RATIONALE AND OBJECTIVES

The burden of acute myeloid leukemia (AML) is felt worldwide with increasing number of diagnosed cases. A recommended treatment option for a longer remission is hematopoietic stem cell transplantation after chemotherapy with cytarabine and an anthracycline antibiotic, either Idarubicin or Daunorubicin. In the Philippines, Doxorubicin, a cheaper and more accessible option for chemotherapy among those who have financial incapabilities. It is no longer part of the National Comprehensive Cancer Network (NCCN) recommendation for use however; it remains to be part of the Philippine National Clinical Practice Guideline in the treatment of AML. This leads us to wonder what the difference in outcome of patients who have received doxorubicin compared to those who received Idarubicin as induction chemotherapy.

RESEARCH DESIGN AND METHODOLOGY

This is a retrospective cohort study. Data was collected through chart review of AML patients admitted for induction chemotherapy. Descriptive statistics was used to analyze the sociodemographic and clinical profile of patients. Survival analysis was done using the Kaplan-Meier computation. The t-test for two proportions was used to compare outcomes between the two groups.

RESULTS

This study included 65 participants, 55 received idarubicin and 10 received doxorubicin. The average age of diagnosis in the Idarubicin group is 41.38 years, and 34.9 years in the Doxorubicin group. Majority of participants are females (58.18% vs 80%) and married (67.27% vs 60%). They are predominantly nonsmokers (89.09% vs 80%), with no maintenance medications (61.82% vs 70%), and comorbidities (70.91% vs 90%). There was no significant difference in the median overall survival of both groups (507 days vs 428 days, logrank test = 0.74).

DISCUSSION AND CONCLUSION

Outcomes of this study leads us to conclude that Doxorubicin is not inferior to Idarubicin in terms of survival.

Human ; Acute Myelogenous Leukemia ; Leukemia, Myeloid, Acute ; Idarubicin ; Doxorubicin ; Induction Chemotherapy ; Survival

OBJECTIVE: To evaluate the efficacy and safety of idarubicin combined with high-dose cytarabine as a post-remission therapy for elderly patients with acute myeloid leukemia (AML). METHODS: From November 2017 to June 2021, 24 AML patients aged ≥60 years who were in complete remission for the first time were enrolled in consolidation chemotherapy with idarubicin (10 mg/m² intravenously once for day 1) combined with high-dose cytarabine (1.5 g/m² intravenously over 3 hours every 12 hours for day 1-3), and the efficacy and safety were observed. RESULTS: Among the 24 patients, there were 12 males and 12 females, the median age was 65 (60-78) years old, and the median follow-up time was 23.3 (2-42.7) months. By the end of the follow-up, 15 patients relapsed and 11 patients died. The median disease-free survival (DFS) was 9 months and there were 3 cases of 2-year DFS. The median overall survival (OS) was 16.2 months, and there were 4 cases of 2-year OS. In terms of safety, 6 patients had grade 1-2 non-hematological adverse reactions, 12 patients had grade 3-4 hematological adverse reactions, and a total of 6 patients developed infection after consolidation chemotherapy. Multivariate analysis showed that two induction cycles and high-risk cytogenetic abnormalities were the adverse factors of DFS and OS in elderly patients with AML in this study. CONCLUSION For AML patients ≥60 years old in first complete remission, idarubicin combined with high-dose cytarabine as post-remission therapy has a better safety, but compared with other regimens does not improve the prognosis of elderly patients, which needs further exploration.
Aged ; Male ; Female ; Humans ; Middle Aged ; Idarubicin/therapeutic use* ; Retrospective Studies ; Cytarabine ; Antineoplastic Combined Chemotherapy Protocols ; Leukemia, Myeloid, Acute/etiology* ; Remission Induction

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.
Adolescent ; Child ; Female ; Humans ; Male ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chromosomal Proteins, Non-Histone/genetics* ; Cladribine/therapeutic use* ; Cytarabine/therapeutic use* ; Daunorubicin/therapeutic use* ; Etoposide/therapeutic use* ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Homoharringtonine/therapeutic use* ; Idarubicin/therapeutic use* ; Leukemia, Myeloid, Acute/genetics* ; Oncogene Proteins/genetics* ; Poly-ADP-Ribose Binding Proteins/genetics* ; Remission Induction ; Retrospective Studies

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cyclophosphamide/therapeutic use* ; Cytarabine/therapeutic use* ; Hematopoietic Stem Cell Transplantation ; Humans ; Idarubicin/therapeutic use* ; Leukemia, Myeloid, Acute/drug therapy* ; Neutropenia ; Prospective Studies ; Recurrence ; Retrospective Studies

Objective: To explore outcomes in adult with de novo acute myeloid leukemia (AML) received IA10 (10 mg/m(2) d1-3 idarubicin plus cytarabine 100 mg/m(2) d1-7) regimen as induction chemotherapy. Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-M(3)) adults treated with IA10 who achieved morphologic leukemia-free state (MLFS) but not accepted allogeneic hematopoietic stem cell transplantation (allo-HSCT) were assessed retrospectively. Results: A total of 198 patients were included in this study with 96 (48.5%) male and a median age of 42 years old (range, 18-62 years old). Using the SWOG cytogenetic classification, 45 (22.7%), 104 (52.5%), 24 (12.1%) and 25 (12.6%) patients belonged to favorable, intermediate, unfavorable and unknown categories, respectively. 6 (3.0%) patients had monosomal karyotype, and 28 (14.1%) positive FLT3-ITD mutation. A complete remission (CR, defined as MLFS with ANC ≥ 1×10(9)/L and PLT ≥ 100×10(9)/L) achieved in 168 (84.8%) patients, a CRp (defined as MLFS with incomplete PLT recovery) in 16 (8.1%) and a CRi (defined as MLFS with incomplete ANC and PLT recovery) in 14 (7.1%). With a median follow-up period of 15 months (range, 1 to 70 months) in survivors, the probabilities of cumulative incident of relapse (CIR), disease free survival (DFS) and overall survival (OS) rates at 2-year were 45.2%, 46.9% and 62.9%, respectively; the median durations of relapse, DFS and OS were 34, 20 and 37 months respectively. At the time of achieving first MLFS, multivariate analyses showed that positive FLT3-ITD mutation and CRi were common adverse factors affecting CIR, DFS and OS; unfavorable-risk of SWOG criteria was an adverse factor affecting CIR and DFS; monosomal karyotype was associated with shorter OS. After first consolidation therapy, FLT3-ITD mutation positive and unfavorable-risk of SWOG criteria had negatively impact on CIR, DFS and OS; peripheral blasts ≥ 0.50 and positive MRD (defined as RQ-PCR WT1 mRNA ≥ 0.6% or any level of abnormal blast population detected by flow cytometry) after first consolidation therapy were common adverse factors affecting CIR and DFS; CRi was an adverse factor affecting DFS and OS. Conclusions: In adult with de novo AML received IA10 regimen as induction regimen, unfavorable molecular markers or cytogenetics at diagnosis and CRi independently predicted poor outcome. In addition, a higher percentage of peripheral blasts, monosomal karyotype and positive MRD after first consolidation therapy had negatively impact on outcomes.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cytarabine/administration & dosage* ; Disease-Free Survival ; Female ; Humans ; Idarubicin/administration & dosage* ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/drug therapy* ; Male ; Middle Aged ; Prognosis ; Remission Induction ; Retrospective Studies ; Young Adult

OBJECTIVETo compare the complete remission rate (CRR) and adverse reaction of the 3 different chemotherapy regimens (daunorubicin, idarubicin, imported idarubicin combined with cytarabine) for the treatment of adult patients with newly diagnosed non-M3 acute myeloid leukemia (AML).

METHODSSeventy-one adult patients with newly diagnosed non-M3 AML were divided into 3 groups: 17 cases treated with daunorubicin plus cytarabine as group A, 24 cases treated with idarubicin plus cytarabine as group B, 30 cases treated with the imported idarubicin plus cytarabine as group C. The curative effects and adverse reactions were compared among the 3 groups after treatment.

RESULTSCCR in group C (86.67%) was significantly higher than that in group A (52.94%) and group B (70.83%), and the CRR in group B was significantly higher than that in group A (P<0.05). The incidence of adverse reaction such as nausea, vomiting, myelosuppression and infection among 3 groups were not statistically significantant (P>0.05).

CONCLUSIONThe curative effect of idarubicin for the treatment of non-M3 AML patients is better than that of daunorubicin, especially the curative efficiency of imported darubicin is much higher; the adverse reaction after treatment by daunorubicin and idarubicin can be controllable, so daunorubicin and idarubicin can be used as first-line drug for the patients with AML, and patients can choose more appropriate drug according to their own economic ability.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Daunorubicin ; Humans ; Idarubicin ; Leukemia, Myeloid, Acute ; Remission Induction

BACKGROUND: Standard remission induction chemotherapy consisting of anthracycline plus cytarabine (3+7) is administered for adult acute myeloid leukemia (AML). However, the effects of intensified regimen on complete remission (CR), relapse and overall survival (OS) remain unknown. METHODS: We analyzed 1195 patients treated with idarubicin plus cytarabine/BHAC (3+7) from 2002 to 2013. Among them, 731 received early intensification with 3-day cytarabine/BHAC (3+10, N=363) or 2-day idarubicin plus cytarabine/BHAC 3 days (5+10, N=368). The 3+10 and 5+10 strategies were applied to patients with bone marrow blast counts of 5–20% and >20% on day 7 of 3+7, respectively. RESULTS: Early intensification correlated with a younger age (median: 40 vs. 45 yr) and higher t(8;21) frequency (20.4% vs. 7.1%), compared to 3+7. After early intensification, the early death rates were higher among the elderly (3+10 [15.7%], 5+10 [21.7%] vs. 3+7 [6.3%], P=0.038), while the post-induction CR rate was higher in young patients (3+10 [79.8%], 5+10 [75.1%] vs. 3+7 [65.1%], P<0.001). Early relapse rate was also decreased (3+10 [11.8%], 5+10 [11.7%] vs. 3+7 [22.0%], P<0.001). In multivariate analysis, early intensification correlated with an inferior 5-year OS among elderly patients (19.2% vs. 22.8%; hazard ratio [HR]=1.84, 95% confidence interval [CI]; 1.11–3.06, P=0.018) and lower overall relapse rate among young patients (33.0% vs. 41.4%, P=0.023; HR=0.71, 95% CI; 0.55–0.93, P=0.012). CONCLUSION: Early intensification correlated with higher CR and lower relapse rates, but not OS in young AML patients. In elderly patients, early intensification correlated with a higher early death rate and poorer OS.
Adult* ; Aged ; Bone Marrow ; Cytarabine ; Drug Therapy* ; Humans ; Idarubicin ; Induction Chemotherapy* ; Leukemia, Myeloid, Acute* ; Mortality ; Multivariate Analysis ; Recurrence ; Remission Induction

BACKGROUND: Although the overall survival of childhood acute lymphoblastic leukemia (ALL) approaches 85-90%, the prognosis of relapsed or refractory (R/R) ALL is grave. This study aimed to identify the treatment pattern, treatment response, and overall survival of these patients.METHODS: We reviewed data of 64 patients with R/R ALL whose initial diagnosis of ALL had been made between 1 and 21 years of age. Patients who received clofarabine as part of an induction regimen were excluded. Relapsed patients were limited to those who relapsed after ≥2 prior induction regimens. Treatment patterns, response rates, and overall survival were analyzed.RESULTS: Patients' median age was 15.0 years (range, 6.0-25.0) at the diagnosis of R/R ALL. The most frequently used agents other than steroid were vincristine (54.0%), cytarabine (44.6%), and idarubicin (36.5%), while L-asparaginase was used in only one patient. The complete remission (CR) and overall response (OR) rates were 38.1 and 42.9%, respectively. Sixteen patients (25.4%) underwent allogeneic hematopoietic stem cell transplantation (HSCT). The 5-year overall survival was 6.7%. The survival of patients with HSCT was significantly higher compared with those without HSCT (35.2% vs 0%, P=0.0097). Among 14 patients who achieved CR or CR without platelet recovery (CRp) before HSCT, the 3-year survival was 46.9%.CONCLUSION: The survival of Korean patients with R/R childhood ALL was dismal despite a reasonable CR rate, whereas that of those who received HSCT after CR or CRp was excellent. More treatment options are needed to improve the overall outcome of R/R childhood ALL.
Blood Platelets ; Cytarabine ; Diagnosis ; Hematopoietic Stem Cell Transplantation ; Humans ; Idarubicin ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Retrospective Studies ; Vincristine

OBJECTIVETo estimate the long-term outcomes and the prognostic factors of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia (AML).

METHODSThe CR rate, overall survival (OS) rate, relapse free survival (RFS) rate were retrospectively assayed in 143 de novo AML patients who received the HAD/HAI induction chemotherapy. The outcomes were compared among prognostic groups according to world health organization (WHO) classification, genetic prognosis and initial white blood cell (WBC) count. The role of consolidation chemotherapy consisting of middle-dosage Ara-C (MD-Ara-C) on long term survival was evaluated.

RESULTSOf 143 patients, 112 (78.3%) achieved CR after the first course of HAD/HAI induction treatment, and early death occurred in only one case. Notably, the CR rate of patients with an initial WBC count ≥100×10(9)/L was not significantly different from those with an initial WBC count<100× 10(9)/L (70.4% vs 80.2%, P=0.266). The CR rate for the patients with favorable, intermediate and unfavorable integrated genetics risk factors was 93.7%, 71.4% and 61.3%, respectively, the difference between groups was statistically significant (P=0.001). Patients with FLT3-ITD mutation obtained similar CR rate (70.6%) to that of patients with FLT3 wild type (79.3%, P=0.528).The estimated 5-year OS rate and 5-year RFS rate for all patients was 40.0% and 37.0%, respectively, with a median follow-up of 24 (range 1-104) months. The median survival time was 30 [95%CI (12, 48)] months. 5-year OS and 5-year RFS of the 96 patients who achieved CR after first course chemotherapy without undergoing allo-HSCT in complete remission was 47.0% and 38.0%, respectively. 5-year OS was significantly higher in MD-Ara-C consolidation group than in no MD-Ara-C consolidation group among CR patients without allo-HSCT (58.0%, 19.0%, respectively, P=0.004). In patients who obtained CR after first course and received MD-Ara-C consolidation without allo-HSCT, the 5-year OS of patients with hyperleukocytosis was not significantly lower than that of patients without hyperleukocytosis (55.5%, 58.8%, respectively,P=0.419). FLT3-ITD mutation patients showed similar 5-year OS to that of wild type FLT3 patients (51.4%, 60.2%, respectively, P=0.482). And furthermore, 5-year OS of favorable, intermediate and unfavorable integrated genetics groups were 59.1%, 62.5%, 51.9%, respectively (P=0.332) in this subgroup.

CONCLUSIONHAD/HAI induction chemotherapy with sequential consolidation of MD-Ara-C could obtain satisfactory CR rate and long-term survival rate in de novo AML, especially for patients with hyperleukocytosis or FLT3-ITD mutation. It yet remains to be verified by large sample, prospective studies.

Cytarabine ; therapeutic use ; Daunorubicin ; therapeutic use ; Harringtonines ; therapeutic use ; Humans ; Idarubicin ; therapeutic use ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; drug therapy ; Leukocyte Count ; Prognosis ; Prospective Studies ; Remission Induction ; Retrospective Studies ; Survival Rate

For decades, maintenance chemotherapy has failed to improve the cure rate or prolong the survival of patients with acute myeloid leukemia (AML), other than those with acute promyelocytic leukemia. Immediately after the first complete remission following consolidation therapy was obtained, oral maintenance chemotherapy (daily 6-mercaptopurine and weekly methotrexate) was given and continued for two years in transplant-ineligible AML patients. Leukemia-free survival (LFS) and overall survival (OS) were studied and compared between these patients and the historical control group who did not receive maintenance therapy. Consecutive 52 transplant-ineligible AML patients were analyzed. Among these patients, 27 received oral maintenance chemotherapy. No significant difference was found in the patients' characteristics between the maintenance and the control groups. The median OS was 43 (95% CI, 19-67) and 19 (95% CI, 8-30) months in the maintenance and the control groups, respectively (P = 0.202). In the multivariate analysis, the presence of maintenance therapy was an independent prognostic factor for better OS (P = 0.021) and LFS (P = 0.024). Clinical benefit from maintenance chemotherapy was remarkable in older patients (> or = 60 yr) (P = 0.035), those with intermediate or unfavorable cytogenetics (P = 0.006), those with initial low blast count in peripheral blood (P = 0.044), and those receiving less than two cycles of consolidation therapy (P = 0.017). Maintenance oral chemotherapy as a post-remission therapy can prolong the survival of patients with AML who are not eligible for transplantation, particularly older patients, those with intermediate or unfavorable cytogenetics, those with initial low blast count, and those receiving less than two cycles of consolidation therapy.
6-Mercaptopurine/*therapeutic use ; Adolescent ; Adult ; Aged ; Antimetabolites, Antineoplastic/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cytarabine/therapeutic use ; Disease-Free Survival ; Female ; Humans ; Idarubicin/therapeutic use ; Leukemia, Myeloid, Acute/*drug therapy/mortality ; Maintenance Chemotherapy/*methods ; Male ; Methotrexate/*therapeutic use ; Middle Aged ; Remission Induction ; Treatment Outcome ; Young Adult