8): 2074-2086. Bonifacio M, Elena C,Mariella D'Adda et al(2020)Do Not Miss Karyotyping at Chronic Myeloid Leukemia Diagnosis: An Italian Campus CML Study on the Role of Complex Variant Translocations. Blood 136:43-44. Issa GC, Kantarjian HM, Yin CC et al(2017) Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome-negative acute lymphoblastic leukemia in the era of minimal residual disease. Cancer 123:459-467. Moorman AV, Harrison CJ, Buck GA et al(2007)Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood 109:3189-3197. Akahoshi Y, Mizuta S, Shimizu H et al(2018)Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation. Additional Cytogenetic Abnormalities with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia on Allogeneic Stem Cell Transplantation in the Tyrosine Kinase Inhibitor Era. Biol Blood Marrow Transplant 24: 2009-2016. Thomas X, Thiebaut A, Olteanu N et al(1998)Philadelphia chromosome positive adult acute lymphoblastic leukemia: characteristics, prognostic factors and treatment outcome. Hematol Cell Ther 40:119-128. Gorre ME, Mohammed M, Ellwood K et al(2001)Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293:876-880. Hochhaus A, Kreil S, Corbin AS et al(2002)Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 16:2190-2196. Wang W, Cortes J E, Tang G et al(2016)Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. Blood 127:2742. Zhao HF, Zhang Y, Zu YL et al(2019）The influence of additive clonal chromosome abnormalities in Ph negative cells on the efficacy of chronic myeloid leukemia. Zhonghua Nei Ke Za Zhi 58:803-807. Heerema NA, Nachman JB, Sather HN et al（2004）Deletion of 7p or monosomy 7 in pediatric acute lymphoblastic leukemia is an adverse prognostic factor: a report from the Children's Cancer Group. Leukemia 18:939-947. Rieder H, Ludwig WD, Gassmann W et al（1996）Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia. Br J Haematol 95:678-691. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 04 Jul, 2024 Read the published version in Annals of Hematology → Version 1 posted Editorial decision: Revision requested 06 May, 2024 Reviews received at journal 05 May, 2024 Reviewers agreed at journal 23 Apr, 2024 Reviewers invited by journal 23 Apr, 2024 Submission checks completed at journal 17 Apr, 2024 Editor assigned by journal 17 Apr, 2024 First submitted to journal 05 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4223756","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":292610104,"identity":"8fde6653-5453-4c1d-800c-9d49f6def760","order_by":0,"name":"Jing zheng","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"zheng","suffix":""},{"id":292610106,"identity":"4873c0a8-6d52-4236-8e13-b51d4385d74d","order_by":1,"name":"Yanmin Zhao","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Yanmin","middleName":"","lastName":"Zhao","suffix":""},{"id":292610111,"identity":"773ca5da-51ff-4cb0-97aa-56fa09418500","order_by":2,"name":"Yi Luo","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Luo","suffix":""},{"id":292610113,"identity":"af8f3c65-c213-448c-94f4-ec3a503e9c28","order_by":3,"name":"Jian Yu","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Jian","middleName":"","lastName":"Yu","suffix":""},{"id":292610115,"identity":"e0564f25-a727-4ec7-85b3-745e4de157e3","order_by":4,"name":"Xiaoyu Lai","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyu","middleName":"","lastName":"Lai","suffix":""},{"id":292610119,"identity":"68fa6761-0b94-4d02-99ed-f6bc07d52aae","order_by":5,"name":"Jinuo Wang","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Jinuo","middleName":"","lastName":"Wang","suffix":""},{"id":292610121,"identity":"30242f36-f473-48e7-81e5-0ccf84e2bc0e","order_by":6,"name":"Yishan Ye","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Yishan","middleName":"","lastName":"Ye","suffix":""},{"id":292610122,"identity":"c7f3d5f0-c84f-45c2-a0dc-7b89d54c2902","order_by":7,"name":"Lizhen Liu","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Lizhen","middleName":"","lastName":"Liu","suffix":""},{"id":292610123,"identity":"f0f5d96f-e52a-4345-b2a4-9ad374dca06d","order_by":8,"name":"Huarui Fu","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Huarui","middleName":"","lastName":"Fu","suffix":""},{"id":292610124,"identity":"c3f11730-c5bb-4193-9477-e2a2cc638c8b","order_by":9,"name":"Luxin Yang","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Luxin","middleName":"","lastName":"Yang","suffix":""},{"id":292610125,"identity":"15655e7d-4f54-4834-816b-f356b611b5f4","order_by":10,"name":"Yibo Wu","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Yibo","middleName":"","lastName":"Wu","suffix":""},{"id":292610126,"identity":"ffb5eaf5-5087-4b2e-80f9-4d87b851f2bb","order_by":11,"name":"Jie sun","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"sun","suffix":""},{"id":292610127,"identity":"5d54c98f-1c8c-4de3-a523-5772b65fa211","order_by":12,"name":"Weiyan zheng","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Weiyan","middleName":"","lastName":"zheng","suffix":""},{"id":292610128,"identity":"6c843017-6aa3-4f7c-8f71-f9d971433571","order_by":13,"name":"Hejing Song","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Hejing","middleName":"","lastName":"Song","suffix":""},{"id":292610129,"identity":"ba2902b5-af17-495a-9288-25709516c1df","order_by":14,"name":"Yi Zhao","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Zhao","suffix":""},{"id":292610130,"identity":"8508eebe-08a4-4ffc-9f6e-981518b43409","order_by":15,"name":"Wenjun Wu","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Wenjun","middleName":"","lastName":"Wu","suffix":""},{"id":292610132,"identity":"7928d2da-8ba1-43fd-97af-db5db4ff3bda","order_by":16,"name":"Zhen Cai","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Zhen","middleName":"","lastName":"Cai","suffix":""},{"id":292610133,"identity":"268fe66b-d300-4b4a-81e3-f74946e5bb9d","order_by":17,"name":"Guoqing Wei","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Guoqing","middleName":"","lastName":"Wei","suffix":""},{"id":292610134,"identity":"31668d42-a216-49d0-bc38-52ba57be2cc1","order_by":18,"name":"He Huang","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"He","middleName":"","lastName":"Huang","suffix":""},{"id":292610136,"identity":"f85b3556-564d-4d8b-8ff2-e3e83a1a53d6","order_by":19,"name":"Jimin shi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYDACCcYGgwQGCQZ+BoYEIJeZBC2SDcRrgdIGB8AUEVrkZzc3FDzMscgzPn/gmQRDhXViA/vZA3i1GNw52GCQuE2i2OzAgTQJhjPpiQ08eQn4tUgkgrUkbjvYkCbB2HY4sUGCxwC/w2ZAtWxuZgBq+UeEFoYbUC0b2EBaGojQYgDTMuMMQ7JFwrF04zaeHEIOS39m+HNbXWJ//5nEGx9qrGX72c8QcBgDAxtUBU8CODLZCKkHAuYHEJr9ABGKR8EoGAWjYCQCAFcuRc/GU1mjAAAAAElFTkSuQmCC","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":true,"prefix":"","firstName":"Jimin","middleName":"","lastName":"shi","suffix":""}],"badges":[],"createdAt":"2024-04-05 15:06:50","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4223756/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4223756/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00277-024-05871-0","type":"published","date":"2024-07-04T06:11:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":55319876,"identity":"90a61ee5-df32-4c18-b23e-1531f71cf18e","added_by":"auto","created_at":"2024-04-25 16:02:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3587269,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTransplantation outcomes stratified by the presence of +der(22) and other ACAs(no +der(22))\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4223756/v1/c6a160cf2f06f8d782ab2536.png"},{"id":55319879,"identity":"e5a80bd2-2a46-40e7-b916-cf2d2c417453","added_by":"auto","created_at":"2024-04-25 16:02:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":353801,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTransplantation outcomes stratified by the presence of -7 and other ACAs(no -7)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4223756/v1/4386d0d0db708307f5bae2b2.png"},{"id":55319877,"identity":"170f3949-8ee5-4aef-9157-e00ca3d8e127","added_by":"auto","created_at":"2024-04-25 16:02:03","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1305795,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTransplantation outcomes stratified by the presence of complex karyotype and sole ACA other than t(9;22)(q34;q11)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4223756/v1/c93bff8189b773f02ca8c78d.png"},{"id":55319878,"identity":"a5e7a2b2-7d87-42a2-b576-41288caea122","added_by":"auto","created_at":"2024-04-25 16:02:03","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":523742,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTransplantation outcomes stratified by the presence of +8 and other ACAs(no +8)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4223756/v1/39b1a1653362691dc17a1486.png"},{"id":61208528,"identity":"5439ed16-a94c-4fa1-9fbd-9236a1d7dd9a","added_by":"auto","created_at":"2024-07-27 06:11:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6188417,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4223756/v1/95999051-607c-4347-a275-604e0d6eadea.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Additional Cytogenetic Aberrations at Diagnosis on Prognosis of Adults Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation：A Retrospective Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePhiladelphia chromosome-positive acute lymphoblastic leukemia(Ph\u0026thinsp;+\u0026thinsp;ALL) accounts for approximately 25\u0026ndash;30% of young patients with ALL and 40\u0026ndash;50% of elderly patients with ALL. It is characterised by the translocation of chromosomes 9 and 22 and the formation of BCR/ABL1 fusion genes[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In the last 20 years, tyrosine kinase inhibitors (TKIs) and allogeneic haematopoietic stem-cell transplantation(HSCT) have significantly improved outcomes of Ph\u0026thinsp;+\u0026thinsp;ALL[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. With the continuous improvement of polymerase chain reaction (RT-PCR) and next-generation sequencing technology, the BCR/ABL1 gene as the primary monitoring indicator of minimal residual disease (MRD) plays an essential role in diagnosis, prognosis and treatment of Ph\u0026thinsp;+\u0026thinsp;ALL[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Nonetheless, the role of cytogenetics is irreplaceable in adults with Ph\u0026thinsp;+\u0026thinsp;ALL[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The presence of additional cytogenetic aberrations (ACAs) has been reported in approximately 40\u0026ndash;80% of patients with Ph\u0026thinsp;+\u0026thinsp;ALL[\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Several previous studies have investigated the prognostic role of ACA in Ph\u0026thinsp;+\u0026thinsp;ALL, but there was no uniform conclusion[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The study aims to investigate the prognosis significance of common ACAs for Ph\u0026thinsp;+\u0026thinsp;ALL patients who had received HSCT in the TKI era.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eData Source and Patient Selection\u003c/h2\u003e\n \u003cp\u003eClinical and cytogenetic data of 136 of 188 patients with Ph\u0026thinsp;+\u0026thinsp;ALL undergoing allogeneic hematopoietic cell transplantation were(HSCT) obtained from Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine. This study includes consecutive adult patients with Ph\u0026thinsp;+\u0026thinsp;ALL who had received allogenic HSCT between January 2015 and May 2023. Written informed consent was obtained from all patients before they enrolled in the study.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient characteristics and Cytogenetic analyses\u003c/h2\u003e\n \u003cp\u003eBaseline characteristics are shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Chromosomal analyses of G-banded bone marrow (136 samples) were performed in cytogenetics laboratories of the First Affiliated Hospital of Zhejiang University School of Medicine according to the International System for Human Cytogenetic Nomenclature (ISCN)[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. Specimens were obtained at diagnosis from all patients. Major-route of ACAs is defined as having an extra chromosome frequency of more than 5%, including\u0026thinsp;+\u0026thinsp;der(22), +der(9), +\u0026thinsp;8, -7, hyperdiploid and complex karyotype. ACAs that were rarely observed in Ph\u0026thinsp;+\u0026thinsp;ALL, such as t(1;5), t(8;9), t(v;22), +der(1), +der(2), +der(5), +der(14), +der(16), +X, +\u0026thinsp;5 and hypodiploid, were designated minor-route ACAs.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003eTreatment\u003c/h2\u003e\n \u003cp\u003eOf the 136 participants, all patients received induction therapy, consolidation therapy and allogeneic HSCT. In addition, all were treated with Tyrosine kinase inhibitors (TKI) prior to transplantation (see Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Most patients received TKI maintenance treatment after HSCT. Patients who relapse after transplantation primarily received the following treatments: higher level TKI targeted therapy, donor lymphocyte infusion, secondary transplantation, chimeric antigen receptor T-Cell immunotherapy, chemotherapy, blinatumomab and inotuzumab ozogamicin. Most of the patients with central nervous system leukemia after transplantation received intrathecal injections and whole-brain radiotherapy.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cstrong\u003eTable 1 Patient and Disease Characteristics\u003c/strong\u003e\u003c/div\u003e\n \u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"599\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.27454242928452%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient\u0026nbsp;and\u0026nbsp;disease\u0026nbsp;characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSingle\u0026nbsp;Ph+ALL\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003en=76)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.95341098169717%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePh+ALL\u0026nbsp;plus\u0026nbsp;ACA(n=60)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.813643926788686%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.27454242928452%\" valign=\"top\"\u003e\n \u003cp\u003eAge(y)\u0026nbsp;median(range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003e36.6\u0026plusmn;12.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.95341098169717%\" valign=\"top\"\u003e\n \u003cp\u003e40.7\u0026plusmn;12.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.813643926788686%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.27454242928452%\" valign=\"top\"\u003e\n \u003cp\u003eMale,n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003e42(55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.95341098169717%\" valign=\"top\"\u003e\n \u003cp\u003e35(58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.813643926788686%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.27454242928452%\" valign=\"top\"\u003e\n \u003cp\u003eBCR-ABL\u0026nbsp;p190\u0026nbsp;transcript,n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003e53(70%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.95341098169717%\" valign=\"top\"\u003e\n \u003cp\u003e46(77%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.813643926788686%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.27454242928452%\" valign=\"top\"\u003e\n \u003cp\u003eBCR-ABL\u0026nbsp;p210\u0026nbsp;transcript,n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003e23(30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.95341098169717%\" valign=\"top\"\u003e\n \u003cp\u003e14(23%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.813643926788686%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.27454242928452%\" valign=\"top\"\u003e\n \u003cp\u003eIKZF1\u0026nbsp;Mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003e11(14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.95341098169717%\" valign=\"top\"\u003e\n \u003cp\u003e8(13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.813643926788686%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.27454242928452%\" valign=\"top\"\u003e\n \u003cp\u003eTKI\u0026nbsp;induction\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Imatinib\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Dasatinib/Flumatinib\u003c/p\u003e\n \u003cp\u003ePonatinib/Overembatinib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31(41%)\u003c/p\u003e\n \u003cp\u003e31(41%)\u003c/p\u003e\n \u003cp\u003e11(14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.95341098169717%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27(25%)\u003c/p\u003e\n \u003cp\u003e29(48%)\u003c/p\u003e\n \u003cp\u003e2(3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.813643926788686%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.27454242928452%\" valign=\"top\"\u003e\n \u003cp\u003eMRD\u0026nbsp;Status\u0026nbsp;Pre-HCT\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; MRD positive\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; MRD negative\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; CR1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; CR2 or beyond\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Non-remission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30(39%)\u003c/p\u003e\n \u003cp\u003e46(61%)\u003c/p\u003e\n \u003cp\u003e66(87%)\u003c/p\u003e\n \u003cp\u003e8(11%)\u003c/p\u003e\n \u003cp\u003e2(3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.95341098169717%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26(43%)\u003c/p\u003e\n \u003cp\u003e33(55%)\u003c/p\u003e\n \u003cp\u003e54(90%)\u003c/p\u003e\n \u003cp\u003e6(10%)\u003c/p\u003e\n \u003cp\u003e0(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.813643926788686%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.27454242928452%\" valign=\"top\"\u003e\n \u003cp\u003eAllo-HCT\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; MA-HCT\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; RIC-HCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958402662229616%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e73(96%)\u003c/p\u003e\n \u003cp\u003e3(4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.95341098169717%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e52(87%)\u003c/p\u003e\n \u003cp\u003e8(13%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.813643926788686%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical analysis\u003c/h2\u003e\n \u003cp\u003eThe primary endpoints for outcome analyses were 3-year cumulative incidence of relapse (CIR), progression-free survival(PFS), overall survival (OS) and non-relapse mortality(NRM). OS is defined as the time from the date of transplant to death. CIR is measured from the date of transplant until the beginning of relapse. PFS is defined as the time from transplant until the beginning of relapse or death from any cause, whichever occurs first. Probabilities of PFS and OS were calculated using the Kaplan-Meier method and compared with the log-rank test. CIR is calculated by using Gray\u0026apos;s method and the competing-risk cumulative function considering NRM as a competing risk. Baseline characteristics were summarised by using the median for continuous variables and percentages for categorical variables, which were compared using a two-sided t-test. To evaluate the influence of chromosome subsets on relapse, the Fine and Gray model was used for multivariate analysis. All analyses were performed using R(version 4.3.2). P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 are considered significant.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eChromosome distribution\u003c/h2\u003e \u003cp\u003eThe following conditions are excluded: 1. Thirteen patients are under the age of 18 2. Thirty-four patients had no cytogenetic information at diagnosis 3. One patient had a history of chronic granulocytic leukemia 4. Four patients were followed for less than 90 days. Finally, 136 patients were eligible for the study, with 76(56%) having the standard translocation t(9;22)(q34;q11) only, and 60 (44%) showing ACAs. Fifty patients (37%) were found to have major ACAs, and ten patients(7%) had minor ACAs.\u003c/p\u003e \u003cp\u003eIn patients with major-route ACAs, 25 patients(18%) were found to have +\u0026thinsp;der(22), with 24 patients(96%) exhibiting complex karyotypes. Concurrent chromosomal abnormalities included\u0026thinsp;+\u0026thinsp;der(9), +\u0026thinsp;8 and \u0026minus;\u0026thinsp;7. +der(9) is observed in 9 patients(6.6%) and all were complex karyotype. Chromosomal abnormalities that can co-exist with +\u0026thinsp;der(9) included\u0026thinsp;+\u0026thinsp;der(22) and \u0026minus;\u0026thinsp;7. Moreover, while\u0026thinsp;+\u0026thinsp;der(9) and +\u0026thinsp;8 were not found together. +8 is observed in 9 patients(6.6%) and all were complex karyotype. Chromosomal abnormalities that can co-exist with +\u0026thinsp;8 included\u0026thinsp;+\u0026thinsp;der(22) and \u0026minus;\u0026thinsp;7. -7 is observed in 13 patients(9.6%), of which 8 patients(62%) were complex karyotypes. Other ACAs, such as +\u0026thinsp;der(22), +der(9) and +\u0026thinsp;8, were also detected. In addition, -7 is the only ACA in 5 cases. A complex karyotype is defined as having at least two abnormalities other than t(9;22)(q34;q11). In the current study, complex karyotypes were observed in 42 patients (31%) and consisted primarily of +\u0026thinsp;der(22), +der(9), +\u0026thinsp;8, and \u0026minus;\u0026thinsp;7.\u003c/p\u003e \u003cp\u003eMinor-route ACAs are defined as having an extra chromosome frequency of less than 5% and were found in 19 patients(14%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePrognostic significance of ACAs\u003c/h2\u003e \u003cp\u003eThe median follow-up was 26.4 months. The three-year OS proportion and PFS of patients with isolated t(9;22) and those with ACAs are not significant (76.3% VS 81.7%, P\u0026thinsp;=\u0026thinsp;0.79;32.9% VS 38.3%, P\u0026thinsp;=\u0026thinsp;0.19). The three-year NRM of patients with isolated t(9;22) and those with ACAs is also not significant (9.2% VS 3.3%, P\u0026thinsp;=\u0026thinsp;0.22). The three-year CIR is higher in patients with ACAs compared with patients with standard t(9;22)(q34;q11) (36.7% VS 19.7%, P\u0026thinsp;=\u0026thinsp;0.04).\u003c/p\u003e \u003cp\u003eThe three-year OS proportion and CIR of patients with major ACAs are 78% and 32%, respectively. The three-year OS proportion and CIR of patients with minor ACAs are 100% and 10%, respectively. Subsequently, the three-year OS proportion and CIR are not statistically different in patients with major ACAs compared with patients with minor ACAs(P\u0026thinsp;=\u0026thinsp;0.1; P\u0026thinsp;=\u0026thinsp;0.07). At the same time, the three-year NRM proportion and PFS of patients with major ACAs and those with minor ACAs are not significantly different (3.3% VS 0%, P\u0026thinsp;=\u0026thinsp;0.52;38.3% VS 10%, P\u0026thinsp;=\u0026thinsp;0.054). To further understand the prognostic value of ACAs for ph\u0026thinsp;+\u0026thinsp;ALL undergoing HSCT, the influence of some chromosome subsets was analysed, such as +\u0026thinsp;der(22), +der(9), +\u0026thinsp;8, -7 and complex karyotype.\u003c/p\u003e \u003cp\u003eIn the predictive analysis of +\u0026thinsp;der(22) on HSCT outcomes, the group was divided into three subgroups: isolated Ph chromosome(Ph\u0026thinsp;+\u0026thinsp;ALL,n\u0026thinsp;=\u0026thinsp;76), Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;+\u0026thinsp;der(22)(n\u0026thinsp;=\u0026thinsp;25), and Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs(no\u0026thinsp;+\u0026thinsp;der(22))(n\u0026thinsp;=\u0026thinsp;35). There is no significant difference between Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;+\u0026thinsp;der(22), Ph\u0026thinsp;+\u0026thinsp;ALL and Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs(no\u0026thinsp;+\u0026thinsp;der(22) regarding the 3-year probability of survival (80% vs. 77.6% vs.82.9%; P\u0026thinsp;=\u0026thinsp;0.78), PFS(48% vs. 32.9% vs.28.6%;P\u0026thinsp;=\u0026thinsp;0.083), NRM(4% vs. 9.2% vs.2.9%; P\u0026thinsp;=\u0026thinsp;0.469). Nevertheless, the 3-year CIR for Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;+\u0026thinsp;der(22) is 44% vs. 23.7% for Ph\u0026thinsp;+\u0026thinsp;ALL vs. 31.4% for Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs(no\u0026thinsp;+\u0026thinsp;der(22))(P\u0026thinsp;=\u0026thinsp;0.045)(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe chromosomal abnormality \u0026minus;\u0026thinsp;7 is the common ACA examined regarding its prognostic significance on HSCT outcomes by splitting the Philadelphia chromosome-positive acute lymphoblastic leukemia into three subgroups: isolated Ph chromosome(Ph\u0026thinsp;+\u0026thinsp;ALL,n\u0026thinsp;=\u0026thinsp;76), Ph\u0026thinsp;+\u0026thinsp;ALL plus \u0026minus;\u0026thinsp;7(n\u0026thinsp;=\u0026thinsp;13), and Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs(no -7)(n\u0026thinsp;=\u0026thinsp;47). Both the three-year OS and PFS were inferior in patients with Ph\u0026thinsp;+\u0026thinsp;ALL plus \u0026minus;\u0026thinsp;7 compared to Ph\u0026thinsp;+\u0026thinsp;ALL and Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs(no -7)(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). At the same time, the three-year CIR of patients with Ph\u0026thinsp;+\u0026thinsp;ALL plus \u0026minus;\u0026thinsp;7 and the other two groups were also statistically significant(Figure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, the three-year NRM of patients with these three groups is not significantly different (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Subsequently, the 3-year proportion of OS for Ph\u0026thinsp;+\u0026thinsp;ALL plus \u0026minus;\u0026thinsp;7 is 46.5% vs 77.6% for Ph\u0026thinsp;+\u0026thinsp;ALL vs. 91.5% for Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs (no -7)(P\u0026thinsp;=\u0026thinsp;0.001). The 3-year PFS for Ph\u0026thinsp;+\u0026thinsp;ALL plus \u0026minus;\u0026thinsp;7 is 61.5% vs. 32.9% for Ph\u0026thinsp;+\u0026thinsp;ALL vs. 31.9% for Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs(no -7)(P\u0026thinsp;=\u0026thinsp;0.033). In addition, the 3-year CIR for Ph\u0026thinsp;+\u0026thinsp;ALL plus \u0026minus;\u0026thinsp;7 is 53.8% vs. 23.7% for Ph\u0026thinsp;+\u0026thinsp;ALL vs. 31.9% for Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs(no -7)(P\u0026thinsp;=\u0026thinsp;0.035).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eComplex karyotype is the most frequent ACA, mainly composed of +\u0026thinsp;der(22), +der(9), +\u0026thinsp;8 and \u0026minus;\u0026thinsp;7. In a prognostic analysis of complex karyotype on HSCT outcomes, the group was divided into three subgroups: isolated Ph chromosome(Ph\u0026thinsp;+\u0026thinsp;ALL,n\u0026thinsp;=\u0026thinsp;76), Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;≧\u0026thinsp;2 ACAs(n\u0026thinsp;=\u0026thinsp;42), and Ph\u0026thinsp;+\u0026thinsp;ALL plus 1 ACA(n\u0026thinsp;=\u0026thinsp;18). There is no statistical difference between Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;≧\u0026thinsp;2 ACAs, Ph\u0026thinsp;+\u0026thinsp;ALL and Ph\u0026thinsp;+\u0026thinsp;ALL plus 1 ACA regarding the 3-year probability of survival (78.6% vs. 77.6% vs. 94.4%; P\u0026thinsp;=\u0026thinsp;0.28) and NRM(4.8% vs. 9.2% vs. 0%; P\u0026thinsp;=\u0026thinsp;0.368). However, the 3-year PFS for Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;≧\u0026thinsp;2 ACAs is 47.6% vs. 23.7% for Ph\u0026thinsp;+\u0026thinsp;ALL vs. 22.2% for Ph\u0026thinsp;+\u0026thinsp;ALL plus 1 ACA(P\u0026thinsp;=\u0026thinsp;0.033) and the 3-year CIR for Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;≧\u0026thinsp;2 ACAs is 42.9% vs. 23.7% for Ph\u0026thinsp;+\u0026thinsp;ALL vs. 22.2% for Ph\u0026thinsp;+\u0026thinsp;ALL plus 1 ACA(P\u0026thinsp;=\u0026thinsp;0.027(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e+\u0026thinsp;8 is also the common ACA. For prognostic analysis of +\u0026thinsp;8, the group was divided into three subgroups: isolated Ph chromosome(Ph\u0026thinsp;+\u0026thinsp;ALL,n\u0026thinsp;=\u0026thinsp;76), Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;+\u0026thinsp;8(n\u0026thinsp;=\u0026thinsp;9), and Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs(no\u0026thinsp;+\u0026thinsp;8)(n\u0026thinsp;=\u0026thinsp;51). Although the OS and NRM of Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;+\u0026thinsp;8 are worse than the other two groups, there is no statistical difference among Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;+\u0026thinsp;der(+\u0026thinsp;8), Ph\u0026thinsp;+\u0026thinsp;ALL and Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs(no\u0026thinsp;+\u0026thinsp;8) regarding the 3-year proportion of OS (55.5% vs. 77.6% vs. 86.3%; P\u0026thinsp;=\u0026thinsp;0.17) and NRM(11.1% vs. 9.2% vs. 2%; P\u0026thinsp;=\u0026thinsp;0.3). However, the 3-year PFS for Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;+\u0026thinsp;der(+\u0026thinsp;8) is 77.8% vs. 23.7% for Ph\u0026thinsp;+\u0026thinsp;ALL vs. 33.3% for Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs(no\u0026thinsp;+\u0026thinsp;8)(P\u0026thinsp;=\u0026thinsp;0.0087) and the 3-year CIR for Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;+\u0026thinsp;der(+\u0026thinsp;8) is 66.7% vs. 23.7% for Ph\u0026thinsp;+\u0026thinsp;ALL vs. 31.4% for Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs(no\u0026thinsp;+\u0026thinsp;8)(P\u0026thinsp;=\u0026thinsp;0.024) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) .\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe prognostic analysis of +\u0026thinsp;der(9) on HSCT outcomes shows no significant difference between Ph\u0026thinsp;+\u0026thinsp;ALL plus\u0026thinsp;+\u0026thinsp;der(9), Ph\u0026thinsp;+\u0026thinsp;ALL and Ph\u0026thinsp;+\u0026thinsp;ALL plus other ACAs(no\u0026thinsp;+\u0026thinsp;der(9)) regarding the 3-year rate of OS(100% vs. 77.6% vs.78.4%; P\u0026thinsp;=\u0026thinsp;0.35), CIR(33.3% vs. 23.7% vs. 37.3%; P\u0026thinsp;=\u0026thinsp;0.35), PFS(33.3% vs. 32.9% vs. 41.2%;P\u0026thinsp;=\u0026thinsp;0.3), and NRM(0% vs. 9.2% vs. 3.9%; P\u0026thinsp;=\u0026thinsp;0.123).\u003c/p\u003e \u003cp\u003eThese statistically significant subgroups were included in a multivariate analysis to explore the effect of ACAs on HSCT outcomes. In the multivariate analysis for IR, regarding\u0026thinsp;+\u0026thinsp;der(22), +\u0026thinsp;8, -7, and complex ACAs, the factors that had a negative impact are +\u0026thinsp;der(22) (P\u0026thinsp;=\u0026thinsp;0.014), +\u0026thinsp;8(P\u0026thinsp;=\u0026thinsp;0.005), -7(P\u0026thinsp;=\u0026thinsp;0.009), and complex ACAs(\u0026thinsp;≧\u0026thinsp;2 ACAs) (P\u0026thinsp;=\u0026thinsp;0.016)(Table\u0026nbsp;3). The factors with a poor prognosis are +\u0026thinsp;der(22) (P\u0026thinsp;=\u0026thinsp;0.035), +\u0026thinsp;8(P\u0026thinsp;=\u0026thinsp;0.005), -7(P\u0026thinsp;=\u0026thinsp;0.011) and complex ACAs(\u0026thinsp;≧\u0026thinsp;2 ACAs)(P\u0026thinsp;=\u0026thinsp;0.022) in multivariate analysis for PFS(Table\u0026nbsp;3). The presence of ACAs at diagnosis is not associated with the risk of NRM in the multivariate analyses(P\u0026thinsp;\u0026gt;\u0026thinsp;0.05)(Table\u0026nbsp;3). In multivariate analysis for OS, considering\u0026thinsp;+\u0026thinsp;der(22), +\u0026thinsp;8, -7 and complex ACAs as variables, the only factor that retains statistical significance is -7(P\u0026thinsp;=\u0026thinsp;0.012)(Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInfluence of additional chromosome abnormalities on Transplantation Outcomes in Multivariate Analyses\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eCIR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003ePFS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eNRM\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSHR(95%\u0026nbsp;CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHR(95%\u0026nbsp;CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSHR(95%\u0026nbsp;CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eHR(95%\u0026nbsp;CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eph\u0026nbsp;alone*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+der(22)\u003c/p\u003e \u003cp\u003e+der(22)\u003c/p\u003e \u003cp\u003eACAs(no\u0026thinsp;+\u0026thinsp;der(22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.54(1.21\u0026ndash;5.32)\u003c/p\u003e \u003cp\u003e1.53(0.72\u0026ndash;3.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003cp\u003e0.270\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.12(1.05\u0026ndash;4.27)\u003c/p\u003e \u003cp\u003e1.04(0.49\u0026ndash;2.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003cp\u003e0.930\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.48(0.06\u0026ndash;3.89)\u003c/p\u003e \u003cp\u003e0.32(0.04\u0026ndash;2.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.490\u003c/p\u003e \u003cp\u003e0.290\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.17(0.44\u0026ndash;3.12)\u003c/p\u003e \u003cp\u003e0.76(0.30\u0026ndash;1.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.750\u003c/p\u003e \u003cp\u003e0.560\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+\u0026thinsp;8\u003c/p\u003e \u003cp\u003e+8\u003c/p\u003e \u003cp\u003eACAs(no\u0026thinsp;+\u0026thinsp;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.64(1.48-9.00)\u003c/p\u003e \u003cp\u003e1.60(0.83\u0026ndash;3.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003cp\u003e0.160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.59(1.49\u0026ndash;8.70)\u003c/p\u003e \u003cp\u003e1.23(0.67\u0026ndash;2.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003cp\u003e0.500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.22(0.14\u0026ndash;10.7)\u003c/p\u003e \u003cp\u003e0.23(0.03\u0026ndash;1.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.860\u003c/p\u003e \u003cp\u003e0.160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2.11(0.71\u0026ndash;6.24)\u003c/p\u003e \u003cp\u003e0.69(0.29\u0026ndash;1.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.180\u003c/p\u003e \u003cp\u003e0.380\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-7\u003c/p\u003e \u003cp\u003e-7\u003c/p\u003e \u003cp\u003eACAs(no -7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.15(1.34\u0026ndash;7.43)\u003c/p\u003e \u003cp\u003e1.62(0.83\u0026ndash;3.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003cp\u003e0.160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.89(1.27\u0026ndash;6.56)\u003c/p\u003e \u003cp\u003e1.18(0.62\u0026ndash;2.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003cp\u003e0.610\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.87(0.10\u0026ndash;7.40)\u003c/p\u003e \u003cp\u003e0.25(0.03\u0026ndash;1.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.900\u003c/p\u003e \u003cp\u003e0.190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.02(1.28\u0026ndash;7.13)\u003c/p\u003e \u003cp\u003e0.41(0.14\u0026ndash;1.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003cp\u003e0.110\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplex\u0026nbsp;ACAs\u003csup\u003e$\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e1 ACA\u003c/p\u003e \u003cp\u003e≧ 2 ACAs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.04(0.35\u0026ndash;3.15)\u003c/p\u003e \u003cp\u003e2.37(1.24\u0026ndash;4.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.940\u003c/p\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.72(0.24\u0026ndash;2.15)\u003c/p\u003e \u003cp\u003e1.99(1.10\u0026ndash;3.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.560\u003c/p\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.87(0.10\u0026ndash;7.40)\u003c/p\u003e \u003cp\u003e0.53(0.15\u0026ndash;2.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.900\u003c/p\u003e \u003cp\u003e0.480\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.24(0.03\u0026ndash;1.74)\u003c/p\u003e \u003cp\u003e1.12(0.50\u0026ndash;2.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.160\u003c/p\u003e \u003cp\u003e0.780\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*: Ph alone was used as a control group.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003e\u003cspan\u003e$:\u003c/span\u003e\u003c/strong\u003e \u003cp\u003eComplex karyotype is defined as the presence of at least two chromosome abnormalities other than t(9;22)(q34;q11).\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eCytogenetic studies have shown that some haematologic malignancies with ACAs at diagnosis had a poor prognosis[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. At present, the prognostic value of ACAs in Ph\u0026thinsp;+\u0026thinsp;ALL has not been determined in the era of TKI and HSCT, which may be attributed to the differences in the number of patients, racial population, and antineoplastic protocols. In view of this, this study details the prognosis effect of different ACAs subgroups on Ph\u0026thinsp;+\u0026thinsp;ALL patients receiving TKI-targeted drugs and HSCT.\u003c/p\u003e \u003cp\u003eThe analysis shows that the incidence of ACA in Ph\u0026thinsp;+\u0026thinsp;ALL is 44%, and the common ACAs include complex karyotypes, +der(22), -7, +\u0026thinsp;8 and +\u0026thinsp;der(9), consistent with previous studies[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Johansson defines ACAs that occur more than 5% as major-route ACAs[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Other ACAs that are rare, such as t(1;5), t(8;9), +der(1), and +\u0026thinsp;der(5), were designated minor-route ACAs.\u003c/p\u003e \u003cp\u003eIn the pre-TKI era, a prospective study analysed the prognoses of ACAs in adults with Ph\u0026thinsp;+\u0026thinsp;ALL and included cytogenetic data from 111 newly diagnosed adults with Ph\u0026thinsp;+\u0026thinsp;ALL[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Seventy-five patients (68%) had ACAs. The results showed that \u0026minus;\u0026thinsp;7 is related to the lower CR rate, and the complex ACAs are related to higher CR rates. At the same time, +der (22) was associated with the high accumulation of recurrence rate. To further understand the prognosis of ACA in the TKI era on adult Ph\u0026thinsp;+\u0026thinsp;ALL, a retrospective study evaluated 152 patients with Ph\u0026thinsp;+\u0026thinsp;ALL patients who received TKI combined chemotherapy[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The research showed that a 5-year survival rate and non-recurrence survival probability were lower in Ph\u0026thinsp;+\u0026thinsp;ALL patients who had\u0026thinsp;+\u0026thinsp;der (22) with or without \u0026minus;\u0026thinsp;9/9p.\u003c/p\u003e \u003cp\u003eThe current study analysed the effects of major ACAs and minor ACAs on the prognosis of Ph\u0026thinsp;+\u0026thinsp;ALL. Patients with major ACAs or minor ACs have a prognosis not significantly different from those with standard t(9,22), consistent with the outcomes reported by Mitelman[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. To further explore the prognostic value of ACAs for Ph\u0026thinsp;+\u0026thinsp;ALL undergoing TKI-targeted drugs and HSCT, the influence of major ACAs, such as +\u0026thinsp;der(22), +der(9), +\u0026thinsp;8, -7, hyperdiploid, and complex karyotypes were analysed.\u003c/p\u003e \u003cp\u003eA complex karyotype is the most frequent ACA in this cohort, which mainly consisted of +\u0026thinsp;der(22), +der(9), +\u0026thinsp;8, and \u0026minus;\u0026thinsp;7. Previous studies have shown that chronic myelogenous leukemia with complex karyotypes has poorer survival and higher rates of disease progression[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Additionally, the complex karyotype is associated with a poor prognosis in Ph-negative ALL[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, Akahoshi et al. emphasised that complex karyotypes had no prognostic significance in Ph\u0026thinsp;+\u0026thinsp;ALL[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The current study shows inferior PFS and higher CIR in patients with Ph\u0026thinsp;+\u0026thinsp;ALL with complex karyotypes compared to those with isolated t(9;22) and Ph\u0026thinsp;+\u0026thinsp;ALL with a secondary ACA, while patients with Ph\u0026thinsp;+\u0026thinsp;ALL with complex karyotypes did not have a positive prognostic effect on OS and NRM. Such results may be due to more aggressive treatments in patients with progressive or recurrent disease following HSCT.\u003c/p\u003e \u003cp\u003ePatients in the current study with +\u0026thinsp;der(22) have a significantly higher CIR and shorter PFS compared to the other groups. Nevertheless, there is no difference in their survival and NRM. Some previous studies have confirmed that +\u0026thinsp;der(22) is associated with an unfavourable prognosis and shorter OS[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Gorre et al. and Hochhaus et al. showed in their studies of chronic myelogenous leukemia that +\u0026thinsp;der(22) may be resistant to imatinib[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Therefore, targeting drugs of the second-generation and third-generation TKI may overcome the poor prognosis caused by +\u0026thinsp;der(22), which is consistent with results in the current study.\u003c/p\u003e \u003cp\u003eThe chromosomal abnormality \u0026minus;\u0026thinsp;7 is the common ACA in the current cohort, as previously reported[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The analysis shows higher CIR and inferior PFS and OS in patients with Ph\u0026thinsp;+\u0026thinsp;ALL with \u0026minus;\u0026thinsp;7 compared to the sole t(9;22) group and the ACA group without monosomy 7. The prognostic value of monosomy 7 in haematological malignancy has been widely discussed. Several studies on CML have concluded that \u0026minus;\u0026thinsp;7 or 7q-, particularly in Philadelphia chromosome-negative myeloid neoplasms, is strongly associated with poor prognosis[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In addition, some studies have demonstrated that \u0026minus;\u0026thinsp;7 or 7q- is inextricably linked to an inferior survival and prognosis in Ph\u0026thinsp;+\u0026thinsp;ALL, consistent with the main findings of the current study[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. However, several other studies did not show an association between \u0026minus;\u0026thinsp;7 and poor outcomes[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Such a different conclusion may be due to the number of enrolled cases, study methods and treatment regimen. Therefore, a further large-scale study was undertaken to analyse the correlation between \u0026minus;\u0026thinsp;7 and prognosis in Ph\u0026thinsp;+\u0026thinsp;ALL and to explore the effects of TKI targeting drugs and HSCT on -7.\u003c/p\u003e \u003cp\u003eThe +\u0026thinsp;8 abnormal chromosome is also a common ACA. The current study shows that patients with +\u0026thinsp;8 have a higher CIR and shorter PFS compared to the other groups. Although Hehlmann et al. have demonstrated that +\u0026thinsp;8 is associated with an inferior OS in CML\u003csup\u003e[19]\u003c/sup\u003e, another study did not[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In Ph\u0026thinsp;+\u0026thinsp;ALL, Akahoshi et al. concluded that +\u0026thinsp;8 was closely associated with a high CIR, which concurs with the results of the current study.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, ACAs at diagnosis, especially in patients with \u0026minus;\u0026thinsp;7, +\u0026thinsp;8, +der(22) and complex karyotype, appear to have a significant prognostic impact on transplantation outcomes in patients with Ph\u0026thinsp;+\u0026thinsp;ALL undergoing HSCT and TKI. Therefore, we may take more aggressive treatment such as second or third-generation TKI drug maintenance after transplantation and earlier donor lymphocyte infusion to improve the prognosis of patients with Ph\u0026thinsp;+\u0026thinsp;ALL with these high-risk chromosome subsets. Finally, more research is needed to explore further the effects of different TKI drugs on the prognosis of Ph\u0026thinsp;+\u0026thinsp;ALL with ACAs at diagnosis or treatment process.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003eJZ writed the manuscript; JY and JS have made great contribution to date collection; YZ, YZ, WW, ZC and YL supported the project design and literature review; HH and JS are corresponding authors and they have made significant contribution to the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eThis study was supported by the National Natural Science Foundation of China (grant\u0026nbsp;\u003c/p\u003e\n\u003cp\u003enumber:82070179) and Yichang City Medical Health Project(A23-1-028).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eData availability statement\u0026nbsp;\u003c/strong\u003eThe datesets will be maded available by the first author.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eEthics statements\u0026nbsp;\u003c/strong\u003ePatient consent for publication. Not applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eJing Zheng\u003csup\u003e1,2\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eYanmin Zhao\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eYi Luo\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eJian Yu\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eXiaoyu Lai\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eJinuo Wang\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eYishan Ye\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eLi zhen Liu\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eHuarui Fu\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eLuxin Yang\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eYibo Wu\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eJie Sun\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eWeiyan Zheng\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eHejing Song\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eYi Zhao\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eWenjun Wu\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eZhen Cai\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eGuoqing Wei\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eHe Huang\u003csup\u003e1,*\u003c/sup\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026middot;\u003c/strong\u003e\u003cstrong\u003eJimin Shi\u003csup\u003e1,*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;1Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2Departments of Hematology, The First College of Clinical Medical Science, China Three Gorges University, Yichang Central People\u0026rsquo;s Hospital, Yichang 443000, China.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003csup\u003e*\u003c/sup\u003eCorresponding to. Professor Jimin Shi, Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, China, [email protected]. Professor He Huang, Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310000, China, [email protected].\u003c/p\u003e\n\u003cp\u003eJZ contributed as first author to this study.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChiaretti S, Vitale A, Cazzaniga G et al（2013）Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts. Haematologica 98: 1702-1710. \u003c/li\u003e\n\u003cli\u003eJabbour E, Pui C-H, Kantarjian H（2018）Progress and innovations in the management of adult acute lymphoblastic leukemia. JAMA Oncol 4:1413-1420. \u003c/li\u003e\n\u003cli\u003eSoverini S, Bassan R, Lion T（2019）Treatment and monitoring of Philadelphia chromosome-positive leukemia patients: recent advances and remaining challenges. J Hematol Oncol 12:39. \u003c/li\u003e\n\u003cli\u003eShort NJ, Kantarjian H, Jabbour E（2012）Optimizing the treatment of acute lymphoblastic leukemia in younger and older adults: new drugs and evolving paradigms. Leukemia 35:3044\u0026ndash;58.\u003c/li\u003e\n\u003cli\u003eSoverini S, Albano F, Bassan R et al（2020）Next-generation sequencing for BCR-ABL1 kinase domain mutations in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A position paper. Cancer Med 9:2960-2970. \u003c/li\u003e\n\u003cli\u003eNishiwaki S, Kim JH, Ito M et al（2020）Multi-Lineage BCR-ABL Expression in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Is Associated With Improved Prognosis but No Specific Molecular Features. Front Oncol 10:586567. \u003c/li\u003e\n\u003cli\u003eArana Trejo R M, Del C M A, Alcal\u0026aacute; Carmona L G et al（2016）Chromosomal abnormalities in patients with haematologic malignancies in the general hospital of Mexico. Revista M\u0026eacute;dica Del Hospital General De M\u0026eacute;xico 80:87-91.\u003c/li\u003e\n\u003cli\u003eAwan UA, Farooq N, Sarwar A et al（2021）Cytogenetic abnormalities in patients with hematological malignancies in Lahore city, Pakistan. Braz J Biol 83: e249911. \u003c/li\u003e\n\u003cli\u003eDombret H, Gabert J, Boiron JM et al（2002）Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia--results of the prospective multicenter LALA-94 trial. Blood 100:2357\u0026ndash;2366.\u003c/li\u003e\n\u003cli\u003eWetzler M, Dodge RK, Mrozek K et al（2004）Additional cytogenetic abnormalities in adults with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a study of the Cancer and Leukaemia Group B. Br J Haematol 124:275\u0026ndash;288.\u003c/li\u003e\n\u003cli\u003eSchultz KR, Carroll A, Heerema NA et al（2014）Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children\u0026rsquo;s Oncology Group study AALL0031. Leukemia 28:1467\u0026ndash;1471.\u003c/li\u003e\n\u003cli\u003eShort NJ, Kantarjian HM, Sasaki K et al（2017）Poor outcomes associated with +der(22)t(9;22) and -9/9p in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia receiving chemotherapy plus a tyrosine kinase inhibitor. Am J Hematol 92:238-243. \u003c/li\u003e\n\u003cli\u003eAldoss I, Stiller T, Cao TM et al（2015）Impact of Additional Cytogenetic Abnormalities in Adults with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 21:1326-9. \u003c/li\u003e\n\u003cli\u003eGonzalez Garcia JR, Meza-Espinoza JP（2006）Use of the International System for Human Cytogenetic Nomenclature (ISCN). Blood 108:3952-3.\u003c/li\u003e\n\u003cli\u003eMalakzai HA, Rahmani S, Haidary AM et al（2020）Complex cytogenetic abnormalities in chronic myeloid leukemia resulting in early progression to blast crisis: a case report. J Med Case Rep 14:231.\u003c/li\u003e\n\u003cli\u003eAnsari S, Verma M（2023）Control of Ph+ and additional chromosomal abnormalities in chronic myeloid leukemia by tyrosine kinase inhibitors. Med Oncol 40: 237. \u003c/li\u003e\n\u003cli\u003eJohansson B, Fioretos T, Mitelman F（2002）Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol 107 :76-94.\u003c/li\u003e\n\u003cli\u003eMitelman F, Levan G, Nilsson PG et al(1976)Non-random karyotypic evolution in chronic myeloid leukemia. Int J Cancer 18:24-30.\u003c/li\u003e\n\u003cli\u003eHehlmann R, Voskanyan A, Lauseker M et al(2020)High-risk additional chromosomal abnormalities at low blast counts herald death by CML. Leukemia 34(8): 2074-2086.\u003c/li\u003e\n\u003cli\u003eBonifacio M, Elena C,Mariella D\u0026apos;Adda et al(2020)Do Not Miss Karyotyping at Chronic Myeloid Leukemia Diagnosis: An Italian Campus CML Study on the Role of Complex Variant Translocations. Blood 136:43-44.\u003c/li\u003e\n\u003cli\u003eIssa GC, Kantarjian HM, Yin CC et al(2017) Prognostic impact of pretreatment cytogenetics in adult Philadelphia chromosome-negative acute lymphoblastic leukemia in the era of minimal residual disease. Cancer 123:459-467.\u003c/li\u003e\n\u003cli\u003eMoorman AV, Harrison CJ, Buck GA et al(2007)Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood 109:3189-3197. \u003c/li\u003e\n\u003cli\u003eAkahoshi Y, Mizuta S, Shimizu H et al(2018)Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation. Additional Cytogenetic Abnormalities with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia on Allogeneic Stem Cell Transplantation in the Tyrosine Kinase Inhibitor Era. Biol Blood Marrow Transplant 24: 2009-2016.\u003c/li\u003e\n\u003cli\u003eThomas X, Thiebaut A, Olteanu N et al(1998)Philadelphia chromosome positive adult acute lymphoblastic leukemia: characteristics, prognostic factors and treatment outcome. Hematol Cell Ther 40:119-128.\u003c/li\u003e\n\u003cli\u003eGorre ME, Mohammed M, Ellwood K et al(2001)Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293:876-880.\u003c/li\u003e\n\u003cli\u003eHochhaus A, Kreil S, Corbin AS et al(2002)Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 16:2190-2196.\u003c/li\u003e\n\u003cli\u003eWang W, Cortes J E, Tang G et al(2016)Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. Blood 127:2742.\u003c/li\u003e\n\u003cli\u003eZhao HF, Zhang Y, Zu YL et al(2019）The influence of additive clonal chromosome abnormalities in Ph negative cells on the efficacy of chronic myeloid leukemia. Zhonghua Nei Ke Za Zhi 58:803-807.\u003c/li\u003e\n\u003cli\u003eHeerema NA, Nachman JB, Sather HN et al（2004）Deletion of 7p or monosomy 7 in pediatric acute lymphoblastic leukemia is an adverse prognostic factor: a report from the Children\u0026apos;s Cancer Group. Leukemia 18:939-947.\u003c/li\u003e\n\u003cli\u003eRieder H, Ludwig WD, Gassmann W et al（1996）Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia. Br J Haematol 95:678-691.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Philadelphia chromosome, Acute lymphoblastic leukaemia, Additional chromosomal abnormalities, Hematopoietic stem cell transplantation","lastPublishedDoi":"10.21203/rs.3.rs-4223756/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4223756/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAdditional chromosomal abnormalities(ACAs) at diagnosis are associated with inferior prognosis in chronic myelogenous leukemia. However, the prognostic significance of ACAs in adult patients with Philadelphia Chromosome Positive acute lymphoblastic leukemia (Ph\u0026thinsp;+\u0026thinsp;ALL) receiving TKI-targeted drugs and allogeneic hematopoietic stem cell transplantation(HSCT) is unknown. One hundred eighty-eight adult patients with Ph\u0026thinsp;+\u0026thinsp;ALL were retrospectively analysed, evaluating the effect of ACAs on outcomes of transplantation. One hundred thirty-six patients were included in the study. ACAs are observed in 60 cases (44%). The major-route ACAs are detected in more than 5% are as follows: +der(22), +der(9), +\u0026thinsp;8, -7 and complex karyotype. The median follow-up was 26.4 months. In the subgroup analyses of major route ACAs, three-year cumulative incidence of relapse (CIR) and progression-free survival(PFS) are statistically significant in +\u0026thinsp;8[66.7% vs.23.7%, P\u0026thinsp;=\u0026thinsp;0.024; 77.8% vs. 23.7%, P\u0026thinsp;=\u0026thinsp;0.0087], -7[53.8% vs. 23.7%, P\u0026thinsp;=\u0026thinsp;0.035%; 61.5% vs. 32.9%, P\u0026thinsp;=\u0026thinsp;0.033], and complex karyotypes[42.9% vs. 23.7%, P\u0026thinsp;=\u0026thinsp;0.027; 47.6% vs. 23.7%] compared with isolated t(9;22). Additionally, the 3-year CIR for Ph\u0026thinsp;+\u0026thinsp;ALL with +\u0026thinsp;der(22) is 44% vs. 23.7% for standard Ph\u0026thinsp;+\u0026thinsp;ALL(P\u0026thinsp;=\u0026thinsp;0.045). The 3-year overall survival (OS) in the \u0026minus;\u0026thinsp;7 group is 46.5%, which is statistically significant compared with the other groups(P\u0026thinsp;=\u0026thinsp;0.001). In multivariate analyses, three years CIR and PFS are statistically significant in +\u0026thinsp;der(22), +\u0026thinsp;8, -7 and complex karyotype compared with standard Ph\u0026thinsp;+\u0026thinsp;ALL(P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). More importantly, Ph\u0026thinsp;+\u0026thinsp;ALL with \u0026minus;\u0026thinsp;7 was negatively associated with the rate of 3-year OS(P\u0026thinsp;=\u0026thinsp;0.012). Partial ACAs at diagnosis appear to have a significant prognostic impact on transplantation outcomes in patients with Ph\u0026thinsp;+\u0026thinsp;ALL.\u003c/p\u003e","manuscriptTitle":"Impact of Additional Cytogenetic Aberrations at Diagnosis on Prognosis of Adults Patients with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation：A Retrospective Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-25 16:01:58","doi":"10.21203/rs.3.rs-4223756/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-06T06:42:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-05T15:35:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"07a69063-783a-40ce-81c0-8604c15d756e","date":"2024-04-23T15:29:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-23T12:41:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-17T13:46:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-17T13:46:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Hematology","date":"2024-04-05T15:05:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"518358b4-f2c6-47af-b52d-3a888f25ed1a","owner":[],"postedDate":"April 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-07-27T06:11:21+00:00","versionOfRecord":{"articleIdentity":"rs-4223756","link":"https://doi.org/10.1007/s00277-024-05871-0","journal":{"identity":"annals-of-hematology","isVorOnly":false,"title":"Annals of Hematology"},"publishedOn":"2024-07-04 06:11:21","publishedOnDateReadable":"July 4th, 2024"},"versionCreatedAt":"2024-04-25 16:01:58","video":"","vorDoi":"10.1007/s00277-024-05871-0","vorDoiUrl":"https://doi.org/10.1007/s00277-024-05871-0","workflowStages":[]},"version":"v1","identity":"rs-4223756","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4223756","identity":"rs-4223756","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}