A preliminary study on the outcome of lower-risk myelodysplastic syndrome by low-dose decitabine / 中华血液学杂志

Objective@#To assess the efficiency and safety of low-dose decitabine in patients with lower-risk myelodysplastic syndrome (MDS) to couple with the clinical significance of MDS-related gene mutations.@*Methods@#This study was done in 4 institutions in Zhejiang Province. A total of 62 newly diagnosed patients with lower-risk MDS were assigned to two groups of decitabine (12 mg·m-2·d-1 for 5 consecutive days) and best supportive care (BSC) . Their bone marrow samples were subject to examinations of MDS-related 15 gene mutations. The primary endpoints were the proportion of patients who achieved overall response (ORR) after at least two cycles and progression-free survival (PFS) , and their relevances to the gene mutations.@*Results@#Of 62 enrolled patients, and 51 cases were included in the final analysis. 16 of 24 patients (66.7%) in decitabine group achieved ORR versus 8 of 27 (29.6%) in BSC group (χ2=6.996, P=0.008) ; PFS prolongation of decitabine versus BSC was statistically significant (not reached vs 13.7 months, P=0.037) . Among 51 patients, at least one gene mutation was identified in 20 patients (39.2%) , including 4 single SF3B1 mutation. PFS in cases with gene mutations (not including single SF3B1 mutation) was significantly shorter than of no gene mutation (9.2 months vs 18.5 months, P=0.008) , but not for ORR (37.5% vs 58.1%, P=0.181) . Among 16 patients with mutated genes, ORR in decitabine and BSC groups were 75% (6/8) and 0 (0/8) , respectively. The most adverse events in decitabine group were grade 3 to 4 neutropenia (45.8%) and grade 3 to 4 infections (33.3%) .@*Conclusion@#This preliminary study showed that low-dose decitabine produced promising results with an acceptable safety in lower-risk MDS patients, especially for those with mutated genes. Further study targeting poor prognostic lower-risk MDS patients should be warranted.

The efficacy and safety of HAA regimen as induction chemotherapy in 150 newly diagnosed acute myeloid leukemia / 中华内科杂志

Objective To explore the efficacy and safety of HAA regimen (homoharringtonine,cytarabine and aclarubicin) in the treatment of 150 newly diagnosed adult acute myeloid leukemia (AML).Methods All patients entered the study from May 1999 to June 2008 were treated with HAA regimen. Coxsurvival analysis was used to estimate the survival rate and differences between M1/M2 and M4/M5 were compared with 2-sided log-rank test. Results Out of the 150 patients, 121 (81%) achieved complete remission (CR). After the first course, CR rate was 68%. The CR rates of 97%, 84% and 38% were achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. For the patients with CR, the median follow-up time was 16.5 ( 1.5-100.5 ) months, and the estimated 3-year survival rate was 45%. The estimated 3-year relapse free survival rate was 52% for the 121 patients with CR.Conclusions HAA regimen may be an efficacious and safe regimen with a good toleration in the induction therapy for newly diagnosed AML, and a high CR rate could be achieved with only one or two courses.

Homoharringtonine mediates myeloid cell apoptosis via upregulation of pro-apoptotic bax and inducing caspase-3-mediated cleavage of poly(ADP-ribose) polymerase (PARP).

Homoharringtonine (HHT) is a plant alkaloid with antileukemia activity that is currently being used for treatment of acute, chronic leukemias and MDS. In this study, we show that HHT can induce apoptosis in a variety of human myeloid leukemia cell lines (U937, HL-60, HEL, THP, and K562). U937 and HL60 cells undergo rapid apoptosis on treatment with HHT, as indicated by increased annexin V binding capacity, caspase-3 activation, and cleavage of poly(ADP-ribose) polymerase (PARP). In addition, the expression of bax is upregulated during HHT-induced cell death, whereas the expression of bcl-2 is only slightly decreased. Importantly, treatment of primary leukemic cells, obtained from acute myeloid leukemia patients, resulted in rapid apoptosis. Thus, our data provide the mechanism of HHT and justify the use of HHT in the treatment of human myeloid leukemia.

Clinical and cytogenetics studies on acute myeloid leukemia with abnormality of chromosome 11 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the incidence of chromosome 11 abnormality in acute myeloid leukemia and its relationship with the clinical aspects and prognosis.</p><p><b>METHODS</b>Conventional cytogenetic analysis of R-band was used to detect the abnormalities of chromosome 11 in 356 acute myeloid leukemia patients.</p><p><b>RESULTS</b>Thirty-four out of 356 patients (9.55%) had abnormalities of chromosome 11, of which 20 (58.8%) involved in 11q23, 7 (19.9%) had translocations involving 11p15, 5 (14.7%) had-11, and the rest had other abnormalities such as +11, and t(11;14). The incidence of 11q23 involvement in M4 and M5 was higher than other subtypes of acute myeloid leukemia (AML). Ten cases with 11q23 abnormality had additional cytogenetic aberrations. In 30 cases treated with chemotherapy, 13 cases acquired complete remission (CR). The CR rate was lower than that of whole cases of acute myeloid leukemia(34.3% versus 64.0%). The CR rate of AML with 11q23 abnormality was lower than that of AML with normal karyotype (25% versus 55.6%). In other 10 patients with additional chromosome aberrations, the CR rate was lower than that of AML with 11q23 alone. In 7 patients with translocations at 11p15, only 3 patients acquired CR, and 2 patients relapsed early. Only 2 patients acquired CR in 5 patients with-11.</p><p><b>CONCLUSION</b>11q23 was a frequent aberration in chromosome 11 anomaly, which was often detected in M4 and M5. It might be associated with the pathogenesis of acute monolytic leukemia. The patients with chromosome 11 anomaly had poorer prognosis.</p>