Late effects of intensive treatment for acute myeloid leukemia and myelodysplasia in childhood.

Liesner, Ri; Leiper, Alison; Hann, IM; Chessells, J M

doi:10.1200/jco.1994.12.5.916

Cited by 92 publications

(73 citation statements)

References 28 publications

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“…110 Finally, the few data available about long-term cardiologic follow-up of patients after HD chemotherapy and HSC transplantation suggest that HD chemotherapy does not cause per se late development of cardiac toxicity, 5,79,90 although subclinical alteration of cardiac performance may last long. 50,90,109,[131][132][133][134] This is particularly important for the proportion of patients who may need a potentially cardiotoxic agent after HD chemotherapy for their relapsing disease. 135 …”

Section: Discussionmentioning

confidence: 99%

Cardiac toxicity of high-dose chemotherapy

Morandi

Ruffini

Benvenuto

et al. 2004

Bone Marrow Transplant

148

104

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Summary:Cardiac toxicity is an uncommon but potentially serious complication of high-dose (HD) chemotherapy and little is known about incidence, severity and underlying mechanisms. We have systematically reviewed the literature of the last 30 years to summarize and appraise the published evidence on cardiac toxicity associated with HD chemotherapy. HD cyclophosphamide-containing regimens have been most commonly associated with cardiac toxicity, with a progressively decreasing incidence over time. Dosage, application regimens and coadministration of other chemotherapeutic agents emerged as risk factors. While cardiac toxicity has been rarely associated with other cytotoxic drugs, an unexpected incidence of severe cardiotoxicity resulted from reduced-intensity conditioning regimens containing melphalan and fludarabine. Predictive value of cardiologic examination of patients is limited, and patients with a slight depression of cardiac performance could tolerate HD chemotherapy. Clinical examination, resting electrocardiography and dosage adjustment in overweight patients remain the mainstay of prevention, with bidimensional echocardiography (2D echo) for patients with a history of anthracycline exposure. Strategies to decrease the long-term negative impact of anthracycline administration on cardiac performance are being investigated. New 2D echo-based techniques and circulating markers of cardiac function hold promise for allowing identification of patients at high risk for and early diagnosis of cardiac toxicity.

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Section: Discussionmentioning

confidence: 99%

Cardiac toxicity of high-dose chemotherapy

Morandi

Ruffini

Benvenuto

et al. 2004

Bone Marrow Transplant

148

104

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“…1,2 Myeloablative therapy consisting of cyclophosphamide, busulfan or melphalan, has been used as an alternative to avoid the side-effects of irradiation on endocrine functions and growth. 1,3,4 Cytotoxics are known to induce ovarian toxicity in adults, dependent upon type of agent, dosage, administration schedule and patient age. [5][6][7] Much less is known about the effects of high-dose chemotherapy on ovarian function in children.…”

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confidence: 99%

“…3,[28][29][30][31] Among 73 women aged 14-57 years at transplant who received busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg), only one recovered normal ovarian function. 31 In the literature, we identified 29 girls who received busulfan in the prepubertal or pubertal period; 26 had signs of ovarian failure 3,[28][29][30][32][33][34] (Table 4). In a study of 15 girls aged 9-17 years treated for thalassemia with allogenic bone marrow transplantation, De Sanctis et al 28 demonstrated ovarian failure in 12 girls after a busulfan-cyclophosphamide conditioning regimen, without conventional chemotherapy.…”

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confidence: 99%

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure

Teinturier

Hartmann

Valteau‐Couanet

et al. 1998

Bone Marrow Transplant

194

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Summary:We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m 2 ) and melphalan (140 mg/m 2 ) with or without cyclophosphamide (3.6 g/m 2 ). Eleven others did not receive busulfan. Twelve girls (57%) had clinical and hormonal evidence of ovarian failure. Among nine others who had completed normal puberty, six had normal gonadotropin levels, one had elevated gonadotropin levels and two had gonadotropin levels at the upper limit of normal. The 10 girls who received busulfan all developed severe and persistent ovarian failure. High-dose busulfan is therefore a major cause of ovarian failure even when given in the prepubertal period. These findings emphasize the need for long-term endocrine follow-up of these patients in order to initiate estrogen replacement therapy. Keywords: ovarian function; high-dose chemotherapy; bone marrow transplantation; busulfan; childhood Increasing numbers of children who receive hematopoietic stem cell transplants (HSCT) for malignancies now survive. It is therefore important to evaluate ovarian toxicity secondary to the therapeutic regimens. New chemotherapy protocols will have to aim towards effecting long-term survival with minimal late morbidity. Chemotherapy is used alone or in combination with total body irradiation. Total body irradiation, used in the preparative regimens for hematologic malignancies, is deleterious to gonadal function. 1,2 Myeloablative therapy consisting of cyclophosphamide, busulfan or melphalan, has been used as an alternative to avoid the side-effects of irradiation on endocrine functions and growth. 1,3,4 Cytotoxics are known to induce ovarian toxicity in adults, dependent upon type of agent, dosage, administration schedule and patient age. 5-7 Much less is known about the effects of high-dose chemotherapy on ovarian function in children. 2,8,9 We report an analysis of ovarian function in long-term survivors following myeloablative chemotherapy and bone marrow transplantation. Patients and methodsWe screened all long-term female survivors older than 11 years who had received high-dose chemotherapy and autologous bone marrow transplantation without abdominal or pelvic radiation for malignant tumors at Institut Gustave Roussy. Twenty-one girls fulfilled these criteria.At time of transplantation, they were aged 2-17 years (median 9 years). Pubertal development was evaluated clinically according to Tanner. 10 Fourteen girls were prepubertal (stage 1), two were undergoing puberty (stage 3) and five had regular menses (stage 5). No hormonal evaluation was carried out before chemotherapy, but pubertal stages of all the patients were appropriate for their age.The study took place 1.2-13 years (median 7 years) after bone marrow transplantation and discontinuation of chemotherapy. At time of study, girls were aged 11.5-21 years (median 14.5 years).Serum concentrations of 17...

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“…16,17 Uderzo et al 16 reported 23% cumulative incidence of SF abnormalities in a multi-centre study of 189 paediatric allogeneic recipients 5 years after HSCT, but none of the patients died of cardiacrelated complications. Liesner et al 22 reported 3.5% significant cardiomyopathy in 83 children, evaluated 3 years after TBI. Most patients have some cardiac dysfunction during and immediately after HSCT and as many as 50% have persistent abnormalities, usually subclinical and rarely limiting the quality of life.…”

Section: Cardiac Function Abnormalitiesmentioning

confidence: 99%

Non-endocrine late complications in children after allogeneic haematopoietic SCT

Faraci¹,

Békássy

Fazio³

et al. 2008

Bone Marrow Transplant

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Late effects of intensive treatment for acute myeloid leukemia and myelodysplasia in childhood.

Abstract: Chemotherapy and TBI before BMT for AML has resulted in growth failure, gonadal and thyroid damage, and cataracts in most children, whereas chemotherapy alone caused cardiac, renal, and hearing abnormalities only.

Cited by 92 publications

References 28 publications

Cardiac toxicity of high-dose chemotherapy

Cardiac toxicity of high-dose chemotherapy

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure

Non-endocrine late complications in children after allogeneic haematopoietic SCT

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