Clinical characteristics and outcome of refractory/relapsed myeloid leukemia in children with Down syndrome

Myeloid leukemia in Down syndrome (ML-DS) is associated with good response to chemotherapy and favorable prognosis. Because little research has been focused on refractory/relapsed (R/R) cases, we conducted a retrospective analysis for R/R ML-DS. Among ML-DS patients diagnosed between 2000 and 2010 in Japan, 26 relapsed (25 in the BM and 1 in the skin), and 3 refractory patients were enrolled. The male/female ratio was 18/11. The median age at initial diagnosis of ML-DS was 2 years, and the median time to relapse was 8.6 months. Each patient initially had been treated with ML-DS-specific protocols. Thirteen of the 26 patients achieved complete remission with various kinds of reinduction chemotherapies; 2 of 8 survived without further recurrence after receiving allogeneic hematopoietic stem cell transplantation, and 4 of 5 maintained complete remissions with chemotherapy alone. Treatment failures mostly were associated with disease progression rather than treatment-related toxicities. The 3-year OS rate was 25.9% ± 8.5%. A longer duration from initial diagnosis to relapse was a significant favorable prognostic factor (P < .0001). We conclude that clinical outcome for patients with R/R ML-DS generally are unfavorable, even in those receiving hematopoietic stem cell transplantation. Novel methods to identify poor prognostic factors for ML-DS are necessary.     

Clinical profile of dasatinib in Asian and non-Asian patients with chronic myeloid leukemia

Resistance and intolerance to imatinib are of particular clinical relevance to Asian patients because of their lower body surface area. Dasatinib is 325-fold more potent than imatinib in inhibiting BCR-ABL in vitro and is indicated for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant or intolerant to imatinib. Data from a series of phase I/II research trials were analyzed to compare the efficacy, safety and pharmacokinetic profile of dasatinib 70 mg twice daily in Asian and non-Asian patients. Results from 55 Asian and 615 non-Asian patients demonstrated that the efficacy and safety of dasatinib was comparable. Dasatinib was well tolerated, with no observed toxicities exclusive to Asian patients. A higher incidence of adverse events and lower rate of response observed among Asian patients with myeloid blast phase CML reflected the aggressive nature of the disease. Analyses of noncompartmental pharmacokinetics (5 Asian and 49 non-Asian patients) and population pharmacokinetics (17 Asian and 382 non-Asian patients) were also comparable. The efficacy, safety and pharmacokinetic profile of dasatinib 70 mg twice daily is similar in Asian and non-Asian patients with CML. Dasatinib is therefore an important therapeutic option for this patient population.     

Front-line treatment of Philadelphia positive chronic myeloid leukemia with imatinib and interferon-alpha: 5-year outcome

In 2004, we reported the short-term results of a multicentric, phase 2 study of imatinib 400 mg daily and pegylated interferon-alpha in the treatment of 76 early chronic phase Philadelphia-positive chronic myeloid leukemia patients. In this report, we update the results with an observation time of five years. After two years of treatment, all but 10 patients (13%) had discontinued pegylated interferon-alpha. The complete cytogenetic response rate at five years was 87%, and 94% of complete cytogenetic responders maintained the complete cytogenetic response after five years. All but one complete cytogenetic response also achieved a major molecular response. These data confirm the excellent response to imatinib front-line and the stability of the complete cytogenetic response. Any possible additional benefit of the combination with interferon-alpha remains uncertain, due to low patient compliance.     

联合应用治疗性白细胞及血小板单采术治疗慢性粒细胞白血病的临床研究

目的 探讨对白细胞、血小板两系均异常增高的慢性粒细胞白血病(CML)患者联合应用治疗性白细胞、血小板单采术的可行性及方法 .方法使用CS 3000 plus血细胞分离机对10例CML患者用单套耗材进行白细胞及血小板单采,先进行一系细胞的单采,中途腾空产品袋,更换程序及更换相应的分离夹.治疗后查血常规,观察治疗前后白细胞、血小板变化情况及临床症状缓解情况.结果 用此法单次治疗,白细胞计数下降(55.2±21.2)%;血小板计数下降(47.8±10.2)%;临床症状、体征改善.结论 利用单套耗材联合应用治疗性白细胞及血小板单采术可同时安全、有效地清除白细胞及血小板,是治疗白细胞、血小板同时异常增高CML患者有效的综合治疗方法之一.     

Pulmonary hypertension in patients with chronic myeloid leukemia

Dasatinib, a tyrosine kinase inhibitor (TKI), induces pulmonary hypertension (PH) in patients with chronic myeloid leukemia (CML). However, information on other TKIs is limited.We retrospectively analyzed PH prevalence by reviewing transthoracic echocardiography (TTE) findings in a population of Korean CML patients treated with TKI at a single hospital between 2003 and 2020. PH was defined as a high PH probability according to the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines.Of the 189 patients treated with TKI(s) during the study period, 112 (59.3%) underwent TTE. Among the 112 patients treated with a TKI for a median of 40.4 months (range: 1.1–167.2 months), PH was found in 12 (10.7%), most frequently in those treated with dasatinib (ie, in 3 [7.5%] of 40 of those treated with imatinib, 1 [3.1%] of 32 of those treated with nilotinib, and 8 [21.6%] of 37 of those treated with dasatinib). PH resolved in 4 (50.0%) of the 8 dasatinib-treated patients after discontinuation of the agent. One nilotinib-treated and all three imatinib-treated patients recovered from PH. In multivariate analyses, age >60 years, dasatinib treatment, and positive cardiopulmonary symptoms/signs at the time of transthoracic echocardiography were statistically significant risk factors for developing PH.These results show that PH is induced not only by dasatinib, but also by imatinib and nilotinib. Careful screening for PH during any TKI treatment may thus be warranted in patients with CML.     

Clinical outcome of treatment with a combined regimen of decitabine and aclacinomycin/cytarabine for patients with refractory acute myeloid leukemia

We conducted a clinical trial of low-dose decitabine plus aclacinomycin/cytarabine (AA) treatment (DAA) for 20 patients with refractory/relapsed de novo acute myeloid leukemia (AML) or AML transformed from myelodysplastic syndrome (MDS/AML) in order to examine its efficacy and tolerability. Additionally, P15^ink4b methylation status was analyzed (for 15 patients) pre- and post-DAA treatment, and in vitro drug sensitivity tests were performed for seven patients (AA or AA?+?decitabine) to explore the role of decitabine in this combination treatment regimen. A total of 11 patients (55.0?%) achieved complete remission (CR) after DAA treatment, including 7 of whom reached CR after only one treatment course. The other two patients achieved partial remission. The median overall survival (OS) was 10?months for all 20 patients. The median OS for those who achieved CR was significantly longer than that of patients with no response (NR; P?=?0.01). The treatment regimen was well tolerated, and there was no treatment-related mortality. The mean levels of P15^ink4b methylation decreased significantly in six patients who achieved CR, whereas very few changes in P15 ^ink4b methylation were detected for the five patients with NR following DAA treatment. The data from the methyl thiazolyl tetrazolium assays showed that the inhibition rates of AA and DAA for tumor cells were identical. We conclude that induction therapy with DAA for refractory/relapsed de novo AML or MDS/AML achieved high levels of CR and improved OS and demonstrated adequate tolerance. Moreover, the decitabine component of DAA may function through a demethylation effect.     

Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821

We determined the type and frequency of chromosomal aberrations in leukemic cells of 478 children diagnosed with acute myeloid leukemia and enrolled in the Pediatric Oncology Group study 8821. Of the 478 cases, 109 (22.8%) had normal karyotypes. Chromosomal abnormalities of 280 patients (58.6%) were classified into subgroups: 11q23 abnormalities (n = 88, 18.4%), t(8;21) (n = 56, 11.7%), t(15;17) (n = 55, 11.5%), inv(16)/t(16;16) (n = 28, 5.9%), trisomy 8 alone (n = 10, 2.1%), monosomy 7 (n = 9, 1.9%), non-Down-associated trisomy 21 alone (n = 7, 1.5%), and rare recurrent chromosomal translocations (n = 27, 5.6%). The remaining 89 patients (18.6%) had miscellaneous clonal abnormalities. Overall, 84.9% of the children achieved a complete remission; the 4-year event-free survival (EFS) estimate was 33.8% +/- 2.4%. Remission rates were significantly higher (96.4%, P =.011) for patients with t(8;21) and inv(16)/t(16;16) but significantly lower (74.5%, P =.022) for those with t(15;17). The 4-year survival rate for all patients was 43.5% +/- 2.4%; for those with an inv(16)/t(16;16), 75.0% +/- 8.6%; a normal karyotype, 53.8% +/- 4.9%; a t(8;21), 51.6% +/- 7.3%; a t(15;17), 39.8% +/- 6.9%; and an 11q23 abnormality, 32.9% +/- 5.1%. Four-year EFS estimates for patients with inv(16)/t(16;16) (58.2% +/- 10.9%, P =.007), t(8;21) (45.1% +/- 7.7%, P =.014), or normal karyotypes (43.1% +/- 5.0%, P =. 012) were higher than the 4-year EFS estimate for all patients, but EFS estimates for patients with t(15;17) (19.6% +/- 8.0%, P =.033) or 11q23 abnormalities (23.8% +/- 4.8%, P =.0013) were lower. EFS estimates did not differ significantly among 11q23 subgroups. Limited analysis suggested that patients with inv(16) can be salvaged better following relapse than those with t(8;21). Thus, patients with an inv(16)/t(16;16) may have high survival rates when treated with chemotherapy alone.     

Clinical characteristics of pediatric patients with chronic constipation according to age group

BACKGROUND: There was no study evaluating clinical characteristics of constipation according pediatric age groups. AIM: To evaluate the clinical characteristics of patients with chronic constipation according to age group. METHODS: This retrospective study evaluated the demographic data and clinical characteristics of pediatric patients with chronic constipation who had been admitted to an outpatient clinic between May 1995 and December 2000. Data was analyzed according to the followings age groups: infants, pre-school, school age and adolescent. RESULTS: Five hundred and sixty one patients were included in the study. The percentage of patients according to age groups were: infants (19.1%), pre-school (42.9%), school age (26.9%), and adolescents (11.0%). There was no statistical gender difference among the four age groups. Less than three bowel movements per week were observed more frequently in pre-school (65.8%) and school age (59.6%) than in infants (52.4%) and adolescents (43.1%). Fecal escape ("soiling") was found in 75.6% of the pre-school patients aged more than 48 months, in 68.2% of the school age and in 76.7% of the adolescents. Soiling was more frequent in boys (80.7%) than in girls (50.0%) only in school age children. Retentive posture (67.6%, 40.7%, 27.2%), fear for defecation (70.2%, 44.2%, 29.7%) and abdominal pain (80.8%, 69.6%, 73.6%) were observed, respectively, more frequently in pre-school than in school age and adolescents. CONCLUSION: There were differences in clinical characteristics according to age group. However, prolonged duration of constipation and an elevated number of complications were observed in all age groups, especially fecal soiling and abdominal pain.