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.

Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia

In adults with non-promyelocytic acute myeloid leukemia (AML), high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years) who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69) received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles). The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27) received an intermediate-high-dose (<27 g/m2), and group 3 (n=35) received a very-high-dose (≥27 g/m2). Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients). The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21) and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96) than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival.

High-dose Cytarabine, Etoposide and Cisplatin Salvage Chemotherapy for Relapsed Adult Acute Myeloid Leukemia / 대한혈액학회지

BACKGROUND: High-dose cytarabine (HDAC) and etoposide, two of the most active drugs in relapsed acute myeloid leukemia (AML), have shown synergistic activity with platinum analogues in both preclinical and clinical studies. The present study was undertaken to assess the efficacy and toxicity of a combination regimen of HDAC, etoposide and cisplatin (HAEP) in adult patients with relapsed AML. METHODS: Between 1990 and 1998, 16 patients with relapsed AML were treated with HAEP salvage therapy, which consisted of HDAC (2.0g/m2, q12hr x2/d), etoposide (100mg/m2/d) and cisplatin (20mg/m2/d, 2-hr infusion) for 5 days. RESULTS: Ten of 16 patients (62.5%) achieved a complete remission (CR). Six patients who could not attain CR died either of infection (5 patients) or CNS hemorrhage (1 patient). The median overall survival (OS) for all patients was 63 (range, 6~253) weeks. Median disease free survival (DFS) for those who achieved CR was 57 weeks. At the time of analysis, 6 patients were alive with a median follow-up of 68 (range, 22~152) months. All patients experienced fever in the setting of grade IV neutropenia. The median length of neutropenia and thrombocytopenia was 36 and 41 days, respectively. The median period of neutropenic fever in complete responders was 20 days. The main non-hematologic grade III~IV toxicities were mucositis(25%) and hepatic dysfunction (40%). CONCLUSIONS: The HAEP salvage regimen appears highly effective in obtaining high CR rate and possibly long-term survival in relapsed AML. The results suggest that the addition of cisplatin may enhance the activity of HDAC and etoposide. Hematologic toxicity was high, but there was no excessive or cumulative non-hematologic toxicity. Further evaluation of this novel combination in AML is indicated.

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.