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.

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.

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

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.

scholarly journals Clinical Features and Cytoreduction Therapy in Children with Newly Diagnosed Acute Myeloid Leukemia and Hyperleukocytosis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2295-2295
Author(s):  
Georgios E. Christakopoulos ◽  
Kendra N Walker ◽  
Lei Wang ◽  
Clifford Takemoto ◽  
Yan Zheng ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Adverse Events ◽  
Blood Cell ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Tumor Lysis Syndrome ◽  
Newly Diagnosed ◽  
Tumor Lysis ◽  
Low Dose Chemotherapy ◽  
Acute Myeloid

Abstract Background Hyperleukocytosis is observed in 5% to 20% of patients with newly diagnosed acute myeloid leukemia (AML) and is associated with an increased risk of early complications and mortality. While being used frequently in patients with AML and hyperleukocytosis, the clinical utility of leukapheresis has not been conclusive. Low-dose chemotherapy has also been used recently as a cytoreduction method in these patients, but the data are limited. Objectives: To describe and compare the clinical and laboratory characteristics, early adverse events, and outcomes of children with newly diagnosed AML and hyperleukocytosis according to cytoreductive methods; leukapheresis, low dose chemotherapy (cytarabine), or no intervention. Methods: We studied patients with newly diagnosed AML treated on three multi-institutional St. Jude protocols, AML97, AML02, and AML08, between 1997 and 2017. Hyperleukocytosis was defined as white blood cell (WBC) counts of 100 x 10 9/L or higher at diagnosis. The decision of cytoreductive treatment was made as the discretion of the treating physician. Leukoreduction was used in the AML97 and AML02 studies, and cytarabine (100mg/m 2/dose every 12 hours) was the first choice for AML08 study. We reviewed baseline clinical characteristics and laboratory data (complete blood cell counts [CBC], chemistries, coagulation) and adverse effects (grade 3 or higher on neurologic, renal, respiratory, and hemorrhagic complications based on Common Terminology Criteria for Adverse Events) from diagnosis to day 14 of protocol-based chemotherapy. Cairo-Bishop criteria was used for laboratory/clinical tumor lysis syndrome. The time from the first CBC to administration of protocol-based chemotherapy was calculated. Results: A total of 49 patients were identified: 8 patients in AML97, 19 in AML02, and 22 in AML08) (Table). The age at diagnosis was 10.8 years with a median initial WBC count of 157.6 x 10 9/L; CNS (CNS 2, 3 or traumatic lumbar puncture with blasts) was seen in 29 (59.2%) cases. FAB M4 or M5 subtype was found in 30 patients (61.2%), 11q23 abnormalities in 15 (30.6%) and inv(16) in 8 (16.3%). In regards to leukoreduction method, 16 patients received leukapheresis (14 patients in AML97/02 and 2 in AML08), 18 cytarabine (all in AML08) and 1 hydroxyurea (in AML08); 14 did not receive leukoreduction (13 patients in AML97/02 and 1 in AML08). Leukapheresis was used more often in patients with higher diagnostic WBC counts (218.7 x 10 9/L) than those treated with cytarabine (152.9 x 10 9/L) or without intervention (127.3 x 10 9/L) (P&lt;0.001). The decrease of WBC counts (%) before and after intervention was more pronounced among patients treated with cytarabine than those treated with leukapheresis (75% vs. 48.5%, P=0.03). When decreases in WBC counts were evaluated from the first CBC to the initiation of protocol therapy, cytarabine treatment was associated with more decreases in WBC counts from baseline (84.8%) than leukapheresis (46.7%) or no intervention (1.8%) (P&lt;0.001). Patients who received cytarabine intervention had a longer median time from the first CBC to initiation of protocol therapy (95.2 hours) compared to those who received leukapheresis (28.1 hours) and no intervention (20.4 hours) (P&lt;0.001). No early deaths were observed from the time of diagnosis to two weeks after initiation of protocol chemotherapy, and no statistically significant differences were noted in the incidences of neurologic, pulmonary, renal, hemorrhagic events, or laboratory/clinical tumor lysis syndrome among these three groups. Conclusion: Low-dose cytarabine treatment appears to be a safe and effective mean of cytoreduction for patients with AML and hyperleukocytosis. Further studies are needed to determine if this approach is preferable among patients treated with contemporary treatment. Figure 1 Figure 1. Disclosures Pui: Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Data Monitoring Committee.

A Phase II Study of Elacytarabine/Idarubicin As Second Course Remission-Induction in Patients with Acute Myeloid Leukemia Who Failed Cytarabine/Anthracycline, and Evaluation of the Impact of the Nucleoside Transporter hENT1 on Response

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1533-1533
Author(s):  
David A. Rizzieri ◽  
Norbert Vey ◽  
Richard F. Schlenk ◽  
Xavier Thomas ◽  
Françoise Huguet ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Confidence Interval ◽  
Myeloid Leukemia ◽  
Fatty Acid Derivative ◽  
Expression Level ◽  
Remission Induction ◽  
Clinical Activity ◽  
Nucleoside Transporter ◽  
The Impact ◽  
Acute Myeloid

Abstract Abstract 1533 Background: Elacytarabine is a fatty acid derivative (elaidic acid ester) of cytarabine. The mechanism of action is similar to cytarabine, but unlike cytarabine, cellular uptake and activity of elacytarabine are independent of nucleoside transporters. Resistance to cytarabine has been associated with decreased expression of the human equilibrative nucleoside transporter 1 (hENT1) (Hubeek et al., 2005). An agent such as elacytarabine, active in low hENT1 expressing, cytarabine resistant acute myeloid leukemia (AML), could therefore improve clinical outcome in patients. Aims: To determine the efficacy and safety of elacytarabine given in combination with idarubicin to patients who have failed the first ”standard” induction course with a cytarabine based regimen, as well as to explore the relationship between the hENT1 status in AML cells and response. Methods: Study therapy consisted of one course elacytarabine 1000 mg/m2/d CIV on d1-5 administered in combination with idarubicin 12 mg/m2/d IV d1-3 in adult patients with AML who after a first cytarabine based induction course have not attained blast clearance (bone marrow (BM) >5 % blasts, circulating blasts, or chloroma etc). Assessment of response was at least 12d after induction start. Responding patients could receive the same course or elacytarabine 2000 mg/m2/d CIV on d1-5 d and then consolidation therapy with two courses of either elacytarabine monotherapy or combination with idarubicin as described above or could proceed to allogeneic SCT at any time point. The hENT1 expression level of BM blasts was analyzed by immunocytochemistry at time of initial AML diagnosis (pre-cytarabine course) and/or before elacytarabine treatment. The planned sample size is 50 evaluable patients, and with a target of 40% CR/CRi rate, the lower limit of the 90% confidence interval for the CR/CRi rate will be greater than 22% with at least 80% probability. The CR/CRi rate will be estimated and its corresponding two-sided 90% confidence interval will be provided. The significance of the association between the hENT1 expression level and response status will be assessed through a Chi-square test of hENT1 expression level (high, low) versus CR/CRi (yes, no). Results: In the ongoing study, 26 patients [16 male, 10 female, median age 61 years (range 18–71), ECOG PS 0–2] have been treated with elacytarabine and idarubicin. 23 patients have currently been response evaluated, and 11 attained a CR/CRi and 3 a PR (post one elacytarabine course). The most frequently reported related non-hematologic adverse events (AEs) CTCAE grade ≥ 3 were febrile neutropenia, infections/sepsis and increased liver function tests. 30 patients have been scored for hENT1 expression level at time of diagnosis. Preliminary results indicate that approximately 50 % of the patients hENT1 expression is low (defined as less than 10% of blasts stained). As to response, only approximately 1/3 of patients with low hENT1 blasts respond to cytarabine while for the high hENT1 2/3 respond. Three deaths occurred within 30 days after start of treatment and were all due to sepsis. All 3 patients had secondary leukemia. Summary/Conclusion: Elacytarabine administered at 1000 mg/m2/d CIV d1-5 in combination with idarubicin 12mg/m2/d IV d1-3 showed promising clinical activity with a CR/CRi rate of approximately 45 %. The adverse event profile, is as expected for cytarabine combination therapy. Preliminary data indicate that the assessment of hENT1 transporter expression in blasts could be used to select patients less likely to benefit from cytarabine and for whom elacytarabine could be an effective therapy. Disclosures: Gianelli-Borradori: Clavis Pharma: Employment. Flem Jacobsen:Clavis Pharma: Employment. Krug:MedA Pharma: Honoraria; Novartis: Honoraria; Alexion: Honoraria; Boehringer Ingelheim: Research Funding; Sunesis: Honoraria.

Mitoxantrone versus daunorubicin in induction-consolidation chemotherapy--the value of low-dose cytarabine for maintenance of remission, and an assessment of prognostic factors in acute myeloid leukemia in the elderly: final report. European Organization for the Research and Treatment of Cancer and the Dutch-Belgian Hemato-Oncology Cooperative Hovon Group.

1998 ◽  
Vol 16 (3) ◽  
pp. 872-881 ◽  
Author(s):  
B Löwenberg ◽  
S Suciu ◽  
E Archimbaud ◽  
H Haak ◽  
P Stryckmans ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Remission Induction ◽  
Final Report ◽  
European Organization ◽  
Secondary Aml ◽  
Postremission Therapy ◽  
Acute Myeloid

PURPOSE AND METHODS Optimization of remission-induction and postremission therapy in elderly individuals with acute myeloid leukemia (AML) was the subject of a randomized study in patients older than 60 years. Remission-induction chemotherapy was compared between daunomycin (DNR) 30 mg/m2 on days 1, 2, and 3 versus mitoxantrone (MTZ) 8 mg/m2 on days 1, 2, and 3, both plus cytarabine (Ara-C) 100 mg/m2 on days 1 to 7. Following complete remission (CR), patients received one additional cycle of DNR or MTZ chemotherapy and were then eligible for a second randomization between eight cycles of low-dose (LD)-Ara-C 10 mg/m2 subcutaneously every 12 hours for 1 2 days every 6 weeks or no further treatment. RESULTS A total of 242 patients was randomized to DNR and 247 to MTZ. Median age of both study groups was 68 years. Secondary AML was documented in 26% and 25% of patients in either arm. The probability of attaining CR was greater (P = .069) with MTZ (47%) than with DNR (38%). Median duration of neutropenia was 19 (DNR) and 22 days (MTZ). The greater response rate to MTZ therapy correlated with reduced occurrence of chemotherapy resistance (32% v 47%, P = .001). With a median follow-up of 6 years, 5-year disease-free survival (DFS) is 8% in each arm. Overall survival estimates are not different between the groups (6% v 9% at 5 yrs). Poor performance status at diagnosis, high WBC count, older age, secondary AML, and presence of cytogenetic abnormalities all had an adverse impact on survival. Secondary AML and abnormal cytogenetics predicted for shorter duration of CR. Among complete responders, 74 assessable patients were assigned to Ara-C and 73 to no further therapy. Actuarial DFS was significantly longer (P = .006) for Ara-C-treated (13% [SE = 4.0%] at 5 years) versus nontreated patients (7% [SE = 3%]), but overall survival was similar (P = .29): 18% (SE = 4.6%) versus 15% (SE = 4.3%). Meta-analysis on the value of Ara-C postremission therapy confirms these results. CONCLUSION In previously untreated elderly patients with AML, MTZ induction therapy produces a slightly better CR rate than does a DNR-containing regimen, but it has no significant effect on remission duration and survival. Ara-C in maintenance may prolong DFS, but it did not improve survival.

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