Clinical Leukemia最新文献

Despite the excellent prognosis for patients with newly diagnosed Down syndrome–associated acute megakaryoblastic leukemia (DS-AMKL), patients with relapsed DS-AMKL have very poor prognosis, and there is no standard treatment for such patients. We report a case of a child with relapsed DS-AMKL who was cured with non-myeloablative chemotherapy. A 19-month-old boy with Down syndrome, who had transient leukemia as a newborn, developed DS-AMKL (positive for GATA1 mutation), after a brief phase of myelodysplastic syndrome. He was treated with cytarabine, daunorubicin, oral thioguanine, and intrathecal cytarabine for induction; and high-dose cytarabine plus L-asparaginase and intrathecal cytarabine for intensification and consolidation. He exhibited remission but relapsed within 6 weeks after the completion of therapy. A second remission was achieved with high-dose cytarabine plus mitoxantrone (HAM), after which he received 4 more cycles of chemotherapy: 1 course of HAM; 1 course of high-dose cytarabine; and 2 courses of cytarabine, fludarabine, and granulocyte colony-stimulating factor. He has been disease-free for 65 months after the completion of chemotherapy. His bone marrow aspirate became negative for GATA1 mutation after the fourth cycle of chemotherapy, and he has remained negative at 5, 7, and 8 months after completion of therapy. A non-myeloablative chemotherapy regimen with high-dose cytarabine, mitoxantrone, and fludarabine could be curative for children with DS-AMKL.

The diagnosis of the chronic myeloproliferative disorders, polycythemia vera, idiopathic myelofibrosis, and essential thrombocytosis is confounded by their low frequency of occurrence, phenotypic variability over time, phenotypic mimicry among themselves, and phenotypic mimicry between them and other malignant and benign disorders of the blood. Recent discoveries of epigenetic and genetic abnormalities shared by these disorders have not only provided insight into their pathogenesis but also an opportunity to reassess the diagnostic approaches to these disorders. The purpose of this review is to integrate the information provided by these new genetic and epigenetic markers into the diagnostic strategies for polycythemia vera, idiopathic myelofibrosis, and essential thrombocytosis.

Background

Minimal residual disease (MRD) detection and quantification in children with TEL/AML1–positive acute lymphoblastic leukemia was performed by qualitative and quantitative polymerase chain reaction (PCR) in 28 patients, uniformly treated.

Patients and Methods

More than 600 bone marrow (BM) or peripheral blood samples were analyzed during 2 years of therapy and subsequent follow-up.

Results

All the patients reached complete hematologic remission at day 42 of treatment, when a BM evaluation was scheduled. At this time, 22 of 28 patients were already negative in the BM at qualitative and quantitative PCR analysis, 6 of 28 showed a quantifiable MRD that lasted between 1 and 10 months, and only 1 patient remained persistently PCR positive and finally relapsed and died of progressive disease. After a median follow-up of 104 months, 18 of 28 patients (64%) are in continuous complete remission and persistently PCR negative. Ten of 28 patients relapsed: 4 died of progressive disease, and 6 are in second complete hematologic and molecular remission after salvage therapy. The event-free survival at 8 years is 64%, and the overall survival is 86%. Notably, all relapses were preceded by a return to PCR positivity between 1.5 and 8 months before hematologic relapse. Moreover, PCR positivity in the BM taken at day 42 after induction therapy was observed in 5 of the 10 patients who subsequently relapsed and only in 1 of the 18 patients who are still in continuous complete remission.

Conclusion

This supports the notion that persistence of detectable MRD at day 42 after induction is associated with an increased risk of subsequent relapse.

Chronic lymphocytic leukemia (CLL) derives from the clonal expansion of small, mature B lymphocytes and is characterized by a very heterogeneous clinical course, with some patients having a relatively indolent disease and others requiring therapeutic intervention shortly after diagnosis. Although the reasons for such a different behavior have been, at least in part, elucidated, the first oncogenic hit in CLL is not yet known, and novel fields of investigation are required. Recently, microRNAs (miRNAs) have emerged as key players in several biologic processes, including differentiation and cancer, and are regarded as an appealing field of research. Indeed, several reports point to a possible role of these tiny RNAs in CLL, suggesting that they are potential candidates for disease initiation as well as putative prognostic markers. In this review, an overall view of the role of miRNAs in hematopoiesis will be provided; furthermore, the most relevant works linking miRNAs to CLL will be extensively described.

Background

After 12 months of treatment, most patients with chronic myeloid leukemia (CML) who receive imatinib as first-line therapy will have complete cytogenetic and molecular response. However, several patients will not exhibit molecular response, but their innate mechanism(s) of resistance remain poorly understood. We explored the molecular events involved in innate resistance in CML.

Patients and Methods

Five patients who were molecular nonresponders and 7 major responders were investigated by using the expression profile of a set of 380 genes. Multiple testing procedure, Significance Analysis of Microarrays, Empirical Bayes Analysis of Microarrays, False Discovery Rate, and support vector machine with linear kernel were used for comparative analysis.

Results

Three hundred twenty-three of 380 genes (85%) were overexpressed in the nonresponder group compared with the responders. After a very stringent statistical analysis, a list of 26 genes was identified, in which overexpression in nonresponders was highly statistically significant. These genes are involved in signal transduction and transcription factors, apoptosis, cell cycle, and adhesion. Discriminative power of the proposed gene set was estimated by 2 different statistical methods, which yielded a correct prediction of the drug response for each patient used as a test sample.

Conclusion

Our study identified a set of 26 genes involved in resistance to imatinib, which can be used as clinical predictors or therapeutic targets. We consider some of them of particular interest: IGFBP2, CDC37, MAPK3, ETS1, and PEA15. Epigenetic mechanisms, such as genome-wide promoter hypomethylation, might be involved as the basic mechanism for innate resistance in CML.

We report a novel case of spontaneous hematologic and cytogenetic remission in a patient with acute myelogenous leukemia with inv(16)(p13q22) after a systemic infection as well as transfusion of blood. Although spontaneous complete remission is a rare occurrence, we present a review of the current literature, emphasizing a diagnostic approach and associated factors.