Results of conventional-dose cytosine arabinoside and idarubicin in elderly patients with acute myeloid leukemia

Heyll, A.; Aul, Carlo; Gogolin, Frank; Runde, Volker; Söhngen, D; Meckenstock, G.; Wolf, H.; Zahner, J; Burk, M.; Winkelmann, M; Schneider, Wolfgang

doi:10.1007/bf01695033

Cited by 13 publications

(4 citation statements)

References 16 publications

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“…29,30 Idarubicin also induced a higher complete remisson rate 4,29,31,32 in older patients. 33 Maintenance of complete remission after remission-induction therapy for AML can be achieved by intensive consolidation therapy followed by allogeneic or autologous stem cell transplantation or by chemotherapy. 8,[12][13][14] Allogeneic BMT usually results in the highest disease-free survival, but its use is limited to younger patients with HLA-identical siblings.…”

Section: Discussionmentioning

confidence: 99%

Idarubicin to intensify the conditioning regimens of autologous bone marrow transplantation for patients with acute myeloid leukemia in first complete remission

Jerjis

Roovers

Muus

et al. 1998

Bone Marrow Transplant

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Summary:In an effort to reduce the relapse rate after unpurged autologous bone marrow transplantation (ABMT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1), the standard conditioning regimens (cyclophosphamide/busulphan and cyclophosphamide/TBI) were intensified by adding idarubicin. Seventeen patients received a continuous infusion of 21 mg idarubicin/m 2 /day for 2 consecutive days in addition to the standard preparative regimen. Thirteen patients served as a historical control group. The 2-year disease-free survival (DFS) of 82% in the study group was significantly (P = 0.047) better compared to 46% DFS in the control group. The relapse rate (RR) was also significantly lower (7% vs 45%; P = 0.035) in the study group. The median time to reach a white cell count (WCC) of 0.5 × 10 9 /l was 20 days in the study group vs 17 days (P = NS) in the control group. The median time until recovery of the platelet counts to 20 × 10 9 /l was 152 days in the study group vs 57 days (P = NS) in the control group. The hypolasia in the study group resulted in a trend towards a higher need for transfusions: a median number of 38 units of erythrocytes vs 23 units in the control group (P = NS) and 23 units of platelet vs 18 units in the control group (P = NS). This pilot study suggests that addition of idarubicin to the standard conditioning regimens may improve DFS and overall survival (OS) of patients with AML treated with ABMT in CR1. These results should be confirmed in a prospective randomized study. Keywords: idarubicin; conditioning regimens; autologous bone marrow transplantation; acute myeloid leukemia; first complete remission A complete remission (CR) rate of 70-80% can be achieved in patients with newly diagnosed acute myeloid leukemia (AML) by currently used remission-induction regimens. Addition of a third drug such as etoposide, 1,2 replacement of daunorubicin by new anthracyclines such as idarubicin, [3][4][5] Correspondence: Dr Sh Jerjis, Division of Hematology, University Hospital St Radboud, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands Received 24 October 1997; accepted 14 February 1998 and high-dose cytarabine (HiDAC) 6,7 have improved the remission percentage of conventional regimens based on 3 days of daunorubicin and 10 days of standard-dose cytarabine. 8 Without further treatment almost all patients are expected to relapse. Only 10-15% of patients will be cured by using standard-dose consolidation and maintenance therapy. A higher DFS of 25-45% may be achieved after intensive consolidation chemotherapy. 9,10Allogeneic BMT as well as ABMT in de novo AML patients when performed during CR1 results in better DFS than intensive consolidation therapy [11][12][13] and greater antileukemic activity when performed in CR2. 14,15 Relapse is the main cause of death in hematologic malignancies after BMT, and even more so after ABMT. Combining the standard conditioning regimens (cyclophosphamide/busulphan and cyclophosphamide/TBI) with non-cross-resistant agents and selectin...

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Section: Discussionmentioning

confidence: 99%

Idarubicin to intensify the conditioning regimens of autologous bone marrow transplantation for patients with acute myeloid leukemia in first complete remission

Jerjis

Roovers

Muus

et al. 1998

Bone Marrow Transplant

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“…[2][3][4][5] Why do older patients with AML have such a poor prognosis? Older AML patients may be relatively "undertreated" compared to younger patients, 2 or there may be significant differences between the molecular biology of AML in older patients and younger patients.…”

Section: Introductionmentioning

confidence: 99%

FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia

Stirewalt

Kopecky

Meshinchi

et al. 2001

Blood

372

269

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The prevalence and significance of genetic abnormalities in older patients with acute myeloid leukemia (AML) are unknown. Polymerase chain reactions and single-stranded conformational polymorphism analyses were used to examine 140 elderly AML patients enrolled in the Southwest Oncology Group study 9031 for FLT3, RAS, and TP53 mutations, which were found in 34%, 19%, and 9% of patients, respectively. All but one of the FLT3 (46 of 47) mutations were internal tandem duplications (ITDs) within exons 11 and 12. In the remaining case, a novel internal tandem triplication was found in exon 11. FLT3 ITDs were associated with higher white blood cell counts, higher peripheral blast percentages, normal cytogenetics, and less disease resistance. All RAS mutations (28 of 28) were missense point mutations in codons 12, 13, or 61. RAS mutations were associated with lower peripheral blast and bone marrow blast percentages. Only 2 of 47 patients with FLT3 ITDs also had a RAS mutation, indicating a significant negative association between FLT3 and RAS mutations (P ‫؍‬ .0013). Most TP53 mutations (11 of 12) were missense point mutations in exons 5 to 8 and were associated with abnormal cytogenetics, especially abnormalities in both chromosomes 5 and 7. FLT3 and RAS mutations were not associated with inferior clinical outcomes, but TP53 mutations were associated with a worse overall survival (median 1 versus 8 months, P ‫؍‬ .0007). These results indicate that mutations in FLT3, RAS, or TP53 are common in older patients with AML and are associated with specific AML phenotypes as defined by laboratory values, cytogenetics, and clinical outcomes.

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“…Nevertheless, a number of recent studies have reported complete remission (CR) rates > 50% in patients aged 5 60 treated with specifically designed combination chemotherapy regimens. This may indicate that aggressive chemotherapy represents the best treatment for selected elderly patients (Ferrara et al, 1992;Heyll et al, 1994;Leoni et al, 1995;Liu Yin et al, 1991). However, selection bias may have accounted for favourable results reported in some of the studies, as confirmed by the well-documented lower inclusion rate of elderly patients in multicentre trials as compared to younger persons (Baudard et al, 1994).…”

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confidence: 99%

Serum LDH value as a predictor of clinical outcome in acute myelogenous leukaemia of the elderly

Ferrara

Mirto

1996

Br J Haematol

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72 patients aged over 60 suffering from acute myelogenous leukaemia (AML) and treated with aggressive chemotherapy were analysed with the aim of finding factors of prognostic relevance. With regard to complete remission achievement, the only variable of statistical significance found was the karyotype at diagnosis. As far as overall survival, in multivariate analysis performed by Cox hazard regression model unfavourable karyotype and serum lactic dehydrogenase (LDH) >400 IU/I were significantly related to an adverse clinical outcome. Finally, serum LDH was the only parameter to significantly influence disease-free survival. We conclude that serum LDH is a main prognostic factor in AML of the elderly and a potentially useful tool for identifying subsets of patients who may obtain a substantial advantage from aggressive chemotherapy.

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Results of conventional-dose cytosine arabinoside and idarubicin in elderly patients with acute myeloid leukemia

Cited by 13 publications

References 16 publications

Idarubicin to intensify the conditioning regimens of autologous bone marrow transplantation for patients with acute myeloid leukemia in first complete remission

Idarubicin to intensify the conditioning regimens of autologous bone marrow transplantation for patients with acute myeloid leukemia in first complete remission

FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia

Serum LDH value as a predictor of clinical outcome in acute myelogenous leukaemia of the elderly

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