Faculty Opinions recommendation of NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS).

2009 ◽  
Author(s):  
Robert Arceci
Keyword(s):  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Normal Karyotype ◽  
Blast Cell ◽  
Cell Clearance

NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS)

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5250-5253 ◽  
Author(s):  
Friederike Schneider ◽  
Eva Hoster ◽  
Michael Unterhalt ◽  
Stephanie Schneider ◽  
Annika Dufour ◽  
...  
Keyword(s):  
Normal Karyotype ◽  
Genetic Alterations ◽  
Blast Cell ◽  
Npm1 Mutation ◽  
Mutation Status ◽  
Cell Clearance ◽  
Blast Cells ◽  
Favorable Clinical Outcome ◽  
Induction Cycle

Abstract Mutations in the NPM1 gene represent the most frequent genetic alterations in patients with acute myeloid leukemia (AML) and are associated with a favorable outcome. In 690 normal karyotype (NK) AML patients the complete remission rates (CRs) and the percentage of patients with adequate in vivo blast cell reduction 1 week after the end of the first induction cycle were significantly higher in NPM1+ (75% and 80%, respectively) than in NPM1− (57% and 57%, respectively) patients, but were unaffected by the FLT3-ITD status. Multivariate analyses revealed the presence of a NPM1 mutation as an independent positive prognostic factor for the achievement of an adequate day-16 blast clearance and a CR. In conclusion, NPM1+ blast cells show a high in vivo sensitivity toward induction chemotherapy irrespective of the FLT3-ITD mutation status. These findings provide insight into the pathophysiology and help to understand the favorable clinical outcome of patients with NPM1+ AML.

scholarly journals Moleculary Confirmed, Cytogenetic Remission in a Case with Myelodysplastic Syndrome Treated with Azacitidne

PRILOZI ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 157-162
Author(s):  
Irina Panovska-Stavridis ◽  
Martin Ivanovski ◽  
Sanja Trajkova ◽  
Aleksandra Pivkova-Veljanovska ◽  
Marija Popova-Labaceska ◽  
...  
Keyword(s):  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Y Chromosome ◽  
Risk Group ◽  
Disease Onset ◽  
Normal Karyotype ◽  
High Risk Group ◽  
Methyl Transferase ◽  
Cytogenetic Remission ◽  
Dependent Probe

Abstract Myelodysplastic syndrome (MDS) is a diverse group of clonal hematologic neoplasms. The only curative treatment for MDS is allogeneic stem cell transplantation (SCT). Epigenetic changes play an important role in the pathogenesis of MDS and treatment with DNA methyl transferase inhibitors, Azacitidine, significantly prolong the survival of high-risk MDS patients. Here we report a case of a 58-year-old male presented with pancytopenia, macrocytosis, and hyperplastic bone marrow with 3-lineage dysplasia with ~14% of myeloid blasts. Cytogenetic studies with G banding showed normal karyotype. Multiplex ligation-dependent probe amplification (MLPA) screening for most predictive cytogenetic abnormalities of MDS showed loss of the Y chromosome. Those findings later were confirmed with Quantitative Fluorescent (QF)-PCR and specific MLPA for Y chromosome, showing loss of the Y chromosome in >80% of cells. He was diagnosed with MDS-RAEB2 according to 2008 WHO classification and stratified into high risk group (IPSS score 5). Unrelated allogeneic SCT was planed and bridging treatment with Azacitidine at a dose of 75mg/m2/daily subcutaneously for 7 days every 28 days was initiated. Hematologic improvements, according to the International Working Group 2006 criteria, were observed after 4 cycles of Azacitidine treatment. After 6 cycles, complete hematological remission was achieved. Interestingly, molecular analysis performed after the 8th cycle showed normal presence of Y chromosome indicating a cytogenetic remission, molecularly confirmed. Maintenance treatment with Azacitidine was assigned, and the scheduled SCT was postponed. Experience from our case showed that the loss of the Y chromosome was related to the disease onset, and indicated that Azacitidine might be consider as effective treatment for MDS cases associated with good cytogenetic

scholarly journals Overexpression of IL-1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS

Blood ◽  
2012 ◽  
Vol 120 (6) ◽  
pp. 1290-1298 ◽  
Author(s):  
Laura Barreyro ◽  
Britta Will ◽  
Boris Bartholdy ◽  
Li Zhou ◽  
Tihomira I. Todorova ◽  
...  
Keyword(s):  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Progenitor Cells ◽  
Normal Karyotype ◽  
Transcriptional Analysis ◽  
Accessory Protein ◽  
Poor Overall Survival ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Receptor Accessory Protein

Abstract Cellular and interpatient heterogeneity and the involvement of different stem and progenitor compartments in leukemogenesis are challenges for the identification of common pathways contributing to the initiation and maintenance of acute myeloid leukemia (AML). Here we used a strategy of parallel transcriptional analysis of phenotypic long-term hematopoietic stem cells (HSCs), short-term HSCs, and granulocyte-monocyte progenitors from individuals with high-risk (−7/7q−) AML and compared them with the corresponding cell populations from healthy controls. This analysis revealed dysregulated expression of 11 genes, including IL-1 receptor accessory protein (IL1RAP), in all leukemic stem and progenitor cell compartments. IL1RAP protein was found to be overexpressed on the surface of HSCs of AML patients, and marked cells with the −7/7q− anomaly. IL1RAP was also overexpressed on HSCs of patients with normal karyotype AML and high-risk myelodysplastic syndrome, suggesting a pervasive role in different disease subtypes. High IL1RAP expression was independently associated with poor overall survival in 3 independent cohorts of AML patients (P = 2.2 × 10−7). Knockdown of IL1RAP decreased clonogenicity and increased cell death of AML cells. Our study identified genes dysregulated in stem and progenitor cells in −7/7q− AML, and suggests that IL1RAP may be a promising therapeutic and prognostic target in AML and high-risk myelodysplastic syndrome.

Randomized Controlled Trial of Azacitidine in Patients With the Myelodysplastic Syndrome: A Study of the Cancer and Leukemia Group B

2002 ◽  
Vol 20 (10) ◽  
pp. 2429-2440 ◽  
Author(s):  
Lewis R. Silverman ◽  
Erin P. Demakos ◽  
Bercedis L. Peterson ◽  
Alice B. Kornblith ◽  
Jimmie C. Holland ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Randomized Controlled Trial ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Supportive Care ◽  
Controlled Trial ◽  
Myelogenous Leukemia ◽  
Leukemic Transformation ◽  
Randomized Controlled

PURPOSE: Patients with high-risk myelodysplastic syndrome (MDS) have high mortality from bone marrow failure or transformation to acute leukemia. Supportive care is standard therapy. We previously reported that azacitidine (Aza C) was active in patients with high-risk MDS.PATIENTS AND METHODS: A randomized controlled trial was undertaken in 191 patients with MDS to compare Aza C (75 mg/m2/d subcutaneously for 7 days every 28 days) with supportive care. MDS was defined by French-American-British criteria. New rigorous response criteria were applied. Both arms received transfusions and antibiotics as required. Patients in the supportive care arm whose disease worsened were permitted to cross over to Aza C.RESULTS: Responses occurred in 60% of patients on the Aza C arm (7% complete response, 16% partial response, 37% improved) compared with 5% (improved) receiving supportive care (P < .001). Median time to leukemic transformation or death was 21 months for Aza C versus 13 months for supportive care (P = .007). Transformation to acute myelogenous leukemia occurred as the first event in 15% of patients on the Aza C arm and in 38% receiving supportive care (P = .001). Eliminating the confounding effect of early cross-over to Aza C, a landmark analysis after 6 months showed median survival of an additional 18 months for Aza C and 11 months for supportive care (P = .03). Quality-of-life assessment found significant major advantages in physical function, symptoms, and psychological state for patients initially randomized to Aza C.CONCLUSION: Aza C treatment results in significantly higher response rates, improved quality of life, reduced risk of leukemic transformation, and improved survival compared with supportive care. Aza C provides a new treatment option that is superior to supportive care for patients with the MDS subtypes and specific entry criteria treated in this study.

A Real Life Turkish Experience Of Venetoclax Treatment In High Risk Myelodysplastic Syndrome And Acute Myeloid Leukemia

2021 ◽  
Author(s):  
Aliihsan Gemici ◽  
Fahir Ozkalemkas ◽  
Mehmet Hilmi Dogu ◽  
Atakan Tekinalp ◽  
Inci Alacacioglu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Real Life ◽  
Acute Myeloid
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