FLT3-ITD,NPM1,and DNMT3A mutations are common in acute myeloid leukemia(AML).However,the prognostic role of FLT3-ITD combined with NPM1 and/or DNMT3A mutations after allogeneic hematopoietic stem cell transplantation(...FLT3-ITD,NPM1,and DNMT3A mutations are common in acute myeloid leukemia(AML).However,the prognostic role of FLT3-ITD combined with NPM1 and/or DNMT3A mutations after allogeneic hematopoietic stem cell transplantation(allo-HSCT)remains unclear.In this retrospective study,100 AML patients were selected from a cohort of 1292 who underwent allo-HSCT between 2014 and 2024.Patients were stratified by co-mutation profiles to compare prognosis,identify predictors of survival and relapse,and assess the efficacy of maintenance therapy.With a median follow-up after allo-HSCT of 16.1 months(interquartile range 8.1-26.2),2-year overall survival(OS)rates were 65.1%,68.3%,and 67.1%;leukemia-free survival(LFS)rates were 61.6%,68.7%,and 63.2%;and cumulative incidence of relapse(CIR)rates were 16.9%,12.5%,and 15.8%,respectively.No significant differences were observed among the groups.In multivariate analysis with FLT3 inhibitor as a time-dependent covariate,FLT3-ITD measurable residual disease(MRD)positivity prior to allo-HSCT was independently associated with inferior OS(hazard ratio[HR]=3.51,95%CI 1.34-9.17),LFS(HR=3.05,95%CI 1.26-7.35),and CIR(HR=4.78,95%CI 1.55-14.81).In contrast,posttransplant maintenance therapy with FLT3 inhibitors independently conferred a favorable impact on OS(HR=0.15,95%CI 0.03-0.66),LFS(HR=0.24,95%CI 0.07-0.83),CIR(HR=0.10,95%CI 0.01-0.66),and nonrelapse mortality(NRM)(HR=0.25,95%CI 0.07-0.89).In conclusion,FLT3-ITD-based double or triple mutations showed comparable posttransplant outcomes.FLT3-ITD MRD status and early maintenance therapy were key prognostic and therapeutic factors.展开更多
Accumulating evidence suggests that a reduction in the number of Foxp3^(+) regulatory T cells(Tregs)contributes to the pathogenesis of acute graft-versus-host disease(aGVHD),which is a major adverse complication that ...Accumulating evidence suggests that a reduction in the number of Foxp3^(+) regulatory T cells(Tregs)contributes to the pathogenesis of acute graft-versus-host disease(aGVHD),which is a major adverse complication that can occur after allogeneic hematopoietic stem cell transplantation(allo-HSCT).However,the precise features and mechanism underlying the defects in Tregs remain largely unknown.In this study,we demonstrated that Tregs were more dramatically decreased in bone marrow compared with those in peripheral blood from aGVHD patients and that bone marrow Treg defects were negatively associated with hematopoietic reconstitution.Tregs from aGVHD patients exhibited multiple defects,including the instability of Foxp3 expression,especially in response to IL-12,impaired suppressor function,decreased migratory capacity,and increased apoptosis.Transcriptional profiling revealed the downregulation of Lkb1,a previously identified critical regulator of murine Treg identity and metabolism,and murine Lkb1-regulated genes in Tregs from aGVHD patients.Foxp3 expression in human Tregs could be decreased and increased by the knockdown and overexpression of the Lkb1 gene,respectively.Furthermore,a loss-of-function assay in an aGVHD murine model confirmed that Lkb1 deficiency could impair Tregs and aggravate disease severity.These findings reveal that Lkb1 downregulation contributes to multiple defects in Tregs in human aGVHD and highlight the Lkb1-related pathways that could serve as therapeutic targets that may potentially be manipulated to mitigate aGVHD.展开更多
Hemorrhagic cystitis(HC)is a common complication of allogeneic hematopoietic stem cell transplantation(HSCT).The incidence is about 7%to 68%,and some patients have to suffer a long period of frequent,urgent,and painfu...Hemorrhagic cystitis(HC)is a common complication of allogeneic hematopoietic stem cell transplantation(HSCT).The incidence is about 7%to 68%,and some patients have to suffer a long period of frequent,urgent,and painful urination,which brings great pain.This study aimed to analyze risk factors of HC and its effect on patient survival.We collected the medical records of 859 patients who underwent HSCT at our hospital between August 2016 and August 2020.Patients with and without HC were matched using propensity score matching at a 1:1 ratio based on sex,age,and diagnosis,and logistic regression analyses were used to identify factors associated with HC.We used Kaplan–Meier curves to analyze the survival rates of patients in the HC and non-HC groups.We also analyzed the relationship between BK viral load and the occurrence of HC using receiver operating characteristic curve(ROC)analysis.After propensity score matching,there were 131 patients each in the HC and non-HC groups.In the HC group,89 patients(67.9%)had mild HC(stage II°)and 43(32.1%)had severe HC(stage III–IV).The median interval between stem cell transplantation and HC development was 31(3–244)days.Univariate analysis indicated that donor age,hematopoietic stem cell source,HLA,acute graft-versus-host disease,busulfan,anti-thymocyte globulin(ATG),total body irradiation,cytomegalovirus(CMV)(urine),and BK polyomavirus(BKV)(urine)were significantly associated with HC.ATG,CMV(urine),and BKV(urine)were independent risk factors for HC based on the multivariate analysis.The Kaplan–Meier survival analysis showed no significant difference between the HC and non-HC groups(P=0.14).The 1-and 2-year survival rates in the HC group were 78.4%and 69.6%,respectively,and the corresponding rates in the non-HC group were 84.4%and 80.7%,respectively.ROC analysis indicated that a urine BKV load of 1×10^(7) copies/mL was able to stratify the risk of HC.In conclusion,when the BKV load is>1×10^(7),we needtobe aware of the potential for the development of HC.展开更多
Invasive fungal diseases(IFDs)are major and lethal infectious complications for patients with neutropenia after chemotherapy.Prophylaxis with intravenous and oral suspended itraconazole(200 mg Q12h intravenously×...Invasive fungal diseases(IFDs)are major and lethal infectious complications for patients with neutropenia after chemotherapy.Prophylaxis with intravenous and oral suspended itraconazole(200 mg Q12h intravenously×2 days followed by 5 mg/kg·d orally in twice)or oral suspension of posaconazole(200 mg Q8h)was administered for preventing IFDs.The only 2 episodes of proven IFDs were not included after propensity-score matching(PSM),while the incidence of possible IFDs was 8.2%(9/110)in itraconazole group and 1.8%(2/110)in posaconazole group,respectively(P=.030).In clinical failure analysis,the failure rate of posaconazole group was lower as compared to the itraconazole group(2.7%vs 10.9%,P=.016).Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs,while posaconazole suspension seems more tolerable.展开更多
To the Editor:Allogeneic hemopoietic stem cell transplantation(allo-HSCT)represents the only long-term survival treatment choice for patients with myelodysplastic syndromes(MDS)and MDS/myeloproliferative neoplasm(MPN)...To the Editor:Allogeneic hemopoietic stem cell transplantation(allo-HSCT)represents the only long-term survival treatment choice for patients with myelodysplastic syndromes(MDS)and MDS/myeloproliferative neoplasm(MPN).Unfortunately,post-hemopoietic stem cell transplantation(HSCT)relapse remains a cause of treatment failure and the results of salvage treatments are poor.Developing better conditioning regimens is urgently needed.Previous studies have shown synergistic antileukemic effects between decitabine(DEC)and idarubicin(IDA).[1]In an attempt to design a conditioning strategy with very low toxicity but considerable myelosuppressive activity and potential immune-enhancing effects for patients with high-risk MDS and MDS/MPN,we combined DEC and IDA with busulfan,cyclophosphamide,andudarabine for a modied myeloablative regimen in this prospective,multicenter cohort study(hereafter referred to as the“DEC/IDA study”).展开更多
Objective:To investigate the risk factors for cytomegalovirus(CMV)infection within 100 days and the relationship between early CMV infection and 1-year relapse for patients with acute leukemia following allogeneic hem...Objective:To investigate the risk factors for cytomegalovirus(CMV)infection within 100 days and the relationship between early CMV infection and 1-year relapse for patients with acute leukemia following allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Three hundred fifty-nine patients with acute leukemia who received allo-HSCT at our center between January 2015 and January 2020 were retrospectively reviewed.Results:Of 359 patients,48.19%(173)patients experienced CMV infection within 100 days posttransplantation.In univariate and multivariate logistic analysis,haploidentical-related donor(HRD)(P<0.001;odds ratio[OR],5.542;95%confidence interval[CI],3.186–9.639),and ratio of CD3^(+)CD8^(+)cells in lymphocytes<14.825%(P<0.001;OR,3.005;95%CI,1.712–5.275)were identified as 2 independent risk factors.One-year relapse rate(RR)between the CMV infection group and the non-CMV infection group was not statistically significant(18.5%vs 19.9%,P=0.688).When we divided the total cohort into AML,ALL,and MAL subgroups,there were no significant differences as well(P=0.138;P=0.588;P=0.117;respectively).Conclusion:In conclusion,donor type(HRD)and the insufficient recovery of CD3^(+)CD8^(+)cells were independent risk factors for CMV infection within 100 days posttransplantation in patients with acute leukemia.CMV infection within 100 days did not influence the incidence of relapse in 1 year for patients with acute leukemia.展开更多
Ten-eleven translocation 2(TET2)functions as a methylcytosine dioxygenase that catalyzes the iterative oxidation of 5-methylcytosine to 5-hydroxymethylcytosine,5-formylcytosine and 5-carboxylcytosine.TET2 has been sho...Ten-eleven translocation 2(TET2)functions as a methylcytosine dioxygenase that catalyzes the iterative oxidation of 5-methylcytosine to 5-hydroxymethylcytosine,5-formylcytosine and 5-carboxylcytosine.TET2 has been shown to be crucial for the maintenance and differentiation of hematopoietic stem cells,and its deletion and/or mutations results in the expansion of HSPCs,and leads to hematological malignancies.TET2 mutations were found in a variety of hematological disorders such as CMML(60%),MDS(30%),MPN(13%)and AML(20%).Interestingly,it was shown that CMML patients with TET2 mutation exhibited fewer platelets than CMML patients without TET2 mutation.However,the role and function of TET2 in platelet hemostasis and thrombogenesis is not well defined.Here in this study,using a genetically engineered Tet2 deletion mouse model,we found that the absence of Tet2 caused a decrease in the proportion of MEP cells and hyperploid megakaryocytes.Additionally,Tet2-deficient mice displayed impaired platelet activation and aggregation under stimulation of ADP and low concentrations of thrombin,although the modestly compromised platelet function and MEP differentiation in Tet2-deficient mice could be compensated without affecting blood coagulation function.Our study indicate that Tet2 deficiency leads to mild impairment of platelet function and thrombopoiesis in mice.展开更多
Colony-stimulating factor 3 receptor(CSF3R)mutations have been identified in a variety of myeloid disorders.Although CSF3R point mutations(eg,T618I)are emerging as key players in chronic neutrophilic leukemia/atypical...Colony-stimulating factor 3 receptor(CSF3R)mutations have been identified in a variety of myeloid disorders.Although CSF3R point mutations(eg,T618I)are emerging as key players in chronic neutrophilic leukemia/atypical chronic myelogenous leukemia,the significance of rarer CSF3R mutations is unknown.Here,we report a 32-year-old female who was diagnosed as Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph^(+)ALL)with the CSF3R M696T mutation and was undergone unrelated donor hematopoietic stem cell transplantation.The patient achieved complete remission with chemotherapy in combination with tyrosine kinase inhibitor(TKI)and long-term survival by unrelated donor transplantation.Meanwhile,we performed a series of experiments using murine interleukin 3(IL-3)-dependent Ba/F3 cell line to evaluate the transforming capacity of the CSF3R M696T mutation.We confirmed the presence of a CSF3R M696T germline mutation in this patient which was inherited from her mother.The in vitro experiment results showed that the CSF3R M696T mutation contributes marginally to the tumor transformation of Ba/F3 cells,indicating that CSF3R M696T mutation was neutral in tumor transformation ability.We concluded that TKI is effective in patients with the CSF3R M696T mutation in Ph+ALL and donors with CSF3R M696T mutation might still be selected as the candidate for transplantation.展开更多
基金supported by funds from National Key R&D Program of China(2023YFC2508900)the CAMS Innovation Fund for Medical Sciences(2023-I2M-2-007)+4 种基金the National Natural Science Foundation of China(82200124)Tianjin Natural Science Foundation(23JCZXJC00220)Fundamental Research Funds for the Central Universities Funds(3332023058)National Clinical Research Center for Hematological Disorders(2023NCRCA0105)Yingkang Lifetime Fund Project(HH25KYHX0008).
文摘FLT3-ITD,NPM1,and DNMT3A mutations are common in acute myeloid leukemia(AML).However,the prognostic role of FLT3-ITD combined with NPM1 and/or DNMT3A mutations after allogeneic hematopoietic stem cell transplantation(allo-HSCT)remains unclear.In this retrospective study,100 AML patients were selected from a cohort of 1292 who underwent allo-HSCT between 2014 and 2024.Patients were stratified by co-mutation profiles to compare prognosis,identify predictors of survival and relapse,and assess the efficacy of maintenance therapy.With a median follow-up after allo-HSCT of 16.1 months(interquartile range 8.1-26.2),2-year overall survival(OS)rates were 65.1%,68.3%,and 67.1%;leukemia-free survival(LFS)rates were 61.6%,68.7%,and 63.2%;and cumulative incidence of relapse(CIR)rates were 16.9%,12.5%,and 15.8%,respectively.No significant differences were observed among the groups.In multivariate analysis with FLT3 inhibitor as a time-dependent covariate,FLT3-ITD measurable residual disease(MRD)positivity prior to allo-HSCT was independently associated with inferior OS(hazard ratio[HR]=3.51,95%CI 1.34-9.17),LFS(HR=3.05,95%CI 1.26-7.35),and CIR(HR=4.78,95%CI 1.55-14.81).In contrast,posttransplant maintenance therapy with FLT3 inhibitors independently conferred a favorable impact on OS(HR=0.15,95%CI 0.03-0.66),LFS(HR=0.24,95%CI 0.07-0.83),CIR(HR=0.10,95%CI 0.01-0.66),and nonrelapse mortality(NRM)(HR=0.25,95%CI 0.07-0.89).In conclusion,FLT3-ITD-based double or triple mutations showed comparable posttransplant outcomes.FLT3-ITD MRD status and early maintenance therapy were key prognostic and therapeutic factors.
基金by grants from the National Basic Research Program of China(2015CB964402)the National Natural Science Foundation of China(81670171,81601369)+2 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-1-003 and 2018-I2M-HL-013)the Tianjin Science Funds for Distinguished Young Scholars(17JCJQJC45800)the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2018PT32034 and 2019-RC-HL-013).
文摘Accumulating evidence suggests that a reduction in the number of Foxp3^(+) regulatory T cells(Tregs)contributes to the pathogenesis of acute graft-versus-host disease(aGVHD),which is a major adverse complication that can occur after allogeneic hematopoietic stem cell transplantation(allo-HSCT).However,the precise features and mechanism underlying the defects in Tregs remain largely unknown.In this study,we demonstrated that Tregs were more dramatically decreased in bone marrow compared with those in peripheral blood from aGVHD patients and that bone marrow Treg defects were negatively associated with hematopoietic reconstitution.Tregs from aGVHD patients exhibited multiple defects,including the instability of Foxp3 expression,especially in response to IL-12,impaired suppressor function,decreased migratory capacity,and increased apoptosis.Transcriptional profiling revealed the downregulation of Lkb1,a previously identified critical regulator of murine Treg identity and metabolism,and murine Lkb1-regulated genes in Tregs from aGVHD patients.Foxp3 expression in human Tregs could be decreased and increased by the knockdown and overexpression of the Lkb1 gene,respectively.Furthermore,a loss-of-function assay in an aGVHD murine model confirmed that Lkb1 deficiency could impair Tregs and aggravate disease severity.These findings reveal that Lkb1 downregulation contributes to multiple defects in Tregs in human aGVHD and highlight the Lkb1-related pathways that could serve as therapeutic targets that may potentially be manipulated to mitigate aGVHD.
基金the National Natural Science Foundation of China(81670171 and 82070192)Key Project of Tianjin Natural Science Foundation(20JCZDJC00410)thrombocytopenia funding from the Yeehong Business School of Shenyang Pharmaceutical University(Sansheng TCP Young Research Funding,No.57).
文摘Hemorrhagic cystitis(HC)is a common complication of allogeneic hematopoietic stem cell transplantation(HSCT).The incidence is about 7%to 68%,and some patients have to suffer a long period of frequent,urgent,and painful urination,which brings great pain.This study aimed to analyze risk factors of HC and its effect on patient survival.We collected the medical records of 859 patients who underwent HSCT at our hospital between August 2016 and August 2020.Patients with and without HC were matched using propensity score matching at a 1:1 ratio based on sex,age,and diagnosis,and logistic regression analyses were used to identify factors associated with HC.We used Kaplan–Meier curves to analyze the survival rates of patients in the HC and non-HC groups.We also analyzed the relationship between BK viral load and the occurrence of HC using receiver operating characteristic curve(ROC)analysis.After propensity score matching,there were 131 patients each in the HC and non-HC groups.In the HC group,89 patients(67.9%)had mild HC(stage II°)and 43(32.1%)had severe HC(stage III–IV).The median interval between stem cell transplantation and HC development was 31(3–244)days.Univariate analysis indicated that donor age,hematopoietic stem cell source,HLA,acute graft-versus-host disease,busulfan,anti-thymocyte globulin(ATG),total body irradiation,cytomegalovirus(CMV)(urine),and BK polyomavirus(BKV)(urine)were significantly associated with HC.ATG,CMV(urine),and BKV(urine)were independent risk factors for HC based on the multivariate analysis.The Kaplan–Meier survival analysis showed no significant difference between the HC and non-HC groups(P=0.14).The 1-and 2-year survival rates in the HC group were 78.4%and 69.6%,respectively,and the corresponding rates in the non-HC group were 84.4%and 80.7%,respectively.ROC analysis indicated that a urine BKV load of 1×10^(7) copies/mL was able to stratify the risk of HC.In conclusion,when the BKV load is>1×10^(7),we needtobe aware of the potential for the development of HC.
基金the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)[2021-I2M-1-017]and[2021-I2M-C&T-B-080]Haihe Laboratory of Cell Ecosystem Innovation Fund[HH22KYZX0036].
文摘Invasive fungal diseases(IFDs)are major and lethal infectious complications for patients with neutropenia after chemotherapy.Prophylaxis with intravenous and oral suspended itraconazole(200 mg Q12h intravenously×2 days followed by 5 mg/kg·d orally in twice)or oral suspension of posaconazole(200 mg Q8h)was administered for preventing IFDs.The only 2 episodes of proven IFDs were not included after propensity-score matching(PSM),while the incidence of possible IFDs was 8.2%(9/110)in itraconazole group and 1.8%(2/110)in posaconazole group,respectively(P=.030).In clinical failure analysis,the failure rate of posaconazole group was lower as compared to the itraconazole group(2.7%vs 10.9%,P=.016).Both intravenous-oral itraconazole and posaconazole suspension are effective in preventing IFDs,while posaconazole suspension seems more tolerable.
基金supported by grants from the Tianjin Health Science and Technology Project(No.TJWJ2022MS001)Clinical research project of Tianjin Society of Hematology and Regenerative Medicine(No.2022 TSHRM08004)+3 种基金Key Project of Tianjin Natural Science Foundation(No.20JCZDJC00410)CAMS Innovation Fund for Medical Sciences(No.2021-I2M-1-073)Haihe Laboratory of Cell Ecosystem Innovation Fund(No.22HHXBSS00034)National Natural Science Foundation of China(Nos.82070192,8230012348,and 82170217)
文摘To the Editor:Allogeneic hemopoietic stem cell transplantation(allo-HSCT)represents the only long-term survival treatment choice for patients with myelodysplastic syndromes(MDS)and MDS/myeloproliferative neoplasm(MPN).Unfortunately,post-hemopoietic stem cell transplantation(HSCT)relapse remains a cause of treatment failure and the results of salvage treatments are poor.Developing better conditioning regimens is urgently needed.Previous studies have shown synergistic antileukemic effects between decitabine(DEC)and idarubicin(IDA).[1]In an attempt to design a conditioning strategy with very low toxicity but considerable myelosuppressive activity and potential immune-enhancing effects for patients with high-risk MDS and MDS/MPN,we combined DEC and IDA with busulfan,cyclophosphamide,andudarabine for a modied myeloablative regimen in this prospective,multicenter cohort study(hereafter referred to as the“DEC/IDA study”).
基金funded by grants from the CAMS Innovation Fund for Medical Sciences(CIFMS)(grant numbers 2021-1-I2M-017 and 2021-I2M-C&T-B-080).
文摘Objective:To investigate the risk factors for cytomegalovirus(CMV)infection within 100 days and the relationship between early CMV infection and 1-year relapse for patients with acute leukemia following allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Three hundred fifty-nine patients with acute leukemia who received allo-HSCT at our center between January 2015 and January 2020 were retrospectively reviewed.Results:Of 359 patients,48.19%(173)patients experienced CMV infection within 100 days posttransplantation.In univariate and multivariate logistic analysis,haploidentical-related donor(HRD)(P<0.001;odds ratio[OR],5.542;95%confidence interval[CI],3.186–9.639),and ratio of CD3^(+)CD8^(+)cells in lymphocytes<14.825%(P<0.001;OR,3.005;95%CI,1.712–5.275)were identified as 2 independent risk factors.One-year relapse rate(RR)between the CMV infection group and the non-CMV infection group was not statistically significant(18.5%vs 19.9%,P=0.688).When we divided the total cohort into AML,ALL,and MAL subgroups,there were no significant differences as well(P=0.138;P=0.588;P=0.117;respectively).Conclusion:In conclusion,donor type(HRD)and the insufficient recovery of CD3^(+)CD8^(+)cells were independent risk factors for CMV infection within 100 days posttransplantation in patients with acute leukemia.CMV infection within 100 days did not influence the incidence of relapse in 1 year for patients with acute leukemia.
基金This work was partially supported by the funds from the CAMS Innovation Fund for Medical Sciences(2016-I2M-1-017 and 2017-I2M-3-015)National Natural Science Foundation of China(81629001,81421002,81600136,81770105,81970149).
文摘Ten-eleven translocation 2(TET2)functions as a methylcytosine dioxygenase that catalyzes the iterative oxidation of 5-methylcytosine to 5-hydroxymethylcytosine,5-formylcytosine and 5-carboxylcytosine.TET2 has been shown to be crucial for the maintenance and differentiation of hematopoietic stem cells,and its deletion and/or mutations results in the expansion of HSPCs,and leads to hematological malignancies.TET2 mutations were found in a variety of hematological disorders such as CMML(60%),MDS(30%),MPN(13%)and AML(20%).Interestingly,it was shown that CMML patients with TET2 mutation exhibited fewer platelets than CMML patients without TET2 mutation.However,the role and function of TET2 in platelet hemostasis and thrombogenesis is not well defined.Here in this study,using a genetically engineered Tet2 deletion mouse model,we found that the absence of Tet2 caused a decrease in the proportion of MEP cells and hyperploid megakaryocytes.Additionally,Tet2-deficient mice displayed impaired platelet activation and aggregation under stimulation of ADP and low concentrations of thrombin,although the modestly compromised platelet function and MEP differentiation in Tet2-deficient mice could be compensated without affecting blood coagulation function.Our study indicate that Tet2 deficiency leads to mild impairment of platelet function and thrombopoiesis in mice.
基金This work was supported by funds from the Ministry of Science and Technology of China(2018YFA0107801 and 2017YFA0103402)the National Natural Science Foundation of China(82070192,81770105,81770155,and 81670171).
文摘Colony-stimulating factor 3 receptor(CSF3R)mutations have been identified in a variety of myeloid disorders.Although CSF3R point mutations(eg,T618I)are emerging as key players in chronic neutrophilic leukemia/atypical chronic myelogenous leukemia,the significance of rarer CSF3R mutations is unknown.Here,we report a 32-year-old female who was diagnosed as Philadelphia chromosome-positive acute lymphoblastic leukemia(Ph^(+)ALL)with the CSF3R M696T mutation and was undergone unrelated donor hematopoietic stem cell transplantation.The patient achieved complete remission with chemotherapy in combination with tyrosine kinase inhibitor(TKI)and long-term survival by unrelated donor transplantation.Meanwhile,we performed a series of experiments using murine interleukin 3(IL-3)-dependent Ba/F3 cell line to evaluate the transforming capacity of the CSF3R M696T mutation.We confirmed the presence of a CSF3R M696T germline mutation in this patient which was inherited from her mother.The in vitro experiment results showed that the CSF3R M696T mutation contributes marginally to the tumor transformation of Ba/F3 cells,indicating that CSF3R M696T mutation was neutral in tumor transformation ability.We concluded that TKI is effective in patients with the CSF3R M696T mutation in Ph+ALL and donors with CSF3R M696T mutation might still be selected as the candidate for transplantation.
