Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study / 中华血液学杂志

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

Caracterización clínica y citogenética de una cohorte de pacientes con leucemia promielocítica aguda atendidos en un Hospital Universitario en Medellín, Colombia / Clinical and cytogenetic characterization of a cohort of patients with acute promyelocytic leukemia treated at a University Hospital in Medellín, Colombia

Introducción. La leucemia promielocítica aguda (LPA) es un subtipo poco frecuente de leucemia mieloide aguda (LMA), que se caracteriza por un comportamiento clínico particularmente agresivo, y en ausencia de tratamiento, su curso generalmente es fatal. El objetivo de este trabajo fue determinar las características clínicas y citogenéticas de una cohorte de pacientes con LPA, con la finalidad de evaluar su relación con las complicaciones, el pronóstico y el desenlace de estos pacientes. Metodología. Se realizó un estudio observacional, descriptivo, retrospectivo de los pacientes mayores de 15 años con diagnóstico de LPA, atendidos en el Hospital Universitario San Vicente Fundación, entre los años 2012 a 2020. Resultados. Un total de 32 pacientes fueron incluidos. La edad media del diagnóstico fue 37 años. El 84,4% de los pacientes tenía la traslocación (15;17) en el cariotipo, y el 93,75% tenían FISH positivo. El 12,5% de los casos tenían cariotipo complejo. La mortalidad en los primeros 30 días fue del 15,6%, siendo el sangrado la causa de muerte más frecuente. Todos los pacientes que sobrevivieron alcanzaron la remisión completa (84,3%). En un promedio de seguimiento de 24 meses, el 14,8% de los casos recayeron. En el análisis bivariado se encontró relación entre sexo masculino y tener cariotipo complejo (p=0,015). No se encontró relación entre cariotipo complejo y mortalidad temprana (p=0,358), tampoco entre cariotipo complejo y recaída (p=0,052). Conclusiones. Se presentan las características clínicas y citogenéticas de una cohorte de pacientes con LPA en Colombia. El sangrado en el sistema nervioso central fue la principal causa de mortalidad temprana, todos los pacientes que sobrevivieron alcanzaron la remisión completa con la terapia de inducción. Las tasas de mortalidad, remisión completa y recaída fueron similares a las reportadas por otras series latinoamericanas, pero inferiores a estudios provenientes de países europeos. Contrario a lo reportado en otros estudios, no se encontró relación entre el cariotipo complejo y la mortalidad temprana o recaída.

Introduction. Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia (AML), characterized by a particularly aggressive clinical behavior, that in the absence of treatment is usually fatal. The objective of this work was to determine the clinical and cytogenetic characteristics of a cohort of patients with APL, in order to evaluate their relationship with the outcome and prognosis of these patients. Methodology. An observational, descriptive, retrospective study of patients older than 15 years with a diagnosis of APL treated at the Hospital Universitario San Vicente Fundación, between 2012 and 2020, was carried out. Results. A total of 32 patients were included. The mean age at diagnosis was 37 years, 84.4% of the patients had the t(15;17) in the karyotype, and 93.75% had positive FISH. 12.5% of cases had a complex karyotype. Mortality in the first 30 days was 15.6%, with bleeding being the most common cause of death. All patients who survived achieved complete remission (84.3%). In an average follow-up of 24 months, 14.8% of cases relapsed. In the bivariate analysis, a relationship was found between the male sex and having a complex karyotype (p<0.015). No relationship was found between complex karyotype and early mortality (p=0.358), nor between complex karyotype and relapse (p=0.052). Conclusions. We present the clinical and cytogenetic characteristics of a cohort of patients with APL in Colombia. Central nervous system bleeding was the main cause of early mortality, with all surviving patients achieving complete remission on induction therapy. Mortality, complete remission and relapse rates were similar to those reported by other Latin American series, but lower than studies from European countries. Contrary to what has been reported in other studies, no relationship was found between complex karyotype and early mortality or relapse

Analysis of the efficacy of pretreatment regimen containing idarubicin in allogeneic hematopoietic stem cell transplantation for high-risk refractory leukemia / 器官移植

Objective To investigate the clinical efficacy of pretreatment regimen containing idarubicin (IDA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk refractory leukemia. Methods A total of 116 patients with high-risk refractory leukemia who received allo-HSCT treated with 7 types of IDA-containing pretreatment regimes were enrolled in this study. The implantation rate of 116 recipients was summed up. The 2-year overall survival (OS), 2-year disease free survival (DFS), cumulative recurrence rate, recurrent mortality, transplantation related mortality (TRM), cumulative incidence of acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) were statistically analyzed by Kaplan-Meier survival curve. Results All 116 recipients successfully implanted. The median follow-up time was 28 (7-70) months. Among them, 64 recipients survived, the 2-year OS was 55.2%, 2-year DFS was 51.7%, 2-year recurrent mortality was 23.3% and 2-year TRM was 18.1%. Among 116 recipients, 72 cases suffered from aGVHD. The 2-year cumulative incidence rate of aGVHD was 62.1% including 20 cases of grade Ⅲ-Ⅳ aGVHD, the 2-year cumulative incidence rate was 17.2%. Among 116 recipients, 59 cases presented with cGVHD. The 2-year cumulative incidence rate was 55.4%, of which the 2-year cumulative incidence rate of extensive cGVHD was 14.7%. Among 116 recipients, 30 cases recurred with a 2-year cumulative recurrence rate of 25.9%. Conclusions IDA-containingpretreatment regime has high safety and effectiveness, and can be used as an effective pretreatment regime for transplantation preprocessing in patients with high-risk refractory leukemia.

Outcomes of adult patients with de novo acute myeloid leukemia received idarubicin plus cytarabine regimen as induction chemotherapy / 中华血液学杂志

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.

Outcomes of adult patients with de novo acute myeloid leukemia received idarubicin plus cytarabine regimen as induction chemotherapy / 中华血液学杂志

Objective@#To explore outcomes in adult with de novo acute myeloid leukemia (AML) received IA10 (10 mg/m2 d1-3 idarubicin plus cytarabine 100 mg/m2 d1-7) regimen as induction chemotherapy.@*Methods@#From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-M3) 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 ≥ 1×109/L and PLT ≥ 100×109/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.

Efficacy observation of standard-dose IA regimen in treatment of ≥ 55 years old newly diagnosed patients with acute myeloid leukemia / 白血病·淋巴瘤

Objective To explore the clinical efficacy and toxicity of standard-dose IA regimen as induction chemotherapy in treating initially diagnosed acute myeloid leukemia (AML) patients ≥55 years old. Methods A total of 32 patients were enrolled in this study. The remission, survival time and adverse effects after IA regimen were retrospectively analyzed. Results The complete remission (CR) rate, partial remission (PR) rate and overall response (OR) rate were 71.9%(23/32), 9.4%(3/32), 81.3%(26/32) after IA regimen. In favorable, intermediate and poor prognosis groups (grouped by cytogenetic or molecular factors), 6, 14 and 3 cases achieved CR (χ2= 5.571, P= 0.067), 1, 2 and 0 cases achieved PR, while OR rates were 100.0 %(7/7), 84.2 % (16/19), 50.0 % (3/6) (χ2= 2.114, P= 0.359). The median overall survival (OS) time of three groups were 28.07 months (6.57-46.33 months), 16.93 months (0.40-87.57 months) and 3.03 months (2.00-6.00 months) (Z=9.630, P=0.008) and the 2-year OS rates were 83.33%, 46.80%and 0, respectively (χ2=12.206, P< 0.001). Myelosuppression and infections due to neutropenia were the main adverse effects and severe non-hemotologic toxicities were not observed. Conclusion The standard-dose IA regimen can increase CR/OR rate and prolong the median OS time of patients with favorable and intermediate prognosis and it can be used as the first induction chemotherapy regimen for elderly AML patients of ≥55 years old.

Outcome of Reinduction Chemotherapy with a Modified Dose of Idarubicin for Children with Marrow-Relapsed Acute Lymphoblastic Leukemia: Results of the Childhood Acute Lymphoblastic Leukemia (CALL)-0603 Study

This multicenter, prospective trial was conducted to develop an effective and safe reinduction regimen for marrow-relapsed pediatric acute lymphoblastic leukemia (ALL) by modifying the dose of idarubicin. Between 2006 and 2009, the trial accrued 44 patients, 1 to 21 years old with first marrow-relapsed ALL. The reinduction regimen comprised prednisolone, vincristine, L-asparaginase, and idarubicin (10 mg/m²/week). The idarubicin dose was adjusted according to the degree of myelosuppression. The second complete remission (CR2) rate was 72.7%, obtained by 54.2% of patients with early relapse < 24 months after initial diagnosis and 95.0% of those with late relapse (P = 0.002). Five patients entered remission with extended treatment, resulting in a final CR2 rate of 84.1%. The CR2 rate was not significantly different according to the idarubicin dose. The induction death rate was 2.3% (1/44). The 5-year event-free and overall survival rates were 22.2% ± 6.4% and 27.3% ± 6.7% for all patients, 4.2% ± 4.1% and 8.3% ± 5.6% for early relapsers, and 43.8% ± 11.4% and 50.0% ± 11.2% for late relapsers, respectively. Early relapse and slow response to reinduction chemotherapy were predictors of poor outcomes. In conclusion, a modified dose of idarubicin was effectively incorporated into the reinduction regimen for late marrow-relapsed ALL with a low toxic death rate. However, the CR2 rate for early relapsers was suboptimal, and the second remission was not durable in most patients.

Efficacy and safety of IA regimen containing different doses of idarubicin in de-novo acute myeloid leukemia for adult patients / 中华血液学杂志

Objective@#To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m2, 10 mg/m2 or 12 mg/m2 as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) .@*Methods@#A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m2) as induction chemotherapy in newly diagnosed patients of adult AML.@*Results@#Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m2 group and IDA 12 mg/m2 group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m2 group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m2 was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m2 when compared with the IDA 8 mg/m2 was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×109/L in IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×109/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) .@*Conclusions@#For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m2 is clinically superior to IDA 8 mg/m2 and IDA 12 mg/m2 in favorable intermediate AML subgroup. However, idarubicin 12 mg/m2 is more suitable to adverse AML subgroup.

Inducing therapy of cytarabine combined with daunorubicin or idarubicin for the newly diagnosed acute myeloid leukemia：comparison of clinical efficacy / 白血病·淋巴瘤

Objective To explore the clinical effect and toxicity of daunorubicin combined with cytarabine (DA regimen) and idarubicin combined with cytarabine (IA regimen) for the treatment of patients with acute myeloid leukemia (AML) as induction chemotherapy. Methods The clinical data of 84 newly diagnosed AML patients (except M3) treated with DA or IA regimen were analyzed retrospectively. DA regimen group included 32 patients (17 males and 15 females with median age of 46 years), while IA regimen group included 52 patients (29 males and 23 females with media age of 49 years). Efficacy index was complete remission (CR), total efficiency and adverse reactions after one course of chemotherapy rate. Results In DA regimen group,the CR rate was 65.6 %(21/32), and the total efficiency rate was 75.0 %(24/32), while in IA regimen group, the CR rate was 71.2 %(31/52), and the total efficiency rate was 80.8 %(42/52), respectively, but, the differences of media survival and 5-year survival rate were not statistically significant (16.8 months vs. 24.9 months, 26 % vs. 44 %, both P>0.05). The main side effect in the two groups included hematologic (bone marrow suppression) and non-hematologic adverse reactions, with no significant difference between the two groups (all P>0.05). Conclusion For newly diagnosed AML patients, remission rate and total efficiency of DA regimen are same as IA regimen after one course treatment, and adverse events between the two regimens do not differ significantly.

Treatment of pediatric patients with refractory acute lymphoblastic leukemia with IHDA regimen / 中华实用儿科临床杂志

Objective To observe the efficacy and adverse effect of IHDA [Idarubicin(IDA) + high-dose Cytarabine(HD-Ara-C)] as a remedy regimen in the treatment of pediatric patients with refractory acute lymphoblastic leukemia(ALL).Methods Twelve children with refractory ALL were treated by IHDA regimen as follows:IDA,10 mg/(m2·d),d1-3;Ara-C,1.0g/m2,q12h,d1-3.The children who achieved complete remission(CR)could get into the following sequential regimens or allogeneic hematopoietic stem cell transplantation (allo-HSCT).The same regimen was given to the children who didn't achieve CR when WBC ＞2.0×109/L.The efficacy and hematology or non-hematology adverse effect were evaluated.Results CR/partial remission (PR)/non-remission (NR) were respectively 4/3/5 cases after giving the first regimen,and CR/PR/NR were 5/3/4 cases after giving the second regimen,respectively.The overall remission was 66.7％ (8/12 cases),of which 5 cases(41.7％) achieved CR,3 cases (25.0％) reached PR and 4 cases(33.3％) reached NR.Grade Ⅳ myelosuppression occurred in all patients,but no severe infection and hemorrhage happened after the application of granulocyte colony stimulating factor (G-CSF),platelet transfusion and anti-infection treatment.Some reversible side effects like liver toxicity,myocardial damage and nerve injury were observed in some patients.There was no chemotherapy related mortality in all the patients.Two cases relapsed again followed up to October 2015.One achieved CR after applying chimeric antigen receptor T-cell immunotherapy and was receiving allo-HSCT now.Another was dead after applying FLAG (Prednisone+Fludarabine+Ara-C+G-CSF) save regimen.The time of the other 3 cases achieving CR was 26,10,4 months,respectively.Among the remaining 7 cases,3 cases were forced to receive hematopoietic stem cell transplantation,2 cases abandoned treatment and 2 cases failed to follow up.Conclusions The IHDA regimen is a well-effective and tolerated treatment for pediatric patients with refractory ALL,and could create an opportunity for the application of allo-HSCT.

Effect of idarubicin combined with medium-dose arabinoside in intensive chemotherapy on the prognosis of acute myeloid leukemia / 白血病·淋巴瘤

Objective To explore the efficacy and feasibility of idarubicin combined with medium-dose arabinoside in intensive chemotherapy for acute myeloid leukemia (AML). Methods Fifty remittent patients with induced chemotherapy who underwent the intensive consolidation therapy with medium-dose arabinoside from January 2010 to January 2015 in hematology department of General Hospital of Beijing Military Area were considered as the treatment group. The single arabinoside (2 g/m 2, 1/12 h, d1-3) treatment for 50 cases in the same period were considered as the control group. Two groups were performed with 6 courses sequential. There were 28 males, 22 females in the treatment group, and average age was 27.6 years (18-52 years), with 3 cases of M 1, 27 cases of M2, 8 cases of M4, 12 cases of M5. In the control group, there were 30 males, 20 females, and average age was 26.8 years (16-50 years), with 2 cases of M1, 30 cases of M2, 8 cases of M4, 10 cases of M5. Then the complications and disease-free survival of two groups were observed respectively. Results Follow-up was done until June 2015. In the treatment group, 1 case died of pulmonary infection, 2 cases died of septic shock and 3 cases died of pulmonary infection, 1 case died of septic shock in the control group. The treatment related mortality of both groups were 6 % (3/50), 8 % (4/50), the related relapse rates were 32 % (16/50), 52 % (26/50), the disease-free survival rates were 62 % (31/50), 40 % (20/50) respectively in two groups. Conclusion Compared with the single arabinoside, the intensive consolidation therapy with medium-dose arabinoside and idarubicin for the treatment of AML has gained lower relapse rate and the related mortality, and the DFS rate has been improved significantly, which need further clinical application.

An evaluation of therapeutic effect of idarubicin combined with CAG regimen on previously untreated elderly patients with acute myeloid leukemia / 中国中西医结合急救杂志

10.3969/j.issn.1008-9691.2013.03.017

Miliaria-rash after neutropenic fever and induction chemotherapy for acute myelogenous leukemia / Miliária 'rash' após neutropenia febril e quimioterapia de indução para a leucemia mielóide aguda

Miliaria is a disorder of the eccrine sweat glands which occurs in conditions of increased heat and humidity. It can be associated with persistent febrile states as well as with certain drugs. We presented a 40 year-old female with myelodysplastic syndrome and progression to acute myelogenous leukemia who was admitted to the hospital for chemotherapy induction. The patient was treated with idarubicin and cytarabine. She became pancytopenic and developed neutropenic fever and was started on vancomycin and cefepime, but was persistently febrile with night sweats. Five days into her fevers, she developed diffuse, nonpruritic and fragile vesicles together with drenching nightsweats. The patient's exanthem was diagnosed as Miliaria crystallina, most probably induced by neutropenic fever and idarubucin exposure.

Miliária é uma desordem das glândulas sudoríparas écrinas, que ocorre em condições de aumento de calor e umidade. Miliária pode ser associada com estados febris persistentes bem como com certos medicamentos. Apresentamos o caso de uma mulher de 40 anos com síndrome mielodisplásica e progressão para leucemia mielóide aguda que foi admitida no hospital para quimioterapia de indução. A paciente foi tratada com idarrubicina e citarabina. Ela se tornou pancitopênica e desenvolveu neutropenia febril. Iniciou tratamento com vancomicina e cefepime, mas a febre com sudorese noturna continou. Cinco dias depois a paciente desenvolveu vesículas difusas, não pruríticas e frágeis juntamente com a persistência de sudorese noturna. O exantema do paciente foi diagnosticado como Miliária cristalina, provavelmente induzida por neutropenia febril e exposição a idarubucin.

Chromosomal aberration and micronucleus studies of two topoisomerase (II) targeting anthracyclines.

Anthracycline antibiotics are widely used in cancer chemotherapy. Doxorubicin and Idarubicin, topoisomerase-targeting anthracyclines, were examined for their effect on chromosomal aberration and micronucleus induction in cultured human lymphocytes employing lymphocyte transformation test and cytokinesis-blocked micronucleus (CBMN) assay. A statistically significant dose-dependent increase in micronucleus frequency (p < 0.001) in binucleated cells was seen as well as a significant increase in chromosomal aberration frequency was also observed for both the drugs. A variety of aberrations were scored including terminal deletions, breaks, gaps, exchanges, fragment formation, ends rejoining, interstitial deletions etc. Nuclear division index was also calculated and showed a cell cycle delay towards higher doses. A number of necrotic and apoptotic cells were also observed at higher concentrations. This confirms the two drugs to be clastogenic and aneugenic.

Improvement of Induction Remission Rate by Modifying the Dose of Idarubicin for Relapsed Childhood Acute Lymphoblastic Leukemia

Relapse is the major cause of treatment failure in acute lymphoblastic leukemia (ALL), yet there is no established treatment for relapsed ALL. To improve the induction remission rate, we modified the dose of idarubicin in the original Children's Cancer Group (CCG)-1884 protocol, and retrospectively compared the results. Twenty-eight patients diagnosed with relapsed ALL received induction chemotherapy according to the CCG-1884 protocol. Complete remission (CR) rate in all patients after induction chemotherapy was 57%. The idarubicin 10 mg/m2/week group showed CR rate of 74%, compared with the 22% CR rate of the idarubicin 12.5 mg/m2/week group (p=0.010). Remission failure due to treatment-related mortality (TRM) was 44% and 5.2% in the idarubicin 12.5 mg/m2/week and 10 mg/m2/week groups, respectively (p=0.011). Overall survival (OS) and 4-yr event-free survival (EFS) were 12.8% and 10.3%, respectively. OS and 4-yr EFS were higher in the idarubicin 10 mg/m2/week group (19.3% and 15.6%) than in the 12.5 mg/m2/week group (0% and 0%). In conclusion, a modified dose of idarubicin from 12.5 mg/m2/week to 10 mg/m2/week resulted in an improved CR rate in the treatment of relapsed ALL, which was due to lower TRM. However, despite improved CR rate with modified dose of idarubicin, survival rates were unsatisfactory.

Effects of FLAG regimen and IA regimen for acute myeloblastic leukaemia cells on P-glycoprotein-positive and P-glycoprotein-negative / 白血病·淋巴瘤

Objective To explore in vitro effects and the mechanism for FLAG regimen compared with IA regimen in P-glycoprotein-positive and -negative acute myeloblastic leukemia(AML) cell lines. Methods The expression of P-glycoprotein in K562 and K562/A02 cells were analyzed by flow cytometry. The effects of FLAG and IA on the proliferation of K562 and K562/A02 cells were detected by MTT assay. The Ara-CTP and Ara-C levels in those cells were measured by HPLC,the gene expression of hENT1 in K562 and K562/A02 cells was detected by real-time PCR. Results The positive rates of P- glycoprotein were (1.32±0.24)% in K562 cell and (97.66±3.77)% in K562/A02 cell, respectively. The expression of P- glycoprotein had no change after treated with FLAG or IA. The cytotoxicity to K562 of IA was better than FLAG [(84.41±9.33) % v.s (73.17±13.20)%, P<0.05], and the cytotoxicity to K562/A02 of FLAG was better than IA [(70.55±11.32)% v.s (48.46±12.81)%, P<0.01]. Ara-C and Ara-CTP accumulation and hENT1 expression in AML cells treated with FLAG were higher than that treated with IA. Conclusion P-glycoprotein-positive AML cells are more sensitive to FLAG regimen than IA regimen. The biochemical modulation of Ara-CTP and Ara-C may be the major mechanism.

Comparison of Combination Induction Chemotherapy using Idarubicin Plus either Enoron(r) or Sunrabin(r) in Adult Patients with Acute Myeloid Leukemia / 대한혈액학회지

BACKGROUND: To evaluate the effects and toxicity of combination chemotherapy using idarubicin (IDA) plus BH-AC as an induction regimen, we studied two groups of patients with adult acute myeloid leukemia (AML) who received IDA plus either Sunrabin(r) or Enoron(r). METHODS: Twenty-four and twenty-five patients in each group eligible for the induction study were enrolled. The remission induction therapy consisted of IDA 12mg/m2 intravenously for three consecutive days in combination with two kinds of BH-AC, that is Sunrabin(r) or Enoron(r), 300mg/m2 intravenously for seven days. Additional augmentation treatment with BH- AC was given for 3 days based on the results of bone marrow examination performed on the seventh day following initial treatment, i.e. depending on the ratio of the remaining leukemic cells. RESULTS: Complete remission was achieved in 75% vs 74% of each group of patients. The treatment-related mortality during induction chemotherapy was 1 patient in each group. There was no statistical difference in the level of toxicities between two groups. The most frequent side effect after these combination chemotherapy was manageable mucositis. Enoron(r) group showed rather rapid recovery of peripheral blood counts than those of Sunrabin(r) group. CONCLUSION: This study indicate Enoron(r) is comparable to Sunrabin(r) which can be used as an effective induction chemotherapeutic agent in adult patient with AML.

Cytarabine and Idarubicin Induction Chemotherapy in Patients with Acute Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: About 60~80% of previously untreated patients with acute myelogenous leukemia (AML) achieve complete remission (CR) when treated with cytarabine and anthracycline. Anthracycline is one of the most important chemotherapeutic agents in AML. It has been claimed that idarubicin showed superior complete remission rate than daunorubicin, which is not completely established. We evaluated idarubicin in combination with cytarabine (AI) as an induction chemotherapy in patient with AML. METHODS: Thirty one patients with newly diagnosed acute myelogenous leukemia were enrolled. Remission induction emotherapy was consisted of cytarabine (100mg/m2 IV over 24 hours on day 1~7) and idarubicin (12mg/m2 IV over 30 minutes on day 1~3). After achievement of CR, patients underwent consolidation therapy with high- dose cytarabine and/or bone marrow transplantation. RESULTS: Median age of the patients was 43 years (range; 17~62) and M2 was the most common subtype. The CR rate was 71% (22/ 31). The median overall and disease-free survival were 67 weeks (95% confidence interval, CI; 43~91) and 65 weeks (95% CI; 26~104), respectively with a median follow-up of 48 weeks. Major toxicities were fever and infection during the neutropenic period. There were three treatment-related mortalities. Causes of death were refractory AML in 1 patient and infection in 2 patients. CONCLUSION: AI induction chemotherapy seems to be effective and safe regimen as an induction chemotherapy in AML.

Treatment of Refractory and Relapsed Acute Myeloid Leukemia with High-dose Cytarabine and Idarubicin / 대한혈액학회지

BACKGROUND: The therapeutic outcome for refractory or relapsed acute myeloid leukemia (AML) is very poor; it is difficult to expect the long-term disease free survival in these patients. We evaluated the therapeutic outcome of a salvage chemotherapy consisting of high- dose cytarabine and idarubicin. METHODS: From December 1995 to September 2000, 20 patients (12 patients with primary refractory AML and 8 patients with first relapsed AML) were treated with the regimen that included cytarabine 3.0g/m2 (1.5g/m2 for patients >or=50 years of age) over 3 hours every 12 hours for 12 doses (D1-6, total 36g/m2) plus 12mg/m2 idarubicin for 3 days (D2-4) by intravenous infusion. RESULTS: The complete remission (CR) rate was 55.0% (95% confidence interval, 31.2 ~ 78.8%): 58.3% (7 of 12) for refractory AML and 50.0% (4 of 8) for relapsed AML. The causes of remission induction failure were resistant disease (15.0%, 3 of 20) and early death from infection (30.0%, 6 of 20). The median duration of disease free survival of the CR patients was 15 months (range, 1~59 months) and the median duration of overall survival of all patients was 6 months (range, 0~61 months). The median time of neutrophil recovery over 500/nL from the initiation of chemotherapy was 31 days and the median time of platelet recovery over 20X10(3)/nL was 32 days. For a total of 20 patients, grade 3 and 4 toxicity were observed in 20.0% for nausea/vomiting, 20.0% for diarrhea and 5.0% for stomatitis. CONCLUSIONS : We found that a combination chemotherapy of high-dose cytarabine and idarubicin was an effective salvage regimen for patients with refractory or relapsed acute myeloid leukemia. However aggressive supportive care is necessary to minimize the treatment related morbidity and mortality resulting from prolonged myelosuppression.

Cytarabine Plus Daunorubicin or Idarubicin as Induction Chemotherapy for the Patients with De novo Acute Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: The combination of cytarabine plus anthracycline has been considered standard chemotherapy for acute myelogenous leukemia (AML). We retrospectively analyzed the treatment results of the patients with de novo AML who received cytarabine plus daunorubicin or idarubicin as induction chemotherapy. METHODS: From 1989 to 1998, 149 patients with AML were included. For induction chemotherapy, the patients received cytarabine 100~ 200 mg/m2/day given by continuous 7-day in fusion plus either daunorubicin 40~45 mg/m2/ day (A+D) or idarubicin 12 mg/m2/day (A+I) administered for the first 3 days of treatment. We reviewed clinical records of the patients and analyzed the treatment results such as complete remission (CR) rate, disease free survival (DFS), and overall survival (OS). RESULTS: The CR rates were 67.1% (100 of 149); 69.3% (70 of 101) in A+D group and 62.5 % (30 of 48) in A+I group (P=0.409). The frequent reason of induction failure was resistant disease in A+D group (54.8%) and early death in A+I group (66.7%). The median DFS was 344 days; 344 days in A+D group and 314 days in A+I group. The median OS was 379 days; 389 days in A+D group and 379 days in A+I group. Age < or =60 years and allogeneic BMT as postremission therapy were independent favorable factors both for DFS and OS. AML M3 was favorable factor only for DFS. CONCLUSION: The combination of cytarabine plus daunorubicin or idarubicin was effective for the treatment of AML. We can not find significant difference in CR rate, disease free survival and overall survival between A+D and A+I group.