Table 3.

Responses to treatment with valproic acid+all-trans retinoic acid (ATRA)+low-dose cytarabine according to the myelodysplastic syndrome (MDS) criteria for hematological improvement (increased cell counts for at least eight weeks); a summary of the observations for nine acute myeloid leukemia (AML) patients fulfilling these criteria (referred to as stable disease, SD)

Patient characteristics and treatment responses	Detailed description of disease characteristics and the clinical course
SD1 - stable disease	Risk factor: previous primary MDS.
Male, 83 years	Status at diagnosis: performance status 0 to 2, 45% blasts in bone marrow; circulating blasts < 0.5 × 109/L.
Duration of treatment: 3 months	Valproic acid level: 340 μmol/L.
Response duration: 2.5 months	Peripheral blood cell counts: (i) platelet counts > 15 × 109/L for 2.5 months; (ii) neutrophils > 0.1 × 109/L for 3 months; and (iii) erythrocyte level > 8.5 × 109 for 2.5 months without transfusions.
Survival: 102 days
SD2 - stable diseasea	Risk factor: previous primary MDS.
Female, 77 years	Status at diagnosis: performance status 0 to 2, 25% blasts in bone marrow; circulating blasts < 0.5 × 109/L.
Duration of treatment: 10 months	Valproic acid level: 324 μmol/L.
Response duration: 3.5 months	Peripheral blood cell counts: (i) platelet counts > 25 for 7 months; (ii) neutrophils > 0.2 × 109 for 5 months; and (iii) erythrocyte level > 8.5 × 109 for 3.5 months without transfusions.
Survival: 419 days
SD3- stable disease	Risk factor: previous primary MDS.
Female, 85 years	Status at diagnosis: performance status 0 to 2, 70% blasts in bone marrow; circulating blasts < 0.5 × 109/L
Duration of treatment: 5.5 months	Valproic acid level: 442 μmol/L.
Response duration: 2 months	Peripheral blood cell counts: (i) platelet counts > 18 × 109 for 2 months; (ii) neutrophils could mostly not be reported; and (iii) erythrocyte level > 8.5 × 109 for 3 months with stable transfusion level
Survival: 171 days
SD4 – stable disease	Risk factor: none
Male, 74 years	Status at diagnosis: performance status 3 to 5, > 20% blasts in bone marrow; circulating blasts > 15 × 109/L
Duration of treatment: 2 months	Valproic acid level: 70 μmol/L.
Response duration: 3 months	Peripheral blood cell counts: (i) platelet counts > 50 × 109 for 3 months, > 100 for 1 month; (ii) neutrophils could mostly not be reported; and (iii) erythrocyte level > 8.5 × 109 for 4 months with stable transfusion level.
Survival: 151 days
SD5 – stable diseasea	Risk factor: previous primary MDS, incomplete response to 5-azacitidine for AML.
Male, 66 years
Duration of treatment: 7.5 months	Status at diagnosis: performance status 0 to 2, > 15% blasts in bone marrow when included in the study; circulating blasts < 0,5 × 109/L.
Response duration: 2 months	Valproic acid level: 419 μmol/L.
Survival: 239 days	Peripheral blood cell counts: (i) platelet counts > 10 × 109 for 2 months; (ii) neutrophils stable 0.1 × 109/L for 3 months; and (iii) erythrocyte level > 8.5 × 109 for 2 months without transfusions.
SD6 - stable disease	Risk factor: none
Female, 78 years	Status at diagnosis: performance status 0 to 2, > 20% blasts in bone marrow; circulating blasts < 0,5 × 109/L.
Duration of treatment: 4.5 months	Valproic acid level: 476 μmol/L
Response duration: 2 months	Peripheral blood cell counts: (i) platelet counts > 30 × 109/L for 2 months; (ii) neutrophils stable around 0.1 × 109/L; and (iii) erythrocyte level > 8.5 × 109/L for 3 months with stable transfusion frequency.
Survival: 147 days
SD7 - stable diseasea	Risk factor: previous primary MDS
Female, 72 years Duration of treatment: 1 month
	Status at diagnosis: performance status 0 to 2, > 30% blasts in bone marrow; circulating blasts > 30 × 109/L
	Valproic acid level: 478 μmol/L.
Response duration: 3 months	Peripheral blood cell counts: (i) platelet counts > 15 × 109 for 3 months with stable transfusion frequency; (ii) neutrophils could not be reported; and (iii) erythrocyte level > 8.5 × 109 for 3 months with stable transfusion frequency.
Survival: 132 days
SD8- stable diseasea	Risk factor: previous polycythemia vera, AML with del(5)
Male, 81 years	Status at diagnosis: performance status 0 to 2, 25% blasts in bone marrow; circulating blasts > 20 × 109/L.
Duration of treatment: 4 months	Valproic acid level: 404 μmol/L
Response duration: 2 months	Peripheral blood cell counts: (i) Platelet counts > 30 × 109 for 3 months; (ii) neutrophils > 0.2 × 109 for 2 months; and (iii) erythrocyte level > 8.5 × 109 for 2 months with stable transfusion frequency.
Survival: > 574 days
SD9 – stable diseasea	Risk factor: previous primary MDS.
Female, 77 years	Status at diagnosis: performance status 0 to 2, 30 % blasts in bone marrow; circulating blasts > 25 × 109/L.
Duration of treatment: 3.5 months	Valproic acid level: 467 μmol/L
Response duration: > 2 months	Peripheral blood cell counts: (i) platelet counts > 25 × 109 for > 2 months; (ii) neutrophils could not be reported; and (iii) erythrocyte level > 8.5 for 4 months with stable transfusion frequency.
Survival: > 141 days

Patient identity refers to the response (SD, stable disease) according to the MDS criteria for hematological improvement [19] and a consecutive numbering. Duration of treatment refers to the time receiving valproic acid, ATRA and low-dose cytarabine according to the protocol. The valproic acid level is presented as the average serum level during the four first weeks of treatment. The duration of responses refers to the time between the first and the last review documenting a peripheral blood cell value above the indicated level.

^aReceived later chemotherapy with hydroxyurea or 5-mercaptopurin to control the blood blast count.