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Table 2 Characteristics of included studies assessing prevalence and incidence of cardiac electrical abnormalities

From: Cardiac electrical abnormalities in childhood acute lymphoblastic leukemia survivors: a systematic review

Authors

Study design

Study aims

Demographics and baseline characteristics

Cancer characteristics

Bertrand et al., 2021 [50]

Cross-sectional study

To examine heart rate response during a maximal cardiopulmonary exercise test

Participants (N = 216)

Eligible for review N = 216 (51.4% males)

Age at cardiac evaluation (years)

mean ± SD: 22.0 ± 6.4 median (range): 22.0 (8.0—40.0)

Geographical region: Canada

Socio-economic status: Not reported*

Ethnicity: French-Canadian descent

Comorbidities: Not reported*

Period of diagnosis: 1987—2010

Age at cancer diagnosis (years)

mean ± SD: 6.4 ± 4.7

median (range): 4.0 (0.9—18.0)

Time since the end of cancer treatment: minimum 5 years

Length of follow-up: N/A

Cancer treatment and absolute cumulative dosage

Anthracycline chemotherapy (doxorubicin) (N = 216)

mean ± SD: 85.4 ± 121.7 mg/m2

median (range): 230.9 (43.6—472.9) mg/m2

Cranial radiotherapy (N = 123) no dosage specified

Cardioprotective treatment: Dexrazoxane (N = 65)

Brouwer et al., 2007 [51]

Cross-sectional study

To re-assesses cardiac status at a very long follow-up of median 22 years post treatment in a subset of the earlier studied survivors

Participants (N = 23)

Eligible for review N = 23 (39.1% males)

Age at cardiac evaluation (years)

median (range): 29.0 (24.0—39.0)

Geographical region: Netherlands

Socio-economic status: Not reported*

Ethnicity: Not reported

Comorbidities: Not reported*

Period of diagnosis: Not reported

Age at cancer diagnosis (years)

median (range): 5.0 (2.0—14.0)

Time since the end of cancer treatment (years)

median (range): 22.0 (19.5—24.5)

Length of follow-up: N/A

Cancer treatment and absolute cumulative dosage

Induction treatment (6 weeks)

Anthracycline (daunorubicin) (N = 13): 100 mg/m2/week

Vincristine: 6 × 2 mg/m2/week

Prednisone: 28 × 40 mg/m2/day

L-Asparaginase: 14 × 200 E/kg/day (weeks 4–6)

Central nervous system prophylaxis (2.5–3 weeks)

Cranial radiotherapy (N = 23): median (range): 25 (18—25) Gy

Methotrexate: 12.5 mg/m2 (maximum 15 mg/m2)

Prednisone: 5 × 12.5 mg/m2

Maintenance and consolidation phase (until 2 years from start of treatment)

6-mercaptopurine: 50 mg/m2/day for 5 weeks

Alternating with 2 weeks:

Methotrexate: 30 mg/m2/week OR Vincristine: 2 mg/m2/week

Prednisone: 40 mg/m2/day

Cardioprotective treatment: Not reported

Halazun et al., 1974 [52]

Randomized controlled trial

To describe the evidence to support the occurrence of cardiotoxicity from daunorubicin

Participants (N = 172)

Eligible for review N = 172 (58.1% males)

Age at cardiac evaluation: Not reported

Geographical region: France, USA

Socio-economic status: Not reported*

Ethnicity: Not reported*

Comorbidities: Not reported*

Period of diagnosis: 1968–1971

Age at cancer diagnosis: Not reported

Time since the end of cancer treatment:

median: 79 days

range: 14–280 days

Length of follow-up: Not reported

Cancer treatment and absolute cumulative dosage

Anthracycline chemotherapy (daunorubicin)

mean: 780 mg/m2

range: 360–1260 mg/m2

Methotrexate

no dosage specified

L-Asparaginase

no dosage specified

Vincristine

no dosage specified

Prednisone

no dosage specified

Cardioprotective treatment: Not reported

Hau Eva et al., 2019 [53]

Case control study

To compare the risk of cardiovascular disease reported by acute lymphoblastic leukemia survivors to that of their siblings, and changes in risk based on the calendar period of diagnosis. It also examines treatment-related risk factors for cardiovascular disease

Participants (N = 511)

Eligible for review N = 511 (50.5% males)

Age at cardiac evaluation (years)

range 16—20 (N = 135)

range 21—30 (N = 251)

range 31—40 (N = 107)

range 41 or more (N = 18)

Geographical region: Swiss

Socio-economic status: Not reported*

Ethnicity: Not reported

Comorbidities: Not reported*

Period of diagnosis: 1976—2005

Age at cancer diagnosis (years)

(range): (0—19)

Time since the end of cancer treatment: minimum 5 years

Length of follow-up: N/A

Cancer treatment and absolute cumulative dosage

Anthracycline (N = 315): no dosage specified

Radiotherapy (N = 151): no dosage specified

Chest radiotherapy (N = 23): no dosage specified

Hematopoietic stem cell transplantation (N = 23)

Cardioprotective treatment: Not reported

Lipshultz et al., 1991 [3]

Cross-sectional study

To evaluate cardiac status in children 1 to 15 years after the successful treatment of acute lymphoblastic leukemia with chemotherapeutic regimens that included doxorubicin

Participants (N = 115)

Eligible for review N = 115 (50.4% males)

Age at cardiac evaluation (years)

mean: 13.6

median (range): 12.6 (3.9—31.7)

Geographical region: USA

Socio-economic status: Not reported*

Ethnicity: Not reported

Comorbidities: Not reported*

Period of diagnosis: 1972—1987

Age at cancer diagnosis

mean: 6.3 years

median (range): 4.8 years (7 months—19.1 years)

Time since the end of cancer treatment (years)

minimum one

median (range): 6.4 (1.0—15.0)

Length of follow-up: N/A

Cancer treatment and absolute cumulative dosage

Anthracycline (doxorubicin) (N = 18): 45 mg/m2

Anthracycline (doxorubicin) (N = 97):

median (range): 360 (228–550) mg/m2

Vincristine: no dosage specified

Methotrexate: no dosage specified

Prednisone: no dosage specified

Mercaptopurine: no dosage specified

l-asparaginase: no dosage specified

Cardioprotective treatment: Not reported

Pihkala et al., 1994 [49]

Cohort study

To evaluate the long-term effects of bone marrow transplant on myocardial function in children

Participants (N = 30)

Eligible for review N = 9 (44.4% males)

Age at cardiac evaluation: Not reported

Geographical region: Finland

Socio-economic status: Not reported*

Ethnicity: Not reported

Comorbidities: Not reported*

Period of diagnosis: Not reported

Age at cancer diagnosis: Not reported

Time since the end of cancer treatment (years)

mean ± SD: 5.5 ± 3.3

median (range): 5.9 (0.5–9.6)

Length of follow-up: N/A

Cancer treatment and absolute cumulative dosage

Anthracycline chemotherapy (N = 9)

mean ± SD: 174.4 ± 87.6 mg/m2

median (range): 140 (120—400) mg/m2

Total body irradiation (N = 9)

mean ± SD: 1110.0 ± 101.7 cGy

median (range): 1200 (970—1200) cGy

Cyclophosphamide (N = 6): no dosage specified

Cytosine arabinoside (N = 3): no dosage specified

Allogenic bone marrow transplantation (N = 9)

Cardioprotective treatment: Not reported

Velensek Prestor et al., 2000 [17]

Cross-sectional study

To analyze the influence of risk factors to anthracycline cardiotoxicity and to define the most suitable method of late cardiac toxicity detection

Participants (N = 46)

Eligible for review N = 46 (37.8% males)

Age at cardiac evaluation (years)

mean: 23.0

range: 18.0—33.0

Geographical region: Slovenia

Socio-economic status: Not reported*

Ethnicity: Not reported

Comorbidities: Not reported*

Period of diagnosis: 1968—1992

Age at cancer diagnosis (years)

mean: 7.0

range: 2.0—17.0

Time since the end of cancer treatment: minimum 5 years

mean: 16

range: 5—23

Length of follow-up: N/A

Cancer treatment and absolute cumulative dosage

Anthracycline chemotherapy (N = 34)

mean: 203.0 mg/m2

range: 50.0—540.0

Cranial radiotherapy (N = 46) range: 12—24 Gy

AA-cyclophosphamide (N = 9): 3 × 1000 mg/m2

AA-cyclophosphamide (N = 1): 2 × 600 mg/m2

AA-cyclophosphamide (N = 3): 8400 mg/m2

Vincristine: no dosage specified

Methotrexate: no dosage specified

Prednisone: no dosage specified

Mercaptopurine: no dosage specified

l-asparaginase: no dosage specified

Cytarabine: no dosage specified

Thioguanine: no dosage specified

Cardioprotective treatment: Not reported

Rammeloo et al., 2000 [54]

Randomized control trial

To investigate late cardiotoxicity in childhood acute lymphoblastic leukemia survivors after induction treatment with or without daunorubicin

Participants (N = 90)

Eligible for review N = 90 (44.4% males)

Age at cardiac evaluation (year)

Group A: median (range): 18.6 (14.7—31.3)

Group B: median (range): 20.1 (14.8—30.0)

Geographical region: Netherlands

Socio-economic status: Not reported*

Ethnicity: Not reported

Comorbidities: Not reported*

Period of diagnosis: 1979—1984

Age at cancer diagnosis (years)

median (range): 4.5 (1.2—14.9)

Time since the end of cancer treatment (years)

median (range): 14.8 (11.4—17.8)

Length of follow-up: N/A

Cancer treatment and absolute cumulative dosage

Vincristine (N = 90): no dosage specified

Prednisone (N = 90): no dosage specified

Asparaginase (N = 90): no dosage specified

Anthracycline (daunorubicin) (N = 50, group B): 100 mg/m2

Cardioprotective treatment: Not reported

Shimomura et al., 2011 [55]

Cross-sectional study

To evaluate Pirarubicin-induced late cardiotoxicity for asymptomatic children who received THP therapy in three consecutive JCCLSG studies (ALL911/ALL941/ALL2000)

Participants (N = 61)

Eligible for review N = 61 (49.2% males)

Age at cardiac evaluation (years)

mean ± SD: 14.7 ± 3.5

median (range): 14.7 (7.6—25.7)

Geographical region: Japan

Socio-economic status: Not reported*

Ethnicity: Not reported

Comorbidities: Not reported*

Period of diagnosis: 1991–2003

Age at cancer diagnosis (years)

mean ± SD: 5.7 ± 3.5

Time since the end of cancer treatment (years)

mean ± SD: 7.2 ± 2.8

median (range): 8.1 (1.7—12.5)

Length of follow-up: N/A

Cancer treatment and absolute cumulative dosage

Anthracycline (Pirarubicin (tetrahydropyranyl-adriamycin))

mean ± SD: 299 ± 192 mg/m2

median (range): 180 (120—740) mg/m2

Anthracycline chemotherapy (doxorubicin and Pirarubicin)

mean ± SD: 346 ± 206 mg/m2

median (range): 207 (135—812) mg/m

Cardioprotective treatment: Not reported

Steinherz et al., 1995 [48]

Cross-sectional study

To describe the clinical course, evolution of cardiac findings, and treatment of our symptomatic patients

Participants (N = 15)

Eligible for review N = 2 (50% males)

Age at cardiac evaluation: Not reported

Geographical region: USA

Socio-economic status: Not reported*

Ethnicity: Not reported

Comorbidities: Not reported*

Period of diagnosis: Not reported

Age at cancer diagnosis: Not reported

Time since the end of cancer treatment: 12 and 19 years

Length of follow-up: N/A

Cancer treatment and absolute cumulative dosage

Anthracycline (daunorubicin) (N = 1): 795 mg/m2

Anthracycline (doxorubicin) (N = 1): 350 mg/m2

Cardioprotective treatment: Not reported

Turner-Gomes et al., 1996 [56]

Cross-sectional study

To assess cardiopulmonary status and exercise capacity after successful treatment

Participants (N = 19)

Eligible for review N = 19 (47.4% males)

Age at cardiac evaluation (years)

mean ± SD: 13.0 ± 3.5

median (range): 12.3 (7.7—23.8)

Geographical region: USA

Socio-economic status: Not reported*

Ethnicity: Not reported

Comorbidities: Not reported*

Period of diagnosis: 1984—1990

Age at cancer diagnosis (years)

mean ± SD: 6.1 ± 4.3

median (range): 4.6 (1.5—17.7)

Time since the end of cancer treatment (years)

Minimum one

mean ± SD: 4.6 ± 1.5

median (range): 4.4. (1.1—7.1)

Length of follow-up: N/A

Cancer treatment and absolute cumulative dosage

Anthracycline (doxorubicin): (N = 7 standard risk) mean ± SD: 50 ± 21 mg/m2

Anthracycline (doxorubicin): (N = 12 high risk/very high risk) mean ± SD: 349 ± 16 mg/m2

Cardioprotective treatment: Not reported