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  • 1
    Online Resource
    Online Resource
    Management of Early Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation by Donor’s Dendritic Cell-Primed Cytokine- Induced Killer Cells
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 829-829
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 829-829
    Abstract: Leukemia relapse after allogeneic hematopoietic stem cell transplantation (HSCT) is one of the main obstacles for survival. Immunosuppressant withdraw, chemotherapy, and donor lymphocyte infusion(DLI) are usually employed for management of recurrence after HSCT, but some patients have poor response to above therapy or have contraindications for DLI due to relapse at early stage after transplant or with active graft-versus-host disease (GVHD). Dendritic cell-primed cytokine-induced killer cells (DC-CIK) have been successfully applied in treatment of minimal residual disease (MRD) in our center for 12 years. In present pilot clinical study, we explore to manage early leukemia relapse after HSCT with donor’s DC-CIK in appropriate patients. The patients who relapsed in hematological (5–20% blasts in BM) or molecular or immunological (MRD 〉 0.1% by flow cytometry) with at least one of the following criteria were included in this clinical trial. 1. No response to DLI; 2. Relapsed within 60 days after HSCT; 3. Relapsed with active GVHD. Total 18 patients (male 9, female 9) with median age 26 (4 to 42) years were eligible to this clinical study. The diagnosis included acute myeloid leukemia (AML 13), acute lymphoblastic leukemia (ALL 4) and chronic myeloid leukemia (CML 1) who failed to reach molecular remission with imatinib before transplant. The types of donor were HLA identical sibling (11), haploidentical family member (5), and unrelated donor (2). Six of 18 patients had either molecular or immunological recurrence, while 12 of 18 cases relapsed hematologically. The median cell dosage of DC-CIK infused was 2.34×109 (0.2–44×109). With DC-CIK treatment, overall 11 of 18 (61.1%) patients achieved complete remission (CR, molecular or immunological or hematological based on the disease status before DC-CIK). Among 6 cases in molecular or immunological recurrence, five of them (83.3%) obtained CR, while 12 patients with early hematological relapse, 6 of them (50%) returned to CR. Seven of 13 patients with AML, and all 4 cases with ALL responded to DC-CIK treatment, while a patient with CML had no therapeutic benefit from it. Among 7 cases without response to DC-CIK, one patient with CML achieved molecular remission with high-dose Imatinib, 1 case obtained CR after DLI later on, 1 patient survived with primary disease so far, and the remaining 4 patients died from leukemia recurrence. In 11 cases who responded to DC-CIK, 10 of them survived with median 359(164 to 1233) days. One patient died from transplant-related complications. Four patients developed GVHD after DC-CIK infusion and controlled completely with Cyclosporin A and Methylprednisolone. Our encouraging results indicate that Donor’s DC-CIK is a safe and effective therapeutic option in management of early leukemia recurrence after allogeneic HSCT, especially for the patients who fail to or ineligible to current standard practice.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.829.829
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    Online Resource
    Online Resource
    Improved Outcomes of Haploidentical Blood and Marrow Transplantation in Hematologic Malignancies: A Single Center Study of 514 Cases
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 3224-3224
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3224-3224
    Abstract: Introduction: With GIAC regimen, haploidentical blood and marrow transplantation (haplo-BMT) has achieved comparable outcomes with identical sibling transplant (Dao-Pei Lu et al., Blood 2006; 107:3065). Our previous study has shown that the third party cell co-infusion in haplo-BMT (GIAC-3 regimen) could significantly reduce aGVHD and transplant-related mortality (TRM). We have also demonstrated that individualized chemotherapy to decrease leukemia burden followed by conditioning could improve disease-free survival (DFS) in refractory/relapsed AML. Objective: To learn the outcomes of our haplo-BMT with these integrated approaches, all patients who received haplo-BMT for hematologic malignancies in our center were analyzed retrospectively. Methods: Between April 2012 and December 2014, consecutive 514 patients with hematologic malignancies who underwent haplo-BMT were included. The median age was 20 (1.8 to 64) years old. The diagnosis included AML 232 (45.1%), ALL 207 (40.3%), MDS 27(5.3%), CML 14 (2.7%), lymphoma 13 (2.5%) and others 21 (4.1%). Transplants at CR1, ≥CR2 or advanced disease were 216 (42.0%), 114 (22.2%), 184 (35.8%), respectively. All patients received unmanipulated bone marrow (BM) and peripheral blood stem cells as graft after myeloablative conditioning plus ATG. Majority of the patients with AML received BuCy-based conditioning, while most ALL patients received TBICy-based regimen. Fludarabine was substituted for cyclophosphamide in some patients due to impaired organ function or high tumor burden. For refractory/relapsed diseases, individualized chemotherapy followed by conditioning was administered. Cyclosporine/tacrolimus, short-term Methotrexate, and Mycophenolate mofetil were employed for GVHD prophylaxis. Either 1ml/kg (recipient's body weight) haploidentical BM from the second haploidentical donor or one unit of unrelated cord blood was infused right after haplo-BMT as the third party cells. Minimal residual disease (MRD) was monitored routinely by quantitative PCR or flow cytometry. The patients with persistent MRD were interfered by immunosuppressant withdrew, adoptive immunotherapy with cytokine induced killer or NK cells or donor lymphocyte infusion. Results: All patients but 5 achieved durable engraftment. The cumulative incidences of grade II to IV aGVHD and grade III to IV aGVHD were 32.2%, 19.8%, respectively. The cumulative incidences of cGVHD and extensive cGVHD were 48.3%, 18.4%, respectively. 100-day TRM and 2-year TRM were 4.1%, 14.9%, respectively. Two-year relapse rate was 22.8%. With the median follow up 17 (6 to 38) months, overall 2-year DFS rates in CR1, ≥CR2 and advanced disease were 75.6%, 70.9%, 49.2%, respectively. For AML, two-year DFS rates in CR1, ≥CR2 and advanced disease were 74.1%, 76.9%, 48.2% (CR1 vs. ≥CR2, p=0.84; CR vs. advanced disease, p=0.000). For ALL, two-year DFS rates in CR1, ≥CR2 and advanced disease were 78.9%, 56.6%, 38%, respectively (CR1 vs. ≥CR2, p=0.018; CR1 vs. NR, p=0.000; ≥CR2 vs. NR P=0.02 ). Conclusions: With our strategies, overall outcomes of haplo-BMT have been improved remarkably and very encouraging. Therefore, haplo-BMT should be an important way to save life for the patients with hematologic malignancies who need urgent BMT but without matched either sibling or unrelated donor. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.3224.3224
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    Tetra-Arsenic Tetra-Sulfide Containing Triple-Agent Regimen as the First Line Therapy for Acute Promyelocytic Leukemia: Expeditiously Consecutive Complete Remission and Improved Disease-Free Survival.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 591-591
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 591-591
    Abstract: Our previous study has demonstrated that tetra-arsenic tetra-sulfide (As4S4) treatment alone is highly effective and safe in both induction and maintenance therapy in acute promyelocytic leukemia (APL) patients (Lu DP et al, Blood2002; 99: 3136). In current clinical study, we explored whether As4S4 combined sequentially or simultaneously with all-trans retinoid acid (ATRA) and cytotoxic agents according to specific clinical condition as the first line therapy could expedite complete remission (CR) but in a safer way and further improve disease-free survival (DFS). The treatment-related toxicities were also studied. From April 2001 to May 2007, 114 patients with APL in a median age of 32.5 years (10–73 years) were enrolled including consecutive 68 newly diagnosed cases and 46 patients in hematological remission. For induction therapy, both As4S4 (60 mg/kg) and, if leukocytosis or retinoid acid syndrome was not a risk, ATRA (25mg/m2) were taken orally per day till CR. Cytotoxic agents such as mitoxantrone and/or hydroxyurea were added when WBC counts were more than 4 × 109/L. After hematological remission, 4 to 6 cycles of combined chemotherapy were given, and followed by alternatively oral use of As4S4 (3 cycles) and ATRA (1 cycle) in outpatient base for maintenance therapy until 4 years after diagnosis. PML/RARa transcript was monitored quantitatively by real-time PCR. Arsenic levels in blood and urine were also monitored with an atomic absorption spectrophotometer. Consecutive 68 newly diagnosed patients all achieved complete hematological remission in a median time of 29.5 days (14 – 62 days) without early death. The median time to achieve molecular remission was 61.5 days (34 – 120 days). Four out of 114 patients relapsed. One of them had obtained CR again. One patient died from leukemia relapse. Treatment with As4S4containing regimen was well tolerated. Mild gastrointestinal discomfort, transient elevation in liver enzyme, rash, and edema were noted in a few cases. Estimated DFS rate for 4 years was 94%, with a median follow-up time of 36.5 months (3–76 months). Our encouraging results show that faster consecutive CR, higher DFS rate and better quality of life have been achieved with the above regimen as the first line therapy for APL patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.591.591
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
    Online Resource
    Online Resource
    Donor-Derived Ex-Vivo Activated NK Cells in Management of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in High-Risk Acute Leukemia
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 312-312
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 312-312
    Abstract: Introduction: Relapse remains the main cause of failure of hematopoietic stem cell transplantation (HSCT) in acute leukemia. NK cells have the property of killing leukemia cells without GVHD aggravation theoretically. Moreover, in some cases, leukemia cells may lost HLA-I and/HLA-II antigens which would result in poor response to the immunotherapy except NK-based adoptive effectors. Objective: In present study, the safety and efficacy of donor-derived ex-vivo activated NK cells in management of relapse after allogeneic HSCT in high-risk acute leukemia were examined. Patients and methods: Between July 2012 and July 2014, 29 patients with acute leukemia who received NK cell infusion after HSCT were analyzed retrospectively. Some cases failed to chemotherapy combined with donor lymphocyte infusion (DLI) before NK cell therapy. The diagnosis were ALL (10 cases), AML (18 cases) and mixed acute leukemia (1 case). All patients were high-risk leukemia. The disease status before transplant was CR1 in 8 cases, CR2 in 7, CR3 in 1 and non-remission in 13. The types of donor included identical sibling (5 cases), haploientical family member (21 cases) and unrelated donor (3 cases). The conditioning and GVHD prophylactic regimens were reported previously (Lu DP et al., Blood 2006; 107:3065). Minimal residual disease (MRD) was detected by either quantitative RT-PCR for fusion genes or flow cytometry or both. The expression of HLA-I and HLA-II antigens in leukemia cells was evaluated by flow cytometry. Donor-derived either peripheral blood stem cells or lymphocytes were cultured for 6 days using original culture system (AIM-V medium with IL-2, IL-12, IL-15 and IL-21) or modified culture system (SCGM medium with IL-2, IL-12, IL-15, IL-18 and IL-21). Escalated dosage of NK cells were infused starting with 1×105 cells/kg (recipient’s body weight) with or without IL-2 injection. Nine patients were in prevention group and 20 cases were in treatment group. The patients with hematologic relapse received NK cells 3 days later after chemotherapy. Results: Compared with our original culture system, the modified culture system enhanced approximately 10% to 20% of the purity and 4 to 8 fold in number of NK cells by day 6. Furthermore, our modified culture system elevated the expression of function phenotype including TRAIL, NKG2D and CD62L on NK cells in approximately 8 to 10 folds at day 6 and simultaneously stimulated higher level of IFN-γ. One to 4 NK cell infusions were given in each case with two week interval. Two of 29 cases developed mild skin GVHD. No transfusion-related side effects were noted. In prevention group, four of 9 cases remain complete remission, and the other 5 patients became MRD positive or relapse. In treatment group, seven of 20 cases have response to NK cell therapy, and two out of 7 cases who response to NK cells had failed to chemotherapy plus DLI before. Among 11 patients who had response to NK cells, eight of them are AML, and the remaining 3 patients are ALL. Higher response rate (10/23 cases) was seen with NK cell therapy by our modified culture system compared with the one (1/6 cases) by our original culture system. Conclusions: Our preliminary results have demonstrated that donor-derived ex-vivo activated NK cells are safe and effective modality in the management of relapse after allogeneic HSCT in high-risk acute leukemia even failed to chemotherapy combined with DLI. Optimal culture system has improved not only NK cell’s purity, number and function phenotype but also clinical efficacy. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.312.312
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    Online Resource
    Online Resource
    Successful Rescue of Refractory/Recurrent Myelogenous Leukemia by Allogeneic Hematopoietic Cell Transplantation and Prophylactic Immunotherapy.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 4095-4095
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4095-4095
    Abstract: Abstract 4095 Poster Board III-1030 The clinical outcomes of refractory/recurrent leukemia that salvaged by allogeneic hematopoietic cell transplantation (HCT) is usually poor. It is crucial for the management of those high-risk patients with appropriate conditioning regimens that balance the efficacy and safety well and with enhanced anti-leukemia effect post-HCT. Our previous study has shown that donor's dendritic cell-primed cytokine-induced killer cells (DC-CIK) is a safe and effective therapy in the management of early leukemia recurrence after allogeneic HCT, which fail to or ineligible for current standard treatment. Objective In present clinical study, we examine the efficacy of refractory/recurrent myelogenous leukemia salvaged by allogeneic HCT and prophylactic immunotherapy. Methods From September 2006 to May 2008, 30 patients with refractory/recurrent myelogenous leukemia (AML 29, CML-BC 1) were enrolled. The median age was 32 (12 to 55) years old. The median blasts in bone marrow were 36% (20% to 87%) prior to conditioning. The grafts were from HLA identical siblings (5), unrelated donors (7), and haploidentical family members (18). Conditioning regiments were individualized according to patients' status as following. Generally, the regimen with high-dose cytarabine plus BUCY2 was used (13 cases). The patients with impaired organ function received above regimen except with fludarabine instead of cyclophosphamide (11 cases). For the recipients with 〉 40% blasts in bone marrow, melphalan (2 cases) or aclarubicin (1 case) was added into the regimen or FLAG followed by reduced-intensified BUCY2 (3 cases) was employed in order to reduce leukemia burden. Cyclosporine A, methotrexate and mycophenolate mofetil were administrated for GVHD prophylaxis. To prevent leukemia relapse, immunosuppressants were tapered off early post-HCT. Prophylactic immunotherapy including cellular (DLI, DC-CIK, NK cells), and humoral (IL-2, IFN-a, thymosin) was used selectively in the patients who had no GVHD 120 days after HCT. Results The median mononuclear cells in the graft were 7.36 (3.49 to 11.5) ×108/kg. The median CD34+ cells were 4.06 (1.57 to 11.4) ×106/kg. The median CD3+ cells were 1.42 (0.75 to 3.61) ×108/kg. Twenty-nine patients attained sustained engraftment. One died of multi-organ failure before hematopoietic reconstitution. The median time for white blood cells 〉 1.0 × 109/L, and platelets 〉 20 × 109/L was 14 (10 to 21) days, 15 (12 to 26) days, respectively. Thirteen patients developed acute GVHD (grade I in 5, grade II in 7, and grade III in 1). Thirteen patients developed chronic GVHD after immunosuppressants' reduction or withdrawal. In addition, 13 patients received prophylactic immunotherapy due to lack of chronic GVHD 120 days post-HCT, then 7 of 13 developed chronic GVHD. With the median follow-up of 15 (3 to 35) months, two (6.7%) patients with AML had hematological recurrence. One patient attained durable complete remission again after treatment with chemotherapy followed by immunotherapy with DLI, DC-CIK, and NK cells. Five (16.7%) patients died (infections in 2, hematological relapse in 1, chronic GVHD in 1, and multi-organ failure in 1). 25 of 30 (83.3%) patients have been in continuous complete remission since salvaged HCT. Conclusion Our preliminary clinical results have shown that the combination of salvaged allogeneic HCT and prophylactic immunotherapy is a promising modality for the treatment of myelogenous leukemia in refractory/recurrent status, even with high leukemia burden. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.4095.4095
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
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  • 6
    Online Resource
    Online Resource
    Effects of Erlong Zuoci decoction on the age-related hearing loss in C57BL/6J mice
    Elsevier BV ; 2016
    In:  Journal of Ethnopharmacology Vol. 181 ( 2016-04), p. 59-65
    Details
    In: Journal of Ethnopharmacology, Elsevier BV, Vol. 181 ( 2016-04), p. 59-65
    Type of Medium: Online Resource
    ISSN: 0378-8741
    URL: Article
    DOI: 10.1016/j.jep.2016.01.025
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 134511-4
    SSG: 15,3
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  • 7
    Online Resource
    Online Resource
    Immunotherapy with Autologous Anti-CD19 Chimeric Antigen Receptor T Cells Followed By Allogeneic Hematopoietic Stem Cell Transplantation Has Remarkably Improved Leukemia-Free Survival in Refractory/Relapsed B-Cell Acute Lymphoblastic Leukemia
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 829-829
    Details
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 829-829
    Abstract: Introduction: The prognosis of refractory/relapsed acute lymphoblastic leukemia (ALL) is poor with chemotherapy or even allogeneic hematopoietic stem cell transplantation (HSCT). Although our immunotherapy with autologous anti-CD19 chimeric antigen receptor T cells (CART) has resulted in 88.6% complete remission (CR) in refractory/relapsed B-cell ALL (B-ALL), many patients relapsed at around 2 months after CART therapy (unpublished data). Our current strategy is to perform HSCT for refractory/relapsed B-ALL in CR by CART therapy to attain continuous leukemia-free survival (LFS). However, majority of the patients with CART therapy developed cytokine release syndrome which may increase transplant-related mortality (TRM). Moreover, all patients with CART therapy have very tough diseases which could result in higher relapse rate after transplant. Objective: In current study, the safety and efficacy of HSCT for refractory/relapsed B-ALL after CART therapy were investigated. The patients with B-ALL who received HSCT during the same time period without CART therapy were as control. Patients and Methods: Between July 2015 and May 2016, consecutive 22 patients with refractory/relapsed CD19+ B-ALL in CR by CART therapy followed by allogeneic HSCT in our hospital were analyzed as CART group; and consecutive 89 patients with B-ALL in CR who received allogeneic HSCT in our hospital during the same time period but without previous CART therapy were as control group. Clinical characteristics between two groups was comparable except more CR1 (22.7% vs. 57.3%) in control group and more CD3+ cells infused (1.93x108/kg vs. 1.46 x108/kg, p=0.026) in CART group. The median age was 8 (2-44) years, 15 (2-52) years in CART and control groups (p=0.147). The median disease course was 19.1 (3.9-53.7) months, 10.6 (3.7-123.0) months in CART and control groups (p=0.385). The median time from CART therapy to HSCT was 86 (31-172) days. Disease status was 22.7% cases in CR1, 54.5% in CR2, 18.2% in CR3 and 4.5% in CR4 in CART group; and 57.3% cases in CR1, 36.0% in CR2 and 6.7% in CR3 in control group (p=0.08). Minimal residual disease pre-conditioning by flow cytometry was positive in 22.7%, 31.5% patients in CART and control groups (p=0.422). Donor source was identical sibling (IS) in 13.6%, unrelated (UR) in 31.8% and haploidentical (HI) in 54.5% in CART group; and IS in 14.6%, UR in 16.9% and HI in 68.5% in control group (p=0.313). Myeloablative conditioning regimens were administered with either total body irradiation (TBI) plus cyclophosphamide (Cy)/ fludarabine (Flu)-based in 90.9% cases or busulfan (Bu) plus Cy/ Flu-based in 9.1% cases in CART group; and TBICY/Flu-based in 85.4% cases or BuCy/Flu-based in 14.6% cases in control group (p=0.498). Antithymocyte globulin was used in UR and HI transplants. Cyclosporine, short-term methotrexate, and mycophenolate mofetil were employed for GVHD prophylaxis. Results: The median time to neutrophil engraftment was similar between two groups (14 days vs. 13 days, p=0.196), but platelet engraftment was slower in CART group (14 days vs. 12 days, p=0.031). Cumulative incidence of grade II-IV acute GVHD (aGVHD) was higher in CART group (57.6% vs. 33.1%, p=0.009), which may related to higher CD3+ cells infused in CART cohort; but the incidences of grade III-IV aGVHD were no statistical significance (25.1% vs. 15.7%, p=0.564) in two groups. No remarkable differences were seen in CMV reactivation (45% vs. 51.7%, p=0.601) and transplant-associated thrombotic microangiopathy (13.6% vs. 9.0%, p=0.514) in two groups. No significant difference was found in TRM between CART and control groups (7.1% vs. 15.2%, p=0.808). Relapse rates were similar in two groups (5.0% vs. 6.9%, p=0.888). With a median follow-up 9 (2-12) months, LFS was comparable in CART and control groups (84.8% vs. 80.9%, p=0.937). Conclusions: Our preliminary results have shown that the strategy with CART therapy followed by allogeneic HSCT in refractory/relapsed B-ALL is very safe and effective with similar outcomes in TRM, relapse rate and LFS compared with control group. CART therapy has resulted in very good CR in refractory/relapsed B-ALL and allowed the patients to achieve continuous LFS by subsequent allogeneic HSCT, which is revolutionary modality for those patients who have otherwise incurable diseases. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V128.22.829.829
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
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    Clinical Features and Outcome of 22 Leukemia Patients with TLS-ERG Fusion Gene
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 3985-3985
    Details
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3985-3985
    Abstract: TLS-ERG fusion gene resulting from translocation changes involving chromosomes 16 and 21 is a rare genetic event mostly observed in acute myeloid leukemia (AML). AML with TLS-ERG has unique clinical and morphological features and showed poor prognosis and a high relapse rate. However, many clinical aspects of this type of leukemia still remain unknown. Here, we report the clinical features and outcome of 22 leukemia patients (20 AML and 2 B-ALL) with TLS-ERG fusion gene. The median age of patients was 6 (2-35) years old. 12 patients were males and 10 were females. The median WBC count at diagnosis was 26.54 (1.3-110.8)X109/L. TLS-ERG is tightly associated with extramedullary disease (EMD), complex chromosome abnormalities, and high risk gene mutations. 9/22 (40.9%) cases had complex chromosome abnormalities, 8/22 (36.4%) cases had EMDs, and a large proportion of cases had hematological malignancies gene mutations such as IKZF1, TET2, WT1, PHF6 and NOTCH2. 9 cases in this study had been examined for congenital inherited diseases (Familial hemophagocytic lymphohistiocytosis, FHLH, Fanconi anemia, FA and Dyskeratosis congenital, DC) gene mutations such as FANCD2, FANCG, FANCA, STXBP2, UNC13D, LAMP1 and LYST, and 7/9 (77.8%) cases had positive results. The details are summarized in Table I. We firstly evaluated the general outcome of these patients. Excluding B-ALL patients, 7/20 (35%) cases achieved complete remission (CR) after induction. The median CR, complete molecular remission (CMR), and overall survival (OS) time of the 20 cases was 7 (0-16), 3 (0-14), and 12 (1-36) months. The 6 months relapse free survival (RFS) of EMD and non-EMD patients was 75% and 83.3% (P=0.017, Figure 1). We evaluated the impact of HCT on the outcome of these patients.11/20 AML received allo-HCT, but 9/20 did not. In non-HCT group, the median CR time was 8 (0-29) months. 7/9 cases achieved CR, 3/9 cases achieved CMR, and all cases had disease progression. The median OS time was 11 (1-76) months. In HCT group, 9/11 cases underwent haploidentical HCT (HID-HCT), and 2/11 underwent HLA-matched unrelated donor HCT (URD-HCT). The median OS time was 19 (9-36) months. 1 year OS in non-HCT and HCT group was 62.5% and 90%, respectively (P=0.026, Figure 2), but 6 month RFS in non-HCT and HCT group was 55.6% and 100% (P=0.192), without statistical significance. We analyzed the effect of diverse clinic factors on the outcome of HCT. At the time of HCT, 1/11 case was NR, 10/11 cases were CR, 7/10 CR cases were not detected blasts by FCM, and 6/10 CR cases were CMR. 6 months RFS of CR and NR case was 67.5% and 0, respectively (P=0.034). 6 months RFS of FCM+ and FCM- cases was 50% and 71.4% (P=0.403). 6 months RFS of CMR and non-CMR cases was 66.7% and 60% (P=0.671). There are 5 EMD cases among the 11 cases that underwent HCT, and 6 months RFS of HCT cases with or without EMDs was 33.3% and 71.4%, respectively (P=0.204). Among the 8 TLS-ERG+ AML patients with EMD, 6/8 cases achieved CR after induction, and 5/8 cases underwent HCT after CR, the 6 months RFS of EMDs with or without HCT was 100% and 33.3% (P=0.203). Among the 12 TLS-ERG+ AML patients without EMD, 10/12 cases achieved CR after induction, and 6/12 cases underwent HCT after CR, the 6 months RFS of them with or without HCT was 100% and 66.7%, respectively (P=0.176). In conclusion, we found TLS-ERG is tightly associated with complex chromosome abnormalities and high risk gene mutations including IKZF1, TET2, WT1, PHF6, FANCD2, FANCG, FANCA, which might partially explain the overall poor prognosis of TLS-ERG patients. The leukemia burden before HCT and EMD has negative impact on the outcome of TLS-ERG patients. HCT could prolong the OS of the patients, but could not overcome the poor prognosis of TLS-ERG. No matter the patients had EMD or not, the RFS could not be improved by HCT. Our study will be valuable for evaluating the therapeutic regimen and prognosis of AML patients with TLS-ERG fusion gene. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V128.22.3985.3985
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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    detail.hit.zdb_id: 80069-7
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  • 9
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    Impact of clinical factors on outcome of leukemia patients with TLS-ERG fusion gene
    Informa UK Limited ; 2017
    In:  Leukemia & Lymphoma Vol. 58, No. 7 ( 2017-07-03), p. 1655-1663
    Details
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 58, No. 7 ( 2017-07-03), p. 1655-1663
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    URL: Article
    DOI: 10.1080/10428194.2016.1260124
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2017
    detail.hit.zdb_id: 2030637-4
    detail.hit.zdb_id: 1042374-6
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    Targeting Late Relapsed Acute Myeloid Leukemia Cells by Cytotoxic T Cells Generated from Late but Not Early Leukemic Antigen-Presenting Dendritic Cells.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 4902-4902
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4902-4902
    Abstract: Cancer-specific cytotoxic T lymphocytes (CTL) have great potential in cancer immunotherapy. We performed a longitudinal study of CTL primed with dendritic cells (DC) exposed to leukemic antigens or DC directly differentiated from leukemic cells in an acute myeloid leukemia (AML) patient. The patient received three HLA locus-mismatched allogeneic bone marrow transplantation, relapsed around day 43, and after a brief remission, suffered an ongoing multi-focal extramedullary relapse. CTL generated against AML cells early during the course of disease (early-AML) effectively targeted the early-AML cells as demonstrated by in vitro CTL assays. The patient received multiple infusions of immune cells specific to the early-AML cells in a pilot trial. While the patient established stable remission in the peripheral blood, extensive extramedullary relapse had occurred. The CTL prepared from DC exposed to the early-AML cells failed to target the late relapsed AML (late-AML) cells isolated from pleural effusion and peripheral blood. Further characterization of the late-AML cells showed complete and partial loss of class II and class I HLA expression, respectively. Interestingly, CTL prepared from the late-AML-derived DC were able to kill the late relapsed cancer cells. This result suggests that the late-AML cells, although escaped from the early-AML-derived CTL, expressed novel immunogenic leukemic antigens. It appeared that selective growth of AML cells resistant to the early-AML-specific immune cells had occurred in vivo. However, CTL primed with the late-AML-derived DC were able to kill the late relapsed cancer cells in vitro. Thus, AML could evolve in vivo under active immunotherapy, but this may be coped with preparation of cancer-specific immune cells using the late-AML cells.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.4902.4902
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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