Clinical Significance of Free Circulating CD34 in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4495-4495
Author(s):  
Menna Hodge ◽  
Francis Giles ◽  
Adam Abdool ◽  
Susan O’Brien ◽  
Michael Keating ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Signal Transduction Pathway ◽  
Leukemic Cells ◽  
Neural Cells ◽  
And Performance ◽  
Wbc Count ◽  
Acute Myeloid

Abstract CD34 is an approximately 116-kd glycophosphoprotein expressed in hematopoietic progenitor cells, endothelial cells, and some mesenchymal and neural cells. CD34 is a typical adhesion molecule capable of inducing the cell signal transduction pathway leading to adhesion and differentiation. We used a newly developed bead-based assay to measure cell-free circulating CD34 (cCD34) in the plasma of patients with acute myeloid leukemia (AML; n = 98) and myelodysplastic syndrome (MDS; n = 50). Levels of cCD34 were significantly higher in AML (median 10983, range: 844–100,4191 U/10 μl than in MDS (median: 8749, range:102–791,350 U/10 μl) patients (P<0.01). cCD34 levels were higher among patients with high-risk cytogenetic abnormalities in AML (P = 0.01) but not MDS (P = 0.92). When grouped together, AML and MDS patients with cCD34 levels higher than the median (10,845 U/μl) had significantly shorter survival than those with lower levels (P = 0.01). This association was independent of cytogenetic grouping, age, and performance status. cCD34 levels did not correlate with percent of blasts or CD34+ cells but did correlate with WBC count (R = 0.36) in patients with AML, suggesting that cCD34 reflects the overall leukemia load. Although further study is needed for confirmation, cCD34 appears to result from turnover of leukemic cells and may affect the activation of certain pathways, therefore influencing survival and clinical outcome. Figure Figure

Clinical Significance of Free Circulating CD33 in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4502-4502 ◽  
Author(s):  
Menna Hodge ◽  
Francis Giles ◽  
Adam Abdool ◽  
Susan O’Brien ◽  
Michael Keating ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Leukemic Cells ◽  
Clinical Behavior ◽  
Cytogenetic Abnormalities ◽  
Cytotoxic Compound ◽  
Wbc Count ◽  
Acute Myeloid

Abstract CD33, a 67-kDa sialoglycoprotein expressed on the cell surface of monocytic/myeloid lineage and early hematopoietic progenitor cells, is frequently expressed in patients with acute myeloid leukemia (AML). Gemtuzumab ozogamicin (GO), an immunoconjugate consisting of a humanized anti-CD33 antibody and a cytotoxic compound (N-acetyl-γ-calicheamicin dimethylhydrazine), targets CD33 and has shown promising results in patients with AML. No evidence of a relationship between the levels of CD33-positive leukemic cells and clinical response has been found. We investigated the possibility that cell-free circulating CD33 (cCD33) might be useful as a marker of clinical behavior. We used a newly developed bead-based immunoassay to measure cCD33 in the plasma of patients with AML (n = 97) or myelodysplastic syndrome (MDS; n = 44). All patients were treated with standard therapy including idarubicin and ara-C. cCD33 levels were significantly higher in patients with MDS (median, 1600 U/μL; range, 102–791,350 U/μL) than in those with AML (median, 2709 U/μL; range: 62–263,349 U/μL) (P = 0.004). High-risk cytogenetic abnormalities were associated with higher cCD33 levels in patients with MDS (P = 0.04) but not in patients with AML (P = 0.72). cCD33 levels correlated with WBC count and % monocytes in patients with AML (R >0.35) but not in patients with MDS. cCD33 levels correlated with clinical behavior only among AML patients with intermediate-risk cytogenetic abnormalities (n = 56); those with cCD33 levels above the median had longer survival (P = 0.04). These data confirm the presence of cCD33 in AML and MDS and also suggest that cCD33 can be used as a tumor marker in patients with AML. Although further study is needed for confirmation, cCD33 appears to result from turnover of leukemic cells, may play a role in patients being treated with GO, and should be considered in the pharmacokinetic and pharmacodynamic studies of such therapy. cCD33 in AML patient with intermediate cytogenetic abnormalities cCD33 in AML patient with intermediate cytogenetic abnormalities

Variations in Proteasome Enzymatic Activities in Plasma of Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome and Their Value in Predicting Clinical Behavior.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4497-4497 ◽  
Author(s):  
Wanlong Ma ◽  
Francis Giles ◽  
Susan O’Brien ◽  
Iman Jilani ◽  
Xi Zhang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Proteasome Inhibitors ◽  
Leukemic Cells ◽  
Clinical Behavior ◽  
Cytogenetic Abnormalities ◽  
Significant Difference ◽  
And Performance ◽  
Acute Myeloid

Abstract The ubiquitin-proteasome pathway is responsible for multiple pathways in cancer cells; proteasome inhibition causes rapid apoptosis of tumor cells. Three different types of peptidase activities have been reported for proteasomes: chymotrypsin-like (Ch-L), trypsin-like (Tr-L), and caspase-like (Cas-L) (postglutamyl peptide hydrolytic-like). Various proteasome inhibitors affect each of the 3 activities differently and at different concentrations. For example, NPI-0052 inhibits Ch-L and Tr-L activities at lower concentrations than does bortezomib, while bortezomib inhibits Cas-L at lower concentrations than does NPI-0052. These enzymatic activities are usually measured in normal or tumor cells to monitor therapy with proteasome inhibitors. Because rapidly proliferating leukemic cells pour their proteins, DNA, and RNA into the circulation, we developed fluorogenic kinetic assays using peripheral blood plasma. The assays used peptide-AMC (7-amino 4-methylcoumoran) substrates to measure Ch-L, Tr-L, and Cas-L activities. We measured proteasome activities in plasma from 188 patients with acute myeloid leukemia (AML) and 58 patients with myelodysplastic syndrome (MDS) and assessed their correlations with clinical behavior. Significantly (P < 0.001) higher Ch-L, Tr-L, and Cas-L activities were seen in AML patients (medians: 1.39, 1.51, and 2.40 pmol AMC/sec/mL, respectively) and MDS patients (medians: 1.16, 1.40, and 1.67 pmol AMC/sec/mL, respectively) than in healthy volunteers (n=42) (medians: 0.80, 0.74, and 0.81 pmol AMC/sec/mL, respectively). The difference in Cas-L activity between AML and MDS was significant (P <0.001). While there was no significant difference between Ch-L and Cas-L activities in healthy controls, there was a significant difference between the 2 activities in both AML and MDS. Cas-L and Ch-L, but not Tr-L, correlated with WBC count and lactic dehydrogenase in AML and MDS patients. In AML patients, higher levels of Ch-L and Cas-L were associated with poor response to a variety of therapies (P = 0.004 and P = 0.001, respectively). Cas-L correlated strongly with survival in AML patients when used as an activity-dependent variable (P <0.001) or when the median was used as a cut-off (P = 0.004). This was independent of cytogenetic abnormalities, age, and performance status. Patients with intermediate-risk cytogenetic abnormalities and Cas-L activity >3 pmol AMC/sec/mL had significantly shorter survival (P = 0.04). Ch-L activity was also predictive of survival in AML independent of age and cytogenetic and performance status, but not independent of Cas-L. In MDS, higher levels of Cas-L, but not Ch-L, correlated with shorter survival and this was independent of cytogenetic abnormalities. The increased cell-free circulating proteasome activities most likely reflect the leukemic cells and may be a marker not only for disease, but also potentially for monitoring therapy. These data also suggest that patients with AML may benefit differentially from proteasome inhibitors depending on the specific therapeutic effect of the inhibitor.

Expression of CD56 Is an Independent Prognostic Factor to Predict Relapse in Acute Myeloid Leukemia with t(8;21): Results of Japan Adult Leukemia Study Group (JALSG) AML97 Protocol.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2511-2511
Author(s):  
Noriyoshi Iriyama ◽  
Yoshihiro Hatta ◽  
Jin Takeuchi ◽  
Yoshiaki Ogawa ◽  
Shigeki Ohtake ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
Univariate Analysis ◽  
Rank Test ◽  
Hematopoietic Stem ◽  
Wbc Count ◽  
Adverse Factor ◽  
Acute Myeloid

Abstract Abstract 2511 Background: Although prognosis of acute myeloid leukemia (AML) with t(8;21) is better than other types of AML, outcome of the patients has not been satisfied. Previously, aberrant antigen expression has been reported as risk factor for AML with t(8;21). However, in the reported series, number of cases was not large enough and chemotherapy regimens were variable. We investigated the association of prognosis and several biomarkers including immunophenotype, WBC count, age, and performance status for large number of AML patients with t(8;21) uniformly treated in JALSG AML97 regimen. Patients and Methods: Seven hundred eighty-nine eligible AML patients were evaluated for the multicenter JALSG AML97 study. Adult patients with de novo AML except for APL, ages 15–64 years, were registered consecutively from 103 institutions that participated in JALSG from December 1997 to July 2001. One hundred forty-four patients with AML with t(8;21) were analyzed in this study with a median 1205 days of observation term from diagnosis. Complete remission (CR), relapse-free survival (RFS), and overall survival (OS) rates were analyzed by Fisher's exact test and log-rank test. Factors that would affect clinical outcome were analyzed by multivariate Cox proportional hazard regression model. Results: AML with t(8;21) frequently expressed CD19, CD34, and CD56 compared to other subtypes of AML. CD11b was rarely expressed. Expression of CD19 favorably affected on CR rate (96% in CD19 positive and 87% in negative patients, p<0.05). Univariate analysis showed WBC>20×109/L, CD19 negativity, and CD56 positivity were adverse factors for RFS. CD56 expression was the only independent adverse factor for RFS by multivariate analysis (73.7% in CD56 negative and 48.2% in CD56 positive patients at 3 yrs) although its expression did not affect on OS. There was no difference of age, sex, WBC count, presence or absence of Auer rod, performance status, or CD15 expression between CD56 positive and negative cases. Expression of CD19 was more common in CD56 negative patients (50% in CD56 negative and 30.6% in CD56 positive patients, p<0.05). Conclusions: We demonstrated that the expression of CD56 was a distinctive adverse factor in a large number of AML patients with t(8;21) treated with JALSG AML97 regimen. CD56 positive AML patients with t(8;21) are possible candidates for hematopoietic stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

Safety and Efficacy of Bendamustine and Idarubicin in Combination Therapy for Patients Age ≥50 with Untreated Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome – Results From a Phase I/II Adaptive Design Study.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2622-2622
Author(s):  
Mazyar Shadman ◽  
Jack M. Lionberger ◽  
Raya Mawad ◽  
Ravinder K Sandhu ◽  
Carol Dean ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Posterior Probability ◽  
Performance Status ◽  
Outpatient Setting ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Acute Myeloid

Abstract Abstract 2622 Background: Acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS with 10–19% blasts) are associated with higher mortality in the elderly population. This poor outcome is in part attributed to therapy resistance and therefore, using combinations of agents with different mechanisms of action may improve outcomes. The nitrogen mustard Bendamustine combines unique alkylating characteristics with putative anti-metabolite activity while Idarubicin inhibits DNA and RNA synthesis by intercalation between DNA base pairs. In this single-arm adaptive phase I/II dose-escalation trial, we assessed increasing doses of Bendamustine in combination with a uniform dose of Idarubicin. We used a Bayesian approach to determine whether there was a dose of Bendamustine which, together with Idarubicin can provide a complete response (CR) rate of at least 40%, with minimal (<30%) grade 3–4 extramedullary toxicity in untreated AML or high-risk MDS patients age > 50. Methods: Eligible patients were age 350 with untreated AML or high-risk MDS, had an ECOG performance status <3 and creatinine and bilirubin each less <2.0. Patients received 1 of 3 doses of Bendamustine (45, 60 or 75 mg/m2 daily days 1–5) together with Idarubicin (12 mg/m2 days 1–2). Response was assessed according to the International Working Group (IWG) criteria (Cheson et. al., JCO, 2003) and non-hematologic toxicities according to the NCI CTCAE v.3. After each cohort of 3 patients at a given dose had been evaluated for toxicity and response, Bayesian posterior probabilities based on the data and non-informative prior probabilities were computed. If no Bendamustine dose was associated with a >95% posterior probability of both grade 3–4 extramedullary toxicity <30% (between the 1/6 and 2/6 of the conventional 3+3) and CR rate >40%, the study stopped. Otherwise, the study would continue at the highest dose that met the above criteria until 45 patients had been treated. Treatments were administered in the outpatient setting and patients were admitted to the hospital only if medically indicated. Results: Between October 2010 and May 2012, 39 patients were treated per protocol. The median age was 73 (range, 56–82). Patients had ECOG performance status of 1 (92%), or 2 (7%). AML patients comprised majority of the cases (34/39; 87%). Among AML patients, 35% (12/34) had primary AML, 47% (16/34) had AHD (antecedent hematologic disorders) and 18% (6/34) had secondary AML with a prior history of chemotherapy or radiation. None of the patients had favorable-risk cytogenetic (CG) and 19 (49%) had poor-risk CG including 9 patients (23%) with monosomal karyotype. None of the patients with normal CG had favorable molecular markers. Treatment was given in 1, 2, and 3 cycles in 25 (64%), 7 (18%) and 7(18%) patients, respectively. The number of patients in each cohort and the treatment efficacy and toxicity is reported in the table below. The MTD (maximum tolerated dose) was established at 60 mg/m2 of Bendamustine as two grade 3 toxicities were seen at the dose of 75 mg/m2 (congestive heart failure and mucositis in one patient each). Patients were treated as outpatients but hospitalization was required in 90% of the patients (35/39; 90%). The leading cause of admission was febrile neutropenia (26/35; 74%) followed by fungal infections (4/35; 11%). Conclusion: The combination of Bendamustine (60 mg/m2 (for 5 days) with Idarubicin (12 mg/m2 for 2 days) can be delivered in the outpatient setting and had a <95% posterior probability of >30% toxicity. However, the posterior probability of a CR rate >40% was also <95%, suggesting that continued exploration of new therapeutic combinations is warranted in elderly patients with AML or high-grade MDS. Disclosures: Off Label Use: Bendamustine is indicated for the treatment of CLL and indolent non-Hodgkin's lymphoma. In our study we are using Bendamustine to treat AML.

A Scoring System for Prediction of FLT3-ITD Positivity in Patients with Newly Diagnosed Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2590-2590
Author(s):  
Fabiana Ostronoff ◽  
Megan Othus ◽  
Hagop M. Kantarjian ◽  
Soheil Meshinchi ◽  
Farhad Ravandi ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Scoring System ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Cancer Center ◽  
Newly Diagnosed ◽  
Wbc Count ◽  
Acute Myeloid

Abstract Abstract 2590 Background FLT3-internal tandem duplication (ITD) is found in about 30% of patients with acute myeloid leukemia (AML) at diagnosis and confers a high risk of relapse. Thus allogeneic hematopoietic transplant (HCT) is recommended for these patients in first complete remission (CR) and after HCT they become candidates for trials of FLT3-ITD inhibitors (such as quizartinib) to prevent relapse. However at referral to tertiary centers after reaching CR, FLT3-ITD status at diagnosis is often unknown, complicating decisions about HCT. FLT3-ITDs are known to be associated with a normal karyotype (NK), translocation 6;9 and a high white blood cell (WBC) count, and we hypothesized that assessment of likely FLT3-ITD status at diagnosis in patients presenting in CR not tested at diagnosis would be improved by examining these covariates simultaneously. Methods Our initial analysis included 434 adult patients with newly diagnosed AML (excluding APL) treated on three SWOG trials (S9031, S9333, and S0106) in whom FLT3-ITD status (positive/negative) was established at diagnosis. Univariate and then multivariate analyses were used to identify covariates independently associated with FLT3-ITD positivity. The relative abilities of these to predict FLT3-ITD positivity were quantified using the area under the receiver operator characteristic curve (AUC); an AUC of 1.0 denotes perfect prediction, whereas an AUC of 0.5 is analogous to a coin flip. The log odds ratios (ORs) from the multivariate models were used to assign a score to each covariate and scores were summed; such that the higher the score, the greater is the likelihood of the FLT3-ITD positivity at diagnosis. We tested the performance of the scoring system in 2 newly-diagnosed populations that had not contributed to the system's development and in whom FLT3-ITD status at diagnosis was known: (a) 210 patients treated at FHCRC (Fred Hutchinson Cancer Research Center) and (b) 1,401 patients treated at MDACC (M.D. Anderson Cancer Center). Covariates examined were: age, sex, performance status (PS), WBC count, platelet count, bone marrow blast percentage, secondary AML, and cytogenetic risk (using SWOG/Eastern Cooperative Oncology Group criteria). Results FLT3- ITD was present in 101 of the 434 SWOG patients (23%) in the scoring system development population. The log OR were rounded to the nearest half point to create the scoring system. Only WBC > 20,000 (reference, WBC < 20,000) and cytogenetics (reference, normal) had non-zero scores, which are summarized below: Scores less than −0.5 were called low, ≥−0.5 and <0.5 intermediate, ≥ 0.5 high. The AUC was 0.75 and contrasted with 0.66 and 0.69 when only WBC or cytogenetics were considered. However when this system was tested in the FHCRC population (16% FLT3-ITD positive) its AUC was only 0.58, not better than when each covariate was examined separately (AUC 0.54 and 0.6 for WBC and cytogenetics, respectively). Similarly at MDACC (17% FLT3-ITD positive) the system's AUC was 0.68 vs. 0.59 and 0.68 for WBC and cytogenetics, respectively. Conclusion Although this scoring system seemed useful tool within the population it was developed (SWOG), such was not the case in two independent cohorts of AML patients with known FLT3-ITD status (FHCRC and MDACC). This indicates that there is no obvious substitute for actual data on FLT3-ITD status. Disclosures: No relevant conflicts of interest to declare.

Comprehensive Geriatric Assessment Does Not Predict Overall Survival in Older Patients with Acute Myeloid Leukemia (AML)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3689-3689 ◽  
Author(s):  
Ellen K. Ritchie ◽  
Danielle C. Marshall ◽  
Molly D. Greenberg ◽  
Tania J. Curcio ◽  
Ashley E. Giambrone ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Geriatric Assessment ◽  
Comprehensive Geriatric Assessment ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Newly Diagnosed ◽  
Wbc Count ◽  
Acute Myeloid

Abstract Background Age and cytogenetics are the strongest predictors of overall survival (OS) in older patients with acute myeloid leukemia (AML), but practitioners recognize that outcomes are also affected by medical comorbidities, physical function and a variety of psychosocial factors. Recent data suggest that geriatric assessment, including measures of physical, cognitive and psychological function, may be predictive of OS and helpful for risk stratification in AML (Klepin 2013). We evaluated the ability of a comprehensive geriatric assessment (CGA) to predict overall survival in newly diagnosed older patients with AML. Patients and Methods All newly diagnosed AML patients age ≥60 years treated at Weill Cornell Medical Center and The New York Presbyterian Hospital completed a CGA including the OARS Physical Health Section, Mental Health Inventory (MHI-17), MOS Social Activity Survey, Activities of Daily Living (ADL) subscale of the MOS Physical Health, OARS Instrumental ADL subscale, Timed Up & Go, Blessed-Orientation-Memory-Concentration Test, and Karnofsky Performance Status (KPS). Laboratory data, medications, transfusions and days of hospitalization were also collected. Comorbidities were assessed using the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI). OS was estimated by the Kaplan-Meier method and the log-rank test was used to compare survival profiles. The independent effects of the CGA and clinical risk factor variables on OS were estimated using hazard ratios in an adjusted Cox regression model. Results In total, 126 patients were evaluated (median age 74, range 60-90). Fifty-one percent of patients had a HCT-CI score >1, with the most common comorbidities being a history of cancer (28.57%), cardiac disease (20.6%), and psychiatric disturbances (17.5%). Half of the patients had prior hematologic disorders and 29% had poor-risk cytogenetics. Most patients (84.9%) received decitabine-based induction strategies; 44 of these patients (34.9%) subsequently received intensive salvage regimens (median age 69). The other 19 patients (15.1%) were treated with standard induction chemotherapy, and 29 patients (21%) underwent allogeneic stem cell transplantation (median age 68). One hundred twenty-three patients (96.6%) completed the CGA with a mean time to completion of 26 minutes (± 8.9 minutes). Thirty-five percent of patients did not complete the entire assessment and only 61.1% completed the follow up CGA. Median OS was 11.1 months (range 0.36-52.64), with 1-year survival of 47.6%, complete remission (CR) rate of 39.8%, and 30-day mortality of 2.4%. In univariate analysis, age (P=0.0289), physician-assigned KPS (P=0.0031), sex (P=0.0074), ELN cytogenetic risk (P=0.0194), creatinine (P=0.027), albumin (P=0.0052), white blood cell (WBC) count (P=0.0135), LDH (P=0.0004), and treatment response (P=0.0001) were significant clinical predictors of OS. Significant CGA variables included Blessed Orientation-Memory-Concentration score (P=0.0035), Bend-Kneel-Stoop (P=0.0239), “someone to prepare your meals” (P=0.0253) and self-reporting of heart disease (P<0.001). In a multivariate analysis controlling for age and cytogenetic risk, physician-assigned KPS (HR, 1.804; 95% CI 1.175 to 2.768), self-reported cardiac history (HR, 2.290; 95% CI 1.383 to 3.794), and WBC count <11.2/ul (HR, 2.360; 95% CI 1.415 to 3.936) were the only independent prognostic factors for overall survival. Conclusion In this study, age and cytogenetics remain the strongest predictors of OS in older patients with AML. While completion of the CGA was feasible, only performance status (KPS) was predictive of OS. Many measures previously reported as significant predictors of outcome, including impaired physical function (Klepin 2013), medication intake (Hurria 2011), pain (Sherman 2013), and HCT-CI score (Sorror 2005, 2009) were not predictive in our study population. The role of the CGA as a predictor of OS in AML requires further evaluation. The utility of the CGA in predicting functional performance and/or quality of life for older AML patients throughout treatment should also be investigated. Disclosures Ritchie: Celgene, Incyte: Speakers Bureau. Feldman:Ariad: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

Myelodysplastic syndrome is not merely “preleukemia”

Blood ◽  
2002 ◽  
Vol 100 (3) ◽  
pp. 791-798 ◽  
Author(s):  
Maher Albitar ◽  
Taghi Manshouri ◽  
Yu Shen ◽  
Diane Liu ◽  
Miloslav Beran ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Growth Factors ◽  
Myelodysplastic Syndrome ◽  
Cell Sorting ◽  
Early Phase ◽  
Myeloid Leukemia ◽  
Leukemic Cells ◽  
Newly Diagnosed ◽  
Therapeutic Approaches ◽  
Acute Myeloid

Abstract Myelodysplastic syndrome (MDS) is a disease characterized by ineffective hematopoiesis. There are significant biologic and clinical differences between MDS and acute myeloid leukemia (AML). We studied a cohort of 802 patients, 279 (35%) with newly diagnosed MDS and 523 (65%) with newly diagnosed AML, and compared clinical and biologic characteristics of the 2 groups. Complete clinical and cytogenetic data were available on all patients, and a subgroup of patients was studied for apoptosis, angiogenesis, proliferation, and growth factors. Our results demonstrate that MDS is a discrete entity that is different from AML and is characterized primarily by increased apoptosis in early and mature hematopoietic cells. Using cell sorting and loss of heterozygosity, we demonstrate that the leukemic cells from MDS patients are capable of differentiation into mature myeloid cells and monocytes. We also demonstrate that there is a significant overlap between AML and MDS when MDS is defined on the basis of an arbitrary percentage of blasts of 20% or 30%. These data suggest that despite similarities between AML and MDS in their responses to treatment and outcomes, MDS is biologically and clinically different from AML and should not be considered an early phase of AML. The data indicate that MDS must be better defined on the basis of its biology rather than the percentage of blasts; further, the data suggest that there is a need to develop therapeutic approaches that specifically address the biologic abnormalities of MDS.

Comorbidity and performance status in acute myeloid leukemia patients: a nation-wide population-based cohort study

Leukemia ◽  
2014 ◽  
Vol 29 (3) ◽  
pp. 548-555 ◽  
Author(s):  
L S G Østgård ◽  
J M Nørgaard ◽  
H Sengeløv ◽  
M Severinsen ◽  
L S Friis ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cohort Study ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Population Based ◽  
And Performance ◽  
Wide Population ◽  
Acute Myeloid
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