Predictable Prognostic Factor of CD56 Expression in Acute Myeloid Leukemia with t(8:21) Including Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3288-3288
Author(s):  
Deok-Hwan Yang ◽  
Yeung-Chul Mun ◽  
Ho-Jin Shin ◽  
Yeo-Kyeoung Kim ◽  
Je-Jung Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Cd56 Expression ◽  
Disease Free ◽  
Acute Myeloid

Abstract CD56 expression in acute myeloid leukemia (AML) has been associated with extramedullary leukemia and multi-drug resistance, but the clinical and prognostic significances are not yet clearly defined. Recently, some investigators reported that AML patients with t(8;21) showed more frequent CD56 expression rate and the expression of CD56 antigen adversely affected disease-free survival (DFS). It could explain a diverse clinical outcome in AML patients with favorable cytogenetics. This study investigated CD56 expression in 37 adult de novo AML patients with t(8:21) between November 1996 and June 2005 at three institutions. Immunophenotyping was performed with flow cytometry (Coulter EPICS XL) and considered positive if at least 20% of blasts expressed. CD56 was expressed in 25 cases (67.6%). There was no statistically significant differences in age, sex, leukocyte count, the percentage of bone marrow blasts or the presence of additional cytogenetic abnormalities between the CD56+ and the CD56- group. The complete remission (CR) rate to standard dose cytarabine or N4-behenoyl-1-D-arabinofuranosylcytosine (BH-AC) and idarubicin was similar in both groups (91.7% v 88.7%; P=0.73), but the relapse rate to high-dose cytarabine or allogeneic hematopoietic stem cell transplantation (HST) was quite different (60% v 25%; P=0.08). Allogeneic HST was performed from siblings in 15 patients (40.5%) who achieved CR, 8 patients (32.0%) in CD56+ and 7 patients (58.3%) in CD56- group (P=0.16). The median durations of DFS were significantly shorter in CD56+ (median, 12.2 months) than in the CD56- group (median, not reached) (P =0.02). Also, the median durations of survival showed the same results in the CD56+ group (median, 14.9 months) compared with the CD56- group (median, not reached) (P=0.01). Within fifteen transplanted patients, the median durations of DFS in eight CD56+ patients was significantly shorter than seven CD56- patients (median, 24.4 months v not reached; P=0.02)(Fig.1 and 2).We concluded that CD56 expression was associated with reduced DFS and survival for AML patients with t(8:21) including transplanted patients. Although further larger studies are needed, we suggested that CD56 expression at diagnosis is a predictable prognostic factor in AML with t(8:21). Fig. 1 Disease-free survival (DFS) and Overall survival (OS) for patients with t(8:21) with CD56+ (n−25) and CD56− (n−12) group. Fig. 1. Disease-free survival (DFS) and Overall survival (OS) for patients with t(8:21) with CD56+ (n−25) and CD56− (n−12) group. Fig. 2 Within transplanted patients, decreases from survival (DFS) for patients with t(8:21) with and without CD56 expression. Fig. 2. Within transplanted patients, decreases from survival (DFS) for patients with t(8:21) with and without CD56 expression.

Autologous Bone Marrow Transplantation as an Intensive Consolidation Therapy for Adult Patients in Remission from Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5121-5121
Author(s):  
Andre S. Jung ◽  
Asad Bashey ◽  
Peter R. Holman ◽  
Eva Carrier ◽  
Januario Castro ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Consolidation Therapy ◽  
Free Survival ◽  
Risk Patients ◽  
Disease Free ◽  
Acute Myeloid

Abstract Introduction: Autologous peripheral blood stem/progenitor cell transplantation (APBSCT) has been investigated as a potential therapeutic option to improve outcome in patients with acute myeloid leukemia. The optimal consolidation therapy for adults in remission without a histo-compatible donor has yet to be clearly established. Patients and Methods: This was a retrospective analysis of forty patients (23 females and 17 males) diagnosed with de novo acute myeloid leukemia, who were without a histo-compatible donor, that underwent APBSCT between the year 2000 and 2006 at a single institution. The patients’ age ranged from 18 to 73 with a median age of 50. Cytogenetic analysis was available on 37 of the patients. Complete remission (CR) was confirmed by bone marrow morphology and immunophenotype analysis by flow cytometry. Patients in remission were further consolidated with variable cycles of chemotherapy prior to stem cell transplantation. For stem cell mobilization, patients received high-dose cytarabine (2000mg/m2) and etoposide (5mg/kg) for three days followed by G-CSF at 10μg/kg, starting 10 days after the chemotherapy, before the peripheral stem cell collection. The preparative regimen prior to transplantation with unpurged stem/progenitor cells consisted of a combination of intravenous busulfan (0.8 mg/kg for 16 doses) and cyclophosphamide (60 mg/kg for two doses) (37 patients) or busulfan and melphalan (3 patients). Patients were then followed for treatment-related mortality, disease free survival, and overall survival. The analysis was stratified according to age, cytogenetic risk, and remission state. Results: There was no treatment-related mortality. Nineteen out of forty patients had relapse of their disease. The relapse rate was lowest in the low risk cytogenetic group who were under the age of 60 and highest in the high risk cytogenetic group who were over the age of 60. The overall 5 year survival for all patients was 47%. When stratified for cytogenetic risk and age, the overall survival for low, intermediate, and high cytogenetic risk patients under the age of 60 were 67%, 59%, and 75% respectively. The overall survival for intermediate and high cytogenetic risk patients over the age of 60 were 33% and 0% respectively. The projected rate of disease free survival at 5 years was 40%. When stratified for cytogenetic risk and age, the disease free survival for low, intermediate, and high cytogenetic risk patients under the age of 60 were 33%, 52%, and 50% respectively. Disease free survival for intermediate and high cytogenetic risk patients over the age of 60 were 33% and 0%. Comparing patients in CR1 versus patients in CR2, the overall survival was 47% in CR1 and 50% in CR2. The disease free survival, when grouped as above, were 41% for those in CR1 and 33% for those in CR2. Conclusion: APBSCT is a reasonable and safe intensive consolidation therapy for those patients without a compatible HLA matched donor in first or second complete remissions, notably for those under the age of 60 regardless of their cytogenetic risk. The number of standard consolidations prior to APBSCT may be an important variable predicting outcome.

scholarly journals The Clinical and Biological Effects of the Expression of Dedicator of Cytokinesis 1 (DOCK1) in Acute Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1695-1695 ◽  
Author(s):  
Lee Sze Hwei ◽  
Wen-Chien Chou
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Gene Set Enrichment Analysis ◽  
Free Survival ◽  
Disease Free ◽  
Lower Expression ◽  
Acute Myeloid

Abstract Background: DOCK1, also known as DOCK180, is the prototype member of the evolutionarily conserved DOCK superfamily. DOCK1 acts as a guanine nucleotide exchange factor (GEF) which regulates the activation of GTPase Rac, thereby influencing several cellular pathways including cell motility, polarity, invasion, phagocytosis and clearance of apoptotic cells. Overexpression of DOCK1 has been associated with cancer cell migration and invasion, however, its significance in acute myeloid leukemia (AML) remains unexplored. Materials and Methods: Expression patterns of DOCK1 were extracted from 347 AML patients recruited in the National Taiwan University Hospital (NTUH) (Illumina HumanHT-12 v4 Expression BeadChip, Illumina, San Diego, CA). We employed several public datasets, including microarray data of various lineages of normal hematopoiesis and AML marrow (GSE12662, GSE24006, and GSE24759) and The Cancer Genome Atlas (TCGA) RNA sequencing data of AML. In our cohort we analyzed the impacts of DOCK1 expression on various clinical parameters and genetic abnormalities. Survival was analyzed in 227 patients who received standard chemotherapy. The global gene expression profiles associated with DOCK1 expression was analyzed by bioinformatics tools. Two independent cohorts, TCGA (N=183) and GSE12417 (N=61), were used for validating the prognostic significance of DOCK1. Results: DOCK1 is a moderately expressed gene in AML (RPKM, 4.2; ranking, 50.5%). Higher DOCK1 expression level was associated with higher percentages of peripheral blasts (p=0.005), but inversely correlated with favorable cytogenetics such as t(8;21) and t(15;17). Moreover, mutations in CEBPA, c-KIT and IDH2 were less often seen in the patients with higher DOCK1 expression, while FLT3-ITD, and mutations in PTPN11, MLL, NPM1, RUNX1, ASXL1 and DNMT3A happened more often in those with higher DOCK1 expression. The Gene Set Enrichment Analysis (GSEA) of published stem cell signatures suggested DOCK1 as a hematopoietic and leukemic stem cell marker (GSEA P < 0.001 and = 0.004, respectively). Furthermore, it was generally co-expressed with homeobox genes, with average correlations ranging from 0.18 to 0.33 in normal samples, and 0.10 to 0.71 in AML datasets. With a median follow up of 57 months, we observed strong correlation between higher DOCK1 expression levels and inferior overall survival (OS) (median 18.0 months vs 116.8 months, P < 0.001) and disease free survival (DFS) (median 6.4 months vs 96.4 months, P < 0.001) (Figure 1A and 1B). These survival impacts could be validated in the two independent cohorts. In addition, multivariate analysis revealed higher DOCK1 expression as a strong unfavorable prognostic factor for OS (p=0.017) independent of age, karyotype, FLT3-ITD, and mutations of PTPN11, RUNX1, MLL and TP53. Conclusion: To our knowledge, we are the first to present the unique clinical, prognostic, and genetic impacts of DOCK1 in AML. Studies on large prospective cohorts are necessary to confirm our observation. The mechanistic functions of DOCK1 in AML await for further studies. Figure 1A Overall survival of AML patients with higher expression versus lower expression of DOCK1 Figure 1A. Overall survival of AML patients with higher expression versus lower expression of DOCK1 Figure 1B Disease free survival of AML patients with higher expression versus lower expression of DOCK1 Figure 1B. Disease free survival of AML patients with higher expression versus lower expression of DOCK1 Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic significance of serum ferritin levels on initial diagnosis in patients with acute myeloid leukemia

2021 ◽  
Vol 2 (4) ◽  
pp. 362-370
Author(s):  
Dejan Dudok ◽  
Marijana Virijević
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Serum Ferritin ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Early Death ◽  
Induction Phase ◽  
Free Survival ◽  
Disease Free ◽  
Acute Myeloid

Introduction/Aim: Acute myeloid leukemia (AML) is a heterogenous malignant disease whose course and outcome are influenced by a number of prognostic factors. Serum ferritin (SF) is often elevated in oncology patients, and it has been shown that it strongly influences an unfavorable outcome in various malignancies. The aim of this study is to assess the effect of high SF values on overall survival and disease-free survival, as well as to assess the correlation of SF values with other prognostic markers, such as clinical and laboratory parameters. Methods: Retrospective analysis included 108 patients diagnosed with AML at the Clinic for Hematology of the Clinical Center of Serbia (CCS), in Belgrade, in the period 2017 - 2019. Patients with acute promyelocytic leukemia, acute mixed lineage leukemia, secondary AML and patients treated with palliative therapy were excluded from the study. Patients were grouped based on the SF cutoff value of 800 µg/L. Results: Patients with higher SF values had a significantly higher incidence of early death (p = 0.020), sepsis in the induction phase of therapy (p < 0.010), and significantly lower initial hemoglobin levels (p = 0.040), as compared to patients with lower SF values. SF at diagnosis appeared to be a significant independent predictive factor of overall survival (p = 0.019) and of disease-free survival (p = 0.040). Conclusion: Our study showed a significant association of high SF values with sepsis in induction, early death, mean hemoglobin, overall survival, and disease-free survival. Identification of SF as an independent prognostic factor and a potential target site of the action of new drugs could contribute to a better prognosis of AML patients.

Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial

Blood ◽  
2001 ◽  
Vol 98 (5) ◽  
pp. 1302-1311 ◽  
Author(s):  
Anthony H. Goldstone ◽  
Alan K. Burnett ◽  
Keith Wheatley ◽  
Alastair G. Smith ◽  
R. Michael Hutchinson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
Disease Free Survival ◽  
Free Survival ◽  
To Receive ◽  
Disease Free ◽  
Acute Myeloid

In an attempt to improve induction chemotherapy for older patients with acute myeloid leukemia (AML),1314 patients were randomized to 1 of 3 induction treatments for 2 courses of DAT (daunorubicin, cytarabine, and thioguanine) 3 + 10, ADE (daunorubicin, cytarabine, and etoposide) 10 + 3 + 5, or MAC (mitoxantrone-cytarabine). The remission rate in the DAT arm was significantly better than ADE (62% vs 50%; P = .002) or MAC (62% vs 55%;P = .04). This benefit was seen in patients younger and older than 70 years. There were no differences between the induction schedules with respect to overall survival at 5 years (12% vs 8% vs 10%). A total of 226 patients were randomized to receive granulocyte colony-stimulating factor (G-CSF) or placebo as supportive care from day 8 after the end of treatment course 1. The remission rate or survival were not improved by G-CSF, although the median number of days to recover neutrophils to 1.0 × 109/L was reduced by 5 days. Patients who entered remission (n = 371) were randomized to stop after a third course (DAT 2 + 7) or after 6 courses, ie, a subsequent COAP (cyclophosphamide, vincristine, cytarabine, and prednisolone), DAT 2 + 5, and COAP. The relapse risk (81% vs 73%), disease-free survival (16% vs 23%), and overall survival at 5 years (23% vs 22%) did not differ between the 3-course or 6-course arms. In addition to a treatment duration randomization, 362 patients were randomized to receive 12-month maintenance treatment with low-dose interferon, but no benefit was seen with respect to relapse risk, disease-free survival, or overall survival.

Constitutive activity of signal transducer and activator of transcription 3 protein in acute myeloid leukemia blasts is associated with short disease-free survival

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 252-257 ◽  
Author(s):  
Mustafa Benekli ◽  
Zheng Xia ◽  
Kathleen A. Donohue ◽  
Laurie A. Ford ◽  
Lynda A. Pixley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Treatment Outcome ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Signal Transducer ◽  
Free Survival ◽  
Stat Proteins ◽  
Disease Free ◽  
Acute Myeloid

Signal transducer and activator of transcription (STAT) proteins are involved in hematopoietic cytokine receptor signaling pathways that regulate cell proliferation, differentiation, and survival. STATs are dysregulated in acute myeloid leukemia (AML); mechanisms of dysregulation include constitutive activation and truncation of the C-terminal transactivation domain; the latter results in a β isoform that has a trans-dominant negative effect on gene induction mediated by the full-length STATα form. It was hypothesized that constitutive STAT activity might correlate with unfavorable treatment outcome in AML. Pretreatment bone marrow samples from 63 adult patients with AML were analyzed by electrophoretic mobility shift assay for the presence of STAT DNA-binding activity. Isoforms and relative levels of STAT proteins were determined by immunoblotting. Constitutive STAT3 activity was detected in samples from 28 (44%) patients. Pretreatment clinical characteristics, expression of STATα/β isoforms, and treatment regimens did not differ significantly between patients with and without constitutive STAT3 activity. Disease-free survival (DFS) was significantly shorter in patients with than in patients without constitutive STAT3 activity (median 8.7 vs 20.6 months;P = .01). Overall survival did not differ significantly. The subgroup of patients with constitutive STAT3 activity and the STAT3β isoform had the shortest DFS (P = .006) and shorter overall survival (P = .049) than all other patients. Whether adverse treatment outcome is attributable to constitutive STAT activity itself or to a process that leads to constitutive STAT activity remains to be determined. This is the first demonstration of a prognostic significance for STAT proteins in a malignancy.

scholarly journals Wilms’ tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dao-Xing Deng ◽  
Juan-Juan Wen ◽  
Yi-Fei Cheng ◽  
Xiao-Hui Zhang ◽  
Lan-Ping Xu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myeloid Leukemia ◽  
Wilms Tumor ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Pediatric Aml ◽  
Disease Free ◽  
Tumor Gene ◽  
Acute Myeloid

Abstract Background Sequential monitoring of Wilms’ tumor gene 1 (WT1) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict relapse in adult acute myeloid leukemia (AML). However, the prognostic role of WT1 in pediatric AML after allo-HSCT is unclear. Thus, we determined to see whether sequential monitoring of WT1 after allo-HSCT could predict relapse in AML children. Methods Pediatric AML patients receiving allo-HSCT from January 21, 2012 to December 20, 2018 at the Peking University Institute of Hematology were included in this study. WT1 expression level was determined by TaqMan-based reverse transcription-polymerase chain reaction. WT1 sequential monitoring was performed 1, 2, 3, 4.5, 6, 9, and 12 months post-transplantation and at 6-month intervals thereafter. The primary end point was relapse. The secondary end points included disease-free survival (DFS), overall survival (OS), and non-relapse mortality (NRM). Kaplan–Meier analysis was used for DFS and OS estimates, while competing risk analysis was used for estimating relapse and NRM. Results Of the 151 consecutive patients included, the median age was 10 years (range, 1–17). The optimal cutoff value of WT1 within 1 year after allo-HSCT to predict relapse was 0.8% (80 WT1 copies/104 ABL copies), with a sensitivity of 60% and specificity of 79%. Compared with WT1 expression < 0.8%, WT1 expression ≥0.8% indicated significantly higher 5-year cumulative incidence of relapse (CIR, 35.1% vs. 11.3%; P = 0.001), lower 5-year disease-free survival (DFS, 60.4% vs. 80.8%; P = 0.009), and lower 5-year overall survival (OS, 64.9% vs. 81.6%; P = 0.038) rates. Multivariate analyses showed that WT1 was an independent risk factor for relapse (HR 2.89; 95% confidence interval (CI), 1.25–6.71; P = 0.014). Both the CIR (5-year CIR: 8.3% vs. 11.3%; P = 0.513) and DFS (5-year DFS: 91.7% vs. 80.8%; P = 0.208) were comparable between patients achieving minimal residual disease (MRD) negativity after preemptive interferon-α (IFN-α) treatment and those without MRD after allo-HSCT, which were better than those of MRD-positive patients without preemptive therapies. Conclusions Sequential monitoring of WT1 could predict relapse in pediatric AML after allo-HSCT. WT1-directed immunotherapy may have the potential to prevent relapse and improve survival.

High Disease-Free and Overall Survival Rate Following Allogeneic Hematopoietic Stem Cell Transplantation for FLT3-Mutated Acute Myeloid Leukemia Even in Non-Remission Status

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2283-2283 ◽  
Author(s):  
Aya Nishida ◽  
Mitsuhiro Yuasa ◽  
Kosei Kageyama ◽  
Kazuya Ishiwata ◽  
Shinsuke Takagi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Poor Prognosis ◽  
Hematopoietic Stem ◽  
Remission Status ◽  
Disease Free ◽  
Acute Myeloid

Abstract [Background] FMS like tyrosine kinase 3 (FLT3) mutations occur in about 30% of patients with acute myeloid leukemia (AML). Patients with FLT3-mutated AML have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1). So far, there is still limited data available on allo-HSCT for FLT3-mutated AML in non-remission status. [Objective and method] To assess the clinical features and outcome of allo-HSCT for FLT3-mutated AML, we retrospectively analyzed patients underwent first allo-HSCT for FLT3-mutated AML excluding acute promyelocytic leukemia (FAB M3) from January 2011 to March 2016. [Result] During the study period, 332 patients received first allo-HSCT for AML in our institute. One hundred and thirty-eight were tested for the presence of FLT3-mutation and 35 showed positive results and were subjected to the analysis. The median follow-up day of survivors was 602 (101-1867). The median age of the patients was 55 years (range, 21-72). Twenty-one patients had de novo AML, 12 had AML with myelodysplasia related changes, and 2 had therapy related AML. Eighteen had normal karyotype, 4 had complex, and 13 had others. Seven were in remission (5 in CR1, and 2 in CR2), and 28 were in non-remission (8 in primary induction failure, 13 in relapse 1, and 7 in chemo naïve status). Twenty-nine patients used unrelated cord blood, 2 did unrelated bone marrow, and 4 did related peripheral blood stem cell as grafts. All but 1 received myeloablative pretransplant conditionings. At 2 years after transplantation, overall survival (OS), disease free survival (DFS), relapse rate (RR), and non-relapse mortality (NRM) of whole studied population were 65.9%, 50.2%, 28.4%, and 21.4%, respectively. Among those in non-remission before transplantation, OS, DFS, RR, and NRM at 2 years post-transplant were 62.2% (Figure 1A), 49.9%(Figure 1B), 24.3%, and 25.8%, respectively. Only younger age (<55 years) was the factor associated with better OS with statistical significance in multivariate analysis. [Conclusion] Our data indicated that allo-HSCT could overcome the poor prognosis of FLT3-mutated AML even for those in non-remission status, despite the profound chemo-resistant character of FLT3-mutated AML. Figure 1A Figure 1A. Figure 1B Figure 1B. Disclosures Izutsu: Abbvie: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Janssen Pharmaceutical K.K.: Honoraria; Eisai: Honoraria; Kyowa Hakko Kirin: Honoraria; Chugai Pharmaceutical: Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria; Mundipharma KK: Research Funding.

scholarly journals Conventional chemotherapy for acute myeloid leukemia: a Brazilian experience

2000 ◽  
Vol 118 (6) ◽  
pp. 173-178 ◽  
Author(s):  
Kátia Borgia Barbosa Pagnano ◽  
Fabiola Traina ◽  
Tatiana Takahashi ◽  
Gislaine Borba Oliveira ◽  
Marta Soares Rossini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Disease Free Survival ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
Disease Free ◽  
Acute Myeloid

CONTEXT: Young patients affected by acute myeloid leukemia (AML) achieve complete remission (CR) using conventional chemotherapy in about 55-85%. However, 30% of patients fail to achieve CR and the remission duration is often only about 12 months. More intensive treatment after CR seems to be necessary in order to maintain CR and obtain a definitive cure. In Brazil, few reports have been published on this important subject. OBJECTIVE: The aim of this study was to describe a Brazilian experience in the treatment of "de novo" acute myeloid leukemia (AML) in younger adult patients (age < 60 years). DESIGN: Retrospective analysis. SETTING: University Hospital, Hematology and Hemotherapy Center, State University of Campinas, Brazil. PARTICIPANTS: Newly diagnosed cases of "de novo" AML in the period from January 1994 to December 1998 were evaluated retrospectively, in relation to response to treatment, overall survival (OS) and disease free survival (DFS). Cases with acute promyelocytic leukemia (APL) were also included in this analysis. RESULTS: On the basis of an intention to treat, 78 cases of AML, including 17 cases of APL, were evaluated. The overall median follow-up was 272 days. The complete remission (CR) rate was 63.6% in the AML group (excluding APL) and 78% in the APL group. The 5-year estimated disease-free survival (DFS) was 80% for the APL group and 34% for the AML group (P = 0.02). The 5-year estimated overall survival (OS) was 52% for the APL group and 20.5% for the AML group, respectively (P = NS). Relapse was observed in 12/39 (30.7%) patients with AML and 1/11 (9%) with APL. CONCLUSIONS: These results are similar to those reported in the literature. However, relapse and mortality rates remain high, and a search for more aggressive strategies in order to prevent relapse is recommended.

scholarly journals Combination of dasatinib with chemotherapy in previously untreated core binding factor acute myeloid leukemia: CALGB 10801

2020 ◽  
Vol 4 (4) ◽  
pp. 696-705 ◽  
Author(s):  
Guido Marcucci ◽  
Susan Geyer ◽  
Kristina Laumann ◽  
Weiqiang Zhao ◽  
Donna Bucci ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Core Binding Factor ◽  
Free Survival ◽  
Binding Factor ◽  
Disease Free ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) with either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) is referred to as core binding factor (CBF) AML. Although categorized as favorable risk, long-term survival for these patients is only ∼50% to 60%. Mutated (mut) or overexpressed KIT, a gene encoding a receptor tyrosine kinase, has been found almost exclusively in CBF AML and may increase the risk of disease relapse. We tested the safety and clinical activity of dasatinib, a multi-kinase inhibitor, in combination with chemotherapy. Sixty-one adult patients with AML and CBF fusion transcripts (RUNX1/RUNX1T1 or CBFB/MYH11) were enrolled on Cancer and Leukemia Group B (CALGB) 10801. Patients received cytarabine/daunorubicin induction on days 1 to 7 and oral dasatinib 100 mg/d on days 8 to 21. Upon achieving complete remission, patients received consolidation with high-dose cytarabine followed by dasatinib 100 mg/d on days 6 to 26 for 4 courses, followed by dasatinib 100 mg/d for 12 months. Fifteen (25%) patients were older (aged ≥60 years); 67% were CBFB/MYH11–positive, and 19% harbored KITmut. There were no unexpected or dose-limiting toxicities. Fifty-five (90%) patients achieved complete remission. With a median follow-up of 45 months, only 16% have relapsed. The 3-year disease-free survival and overall survival rates were 75% and 77% (79% and 85% for younger patients [aged &lt;60 years], and 60% and 51% for older patients). Patients with KITmut had comparable outcome to those with wild-type KIT (3-year rates: disease-free survival, 67% vs 75%; overall survival, 73% vs 76%), thereby raising the question of whether dasatinib may overcome the negative impact of these genetic lesions. CALGB 10801 was registered at www.clinicaltrials.gov as #NCT01238211.

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