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  • 1
    In: Blood Cancer Journal, Springer Science and Business Media LLC, Vol. 11, No. 12 ( 2021-12-06)
    Abstract: We aimed to investigate outcomes of different post-remission treatment (PRT) choices based on dynamic measurable residual disease (MRD) by multiparameter flow cytometry in favorable-risk AML (FR-AML). Four hundred and three younger patients with FR-AML in first complete remission (CR1) were enrolled in this registry-based cohort study, including 173 who received chemotherapy (CMT), 92 autologous stem cell transplantation (auto-SCT), and 138 allogeneic SCT (allo-SCT). The primary endpoint was the 5-year overall survival (OS). Subgroup analyses were performed based on dynamic MRD after the 1st, 2nd, and 3rd courses of chemotherapy. In subgroups of patients with negative MRD after 1 or 2 course of chemotherapy, comparable OS was observed among the CMT, auto-SCT, and allo-SCT groups ( p  = 0.340; p  = 0.627, respectively). But CMT and auto-SCT had better graft-versus-host-disease-free, relapse-free survival (GRFS) than allo-SCT in both subgroups. For patients with negative MRD after three courses of chemotherapy, allo-SCT had better disease-free-survival than CMT ( p  = 0.009). However, OS was comparable among the three groups ( p  = 0.656). For patients with persistently positive MRD after 3 courses of chemotherapy or recurrent MRD, allo-SCT had better OS than CMT and auto-SCT ( p  = 0.011; p  = 0.029, respectively). Dynamic MRD might improve therapy stratification and optimize PRT selection for FR-AML in CR1.
    Type of Medium: Online Resource
    ISSN: 2044-5385
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 2
    In: JAMA Network Open, American Medical Association (AMA), Vol. 4, No. 7 ( 2021-07-07), p. e2115991-
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
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  • 3
    In: Leukemia, Springer Science and Business Media LLC, Vol. 34, No. 5 ( 2020-05), p. 1433-1443
    Type of Medium: Online Resource
    ISSN: 0887-6924 , 1476-5551
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
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  • 4
    In: Signal Transduction and Targeted Therapy, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2023-09-14)
    Abstract: Sorafenib therapy improves overall survival (OS) in patients with FLT3 internal tandem duplication (ITD) acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation. We explored the efficacy of sorafenib therapy in this population with different concomitant genetic patterns. In this multi-center, cohort study, we enrolled patients with FLT3-ITD AML undergoing allogenic hematopoietic cell transplantation. Patients with sorafenib maintenance post-transplantation for at least four weeks were allocated to the sorafenib group, and otherwise to the control group. Endpoints were OS, disease-free survival, and relapse for the whole cohort and OS for genetic pattern subgroups. Among 613 patients enrolled, 275 were in the sorafenib and 338 the control group. Median follow-up was 36.5 (interquartile range (IQR), 25.2–44.7) months post-transplantation. The 3-year OS post-transplantation was 79.6% (95% confidential interval (CI) 74.8%–84.6%) and 65.2% (95% CI 60.3%–70.6%) (Hazard ratio (HR) 0.50, 95% CI 0.37–0.69; P   〈  0.0001) in both groups. Sorafenib maintenance post-transplantation improved OS in the favorable (HR 0.33, 95% CI 0.14–0.77; P  = 0.011) and adverse (HR 0.56, 95% CI 0.33–0.93; P  = 0.026) ELN 2017 risk subgroups. Patients with mutated NPM1, DNMT3A, co-occurring NPM1/DNMT3A, “activated signaling” and “DNA methylation” genes benefited in OS from sorafenib maintenance, while those carrying CEBPA, “tumor suppressors” and “myeloid transcription factors” genes did not. Patients with FLT3-ITD high and FLT3-ITD low AML both benefited in OS from sorafenib maintenance. Our results identify the response of genetic patterns to sorafenib maintenance, providing new viewpoints for the optimal use of sorafenib in FLT3-ITD AML in the transplantation setting.
    Type of Medium: Online Resource
    ISSN: 2059-3635
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 5
    In: Journal of Hematology & Oncology, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2020-12)
    Abstract: Compared with HLA-matched sibling donor (MSD) transplant, the outcomes of haploidentical donor (HID) transplant for refractory acute leukemia need to be further explored. In this study, we compared the outcomes of HID with MSD for refractory acute leukemia. Patients and methods This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Two hundred and seventy-eight patients with refractory acute leukemia were enrolled in this study, including 119 in HID group and 132 in MSD group. Sequential intensified conditioning was employed in all patients, and donor lymphocyte infusion (DLI) was administered in patients in the absence of active GVHD and according to minimal residual disease (MRD) from day + 60 post-transplantation for preventing relapse. Results The complete remission of leukemia by day + 30 post-transplant were 94% and 93%, respectively, in HID and MSD groups ( p = .802). The 1-year incidence of grades II–IV acute GVHD was 62% and 54% ( p = .025), and 3-year incidence of chronic GVHD was 55% and 55% ( p = .789), respectively, in two groups. HID transplant had lower incidence of first episode of MRD positivity and relapse than MSD transplant (28% vs 45%, p = .006; 26% vs 38%, p = .034). There was higher infection-related mortality in HID than MSD (8% vs 2%, p = .049) within the first 100 days’ post-transplant. The 5-year overall survival was 46% and 42% ( p = .832), respectively; the 5-year disease-free survival was 43% and 39% ( p = .665), in HID and MSD groups, respectively. Conclusions HID transplant has lower relapse, but higher infection-related mortality and similar survival rates in refractory acute leukemia by the strategy of sequential intensified conditioning followed by DLI compared with MSD transplant.
    Type of Medium: Online Resource
    ISSN: 1756-8722
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
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  • 6
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 4556-4556
    Abstract: Acute hemorrhagic cystitis (HC), a severe complication of hematopoietic stem cell transplantation (HSCT), being considered mainly as a result of cyclophosphamide (CTX), seriously affects the quality of life of patients. Mesna, whose half-life is about 70min, is widely used to prevent HC. Aim of this research is to explore the effect of preventing HC in HSCT by continuous intravenous injection of mesna using micro pump on HC in HSCT. Methods (1) 359 patients who underwent allogenic HSCT in Nanfang hospital from January 2003 to December 2012 were recruited into this study (227 male and 132 female). Conditioning regimens were BuCy or TBI-Cy, in which CTX were given 60mg/kg·d,d-3,-2; or GIAC, in which CTX were given 1.8g/m2, d-5, -4. Intravenous injection of mesna was used to prevent HC continuously using micro pump (continuous group, n=250) or intermittently (intermittent group, n=185). Graft versus host disease (GVHD) prevention regimen was cyclosporine A+MTX for HLA-matched sibling donors and cyclosporine A+MTX+ATG for unrelated donors or HLA partial-matched related donors. (2) Both groups received the same daily dose of mesna, which is about 150% of CTX daily dosage. In the intermittent group, 25% of mesna’s daily dosage was injected at 0h, 3h, 6h and 9h after the use of CTX at each time-point; while in the continuous group, 25% of mesna’s daily dosage was injected before the use of CTX, with the rest dosage being continuously injected intravenously for 24hs using micro-infusion pump (25% daily dosage of mesna dissolved in 40ml 0.9% sodium chloride lasting for 8h was given, q8h), from the first dose of CTX till 48hs after the last injection of CTX. Incidences and grades of HC in the two groups were followed up and analyzed. (3)The mesna concentration in urine of two groups was detected by High Performance Liquid Chromatography (HPLC), with the comparison of the trough concentrations and the peak concentration. Results (1) Within 30d after transplantation, HC occurs in 30 of the 160 (18.75%) cases in the intermittent group vs. 16 of 199(8.04%) in the continuous group (P=0.00077). Within 60d after transplantation, HC occurs in 45 of 160 (28.13%) cases in the intermittent group (17cases of I°, 18cases of II°, 8 cases of III°, 2 cases of IV°) with the mean occurrence time being +18.16d (-5-+41d); while only 24 of 199 (12.06%) cases (15 cases of I°, 6 cases of II°, 3 cases of III°, 0 cases of IV°) in the continuous group with the mean time of +26.58d (+2d-+58d). There were statistical significances of the incidence within 60d(P=0.000123) and occurrence time(P=0.018), however there was no statistical significances of grade/severity (P=0.057) of HC between the two groups. (2) Logistic regression analysis shows that within 30d after transplantation, the HC occurrences relates with the way of using mesna (P=0.004), with continuous mesna injection being a protective factor (OR=0.299, 95% CI=0.130-0.684); while age, sex, 24h mean liquid intake, 24h mean excretion, 24h mean urinary volume (each P 〉 0.2) and HLA matching (P=0.099) were unrelated factor. Within 60d after transplantation, the HC occurrences relates with the way of using mesna (P=0.001)and GVHD (P=0.007); continuous mesna injection is a protective factor (OR=0.296, 95% CI=0.146-0.600) and HLA matching is a risk factor (OR=2.422, 95%CI=1.280-4.580). (3) Althrough 73 samples were detected by HPLC for mesna in urine, there were no significant difference of peak and trough concentration between groups. Discussion Early occurrence of HC is mostly related to high dose of cyclophosphamide, while late occurrence of HC can also be related with GVHD and infections. The continuous injection of mesna is a better way for the prevention of HC in HSCT patients, due to its short half-life of mesna. While injection with micro-infusion pump can reduce liquid intake, especially suitable for those who have heart or kidney dysfunctions. Conclusion Continuous intravenous injection of mesna is efficient to prevent HC in hematopoietic stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 7
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 825-825
    Abstract: Background: Antithymocyteglobulin (ATG), used as conditioning regimen, can reduce graft-versus-host disease (GVHD) in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Notwithstanding, immunosuppressive effect of ATG may increase the risk of viral infections after HSCT. To evaluate the effect of different doses of ATG on post-transplant viral infection, we conducted a multicenter prospective study to compare EBV and CMV infection in haplo-HSCT recipients receiving 7.5 mg/kg or 10 mg/kg ATG. Methods Between May 2013 and November 2015, 350 consecutive patients with hematological malignancies undergoing haplo-HSCT were randomized in 5 hospitals. One hundred and seventy-two patients received ATG with a total dosage of 7.5 mg/kg and 175 received 10 mg/kg ATG. Three patients did not received allocated intervention and transplantation due to leukemia relapse before transplant or toxicity of conditioning regimens. Results The cumulative incidence of EBV viremia on day 180 was 23.3±3.2% in 7.5 mg/kg ATG arm which was lower than that in 10 mg/kg arm (34.6±3.7%, P=0.037). CMV viremia were comparable in the two arms (7.5 mg/kg arm: 79.0±3.1% vs. 10 mg/kg arm: 76.9±3.2%, P=0.950). The incidences of CMV diseases were 0.6±0.6% and 2.4±1.2% in 7.5 mg/kg and 10 mg/kg arms, respectively (P=0.093). No difference in the incidence of post-transplant lymphoproliferative disorder (PTLD) was found between the two arms (2.4±1.2% in 7.5 mg/kg arm vs. 5.4±1.8% in 10 mg/kg arm, P=0.150). Besides, acute GVHD grade II to IV within 100 days occurred in 55 recipients with the incidence of 31.4% in 7.5mg/kg ATG arms and 45 recipients in 10 mg/kg arms with the incidence of 26.2% (P=0.279). The incidences of aGVHD grade III to IV were similar in the two arms (8.0% in 7.5 mg/kg arm: vs. 4.7% in 10 mg/kg arm, P=0.196). The 2-years overall survival were 69.5±4.7% and 69.4±3.9% for 7.5 mg/kg and 10 mg/kg group (P=0.540). Conclusion Compared with 10 mg/kg of ATG, the application of 7.5 mg/kg might reduce the risk of EBV infection after haplo-HSCT and not increase aGVHD. Disclosures Lin: National Natural Science Foundation of China 81270647: Research Funding; Science and technology planning project of Guangdong Province 2014B020226004: Research Funding; The project of health collaborative innovation of Guangzhou City 201400000003-4: Research Funding; National Natural Science Foundation of China 81400141: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 8
    In: Cancer, Wiley, Vol. 128, No. 11 ( 2022-06), p. 2138-2147
    Abstract: Sorafenib combined with conventional therapies is effective and safe for refractory central nervous system leukemia.
    Type of Medium: Online Resource
    ISSN: 0008-543X , 1097-0142
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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  • 9
    In: The Lancet Oncology, Elsevier BV, Vol. 21, No. 9 ( 2020-09), p. 1201-1212
    Type of Medium: Online Resource
    ISSN: 1470-2045
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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  • 10
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 3693-3693
    Abstract: Engraftment failure (EF) is a formidable complication after autologous hematopoietic stem cell transplantation (auto-HSCT). Mesenchymal stem cells (MSCs) and cord blood (CB) have been found to support hematopoiesis. Thus, we designed a multicenter randomized clinical trial to investigate the effects and safety of MSCs alone or combined with CB infusion for patients with EF. Methods Twenty-two patients were randomly assigned to receive the treatment with MSCs alone (MSCs group, n=11) or MSCs combined with CB (CB group, n=11). MSCs were administered once every 2 weeks (2 doses were a cycle) in both groups, and single-unit CB was administered at the same day with the first application of MSCs in CB group; After one cycle of treatments (within 28 days), the patients who did not response to MSCs would receive the therapeutic schedule in CB group, and those patients with partial response (PR) in MSCs group and those without complete response (CR) in CB group would continue another cycle of MSCs treatment. If patients did not obtain CR after two cycles of treatments (within 56 days), they would receive other treatments including allogeneic HSCT. Results After the first treatment cycle, the effect rates were not significant difference in MSCs and CB groups (7/11 vs. 9/11, P=0.635), and the median time of hematopoietic reconstruction was 22 (18-28) and 17 (13-22) days, respectively (P=0.036) in MSCs and CB group. There was statistically significant difference regarding neutrophil engraftment, with 17 (range 9-28) and 8 (range 6-14) days respectively (P=0.030), but no difference regarding platelet engraftment, with 21 (range 18-28) and 18 (range 11-21) days respectively (P=0.092) between MSCs and CB groups. After two cycles of treatments, 17 patients obtained CR, 2 PR and 3 NR. CB chimerisms were not detected by short tandem repeat (STR) at +15 and +30 days after CB infusion. None of the patients experienced any adverse events of grade 3/4 with the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0) and acute GVHD or chronic GVHD during the period of study treatment and follow-up. One patient with PR in MSCs group and 1 NR in CB group received allogeneic HSCT at +249 and +273 days after auto-HSCT because of EF and primary disease relapse, respectively. At a median follow-up time of 345 (range 129–784) days post-transplantation, 16 patients remained alive, 3 died of relapse of primary diseases and 1 died of CMV pneumonia following allo-HSCT. None of patients developed EBV-DNA viremia and EBV-associated diseases in two groups. The 2-year overall survival, disease-free survival and tumor relapse post-transplantation were 75.2% (95% CI, 63.2-87.2%), 79.5% (95% CI, 70.1-88.9%) and 20.5% (95% CI, 11.1-29.9%) respectively. Conclusions Our data suggest that ex-vivo-expanded MSCs derived from HLA-mismatched BM alone or combined with unrelated CB are effective to EF after auto-HSCT. CB can facilitate the effect of MSCs to EF. Both two strategies do not result in GVHD or increase the risk of primary diseases relapse in patients with EF. This trial was registered at www.clinicaltrials.govas#NCT01763099. Disclosures: Liu: It was supported by 863 Program (No. 2011AA020105) and National Public Health Grand Research Foundation (Grant No. 201202017).: Research Funding; It was supported by National Natural Science Foundation of China (Grant No.81000231, No.81270647) and Science and Technology Program of Guangzhou of China (11A72121174). : Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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