scholarly journals Combined Thalidomide and Recombinant Human Interferon-α-1b and Interleukin-2 for Acute Myeloid Leukemia of Various Disease Status: A Multi-Center Prospective Study

2021 ◽  
Author(s):  
Ruihua Mi ◽  
Lin Chen ◽  
Xiaojiao Wang ◽  
Qingsong Yin ◽  
Zhanfang Wang ◽  
...  
Keyword(s):  
Complete Remission ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Interleukin 2 ◽  
Disease Status ◽  
Human Interferon ◽  
Interferon Α ◽  
Cytokine Levels ◽  
Acute Myeloid

Abstract Objectives: This study investigated the therapeutic effects of combined recombinant human interferon-α-1b (IFN-α1b), thalidomide, and recombinant interleukin-2 (IL-2) in treating acute myeloid leukemia (AML) in patients of various disease status and vulnerabilities. Methods: Patients with AML (n = 166) were treated with combined recombinant IFN-α1b, thalidomide, and recombinant IL-2 (ITI regimen). The rates of partial and complete remission, minimal residual disease (MRD) status, quality of life, and long-term survival were compared among 3 patient groups. Lymphocyte profiles and relevant cytokine levels determined from peripheral blood samples of patients (pre- and post-treatment) and healthy individuals were compared. (Registration number: ChiCTR-ONC-14004688; Registered 23 May 2014, www.chictr.org.cn)Results: Sixty patients with primary AML who were unable to receive chemotherapy, or with relapsed/refractory AML, showed a total response rate of 30% after undergoing the ITI regime, and maintained a good quality of life. Eighteen patients with morphologically complete remission and consistently positive MRD achieved a response rate of 72.2%: the MRD converted to negative or was mitigated in 9 and 4 patients, respectively; 5 patients did not respond. For 88 patients with initial complete remission and negative MRD, 11 failed to maintain the negative MRD, and the relapse rate was 12.5%. The ITI regime was associated with substantial anti-leukemic changes in peripheral blood lymphocyte profiles and cytokine levels. Conclusions: The ITI regimen may be an effective and affordable option for patients with AML who cannot tolerate conventional chemotherapy, including those with relapsed/refractory disease, or complete remission status but MRD-positive, or after initial complete remission.

scholarly journals Combined Thalidomide and Recombinant Human Interferon-α-1b and Interleukin-2 for Acute Myeloid Leukemia of Various Disease Status: A Multi-Center Prospective Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3865-3865
Author(s):  
Ruihua Mi ◽  
Lin Chen ◽  
Xudong Wei ◽  
Xiaojiao WANG ◽  
Yongping Song
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Interleukin 2 ◽  
Disease Status ◽  
Human Interferon ◽  
Interferon Α ◽  
Group B ◽  
Acute Myeloid ◽  
Human Interferon Α

AML (acute myeloid leukemia) patients with relapsed refractory diseases or in poor physical conditions have very limited choices of appropriate treatment regimens, and most alternative options are costly. Here, we reported that an affordable regimen with combined recombinant human interferon-α-1b (IFN-α1b), thalidomide, and recombinant interleukin-2 (IL-2) (the ITI regimen) achieved varying degrees of therapeutic effects in AML patients of various disease status and vulnerabilities. ITI regimen was administrated as follow: a subcutaneous injection of IFN-α1b 60 μg qod, IL-2 1 million unit qod, and 200mg thalidomide tablet orally taken every night before sleep. Group A Sixty-eight patients who were with relapsed or refractory AML were enrolled, sixty finished at least one course, a response rate (CR+CRi) of 16.7% (10/60) was observed, and, and 7 (11.7%) patients achieved partial remission.(Table 1) Group B Eighteen patients with morphologically complete remission and consistently positive MRD were enrolled, each patients underwent ITI regimen for 2 months at least. According to the criteria of the WHO risk stratification, 7 were with a favorable risk, 8 were with a intermediate risk, and 3 were with a high risk. Patients with FLT3-ITD mutations were treated with oral sorafenib during early induction and consolidation treatment. These 18 patients received conventional dosage of ITI regimen. Seven patients had a negative MRD after 1 or 2 months. The MRD levels of 3 patients significantly decreased after one or two months. Five patients suffered a Morphological relapse. Another 3 patients failed to the conventional dosage of ITI regimen with an increased MRD rate, but it decreased after we made a modification of IFN-α1b and IL-2 administration daily. The response rate of the 18 patients in Group B was 72.2%, where MRD < 0.01% was defined as the negative threshold. (Table 2) Group C Eighty-eight patients with MRD-negative AML after consolidation were enrolled. Among the 88 patients with initial CR, 11 (12.5%) relapsed during the maintenance period (Figure 1). All these 11 patients relapsed within 2 years, with a median recurrence period of 20 months, of which 2, 4, and 5 patients, respectively, were with favorable, intermediate, and high risk. The indicated that this regimen effectively reduced the relapse rate.(Table 3) Disclosures No relevant conflicts of interest to declare.

scholarly journals Compound Application of Thalidomide and Recombinant Human Interferon-α-1b, Interleukin-2 in Different Disease Status of Acute Myeloid Leukemia a Multi-Center Prospective Study of a New Combination of Old Drugs

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5219-5219
Author(s):  
Lin Chen ◽  
Ruihua Mi ◽  
Xudong Wei ◽  
Qingsong Ying ◽  
Fangfang Yuan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Myeloid Leukemia ◽  
Interleukin 2 ◽  
Human Interferon ◽  
Interferon Α ◽  
Group A ◽  
Group B ◽  
Acute Myeloid ◽  
Human Interferon Α

Abstract Objectives: The aim of this study was to investigate the therapeutic effects of combinational application of thalidomide and recombinant human interferon-α-1b, interleukin-2 (the ITI scheme) in treating acute myeloid leukemia (AML) in different settings. Methods: AML patients with different disease states were categorized into three groups and received treatments following the ITI scheme. Group A consisted of relapsed or refractory AML patients (R/R-AML) and primary AML patients who were unable to receive chemotherapy. Group B included patients with morphologically complete remission (CR) and consistently positive minimal residual disease (MRD). Group C is composed of AML patients with initial complete remission and negative MRD. The CR rate, partial remission rate, MRD status, quality of life, and long-term survival were observed accordingly. ITI scheme is administrated as: IFNα-1b 60ug/d qod ih, IL-2 1001 million units/d qod ih, Thalidomide 200mg qn po. the Compound Salvia Tablets were recommended orally taken in order to prevent deep venous thrombosis. Results: a. With a total response rate of 30% in 60 AML patients of Group A, 4 CR, 6 CRi and 8 PR, who maintained good quality of life with no transfusion with red blood cells or platelet components any more (Table1).The MRD of 13 cases (72.2%) turned negative among 18 patients in Group B. MRD levels turned unmeasurable in seven patients receiving a conventional dose of ITI regimen, and MRD levels significantly decreased in three patients. MRD levels turned unmeasurable after receiving a higher dose of ITI regimen in two patients, and one patients MRD level decreased. Five patients failed to this regimen and suffered a hematologic recurrence. The efficacy is positively correlated with level of MRD level before ITI administration. 81.8% (9/11) patients responded to ITI regimen in whose MRD level ≤1.0%. However, only 57.1% (4/7) responded in whose MRD≥1.0%. 3 patients responded to a extra dose of ITI after no response to a normal dose. Indicated that the efficacy of this regimen is positively correlated with the dose of the regimen.(Table 2)In group C of 88 patients, 11 patients failed to maintain MRD negative, and the relapse rate was 12.5% (Table 3and figure 1). Conclusions: The ITI scheme can provide a new, effective, and affordable treatment option for AML patients that are intolerant to conventional chemotherapy, including R/R-AML patients, patients with CR status but MRD positive, and patients after initial CR. Disclosures No relevant conflicts of interest to declare.

scholarly journals Outcome of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse–Bordeaux DATAML Registry Study

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 773 ◽  
Author(s):  
Sarah Bertoli ◽  
Pierre-Yves Dumas ◽  
Emilie Bérard ◽  
Laetitia Largeaud ◽  
Audrey Bidet ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Intensive Chemotherapy ◽  
Line Treatment ◽  
First Line ◽  
Low Intensity ◽  
First Line Treatment ◽  
Acute Myeloid

A recent phase 3 trial showed that the outcome of patients with relapsed/refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) improved with gilteritinib, a single-agent second-generation FLT3 tyrosine kinase inhibitor (TKI), compared with standard of care. In this trial, the response rate with standard therapy was particularly low. We retrospectively assessed the characteristics and outcome of patients with R/R FLT3-mutated AML included in the Toulouse–Bordeaux DATAML registry. Among 347 patients who received FLT3 TKI-free intensive chemotherapy as first-line treatment, 174 patients were refractory (n = 48, 27.6%) or relapsed (n = 126, 72.4%). Salvage treatments consisted of intensive chemotherapy (n = 99, 56.9%), azacitidine or low-dose cytarabine (n = 9, 5.1%), other low-intensity treatments (n = 17, 9.8%), immediate allogeneic stem cell transplantation (n = 4, 2.3%) or best supportive care only (n = 45, 25.9%). Among the 114 patients who previously received FLT3 TKI-free intensive chemotherapy as first-line treatment (refractory, n = 32, 28.1%; relapsed, n = 82, 71.9%), the rate of CR (complete remission) or CRi (complete remission with incomplete hematologic recovery) after high- or low-intensity salvage treatment was 50.0%, with a bridge to transplant in 34.2% (n = 39) of cases. The median overall survival (OS) was 8.2 months (interquartile range, 3.0–32); 1-, 3- and 5-year OS rates were 36.0% (95%CI: 27–45), 24.7% (95%CI: 1–33) and 19.7% (95%CI: 1–28), respectively. In this real-word study, although response rate appeared higher than the controlled arm of the ADMIRAL trial, the outcome of patients with R/R FLT3-mutated AML remains very poor with standard salvage therapy.

Correlation between cytokine levels and changes in fatigue and quality of life in patients with acute myeloid leukemia

2013 ◽  
Vol 37 (3) ◽  
pp. 274-279 ◽  
Author(s):  
Filgen Y. Fung ◽  
Madeline Li ◽  
Henriette Breunis ◽  
Narhari Timilshina ◽  
Mark D. Minden ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cytokine Levels ◽  
Acute Myeloid

Associations between quality of life, fatigue, and cytokine levels in patients aged 50+ with acute myeloid leukemia

2008 ◽  
Vol 17 (5) ◽  
pp. 539-546 ◽  
Author(s):  
Abbas H. Panju ◽  
Ali Danesh ◽  
Mark D. Minden ◽  
David J. Kelvin ◽  
Shabbir M. H. Alibhai
Keyword(s):  
Quality Of Life ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cytokine Levels ◽  
Acute Myeloid

scholarly journals Complete Remission with Incomplete Count Recovery (CRi) Prior to Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia Is Associated with a High Non-Relapse Mortality without Increased Relapse Risk

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4650-4650
Author(s):  
Andrew James Innes ◽  
Philippa Woolley ◽  
Richard Szydlo ◽  
Sara Lozano ◽  
Fiona Fernando ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Disease Status ◽  
Risk Of Relapse ◽  
Acute Myeloid ◽  
Count Recovery

Abstract Background: For the majority of patients with acute myeloid leukemia (AML), allogeneic hematopoietic cell transplantation (HCT) offers the best prospect of long-term survival. However both the risk of relapse and non-relapse mortality remain stubborn barriers to successful outcome. Remission status is one of the strongest predictors of outcome, and while conventional risk stratification models account for this, complete remission with incomplete count recovery (CRi) is typically ascribed the same predictive value as complete remission (CR). Methods: In this single center retrospective study we assessed the impact of incomplete count recovery on outcome of allogeneic HCT for AML. Patients' disease status was classified immediately prior to HCT as complete remission (CR), complete remission with incomplete count recovery (CRi) or no complete remission (no CR/CRi). The conventional definition of complete remission (&lt;5% marrow blasts by morphology) was employed and incomplete count recovery was defined as platelet count &lt;100 x 109/L and/or absolute neutrophil count &lt; 1 x 109/L. Measurable residual disease (MRD) was defined by detectable disease by a contemporaneously accepted standard methodology at the time of transplant (e.g. PCR or immunophenotyping). The primary outcome measure was overall survival, and secondary endpoint of non-relapse mortality and relapse were also assessed. Results: Between January 2005 and December 2017, 155 patients underwent allogeneic HCT for AML in our institution. Disease status was defined as CR in 82 (53%), CRi in 54 (35%) and no CR/CRi in 19 (12%). No significant demographic or transplant characteristics were observed between the groups. With a median follow-up of 3.4 [0.1 - 12.8] years, survival at 3 years was 42.5% for the whole cohort with significant differences between the three groups: 54.3% for CR, 34.8% for CRi and 13.4% for no CR/CRi (p&lt;0.001; fig 1A; HR 1.94 for CRi, and 3.4 for no CR). These differences remained after corrections for standard transplant risk factors. The significant differences in overall survival between CR and CRi groups were accounted for by increased non-relapse mortality (7.5% vs. 24.2% at 100 days and 28.7 vs 44.9% at 3 years (p=0.003), fig 1B). The overall cumulative incidence (CI) of relapse at 3 years was 32.4%, and while those patients transplanted not in CR/CRi has a significantly increased CI of relapse (55.3%, p=0.006), there were no significant differences between the CR and CRi groups (25.1 and 36.7% respectively (p=0.441; fig 1C). Patients without MRD (n=107) had a lower incidence of relapse compared to those with MRD (n=48, 21.9% vs. 48.1%, p=0.009), however MRD negative patients with incomplete recovery still had a significantly worse 3-year survival than those with complete recovery (37.5 vs 56.7, p=0.006) resulting from higher NRM (46.4% vs 30.4%%, p=0.003, fig 1D). Discussion: CRi patients have a poorer survival and higher NRM than CR patients with full marrow recovery, without evidence of increased relapse. While death from NRM is a competing risk for relapse, the increased incidence of relapse remains overtly demonstrable in those patients transplanted not in CR/CRi, despite an equally high NRM. Additionally, the persistently increased NRM in CRi patients without MRD, suggests that the poorer survival may result from poor fitness for transplant and increased susceptibility to transplant related complications rather than an imminent relapse. With the advent of increasingly sensitive MRD technologies, these data may suggest that further pre-transplant optimization to promote marrow recovery may be permissible in order to minimize NRM without risking increased risk of relapse in CRi patients. Figure 1. Figure 1. Disclosures Apperley: Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Incyte: Honoraria, Speakers Bureau.

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