Cohort studycited by the Tayebat archiveabstract only checked A-CHM-02 standard review

Doxorubicin in childhood can affect heart growth years later

Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood.

Overview

Lipshultz SE et al.. N Engl J Med 1991 · PMID 1997853 · DOI 10.1056/NEJM199103213241205

More than half of 115 childhood leukaemia survivors had heart function abnormalities, more often at higher doses.

Does the study support the specific claim? Yes · Methodological quality: moderate

Study explained simply

What did the researchers want to find out?: Assess late heart effects of doxorubicin.
How was the study done?: Cardiac testing of survivors.
How many people, animals or samples were studied?: 115 survivors.
What was actually found?: Dose-dependent abnormalities, progressive afterload rise.
How large was the observed effect?: 65% abnormal at >=228 mg/m2.
What do the results mean in everyday life?: Childhood cancer survivors need long-term heart follow-up.
What are the study's limitations?: Small, old doses, no control group.
What does it say about Elawady's specific claim?: Supports existence of late harm.
Do the results apply to Germany and Europe?: Moderate.
What can explicitly not be concluded from this study?: Whether leaving leukaemia untreated would be better (it is not).

Authors: Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP
Journal: N Engl J Med
Year: 1991
Identifier: PMID 1997853 DOI 10.1056/NEJM199103213241205
Verification: verified – PubMed E-utilities efetch, 2026-10-25
Retracted: no
Corrections: none
Extent checked: abstract only
Conflicts of interest and funding: not stated in abstract | Grants: NCI NIH HHS, NHLBI NIH HHS

Long-term cardiac effects of doxorubicin given for childhood ALL.

Study design: Cohort study – Cross-sectional cardiac evaluation with partial serial follow-up of a treated cohort
Population: Children treated for ALL with doxorubicin 1-15 years earlier, in continuous remission
Country: USA (not stated in abstract; NCI/NHLBI funding)
Period: Evaluation median 6.4 years after treatment
Sample size: 115
Inclusion and exclusion criteria: ALL in continuous remission after doxorubicin

Exposure / intervention: Doxorubicin, single dose 45 mg/m2 (n=18) or cumulative 228-550 mg/m2 (n=97, median 360)
Comparator: Dose groups; age-adjusted norms
Endpoints: Afterload (end-systolic wall stress), contractility, exercise capacity, heart failure
Statistical methods: Multivariate analyses

Results: 57% had abnormal afterload or contractility. Cumulative dose was the strongest predictor (P<0.002). In patients with >=228 mg/m2: 65% abnormal (59% increased afterload, 23% decreased contractility). Afterload increased progressively in 24 of 34 serially evaluated (71%). 11 had heart failure within one year of treatment; 5 had recurrent failure later; 2 needed transplantation.
Absolute risks: 57% with echocardiographic abnormality in this cohort
Authors' conclusion: Doxorubicin in childhood impairs myocardial growth dose-dependently, with progressive increase in afterload, sometimes reduced contractility.

Strong dose-response supports causality; prevalence estimates imprecise because of small n.

Supports late cardiac effects of anthracyclines in children.

A-CHM-11 shows reduced anthracycline exposure in later decades and falling late mortality.

Moderate: dosing protocols have changed since the 1970s-80s.

Classic early evidence of late anthracycline cardiotoxicity; correctly but somewhat loosely cited.

Multidimensional assessment
Multidimensional assessment
Authenticity of the source	verified
Methodological quality	moderate
Risk of bias	some concerns
Precision of results	low
Directness	direct
Reproducibility	replicated
Consistency with the overall evidence	consistent
Regional transferability	moderate
Adequacy of the interpretation (by the archive)	essentially correct but incomplete

Effect size under contemporary lower cumulative doses and cardioprotection.

Note: according to the archive, the studies were compiled by the archive operators. Whether Dr. Elawady himself cited this study is not established.

What the archive says about the study: Childhood leukaemia survivors who received doxorubicin developed progressive left-ventricular contractile impairment years later.
A. What was actually studied?: Cardiac function years after doxorubicin for childhood ALL.
B. What did the authors find?: Dose-related abnormalities, mainly progressive increase in afterload due to thin ventricular walls; reduced contractility in a minority (23% of the high-dose group).
C. What conclusions do the authors themselves draw?: Doxorubicin impairs myocardial growth in a dose-related fashion.
D. What does the archive derive from it?: Long-term progressive cardiac impairment.
E. Is this derivation scientifically justified?: Largely yes; 'progressive contractile impairment' is slightly imprecise: the progressive finding was increased afterload, while reduced contractility affected a minority. All patients were survivors in remission of a disease that is usually fatal without treatment.
Adequacy of the interpretation (by the archive): essentially correct but incomplete