scholarly journals Immunomodulatory Effect of Green Tea Treatment in Combination with Low-dose Chemotherapy in Elderly Acute Myeloid Leukemia Patients with Myelodysplasia-related Changes

2021 ◽  
Vol 20 ◽  
pp. 153473542110026
Author(s):  
Andrana K. Calgarotto ◽  
Ana L. Longhini ◽  
Fernando V. Pericole de Souza ◽  
Adriana S. Santos Duarte ◽  
Karla P. Ferro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Green Tea ◽  
Regulatory T Cell ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Related Factor ◽  
Low Dose Chemotherapy ◽  
Acute Myeloid

Green tea (GT) treatment was evaluated for its effect on the immune and antineoplastic response of elderly acute myeloid leukemia patients with myelodysplasia-related changes (AML-MRC) who are ineligible for aggressive chemotherapy and bone marrow transplants. The eligible patients enrolled in the study (n = 10) received oral doses of GT extract (1000 mg/day) alone or combined with low-dose cytarabine chemotherapy for at least 6 months and/or until progression. Bone marrow (BM) and peripheral blood (PB) were evaluated monthly. Median survival was increased as compared to the control cohort, though not statistically different. Interestingly, improvements in the immunological profile of patients were found. After 30 days, an activated and cytotoxic phenotype was detected: GT increased total and naïve/effector CD8+ T cells, perforin+/granzyme B+ natural killer cells, monocytes, and classical monocytes with increased reactive oxygen species (ROS) production. A reduction in the immunosuppressive profile was also observed: GT reduced TGF-β and IL-4 expression, and decreased regulatory T cell and CXCR4+ regulatory T cell frequencies. ROS levels and CXCR4 expression were reduced in bone marrow CD34+ cells, as well as nuclear factor erythroid 2–related factor 2 (NRF2) and hypoxia-inducible factor 1α (HIF-1α) expression in biopsies. Immune modulation induced by GT appears to occur, regardless of tumor burden, as soon as 30 days after intake and is maintained for up to 180 days, even in the presence of low-dose chemotherapy. This pilot study highlights that GT extracts are safe and could improve the immune system of elderly AML-MRC patients.

Achieving Hematologic Remission with Combination Chemotherapy and Donor Leukocyte Infusions for Relapse of Acute Myeloid Leukemia Six Years After Human Leukocyte Antigen-Mismatched Transplantation: A Case Report

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4476-4476
Author(s):  
Jingyan Xu ◽  
Jian Ouyang ◽  
Rong-Fu Zhou
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Combination Chemotherapy ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Mononuclear Cells ◽  
Bone Marrow Examination ◽  
Intensive Chemotherapy ◽  
Bone Marrow Blast ◽  
Acute Myeloid

Abstract Abstract 4476 Hematopoietic Stem Cell Transplantation (HSCT) from partially HLA-matched (haploidentical) family donors represents a promising therapy for high-risk acute myeloid leukemia (AML). However, for patients with AML relapsed after HSCT from an HLA-mismatched familial donor, there is no standard therapy. They may receive conventional chemotherapy, cyclosporine withdrawal, second HSCT, and donor leukocyte infusion (DLI) with or without prior mobilization. Recently, combination chemotherapy and DLI showed achieving hematologic remission. We report a case of successful combination chemotherapy and donor leukocyte infusions from original donor in a patient with AML relapsing 6 years after HSCT from an HLA-Mismatched Familial Donor. A 37-year-old male presented with fever in June 2003.Bone marrow aspirate confirmed the diagnosis of AML(M5 subtype according to FAB classification). The patient initially received intensive chemotherapy. However, the patient with AML that was refractory to conventional therapy. He received HSCT in first CR from his mother 1-loci HLA-mismatched (HLA-A) using BuCY- Conditioning regimen on June 11, 2004. He showed a medullary relapse 6 years after HSCT. His bone marrow blast counts exceeded 80% with 8.25% of donor karyotypes (46 XX FISH). We decided to try to use his mother as the donor for DLI. Cytoreductive chemotherapy was commenced prior to DLI. He was treated twice with DLI on August 02, 2010 and September 23, 2011. He was treated chemotherapy before in first DLI, chemotherapy regimens; FLAG-ida [fludarabine 30 mg/m2/d from day-6 to-2 of cell infusion, cytosine arabinoside 2 g/m2/d from day-6 to-2 of cell infusion, idarubicine 20 mg/d day-1 and G-CSF 300μ g/day from day-7 to +30]. The donors received G-CSF 10μ g/kg subcutaneously daily starting day-3 of cell infusion for 5 days. Donor peripheral blood mononuclear cells were collected by CS-3000 Plus cell separator (Baxter Corp.) on the fifth days of G-CSF administration and infused through a central venous catheter into the patients on the same day. 8.33×107/kg mononuclear cells, 6×107/kg CD3+ cells were reinfused without manipulation. Cyclosporine at the dose of 3 mg/kg were administered for the prevention of GVHD. On days 36 Bone marrow blast counts exceeded 45% with 44% of donor karyotypes (46 XX FISH) after first Chemo-DLI. He received cyclosporine withdrawal. He was treated chemotherapy by low-dose Ara-C and aclarubicin with concomitant use of G-CSF before in second DLI.,chemotherapy regimens;CAG[ Low-dose Ara-C was given subcutaneously at a dosage of 10 mg/m2 every 12 hours on days-14 to-1. Aclarubicin was administered intravenously at a dosage of 7 mg/m2 on days-14 to-7. Recombinant G-CSF was given subcutaneously at a dosage of 200μ g/m2 per day on days-14 to-1]. On day 0,1.4×108/kg mononuclear cells,1×108/kg CD3+ cells were reinfused. On days 25 bone marrow examination showed CR with 89% of donor karyotypes (46 XX FISH). He was treated consolidation chemotherapy by regimens; CAG.On days 62 bone marrow examination showed CR with 100% of donor karyotypes (46 XX FISH). He developed chronic GVHD with limited disease at day 123 of DLI. In the patient whose cGVHD resolved with the use of steroid, cyclosporine plus methotrexate. The patient died from pneumonia without evidence of recurrent leukemia on day +230. From the cases reported, combination chemotherapy and subsequent mobilized DLI produced a CR with AML in relapse six years after HLA-Mismatched transplantation. We demonstrate that of the patient who relapsed after 6 years, treatment with chemotherapy followed by intensive chemotherapy followed by DLI, can effectively salvage a patient with attainment of durable remissions. Although limited by the small number of one patient, AML in relapse six years after HLA-Mismatched transplantation requires particular attention in future studies, as well as in designing future treatment programs. Clearly a large number of patients is required to confirm the real efficacy of this treatment. Disclosures: No relevant conflicts of interest to declare.

Leukapheresis and low-dose chemotherapy do not reduce early mortality in acute myeloid leukemia hyperleukocytosis: A systematic review and meta-analysis

2014 ◽  
Vol 38 (4) ◽  
pp. 460-468 ◽  
Author(s):  
Sapna Oberoi ◽  
Thomas Lehrnbecher ◽  
Bob Phillips ◽  
Johann Hitzler ◽  
Marie-Chantal Ethier ◽  
...  
Keyword(s):  
Systematic Review ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Meta Analysis ◽  
Early Mortality ◽  
Low Dose Chemotherapy ◽  
Acute Myeloid

Upregulation of CD200 is associated with Foxp3+ regulatory T cell expansion and disease progression in acute myeloid leukemia

Tumor Biology ◽  
2012 ◽  
Vol 34 (1) ◽  
pp. 531-542 ◽  
Author(s):  
Ali Memarian ◽  
Maryam Nourizadeh ◽  
Farimah Masoumi ◽  
Mina Tabrizi ◽  
Amir Hossein Emami ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Disease Progression ◽  
Regulatory T Cell ◽  
Cell Expansion ◽  
Myeloid Leukemia ◽  
T Cell Expansion ◽  
Acute Myeloid

scholarly journals Ecological principle meets cancer treatment: treating children with acute myeloid leukemia with low-dose chemotherapy

2019 ◽  
Vol 6 (3) ◽  
pp. 469-479 ◽  
Author(s):  
Yixin Hu ◽  
Aili Chen ◽  
Xinchang Zheng ◽  
Jun Lu ◽  
Hailong He ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Randomized Study ◽  
Remission Induction ◽  
Molecular Response ◽  
Standard Chemotherapy ◽  
Low Dose Chemotherapy ◽  
The Impact ◽  
Acute Myeloid

Abstract Standard chemotherapy regimens for remission induction of pediatric acute myeloid leukemia (AML) are associated with significant morbidity and mortality. We performed a cohort study to determine the impact of reducing the intensity of remission induction chemotherapy on the outcomes of selected children with AML treated with a low-dose induction regimen plus granulocyte colony stimulating factor (G-CSF) (low-dose chemotherapy (LDC)/G-CSF). Complete response (CR) after two induction courses was attained in 87.0% (40/46) of patients receiving LDC/G-CSF. Post-remission therapy was offered to all patients, and included standard consolidation and/or stem cell transplantation. During the study period, an additional 94 consecutive children with AML treated with standard chemotherapy (SDC) for induction (80/94 (85.1%) of the patients attained CR after induction II, P = 0.953) and post-remission. In this non-randomized study, there were no significant differences in 4-year event-free (67.4 vs. 70.7%; P = 0.99) and overall (70.3 vs. 74.6%, P = 0.69) survival in the LDC/G-CSF and SDC cohorts, respectively. After the first course of induction, recovery of white blood cell (WBC) and platelet counts were significantly faster in patients receiving LDC/G-CSF than in those receiving SDC (11.5 vs. 18.5 d for WBCs (P < 0.001); 15.5 vs. 22.0 d for platelets (P < 0.001)). To examine the quality of molecular response, targeted deep sequencing was performed. Of 137 mutations detected at diagnosis in 20 children who attained hematological CR after two courses of LDC/G-CSF (n = 9) or SDC (n = 11), all of the mutations were below the reference value (variant allelic frequency <2.5%) after two courses, irrespective of the treatment group. In conclusion, children with AML receiving LDC/G-CSF appear to have similar outcomes and mutation clearance levels, but significantly lower toxicity than those receiving SDC. Thus, LDC/G-CSF should be further evaluated as an effective alternative to remission induction in pediatric AML.

Constitutively Active AKT Induces Myeloproliferative Disease, Acute Myeloid Leukemia, and T Cell Lymphoma despite Impaired Engraftment

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3793-3793
Author(s):  
Kira Gritsman ◽  
Michael G Kharas ◽  
D. Gary Gilliland
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Myeloid Leukemia ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Akt Pathway ◽  
Myeloproliferative Disease ◽  
Constitutive Activation ◽  
Acute Myeloid

Abstract The phosphoinositide 3-kinase (PI3K)/AKT pathway is commonly dysregulated in human malignancies, including leukemia. AKT, a downstream effector of PI3K, is constitutively phosphorylated in myeloproliferative disease (MPD) and acute myeloid leukemia (AML) patient samples, suggesting that the PI3K/AKT pathway may be an attractive therapeutic target. In myeloid malignancies, this pathway is most commonly activated not by mutations in PI3K, AKT or loss of PTEN, but rather by mutations in a spectrum of upstream tyrosine kinases, such as BCR-ABL, ETV6-PDGFRb, FIPL1-PDGFRa, JAK2V617F, or FLT3-ITD. To further understand the contribution of PI3K/AKT activation to disease pathogenesis, we modeled the activation of AKT in myeloid neoplasms by such upstream effectors using a myristoylated allele of AKT (myr-AKT) that is constitutively activated. Bone marrow from 5-fluorouracil-primed C57 Bl/6 donor mice was transduced with a bicistronic retrovirus expressing myr-AKT and enhanced green fluorescent protein (EGFP) or control retrovirus expressing EGFP alone, and transplanted into 30 and 5 lethally irradiated syngeneic recipients, respectively. The myr-AKT transplant recipients had a median survival of 53 days. Of 30 myr-AKT mice, 27 (90%) developed a myeloproliferative disease (MPD), characterized by splenomegaly, hepatomegaly, expanded Mac1+Gr1+, Mac1+ckit+, and CD71+Ter119+ populations in the bone marrow and spleen, and increased splenocyte myeloid colony formation. Of these 27 myr-AKT mice with MPD, 19 (70%) also had thymic T cell lymphoma, characterized by infiltration of the thymus, heart, lungs, and muscle with CD4+/CD8+ lymphoblasts. Three of 30 (10%) myr-AKT mice developed acute myeloid leukemia (AML) with phenotypic attributes of erythroleukemia (AML M6) in humans, characterized by infiltration of the spleen, liver and bone marrow with CD71hickit+ blasts. Control EGFP recipients had no evidence of disease. Splenocytes from mice with AML and thymocytes from mice with T cell lymphoma caused disease when transplanted into secondary recipients, whereas splenocytes from mice with MPD were unable to transplant disease. Of note, we observed that myr-AKT expression caused impaired engraftment in recipient mice, as evidenced by a decrease in the %EGFP in the bone marrow over time. Although myr-AKT expressing cells can home normally to the bone marrow, myr-AKT significantly impairs the lodging ability of transduced bone marrow in irradiated recipients by 2 weeks after transplant. Furthermore, we observed an increased rate of apoptosis in myr-AKT-expressing bone marrow and spleen cells in myr-AKT recipient mice. Taken together, these data suggest that constitutive activation of AKT paradoxically increases apoptosis and impairs engraftment of transduced cells, but demonstrate that constitutive activation of AKT alone nonetheless recapitulates the spectrum of human myeloid neoplastic phenotypes associated with activation of upstream tyrosine kinase effectors.

Three Novel Clonal Non-Characteristic Chromosome Aberrations in Acute Myeloid Leukemia Resembling Acute Promyelocytic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4912-4912
Author(s):  
Hongxing Liu ◽  
Wenjun Tian ◽  
Fang Wang ◽  
Juan Zhu ◽  
Wen Teng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Chromosome Aberrations ◽  
Myeloid Leukemia ◽  
Cell Markers ◽  
Blood Tests ◽  
Hla Dr ◽  
D Dimer ◽  
Acute Myeloid

Abstract Abstract 4912 We report here three acute myeloid leukemia cases with novel clonal non-characteristic chromosome aberrations and morphologically resembling acute promyelocytic leukemia (APL). Case No.1: A 57-year-old woman came with mucosal bleeding, ecchymoses, and fever. Blood tests showed hemoglobin (Hb) of 9.3g/dL, platelet count (Plt) of 29×109/L and white blood cell count (WBC) of 1.3×109/L. D-dimer was 3.6ug/ml and Fibrin degradation product (FDPs)>5ug/ml. Bone marrow (BM) morphology showed 91% atypical hypergranular cells with Auer rods and resembling APL. The immunophenotype of peripheral blood (PB) blasts showed 83% positive for CD9, CD13, CD15, CD33, CD64, CD117 and negative for CD34, HLA-DR and B, T-cell markers. PML-RARA and t(15;17) negative but clonal t(1;16)(q44;q22) positive. The patient was initially treated with all-trans retinoic acid (ATRA), As4S4 and mitoxantrone and then switched to harringtonine and ara-C treatment but couldn't get remission. Case No.2: A 39-year-old woman came with asthenia, mucosal bleeding and ecchymoses. Blood tests showed Hb of 10g/dL, Plt of 49×109/L and WBC of 6.2×109/L. D-dimer >20ug/ml and FDPs >20ug/ml. BM morphology showed 84% atypical hypergranular cells with Auer rods and resembling APL. The immunophenotype of PB blasts showed 76% positive for CD13, CD33, CD64, CD117, cMPO and negative for CD9, CD34, HLA-DR and B, T-cell markers. PML-RARA and t(15;17) negative but clonal t(7;17)(p10;q10) positive. The patient was initially treated with ATRA and As4S4 and mitoxantrone but couldn't get a good response. He was then switched to idarubicin and ara-C treatment and got partial response. He is now waiting for allogeneic hematopoietic stem cell transplantation. Case No.3: A 62-year-old man came with asthenia. Blood tests showed Hb of 68 g/dL, Plt of 61×109/L and WBC of 3.3×109/L. D-dimer was 10.2ug/ml and FDPs was not tested. Bone marrow (BM) morphology showed 63.5% atypical hypergranular cells with Auer rods and resembling APL. The immunophenotype of Bone marrow showed 71.2% positive for CD13, CD15, CD33, CD117, cMPO and negative for CD34, HLA-DR,and B, T-cell markers. PML-RARA and t(15;17) negative but clonal (47,XY,+mar1) positive. The patient was initially treated with ATRA and As4S4 but couldn't get a good response. He was then swiched to Daunorubicin and ara-C treatment and got partial remission. APL should be distinguished from other subtypes of acute myeloid leukemia (AML) because of the increased risk of disseminated intravascular coagulation (DIC) and its response to ATRA and arsenic compounds. Some cases of AML seem morphologically similar to APL but lack the characteristic t(15;17) or other RARA-related translocations, and they generally didn't response to ATRA and arsenic compounds treatment. The 3 cases reported here reiterate the lack of specificity of morphologic and Immunophenotyping findings in APL-like AMLs. Karyotypic analysis, as well as FISH and RT-PCR, must be conducted on these cases to rule out APL and other chemotherapy regimens should be considered. APL-like AMLs that do not demonstrate RARA-related translocations may constitute a heterogeneous population of AML with diverse clonal non-characteristic chromosome aberrations, and the molecular mechanisms is worthy of further study. Disclosures: No relevant conflicts of interest to declare.

Efficiency Of 7+3 Chemotherapy Followed By Donor Lymphocyte Infusion In Patients With Relapsed Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4500-4500
Author(s):  
Rashit Bogdanov ◽  
Larisa Mendeleeva ◽  
Elena Parovichnikova ◽  
Larisa Kuzmina ◽  
Irina Galtseva ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Low Dose Chemotherapy ◽  
Acute Myeloid

Relapses after allogeneic stem cell transplantation (allo-SCT) are the main cause of treatment failure in acute myeloid leukemia (AML). Chemotherapy with subsequent donor lymphocyte infusions (DLI) is considered to be the optimal approach for complete remission (CR) achievement and induction of “graft versus leukemia” effect. There is a tendency to use low-dose chemotherapy (i.e. Low-dose Ara-C) in this setting because of less toxicity. However the efficacy of low-dose chemotherapy is not satisfactory and leads to 45-67% CR rate. In this study we apply intensive chemotherapy (7+3) followed by DLI in aplasia in with relapsed AML. Aim To investigate the efficacy of DLI perfomed in neutropenia after reinduction chemotherapy 7 +3 (Cytarabine 100 mg/m^2 every 12 hours daily for 7 days, and Idarubicin 12 mg/m^2 daily on days 1, 2, and 3) in AML patients (pts) with overt relapse after allo-SCT. Methods The study comprised 16 AML patients. The median age was 31 years (16 - 57 years), male – 11 female - 5. Twelve patients underwent allo-SCT in first remission, 4 pts - in overt relapse of AML. Allo-SCT was carried out from HLA-matched sibling donor in all pts. Myeloablative conditioning regimen was performed in 10 pts. Reduced intensity conditioning (RIC) - in 6 pts. AML relapse occurred at a median 4,7 months (range from 1 to 51 months) after allo-SCT. Patients received DLI at day 7 (7-14 days) after chemotherapy during myelotoxic agranulocytosis. The number of infusions ranged from 1 to 4 (median 2 DLI) per patient. DLI after chemotherapy were carried out twice in 1 patient due to the second relapse. So we analysed 17 cases of relapse in 16 pts. Total amount of the CD3+cells varied from 1 to 16,7x10^7 CD3+cells/kg (median 6,0x10^7 CD3+ cells/kg). The interval between DLI was 1-4 weeks. All pts received 2 - 6 MUE Interleukin-2 (IL-2) subsequently after DLI. Chimerism was monitored by PCR analysis (VTTR and STR) and by FISH – analysis for centromers of X and Y – chromosomes after DLI each 2-4 weeks up to 6 months, then every 3 months. Results Complete remission with 100% donor chimerism was achieved in 14 (82%) out of the 17 cases. There were no toxic deaths, 3 pts died in leukemia progression. All pts developed severe infections in neutropenic phase (mucositis, pneumonia, sepsis), but they were cured. Eight pts (57%) out of 14 developed a relapse in 5 months after DLI (from 1 to 17 months) and 6 pts (35%) remained in remission. Follow-up period was 12 months (1 - 124 months). Median overall survival constituted 15 months. Acute graft versus host disease (GVHD) after DLI was diagnosed in 8 patients 47% (6 - I-II grade; 2 - III-IV grade). Chronic GVHD was diagnosed in 8 pts (47%): limited -6 pts (35%), extensive - 2 pts (12%). Conclusion Our data show that despite myelotoxicity and infections 7+3 and subsequent DLI+ IL-2 is an effective treatment for AML pts with overt relapse after allo-SCT. Disclosures: No relevant conflicts of interest to declare.

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