Growth and endocrine consequences of being treated for leukemia as a baby
also called short stature after infant leukemia · growth hormone deficiency leukemia survivor · endocrine late effects infant ALL · obesity metabolic syndrome ALL survivor · bone density osteonecrosis leukemia
Children treated for leukemia as babies often end up shorter than they should have been, and many develop thyroid, growth-hormone, weight or bone problems years later. Growth was the single commonest late effect in the only study that followed infant-leukemia survivors specifically: two out of three had a growth problem.
The same thing, for a scientist
Growth was the most frequent late effect in the only dedicated infant-leukemia survivor cohort, affecting 66%, alongside hypothyroidism in 15% and abnormal pubertal development in 12%; the fall in height Z score at five years was significantly steeper in children who had received cranial radiotherapy with or without transplant [E1]. In the much larger Childhood Cancer Survivor Study, adult ALL survivors were shorter than siblings in every exposure group, and even survivors treated with chemotherapy alone had a threefold-plus excess of adult short stature (height SDS < -2; OR 3.4, 95% CI 1.9-6.0), with diagnosis before puberty, cranial radiotherapy >= 20 Gy, any spinal radiotherapy and female sex as independent risk factors [E2]. Growth hormone replacement partially rescues the deficit but does not normalise it: mean height SDS improved from -2.03 at the start of GH to -1.48 at final height [E3]. Obesity risk in ALL survivors is concentrated in those irradiated at >= 20 Gy and is highest in females diagnosed at 0-4 years (OR 3.81 vs siblings), while chemotherapy-only and 10-19 Gy exposures showed no obesity excess [E4]. Dental and craniofacial injury behaves like a classic developmental exposure, with a dose-dependent alkylating-agent effect confined to children diagnosed under five [E5]. Osteonecrosis is the striking exception: it is overwhelmingly an adolescent complication and infants are at very low risk.
Growth: the commonest late effect, and it is not only radiation2 deeper
In the St Jude infant-leukemia series, growth problems were the single most frequent late sequela, present in 66% of survivors diagnosed at 12 months or younger, ahead of learning problems (50%), hypothyroidism (15%) and abnormal pubertal development (12%) 1. Survivors who received cranial radiotherapy with or without bone marrow transplant had a significantly greater decrease in height Z score at five years than those given chemotherapy alone (P = 0.023) 1.
The critical point for a modern infant protocol is that removing radiation does not remove the growth penalty. In 2,434 adult ALL survivors compared with 3,009 siblings, all exposure groups - including chemotherapy alone - had decreased adult height and an increased risk of adult short stature defined as height SDS < -2 (P < 0.001), and for the chemotherapy-alone group the odds ratio for short stature was 3.4 (95% CI 1.9-6.0) 2. Independent risk factors within survivors were diagnosis before puberty, cranial radiotherapy >= 20 Gy versus < 20 Gy, any spinal radiotherapy, and female sex 2. An infant is, by definition, diagnosed before puberty.
| Exposure group | Population | Effect on adult stature |
|---|---|---|
| Chemotherapy alone | CCSS ALL survivors vs siblings | OR 3.4 (1.9-6.0) for height SDS < -2 2 |
| Cranial RT >= 20 Gy | CCSS ALL survivors | Higher risk than < 20 Gy 2 |
| Any spinal RT | CCSS ALL survivors | Independent risk factor 2 |
| Cranial RT +/- BMT vs chemo only, infants | 34 infant-leukemia survivors | Steeper fall in height Z score at 5 y (P = 0.023) 1 |
| GH-treated survivors | 183 CCSS survivors with final height | Height SDS -2.03 at GH start, -1.48 at final height (P < 0.001) 3 |
Growth hormone replacement helps and does not fix it
Among 361 Childhood Cancer Survivor Study participants treated with growth hormone, final height data were available for 183 (120 male; 64 with acute leukemia). Median age at cancer diagnosis was 4.6 years and median age at starting GH was 11.3 years - a six-and-a-half-year gap. Mean height SDS was -2.03 +/- 0.8 at the start of GH and -1.48 +/- 0.10 at final height (P < 0.001) 3. Final height was positively associated with target height and GH dose and negatively associated with concomitant endocrinopathies and spinal radiotherapy dose; risk factors for a final height at or below -2.0 SD were lower GH doses and higher spinal radiotherapy doses 3.
The operational conclusion the authors drew is the one that matters for a survivor treated in infancy: start GH at the earliest clinically feasible bone age, use conventional higher doses, and minimise spinal radiotherapy 3. A child treated at eight months who is not referred to endocrinology until age eleven has already lost most of the recoverable growth.
Thyroid and pituitary axis
Hypothyroidism affected 15% of the infant-leukemia survivors, and in that cohort thyroid papillary carcinoma appears among the radiation-associated second neoplasms 1. Abnormal pubertal development affected 12%, concentrated in the transplanted group 1.
When the endocrine axis is assessed by systematic clinical testing rather than by questionnaire, the burden is much larger than self-report suggests: in 1,713 adult survivors of childhood cancer given exposure-based medical assessments, 62.0% (95% CI 59.5-64.6) had at least one endocrine or reproductive condition, and the estimated cumulative prevalence of pituitary dysfunction by age 50 among at-risk survivors was 76.8% (95% CI 73.6-80.0) - see the counter-evidence attached to 4. That cohort is childhood cancer of all types and ages, so the number is a ceiling, not an infant estimate.
Body composition: obesity is a radiation story, and it is worst in the youngest girls
In 1,765 adult ALL survivors versus 2,565 siblings, the age- and race-adjusted odds ratio for obesity (BMI >= 30) after cranial radiotherapy >= 20 Gy was 2.59 (95% CI 1.88-3.55) in females and 1.86 (95% CI 1.33-2.57) in males, and the highest risk of all was in females diagnosed at 0-4 years and irradiated at >= 20 Gy: OR 3.81 (95% CI 2.34-5.99) 4. Crucially, obesity was not associated with chemotherapy-only treatment or with cranial radiotherapy at 10-19 Gy 4.
This is the second late-effect domain, after neurocognition, where the removal of cranial irradiation from infant protocols should have banked most of the available benefit. It also means that a survivor of infant ALL treated on Interfant-06 should not be counselled using the historical obesity figures: the exposure that drove them is gone.
The honest gap: a measured metabolic-syndrome prevalence for survivors treated as infants was not found in the literature reviewed. The French LEA cohort prospectively collects metabolic syndrome, cardiac function, bone density and fertility in survivors of childhood acute leukemia from 1980 onward and had enrolled 2,385 survivors by 2013, which makes it the most likely source of such a figure - but the figure itself is not quoted here because it was not verified (see counter-evidence on 4).
Bone: the one late effect where being a baby protects you1 deeper
Osteonecrosis is glucocorticoid-driven and is overwhelmingly a complication of adolescence, not infancy. In 1,409 children aged 1-20 years treated for high-risk ALL on CCG-1882, the three-year life-table incidence of symptomatic osteonecrosis was 9.3% +/- 0.9% overall, but 0.9% +/- 0.4% in children under 10 years versus 14.2% +/- 1.3% in those aged 10 or more (P < 0.0001), peaking at 19.2% +/- 2.3% in girls aged 10-15 and 20.7% +/- 4.7% in boys aged 16-20 - see the counter-evidence on 1. Where it occurred it was serious: weight-bearing joints in 94%, multifocal in 74%, chronically symptomatic in 84%, with 24% having undergone an orthopaedic procedure.
This is worth stating plainly because it cuts against the reflex that every late effect is worse in the youngest patients. Prednisone and dexamethasone exposure in Interfant-06 is substantial (a 7-day prednisone prephase, then dexamethasone 6 mg/m²/day for 21 days in induction and 14 days in OCTADA(D)), yet the osteonecrosis risk that this exposure creates in a teenager is largely absent in an infant. Reduced bone mineral density is a separate and real concern - clinically ascertained osteoporosis was present in 9.6% (95% CI 8.0-11.5) of adult survivors of childhood cancer (counter-evidence on 4) - but it is not the same entity as steroid osteonecrosis and it is not concentrated in the youngest.
Dental and craniofacial: a true developmental exposure
Dental injury behaves exactly as an exposure to a developing organ should. Among 9,308 survivors and 2,951 siblings, survivors reported excess microdontia (OR 3.0, 95% CI 2.4-3.8), hypodontia (OR 1.7, 1.4-2.0), root abnormalities (OR 3.0, 2.2-4.0), abnormal enamel (OR 2.4, 2.0-2.9), loss of six or more teeth (OR 2.6, 1.9-3.6) and xerostomia (OR 9.7, 4.8-19.7) 5. Radiation >= 20 Gy to the dentition was an independent risk factor, and - the key finding for this node - dose-dependent alkylating-agent therapy significantly increased the risk of one or more anatomic or developmental dental abnormalities specifically in survivors diagnosed under five years of age, with ORs of 1.7, 2.7 and 3.3 for rising alkylating-agent scores 5. The authors' explicit recommendation was that patients receiving alkylating agents under age five be closely monitored.
Interfant-06 delivers cyclophosphamide 1,000 mg/m² x 2 in protocol IB and 500 mg/m² x 2 in OCTADA(D) on the standard arm, and transplanted high-risk infants receive busulfan 20 mg/kg plus cyclophosphamide 120 mg/kg plus melphalan 140 mg/m². Every infant on this protocol is therefore in the exposure category that 5 flags.
What is measured and what is borrowed
Infant-specific and measured: growth problems 66%, hypothyroidism 15%, pubertal problems 12%, steeper height Z-score fall with radiotherapy 1 - in 34 survivors from one institution, most of whom received exposures now abandoned.
Borrowed from older-child cohorts: the chemotherapy-alone short-stature odds ratio 2, the GH-response magnitude 3, the obesity odds ratios 4, the dental odds ratios 5, the osteonecrosis age gradient, and the clinically ascertained endocrine prevalences. None of these cohorts has enough infant-treated patients to produce an infant-specific estimate, and where the age term is reported it is usually 'diagnosed under 5' or 'before puberty' rather than 'under 1'.
The two effects for which the age term points most strongly toward infants being the worst-affected group are final height (diagnosis before puberty is an independent risk factor, and an infant has the maximum remaining growth to lose) and dental/craniofacial development (alkylator effect confined to diagnosis under five). Those are the two to quote when arguing the case for an anthracycline- and alkylator-sparing regimen.
| kind | late_effect_domain |
|---|---|
| domain | growth_and_endocrine |
| evidence quality note | Only the 34-patient Leung 2000 series is infant-specific. Stature, obesity, dental and osteonecrosis effect sizes are all from older-child or all-cancer cohorts treated in a radiation-heavy era. |
infant specific outcomes
{
"cohort": "St Jude infant leukemia survivors (Leung 2000)",
"n": 34,
"age_at_diagnosis": "<=12 months",
"median_follow_up_years": 13,
"growth_problems_pct": 66,
"learning_problems_pct": 50,
"hypothyroidism_pct": 15,
"abnormal_pubertal_development_pct": 12,
"cataract_cardiac_hearing_pct": 6,
"free_of_any_late_effect_pct": 24,
"height_z_score": "significantly greater decrease at 5 y in cranial-RT +/- BMT groups vs chemotherapy alone, P = 0.023 (magnitude not reported)"
}stature
{
"cohort": "CCSS, 2434 ALL survivors vs 3009 siblings, diagnosed 1970-1986",
"short_stature_definition": "height SDS < -2",
"odds_ratio_chemotherapy_alone": 3.4,
"ci95": [
1.9,
6
],
"independent_risk_factors": [
"diagnosis before puberty",
"cranial radiotherapy >= 20 Gy",
"any spinal radiotherapy",
"female sex"
]
}growth hormone treatment
{
"cohort": "CCSS GH-treated survivors with final height",
"n": 183,
"median_age_at_cancer_diagnosis_years": 4.6,
"median_age_at_gh_start_years": 11.3,
"height_sds_at_gh_start": -2.03,
"height_sds_sd": 0.8,
"final_height_sds": -1.48,
"final_height_sds_se": 0.1,
"p_value": "<0.001"
}obesity
{
"cohort": "CCSS, 1765 adult ALL survivors vs 2565 siblings",
"definition": "BMI >= 30",
"or_female_crt_ge_20gy": 2.59,
"or_female_ci95": [
1.88,
3.55
],
"or_male_crt_ge_20gy": 1.86,
"or_male_ci95": [
1.33,
2.57
],
"or_female_diagnosed_0_to_4y_crt_ge_20gy": 3.81,
"or_female_0_to_4y_ci95": [
2.34,
5.99
],
"no_excess_with": [
"chemotherapy only",
"cranial radiotherapy 10-19 Gy"
]
}osteonecrosis
{
"cohort": "CCG-1882 high-risk ALL, n = 1409, ages 1-20 y",
"three_year_incidence_overall_pct": 9.3,
"three_year_incidence_under_10y_pct": 0.9,
"three_year_incidence_10y_and_over_pct": 14.2,
"peak_girls_10_to_15y_pct": 19.2,
"peak_boys_16_to_20y_pct": 20.7,
"p_value_age": "<0.0001",
"weight_bearing_joint_pct": 94,
"multifocal_pct": 74,
"chronic_symptoms_pct": 84,
"orthopaedic_procedure_pct": 24,
"interpretation": "infants are near-exempt despite heavy glucocorticoid exposure - the one late effect where young age protects"
}dental
{
"cohort": "CCSS, 9308 survivors vs 2951 siblings",
"or_microdontia": 3,
"or_hypodontia": 1.7,
"or_root_abnormalities": 3,
"or_abnormal_enamel": 2.4,
"or_six_or_more_teeth_lost": 2.6,
"or_xerostomia": 9.7,
"alkylator_effect_restricted_to": "diagnosed at age < 5 years",
"or_by_alkylating_agent_score": {
"1": 1.7,
"2": 2.7,
"3": 3.3
}
}clinically ascertained endocrine burden
{
"cohort": "St Jude Lifetime Cohort, 1713 adults, median 25 y from diagnosis",
"any_endocrine_or_reproductive_condition_pct": 62,
"ci95": [
59.5,
64.6
],
"cumulative_pituitary_dysfunction_by_age_50_pct": 76.8,
"osteoporosis_pct": 9.6,
"any_chronic_health_condition_by_age_45_pct": 95.5,
"note": "all childhood cancers pooled, not infant-specific"
}relevant interfant 06 exposures
{
"prednisone_prephase_mg_per_m2_per_day": 60,
"prednisone_prephase_days": 7,
"dexamethasone_induction_mg_per_m2_per_day": 6,
"dexamethasone_induction_days": 21,
"dexamethasone_octadad_mg_per_m2_per_day": 6,
"dexamethasone_octadad_days": 14,
"cyclophosphamide_protocol_ib_mg_per_m2": 2000,
"cyclophosphamide_octadad_mg_per_m2": 1000,
"transplant_conditioning": "busulfan 20 mg/kg total + cyclophosphamide 120 mg/kg total + melphalan 140 mg/m2, no TBI",
"source": "Interfant-06 protocol, SKION version 01 April 2006"
}- A targeted agent that spares anthracyclines and alkylators but keeps or increases glucocorticoid exposure would leave the growth and bone-density burden intact while claiming a toxicity win.
- The largest measured drivers of endocrine late effects in the historical literature - cranial radiotherapy >= 20 Gy and total body irradiation - have already been removed from infant protocols, so the marginal endocrine benefit available to a new agent is smaller than the historical odds ratios suggest.
- If a new agent extends therapy duration (for example chronic menin inhibition rather than two years of chemotherapy), chronic exposure of a growing skeleton and pituitary becomes a new and unstudied risk rather than an avoided one.
- Better survival will expose more children to the growth-hormone-deficiency pathway for longer, which shifts cost onto endocrine services that infant-leukemia survivorship programmes are not currently sized for.
- What is the mean final-height SDS of survivors of infant KMT2A-rearranged ALL treated on Interfant-06 with no cranial or total-body irradiation? No cohort has reported it, and the CCSS chemotherapy-alone odds ratio of 3.4 for short stature is the only basis for expecting a deficit at all.
- What is the prevalence of metabolic syndrome in survivors treated as infants? The LEA cohort collects the data prospectively; the analysis restricted to infants has not been published.
- Does the age-by-body-surface-area dose reduction used in Interfant-06 (two-thirds of calculated dose under 6 months, three-quarters from 6-12 months) under- or over-expose the growth plate and the hypothalamic-pituitary axis relative to older children?
- Would earlier endocrine surveillance and earlier growth-hormone referral in infant-treated survivors close the residual 1.48 SD height gap, given that the CCSS GH cohort started replacement a median of 6.7 years after diagnosis?
- E1moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
Among 34 five-year survivors of leukemia diagnosed at 12 months or younger (median follow-up 13 years), growth problems affected 66%, learning problems 50%, hypothyroidism 15% and abnormal pubertal development 12%; only 24% had no late effect, and survivors given cranial radiotherapy with or without bone marrow transplant had a significantly greater decrease in height Z score at five years than those given chemotherapy alone (P = 0.023).
Late effects in survivors of infant leukemia · Leung W, Hudson M, Zhu Y, Rivera GK, Ribeiro RC, Sandlund JT, Bowman LC, Evans WE, Kun L, Pui CH · Leukemia 2000What this evidence cannot show
34 survivors (19 ALL, 15 AML) from one institution, diagnosed over an era in which 24 of 34 received cranial radiotherapy and 7 received bone marrow transplant with total body irradiation. Neither KMT2A status nor the magnitude of the height Z-score change is reported in the abstract. Contemporary infant protocols use no cranial irradiation and no TBI, so these absolute prevalences overstate current risk; the value of the paper is that it is the only infant-specific denominator available.
Evidence that argues against this (2)
- The assumption that younger age always means worse late effects fails for osteonecrosis: on CCG-1882 the three-year incidence was 0.9% in children under 10 versus 14.2% in those 10 or older (P < 0.0001), so despite heavy glucocorticoid exposure infants are near-exempt from the commonest disabling musculoskeletal toxicity of ALL therapy. Mattano LA et al. 2000
- A companion series of 77 survivors of childhood AML from the same institution found growth abnormalities in 51% and endocrine abnormalities in 16% - lower than the infant figures, consistent with age at treatment mattering, but also showing how much the numbers move with cohort composition. Leung W et al. 2000
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Among 2,434 adult survivors of childhood ALL compared with 3,009 siblings, every treatment-exposure group had decreased adult height and increased risk of adult short stature (height SDS < -2); for survivors treated with chemotherapy alone the odds ratio for short stature was 3.4 (95% CI 1.9-6.0), and independent risk factors were diagnosis before puberty, cranial radiotherapy >= 20 Gy, any spinal radiotherapy and female sex.
Decreased adult height in survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study · Chow EJ, Friedman DL, Yasui Y, Whitton JA, Stovall M, Robison LL, Sklar CA · The Journal of Pediatrics 2007What this evidence cannot show
Cross-sectional with self-reported heights and weights, in survivors diagnosed 1970-1986 - an era of routine cranial irradiation and of chemotherapy regimens that differ from current infant protocols. Siblings are a good but imperfect comparator for genetic target height. 'Diagnosis before puberty' is the youngest age term available and does not isolate infants; the paper cannot say whether an infant does worse than a four-year-old. Self-reported height tends to be over-reported, which would bias the short-stature prevalence downward.
Evidence that argues against this (1)
- No identified study finds normal adult stature after chemotherapy-only childhood ALL therapy, so this finding is not contested in direction. What is contested is attribution: the same cohort cannot separate leukemia-related illness, nutrition during two years of therapy, glucocorticoid exposure and direct growth-plate effects. Brownstein CM et al. 2004
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
Among 183 childhood cancer survivors treated with growth hormone who reached final height (median age at cancer diagnosis 4.6 years, median age at GH start 11.3 years), mean height SDS rose from -2.03 +/- 0.8 at the start of GH to -1.48 +/- 0.10 at final height (P < 0.001); final height was negatively associated with concomitant endocrinopathies and spinal radiotherapy dose, and risk factors for a final height <= -2.0 SD were lower GH dose and higher spinal radiotherapy dose.
Factors that affect final height and change in height standard deviation scores in survivors of childhood cancer treated with growth hormone: a report from the Childhood Cancer Survivor Study · Brownstein CM, Mertens AC, Mitby PA, Stovall M, Qin J, Heller G, Robison LL, Sklar CA · The Journal of Clinical Endocrinology and Metabolism 2004What this evidence cannot show
Observational and uncontrolled: there is no untreated comparison group, so the +0.55 SDS change cannot be attributed to GH with certainty. Final height was available for only 183 of 361 GH-treated survivors, and the diagnostic mix is dominated by CNS tumours (n = 90) with only 64 acute leukemias. GH doses and formulations are those of the 1980s-1990s. Median age at GH start of 11.3 years means these children were referred late by current standards, so the achievable catch-up with earlier referral is unknown and probably better than shown.
Evidence that argues against this (1)
- Because survivors with better growth potential may have been selected for GH treatment and those with the worst endocrinopathies excluded, the apparent benefit may be inflated; conversely late referral means it may be understated. The study cannot resolve which. Chow EJ et al. 2007
- E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Among 1,765 adult survivors of childhood ALL versus 2,565 siblings, the adjusted odds ratio for obesity (BMI >= 30) after cranial radiotherapy >= 20 Gy was 2.59 (95% CI 1.88-3.55) in females and 1.86 (95% CI 1.33-2.57) in males, rising to 3.81 (95% CI 2.34-5.99) in females diagnosed at 0-4 years and irradiated at >= 20 Gy; obesity was not associated with chemotherapy-only treatment or with cranial radiotherapy at 10-19 Gy.
Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study · Oeffinger KC, Mertens AC, Sklar CA, Yasui Y, Fears T, Stovall M, Vik TA, Inskip PD, Robison LL · Journal of Clinical Oncology 2003What this evidence cannot show
BMI was calculated from self-reported height and weight, which systematically underestimates obesity prevalence. Retrospective cohort diagnosed 1970-1986. The critical caveat for this node is directional and favourable: because the effect was confined to cranial radiotherapy >= 20 Gy and absent with chemotherapy alone, these odds ratios should NOT be applied to an infant treated on a radiation-free protocol. The 0-4 year age stratum is the youngest available and still does not isolate infants.
Evidence that argues against this (2)
- Systematic clinical assessment rather than self-report finds a far heavier endocrine burden than questionnaire studies imply: in 1,713 adult survivors, 62.0% had at least one endocrine or reproductive condition, estimated cumulative pituitary dysfunction by age 50 was 76.8% among at-risk survivors, clinically ascertained osteoporosis was present in 9.6%, and 95.5% had some chronic health condition by age 45. Self-report-based prevalences are therefore a floor, not an estimate. Hudson MM et al. 2013
- A prospective cohort designed to measure exactly the missing quantity - metabolic syndrome, bone density, cardiac function and fertility in survivors of childhood acute leukemia treated from 1980 onward, with 2,385 survivors enrolled by 2013 - exists, so the absence of an infant-specific metabolic-syndrome figure here reflects unanalysed data rather than unanswerable biology. Berbis J et al. 2014
- E5strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
Among 9,308 childhood cancer survivors and 2,951 siblings, survivors reported excess microdontia (OR 3.0), hypodontia (OR 1.7), root abnormalities (OR 3.0), abnormal enamel (OR 2.4), loss of six or more teeth (OR 2.6) and xerostomia (OR 9.7); radiation >= 20 Gy to the dentition was an independent risk factor, and dose-dependent alkylating-agent therapy increased the risk of one or more anatomic or developmental dental abnormalities specifically in survivors diagnosed under five years of age (OR 1.7, 2.7 and 3.3 for rising alkylating-agent scores).
Impact of radiation and chemotherapy on risk of dental abnormalities: a report from the Childhood Cancer Survivor Study · Kaste SC, Goodman P, Leisenring W, Stovall M, Hayashi RJ, Yeazel M, Beiraghi S, Hudson MM, Sklar CA, Robison LL, Baker KS · Cancer 2009What this evidence cannot show
Outcomes are self-reported on a survey rather than examined by a dentist, so both recall bias and misclassification of technical dental terms are likely, and the huge xerostomia odds ratio with a wide confidence interval (4.8-19.7) suggests reporting effects. Survivors were diagnosed 1970-1986 with all cancer types pooled, not ALL-specific. The alkylating-agent score is an ordinal composite, not a mg/m2 dose, so the effect cannot be converted into a cyclophosphamide-equivalent threshold. The 'diagnosed under 5' stratum is the relevant one for infants but still does not isolate them.
Evidence that argues against this (1)
- No identified study disputes that odontogenesis is disrupted by childhood cancer therapy. The unresolved question is the relative contribution of alkylators versus radiation versus glucocorticoids in a modern radiation-free infant regimen, which this survey cannot separate. Leung W et al. 2000
a bone-directed agent read against infant skeletal late effects
- ← supportsNine survivors in ten carry a long-term complication, and it is worse the younger they were
short stature 7.5%, pubertal delay 11.9%, high BMI in 24 of 67
- ← related toPituitary adenoma in MEN1: the third manifestation, and the one that matters most for a growing child
a pituitary hit would be additive on a growth axis already damaged in 66% of infant-leukaemia survivors
lands on a population in which growth is already the commonest late effect (66% in the only infant-specific cohort)
uncosted late effect
the growth axis an ERalpha effect would land on
much of the long-term cost of cure in an infant
- ← co-occurs withIn a live mouse, losing menin in bone cells means less bone - and menin overexpression means more
A drug-induced osteoblast menin deficit would be additive on the corticosteroid, methotrexate and transplant bone burden this population already carries
growth hormone deficiency 59% and hypothyroidism 35% in survivors transplanted under 3 years, most TBI-conditioned