Second malignant neoplasms in patients treated for childhood leukemia. A population-based cohort study from the Nordic countries. The Nordic Society of Pediatric Oncology and Hematology (NOPHO).

Among a cohort of 981 children who were followed up 4.3-26.5 years after cessation of antileukemic therapy, eight patients in remission of acute lymphoblastic leukemia (ALL) developed a distinctively new malignant disease. The second malignant neoplasms (SMN) included brain tumors, basal cell carcinomas, thyroid cancer, leiomyosarcoma and finally rhabdomyosarcoma in a patient who also had suffered from Hodgkin's disease while still on antileukemic treatment. Cranial radiation had been given to 58.4% of the patients in the study group, which consisted of 895 ALL patients who had completed various chemotherapy protocols. With one exception, the SMN appeared after 7.5-16.5 years at a location previously exposed to radiotherapy (RT). The estimated cumulative risk of SMN appearing within 20 years after diagnosis was 2.9%, and the corresponding risk for cases with RT was 8.1% compared to 0.3% for those without (p = 0.05). In a Cox regression analysis, the incidence rate ratio of SMN between patients with and without RT was 6.7 (95% CI = 0.8, 57.7). Based on age-, year- and sex-specific cancer incidence figures for Norway, the overall standardized incidence rate ratio (SIR) of SMN after treatment for ALL was 5.9 (95% CI = 2.2, 12.9). The number of brain tumors among patients who had received cranial radiation was nearly 27 times greater than expected, whereas no such tumors were seen after chemotherapy. Individuals treated for childhood ALL are at increased risk of a new malignancy, and this seems mainly to be associated with previous irradiation.     

Secondary neoplasms after radiotherapy for a childhood solid tumor

This study was conducted to determine the outcome of patients who develop a second neoplasm after radiotherapy (RT) for a childhood solid tumor. From 1956 to 1998, 429 children with a malignant solid tumor were treated at a single radiation oncology facility. The medical records and radiotherapy charts were reviewed to determine if the patient developed a secondary neoplasm after treatment for malignancy. Twenty-three (5.4%) patients developed a second neoplasm. There were 12 males and 11 females with a median age at RT of 6.6 years (range, 2 months to 20 years). There were 14 malignant neoplasms in 13 (3.0%) and 14 benign neoplasms in 11 patients (2.6%). The types of initial solid tumors treated with RT were Ewing sarcoma in 6, Wilms tumor in 6, medulloblastoma in 5, neuroblastoma in 3, and other in 3. Median RT dose was 45 Gy (range, 12.3 to 60 Gy) using 4 MV in 9, 1.25 MV in 8, 250 KV in 4, and 6 MV photons in 1 patient. One child was treated using 15-MeV electrons. Fourteen had chemotherapy. Median follow-up was 23.2 years (range, 5.3 to 44.4 years). For the 14 malignant neoplasms, the median time interval from initial tumor to second malignancy was 10.1 years. The 14 second malignant neoplasms (SMN) were osteosarcoma in 3, breast carcinoma in 2, melanoma in 2, malignant fibrous his- tiocytoma in 1, dermatofibrosarcoma in 1, leiomyosarcoma in 1, mucoepidermoid carcinoma in 1, colon cancer in 1, chronic myelogenous leukemia in 1, and basal cell carcinoma in 1. Ten of the 14 SMN (71%) were at the edge or inside the RT field. The 5- and 10-year overall survival rate after diagnosis of an SMN was 69.2%; it was 70% for children with a SMN at the edge or inside the RT field and 66.7% for those outside of the RT field. The 14 benign neoplasms appeared at a median time of 16.9 years and included cervical intraepithelial neoplasia in 3, osteochondroma in 3, thyroid adenoma in 1, duodenal adenoma in 1, lipoma in 1, cherry angioma in 1, uterine leiomyoma in 1, ovarian cystadenofibroma in 1, and giant cell tumor in 1. Only 5 (36%) of the 14 benign tumors occurred in the RT field, with osteochondroma being the most common. Of 189 deaths occurring in 429 patients, only 3 (1.6%) were secondary to radiation-induced malignancy. Not all SMN in children receiving RT occur in the irradiated field. More than two-thirds of children with a radiation-induced malignancy are alive 10 years after the diagnosis of a SMN.     

Parotid carcinoma as a second malignancy after treatment of childhood acute lymphoblastic leukemia

The occurrence of second malignant neoplasms (SMN) in children who survive their primary malignancy is a major cause for concern. Two children with diagnoses of intermediate-risk acute lymphoblastic leukemia (ALL) at 22 months and 2 years of age were treated with multiagent chemotherapy and prophylactic cranial irradiation. They experienced painless parotid swelling 6 and 7 years after successful treatment of the ALL. The patients underwent total parotidectomy, and a diagnosis of mucoepidermoid carcinoma was made. Both patients experienced transient facial nerve paresis. The incidence of SMN in children successfully treated for primary malignancies is 3% to 12%. Salivary gland tumors are being increasingly described in this setting. Long-term follow-up for survivors of childhood ALL is recommended with prompt assessment and resection of parotid swellings, particularly in children who have received cranial irradiation.     

Second malignant neoplasms following childhood Hodgkin's disease: treatment and splenectomy as risk factors

The risk of second malignant neoplasm (SMN) was evaluated in 979 children with Hodgkin's disease. This cohort was diagnosed between 1955 and 1979 at one of the institutions of the Late Effects Study Group. Solid tumors, non-lymphocytic leukemia, and non-Hodgkin's lymphoma (NHL) developed in 18, 17, and 3 patients, respectively. The estimated cumulative probability of developing any SMN was 2% at 5 years from diagnosis, 5% at 10 years, and 9% at 15 years. The incidence is ninefold greater than the risk of acquiring cancer in 19 year-olds, the median age at which the diagnosis of SMN was made in this study population. For leukemia and NHL the corresponding probabilities were 1%, 3%, and 4% for the group as a whole but were increased (2%, 6%, and 8%) in patients who had suffered one or more recurrences. In order to analyze the risk of leukemia and NHL associated with alkylating agent chemotherapy, each patient was assigned a score of one for each alkylating agent administered for a 6-month period. Scores of 2, 4, 6, and 8 were associated with probabilities of leukemia or NHL of 2%, 3%, 6%, and 10%, respectively. In a multivariate analysis for leukemia/lymphoma that included AAD score, stage, and splenectomy, the effect of AAD score and splenectomy did not change substantially compared to the univariate results. AAD score remained statistically significant (P = .0001), and splenectomy was of borderline significance (P = .09). Of the 18 solid tumor SMNs, 15 developed within the field of radiation, and one other developed in tissue irradiated 34 years earlier for hemangioma. This study of a large and unselected group of children with Hodgkin's disease who received a variety of therapies demonstrates that children are as likely as adults to develop acute leukemia after alkylating agents and solid tumors in the field of radiation therapy.     

An analysis of SEER data of increasing risk of secondary malignant neoplasms among long-term survivors of childhood brain tumors

BACKGROUND: Advances made in treatment of a childhood brain cancer have extended the lives of many children and adolescents. Treatment success, however, brings the opportunity to assess late effects; most worrying among these are secondary malignant neoplasms (SMN). Even though the cumulative incidence is quite small, long-term follow-up is required because treatment-induced cancers can occur years after initial treatment. PROCEDURE: The purpose of this project was to determine what treatments and what host characteristics of children treated for a primary brain cancer are associated with an increase in the risk of a SMN in long-term survivors. Data were analyzed from 2,056 5-year survivors, of primary brain cancer in the surveillance, epidemiology, and end results (SEER) database between 1973 and 1998. Thirty-nine patients developed a SMN. Cox regression models were used to evaluate the independent contribution of a number of risk factors. RESULTS: The most important risk factor for developing a SMN in 5-year survivors was the era in which the primary cancer was treated. Compared to treatment prior to 1979, patients treated between 1979 and 1984 had a 4.7-fold increase in risk (P = 0.001), while those treated after 1985 had a 6.7-fold increase in risk. (P = 0.002). Patients treated most recently carry the greatest risk of SMN development even after controlling for radiotherapy. This could be due to the increase in intensive treatment compared to earlier years. CONCLUSION: Although the absolute excess risk of SMN remains quite low, continued surveillance is needed to evaluate long-term effects of new therapies for primary brain tumors.     

Cutaneous angiosarcoma as a second malignant neoplasm after peripheral primitive neuroectodermal tumor

Second malignant neoplasms (SMN) in late childhood or young adulthood in individuals who have been successfully treated for an initial malignancy have emerged as a late effect of therapy in survivors of childhood cancer. Although radiation therapy is frequently implicated, chemotherapy with alkylating agents and antimetabolites has also been associated with SMN. Soft tissue sarcomas are among the most frequent primary malignancies complicated by a SMN and account for a majority of nonhematolymphoid SMN. We present the clinical and pathologic findings in a patient who had a peripheral neuroepithelioma (primitive neuroectodermal tumor, PNET) of the soft tissues diagnosed at 17 years of age, was treated with high-dose irradiation and multidrug chemotherapy, and developed an angiosarcoma 14 years later. This case represents an uncommon combination of mesenchymal malignancies in a young patient with an unusually favorable clinical course following the diagnosis of PNET. © 1992 Wiley-Liss, Inc.     

Secondary Malignant Neoplasms Following Radiotherapy for Primary Cancer in Children and Young Adults

A study was conducted to investigate secondary malignant neoplasm (SMN) occurrence following radiotherapy (RT) for cancer in children and young adults, to examine the spatial distribution of SMNs in relation to the irradiated field, and to evaluate a possible role of bystander effects in SMN distribution. Forty-two SMNs were identified among 7257 subjects diagnosed with cancer while living in Yorkshire, UK. Thirty-two of these occurred in patients receiving RT. Distances between SMN locations and RT field edge were estimated along with dose at SMN site. Expected radiation-induced SMN frequency in remote tissues receiving less than 0.1 Gy was predicted using risk estimates based on atomic bombing data. After a median follow-up period of 7.58 years, patients treated with RT were at a nearly five-fold increased risk of developing a subsequent primary neoplasm than the general population in the 0–29 years age range. The most common type of secondary malignancy associated with RT was of the central nervous system (28%), followed by sarcoma (25%) and leukemia (19%). Considering only solid SMNs developing 5 years or more from treatment, the spatial distribution showed a strong pattern of proximity to the irradiated field, with 68% occurring in-field or within 8 cm of the field edge. The SMN frequency in distant tissues receiving doses of less than 0.1 Gy was low but compatible with local absorbed dose.     

Late effects of treatment for germ cell tumors during childhood and adolescence

PURPOSE: To evaluate the long-term sequelae of treatment for malignant germ cell tumors (GCT) during childhood and adolescence. PATIENTS AND METHODS: Of 128 patients treated for GCT at St. Jude Children's Research Hospital between 1962 and 1988, 73 are long-term survivors (continuously disease-free for > or =5 years after diagnosis), with a median follow-up of 11.3 years). Survivors' ages at diagnosis ranged from birth to 18.3 years (median, 9.2 years); 64% (47 patients) were female. Initial surgical resection was followed by observation for stage I germinomas (n = 2), testicular tumors (n = 13), and selected cases of ovarian or sacrococcygeal tumors (n = 2), and by radiation therapy (RT) for patients with stage II to III germinoma (n = 8). The remaining 48 patients received postoperative chemotherapy (vincristine, dactinomycin, and cyclophosphamide [VAC] +/- doxorubicin, 1962 to 1978; VAC and/or cisplatin, vinblastine, and bleomycin [PVB], 1979 to 1988). RT was added to the chemotherapy for 21 patients. Late complications involving various organ systems and their relationship to treatment were evaluated. RESULTS: More than two-thirds of long-term survivors (n = 50) had at least 1 complication, and half (n = 38) had > 1 organ system affected. The systems most often involved included the musculoskeletal (41% of survivors), endocrine (42%), cardiovascular (16% excluding those who had only abnormal chest radiograph), gastrointestinal (25%), genitourinary tract (23%), pulmonary (19%), and neurologic (16%) systems. High-frequency hearing loss occurred in 58% (11 of 19) of patients treated with cisplatin. Musculoskeletal, gastrointestinal, and urinary tract abnormalities were most frequent in patients whose treatment included RT. CONCLUSIONS: A high frequency of late effects after treatment for pediatric GCT, particularly in patients who received RT, was demonstrated. Treatment sequelae could be anticipated from the intensity and type of therapeutic modalities. Treatment-directed screening evaluations may improve quality of life in long-term survivors of pediatric GCT through timely identification of sequelae that can be prevented or ameliorated.     

Second intracranial neoplasms following treatment of childhood acute lymphoblastic leukaemia

We report a boy with acute lymphoblastic leukaemia (ALL) treated with chemotherapy and prophylactic cranial irradiation to a dose of 24 Gy. Six years after diagnosis he developed a glioma and died. Prior to 1979, four cases of second malignant neoplasm (SMN) of the brain had been reported in children treated for ALL. These SMNs occurred within 2 years of the original diagnosis (median 1.3 years) and at least two of four patients had not received prior radiotherapy. Since 1979, 28 cases of SMN of the brain have been reported including nine of 468 (1.9%) long-term survivors in one study. All occurred more than 3.7 years from diagnosis (median 6.5 years; range 4-13 years) and all received cranial irradiation (median 24 Gy; range 20-48 Gy). These data indicate a change in the pattern of SMNs which is most likely due to the introduction of cranial irradiation. As well, the frequency of SMNs in children treated for ALL appears to have increased, although it is still no greater than the risk of SMNs developing following the treatment of any other primary childhood neoplasm.     

Hodgkin lymphoma as second malignancy during continuing chemotherapy for childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy in most parts of the world with a 5-year survival rate above 70%. Long-term survivors are at risk for treatment-related late effects and second malignant neoplasms (SMNs). SMNs occur with a mean latency of 6-6.7 years after ALL diagnosis but are rarely observed during maintenance chemotherapy (CT). Hodgkin lymphoma (HL) as a complication of ALL is very rare. We report two children with ALL who developed HL while receiving maintenance CT. Both received appropriate chemo- and radiotherapy (CT/RT) and have survived for more than10 years.     

Osteonecrosis: a treatment related toxicity in childhood acute lymphoblastic leukemia (ALL)--experiences from trial ALL-BFM 95

BACKGROUND: Osteonecrosis (ON) as a complication during treatment of acute lymphoblastic leukemia (ALL) has gained rising attention over the past decade. Corticosteroids, representing an essential element of antileukemic therapy, are known to induce ON, which in turn may cause significant morbidity. Due to spontaneous reporting of affected patients with ON, a group-wide evaluation was performed to determine incidence, risk factors, and morbidity for ON. PROCEDURE: Patients were identified via spontaneous reporting to the study center and via questionnaire, addressing all 64 participating centers. We retrospectively analyzed 1,951 patients below 18 years of age who were treated according to trial ALL-BFM 95 between 01.01.1996 and 30.06.2000. RESULTS: Thirty-one patients (14 male, 17 female) affected by ON were identified. The overall 5-year cumulative incidence for ON is 1.8%. The incidence for patients <10 years is 0.2%, whereas for patients >/=10 years it is 8.9% (P = 0.00) and 16.7% (P = 0.003) for patients >/=15 years. The majority (n = 20) showed ON in two or more joints, and the joints most commonly affected were knees (14 patients, 24 affected knees) and hips (11 patients, 20 affected joints). Thirteen out of 31 patients had to undergo surgery in the course of their disease. CONCLUSIONS: Symptomatic ON is a rare event in patients treated with BFM-type chemotherapy with an overall 5-year cumulative incidence of 1.8%. The age group >/=10 years, and particularly adolescents >/=15 years have a significantly higher risk of developing ON.     

Second malignancies in patients treated for Ewing sarcoma: A systematic review

The therapies used to treat Ewing sarcoma are associated with a risk of second malignant neoplasm (SMN). We conducted a systematic review to pool available evidence on the risks, types, and outcomes after SMN. We obtained 52 articles that met inclusion criteria. Cumulative incidence rates of SMN ranged from 0.9 to 8.4% and 10.1 to 20.5% at 5 and 30 years after initial diagnosis. Of the 327 reported SMNs, 63.6% were solid tumors, although acute myeloid leukemia /myelodysplastic syndrome was the single most commonly diagnosed SMN, with generally poor outcomes. Patients treated for Ewing sarcoma are at substantial risk of SMN, with a broad range of reported secondary cancers.     

Neoplasias malignas secundarias después de un trasplante de progenitores hematopoyéticos en edad pediátrica

Introduction

Survival after hematopoietic stem cell transplantation has improved dramatically in recent years. Unfortunately, there is an increased risk of subsequent malignant neoplasms (SMN) in this population and this represents a significant cause of late mortality.

Second malignant tumors following treatment during childhood and adolescence for cancer

Many pediatric and adolescent cancer patients are treated with carcinogenic chemotherapeutic agents and radiation therapy to achieve permanent control of their malignancy. These modalities may induce a new cancer in the successfully treated patient. To identify disease and treatment factors which increased the risk of occurrence of a second malignant tumor following modern treatment for cancer during childhood or adolescence, we reviewed the courses of 1,406 previously untreated patients who were less than 20 years of age at diagnosis and were treated at Roswell Park Cancer Institute between January 1, 1960 and December 31, 1989. Eighteen patients developed a second malignant tumor, including two meningiomas, 2.65-25.65 years after diagnosis of the first cancer. The actuarial risk of a second malignant tumor was 5.6% at 25 years after diagnosis. Using Cox proportional hazards modelling, we identified prior therapy with BCNU (P = 0.0055) and doxorubicin (P = 0.0254) as the only factors that were significantly associated with the risk of a second malignant tumor. Three second malignant tumors of the central nervous system occurred following treatment with a nitrosourea. Successfully treated patients must be carefully followed to identify treatment related malignant tumors at an early Stage. © 1994 Wiley-Liss, Inc.     

Second malignant neoplasms in childhood malignant brain tumour: A long‐term population‐based study

Aim: To provide a profile of second malignant neoplasms (SMN) in patients with childhood primary malignant brain tumour originating from neuroepithelial tissues with latest data in a population‐based study. Methods: Surveillance, Epidemiology, and End Results (SEER) database (1973–2007) was used to identify above‐stated patients. SMN patients were further identified, and standardised incidence ratios (SIRs) and excess absolute risks (EARs) for risk‐factor‐decided subgroups were calculated. Univariate and multivariate analyses of the association between cumulative incidence of SMN and the risk factors were performed in the whole population. Results: A total of 106 patients were identified as having SMNs. EARs peaked at age at primary diagnosis of 10–14. Males had higher SIRs and EARs than females. Both SIRs and EARs increased after 1990. Age was statistically significant in both univariable and multivariable analyses for cumulative incidence of SMN and RT was not significant in both the analyses, in the whole population of 9075 patients. After follow‐up recalculation, matched patients in the ≥1990 group had slightly shorter median interval between primary and secondary cancer than those in the <1990 group, but with no significance. Conclusion: The risk of SMN in children with primary malignant brain tumours in a more advanced treatment era might have changed. During making further advances in the treatment of these neoplasms, minimising toxicities while maintaining promising prognostic outcomes will keep being our goal.     

High incidence of meningioma in cranial irradiated survivors of childhood acute lymphoblastic leukemia

BACKGROUND: Most survivors of childhood acute lymphoblastic leukemia (ALL) and T-cell lymphoma (T-NHL) treated before 1990 received cranial radiation. This study assessed the occurrence of second tumors in irradiated and non-irradiated survivors. METHODS: Two hundred and ten survivors of ALL and T-NHL were treated between 1974 and 1997 by several protocols. Imaging (MRI, CT) was performed every 3-6 years in 76/88 irradiated and 74/122 non-irradiated patients for the last 20 years. RESULTS: From January 1998 through 2004, meningiomas were detected in 16 survivors (8 female, 8 male) at age 20-39 years (median 28.7); 15 were asymptomatic. Cranial imaging done 2-8 years previously in 11 revealed no abnormalities. Fifteen had been diagnosed with ALL or T-NHL 10-29 years earlier (median 21) and received cranial irradiation (24 Gy in 14) at age 2-14 years (median 7.6). Fifteen tumors arose in the convexity. Three patients had multiple lesions. Complete resection was performed in 12 patients, with one complication. One patient had a recurrence, and four with small tumors are under surveillance. Only one low-grade glioma and two basal-cell carcinomas were found. Only one of the 74 non-irradiated patients (median follow-up 14 years) developed meningioma. The Kaplan-Meier estimate of incidence of meningioma was 14.8+/-7.6 at 20 years. CONCLUSIONS: Survivors of childhood ALL treated with cranial radiation require prolonged surveillance because of a high incidence of late meningiomas. Early detection, when the tumor is still small, facilitates resection and may reduce complications.     

Nonleukaemic second malignancies following childhood acute lymphocytic leukaemia. A report of 19 cases from the Federal Republic of Germany

Nineteen second malignant neoplasms (SMN)2 occurring after successful treatment of childhood acute lymphoblastic leukaemia (ALL) are reported from the Federal Republic of Germany. Eighteen children were diagnosed as having ALL within a ten-year period, in which the total number of newly diagnosed ALL was about 5600 in this country. The incidence of a SMN following childhood ALL is calculated to be 2% after a 4-14 years' follow-up period. Of the 19 SMN, 7 are Hodgkin's disease, 1 malignant histiocytosis, 3 thyroid carcinomas, 3 brain tumours, and 5 other solid neoplasms. Second leukaemias were not observed. Immunoregulatory dysfunction, genetic influences and irradiation are the factors which have etiologically been discussed. Chemotherapy seems not to play a major role in the development of SMN after ALL.     

Intellectual development after treatment in children with acute leukemia and brain tumor

Background: The influence of central nervous system (CNS)‐directed chemotherapy on intelligence remains controversial. In this study, we investigated the influence of treatment on intellectual development in acute lymphoblastic leukemia (ALL) and brain tumor patients undergoing CNS‐directed treatments. Methods: Among patients treated in the Department of Pediatrics, St Luke's International Hospital between April 2000 and March 2009, the subjects were 38 patients with ALL or brain tumors who underwent regular Wechsler intelligence tests. Results: The subjects consisted of 26 patients with ALL and 12 with brain tumors. Prophylactic cranial irradiation was not performed in patients with ALL, whereas it was done for all those with brain tumor. In patients with ALL, the IQ 1 year later was not changed from the start of treatment. In those with brain tumors, the verbal IQ 1 year later was significantly lower than that at the start of treatment. In patients with ALL, intelligence tests were performed 3 years after the start of treatment and there were no marked changes between the two time‐points (n= 11). In those with a brain tumor, intellectual functions further decreased after the completion of treatment to as late as 5 years after the initiation of treatment (n= 7). Conclusions: There is no intellectual impairment in any patient with ALL at post‐treatment follow‐up 3 years after the start of treatment, while intelligence is serially reduced in brain tumor patients. An innovative intervention may be needed for this group of patients.     

Endothelial function in young adult survivors of childhood acute lymphoblastic leukemia

BACKGROUND: Adult survivors of childhood acute lymphoblastic leukemia (ALL) have an earlier than expected mortality from cardiovascular disease. This study examined endothelial function in 75 young (age 30.2+/-7.1 y) adult survivors of childhood ALL who received chemotherapy without cranial radiation (n=25) or chemotherapy combined with cranial radiation (n=50) compared with a healthy control group of similar sex, age, and weight (n=59). PROCEDURE: As part of a clinical follow-up study, endothelial-dependent flow-mediated dilation (FMD: % change in artery diameter after 5 min of occlusion) was assessed using high-resolution ultrasound of the brachial artery. Fifteen minutes after the measurement of FMD, sublingual nitroglycerin (0.4 mg) was administered and the brachial artery was imaged using ultrasound to assess endothelial-independent dilation (EID). All ultrasound imaging data were adjusted for baseline diameter. RESULTS: The healthy comparison group had a significantly greater FMD response (9.5%+/-2.9%) than both the chemotherapy only (6.5%+/-2.6%) and chemotherapy combined with radiation (7.1%+/-2.6%) groups. No statistical differences were observed in nitrate-mediated EID between the healthy comparison group (27.0%+/-5.0%) and the chemotherapy only (24.7%+/-6.7%) or chemotherapy combined with radiation (25.2%+/-7.1%) groups. Among the ALL survivors, female subjects had a significantly greater FMD and nitrate-mediated EID than male subjects even after correcting for baseline brachial artery diameter. CONCLUSIONS: These data suggest that young adults treated for ALL during childhood are at risk for impaired FMD regardless of whether or not they received cranial irradiation. The extent to which this mechanism relates to early development of cardiovascular disease in long-term childhood ALL survivors remains to be determined.     

Screening Survivors of Childhood Acute Lymphoblastic Leukemia for Obesity,Metabolic Syndrome,and Insulin Resistance

Acute lymphoblastic leukemia (ALL) survivors were screened for risk factors of cardiovascular disease. Forty-four ALL survivors in first remission were enrolled. Twenty-six also received 12–18 Gy cranial radiotherapy (RT). Patients’ body mass indexes (BMIs) at dignosis and during the study were compared. Metabolic syndrome (MS) evaluation was performed in patients, parents, and siblings older than 6 years. Homeostasis Model Assessment (HOMA) index of the survivors was also calculated. In survivors with impaired fasting glucose levels, oral glucose tolerance test (OGTT) was performed. Thyroid functions and IGF-1 and/or IGFBP-3 levels of the survivors who received cranial RT were evaluated. Median age of the survivors was 11.5 years (6–23). At diagnosis, mean BMI percentile was 46.7 (3–95) and mean z-score was ?0.09 ± 1.14; during the study, these values rose to 71.1 ± 25.6 (3–100) and 0.8 ± 0.94, respectively (P < .001). One patient (2.2%) and nine survivors (20%) were obese at diagnosis and during the study, respectively (P = .005). Survivors had significantly higher BMI percentile and BMI z-score compared to their siblings (P = .006 and P = .011, respectively). The study group was small and we could not show a correlation of the patients’ obesity with RT, thyroid functions, IGF-1, and IGFBP-3 levels. In three survivors (6.8%), there was MS. Maternal and paternal MS was not found as a risk factor for MS of the survivors (P = .1, P = .5, respectively). The HOMA index revealed insulin resistance (IR) in 12 (27.2%) of the survivors, whereas OGTT revealed abnormal glucose regulation and/or IR in four. As a conclusion, ALL survivors have high risk for obesity and MS.