Therapy of childhood acute myelogenous leukemias

Vormoor, Josef; Boos, Joachim; Stahnke, Karsten; Jürgens, H.; Ritter, J.; Creutzig, Ursula

doi:10.1007/s002770050193

Cited by 24 publications

(12 citation statements)

References 46 publications

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“…However, very high telomerase activity as of 90-100% and long-term remission rates of Ͼ70%. [37][38][39][40]44 11 (F)). In leukemia, after induction chemotherapy, telomeres in MNCs gained on average 2.2 kbp, but decreased 1 kbp with the continuation of chemotherapy treatment (lanes 7-9).…”

Section: Bone Marrow (Bm) 31mentioning

confidence: 99%

“…ALL patients were treated according to the modified ution of Percoll, diluted with 10 × PBS without Ca and Mg (Gibco, Grand Island, NY, USA), 78% and 62% Percoll sol-BFM (Berlin-Frankfurt-Mü nster) protocol. [37][38][39][40] The AML patient was treated according to the Children's Cancer Group utions were prepared, using 1 × HBSS clear (Hanks balanced salt solution, Gibco) and 1 × HBSS with phenol red, respect-(CCG) protocol 2961 with idarubicin 20 mg/m 2 , daunomycin 80 mg/m 2 , cytosine arabinoside 800 mg/m 2 , etoposide ively. PB and BM specimens were diluted 1:2 with PBS prior to the Percoll separation.…”

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Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy

et al. 1998

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Telomerase activity and telomere length in mononuclear cells proliferation of lymphoid or myeloid precursors with arrested (MNCs) and granulocytes from peripheral blood (PB) and bone maturation. 1 In this disorder, the leukemic clone expands in marrow (BM) specimens were studied in pediatric acute leukethe bone marrow (BM), interferes with normal hematopoiesis mia (ALL, n = 15; AML, n = 1) and pediatric solid tumor (ST) and eventually, non-hematopoietic tissues are infiltrated. patients (n = 9) at diagnosis, during and after chemotherapy. In Acute lymphocytic leukemia (ALL) was one of the first maligfour ST patients, tumor tissue was also available. For comparative analysis, MNCs from healthy donors (n = 53) were ananancies reported to respond to chemotherapy and is curable that can synthesize telomeric repeats onto chromosomes. [3][4][5][6] telomere loss in granulocytes as compared to MNCs was more Recently, borderline telomerase activity has been detected in pronounced with 1.8 vs 1 kbp, respectively (P = 0.014). Our results demonstrate that at diagnosis, telomerase was consisthuman primitive hematopoietic cells and in stimulated lymently and highly upregulated in BM and PB specimens in leukephocytes which increased significantly with cytokine-induced mia, decreased after induction therapy, and correlated with ex vivo expansion. 7-10 However, in most other normal remission. BM specimens in leukemia had higher telomerase somatic cells, telomerase has not been detected, and conseactivity, probably due to the greater leukemic burden than in quently telomere shortening may be anticipated after a limited PB. Telomeres were significantly longer in children than in number of population doublings. [11][12][13] In contrast, spon- progressive telomere length shortening in the absence of telo-

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Section: Bone Marrow (Bm) 31mentioning

confidence: 99%

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confidence: 99%

Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy

et al. 1998

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“…1,2 From 1982 to 2001, in Italy, four consecutive studies on childhood AML have been performed by the AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) cooperative group. Table 1 presents some details of these four studies, including patient number per trial, number of centres involved, and their median patient accrual.…”

Section: Introductionmentioning

confidence: 99%

Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols

et al. 2005

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Since 1982, four consecutive studies on childhood acute myeloid leukaemia (AML) (namely have been conducted in Italy by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. The induction therapy of the first three studies consisted of daunorubicin and cytarabine structured in a 3 þ 7 backbone. In the most recent protocol (LAM92), patients received two induction courses including idarubicin, cytarabine and etoposide. Patients with acute promyelocytic leukaemia (20% of diagnoses) were included in LAM-87 and 87M studies. Postremissional therapy significantly changed over time, with an ever-increasing role given to stem cell transplantation (SCT). The long-term outcome of patients enrolled in the LAM-82, 87 and 87M studies was comparable, whereas that of children treated according to LAM-92 study was significantly better (Po0.005). Either allogeneic or autologous SCT was employed as consolidation therapy in more than 75% of cases enrolled in this latter study. Patients enrolled in the LAM-92 study were stratified in standard and high-risk groups with different outcome (67 vs 47%, respectively, P ¼ 0.04). Altogether, the results obtained in these four studies have permitted a progressive refinement of treatment, contributing to the structure of the ongoing LAM-2002 protocol that stratifies patients according to the presence of definite genetic anomalies and response to induction therapy.

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“…13,[22][23][24][25] Relapse in eyes and CNS after BMT, however, appeared to be rare compared to the incidence of relapse in eyes and CNS after conventional treatment without the use of BMT. 26 Since cataract is a very disagreeable late complication in children and young adults, we decided to use eye shielding during TBI to prevent severe cataracts.…”

Section: Discussionmentioning

confidence: 99%

Eye shielding during total body irradiation for bone marrow transplantation in children transplanted for a hematological disorder: risks and benefits

Kempen-Harteveld

Weel-Sipman

Emmens

et al. 2003

Bone Marrow Transplant

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Summary:This is a retrospective analysis of 188 children who underwent total body irradiation (TBI) in one or two fractions before bone marrow transplantation (BMT) for a hematological disorder. While 139 children had eye shielding during TBI to decrease cataract formation, 49 did not. The blocks used for shielding caused cylindrical areas of decreased dose intensity in the brain. The aim of the study was to determine if there was an increased risk of relapse in the eyes or in the CNS after shielding of the eyes. The probability and severity of cataract formation with and without shielding were also evaluated. None of the 49 children without shielding had a relapse in their eyes or in the CNS after BMT. Of the children with shielding, none had a relapse in the eyes but two of the 139 (1.4%) had a CNS relapse. The incidence of cataracts without shielding was 90% (19 of 21 evaluable patients), while with shielding it was 31% (20 of 64). Severe cataracts were present in eight of 21 (38%) patients without and two of 64 (3%) patients with shielding. The probability of staying cataract free for at least five years was 0.77 with and 0.33 without shielding, at 8 years it was 0.53 and 0.24 respectively. The relative risk of developing a cataract without shielding vs shielding was three (95% CI ¼ 1.5; 5.9). It appears that the incidence of relapse in the eyes and CNS is not increased when the eyes are shielded during TBI. Shielding increased the latency time of cataract formation and decreased the severity of cataracts. Bone Marrow Transplantation (2003) 31, 1151-1156. doi:10.1038/sj.bmt.1704076 Keywords: TBI; eye shielding; eye relapse; CNS relapse; cataract Total body irradiation (TBI) is an important part of the conditioning for bone marrow transplantation (BMT) for many hematological disorders in children and adults. 1-3Cataract formation is a known side effect of TBI.4-7 After single-dose TBI the probability of developing a cataract is reported to be 70-100%. [6][7][8][9][10][11][12] In more than 50% of these patients visual impairment is severe and cataract surgery may be necessary. 6,9 An effective way of decreasing the risk of severe cataracts is to lower the radiation dose on the eye lenses by shielding the eyes. We applied this technique successfully to children who had TBI before BMT in Leiden and Utrecht. Shielding of the eyes, however, is controversial as the eyes (just as the CNS) are considered to be extramedullary sanctuaries. 13 We evaluated the data of all children who had a BMT with TBI as part of the conditioning in Leiden and Utrecht with the aim of investigating relapse incidence in the eyes after eye shielding during TBI. As the blocks used for shielding cause tiny but tall cylindrical areas of decreased dose intensity to the brain, we also evaluated the incidence of relapse in the CNS. Furthermore, we evaluated the effect of eye shielding on cataract formation. Methods Study designWe evaluated retrospectively the risk of relapse in the eyes and CNS after shielding the eyes during TBI. Participants ...

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Therapy of childhood acute myelogenous leukemias

Cited by 24 publications

References 46 publications

Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy

Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy

Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols

Eye shielding during total body irradiation for bone marrow transplantation in children transplanted for a hematological disorder: risks and benefits

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