No Preferential Sensitivity of t(8;21) Acute Myeloid Leukemias to Cytosine Arabinoside in Vitro: Is Intensity of Therapy or High Dose Ara-C Crucial for Response?

Visani, Giuseppe; Isidori, Alessandro; Grafone, Tiziana; Tosi, Patrizia; Malagola, Michele; Martinelli, Giovanni; Piccaluga, Pier Paolo; Gaziev, D; Ottaviani, Emanuela; Sparaventi, Giovanni; Tura, S

doi:10.1080/10428190310001653673

Cited by 3 publications

(1 citation statement)

References 15 publications

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“…Mechanism of response to chemotherapy for t(8;21)-positive cells is probably different than in AML cells with inv(16) [54]. Blast cells from inv(16)-positive AML patients are characterized by an increased sensitivity to AraC with higher incorporation of 3H AraC into DNA and the increase of induced apoptosis in vitro, while the incorporation of 3H AraC into DNA in cells with t(8;21) was significantly lower than in cells with inv (16), and AraC induced apoptosis was not increased in t(8;21)-positive AML cells.…”

Section: Cellular Drug Resistance In Childhood Acute Myeloid Leukemiamentioning

confidence: 96%

Drug Resistance in Childhood Acute Myeloid Leukemia

Styczyński

2007

CPB

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Therapy results in childhood AML differ from those of ALL. The development of drug resistance is the limiting factor in the therapy of AML. Different problems of drug resistance in childhood AML, with emphasis to age and in comparison to adult AML are presented. In vitro and in vivo aspects are discussed, together with mechanisms of resistance to cytostatic drugs, focused on clinical relevance of cellular drug resistance profile and its prognostic value. Possibilities of modulation and circumvention of drug resistance are reviewed, with stress on new drugs being tested. Taking into account both children and adults, it seems that age is adversely related to therapy outcome in AML, and the percentage of patients with favorable cytogenetics decreases with age; however, age is positively correlated with multi-drug resistance and the proportion of patients with unfavorable cytogenetics. AML is considered a stem cell disease. BCRP, PGP and MRP's are preferentially expressed in leukemic stem cells, making this disease drug resistant. Cellular drug resistance in AML cells seems to be similar throughout all other age groups, however the higher the age, the worse the outcome. In childhood AML, no drug is more effective in comparison to ALL, and cellular drug resistance is partially related to chromosomal abnormalities. Pediatric AML is equally resistant as adult AML. Pediatric and adult AML, respectively, are possibly equally drug resistant on initial diagnosis and at relapse. In contrast to ALL, the prognostic value of in vitro drug resistance in childhood AML has not been well documented yet.

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Section: Cellular Drug Resistance In Childhood Acute Myeloid Leukemiamentioning

confidence: 96%

Drug Resistance in Childhood Acute Myeloid Leukemia

Styczyński

2007

CPB

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Prognosis and treatment outcome in patients with acute myeloid Leukemia with t(8;21)(q22;q22)

Chen

et al. 2007

Adv Therapy

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Patients with acute myeloid leukemia (AML) with the t(8;21) karyotype generally have a favorable clinical course, but key prognostic factors remain poorly defined. This study was conducted to determine the prognoses and treatment outcomes of patients with AML with this unique cytogenetic change. A total of 22 patients with AML with t(8;21)(q22;q22) were studied. Various parameters were tested for their impact on disease-free survival (DFS) and overall survival (OS). Another 55 patients with AML with a normal karyotype were included for comparison of clinical outcomes. Between patients with t(8-21) and those with a normal karyotype, no significant differences were noted in DFS (median survival, 15.23 vs 12.03 mo; P=.7626) and OS (median survival, 19.17 vs 18.93 mo; P=.7543). Among t(8;21)(q22;q22) patients, no clinical parameters showed a significant impact on DFS. Univariate analysis revealed that a higher platelet count (>15.10(9)/L) at diagnosis, a low white blood cell count (index < or =20), and hematopoietic stem cell transplantation (HSCT) as postremission therapy were associated with improved OS. On multivariate analysis, HSCT as postremission therapy and white blood cell count index <20 remained good independent prognostic factors for OS. The data presented here suggest that t(8;21)(q22;q22) cytogenetic changes in patients with AML had prognostic significance similar to that in patients with a normal karyotype; patients who harbored either karyotype had parallel clinical outcomes. It is concluded that patients with AML with t(8;21)(q22;q22) would be compromised by treatment approaches that do not include HSCT as postremission therapy.

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t(8;21) (q22;q22) Acute myelogenous leukemia in México: A single institution experience

et al. 2006

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We analyze the prevalence and clinical features of a group of patients with t(8;21) (q22;q22) acute myeloblastic leukemia, identified in a single institution in México over a 10-year period. Fifteen patients presented at the Centro de Hematología y Medicina Interna de Puebla from February 1995 to August 2005; only nine were treated and followed in the institution. Median age was 24 years, (range 7-49); there was only one male. According to the French-American-British (FAB) morphological classification of leukemia, the morphology was M2 in four cases, M4 in three cases, M3 in one case and M0 in one. In addition to the myeloid markers, lymphoid markers were identified in 6 patients. Patients were induced to remission with combined chemotherapy and three subsequently underwent bone marrow transplantation (BMT). The median overall and disease-free survival has not been reached, being above 3390 days, the probability of survival at this time was 73%. In this single-center experience in México, we found that the t(8;21) (q22;q22) variant of leukemia was more frequent than in Caucasian populations, that the co-expression of lymphoid markers in the blast cells is very frequent and that this malignancy is associated with a relatively good prognosis.

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No Preferential Sensitivity of t(8;21) Acute Myeloid Leukemias to Cytosine Arabinoside in Vitro: Is Intensity of Therapy or High Dose Ara-C Crucial for Response?

Cited by 3 publications

References 15 publications

Drug Resistance in Childhood Acute Myeloid Leukemia

Drug Resistance in Childhood Acute Myeloid Leukemia

Prognosis and treatment outcome in patients with acute myeloid Leukemia with t(8;21)(q22;q22)

t(8;21) (q22;q22) Acute myelogenous leukemia in México: A single institution experience

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