Low-dose melphalan in elderly patients with relapsed or refractory acute myeloid leukemia: A well-tolerated and effective treatment after hypomethylating-agent failure

Abstract Background Acute myeloid leukemia (AML) is a malignant hematologic disease with high incidence in the elderly peoples. The median age of onset is 65 years. There is no standard chemotherapy regimen for elderly AML, especially for AML patients older than 70 years old. Six to eight courses of low-dose or reduced-dose chemotherapy were commonly used in clinical treatment. However, most patients. However, most patients relapsed within six months after chemotherapy. How to prolong the survival of elderly patients with AML is a realistic problem that needs to be urgently solved. Patients and Methods From Jan 2017 to May 2018, six elderly patients with AML in our center include in the study. The median age was 74 (70-78) years. According to cytogenetics and molecular mutation, 1 patient were favorable risk with t (8, 21) and AML1-ETO, 3 patients were intermediate risk with karyotype abnormality, and 2 patients were unfavorable risk with complex karyotype and FLT3-ITD mutation. One patient received complete remission (CR) after IA induce scheme, and then, he received 4 courses of DA regimen for consolidation therapy. At last, he stopped chemotherapy because of severe atrial fibrillation and heart failure. Other 5 patients treated with 4-8 courses of decitabine (Dec) +CAG or HAG regimen. Minimal residual disease (MRD) of four patients were negative and two patients were positive before include in the study. Six patiens were given 10-day low dose Dec regimen treatment (5mg/m2/day×10 days) for every six weeks, until AML progress. Results For 2 MRD positive patients, after 10-day low dose Dec regimen treatment, one patient MRD turn to negative, one patient MRD remained positive, and died after 4 months. Till Jul 2018 (median observation time 10 months), 5/6 patients remained CR and survival with better quality of life. the most common treatment-emergent adverse events (TEAEs) were related to hematocytopenia. The most significant reduction of blood cells was hypoleucocytosis, and mainly in the first 2 courses of G-Dec treatment. Conclusion Preliminary research shows 10-day low dose Dec regimen treatment has Significant effect and mild side effect on the survival of elderly AML patients. The multicenter, randomized controlled clinical study will conduct to further verify its effectiveness and safety. Disclosures No relevant conflicts of interest to declare.

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The Efficacy and Safety of Decitabine in Combination with ATRA, G-CSF and Low Dose Cytarabine(Dlaag Regimen)in Relapsed/Refractory Acute Myeloid Leukemia Not Suitable for Strong Chemotherapy : A Phase 2, Prospective, Single-Arm, Multicenter Study

Blood ◽

10.1182/blood-2019-131671 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5108-5108

Author(s):

Li Yang ◽

Ligen Liu ◽

Limin Zhao ◽

Yingting Lu ◽

Jing Zhang ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Multicenter Study ◽

Myeloid Leukemia ◽

Low Dose ◽

Response Rate ◽

Intensive Therapy ◽

Significant Difference ◽

Refractory Acute Myeloid Leukemia ◽

Low Dose Cytarabine ◽

Acute Myeloid

Background. Patients with relapsed or refractory acute myeloid leukemia (R/R AML)who are intolerant of strong regimen chemotherapy have poor responsibility to chemotherapy and clinic remission is lower. The DNMT is depleted to reactivate the silencing tumor suppressor gene to exert anti-tumor effects. Vitro experiments confirmed that ATRA has an anti-leukemia effect on non-M3-AML cell lines. We perform the 2 phase, single-arm, multicenter study of Decitabine in Combination with ATRA, G-CSF and low dose cytarabine(DLAAG Regimen)in R/R AML not suitable for strong chemotherapy (NCT03356080). Methods. R/R AML patients aged more than 18 years not suitable for strong chemotherapy were eligible to enroll on this study. The objective was to assess the responses and safety of this therapy. All patients received subcutaneous decitabine injection 0.1-0.2mg/kg on days 1-3 ,8-10,15-17 .ATRA was taken orally at 45mg/m2 on day 4-6 and 15mg/m2on days 7-20. Subcutaneous injection cytarabine 15mg/m2 every 12 hours on days 1-10 and G-CSF 300ug/d on day 0 until disease remission or absolute neutrophils count ≥ 0.5×109/L were administered. The FLT3 inhibitor, arsenious acid, and the JAK-2 inhibitor, rotectinib, were allowed to be combined.All patients received one or two courses of induction treatments. Results. During the period from December 1, 2017 to July 2019, a total of 33 patients were recruited, including 17 women and 16 men. The median age is 64 years (range 46-82). In 33 patients, the overall response rate (ORR = CR + PR) was 36.3%, and the complete response rate (CRR = CR + CRi) was 33.3%. The early treatment-related mortality rate was 6.0%. One died of infection and one died of organ bleeding. Of the 26 patients with karyotype data, 11 received CR. Seven patients (63.6%) in CR showed normal karyotype, 2 patients (18.1%) in CR, and 1 patient (9.0%) in PR showed other moderate karyotypes. One case (9.0%) of the CR group had a poor karyotype. Statistical analysis showed that there was a statistically significant difference between the different karyotype groups (P < 0.05). Only 2 of the 10 FLT3 mutant patients achieved CR (20%). Two patients with abnormal MLL gene did not receive CR. Conclusions DLAAG regimen is effective and tolerated in patients with R/R AML who are not suitable for intensive therapy and could be as a bridging therapy regimen followed by HSCT. Disclosures No relevant conflicts of interest to declare.

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A Retrospective Observation of Treatment Outcomes Using Decitabine-Combined Standard Conditioning Regimens Before Transplantation in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Frontiers in Oncology ◽

10.3389/fonc.2021.702239 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yuhang Li ◽

Longcan Cheng ◽

Chen Xu ◽

Jianlin Chen ◽

Jiangwei Hu ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Low Dose ◽

High Dose ◽

Hematopoietic Stem ◽

Hematopoietic Reconstitution ◽

Conditioning Regimens ◽

Refractory Acute Myeloid Leukemia ◽

Acute Myeloid ◽

Refractory Aml

Hypomethylating agents, decitabine (DAC) and azacitidine, can act as prophylactic and pre-emptive approaches after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a non-intensive bridging approach before allo-HSCT. However, they are rarely used as a part of conditioning regimens in patients with relapsed or refractory acute myeloid leukemia (AML). This retrospectively study included a total of 65 patients (median, 37; range, 13–63) with relapsed or refractory AML who were treated by allo-HSCT after myeloablative conditioning regimens without or with DAC (high-dose DAC schedule, 75 mg/m2 on day −9 and 50 mg/m2 on day −8; low-dose DAC schedule, 25 mg/m2/day on day −10 to −8). DAC exerted no impact on hematopoietic reconstitution. However, patients who were treated with the high-dose DAC schedule had significantly higher incidence of overall survival (OS, 50.0%) and leukemia-free survival (LFS, 35.0%), and lower incidence of relapse (41.1%) and grade II–IV acute graft versus host disease (aGVHD, 10.0%) at 3 years, when compared with those treated with standard conditioning regimens or with the low-dose DAC schedule. In conclusion, high-dose DAC combined with standard conditioning regimens before allo-HSCT is feasible and efficient and might improve outcomes of patients with relapsed or refractory AML, which provides a potential approach to treat these patients.

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Effect of low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor priming (CAG regimen) on the outcome of elderly patients with acute myeloid leukemia

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.7067 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 7067-7067

Author(s):

S. Qian ◽

J. Li ◽

S. Zhang

Keyword(s):

Acute Myeloid Leukemia ◽

Elderly Patients ◽

Myeloid Leukemia ◽

Low Dose ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Cytogenetic Aberrations ◽

Stimulating Factor ◽

Low Dose Cytarabine ◽

Acute Myeloid

7067 Background: To evaluate the efficacy and toxicity of low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF) protocol in elderly patients with acute myeloid leukemia (AML). Methods: A total of fifty-two elderly patients were enrolled. Twenty-eight patients were male, and 24 were female, with ages ranging from 60 to 81 years (median, 65 years). Complete remission (CR) had not been achieved in five patients after 2 courses of a standard induction regimen including daunorubicin and cytarabine or an equivalent anthracycline-based regimen. Cytogenetic analysis was performed in 40 patients, and unfavourable cytogenetic aberrations were showed in 10 patients. All patients were treated with CAG regimen including low-dose cytarabine (10 mg/m2 per 12 hours, days 1 to 14), aclarubicin (10 mg per day, days 1 to 8), and G-CSF priming (200 μg/m2 per day, days 1 to 14). Results: The overall response rate was 69.2%, and 29 of 52 (55.8%) patients achieved CR, including 23 of 35 (65.8%) patients with previously untreated AML, 6 of 17 (35.2% ) patients with refractory, relapsed and secondary AML, 4 of 9 (44.4%) patients aged over 70 years, 4 of 10 (40.0%) patients with unfavourable cytogenetic aberrations. The early death rate was 7.6%. The median overall survival duration 14 months. Myelosuppression was mild to moderate, severe nonhematologic toxicity was not observed. Conclusions: CAG priming regimen as the induction therapy is well tolerable and effective in elderly patients with AML. No significant financial relationships to disclose.

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