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Clinical trial of valproic acid and all‐trans retinoic acid in patients with poor‐risk acute myeloid leukemia

Bug, Gesine ; Ritter, Markus ; Wassmann, Barbara ; Schoch, Claudia ; Heinzel, Thorsten ; Schwarz, Kerstin ; Romanski, Annette ; Kramer, Oliver H. ; Kampfmann, Manuela ; Hoelzer, Dieter ; Neubauer, Andreas ; Ruthardt, Martin ; Ottmann, Oliver G.

Cancer, 2005-12, Vol.104 (12), p.2717-2725 [Periódico revisado por pares]

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

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Título:
Clinical trial of valproic acid and all‐trans retinoic acid in patients with poor‐risk acute myeloid leukemia
Autor: Bug, Gesine ; Ritter, Markus ; Wassmann, Barbara ; Schoch, Claudia ; Heinzel, Thorsten ; Schwarz, Kerstin ; Romanski, Annette ; Kramer, Oliver H. ; Kampfmann, Manuela ; Hoelzer, Dieter ; Neubauer, Andreas ; Ruthardt, Martin ; Ottmann, Oliver G.
Assuntos: acute myeloid leukemia ; Administration, Oral ; Aged ; Aged, 80 and over ; all‐trans retinoic acid ; Biological and medical sciences ; Blotting, Western ; clinical trial ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Flow Cytometry ; Follow-Up Studies ; Hematologic and hematopoietic diseases ; histone deacetylase inhibitor ; Humans ; In Situ Hybridization, Fluorescence ; isochromosome 17 ; Leukemia, Myeloid, Acute - diagnosis ; Leukemia, Myeloid, Acute - drug therapy ; Leukemia, Myeloid, Acute - mortality ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Maximum Tolerated Dose ; Medical sciences ; Middle Aged ; myeloproliferative disorder ; normal hematopoiesis ; Prospective Studies ; Risk Assessment ; Severity of Illness Index ; Survival Analysis ; Treatment Outcome ; Tretinoin - administration & dosage ; Tretinoin - adverse effects ; Tumors ; valproic acid ; Valproic Acid - administration & dosage ; Valproic Acid - adverse effects
É parte de: Cancer, 2005-12, Vol.104 (12), p.2717-2725
Notas: Fax: (011) 49‐69‐6301‐7463
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Descrição: BACKGROUND Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, induced in vitro differentiation of primary acute myeloid leukemia (AML) blasts, an effect enhanced by all‐trans retinoic acid (ATRA). Clinical responses to VPA were recently observed in patients with myelodysplastic syndrome (MDS). Herein, the authors have described results of a clinical trial with VPA plus ATRA in 26 patients with poor‐risk AML. METHODS VPA (5–10 mg/kg starting dose) and ATRA (45 mg/m2) were administered orally. Low‐dose AraC or hydroxyurea were permitted to control leukocytosis. Biologic activity of VPA was confirmed by serial analysis of HDAC2 protein levels in peripheral blood (PB) mononuclear cells. RESULTS Nineteen of 26 patients completed at least 4 weeks of VPA/ATRA treatment; 7 patients were withdrawn prematurely because of rapidly progressive disease (n = 3) or unacceptable neurologic and cardiovascular toxicity (n = 4). Additional cytoreductive treatment was required in 58% of patients enrolled. Median treatment duration was 3 months. No patient achieved complete remission, one with de novo AML had a minor response, and two patients with secondary AML arising from myeloproliferative disorder (MPD) achieved a partial remission and clearance of PB blasts, respectively. The latter responses were accompanied by profound granulocytosis and erythrocytosis in both patients, reminiscent of the response pattern known from ATRA treatment of acute promyelocytic leukemia. However, cytogenetic analysis of isolated CD34+ cells and granulocytes did not reveal terminal differentiation of leukemic blasts. CONCLUSIONS Treatment with VPA/ATRA results in transient disease control in a subset of patients with AML that has evolved from a myeloproliferative disorder but not in patients with a primary or MDS‐related AML. Cancer 2005. © 2005 American Cancer Society. The histone deacetylase inhibitor, valproic acid (VPA), has been shown to overcome the differentiation block in leukemic blasts, an effect enhanced by all‐trans retinoic acid (ATRA). In a clinical trial including 26 patients with poor‐risk acute myeloid leukemia (AML), treatment with VPA and ATRA resulted in transient disease control in a subset of patients with an AML that had evolved from a myeloproliferative disorder but not in patients with a primary or myelodysplastic syndrome‐related AML.
Editor: Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Idioma: Inglês

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Clinical trial of valproic acid and all‐trans retinoic acid in patients with poor‐risk acute myeloid leukemia

Bug, Gesine ; Ritter, Markus ; Wassmann, Barbara ; Schoch, Claudia ; Heinzel, Thorsten ; Schwarz, Kerstin ; Romanski, Annette ; Kramer, Oliver H. ; Kampfmann, Manuela ; Hoelzer, Dieter ; Neubauer, Andreas ; Ruthardt, Martin ; Ottmann, Oliver G.

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

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