Association of the type of 5q loss with complex karyotype, clonal evolution,TP53mutation status, and prognosis in acute myeloid leukemia and myelodysplastic syndrome

Abstract Objectives TP53 mutation is found frequently in therapy related acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS), AML and MDS patients with monosomy or complex karyotype. However, the prevalence and treatment outcome in TP53 mutated AML/MDS patients in Asian population are scarce. We therefore conducted this study to analyze the prevalence and the treatment outcomes of TP53 mutation in AML and MDS-EB patients. Methods Patients with newly diagnosed AML and MDS-EB were recruited, extraction of deoxyribonucleic acid from bone marrow samples were done and then performing TP53 mutation analysis, using MassArray® System (Agena Bioscience, CA, USA). Results A total of 132 AML/MDS patients were recruited, patients with de novo AML, secondary AML, MDS-EB1, MDS-EB2 and T-AML/MDS were seen in 66, 13, 9, 9 and 3%, respectively. TP53 mutation was found in 14 patients (10.6%), and prevalence of TP53 mutation in T-AML/MDS, secondary AML, de novo AML and MDS-EB patients were 50, 17.6, 9.2 and 8%, respectively. Three patients had double heterozygous TP53 mutation. Mutated TP53 was significantly detected in patients with monosomy and complex chromosome. Common TP53 mutation were R290C, T220C, A249S and V31I which V31I mutation was reported only in Taiwanese patients. Most variant allele frequency (VAF) of TP53 mutation in the study were greater than 40%. Three year-overall survival (OS) in the whole population was 22%, 3y-OS in AML and MDS-EB patients were 22 and 27%, respectively. The 1y-OS in patients with TP53-mutant AML/MDS were shorter than that in TP53 wild-type patients, 14% versus 50%, P = 0.001. In multivariate analysis, factors affecting OS in 132 AML/MDS patients was mutant TP53 (P = 0.023, HR = 1.20–7.02), whereas, WBC count> 100,000/μL (P = 0.004, HR = 1.32–4.16) and complex karyotype (P = 0.038, HR = 1.07–9.78) were associated with shorter OS in AML patients. Discussion In this study, the prevalence of TP53 mutation in de novo AML and MDS-EB patients were low but it had impact on survival. Patients with monosomy or complex karyotype had more frequent TP53 mutation.

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TP53 Mutation in Newly Diagnosed Acute Myeloid Leukemia and Myelodysplastic Syndrome

10.21203/rs.3.rs-148593/v1 ◽

2021 ◽

Author(s):

Pimjai Niparuck ◽

Pornnapa Police ◽

Phichchapha Noikongdee ◽

Kanchana Siriputtanapong ◽

Nittaya Limsuwanachot ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myelodysplastic Syndrome ◽

Myeloid Leukemia ◽

Tp53 Mutation ◽

De Novo ◽

Complex Karyotype ◽

Newly Diagnosed ◽

Secondary Aml ◽

De Novo Aml ◽

Acute Myeloid

Abstract Objectives: TP53 mutation is found frequently in therapy related acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS), AML and MDS patients with monosomy or complex karyotype. However, the prevalence and treatment outcome in TP53 mutated AML/MDS patients in Asian population are scarce. We therefore conducted this study to analyze the prevalence and the treatment outcomes of TP53 mutation in AML and MDS-EB patients. Methods: Patients with newly diagnosed AML and MDS-EB were recruited, extraction of deoxyribonucleic acid from bone marrow samples were done and then performing TP53 mutation analysis, using MassArray® System (Agena Bioscience, CA, USA). Results: A total of 132 AML/MDS patients were recruited, patients with de novo AML, secondary AML, MDS-EB1, MDS-EB2 and T-AML/MDS were seen in 66%, 13%, 9%, 9% and 3%, respectively. TP53 mutation was found in 14 patients (10.6%), and prevalence of TP53 mutation in T-AML/MDS, secondary AML, de novo AML and MDS-EB patients were 50%, 17.6%, 9.2% and 8%, respectively. Three patients had double heterozygous TP53 mutation. Mutated TP53 was significantly detected in patients with monosomy and complex chromosome. Common TP53 mutation were R290C, T220C, A249S and V31I which V31I mutation was reported only in Taiwanese patients. Most variant allele frequency (VAF) of TP53 mutation in the study were greater than 40%. Three year-overall survival (OS) in the whole population was 22%, 3y-OS in AML and MDS-EB patients were 22% and 27%, respectively. In multivariate analysis, factors affecting OS in 132 AML/MDS patients was mutant TP53 (P= 0.023, HR= 1.20- 7.02), whereas, WBC count> 100,000/μL (P= 0.004, HR= 1.32- 4.16) and complex karyotype (P= 0.038, HR= 1.07- 9.78) were associated with shorter OS in AML patients. Discussion: In this study, the prevalence of TP53 mutation in de novo AML and MDS-EB patients were low but it had impact on survival. Patients with monosomy or complex karyotype had more frequent TP53 mutation.

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Sequential Treatment with Chemotherapy and Reduced-Intensity Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Fanconi Anemia Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome.

Blood ◽

10.1182/blood.v120.21.2363.2363 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2363-2363

Author(s):

Alexis Talbot ◽

Regis Peffault de Latour ◽

Nimrod Buchbinder ◽

Reza Tabrizi ◽

Etienne Lengliné ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Myelodysplastic Syndrome ◽

Myeloid Leukemia ◽

Clonal Evolution ◽

Reduced Intensity Conditioning ◽

Hematopoietic Stem ◽

Sequential Strategy ◽

Reduced Intensity ◽

Acute Myeloid

Abstract Abstract 2363 Background: Fanconi anemia (FA) is a rare, genetically and phenotypically heterogeneous inherited disorder. The natural history of FA is characterized by progressive marrow failure and an increased risk for clonal evolution. Evolution to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) is the main cause of premature mortality. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is considered the treatment of choice in this situation but the evolution is usually poor post-HSCT, mainly due to treatment-related mortality. We report here the outcome of 6 FA patients who received a sequential regimen strategy because of clonal evolution. Patients, disease and methods: From August 2006 to December 2011, 6 consecutive patients with FA who received a sequential treatment with chemotherapy and reduced-intensity conditioning for clonal evolution in four different French institutions were reviewed. Five patients presented an AML (3 high risk and 2 standard risk according to Medical Research Council) and 1 a myelodysplastic syndrome considered high risk according to the International Pronostic Scoring System. The sequential strategy consisted in a pre-transplant chemotherapy by fludarabine 30 mg/m2/d 5 days and cytarabine 1gr/m2x2/d 5 days with granulocyte-colony stimulating factor injections (FLAG) followed early after by a reduced-intensity conditioning [4 days cyclophosphamide 10 mg/kg (low dose cyclophosphamide because of FA), 4 days fludarabine 30 mg/m2, 2 days anti-thymocyte globulin (3.75 mg/kg) and TBI (2 Gy)]. The source of stem cells was cord blood for three patients (Double units in 2 patients) and bone marrow for others. Graft versus host disease (GvHD) prophylaxis consisted in cyclosporine (CSA) plus MMF (except 1 patient who received CSA plus methotrexate). Results: Median age of the patients at HSCT was 20.5 years (5–28). Pre-transplant chemotherapy as well as conditioning regimen were well tolerated. The median time between the first day of chemotherapy and the date of HSCT was 30 days (range 12 to 80). During evolution, all patients engrafted. Median time to engraftment was 21 days (range 14 to 35) for neutrophils and 29 days for platelets (range 21 to 42). Donor chimerism was complete at day 100 for 5 patients. Septicemias were encountered in three patients (Staphylococcus, Enterobacter, and Candida) at 1, 3 and 4 months after HSCT, respectively. One patient developed a diarrhea to Campylobacter jejuni one month after HSCT and another patient underwent meatotomy for chronic maxillary sinusitis six months post-HSCT. Acute GvHD (1 grade I and 1 grade II) occurred in 2 patients. Both responded to steroid therapy. Chronic GvHD occurred in two patients. After a median follow-up (FU) of 30 months (8–72), all patients are still alive in complete remission from the clonal evolution. Conclusion: We report here 6 FA patients (5 AML and 1 MDS) who were successfully treated by a sequential strategy approach (FLAG and RIC HSCT). With a median FU of 30 months, all patients are alive and free from their original AML or MDS. The number of patients is little but the usual evolution is very poor post-HSCT in this particular situation. We thus believe this study supports the use of a sequential strategy (FLAG and RIC HSCT) in FA patients with AML or MDS. Disclosures: No relevant conflicts of interest to declare.

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