AZACYTIDINE (A) ASSOCIATED WITH VITAMINS (B1, C, AND D) IN THE TREATMENT OF ACUTE MYELOID LEUKEMIA.
Objective: To report the clinical evolution of AML with complex karyotype in an elderly individual using the AZAVIT-ABCDEF protocol. Method: Information was obtained through electronic medical record review (HSPE–IAMSPE-SP). Introduction: The cellular proliferation that occurs in AMLs requires signi...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Hematology, Transfusion and Cell Therapy |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2531137923006703 |
| _version_ | 1827788521889333248 |
|---|---|
| author | R Conserva VM Sthel VLP Figueiredo |
| author_facet | R Conserva VM Sthel VLP Figueiredo |
| author_sort | R Conserva |
| collection | DOAJ |
| description | Objective: To report the clinical evolution of AML with complex karyotype in an elderly individual using the AZAVIT-ABCDEF protocol. Method: Information was obtained through electronic medical record review (HSPE–IAMSPE-SP). Introduction: The cellular proliferation that occurs in AMLs requires significant energy access. Warburg described in 1956 that neoplastic cells, even in the presence of O2, utilize anaerobic metabolism. Improving the use of aerobic pathways with high doses of vitamins may favor the differentiation of hematopoietic cells. The AZAVIT-ABCDEF protocol (AZACYTIDINE 75 mg/m2 subcutaneously for 7 days associated with high intravenous doses of Vitamins B1 (15-20 mg/kg every 12/12 hours), C (300 - 400 mg/kg intravenously every 12/12 hours), calcitriol 0.25 mcg orally every 6/6 hours, erythropoietin 10,000 IU subcutaneously once a day, and filgrastim 5-10 mcg/kg subcutaneously once a day) in a 28/28-day cycle. Between cycles, oral use includes Vitamin C 2 g every 8/8 hours, Benfotiamine 150 mg every 12/12 hours, Vitamin D 50,000 IU once a day until levels reach 80-100 ng/mL, and Famotidine 40 mg every 12/12 hours - (Plataforma Brasil CAAE: 53015421.0.0000.5463). After obtaining informed consent. Case report: Male 80-year-old in NOV/22 presented with anemic syndrome, Hb = 5.5 g/dL; Leukocytes = 3719/mm3 (20/11/0/55/14); Platelets = 38,000/mm3. Bone marrow: 30% blasts with phenotype: CD10, CD13, CD33, CD34, CD38, CD71, CD117, CD123, HLA-DR, and MPO. Karyotype: 45 XY add (3) (q21), del5, add(7) (p11.2), -9, der (12)t(1214) (p11.2q11.2), -14, +2mar [17] /46, XY [4]. FISH: Deletion of Chromosome 5 in 130/200 metaphases. He received 4 cycles of the protocol. Progressed with Hemogram: Hb = 14.1 g/dL; leukocytes = 13,670/mm3 (neutrophils = 10,130) and platelets = 273,000/mm3. Bone marrow: Hypercellular and normomaturative with negative minimal residual disease. Karyotype: 46, XY [20] and FISH: normal. As of August 2023, he is on the 8th cycle with stable hemogram. Discussion: Vitamins are closely linked to the Krebs cycle, not providing energy but releasing it through intense redox mechanisms. This may contribute to better epigenetic regulation of primitive hematopoietic cells. Genes linked to epigenetics: DNMT3A, TET2, ASXL1, IDH1, and IDH2 are frequently mutated in AML and are considered important for directly or indirectly leading to DNA methylation. Azacytidine: inhibits DNMT3A and promotes cell differentiation. Vitamin: An effective guardian of aerobic metabolism, serving as a cofactor for pyruvate dehydrogenase complex (PDHC), the enzyme allowing pyruvate to enter the Krebs cycle. It also acts on alpha-ketoglutarate metabolism, reducing 2-Hydroxyglutarate (2-HG) formation and DNA methylation. Vitamin C: Cofactor of TET2 gene in DNA demethylation. Vitamin D: Binds to VDR, which heterodimerizes with retinoid-X receptor (RXR) within the cell nucleus, serving as a transcription factor for numerous target genes. Conclusions: The patient exhibited an excellent response, and the AZAVIT-ABCDEF protocol should be studied in a prospective cohort to better define its role in treating AML in patients without performance status for intensive treatment. The main objective is to reduce transfusion dependence and extend survival in this population. |
| first_indexed | 2024-03-11T17:06:56Z |
| format | Article |
| id | doaj.art-0042da247b17406c9e136e15f2a086ec |
| institution | Directory Open Access Journal |
| issn | 2531-1379 |
| language | English |
| last_indexed | 2024-03-11T17:06:56Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Hematology, Transfusion and Cell Therapy |
| spelling | doaj.art-0042da247b17406c9e136e15f2a086ec2023-10-20T06:41:57ZengElsevierHematology, Transfusion and Cell Therapy2531-13792023-10-0145S243AZACYTIDINE (A) ASSOCIATED WITH VITAMINS (B1, C, AND D) IN THE TREATMENT OF ACUTE MYELOID LEUKEMIA.R Conserva0VM Sthel1VLP Figueiredo2Serviço de Hematologia, Hospital do Servidor Público do Estado de São Paulo (HSPE), Instituto de Assistência Médica ao Servidor Público Estadual (IAMSPE), São Paulo, BrazilServiço de Hematologia, Hospital do Servidor Público do Estado de São Paulo (HSPE), Instituto de Assistência Médica ao Servidor Público Estadual (IAMSPE), São Paulo, BrazilServiço de Hematologia, Hospital do Servidor Público do Estado de São Paulo (HSPE), Instituto de Assistência Médica ao Servidor Público Estadual (IAMSPE), São Paulo, BrazilObjective: To report the clinical evolution of AML with complex karyotype in an elderly individual using the AZAVIT-ABCDEF protocol. Method: Information was obtained through electronic medical record review (HSPE–IAMSPE-SP). Introduction: The cellular proliferation that occurs in AMLs requires significant energy access. Warburg described in 1956 that neoplastic cells, even in the presence of O2, utilize anaerobic metabolism. Improving the use of aerobic pathways with high doses of vitamins may favor the differentiation of hematopoietic cells. The AZAVIT-ABCDEF protocol (AZACYTIDINE 75 mg/m2 subcutaneously for 7 days associated with high intravenous doses of Vitamins B1 (15-20 mg/kg every 12/12 hours), C (300 - 400 mg/kg intravenously every 12/12 hours), calcitriol 0.25 mcg orally every 6/6 hours, erythropoietin 10,000 IU subcutaneously once a day, and filgrastim 5-10 mcg/kg subcutaneously once a day) in a 28/28-day cycle. Between cycles, oral use includes Vitamin C 2 g every 8/8 hours, Benfotiamine 150 mg every 12/12 hours, Vitamin D 50,000 IU once a day until levels reach 80-100 ng/mL, and Famotidine 40 mg every 12/12 hours - (Plataforma Brasil CAAE: 53015421.0.0000.5463). After obtaining informed consent. Case report: Male 80-year-old in NOV/22 presented with anemic syndrome, Hb = 5.5 g/dL; Leukocytes = 3719/mm3 (20/11/0/55/14); Platelets = 38,000/mm3. Bone marrow: 30% blasts with phenotype: CD10, CD13, CD33, CD34, CD38, CD71, CD117, CD123, HLA-DR, and MPO. Karyotype: 45 XY add (3) (q21), del5, add(7) (p11.2), -9, der (12)t(1214) (p11.2q11.2), -14, +2mar [17] /46, XY [4]. FISH: Deletion of Chromosome 5 in 130/200 metaphases. He received 4 cycles of the protocol. Progressed with Hemogram: Hb = 14.1 g/dL; leukocytes = 13,670/mm3 (neutrophils = 10,130) and platelets = 273,000/mm3. Bone marrow: Hypercellular and normomaturative with negative minimal residual disease. Karyotype: 46, XY [20] and FISH: normal. As of August 2023, he is on the 8th cycle with stable hemogram. Discussion: Vitamins are closely linked to the Krebs cycle, not providing energy but releasing it through intense redox mechanisms. This may contribute to better epigenetic regulation of primitive hematopoietic cells. Genes linked to epigenetics: DNMT3A, TET2, ASXL1, IDH1, and IDH2 are frequently mutated in AML and are considered important for directly or indirectly leading to DNA methylation. Azacytidine: inhibits DNMT3A and promotes cell differentiation. Vitamin: An effective guardian of aerobic metabolism, serving as a cofactor for pyruvate dehydrogenase complex (PDHC), the enzyme allowing pyruvate to enter the Krebs cycle. It also acts on alpha-ketoglutarate metabolism, reducing 2-Hydroxyglutarate (2-HG) formation and DNA methylation. Vitamin C: Cofactor of TET2 gene in DNA demethylation. Vitamin D: Binds to VDR, which heterodimerizes with retinoid-X receptor (RXR) within the cell nucleus, serving as a transcription factor for numerous target genes. Conclusions: The patient exhibited an excellent response, and the AZAVIT-ABCDEF protocol should be studied in a prospective cohort to better define its role in treating AML in patients without performance status for intensive treatment. The main objective is to reduce transfusion dependence and extend survival in this population.http://www.sciencedirect.com/science/article/pii/S2531137923006703 |
| spellingShingle | R Conserva VM Sthel VLP Figueiredo AZACYTIDINE (A) ASSOCIATED WITH VITAMINS (B1, C, AND D) IN THE TREATMENT OF ACUTE MYELOID LEUKEMIA. Hematology, Transfusion and Cell Therapy |
| title | AZACYTIDINE (A) ASSOCIATED WITH VITAMINS (B1, C, AND D) IN THE TREATMENT OF ACUTE MYELOID LEUKEMIA. |
| title_full | AZACYTIDINE (A) ASSOCIATED WITH VITAMINS (B1, C, AND D) IN THE TREATMENT OF ACUTE MYELOID LEUKEMIA. |
| title_fullStr | AZACYTIDINE (A) ASSOCIATED WITH VITAMINS (B1, C, AND D) IN THE TREATMENT OF ACUTE MYELOID LEUKEMIA. |
| title_full_unstemmed | AZACYTIDINE (A) ASSOCIATED WITH VITAMINS (B1, C, AND D) IN THE TREATMENT OF ACUTE MYELOID LEUKEMIA. |
| title_short | AZACYTIDINE (A) ASSOCIATED WITH VITAMINS (B1, C, AND D) IN THE TREATMENT OF ACUTE MYELOID LEUKEMIA. |
| title_sort | azacytidine a associated with vitamins b1 c and d in the treatment of acute myeloid leukemia |
| url | http://www.sciencedirect.com/science/article/pii/S2531137923006703 |
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