scholarly journals Jumping Translocation in a Patient with Acute Leukemia and Fatal Evolution

2020 ◽  
Vol 13 (2) ◽  
pp. 1026-1030
Author(s):  
Irene Sánchez Prieto ◽  
Montserrat López Rubio ◽  
Eva Arranz ◽  
Rosa Ayala ◽  
Marta Callejas Charavía ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Tp53 Gene ◽  
Epigenetic Alterations ◽  
Poor Clinical Outcome ◽  
Telomere Shortening ◽  
Chromosome 1Q ◽  
Pathogenic Variants ◽  
History Of ◽  
Risk Of Disease ◽  
Donor Chromosome

Jumping translocations are uncommon cytogenetic abnormalities in which a segment of a donor chromosome, often 1q, is transferred to two or more receptor chromosomes. We describe the case of a 64-year-old man with a history of acute myeloid leukemia associated with myelodysplastic syndrome, who presented with a relapse of the leukemia and, concomitantly, with the appearance of a jumping translocation involving chromosome 1q. The patient had a poor clinical course without the possibility of performing targeted treatment, and he died 5 months after relapse. Jumping translocations are a reflection of chromosomal instability, and they could be related to epigenetic alterations such as pericentromeric chromatin hypomethylation, telomere shortening, or pathogenic variants of the TP53 gene. The existing data suggests a poor clinical outcome, a high risk of disease progression, and an unfavorable prognosis. More molecular studies are required to gain an in-depth understanding of the genetic mechanism underlying these alterations and their clinical significance and to be able to apply an optimal treatment to patients.

A Large Mennonite Family with a Novel K570N TERT Gene Mutation: Association with a Clinical Spectrum of Bone Marrow Failure, Acute Myeloid Leukemia, and Acute Liver Failure.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 992-992 ◽  
Author(s):  
Joshua A. Regal ◽  
Rodrigo T. Calado ◽  
Aarthi Shenoy ◽  
Peter M. Lansdorp ◽  
Neal S. Young
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Myeloid Leukemia ◽  
Bone Marrow Failure ◽  
Index Patient ◽  
Telomerase Activity ◽  
Wild Type ◽  
Telomere Shortening ◽  
Paternal Aunt ◽  
History Of

Abstract Mutations in telomere repair complex genes TERT (encoding telomerase reverse transcriptase) and TERC (telomerase RNA component) are associated with bone marrow failure, especially acquired aplastic anemia and dyskeratosis congenita. Low telomerase activity leads to short telomeres of leukocytes, predisposing highly proliferative tissues such as the bone marrow to early senescence and exhaustion of the stem cell compartment. Telomere repair gene mutations have been suggested to result in disease anticipation, defined as earlier and/or worsening clinical manifestations in successive generations. We have identified a six-generation pedigree in a large Mennonite family carrying a novel TERT mutation (K570N), which localizes in the catalytic domain with reverse transcriptase activity (RT domain). The index patient is a 26 year old male dairy farmer with a ten-year history of severe aplastic anemia (5% bone marrow cellularity) unresponsive to immunosuppression. A long history of hematologic diseases was well known and named in the family--the patient’s paternal great-great-grandmother had died of a severe blood disorder at age 65 years. However, the great-grandmother and the grandfather had never presented any hematological disease. The patient’s father had myelodysplastic syndrome at age 33 years, evolving to acute myeloid leukemia and death due to failure to recover blood counts after chemotherapy. One of the proband’s paternal aunts had aplastic anemia develop when she was a young woman and has been transfusion-independent for decades in response to chronic androgen therapy. A second proband’s paternal aunt underwent a liver transplant at age 20 for submassive hepatic necrosis with fibrosis. A third proband’s paternal aunt has macrocytosis only at age 47. Two sisters (ages 21 and 23) also have macrocytosis in the absence of other hematological abnormality, and two other sisters are healthy. Genetic analysis showed that TERT K570N mutation is present in the patient’s paternal (including grandfather, three aunts and two affected sisters) but not maternal relatives (making his father an obligatory carrier). The patient’s oldest of three sons, now age four years, has the mutation but is asymptomatic. There was no nail dystrophy, leukoplakia or skin hyperpigmentation in any of the TERT K570N carriers; although the index patient and some of his relatives showed early graying of hair, this characteristic did not track with the mutation. Telomere shortening of leukocytes, as measured by Flow-FISH, tracked to the mutation in three generations analyzed, being shortest in the proband and in his aunt with marrow failure. Mutagenized TERT vectors transfected into telomerase-deficient VA13 cell lines yielded no telomerase activity using the telomeric repeat amplification protocol (TRAP) assay, whereas when wild-type TERT vectors were co-transfected, telomerase activity was approximately half of wild-type transfected only, indicating haploinsufficiency as a mechanism of telomere shortening. Our results confirm the association between aplastic anemia and TERT mutations. The pattern of hematologic disease in this kindred does not support disease anticipation in TERT mutations. Most remarkably, there is a likely relationship between a telomerase gene mutation and hematological malignancy and severe liver disease.

scholarly journals Eculizumab discontinuation in atypical hemolytic uremic syndrome: TMA recurrence risk and renal outcomes

2021 ◽  
Author(s):  
Gema Ariceta ◽  
Fadi Fakhouri ◽  
Lisa Sartz ◽  
Benjamin Miller ◽  
Vasilis Nikolaou ◽  
...  
Keyword(s):  
Family History ◽  
Hemolytic Uremic Syndrome ◽  
Univariate Analysis ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Renal Response ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
History Of ◽  
Uremic Syndrome

ABSTRACT Background Eculizumab modifies the course of disease in patients with atypical hemolytic uremic syndrome (aHUS), but data evaluating whether eculizumab discontinuation is safe are limited. Methods Patients enrolled in the Global aHUS Registry who received ≥1 month of eculizumab before discontinuing, demonstrated hematologic or renal response prior to discontinuation and had ≥6 months of follow-up were analyzed. The primary endpoint was the proportion of patients suffering thrombotic microangiopathy (TMA) recurrence after eculizumab discontinuation. Additional endpoints included: eGFR changes following eculizumab discontinuation to last available follow-up; number of TMA recurrences; time to TMA recurrence; proportion of patients restarting eculizumab; and changes in renal function. Results We analyzed 151 patients with clinically diagnosed aHUS who had evidence of hematologic or renal response to eculizumab, before discontinuing. Thirty-three (22%) experienced a TMA recurrence. Univariate analysis revealed that patients with an increased risk of TMA recurrence after discontinuing eculizumab were those with a history of extrarenal manifestations prior to initiating eculizumab, pathogenic variants, or a family history of aHUS. Multivariate analysis showed an increased risk of TMA recurrence in patients with pathogenic variants and a family history of aHUS. Twelve (8%) patients progressed to end-stage renal disease after eculizumab discontinuation; 7 (5%) patients eventually received a kidney transplant. Forty (27%) patients experienced an extrarenal manifestation of aHUS after eculizumab discontinuation. Conclusions Eculizumab discontinuation in patients with aHUS is not without risk, potentially leading to TMA recurrence and renal failure. A thorough assessment of risk factors prior to the decision to discontinue eculizumab is essential.

scholarly journals Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling

2021 ◽  
Vol 22 (15) ◽  
pp. 7962
Author(s):  
Arisa Ueki ◽  
Kokichi Sugano ◽  
Kumiko Misu ◽  
Eriko Aimono ◽  
Kohei Nakamura ◽  
...  
Keyword(s):  
Fumarate Hydratase ◽  
European Origin ◽  
Pathogenic Variants ◽  
Multiple Metastases ◽  
History Of ◽  
Genetic Deletion ◽  
Aggressive Clinical Course ◽  
Written Informed Consent ◽  
Tumor Profiling

Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing. A 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC. Although the patient had neither skin tumors nor a family history of HLRCC, an aggressive clinical course at her age and pathological diagnosis of FH-deficient RCC suggested a germline FH variant. After counseling, the patient provided written informed consent for germline genetic testing. She was simultaneously subjected to paired tumor profiling tests targeting the exome to identify a therapeutic target. Although conventional germline sequencing did not detect FH variants, exome sequencing revealed a heterozygous germline FH deletion. As such, paired tumor profiling, not conventional sequencing, was required to identify this genetic deletion. RCC caused by a germline FH deletion has hitherto not been described in Japan, and the FH deletion detected in this patient was presumed to be of maternal European origin. Although the genotype-phenotype correlation in HLRCC-related tumors is unclear, the patient’s family was advised to undergo genetic counseling to consider additional RCC screening.

BILATERAL PROPTOSIS - INITIAL AND RARE PRESENTATION: AML

2021 ◽  
pp. 17-18
Author(s):  
Tejasvini Chandra ◽  
Perwez Khan ◽  
Lubna Khan ◽  
Anshika Gupta
Keyword(s):  
Myeloid Leukemia ◽  
Blood Count ◽  
Complete Blood Count ◽  
Rare Condition ◽  
Metastatic Tumour ◽  
Blood Picture ◽  
Rare Presentation ◽  
Radiological Investigation ◽  
Presumptive Diagnosis ◽  
History Of

We report bilateral proptosis as the initial presentation of Acute Myeloid Leukemia (AML) in a child. An Eight year child presented with a history of painless proptosis in the both eyes within 10 days. Radiological investigation (CT scan) showed inltration of orbit with the metastatic tumour cell. AML was diagnosed with complete blood count, General Blood Picture (GBP) and bone marrow biopsy. The presumptive diagnosis of leukemic inltration of the orbit is made. We report this case as AML can rarely present in child as a bilateral proptosis due to leukemic inltration. Urgent treatment modality for this rare condition is radiation.

scholarly journals Jumping Translocations of 1q in Myelodysplastic Syndrome and Acute Myeloid Leukemia: Report of Three Cases and Review of Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
T. Couture ◽  
K. Amato ◽  
A. DiAdamo ◽  
P. Li
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Pericentromeric Region ◽  
Review Of Literature ◽  
Cell Lineages ◽  
Chromosome 1Q ◽  
Acrocentric Chromosomes ◽  
Acute Myeloid

Jumping translocations of 1q refer to the break-off of chromosome 1q as a donor fusing to two or more recipient chromosomes. We detected jumping translocations of 1q in three patients with initial diagnosis of myelodysplastic syndrome (MDS) and later progression to acute myeloid leukemia (AML). Review of literature found jumping translocations of 1q in 30 reported cases of MDS and AML. The cytogenetic findings from these 33 cases showed that seven cases had a stemline clone and 26 cases had de novo jumping translocations of 1q in which 5% of cell lineages had additional structural rearrangements. In 75% of cases, the 1q donor jumped to the short arm of recipient acrocentric chromosomes. Approximately 82% of the fusions occurred in the telomeric regions of short and long arms and 18% occurred in the pericentric or interstitial regions of recipient chromosomes. Hypomethylation of the donor 1q pericentromeric region and shortened telomeres in recipient chromosomes were associated with the formation of jumping translocations. Jumping translocations of 1q as an indication of chromosomal instability pose high risk for progression of MDS to AML and a poor prognosis. Further understanding of underlying genomic defects and their clinical significance will improve overall treatment and patient care.

INPP4B overexpression is associated with poor clinical outcome and therapy resistance in acute myeloid leukemia

Leukemia ◽  
2015 ◽  
Vol 29 (7) ◽  
pp. 1485-1495 ◽  
Author(s):  
I Dzneladze ◽  
R He ◽  
J F Woolley ◽  
M H Son ◽  
M H Sharobim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Outcome ◽  
Myeloid Leukemia ◽  
Therapy Resistance ◽  
Poor Clinical Outcome ◽  
Acute Myeloid

scholarly journals Identifying Factors That Predict for Unplanned Readmissions for Acute Myeloid Leukemia Patients Receiving Consolidation Cytarabine Based Therapies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3433-3433
Author(s):  
Caitlin Siebenaller ◽  
Madeline Waldron ◽  
Kelly Gaffney ◽  
Brian P. Hobbs ◽  
Ran Zhao ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Smoking Status ◽  
Consolidation Therapy ◽  
Peripheral Vascular ◽  
Consolidation Chemotherapy ◽  
Advisory Committees ◽  
History Of ◽  
Acute Myeloid

Background: Younger patients (pts) with acute myeloid leukemia (AML) who enter a remission after intensive induction chemotherapy routinely receive at least one cycle of consolidation therapy with high dose cytarabine (HiDAC). This is commonly administered over a five-day inpatient stay, after which pts are discharged home as their blood counts nadir. It is thus a natural consequence of therapy that readmission for febrile neutropenia (FN) occurs, which can impact measures of quality and value in this population. Precise descriptions of incidence, type, and severity of infection, if identified, are lacking, and thus it is unknown to what standard cancer centers should be held for anticipated readmission. We measured these rates, and attempted to identify predictive factors for readmission. Methods: Adult AML pts ≥ 18 years of age who received at least one cycle of HiDAC consolidation (1000-3000 mg/m2 for six doses) in 2009-2019 were included. Our primary aim was to identify predictive factors for readmission after the first cycle of consolidation chemotherapy. The following pt characteristics and co-morbid conditions were analyzed: age, gender, body mass index (BMI), smoking status, AML cytogenetic risk status, history of diabetes, peripheral vascular disease, cardiovascular disease, chronic pulmonary disease, hepatic impairment, and other cancers. Secondary aims included: estimating rates of all-cause readmissions among all HiDAC cycles, defining the rate of FN readmissions, estimating rates of intensive care unit (ICU) admissions, clinical (e.g., probable pneumonia per imaging) and microbiologically-documented infections, prophylactic (ppx) medications used, and mortality. Statistical analyses interrogated potential risk factors for evidence of association with hospital readmission after the first cycle of consolidation chemotherapy. Results: We identified 182 AML pts who fit inclusion criteria. The median age was 50 years (range 19-73); 55% were female and 45% were male. Statistical analyses revealed no association with readmission after cycle 1 for cytogenetic risk (p=0.85), history of heart failure (p= 0.67), chronic pulmonary disease (p=1), connective tissue disease (p=0.53), cerebrovascular accident (p=0.63), diabetes (p=0.63), gender (p=0.07), history of lymphoma (p=0.53), other solid tumors (p=0.53), liver disease (p=1), myocardial infarction (p=0.71), peripheral vascular disease (p=1), or smoking status (p= 0.52). For 480 HiDAC cycles analyzed (88% at 3000 mg/m2), the overall readmission rate was 50% (242/480), of which 85% (205/242) were for FN. Those readmissions which were not FN were for cardiac complications (chest pain, EKG changes), non-neutropenic fevers or infections, neurotoxicity, bleeding or clotting events, or other symptoms associated with chemotherapy (nausea/vomiting, pain, etc.). Median time to FN hospital admission was 18 days (range 6-27) from the start of HiDAC. Of the 205 FN readmissions, 57% had documented infections. Of these infections, 41% were bacteremia, 23% fungal, 16% sepsis, 12% other bacterial, and 8% viral. Of 480 HiDAC cycles, ppx medications prescribed included: 92% fluoroquinolone (442/480), 81% anti-viral (389/480), 30 % anti-fungal (142/480), and 3% colony stimulating factor (14/480). Only 7% (14/205) of FN readmissions resulted in an ICU admission, and 1% (3/205) resulted in death. Conclusions: Approximately half of patients treated with consolidation therapy following intensive induction therapy can be expected to be readmitted to the hospital. The majority of FN readmissions were associated with clinical or microbiologically documented infections and are not avoidable, however ICU admission and death associated with these complications are rare. Readmission of AML pts following HiDAC is expected, and therefore, should be excluded from measures of value and quality. Disclosures Waldron: Amgen: Consultancy. Hobbs:Amgen: Research Funding; SimulStat Inc.: Consultancy. Advani:Macrogenics: Research Funding; Abbvie: Research Funding; Kite Pharmaceuticals: Consultancy; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Glycomimetics: Consultancy, Research Funding. Nazha:Incyte: Speakers Bureau; Abbvie: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmacutical: Research Funding; Novartis: Speakers Bureau; MEI: Other: Data monitoring Committee; Tolero, Karyopharma: Honoraria. Gerds:Imago Biosciences: Research Funding; Roche: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pfizer: Consultancy; CTI Biopharma: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Sierra Oncology: Research Funding. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees. Mukherjee:Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees.

scholarly journals N6-Methyladenosine and Rheumatoid Arthritis: A Comprehensive Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Sha Wu ◽  
Xiao-Feng Li ◽  
Yuan-Yuan Wu ◽  
Su-Qin Yin ◽  
Cheng Huang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Cells ◽  
Myeloid Leukemia ◽  
Immune Cell ◽  
Bone Destruction ◽  
Synovial Cell ◽  
Biological Processes ◽  
Cell Life ◽  
History Of ◽  
The Relationship

Rheumatoid arthritis (RA), one of the most common autoimmune diseases, is characterized by immune cell infiltration, fibroblast-like synovial cell hyperproliferation, and cartilage and bone destruction. To date, numerous studies have demonstrated that immune cells are one of the key targets for the treatment of RA. N6-methyladenosine (m6A) is the most common internal modification to eukaryotic mRNA, which is involved in the splicing, stability, export, and degradation of RNA metabolism. m6A methylated-related genes are divided into writers, erasers, and readers, and they are critical for the regulation of cell life. They play a significant role in various biological processes, such as virus replication and cell differentiation by controlling gene expression. Furthermore, a growing number of studies have indicated that m6A is associated with the occurrence of numerous diseases, such as lung cancer, bladder cancer, gastric cancer, acute myeloid leukemia, and hepatocellular carcinoma. In this review, we summarize the history of m6A research and recent progress on RA research concerning m6A enzymes. The relationship between m6A enzymes, immune cells, and RA suggests that m6A modification offers evidence for the pathogenesis of RA, which will help in the development of new therapies for RA.

scholarly journals Expanding the search for germline pathogenic variants for breast cancer. How far should we go and how high should we jump? The missed opportunity!

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Hikmat Abdel-Razeq
Keyword(s):  
Breast Cancer ◽  
Brca1 And Brca2 ◽  
Healthy Women ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
History Of ◽  
Risk Reducing ◽  
Current Guidelines ◽  
Missed Opportunity

Since the identification of BRCA1 and BRCA2 genes 3 decades ago, genetic testing and genetic counseling have become an integral part of routine clinical practice. The risk of breast cancer among carriers of germline pathogenic variants, like BRCA1 and BRCA2, is well established. Risk-reducing interventions, including bilateral mastectomies and salpingo-oophorectomies are both effective and have become more acceptable. Many researchers and professional societies view current guidelines as restrictive and may miss many at-risk women, and are calling to expand testing to include all patients with breast cancer, regardless of their personal or family history of cancer, while others are calling for wider adoption to even include all healthy women at age 30 or older. This review will address expanding testing in two directions; horizontally to include more patients, and even healthy women, and vertically to include more genes using next-generation sequencing-based multi-gene panel testing.

scholarly journals Survival Improvement Of Secondary Acute Myeloid Leukemia Over Time: Experience From 962 Patients Included In 13 EORTC-Gimema-HOVON Leukemia Group Trials

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 829-829 ◽  
Author(s):  
Safaa M. Ramadan ◽  
Stefan Suciu ◽  
Marian J.P.L. Stevens-Kroef ◽  
Roelof Willemze ◽  
Sergio Amadori ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Malignant Disease ◽  
Risk Group ◽  
Toxic Exposure ◽  
Secondary Acute Myeloid Leukemia ◽  
History Of ◽  
Over Time ◽  
Acute Myeloid

Abstract Background Secondary acute myeloid leukemia (sAML) describes patients (pts) with a history of malignant or non-malignant disease or AML secondary to environmental, occupational or therapeutic exposures. They are generally associated with poor outcome despite the use of intensive treatments. The impact of clinical features and type of treatment on pts' outcome is still not well established. In the current analysis we evaluated sAML pts who were treated in 13 EORTC collaborative trials conducted between May 1986 and January 2008. sAML pts in the database were pooled to characterize clinical features of the disease and evaluate changes in survival over these years (yrs). Method Main selection criteria were AML with bone marrows blasts ≥20% and documented history of prior malignancy, non-malignant disease and/or toxic exposure. AML-M3 and MDS without confirmed diagnosis ≥2 months before AML were excluded. All pts were eligible for standard treatment. Induction regimens were anthracycline and AraC based: 7+3, including etoposide, intensified with high dose (HD)-AraC randomized to standard doses (SD) in younger (AML12) or gemtuzumab ozogamicin in elderly pts. Consolidation regimens were age adapted. In mid-1980s, autologous transplant was tested vs a 2nd consolidation cycle (AML8A) in pts ≤45 yrs and thereafter used systematically in pts ≤60 yrs without available donor. Allogeneic transplant (Allo-SCT) was offered to pts ≤46 yrs with HLA-compatible sibling since mid-1980s and expanded in the last decade to pts up to 59 yrs. Selected pts were divided into 3 sAML cohorts, cohort A after MDS, cohort B after other malignant diseases and cohort C after non-malignant conditions and/or toxic exposure. Results Of 8858 pts enrolled in the 13 evaluated studies, 962 were sAML. Median age was 63 yrs (range 16-85), 413 were young (≤60 yrs) and 549 were elderly (≥61 yrs); 54% were males. Cohort A consisted of 509 pts (median age 64 yrs), cohort B of 362 pts (median age 59 yrs) and cohort C of 91 pts (median age 61 yrs). In cohort B, breast cancer (24%) and lymphoma (14%) were the most frequent primary tumors. Autoimmune diseases represented 22% of non-malignant conditions. In young pts, complete remissions (CR/CRi) rate was 59%; 55% in SD-AraC vs 89% in HD-AraC treated pts. Allo-SCT in CR1 was performed in 21% of all pts. The Allo-SCT rate increased from 5% before 1990, 20% in 1990-1999 to 25% from 2000 (20% in SD-AraC vs 31% of HD-AraC treated pts). CR/CRi was achieved in 45% of elderly pts. Median follow-up was 6 yrs. Median overall-survival (OS) was 14.5 months in young and 9 months in elderly pts. The 5-yr OS was 28% and 7% respectively. Five-yr OS was 11% in cohort A and 22% in both cohort B and C. Treatment outcome of younger pts according to disease features and treatment type over time in cohort A and B are detailed in table 1 & 2. Using Cox model stratified by cohort age, gender, WBC, risk group, year of treatment and HD-AraC were independent prognostic factors for OS. In the AML12 study, compared to denovo pts, sAML pts ≤45 yrs had worse outcome if treated with SD-AraC whereas a better OS was seen if treated with HD-AraC. In elderly pts only the good/intermediate risk group of cohort B had a relatively better 5-yr OS (15%). Conclusions The outcome of sAML in younger pts has improved over the yrs in parallel with HD-AraC introduction in induction of remission. HD-AraC should be considered for younger pts with sAML. Disclosures: Ramadan: Alwaleed Bin Talal Foundation : A research funding is under advanced negotiation with the foundation Other. Suciu:Alwaleed Bin Talal Foundation : A research funding is under advanced negotiation with the foundation Other. Meert:Alwaleed Bin Talal Foundation : A research funding is under advanced negotiation with the foundation Other. de Schaetzen:Alwaleed Bin Talal Foundation : A research funding is under advanced negotiation with the foundation Other Other.

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