ALL Survivors Research Articles

Late cardiac status in long-term survivors of childhood high-risk ALL 8 years after continuous or bolus infusion of doxorubicin: The DFCI Childhood ALL 91-01 randomized trial.

9513 Background: Continuous infusion (CI) of doxorubicin (DOX) reportedly reduces cardiotoxicity during or shortly after treatment in adults; however, its long-term cardioprotective effects in chil...

Temporal trends in cause-specific late mortality among five-year survivors of childhood cancer

10004 Background: Five-year survival rates for childhood cancer have increased over the past 4 decades, increasing the number of long-term survivors. Among 5-yr survivors, the impact of changes in therapy on cause-specific late mortality has not been thoroughly assessed. Methods: Late mortality was evaluated over 3 eras (1974–81, 1982–90, 1991–2000) in 26,643 5-year survivors diagnosed <21 years of age from the SEER population-based registry. Cause-specific mortality was categorized as death from recurrence/progression of primary disease, external causes, and non-recurrence/non-external causes (Non-Recur/Ext) (i.e., deaths from health conditions including sequelae of cancer therapy). Results: All-cause and Recurrence mortality was significantly lower in more recent eras ( Table ). No significant improvement in late mortality attributable to Non-Recur/Ext causes was seen. Additionally, all-cause mortality was significantly lower in more recent eras for 5-year survivors of ALL, AML, Hodgkin, NHL, and CNS tumors, but not neuroblastoma and Ewing's Sarcoma where an increase in cumulative incidence of late mortality was seen in more recent eras. Significant improvement in late mortality from Recurrence by era was seen in most diagnostic groups. Conclusions: All-cause late mortality has improved with more recent eras, attributable to reduced rates of mortality from progression of primary disease (i.e., durable remission). Importantly, however, efforts to reduce the toxicity of more recent therapies have not produced detectable reduction in mortality attributable to other health conditions including sequelae of cancer therapy (non-Recur/Ext causes of death), which would include death from second malignancy, cardiac and pulmonary conditions. Worsening late mortality for 5-year survivors of neuroblastoma and Ewing's sarcoma may be due to improved use of salvage therapies that delay, but do not ultimately prevent death. [Table: see text] No significant financial relationships to disclose.

Longitudinal health-related quality of life outcomes and related factors after pediatric SCT

Our purpose was to investigate longitudinally health-related quality of life (HRQOL) outcomes and related factors up to 2 years post-pediatric SCT. A total of 99 mothers of patients, aged 1.5-17 years, completed two standardized HRQOL questionnaires, generic and disease specific (DS), about the child, and reported on their own symptoms of depression and family function pre-SCT, 12 and 24 months post-SCT. Clinical (diagnosis, radiation), child (age) and family (maternal depression) information was also obtained. Significant improvement in physical and psychosocial HRQOL from pre-SCT to 1 or 2 years post-SCT was reported. Survivors of ALL were reported to have poorer physical and psychosocial HRQOL than survivors of solid tumors on the DS measure. Maternal depression was negatively associated with physical and psychosocial HRQOL. Maternal education (higher) at pre-SCT predicted improvements in physical domains 2 years post-SCT; mother's age (older) and child's age (younger) also predicted improvements of physical and emotional HRQOL. We conclude that survivors of pediatric SCT improved physical and psychosocial HRQOL by 1 and 2 years post-SCT. Older survivors whose mothers are younger and distressed, with lower education at SCT have compromised HRQOL compared to other survivors. This study has important implications for the care of SCT survivors and their families.

“Chemobrain” in Survivors of Childhood ALL?

“Chemobrain” in Survivors of Childhood ALL?

"Chemobrain" in Survivors of Childhood ALL?

"Chemobrain" in Survivors of Childhood ALL?

Obesity in adult survivors of childhood acute lymphoblastic leukemia: A follow-up report from the Childhood Cancer Survivor Study

9518 Background: We previously reported an association between ≥ 20 Gy cranial radiotherapy (CRT) and obesity in adult survivors of childhood ALL. This follow-up study aimed to determine if, with time, (1) the prevalence of obesity and (2) the rate of BMI change were increased in ALL survivors in comparison with sibling controls. Methods: A longitudinal cohort comparing 1,451 adult survivors of childhood ALL (mean age 32.3 years) to 2,167 siblings of childhood cancer survivors (mean age 35.9 years). BMI was calculated from self- reported heights and weights and used to determine the prevalence of being overweight (25.0 ≤ BMI < 30.0) or obese (BMI ≥ 30.0). Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for being overweight or obese among ALL survivors compared to sibling controls. BMIs at baseline and follow-up (with a mean interval of 7.8 years) were used to calculate mean BMI increases per year occurring between these timepoints. Results: Age- and race-adjusted ORs for obesity among survivors compared with siblings are shown in the table . Notably, 10–19 Gy CRT was associated with an increased likelihood of being obese in comparison with siblings. In longitudinal analysis, survivors who were treated with CRT had a significantly greater net increase in BMI/year in comparison with siblings. At follow-up, 69.7% of females treated with ≥ 20 Gy CRT prior to the age of 10 were overweight (31.1%) or obese (38.6%). Conclusion: Cranial radiotherapy ≥ 10 Gy employed in the treatment of childhood ALL is strongly associated among both male and female survivors with increases in the prevalence of obesity and average BMI gains over time. Female survivors who received CRT ≥ 20 Gy, particularly those treated at a younger age, were most affected. [Table: see text] No significant financial relationships to disclose.

A meta‐analysis of the neurocognitive sequelae of treatment for childhood acute lymphocytic leukemia

Impaired neurocognitive functioning is one increasingly recognized long-term consequence of childhood ALL treatment. However, research findings have been inconsistent regarding the domains affected and the degree to which they are compromised. A comprehensive meta-analytic review of the long-term neurocognitive effects of childhood ALL was conducted. Studies were included if they were published in English, reported original quantitative data on the post-treatment neurocognitive functioning of childhood ALL patients in first remission and control groups, and used neurocognitive measures with adequate psychometric properties and published normative data. Data from 28 empirical studies yielding 13 effect sizes across nine domains were extracted and analyzed. All effects were negative (g = -0.34 to -0.71), demonstrating that ALL survivors consistently experienced significant deficits in intellectual functioning, academic achievement, and specific neurocognitive abilities compared to control groups. The role of potential moderators, including treatment with cranial irradiation, age at time of diagnosis, and time since treatment ended, was examined. However, no effects emerged as clearly and consistently moderated by these variables. The results from this meta-analysis suggest that declines in both global and specific areas of areas of neurocognitive functioning occur as a result of contemporary ALL treatment. Such deficits have significant implications for survivors' academic achievement and overall quality of life. Neurocognitive assessment plays a critical role in determining what remedial or specialized instruction is needed in childhood ALL survivors and should be included as a standard part of long-term follow-up care.

Twenty Year Follow up of Survivors of Childhood Acute Lymphoid Leukemia: A Report from the Childhood Cancer Survivor Study (CCSS).

Background: Survival for ALL has improved substantially: current five-year survival rates are approximately 80% yet survivors continue to experience late medical and social effects.Objective: To report rates of mortality and second neoplasm (SN) and selected social outcomes from a large cohort of childhood ALL survivors.Methods: Five year survivors of ALL (n=4151) diagnosed < age 21, from 1970–1986 were compared to population rates or a sibling control group (n=3899) for mortality, SN, education, marriage, health insurance and employment.Results: Survivors and siblings were 53% and 48% male; median ages were 26 and 31yrs respectively. Survivors had a mean age of 6 yrs (range 0–20) at diagnosis and had a mean follow-up of 22 yrs (range 16–34). Sixty two percent received chemotherapy (CT) + radiation therapy (RT), 5.2% underwent marrow transplant with CT +/− RT, while 27% received CT only. Among 5yr survivors, 417 deaths occurred; cumulative mortality was 12% at 25 yrs. Recurrent ALL accounted for 67% of deaths, while 13% (n=55) died of SN. Standardized mortality rate (95% confidence intervals) for malignant SNs was 14.0 (10.7–17.9). Survival at 25 yrs was 94% for patients who never reported relapse and 59% for patients who reported a relapse (p<0. 001). For patients treated between 1970–1974, 1975–1979 and 1980–1986, 15-yr survival from cohort entry improved from 85% to 90% to 92%, (p< 0. 001). Improvement was seen both in non-relapsed (94%, 95% and 97% respectively, p= 0.015) and relapsed survivors (41%, 62% and 70% respectively, p< 0. 001) for the same era. 199 SNs (excluding non-melanoma skin cancer) occurred among 185 survivors; 52% occurred in the CNS. 89% of all SNs occurred in RT patients. Cumulative incidence at 25 yrs was 9% and the standardized incidence rate was 5.6 (95% CI 4.8–6.4). Age standardizing to siblings aged 25–49, rates for high school completion among survivors and siblings were 93% and 97%, respectively, with college graduation rates of 41% and 52% (p< 0.001, for education overall). 35% of survivors never married, compared to 21% siblings (p<0.001), 97% of survivors reported ever working vs. 100% of siblings (p<0.001), rate of health insurance was lower for survivors (86%) vs. siblings (90%), p<0.001. Comparison of rates for selected social outcomes among survivors who did or did not experience a recurrence are reported in Table-1.Conclusion: In the largest long-term follow-up study of its kind, the CCSS cohort demonstrated a significant improvement in survival over time among 5-yr survivors of ALL with and without history of relapse. Death after cohort entry was due most commonly to ALL, although SNs contributed substantially. HS graduation rates for survivors were comparable to the sibling cohort, but the rates were significantly lower for college graduation and for marraige. Although lower than siblings, majority of survivors reported being employed and having health insurance. There was no significant difference between the survivors of relapsed and non-relapsed ALL, with respect to their socioeconomic outcomes.Rates (percentage), Age Standardized to SiblingsSiblingNon-relapseRelapsep-value Relapse vs. NonHS grad979397College grad524141.78*Never married213446.10Ever employed1009897.07Health Insurance908688.86* p for rows 1 & 2

Psychosocial Impairment and Lower Quality of Life among Childhood Cancer Survivors in Egypt, Single Institution Experince.

Survival itself has, until recently, been the marker of successful cancer therapy, but now more attention is being focused on the long-term effects of cancer therapy and the quality of life (QOL)of the survivors.OBJECTIVE: To assess health related quality of life and behavior and emotional problems among childhood cancer survivors at Ain Shams Pediatric Oncology Clinic, Cairo, Egypt.DESIGN: This study was conducted on 30 childhood cancer survivors attending the cancer survivors' clinic at Ain Sham Children's University Hospital in the period of October 2004–April 2005. The PedsQL™ 4.0 Generic Core Scales (physical, emotional, social and, school functioning) translated into Arabic language has been utilized. Parallel child self-report and parent proxy-report questionnaire formats have been used. Items were reverse-scored and linearly transformed to a 0–100 scale, so that higher scores indicate better QOL. Assessment of behavioral and emotional disturbance was performed using The Child Behavior Checklist (CBCL)Results: Age range 6–16 years with a mean age of 10.7±2.9 years, 18 (60%) were males and 12(40%) were females. Seventeen patients (56.6%) were acute leukemia survivors and 10(43.4%) lymphomas and solid tumors. There was statistically significant (p<0.001) decrease in the overall generic PedsQL in cancer survivors (mean 67±11.6) compared to normal children (mean 83.9±12.5) with school functioning area being the most affected (score 47.5±13). ALL survivors had significantly lower mean QOL (62.5±11.8) compared to other cancer survivors (72.8±8.8) (p<0.05). Gender (females) and CNS-directed therapy were risk factors for poorer QOL. Strong agreement between parents and their children QOL rating was seen in most of the QOL domains {overall QOL (p=0.001) physical well being (p=0.04), emotional feelings (p=0.0004), and social interaction (p=0.003) with the strongest correlation in the school domain (p=0.000004)}. Fifty three percent of the survivors showed clinical range of social incompetence with survivors who were diagnosed before the age of 3 were less socially competent than those who were diagnosed after this age (p<0.05), 63% expressed Internalizing behavioral problems and while 23% had Externalizing problems.CONCLUSION: This results demonstrate Chidhood cancer survivors are at significant risk of poor psychosocial functioning and QOL.

Follow-up after childhood cancer: Evaluation of a three-level model

Introduction Follow-up for cancer survivors is recommended to detect recurrence; monitor late-effects; record toxicity and provide care and education. We describe our experience with a three-level model developed to guide decisions about intensity and frequency of follow-up [Wallace WHB, Blacklay A, Eiser C, et al. Developing strategies for the long term follow-up of survivors of childhood cancer. BMJ 2001; 323:271–274]. Procedure One hundred and ninety eight survivors (52% male) recruited over 12-months: (mean age = 23.8 years, range = 16–39 years; mean time since diagnosis = 16.2 years, range 2.4–32.7 years) reported their number of symptoms and late-effects. Information was taken from the medical records to assign each survivor to the appropriate levels by six clinic staff independently. Results The survivors were assigned to level 1 ( n = 8), level 2 ( n = 97) and level 3 ( n = 93). There were seven cases of disagreement. Level 3 survivors self-reported more symptoms and late-effects than level 2 survivors. Conclusions Coding was relatively simple for experienced clinic staff, although there were some disagreements for the survivors of ALL. The relationship between assigned level and self-reported symptoms and late-effects provides some evidence for validity of the model. We conclude that it is important to maintain flexibility to allow movement between levels for individual patients and that the default should always be to the higher level.

Growth Hormone Treatment and Quality of Life among Survivors of Childhood Cancer

Background: We report the health-related quality of life (QOL) of survivors of childhood cancer (acute lymphoblastic leukaemia, ALL, or central nervous system, CNS, tumour), and whether or not they had growth hormone deficiency (GHD) requiring growth hormone treatment (GHT). Method: We assessed 77 survivors of childhood ALL (n = 51) or CNS tumours (n = 26), aged between 8–18 years, and free from disease for ≧4 years. Survivors and their mothers independently rated survivors’ QOL, and mothers completed semi-structured interviews to determine their views of the benefits and disadvantages of GHT. Results: Survivors, especially those treated for a CNS tumour, reported poorer QOL compared with UK population norms. Although survivors of ALL reported better QOL than survivors of CNS tumours, there were no differences depending on whether or not they were prescribed GHT. However, mothers reported that those prescribed GHT had worse QOL than those not. All but 2 survivors were responsible for their own injections. A minority of mothers were disappointed with the child’s rate of growth, and reported that children experienced pain with injections. Conclusion: We conclude that QOL in survivors of childhood cancer is compromised compared with the normal population, especially following CNS tumours. Longitudinal studies are vital to determine whether GHT can contribute to improved QOL for cancer survivors, especially those who experience more intensive initial therapy regimes.

Reduction of adult height in childhood acute lymphoblastic leukemia survivors after prophylactic cranial irradiation

Impaired linear growth is a well-recognized complication in long-term childhood ALL survivors who received cranial irradiation. However, as many patients achieve a final height between the 5th and the 95th centile, the true incidence of linear growth impairment might be underestimated. Reduction of adult height (RAH) was estimated in adult childhood ALL survivors with and without cranial irradiation. RAH was calculated as the difference between target height (TH) and final height (FH). TH was calculated according to the formula TH = {[(height father + height mother +/- 12)/2] + 3}. RAH was assessed in 79 adult childhood ALL survivors in first complete remission who had received cranial irradiation 25 Gy (Group I, n = 53), 18 Gy (Group II, n = 10) or chemotherapy alone (controls, n = 16). RAH was 8.6 +/- 8.2 cm in Group I (P = 0.001 vs. controls), 6.2 +/- 3.2 cm in Group II (P = 0.01 vs. controls), and 1.7 +/- 4.6 in controls (chemotherapy only). There was no significant difference between Group I and Group II. In Group I females had more RAH than males (P = 0.02). RAH was related to younger age at diagnosis (P = 0.001). The deficit between target height and final height highlights the reduction of adult height in the majority of male and female childhood ALL survivors who had received prophylactic cranial irradiation, in particular in those who were diagnosed at a younger age. This reduction would have been masked if patients FH was only compared with standard methods. RAH might be a sensitive predictor for growth hormone deficiency as these results suggest that radiation-induced growth hormone deficiency in these patients is the rule rather than the exception.

No difference between prednisolone and dexamethasone treatment in bone mineral density and growth in long term survivors of childhood acute lymphoblastic leukemia

Dexamethasone is known to have both more potent leukemic activity and is associated with a higher incidence of side effects than prednisolone. In this study, we compared the long-term effects of dexamethasone and prednisolone on bone mineral density (BMD), body composition and growth in long-term survivors of ALL in first complete remission. Ninety patients (51 male, 49 female; 8.6-38.5 year), treated with either a prednisolone containing protocol (n = 47; n = 19 also with CNS-irradiation) or a dexamethasone containing protocol (n = 43; no cranial irradiation) participated in this cross-sectional single center study. Mean follow-up was 12.7 years (2.0-29.7 years). BMD of lumbar spine and total body, and body composition were expressed as standard deviation scores (SDS) using dual energy X-ray absorptiometry. Bone mineral apparent density of the lumbar spine (BMAD) was calculated to correct for bone size. There was no difference in height, height corrected for target height, BMD, or lean body mass between prednisolone and dexamethasone treated patients. Prednisolone treated patients had an increased percentage body fat (SDS +0.46; P < 0.05) and increased body mass index (SDS 0.88; P < 0.01) compared to normal. Dexamethasone treated patients had only an increased body mass index (SDS 0.52; P < 0.05). Height, total body BMD, and lean body mass were lower in patients treated with cranial irradiation as compared to non-irradiated patients, but differences in the latter two disappeared when corrected for height. BMAD was normal after CNS-irradiation. Long term survivors of ALL treated with prednisolone or dexamethasone containing regimens do not differ in height, BMD, or body composition.

Nouvelles approches dans le traitement des leucémies aiguës de l'enfant

The cure rate of children with acute lymphoblastic leukemia approaches 80 %. Numerous prognostic factors have been identified, based on clinical, biological and therapeutic data. The treatment can be more intensive for patients with a high risk of relapse. On the other hand, a less aggressive therapy may be administered to patients with good probability of long term survival. Prognostic factors of childhood ALL include : age, white blood cell count, cytogenetics, early response to treatment. The detection of minimal residual disease with new molecular or immunological techniques is useful to adapt the intensity of the treatment. Treatment consists of multiagent chemotherapy, with remission induction, consolidation, prevention of central nervous system relapses. For the majority of children with ALL, this treatment is based on intensive systemic therapy and methotrexate administered intrathecally. Delayed intensification has contributed to improve the outcome of childhood ALL. Continuation therapy is required in ALL, with daily administration of 6-mercaptopurine and weekly administration of methotrexate. With more and more patients who become long term survivors of childhood ALL, it is important to evaluate and to prevent the late sequelae. The outcome of patients with acute myeloid leukemia is not as successful as for patients with ALL. Treatment consists of several courses of an association of anthracyclines and aracytine. Genoidentical bone marrow transplantation in first complete remission is indicated for the majority of the patients ; ATRA has substantially improved the prognosis of patients with acute promyelocytic leukemia. The studies of gene expression profile at diagnosis of acute leukemia could improve the characterization of prognostic factors and could help to find new therapeutic targets.

Late effects in long-term survivors of ALL in childhood: experiences from the SPOG late effects study.

With the use of more intensive regimens including prophylactic CNS treatment, the prognosis of children with ALL has dramatically improved over the last three decades. The aim of this cross-sectional, nationwide study was to comprehensively assess long-term toxicity in ALL survivors, with special attention given to neuropsychological morbidity, and to look for possible differences in cognitive outcome between children having received prophylactic cranial irradiation and those not having received it. Between 1994 and 1996, long-term survivors of ALL were assessed in a multi-center setting according to a standardized protocol which included, besides usual clinical and laboratory investigations, a comprehensive endocrine work-up. Additionally, children having received anthracyclines were checked for possible late cardio-toxicity with echocardiography and ECG. Intellectual performance was evaluated with standardized neuropsychological tests (age-adapted versions of the Wechsler test). One-hundred and fifty patients were eligible for the study. The median age at diagnosis was 5 years and at evaluation 16 years, for a median follow-up of 10 years. Thirty-five patients had cranial irradiation as part of the prophylactic CNS treatment. One-hundred and forty (93%) of the 150 eligible patients were completely evaluated in terms of global long-term toxicity: 117 (83%) long-term survivors had no (n = 61) or only minimal (n = 56) late toxicity; 19 (14%) suffered from moderate impairments; 4 (3%) showed severe somatic or neuropsychological sequelae. Intellectual performance could be assessed in 147 (98%) of the 150 eligible patients. The mean global, verbal and non-verbal IQs (103, 105 and 101 respectively) of the ALL survivors as a group were comparable with those found in the general population. The results of the comparison between children having and those not having received prophylactic cranial irradiation showed: 1) significantly higher scores in chemotherapy-only treated patients, both for the global and the verbal performances; 2) significantly poorer results in specific items of the Wechsler test (short-term verbal memory, arithmetics, concentration/speed of processing) in irradiated children. These findings which show the deleterious role of cranial irradiation correlate well with many other reports found in the literature. However, they could have been influenced by the significantly longer time interval observed between therapy and evaluation in our irradiated patients. Prospective studies are needed to further characterize the potential neuropsychological hazards of chemotherapy and their evolution over time.

Late effects in long-term survivors of ALL in childhood: experiences from the SPOG late effects study.

With the use of more intensive regimens including prophylactic CNS treatment, the prognosis of children with ALL has dramatically improved over the last three decades. The aim of this cross-sectional, nationwide study was to comprehensively assess long-term toxicity in ALL survivors, with special attention given to neuropsychological morbidity, and to look for possible differences in cognitive outcome between children having received prophylactic cranial irradiation and those not having received it. Between 1994 and 1996, long-term survivors of ALL were assessed in a multi-center setting according to a standardized protocol which included, besides usual clinical and laboratory investigations, a comprehensive endocrine work-up. Additionally, children having received anthracyclines were checked for possible late cardio-toxicity with echocardiography and ECG. Intellectual performance was evaluated with standardized neuropsychological tests (age-adapted versions of the Wechsler test). One-hundred and fifty patients were eligible for the study. The median age at diagnosis was 5 years and at evaluation 16 years, for a median follow-up of 10 years. Thirty-five patients had cranial irradiation as part of the prophylactic CNS treatment. One-hundred and forty (93%) of the 150 eligible patients were completely evaluated in terms of global long-term toxicity: 117 (83%) long-term survivors had no (n = 61) or only minimal (n = 56) late toxicity; 19 (14%) suffered from moderate impairments; 4 (3%) showed severe somatic or neuropsychological sequelae. Intellectual performance could be assessed in 147 (98%) of the 150 eligible patients. The mean global, verbal and non-verbal IQs (103, 105 and 101 respectively) of the ALL survivors as a group were comparable with those found in the general population. The results of the comparison between children having and those not having received prophylactic cranial irradiation showed: 1) significantly higher scores in chemotherapy-only treated patients, both for the global and the verbal performances; 2) significantly poorer results in specific items of the Wechsler test (short-term verbal memory, arithmetics, concentration/speed of processing) in irradiated children. These findings which show the deleterious role of cranial irradiation correlate well with many other reports found in the literature. However, they could have been influenced by the significantly longer time interval observed between therapy and evaluation in our irradiated patients. Prospective studies are needed to further characterize the potential neuropsychological hazards of chemotherapy and their evolution over time.

Degree of fatness after allogeneic BMT for childhood leukaemia or lymphoma

Excess fatness is frequent after childhood ALL treated without BMT. We measured the whole-body percent fat by dual-energy X-ray absorptiometry and the body-mass index (weight/height(2) (kg/m(2)), BMI) in 25 survivors of childhood leukaemia or lymphoma (21 with ALL) who had received TBI and allogeneic BMT a median of 8 years ago (range 4-13). Adjusted for sex and age, the mean BMI was slightly but significantly reduced (0.4 s.d. below predicted) and the whole-body percent fat was significantly increased compared with healthy controls (1.1 s.d. above predicted). Eleven of 25 patients had a percent fat above the 90 percentile of the reference values, which indicates excess fatness. Adjusted for sex and age, a higher percent fat was related to additional cranial irradiation. Controlled for this, the whole-body percent fat seemed to be unrelated to age at BMT, length of follow-up, and previous chemotherapy. Compared with untransplanted ALL survivors treated with cranial irradiation, BMT survivors had significantly reduced BMI but similar whole body percent fat. BMI was a poor measure of body fatness in these patients. In conclusion, survivors of BMT for childhood leukaemia or lymphoma are adipose and slightly underweight and consequently have a substantially reduced lean body mass.

Bone mineral density, body composition, and height in long‐term survivors of acute lymphoblastic leukemia in childhood

Background Childhood leukemia has increasing numbers of survivors, so more emphasis is being placed on long-term effects. The ALL-6 protocol of the Dutch Childhood Leukemia Study Group involved high-dose dexamethasone and methotrexate and no cranial irradiation. Therefore, we studied the long-term effects on bone mineral density (BMD), body composition, and growth in survivors of nonhigh-risk ALL treated with the ALL-6 protocol. Procedure Twenty-three subjects (12.2–25.4 years) participated in this cross-sectional study. Mean follow-up was 9.6 years (range 7.9–11.4 years). BMD of lumbar spine (LS) and total body (TB) and body composition were measured by dual energy X-ray absorptiometry; results are expressed as standard deviation scores (SDS). Bone mineral apparent density (BMADLS) was calculated to correct for bone size. A question-naire was administered to determine physical activity, calcium intake, and medical history. Results Mean SDS for BMDLS, BMDTB, and BMADLS were normal. None of the subjects had BMD below −2 SDS; one subject had BMADLS below −2 SDS. Mean SDS for lean body mass, percentage fat, and height were not significantly different from zero. Calcium intake correlated positively with BMD. Nine subjects reported traumatic fractures (eight during or shortly after therapy). Conclusions Ten years after ALL-6 treatment, no long-term side effects on height, BMD, or body composition were found in this small group of patients, despite high-dose dexamethasone and methotrexate. This study suggests that ALL treatment without cranial irradiation might not be associated with long-term side effects on growth and BMD. Med. Pediatr. Oncol. 35:415–420, 2000. © 2000 Wiley-Liss, Inc.

The management of high-risk lymphoblastic leukaemia in children.

The management of high-risk lymphoblastic leukaemia in children.

Bone mass after allogeneic BMT for childhood leukaemia or lymphoma

The bone mass was measured by dual energy X-ray absorptiometry in 25 survivors of childhood leukaemia or lymphoma (21 with ALL) who had received TBI and allogeneic BMT a median of 8 years ago (range 4-13). Results were compared with local data on 463 healthy controls and 95 survivors of childhood ALL treated without BMT. Adjusted for sex and age, the mean whole-body bone mineral content (BMC) and bone mineral areal density were significantly less than in healthy controls (0.8 and 0.5 s.d. less than predicted). The reduced BMC was caused by a significantly reduced height for age, whereas bone area for height and BMC for bone area were similar to controls. Less bone mass tended to be related to additional cranial irradiation and age above 20 years at follow-up. Controlled for this, the whole-body bone mass seemed to be unrelated to previous chemotherapy and endocrine status at follow-up and tended to be only marginally less in BMT patients than in ALL survivors treated without BMT. In conclusion, 8 years after allogeneic BMT for childhood leukaemia or lymphoma, the whole-body bone mass was only slightly reduced and the size-adjusted bone mass (BMC for bone area) was normal. Bone Marrow Transplantation (2000) 25, 191-196.