Survivors Of Acute Leukemia Research Articles

A French Cohort of Childhood Leukemia Survivors: Impact of Hematopoietic Stem Cell Transplantation on Health Status and Quality of Life

The late effects and quality of life (QoL) in childhood acute leukemia survivors were compared between hematopoietic stem cell transplantation (HSCT) recipients and patients who underwent conventional therapy. The study included 943 patients, 256 of whom underwent HSCT (27.1%). Medical visits were conducted to detect the occurrence of physical late effects. Based on patient age, different questionnaires were used to assess QoL. To evaluate the association between HSCT and each type of late effect or QoL dimension, the appropriate multivariate regressions were performed. QoL mean scores were compared with those obtained for age- and sex-matched French control subjects. Of all the survivors, 674 (71.5%) had at least 1 late effect, with the risk being 5.0 CI95 (3.0-8.6) times higher for transplantation survivors. For child survivors, scoring of QoL showed no significant differences between the treatment groups. The adult HSCT survivors reported lower physical dimension QoL scores than chemotherapy survivors. Compared with French norms, the survivor group reported a significantly lower mental composite score; however, the physical composite score showed no significant difference. Thus, transplanted survivors have a high risk of developing late effects, resulting in a decreased physical well-being in adulthood. However, long after treatment completion, childhood leukemia survivors report that effects on psychological well-being are more important than they are in physical QoL dimensions.

Cranial radiotherapy predisposes to abdominal adiposity in survivors of childhood acute lymphocytic leukemia

BackgroundAdvances in treatment of acute lymphocytic leukemia increased the likelihood of developing late treatment-associated effects, such as abdominal adiposity, increasing the risk of cardiovascular disease in this population. Cranial radiotherapy is one of the factors that might be involved in this process. The aim of this study was to determine the effect of cranial radiotherapy on adiposity indexes in survivors of acute lymphocytic leukemia.MethodsA comparative cross-sectional study of 56 acute lymphocytic leukemia survivors, chronological age between 15 and 24 years, assigned into two groups according to the exposure to cranial radiotherapy (25 irradiated and 31 non-irradiated), assessed according to body fat (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, lipid profile, and insulin resistance.ResultsCranial radiotherapy increased body fat and abdominal adipose tissue and altered lipid panel. Yet, lipids showed no clinical relevance so far. There were significantly more obese patients among those who received cranial radiotherapy (52% irradiated versus 22.6% non-irradiated), based on dual energy X-ray absorptiometry body fat measurements. Nonetheless, no association was observed between cranial radiotherapy and body mass index, waist circumference, waist-to-height ratio or insulin resistance.ConclusionsAdolescent and young adult survivors of childhood acute lymphocytic leukemia showed an increase in body fat and an alteration of fat distribution, which were related to cranial radiotherapy. Fat compartment modifications possibly indicate a disease of adipose tissue, and cranial radiotherapy imports in this process.

From Life-Threatening Experiences to Ideas of Rescue: Coping with “Trajectories of Suffering” in Adult Acute Leukaemia Survivors

We investigated the illness records and life stories of 17 leukaemia survivors using narrative autobiographical interviews. Audio tapes were transcribed and analysed according to qualitative methodology. Using the sociological concept of “trajectory of suffering” (TOS) as a means of analysis we focused on the survivors’ mechanisms of psychosocial adaptation including integration of disease-related experiences as part of their autobiographical narration. Verbal data show how the diagnosis pulls affected people out of their everyday life from healthy, strong and with plans for the future to seriously ill, weak and facing death, and thus suspends their self-confidence and social action competence. Analysing the interview transcripts we found six categories of coping with TOS: (1) personal meaningful nourishments, (2) challenging experience with significant others, (3), courage to persevere, (4) family support, (5) dramatic family events, and (6) dreams. The results of our study demonstrate that the cancer is still a dark shadow over the lives of all survivors. They are discussed in the context of coping theory postulating creativity as an up to now underestimated resource of coping behaviour. As a consequence it seems to be vital that medical staff should recognize and discuss these individual needs and feelings of their patients in daily clinical practice.

Endocrine sequelae and metabolic syndrome in adult long-term survivors of childhood acute myeloid leukemia

This study focuses on the effect of chemotherapy on endocrinopathies and the metabolic syndrome in adult survivors of childhood acute myeloid leukemia (AML). Endocrine function and metabolic syndrome were evaluated in 12 AML survivors, treated with chemotherapy, and in 9 survivors of myeloid leukemias treated with stem cell transplantation (SCT), after a median follow-up time of 20 years (range 9–31). In survivors treated with chemotherapy, no endocrinopathies or metabolic syndrome were present, although AMH and Inhibin B levels tended to be lower than in controls. In SCT survivors, pituitary deficiencies and metabolic syndrome were more frequent.

Bone mineral density in adult survivors of childhood acute leukemia: impact of hematopoietic stem cell transplantation and other treatment modalities

Bone mineral density in adult survivors of childhood acute leukemia: impact of hematopoietic stem cell transplantation and other treatment modalities

Trends in transfusion burden among long-term survivors of childhood hematological malignancies

The risk from cumulative erythrocyte transfusions is poorly understood in oncology populations. This analysis among long-term survivors explored variation in transfusional burden over progressive eras of treatment identifying those at risk for iron overload. Transfusion records of 982 survivors of hematological malignancies treated at St. Jude were reviewed. After exclusions, 881 (90%) were assessed for cumulative volume, weight-adjusted volume and transfusion number. Treatment intensity was assigned using the Intensity of Treatment Rating Scale version 3.0 (ITR-3). Hematopoietic stem cell transplant and acute myeloid leukemia survivors had greater transfusional burden than conventional therapy recipients and acute lymphoblastic leukemia survivors, respectively. Survivors of 5–10 years were more likely than survivors of > 10 years to receive ≥ 10 transfusions (odds ratio = 2.0, 95% confidence interval 1.5–2.8). Those with higher ITR-3 scores and more recent decades of treatment had a higher transfusional burden. Comprehensive transfusion histories are useful in identifying those at highest risk for iron overload.

Endocrine Sequelae and Metabolic Syndrome in Adult Long-Term Survivors of Childhood Acute Myeloid Leukemia

AbstractAbstract 4228 Background:Survival of childhood acute myeloid leukemia (AML) has increased significantly over the past decades. Improved treatment strategies include intensive chemotherapy, by which stem cell transplantation (SCT) has been replaced in most of the current protocols for more than 80% of the cases. Limited data exist on endocrine late effects in AML survivors treated with chemotherapy only. The current study focuses on the effect of chemotherapy only on endocrine function and components of the metabolic syndrome (MetS) in adult survivors of childhood AML. Methods:In this prospective study with a cross-sectionally recruited controlgroup, endocrine function and components of the MetS were assessed in 12 AML survivors (3 females), treated with chemotherapy only, and in 9 survivors of myeloid leukemias treated with SCT, including TBI as conditioning regimen, after a median follow up time of 20 years (range 9–31). Data were compared with those of 60 controls (23 females). Results:In survivors treated with chemotherapy only no endocrinopathies were observed, although AMH and Inhibin B levels tended to be lower than in controls. In chemo-only survivors, frequency of the components of the MetS was not different from controls. In transplanted AML survivors one subject was growth hormone deficient, five had thyroid dysfunction and all survivors had gonadal dysfunction. SCT survivors had a higher risk for components of the MetS, especially a significantly higher frequency of dyslipidemia than controls (63% vs. 6%, P<0.001). Conclusion:At twenty years of follow up, survivors of AML treated with chemotherapy only did not show an increased risk at most endocrinopathies and metabolic syndrome as compared to healthy controls, which is in contrast to childhood AML survivors treated with SCT. Gonadal function should however be evaluated with care. [Display omitted] SCT: stem cell transplantation; [Display omitted] SCT: stem cell transplantation Disclosures:No relevant conflicts of interest to declare.

The Evaluation of Factors Believed to Contribute to Obesity in Acute Lymphocytic Leukemia Survivors

Background. Obesity rates for pediatric acute lymphocytic leukemia (ALL) survivors vary from 11% to 57%. Researching dietary behaviors may identify dietary risks leading to obesity and opportunities for intervention. Objective. To evaluate the relationship between caloric and macronutrient intake on the incidence of obesity in pediatric ALL. Design/setting/participants. Retrospectively reviewed data of 142 participants was examined. Participants were grouped into categories based on body mass index (BMI) for adults and Centers for Disease Control and Prevention growth charts for children. Twenty-four-hour food recall records were reviewed to assess dietary intake. Confounding factors and caloric/macronutrient intake were compared across obesity classes. Main outcome measurements. Macronutrient levels were compared between groups. Descriptive data examined. BMI at enrollment on BONEII, age at diagnosis, ethnicity, gender, corticosteroid use, cranial radiation therapy, and standard/high risk. ALL group. Results. Thirty-nine percent of participants were overweight/obese. ALL survivors who consumed a higher percentage of their calories from protein were more likely to be underweight/normal weight while participants who consumed more calories and total carbohydrates were more likely to be overweight/obese. There was no relationship with the other factors examined. Conclusion. Dietary interventions should be designed to ensure patients consume adequate amounts of protein while limiting portion sizes and carbohydrate-based snacks.

Understanding disparities in leukemia: a national study

Disparities in solid tumors have been well studied. However, disparities in hematologic malignancies have been relatively unexplored on population-based levels. The purpose of this study is to examine the relationship between race/ethnicity and acute leukemia mortality. All patients with acute leukemia [acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML)] were identified in the Surveillance Epidemiology and End Results database, 1999-2008. Kaplan-Meier curves were generated to reflect survival probabilities by race/ethnicity. Multivariable Cox proportional hazard models estimated hazard of mortality by race with adjustment for individual (age, gender, year of diagnosis) and select genetic factors. A total of 39,002 patients with acute leukemia were included in the study. Overall, there was a mortality disparity in acute leukemia for blacks (HR 1.17, p < 0.0001) and Hispanics (HR 1.13, p < 0.0001) compared with non-Hispanic whites. In stratified analysis, disparities in ALL were greater than AML; blacks (HR[ALL]1.45, p < 0.0001; HR[AML]1.12, p < 0.0011); Hispanics (HR[ALL]1.46, p < 0.0001; HR[AML]1.06, p < 0.0001). Adjustment for individual patient and select genetic factors did not explain disparities. Blacks and Hispanics suffer decreased survival in acute leukemia as compared to others. Further investigation is needed to understand the drivers of poor cancer outcomes in these populations.

Evaluating Joint Effects of Induction–Salvage Treatment Regimes on Overall Survival in Acute Leukaemia

Typical oncology practice often includes not only an initial, frontline treatment, but also subsequent treatments given if the initial treatment fails. The physician chooses a treatment at each stage based on the patient's baseline covariates and history of previous treatments and outcomes. Such sequentially adaptive medical decision-making processes are known as dynamic treatment regimes, treatment policies, or multi-stage adaptive treatment strategies. Conventional analyses in terms of frontline treatments that ignore subsequent treatments may be misleading, because they actually are an evaluation of more than front-line treatment effects on outcome. We are motivated by data from a randomized trial of four combination chemotherapies given as frontline treatments to patients with acute leukemia. Most patients in the trial also received a second-line treatment, chosen adaptively and subjectively rather than by randomization, either because the initial treatment was ineffective or the patient's cancer later recurred. We evaluate effects on overall survival time of the 16 two-stage strategies that actually were used. Our methods include a likelihood-based regression approach in which the transition times of all possible multi-stage outcome paths are modeled, and estimating equations with inverse probability of treatment weighting to correct for bias. While the two approaches give different numerical estimates of mean survival time, they lead to the same substantive conclusions when comparing the two-stage regimes.

Testing a Diathesis-Stress Model: Potential Genetic Risk Factors for Development of Distress in Context of Acute Leukemia Diagnosis and Transplant

Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animals and may be implicated in the etiology of mood-related phenotypes, specifically in the context of stressful life events. We hypothesized that this single-nucleotide polymorphism will predict the development of psychological distress among patients diagnosed with acute leukemia and preparing for hematopoietic stem cell transplant (HSCT). We also explored the relationship of other genetic factors to psychological distress, including 5HTTLPR and STin2, FKBP5, and the CRHR1 TAT haplotype. In a retrospective cohort design, 107 adult acute leukemia survivors preparing for HSCT at a major medical center completed a pre-HSCT psychological evaluation and volunteered to donate blood to the HSCT Cell and Serum Research Repository for future research studies. There was evidence of a potential association between BDNF (Val66Met) and psychological distress. More specifically, rs6265 was related to both personal mental health history (P = 0.09, 0.06 adjusted) and diagnosis of depression/adjustment disorder at time of pre-transplant evaluation (P = 0.11, 0.09 adjusted). Other genetic factors were unrelated to distress. The BDNF Val66Met polymorphism may contribute to development of depressive symptomatology in patients undergoing stressful life events, such as diagnosis of acute leukemia and preparation for HSCT. The SNPs in BDNF might be applicable in identifying patients at risk for developing psychological distress and depression in the context of coping with stressful medical conditions. Polymorphism in other genes (FKBP5, CRHR1, and 5HTT) did not show any significant relationships. Replication studies are needed with larger samples of people undergoing similar significant life stressors.

Differential effects of radiotherapy on growth and endocrine function among acute leukemia survivors: A childhood cancer survivor study report

The differential effects of cranial radiotherapy (CRT), spinal radiotherapy (SRT), and total body irradiation (TBI) on growth and endocrine outcomes have rarely been examined in combination among childhood acute leukemia survivors. Self-reported height/weight, hypothyroidism, and pregnancy/live birth were determined among acute lymphoblastic and myeloid leukemia survivors (n = 3,467) participating in the Childhood Cancer Survivor Study, an ongoing cohort study of 5-year survivors of pediatric cancers diagnosed from 1970 to 1986. Compared with no radiotherapy, risk estimates were consistent across outcomes (adult short stature, hypothyroidism, absence of pregnancy/live birth) with CRT treatment associated with 2-3-fold increased risks, TBI associated with 5-10 fold increased risks, and CRT + TBI associated with >10 fold increased risks. Exposure to any SRT further increased risk of these outcomes 2-3-fold. Changes in body composition were more nuanced as CRT only was associated with an increased risk of being overweight/obese (OR 1.6, 95% CI 1.3-1.9) whereas TBI only was associated with an increased risk of being underweight (OR 6.0, 95% CI 2.4-14.9). Although patients treated with CRT + TBI were at greatest risk for short stature, hypothyroidism, and a reduced likelihood of pregnancy/live birth, those treated with either modality alone had significantly increased risks as well, including altered body composition. Any SRT exposure further increased risk in an independent fashion.

Biomarkers and early detection of late onset anthracycline-induced cardiotoxicity in children

BackgroundThe main strategy for minimizing anthracycline cardiotoxicity is early detection of high-risk patients.Aim of the studyTo investigate the role of cardiac biomarkers; cardiac troponin T (cTnT) and N-terminal probrain natriuretic peptide (NT-pro-BNP), and tissue Doppler imaging (TDI), as early predictors of chronic cardiotoxicity in survivors of acute leukemia.Patients and methodsWe carried a retrospective study on 50 asymptomatic survivors of acute leukemia who received anthracycline in their treatment protocols. All patients underwent blood sampling to determine the levels of NT-pro-BNP and cTnT along with conventional echocardiography and TDI.ResultsNone had abnormal cTnT levels. About 20% had abnormal NT-pro-BNP levels. Diastolic dysfunction of the left ventricle was the most significant in conventional echocardiography. TDI was superior as it detected myocardial affection in 10% more than echo. TDI demonstrated global myocardial damage with significant aberrations in peak myocardial velocities and ratios.ConclusionsNT-pro-BNP can be used as a sensitive cardiac biomarker in monitoring of anthracycline-induced cardiotoxicity. Follow up is essential to validate the role of NT-pro-BNP as an early marker for late onset anthracycline-induced cardiotoxicity. Tissue Doppler is marvelous as it could detect early cardiac dysfunction even in those with normal study by conventional echocardiography.

Avaliação da qualidade de vida de sobreviventes de leucemia na infância

The progressive success of therapeutic plans for malignant neoplasias that started in childhood allowed an important increase in the survival rate of carriers during the last decades. However, late sequelae secondary to the toxicity of such plans shall be duly monitored. Considering the importance of evaluating the aspects of physical and mental health, as well as emotional and social factors of the survivors, the quality of life of the interviewed persons was evaluated by an alternative approach: telephone calls. The SF-36 questionnaire (Medical Outcomes Study 36 – Item Short Form Health Survey), validated for the Portuguese language, was applied to thirty persons with more than 18 years of age and of both sexes, survivors of acute lymphocytic leukemia, without antineoplastic therapy for at least five years, under medical attendance at the Ambulatory outside the ITACI therapy (experimental group), and also to thirty healthy persons, matched by sex and age to the experimental group (control group). Analyzed survivors scored higher in all aspects SF-36 than the average value. The average results of the total points were statistically similar to the control group. SF-36 provides valuable data for the health team to establish therapeutic procedures to survivors. Evaluation by phone became an important resource in the ambulatory follow-up of this population. Survivors of Acute Lymphocytic Leukemia are presently showing appropriate scores of quality of life.

Senfølger etter akutt lymfatisk leukemi - hva vet pasientene?

Over 80% of children with acute lymphatic leukaemia (ALL) survive, but many develop long-term effects after the therapy. The aim of the study was to reveal how much Norwegian adults treated for acute lymphatic leukaemia before the age of 16 know about the risk of long-term effects. The participants (n = 139) were recruited from a cross-sectional study (ALLBARN) of adults treated for acute lymphatic leukaemia before the age of 16 in the period 1970-2002. Their knowledge of diagnosis, treatment and long-term effects was investigated in a semi-structured interview. A median number of 23 years after treatment for acute lymphatic leukaemia, 85 (61%) of the participants were unable to give examples of possible long-term effects of cancer treatment. Reduced fertility was known to 35 participants (25%), while few were aware of the risk of heart failure (n = 3) or secondary malignancy (n = 5). Those who were aware of long-term effects usually had personal experience of the problem. However, the participants had a sound knowledge of their own diagnosis and the therapy they had been submitted to. Long-term survivors of acute lymphatic leukaemia in childhood and adolescence know little of the risk of long-term effects. The dissemination of information about the potential consequences of the therapy should be improved.

The limited screening value of insulin‐like growth factor‐i as a marker for alterations in body composition in very long‐term adult survivors of childhood cancer

The clinical relevance of low IGF-I levels, caused by cranial radiotherapy, in adult childhood cancer survivors has not been studied extensively. We evaluated whether IGF-I is a useful marker for altered body composition and growth hormone deficiency (GHD) in this group. We analyzed retrospective data from 610 adult childhood cancer survivors, retrieved from the late effects clinic. Median age at diagnosis was 6 years (interquartile range 3-11) and follow-up time was 18 years (13-24). We assessed IGF-I standard deviation scores (SDS), anthropometrical measures, growth hormone stimulation tests in patients with clinical signs of GHD, and measures of body composition (assessed by dual X-ray absorptiometry, Lunar Prodigy). In 58 cranially irradiated acute leukemia survivors (25 Gy (24-25)) and 56 locally irradiated brain tumor survivors (42 Gy (35-54)) we found significantly lower IGF-I SDS (P < 0.001), lower height SDS (P < 0.001), higher body mass index (P = 0.01), higher waist-hip ratio (WHR; P = 0.001), higher total fat percentage SDS (P < 0.001), and lower lean body mass SDS (P < 0.001), as compared to 452 not cranially irradiated survivors. IGF-I showed a weak inverse correlation with BMI (r = -0.12, P = 0.04), WHR (r = -0.15, P = 0.01), total fat percentage (r = - 0.14, P = 0.02), and a positive correlation with lean body mass (r = 0.15, P = 0.01). In patients with low IGF-I levels, IGF-I did not significantly differ between subjects with and without GHD as determined by GH-stimulation testing (P = 0.39). This study shows that IGF-I has limited value as a marker for alterations in body composition in adult childhood cancer survivors.

The Limited Screening Value of Insulin-Like Growth Factor-I in 610 Very Long Term Adult Survivors of Leukemia and Other Types of Childhood Cancer

Abstract 506▪FN2▪This icon denotes a clinically relevant abstract IntroductionOver the last decades childhood cancer survival rates have improved significantly. Currently, 70–80% of patients become long term cancer survivors. It has been estimated that 1 out of 640 young adults in the U.S. is a survivor of childhood cancer. Consequently, the incidence of late, treatment-related complications is increasing. Endocrine sequelae, such as the metabolic syndrome, osteopenia, sub fertility, thyroid dysfunction and growth hormone deficiency represent an important category of such late effects. Growth hormone deficiency (GHD) in childhood cancer survivors, mainly caused by cranial radiotherapy, is reflected by low levels of insulin like growth factor 1 (IGF-I). Whereas the value of IGF-I measurement for the diagnosis of GHD is controversial, low IGF-I levels are associated with high body mass index and high visceral fat percentage. However the clinical relevance of low IGF-I levels in long term childhood cancer survivors is not extensively studied. In this study we evaluated whether IGF-I is useful as a marker for altered body composition and growth hormone deficiency in this group. MethodsWe retrospectively analyzed data of 610 adult childhood cancer survivors, retrieved from the Rotterdam late effects clinic, which starts 5 years after cessation of therapy. Median age at diagnosis was 6 years (interquartile range (IQR) 3–11) and follow up time was 18 years (13–24). We assessed IGF-I Z-scores, anthropometrical measures, growth hormone stimulation tests in patients with clinical suspicion of GHD and measures of body composition (assessed by dual X-ray absorptiometry, Lunar Prodigy). ResultsCranial irradiated acute leukaemia survivors (25 Gy (24–25)) and locally irradiated brain tumour survivors (42 Gy (35–54)) had significantly lower IGF-I Z-scores (p<0.001), lower height SDS (p<0.001), higher body mass index (p=0.01), higher waist-hip ratio (p=0.001), higher visceral fat percentage (p<0.001), higher total fat percentage (p<0.001) and lower lean body mass (p<0.001), compared to non cranial irradiated survivors. IGF-I did not show a strong correlation with BMI (r=-0.12, p=0.04), waist hip ratio (r=-0.15, p=0.01), total fat percentage (r=-0.14, p=0.02) and lean body mass (r=0.15, p=0.01). In the patients with low IGF-I levels who had growth hormone stimulation, IGF-I Z-scores did not significantly differ between the patients with and without severe GHD (p = 0.39). ConclusionThis study shows that there is a limited value of IGF-I as marker for alterations in body composition, and confirms the fact that low IGF-I levels are not predictive for GHD, in a large cohort of childhood cancer survivors. Therefore the use of IGF-I should not be encouraged in adult childhood cancer survivors. Disclosures:No relevant conflicts of interest to declare.

Emotional Functioning and School Contentment in Adolescent Survivors of Acute Myeloid Leukemia, Infratentorial Astrocytoma, and Wilms Tumor

Purpose: Cancer in childhood may disrupt normal developmental processes and cause psychosocial problems in adolescent survivors of childhood cancers (ACCSs). Previous studies report inconsistent findings. Study aims were to assess subjective well-being (SWB), psychological distress, and school contentment in survivors of three dissimilar childhood cancers. Patients and methods: Nordic patients treated for acute myeloid leukemia (AML), infratentorial astrocytoma (IA), and Wilms tumor (WT) in childhood from 1985 to 2001, aged ≥1 year at diagnosis, and aged 13-18 years at the time of study were eligible for this questionnaire-based survey that included items on SWB, psychological distress, school contentment, self-esteem, and personality traits; 65% (151/231) responded. An age-equivalent group from a Norwegian health survey (n=7910) served as controls. Results: The median age of ACCSs was 16 years; 52% were males. ACCSs reported better SWB (p=0.004) and self-esteem (p<0.001). They had fewer social problems in school (p=0.004) and their school contentment tended to be higher than controls. SWB and school contentment were positively influenced by self-esteem. However, ACCSs reported higher levels of psychological distress (p=0.002), mostly attributable to general worrying. No significant differences in outcomes were found across diagnoses, and time since diagnosis did not significantly affect the results. Conclusion: The overall emotional functioning of ACCSs was good, possibly due to changes in their perception of well-being after having survived a life-threatening disease. However, they seemed more worried than their peers. This may cause an additional strain at a vulnerable period in life.

Bone mineral density in adult survivors of childhood acute leukemia: impact of hematopoietic stem cell transplantation and other treatment modalities

AbstractFemoral and lumbar bone mineral densities (BMDs) were measured in 159 adults enrolled in the Leucémies de l'Enfant et de l'Adolescent program, a French prospective multicentric cohort of childhood leukemia survivors. BMDs were expressed as Z-scores, and multivariate linear regression analyses were used to construct association models with potential risk factors. Mean age at evaluation and follow-up was 23 and 14.7 years, respectively. In the whole cohort, mean femoral Z-score was −0.19 ± 0.08. Two factors were associated with lower femoral BMD transplantation (−0.49 ± 0.15 vs −0.04 ± 0.10 in the chemotherapy group; P = .006) and female sex (−0.34 ± 0.10 vs −0.03 ± 0.13; P = .03). Among patients who received a transplant, the only significant risk factor was hypogonadism (−0.88 ± 0.16 vs −0.10 ± 0.23; P = .04). A slight reduction in lumbar BMD (mean Z-score, −0.37 ± 0.08) was detected in the whole cohort without difference between the transplantation and chemotherapy groups. Among patients who received a transplant, younger age at transplantation was correlated with a low lumbar BMD (P = .03). We conclude that adults who had received only chemotherapy for childhood leukemia have a slight reduction in their lumbar BMD and a normal femoral BMD. Patients who received a transplant with gonadal deficiency have a reduced femoral BMD which might increase the fracture risk later in life.

Leukemia-free survival as a surrogate end point for overall survival in the evaluation of maintenance therapy for patients with acute myeloid leukemia in complete remission

In trials designed to evaluate new therapies for hematologic malignancies, end points such as leukemia-free survival are often used as surrogates for overall survival in acute leukemia. We aimed to assess whether leukemia-free survival is an acceptable statistical surrogate for overall survival when applied to remission maintenance therapy for acute myeloid leukemia. Data were analyzed from a randomized Phase III trial of remission maintenance immunotherapy with histamine dihydrochloride plus low-dose interleukin-2 versus no treatment in adults with acute myeloid leukemia. A two-stage surrogate validation model was applied in which correlations between Kaplan-Meier estimates of leukemia-free survival and overall survival, and between log hazard ratios reflecting treatment effects were analyzed. Country of patient enrollment was the unit of analysis. Kaplan-Meier estimates of overall survival at 36, 48, and 60 months and leukemia-free survival at 24 months were reasonably correlated (R(2) ranging from 0.44 to 0.84) both for the overall (n=320) and first complete remission (n=261) populations. The effects of histamine dihydrochloride/interleukin-2 on log hazard ratios for leukemia-free survival and overall survival were well correlated (R(2)=0.88-0.93). The significant correlations between overall survival and the surrogate end point (leukemia-free survival) and between the effect of histamine dihydrochloride/interleukin-2 on leukemia-free survival and overall survival satisfy the two-stage surrogate validation model.