MYELODYSPLASTIC SYNDROME RESPONDING TO THE AZACITIDINE PROTOCOL ASSOCIATED WITH HIGH DOSES OF VITAMINS

Abstract

Objective: To report four patients with Myelodysplastic Syndrome (MDS) who had improvements while on AZAVIT-ABCDEF protocol [Azacytidine associated with Erythropoietin (EPO), Filgrastim (G-CSF) and high doses of vitamins B1, C and D], after signing the consent form. This protocol is registered in the Plataforma Brasil-CAAE: 53015421.0.0000.5463. Methodology: This descriptive study was made through data collection from HSPE's medical records. Case 1: 81-year-old (y.o.) male (M) diagnosed (dx) with MDS-IB2; IPSS-R 7. Complete Blood Count (CBC): Hb 7.3 g/dL, White blood count (WBC) 2090/mm3 ANC 794/mm3 platelets (Ptl): 53000/mm3. Bone Marrow Aspirate (BMA): dysplasia with 11 % blasts. Flow Cytometry (FC): positive for D7, CD13, CD33, CD34, CD71, CD117, CD123, HLA-DR, MPO. FISH: Chromosome 8 trisomy. 47, XY +8[18]/ 46, XY [2]. He received 12 cycles of chemo. His last transfusion was 4 months (mo) after dx. Fourteen mo after dx, CBC: Hb 12.6, WBC 3010 (2/49/12/3/4) Pts 168000. He's been surviving for 14 months. Case 2: 69 y.o. M, diagnosed with MDS-IB2; IPSS-R4.5. CBC: Hb 10.9 g/dL, WBC 3890/mm3 ANC 1594/mm3 Plt 67000/mm3; BMA: dysplasia (11% blasts), FC: CD13, CD33, CD34, CD71, CD117. FISH: Normal.46, XY. He received 8 cycles of Chemo and has no need for transfusion. 10 mo after dx, CBC: Hb12.5 g/dL, WBC 2.840/mm3 Platelets 65000/mm3; He's been surviving for 10 months. Case 3: 73 y.o. M diagnosed with low blasts and ring sideroblasts MDS. IPSS-R: very low risk. He maintained low transfusion requirements while on EPO. 10 years after dx, CBC: Hb 7.2 g/dL, ANC 7978/mm3, Ptl 49000/mm3 while on G-CSF and EPO, this time requiring packed red blood cell (pRBC) transfusions; Ferritin level: 2243 ng/mL. BMA: dysplasia (0.5% blasts) and 46% ringed sideroblasts. FISH: normal; 46, XY. His last pRBC transfusion was in Oct/22. In Aug/23, CBC: Hb 11 g/dL, ANC 5798/mm3, Ptl 79,000/mm3; ferritin:316. He's currently not on EPO or G-CSF. Survival so far: 11 years. Case 4: 70 y.o.Mdiagnosed with MDS-IB1. IPSS-R: very high risk. CBC: Hb 4.9 g/dL, WBC 900/mm3 (ANC 330) / Ptl 11000/mm3. BMA: dysplasia (6.1% of blasts). FC: CD13, CD 33, CD 34, CD 38, CD 45, CD 117, CD 123, HLA-DR. FISH: normal; 46, XY, t(2;4)[7]/XY[14]. His initial transfusion needs were 2 pRBC/month and platelets transfusion once and while; Ferritin level: 952 ng/mL. He's been with no need for transfusion for 17 months. 28 mo after dx, CBD: Hb 7.1 g/dL, WBC 4310/mm3 ANC 2930/mm3, Ptl 20,000/mm3; Survival so far: 28 months. Discussion: MDS is characterized by genetic, epigenetic and metabolic disturbances in hematopoietic cells causing them to increase their proliferation rate and apoptosis and to lose their ability to differentiate. Clonal expansion is influenced by bone marrow's microenvironment and patients may end up dying from the disease due to cytopenia related complications or due to progressive increase in blast counts. That protocol was well tolerated, conferring improvements in cellular aerobic metabolism thereby making possible hematopoietic cells to differentiate. Conclusion: Patients had improvements in their transfusion needs along with better quality of life. Once compared to the IPSS-R at diagnosis, there have been improvements in patients’ overall survival, even for high riskMDS. We believe such treatment may be beneficial for MDS and low-risk patients may have longer survival in association with less transfusion of blood components.