Acute monocytic leukemia in children: Response to VP-16-213 as a single agent

Nishikawa, Atsushi; Nakamura, Yukari; Nobori, Urara; Aoki, Takao; Higashino, Hirohiko; Matsui, Tetsuo; Kobayashi, Yohnosuke; Yamashita, Miyoko; Unishi, Gen

doi:10.1002/1097-0142(19871101)60:9<2146::aid-cncr2820600904>3.0.co;2-n

Cited by 23 publications

(7 citation statements)

References 19 publications

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“…There have been reports that VP16 has specific activity in acute monocytic leukemia. 29,30 For AraC, we found that, when comparing median values, M0 was more resistant than any other subtype; however, the difference was only significant against M4 (P = 0.016). The relationship between the biological characteristics classified by the FAB subtypes and AraC metabolism requires further research.…”

Section: Discussionmentioning

confidence: 82%

Clinical relevance of in vitro chemoresistance in childhood acute myeloid leukemia

et al. 2001

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To determine the clinical relevance of in vitro drug chemoresistance in childhood acute myeloid leukemia, we used an MTT assay to test leukemic cells from 132 newly diagnosed children. Patients were diagnosed according to the French-AmericanBritish (FAB) classification as follows: M0 (n = 12), M1 (n = 16), M2 (n = 53), M4 (n = 17), M5 (n = 19) and M7 (n = 15). The results revealed that, compared to leukemic cells from completeresponders (n = 107), those from non-responders who failed induction therapy (n = 17) were 1.4 to 5.0 times more resistant in vitro to cytarabine (P = 0.005), melphalan (P = 0.003), etoposide (P = 0.011), L-asparaginase (P = 0.017), aclarubicin (P = 0.026) and dexamethasone (P = 0.039). For seven other drugs tested, the median lethal dose of 70% and leukemic cell survival of non-responders were higher than those of complete-responders, but the difference was not statistically significant. We sought correlations between FAB subtypes and in vitro drug resistance. Leukemias of the FAB M4 and M5 subtype were more sensitive to L-asparaginase (P = 0.01, P = 0.0036) than those of the FAB M2 subtype. FAB M5 leukemia was more sensitive to etoposide than were the FAB M2, M4 and M7 subtypes (P = 0.001, P = 0.034, P = 0.023, respectively). By contrast, FAB M5 leukemia was significantly more resistant to prednisolone and dexamethasone than were the FAB M0, M1, M2, M4 and M7 subtypes. We sought correlations between in vitro drug resistance and long-term clinical outcome, but found no associations in this case. These results suggest that in vitro resistance to cytarabine, melphalan, etoposide, L-asparaginase, aclarubicin and dexamethasone might represent factors that can predict response to the early course of therapy. Selecting an appropriate anti-cancer drug according to the FAB classification together with drug sensitivity testing may contribute to improved prognoses in childhood acute myeloid leukemia. Leukemia (2001Leukemia ( ) 15, 1892Leukemia ( -1897

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Section: Discussionmentioning

confidence: 82%

Clinical relevance of in vitro chemoresistance in childhood acute myeloid leukemia

et al. 2001

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“…This difference in the prognostic impact of M4 and M5 subtypes could be due to the use of different treatment regimens. Our treatment protocols included the epipodophyllotoxins, which are highly effective against M5 leukemia in infants 34,35 and in recent years they also incorporated 2-chlorodeoxyadenosine, an agent which appears particularly effective against M5 AML (RC Ribeiro, unpublished observation). While male gender is a recognized adverse feature in childhood ALL, 36,37 it generally lacks prognostic significance in studies of AML.…”

Section: Discussionmentioning

confidence: 99%

Prognostic factors in infants with acute myeloid leukemia

et al. 2000

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Little is known about the factors that affect treatment outcome in very young children with acute myeloid leukemia (AML). We therefore analyzed the prognostic impact of various presenting clinical and laboratory features by discrete age group in 299 children with AML treated in four consecutive clinical trials between 1980 and 1997. Differences in presenting features, as well as treatment outcome, were compared between children aged 12 months or less (n = 28) or 13 to 24 months (n = 28) and those more than 24 months of age (n = 243). Children in the two youngest groups (24 months of age or less) had similar presenting features and treatment outcome. Collectively, these 56 children were significantly more likely than the 243 older patients to have M4 or M5 leukemia (70% vs 30%), CNS leukemia (33% vs 22%), the t(9;11) (p22;q23) (18% vs 6%) or other 11q23 translocations (23% vs 3%), and less likely to have Auer rods (2% vs 54%) or the t(8;21) (q22;q22) (0% vs 17%). Among patients aged 24 months or less, two factors independently predicted a favorable prognosis: FAB M4 or M5 leukemia (relative risk of relapse, 0.4; 95% confidence interval, 0.2-0.9) and the t(9;11) (relative risk, 0.3; 95% confidence interval , 0.1-1.0). Leukocyte count and 11q23 translocations other than the t(9;11) lacked prognostic significance. Among older patients, a leukocyte count Ͻ50 × 10 9 /l and the presence of the t(9;11) conferred a favorable prognosis. Leukemia (2000) 14, 684-687.

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“…Repetitive cycles or postinduction courses of HD-AraC have been effective for AML. 21,22 Regimens including etoposide are also highly effective against acute monoblastic leukemia, 23,24 which is frequently seen in infant AML. In children with AML who were treated with the same protocol, the diseasefree survival rate was 62.4%, 25 which was also superior compared with the findings of other studies of childhood AML (EFS rate was 34%-43%).…”

Section: Discussionmentioning

confidence: 99%

Superior outcome of infant acute myeloid leukemia with intensive chemotherapy: results of the Japan Infant Leukemia Study Group

Kawasaki

Isoyama²,

Eguchi³

et al. 2001

Blood

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This study analyzed data on 35 infants with acute myeloid leukemia (AML) who were treated with intensive chemotherapy between 1995 and 1998 in Japan. The incidence of boys, younger age (< 6 months old), and hyperleukocytosis at onset was high in patients with the M4/M5 subtype (n ‫؍‬ 23) in the French-AmericanBritish classification, compared with the non-M4/M5 subtype (n ‫؍‬ 12). Thirteen (56%) and 16 (70%) patients with the M4/M5 subtype also showed 11q23 translocations and MLL gene rearrangements, respectively, whereas only one patient with the non-M4/M5 subtype had this rearrangement. All 35 patients were treated with the ANLL91 protocol consisting of etoposide, high-dose cytarabine, and anthracyclines. Overall survival and the event-free survival (EFS) rates at 3 years of all patients were 76% (95% confidence interval [CI], 61.3%-90.7%) and 72% (95% CI, 56.4%-87.9%), respectively. EFS showed no significant difference between 2 subgroups divided by age, gender, presence of the MLL gene rearrangements, and white blood cell count at onset; EFS in patients with the M4/M5 subtype tended to be better than those with the non-M4/M5 subtype. Although all 6 patients who underwent allogeneic stem cell transplantation (SCT) have been in complete remission, no benefit of SCT was confirmed. These findings suggest that the intensive chemotherapy with the ANLL91 protocol might have been responsible for the observed good outcome of infant AML, even without SCT. The presence of the MLL gene rearrangements or the age at onset had no impact on the outcome of infant AML. IntroductionInfants with acute myeloid leukemia (AML) generally show monoblastic or myelomonoblastic features with hyperleukocytosis, extramedullary involvement, and MLL gene rearrangements by cytogenetic analysis. 1,2 The outcome and prognostic factors in infants with AML remain generally obscure. Several studies have reported that the presence of MLL gene rearrangements was of prognostic significance, in addition to the high white blood cell (WBC) count at diagnosis in both adults and infants with AML. 3,4 Pui and coworkers 5 reported that male gender and a WBC count of more than 50 000/L were significantly associated with an inferior outcome in infant AML. Molecular abnormalities of 11q23 translocations or MLL gene rearrangements in infant AML have been correlated with an M4 or M5 subtype in the French-AmericanBritish (FAB) classification and hyperleukocytosis. 1,2,[4][5][6] The event-free survival (EFS) of infants with AML treated with chemotherapy has been reported to be 32% to 34%. 7,8 However, the presence of MLL gene rearrangements failed to correlate with treatment response, 5,6 in contrast to the extremely poor outcome of infants with acute lymphoblastic leukemia (ALL) with the rearrangements. [9][10][11] The clinical outcomes of infant AML with MLL gene rearrangements were also similar to those of childhood AML. 6 The reason for this apparent discrepancy in the treatment outcome between patients with ALL and AML is not clear. Moreover, indications of...

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Acute monocytic leukemia in children: Response to VP-16-213 as a single agent

Cited by 23 publications

References 19 publications

Clinical relevance of in vitro chemoresistance in childhood acute myeloid leukemia

Clinical relevance of in vitro chemoresistance in childhood acute myeloid leukemia

Prognostic factors in infants with acute myeloid leukemia

Superior outcome of infant acute myeloid leukemia with intensive chemotherapy: results of the Japan Infant Leukemia Study Group

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