Treatment Of Childhood Acute Leukemia Research Articles

Late Adverse Effects after Treatment for Childhood Acute Leukemia

The aim of this review is to raise awareness and knowledge among healthcare professionals and policymakers about late adverse effects in survivors of childhood leukemia. With contemporary treatment, over 90% of children with acute lymphoblastic leukemia (ALL) and over 60% with acute myeloid leukemia (AML) are cured. Large cohort studies demonstrate that 20% of ALL and most AML survivors have at least one chronic health condition by 20-25 years after diagnosis. These are life-changing or threatening in some survivors and contribute to increased premature mortality. We describe the frequency, causes, clinical features, and natural history of the most frequent and severe late adverse effects in childhood leukemia survivors, including subsequent malignant neoplasms, metabolic toxicity, gonadotoxicity and impaired fertility, endocrinopathy and growth disturbances, bone toxicity, central and peripheral neurotoxicity, cardiotoxicity, psychosocial late effects, accelerated ageing and late mortality. The wide range of late effects in survivors of haemopoietic stem cell transplant is highlighted. Recent developments informing the approach to long-term survivorship care are discussed, including electronic personalized patient-specific treatment summaries and care plans such as the Survivor Passport (SurPass), surveillance guidelines and models of care. The importance of ongoing vigilance is stressed given the increasing use of novel targeted drugs with limited experience of long-term outcomes. Conclusion. It is vital to raise awareness of the existence and severity of late effects of childhood leukemia therapy among parents, patients, health professionals, and policymakers. Structured long-term surveillance recommendations are necessary to standardize follow-up care.

Markers of intestinal mucositis to predict blood stream infections at the onset of fever during treatment for childhood acute leukemia.

Despite chemotherapy-induced intestinal mucositis being a main risk factor for blood stream infections (BSIs), no studies have investigated mucositis severity to predict BSI at fever onset during acute leukemia treatment. This study prospectively evaluated intestinal mucositis severity in 85 children with acute leukemia, representing 242 febrile episodes (122 with concurrent neutropenia) by measuring plasma levels of citrulline (reflecting enterocyte loss), regenerating islet-derived-protein 3α (REG3α, an intestinal antimicrobial peptide) and CCL20 (a mucosal immune regulatory chemokine) along with the general neutrophil chemo-attractants CXCL1 and CXCL8 at fever onset. BSI was documented in 14% of all febrile episodes and in 20% of the neutropenic febrile episodes. In age-, sex-, diagnosis- and neutrophil count-adjusted analyses, decreasing citrulline levels and increasing REG3α and CCL20 levels were independently associated with increased odds of BSI (OR = 1.6, 1.5 and 1.7 per halving/doubling, all p < 0.05). Additionally, higher CXCL1 and CXCL8 levels increased the odds of BSI (OR = 1.8 and 1.7 per doubling, all p < 0.0001). All three chemokines showed improved diagnostic accuracy compared to C-reactive protein and procalcitonin. These findings underline the importance of disrupted intestinal integrity as a main risk factor for BSI and suggest that objective markers for monitoring mucositis severity may help predicting BSI at fever onset.

Oral–visceral iatrogenic Kaposi sarcoma following treatment for acute lymphoblastic leukemia: a case report and review of the literature

BackgroundThere have hardly been any reported cases of children presenting with Kaposi sarcoma as a second malignancy following treatment for acute lymphoblastic leukemia outside a transplant setting.Case presentationWe report a case of a 5-year-old boy of Bantu origin, which, to our knowledge, could be only the second reported case of oral–visceral Kaposi sarcoma after acute lymphoblastic leukemia treatment. The patient presented with a 1-month history of progressive, non-painful, soft tissue oral mass, 1 month after completing treatment for high-risk acute lymphoblastic leukemia. He was successfully treated for Kaposi sarcoma on a two-drug regimen (bleomycin and vincristine) with good clinical response.ConclusionVisceral Kaposi sarcoma as a second malignancy may occur after pediatric acute lymphoblastic leukemia treatment, but its rarity makes it unlikely to raise suspicion among clinicians, thus precluding early diagnosis and treatment. We recommend routine evaluation for Kaposi sarcoma lesions in children undergoing long-term surveillance following treatment for childhood acute leukemia.

Clinical, laboratory features and some genetic abnormalities in childhood acute leukemia at Hue Central Hospital, Viet Nam

Background: Acute leukemia is the most common malignant disease in children. Some genetic abnormalities have been recognized to have prognostic or therapeutic relevance. Objective: To analyze the clinical presentations, laboratory features, and genetic abnormalities in childhood acute leukemia patients. Materials and methods: It was a descriptive cross-sectional study on childhood acute leukemia patients who admitted to the hospital between November, 2017 and May-2022. Results: There were 83 new patients with acute lymphoblastic leukemia (ALL) (70.3%) and 35 patients with acute myeloid leukemia (AML) (29.7%), the ratio of male to female was 1.51:1. The median age was 5.8 ± 4.0 years. The most common symptoms were anemia (87.3%), hepatomegaly (48.3%), enlarged lymph nodes (44.9%), fever (44.9%), splenomegaly (41.5%), bleeding (39.8%) and bone pain (21.2%). Regarding laboratory features, white blood cell (WBC) median is 12.3x109/l, there is 28.8% of the patients with WBC ≥ 50x109/l. Platelet (PLT) median is 43,5x109/l, there is 75.4% patients with PLT &lt;100x109/l. Hemoglobin (Hb) mean is 8.0 ± 2.3 g/dl, there is 78.9% patients with Hb &lt; 10 g/dl. In ALL, genetic analysis showed that 18.1% patients have NUDT15 polymorphism, 6.9% patients have TPMT polymorphism, 12.1% patients have TEL/AML1, 4.8% patients with BCR/ABL1, 2.4% patients with MLL/AF4, 3.6% patients with E2A/PBX1 and 1.2% patient with SET/NUP214. In AML, the percentage of AML1/ETO, AML1/ETO+BCR/ABL1, PML/RARA, MLL/AF6 and KMT2A/MLLT10 were 14.2%, 2,9%, 8.6%, 5.7% and 2.9% respectively. Conclusions: The most common clinical presentations were anemia, hepatosplenomegaly, fever, enlarged lymph nodes, bleeding and bone pain. Some genetic abnormalities help classification, prognosis and treatment for childhood acute leukemia. Key words: Acute leukemia, children, genetic abnormalities.

Clinical value of the quantitation of average daily platelet increase during the recovery period in childhood acute lymphoblastic leukaemia

The time to platelet recovery (TPR) is becoming a predicting factor during the treatment of childhood acute leukaemia. However, the initial pre-treatment platelet count (PPC) could interfere with TPR. Here, we integrated both TPR and PPC as the average daily platelet amount increase (Ap) to predict the prognosis in childhood B-ALL during the recovery period.148 patients were enrolled. The relationship between the Ap and MRD was evaluated, and Multivariate analysis was performed to evaluate whether Ap was independently associated with a better EFS. The PPC was inversely correlated with TPR (rs = −0.519, P = 0.021). Patients in Ap >3.9 × 109/L group had better EFS (x2 = 3.109, P = 0.028) than TPR ≤ 16d. Multivariate analysis indicated that Ap > 3.9 × 109/L was independently associated with a longer EFS (RR = 3.468; 95%CI: 1.037–11.597, P = 0.043). However, when introducing both MRD and Ap > 3.9 × 109/L as candidate variables, the Ap > 3.9 × 109/L lost its independent effect (P = 0.081). The strong association between MRD on treatment day 33 and Ap > 3.9 × 109/L (x2 = 148.00, P = 0.000) was responsible for this phenomenon. Ap could be a valuable prognostic indicator in childhood B-ALL.

The pheno-genotypic characteristics of infantile acute leukemia in a regional cancer center from South India

Introduction: Acute leukemia (AL) is uncommon in infants, with an annual incidence of 30 per million live births. They have peculiar biological characteristics. Although remarkable progress is seen in treatment of childhood AL, infantile AL remains a resistant subset with a dismally low 4-year survival of 35%. Objectives: To study the morphological, immunophenotypic, and cytogenetic features of infantile AL. A retrospective study of AL cases in children from birth up to 1 year of age, presenting to the departments of pediatric oncology and hematopathology between January 2010 and April 2015, was conducted. Results: Thirty-eight cases of infantile AL were included. The mean age at presentation was 10.2 months, and a female preponderance (M–F ratio: 0.65:1) was noted. Hyperleukocytosis (total white cell count >50 × 109/mm3) was seen in 13 (39.4%) cases. Immunophenotyping done in 31 cases showed pre-B acute lymphoblastic leukemia (B ALL) in 18 (58%), pre-T ALL in three (9.7%), and acute myeloid leukemia (AML) in 10 (32.3%). CD10 positivity was seen in 12 (57.1%) cases of ALL. Cytogenetic study done in 34 cases showed AML with recurrent genetic abnormalities in four. Mixed lineage leukemia (11q23) abnormality was seen in three cases of ALL. Two cases of AML were associated with trisomy 21. One case with features of AML M7 in a 4-day-old baby turned out to be transient abnormal myelopoiesis on follow-up. Conclusion: Literature on infantile AL from Indian studies is scarce compared to the available Western literature. Hence an epidemiological study of AL cases was done with review of literature, in an attempt to understand their pheno-genotypic features that influence their behavior. This may help in standardizing the treatment of these rare cases.

Novel agents for the treatment of childhood acute leukemia.

Together, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) make up approximately one-third of all pediatric cancer diagnoses. Despite remarkable improvement in the treatment outcomes of these diseases over the past several decades, the prognosis for certain high-risk groups of leukemia and for relapsed disease remains poor. However, recent insights into different types of 'driver' lesions of leukemogenesis, such as the aberrant activation of signaling pathways and various epigenetic modifications, have led to the discovery of novel agents that specifically target the mechanism of transformation. In parallel, emerging approaches in cancer immunotherapy have led to newer therapies that can exploit and harness cytotoxic immunity directed against malignant cells. This review details the rationale and implementation of recent and specifically targeted therapies in acute pediatric leukemia. Topics covered include the inhibition of critical cell signaling pathways [BCR-ABL, FMS-like tyrosine kinase 3 (FLT3), mammalian target of rapamycin (mTOR), and Janus-associated kinase (JAK)], proteasome inhibition, inhibition of epigenetic regulators of gene expression [DNA methyltransferase (DNMT) inhibitors, histone deacetylase (HDAC) inhibitors, and disruptor of telomeric signaling-1 (DOT1L) inhibitors], monoclonal antibodies and immunoconjugated toxins, bispecific T-cell engaging (BiTE) antibodies, and chimeric antigen receptor-modified (CAR) T cells.

Diet, Physical Activity, and Body Composition Changes During the First Year of Treatment for Childhood Acute Leukemia and Lymphoma

Children who undergo treatment for childhood acute lymphoblastic leukemia (ALL) and lymphoma are at risk for several long-term health problems. Obesity, for which survivors of ALL and lymphoma are also at risk, may further exacerbate these problems. This pilot study evaluates changes in physical activity and body composition among children being treated for ALL and lymphoma and their parents. Recently diagnosed adolescent ALL and lymphoma patients were recruited from 2 pediatric hematology and oncology clinics, and matched on age, race, and sex to healthy individuals in the community. Changes in diet, physical activity, and body composition were collected at baseline, 6, and 12 months. All children (n=15) were, on average, 10.3 years of age at enrollment, and were fairly evenly distributed with regard to sex. Analyses revealed a significant difference between cases and controls with respect to the change in body mass index from baseline to 12 months (P=0.01). In addition, controls demonstrated a significantly greater increase in moderate-vigorous physical activity than the cases [229.8 metabolic equivalent of tasks (METs) vs. 23.5 METs]; indicating cases remained fairly inactive over the course of treatment. Our data corroborate previous findings that following treatment for ALL and lymphoma, childhood cancer survivors tend to be less active and at greater risk for obesity than their healthy peers. The present study, which assessed cases prospectively over a 12-month period during the early phases of treatment, extends prior reports by demonstrating that these outcomes are evident at an early stage in treatment.

Aurora Kinases in Childhood Acute Leukemia: The Promise of Aurora Kinase B As Drugable Target

Abstract 1476 AIM:Aurora kinases (AURK) A and B are known regulators of mitosis and are overexpressed in a large number of human cancers, including leukemia. Several AURK-inhibitors have shown anti-tumor activity in vitro and in vivo. However, the efficacy of AURK inhibition in the treatment of childhood acute leukemia is unexplored. We therefore investigated the effect of targeting AURKA and AURKB in leukemic cells of children with newly diagnosed acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Materials & Methods:Affymetrix gene expression data of 297 ALL, 237 AML and 8 normal bone marrow (nBM) samples were analyzed for AURKA and B mRNA expression levels. Protein expression levels in 172 pediatric ALL and 10 nBM samples were determined with a reverse phase protein array. Functional studies were performed in ALL and AML cell lines, in which AURKA and B were silenced using a short hairpin RNA with a lentiviral delivery system or LNA-containing oligonucleotides. Sensitivity of leukemic cell lines to the AURKB-selective inhibitor Barasertib-hQPA (AZD1152-hQPA) was tested in vitro with an MTS assay. Results:AURKA and B mRNA levels were low in ALL and AML patients. In contrast, Aurora A and B proteins were expressed to a greater extent in patients (p<0.0002), especially in ALL cases with an E2A-PBX1 translocation (p<0.0001) than in nBM mononuclear cells. Silencing of AURKA by shRNA and by LNA-oligonucleotide caused no or only minor growth delay in several cell lines reflecting genetic subtypes typically found in pediatric ALL and AML. In contrast, silencing of AURKB resulted in proliferation arrest and apoptosis in these cells. Furthermore, 18 out of 20 ALL and AML cell lines tested were highly sensitive to the AURKB-selective inhibitor Barasertib-hQPA in the nanomolar range (IC50 = 19–233 nM) whereas less sensitivity was seen for other inhibitors. Conclusion:These data show that inhibition of AURKB but not AURKA has an anti-proliferative and pro-apoptotic effect on acute leukemic cells. Thus, targeting Aurora Kinase B may offer a new strategy to treat pediatric ALL and AML. Disclosures:No relevant conflicts of interest to declare.

Pre-screening and follow-up of childhood acute leukemia using biochemical infrared analysis of peripheral blood mononuclear cells

BackgroundRecent advances in chemotherapeutic treatment of childhood acute leukemia have improved remission rates to about 80%. With the development of novel drugs and treatment protocols adapted for specific individual patients, a simple diagnostic tool for following patients' responses on a daily basis is required. In the present clinical study, we have investigated the usefulness of Fourier transform infrared microscopy (FTIR-MSP) for pre-screening and follow-up of leukemia patients undergoing chemotherapy. MethodsBlood samples were collected from leukemia patients before and during treatment as well as from patients with high fever and healthy subjects which served as control groups. Peripheral blood mononuclear cells (PBMCs) were isolated and their spectra obtained using FTIR-MSP. The presence of blasts in bone marrow and other diagnostic and prognostic clinical parameters were determined during follow-up up to 1000days. ResultsLeukemia was efficiently indicated by a reduced lipids and elevated DNA absorption of PBMC together with additional characteristic spectral bands. These diagnostic markers were used for monitoring the biochemical changes in PBMCs during chemotherapy. The trends of several markers were found to be in agreement with blast percentage as determined by flow cytometry. ConclusionsOur findings reveal the utility of FTIR-MSP for leukemia pre-screening independently of symptoms common to leukemia. Furthermore, FTIR-MSP supplies precursor indication regarding patient response to treatment compared to current methods. General significanceThis preliminary study shows a great potential of FTIR-MSP as a complementary tool for childhood leukemia pre-screening and follow-up which may allow faster response to critical problems arise during treatment.

How new advances in genetic analysis are influencing the understanding and treatment of childhood acute leukemia

This review describes the recent advances in genomic profiling that have provided critical new insights into the biology of acute leukemia in children. Acute leukemia genomes commonly harbor submicroscopic gains and deletions of DNA which target key cellular pathways that influence leukemogenesis and the likelihood of treatment failure, particularly in acute lymphoblastic leukemia (ALL). Notably, genetic alterations targeting transcriptional regulators of lymphoid development are a hallmark of B-progenitor ALL, and alteration of specific genes in this pathway, such as IKZF1 (encoding IKAROS), are associated with high-risk ALL. Integrated genomic profiling has identified potential therapeutic targets in ALL, including aberrant cytokine receptor signaling mediated by rearrangements and mutation of CRLF2 and JAK2. Genome-wide association studies are also providing important insights into the role of inherited genetic variation and susceptibility to ALL. In contrast, genomic profiling of acute myeloid leukemia (AML) has thus far yielded fewer insights, but ongoing resequencing of leukemia genomes is uncovering novel mutations in both ALL and AML. Genomic profiling has identified important new genetic lesions that contribute to leukemogenesis. These findings will have important implications for the development of new diagnostic tests and treatment approaches in high-risk leukemia. Future studies will be increasingly reliant on comprehensive genomic sequencing to reveal the spectrum of genetic alterations in this disease, with the ultimate aim of improving the treatment outcome for leukemia patients.

Late Effects in Long-Term Survivors After Treatment for Childhood Acute Leukemia

Late Effects in Long-Term Survivors After Treatment for Childhood Acute Leukemia

Novel targeted drug therapies for the treatment of childhood acute leukemia

The cure rates for childhood acute leukemia have dramatically improved to approximately 70% overal, with treatments that include intensive cytotoxic chemotherapy and, in some cases, hematopoietic stem cell transplantation. However, many children still die of their disease or of treatment-related toxicities. Even in patients that are cured, there can be significant and, not uncommonly debilitating, acute and late complications of treatment. Improved understanding of the molecular and cellular biology of leukemia and the increasing availability of high-throughput genomic techniques have facilitated the development of molecularly targeted therapies that have the potential to be more effective and less toxic than the standard approaches. In this article, we review the progress to date with agents that are showing promise in the treatment of childhood acute leukemia, including monoclonal antibodies, inhibitors of kinases and other signaling molecules (e.g., BCR–ABL, FLT3, farnesyltransferase, mTOR and γ-secretase), agents that target epigenetic regulation of gene expression (DNA methyltransferase inhibitors and histone deacetylase inhibitors) and proteasome inhibitors. For the specific agents in each of these classes, we summarize the published preclinical data and the clinical trials that have been completed, are in progress or are being planned for children with acute leukemia. Finally, we discuss potential challenges to the success of molecularly targeted therapy, including proper target identification, adequate targeting of leukemia stem cells, developing synergistic and tolerable combinations of agents and designing adequately powered clinical trials to test efficacy in molecularly defined subsets of patients.

Late Effects in Long-Term Survivors After Treatment for Childhood Acute Leukemia

This is a report of late effects in childhood cancer survivors seen in the follow-up clinic of a single institution. There were 324 acute leukemia survivors in the database of the Long Term Follow Up Clinic of Children's National Medical Center from January 1, 1997, through June 30, 2005. Of the 324 acute leukemia survivors, 228 were white, 48 black, 20 Hispanic, and 12 other. Their follow-up time was 0 to 25 years (mean 5.3 years). One or more adverse events occurred in 74.1% of the 324 survivors. Defective physical growth was most commonly reported, followed by disturbed neurocognitive function, emotional difficulties, cardiac abnormalities, hypertension, osteoporosis/osteopenia, fractures, and second neoplasms. More black and Hispanic children had acute myeloid leukemia, relapses, cardiac problems, and hypertension than white and other subjects. Childhood cancer survivors require lifelong monitoring, with prompt identification and treatment of adverse late effects.

Relationship between the expression of the genes encoding the key enzymes for cytarabine metabolism and the pharmacokinetics of cytarabine in the treatment of childhood acute leukemia with high-dose cytarabine

It has been reported that high-dose cytarabine (HD-AraC) was very effective for childhood hematological malignancies, especially for improving the long-term survival of high-risk acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and T-cell lymphoid malignancies (T-ALL, T-cell non-Hodgkin's lymphoma). This study aimed to evaluate the pharmacokinetics of HD-AraC for childhood hematological malignancies, and the relationship between the expression of the genes coding the key enzymes for Ara-C metabolism with the outcome of the patients. The drug levels of Ara-C in plasma and cerebrospinal fluid were detected with HPLC while HD-AraC was used, the expression of deoxycytidine kinase (dCK) and cytidine deaminase (CDA) mRNA in human leukemia cell lines and the bone marrow cells were investigated in 48 cases of childhood hematological malignancies with RT-PCR methods, and the relationship between the expression of these enzymes mRNA and the outcome of the patients was analyzed. (1) When HD-AraC was used, the plasma levels of Ara-C and Ara-U could be respectively about 50 times and 25 times higher than those obtained when the patients were treated with regular dose of Ara-C treatment, and the level of Ara-C in cerebrospinal fluid could reach about 10% of plasma level of Ara-C. (2) There were significantly different expressions of dCK mRNA in different childhood acute leukemia (AL) patients, which were markedly related to the chemotherapy results. The expression of dCK in ALL was much higher than that in AML and relapsed AL cases. There were no significant differences in expressions of dCK in T-ALL and B lineage ALL. (3) In vitro study found that the expressions of dCK and CDA mRNA did not change in leukemia cell lines incubated at different doses and times of Ara-C. HD-AraC was a very effective protocol for childhood hematological malignancies for it could significantly elevate the plasma and cerebrospinal fluid drug levels. The expression of dCK may be an important factor in predicting the long-term outcomes of children with hematological malignancies. Good long-term outcomes of the childhood T-ALL could be achieved as the B lineage ALL had been treated with HD-AraC regimen. As the expression levels of dCK were much lower, it may be necessary for the treatment of AML with HD-AraC for consecutive three days.

In Vivo Models of Childhood Leukemia for Preclinical Drug Testing

The number of new anti-cancer drugs emerging for clinical trials in humans far exceeds the availability of pediatric acute leukemia patients to be entered into clinical trials. Therefore, preclinical testing of new agents for the treatment of childhood acute leukemia is essential to ensure that the most promising drugs are prioritized to enter clinical trials. Historically, the murine system has been central to modeling human leukemia in vivo. A greater knowledge of the molecular lesions underlying particular subtypes of leukemia has led to the generation of genetically engineered murine models, generally involving the knockin or knockout of certain genes and fusion genes at their normal genetic locus. However, the most predominant in vivo models for preclinical drug testing have been human leukemia xenografts. Successful engraftment of all subtypes of acute lymphoblastic leukemia, most subtypes of acute myeloid leukemia as well as juvenile myelomonocytic leukemia, chronic myeloid leukemia and chronic lymphocytic leukemia have been described in various immune-deficient murine hosts. Preclinical testing of novel therapeutics in vivo will likely identify the most promising new agents to enter clinical trials, and will allow their future use to be optimized in combination with other novel and conventional chemotherapeutics.

Inv(11)(q21q23) Fuses MLL to the NOTCH Co-Activator Mastermind-Like 2 in Secondary T Cell Acute Lymphoblastic Leukemia.

Development of a secondary leukemia after chemotherapeutic treatment for childhood acute leukemia is associated with rearrangements of the MLL gene on chromosome 11q23 and characteristically results in acute myeloid leukemia (AML). We identified the NOTCH co-activator Mastermind-like 2 as MLL fusion partner in two cases of pediatric secondary leukemia. The MLL-MAML2 fusion results from a cryptic inv(11)(q21q23) only detectable by interphase fluorescence in situ hybridization with an MLL split signal probe. With a latency of twenty months and five years after initial diagnosis for MLL negative AML and precursor B acute lymphoblastic leukemia (ALL), respectively, both patients developed a therapy-related T-cell acute lymphoblastic leukemia.MAML2 is the first MLL fusion partner involved in human Notch-signaling and was only recently identified as recurrent translocation fusion partner in a subset of salivary gland tumors. The genomic MLL breakpoint shows similar localization and sequence features described for etoposide induced treatment-related AML. MLL-MAML2 positive cells were detectable up to two years prior to clinical apparent secondary leukemia in one case. The discrepant dynamics of clone expansion quantified by either the genomic fusion sequence or Ig/TCR gene rearrangements as clone specific markers suggests a selection process within the inversion positive population and the need for additional mutation events to promote overt leukemic disease. Whole genome expression profiles demonstrated differential expression of both typical MLL and NOTCH downstream genes, which suggests a modulatory role of the MAML2 transcriptional activation domain in MLL leukemogenesis and lineage assignment induced by the MLL-MAML2 fusion protein.MSM21620813WSF3401600.

Medical follow‐up visits in adults 5–25 years after treatment for childhood acute leukaemia, lymphoma or Wilms’ tumour

One aspect of organizing medical follow-up for adult survivors of childhood cancer is to determine to what extent the former patient experiences a need for health services. In the present paper, we studied how the healthcare needs, both subjectively and objectively, were fulfilled for our former patients. 335 survivors over 18 y of age, with a follow-up time of more than 5 y after completion of therapy, were sent a questionnaire probing their present use of health services. The response rate was 73%. A majority (60%) of the survivors had no regular follow-up visits, and 42% of these reported that they missed not having one. More than one third were thus far dissatisfied with the follow-up programme. Only 3% of those who had regular follow-ups found them "unnecessary". Complaints subjectively related to their diseases or treatments were reported by 47%. Out of all responders, 34% did not miss having regular follow-up visits. Neither perceived disease-related complaints nor radiation therapy was a predictor for having a scheduled follow-up visit. In the absence of a long-term follow-up programme, many survivors were not receiving proper medical healthcare, whether from their perspective or from a professional one.

Use of radiolabeled antibodies in the treatment of childhood acute leukemia.

Despite advances in therapy for acute leukemia, relapse continues to be the major cause of treatment failure. Hematopoietic stem cell transplant can rescue some patients after relapse, but the ability to escalate the intensity of preparative regimens is limited by toxicity to normal organs. Radiolabeled monoclonal antibodies against hematopoietic antigens have emerged as an alternative to deliver targeted supplemental radiation to sites of leukemic involvement while relatively sparing normal organs. This paper will review the rationale for using this approach, our current experience with radiolabeled anti-CD45 antibody, and the potential challenges encountered in treating children with radiolabeled antibodies.

OLFACTORY NEUROBLASTOMA AS A SECOND MALIGNANT NEOPLASM IN A PATIENT PREVIOUSLY TREATED FOR CHILDHOOD ACUTE LEUKEMIA

Various kinds of second malignant neoplasms after successful treatment for childhood acute leukemia have been reported. The authors describe an unusual case of an olfactory neuroblastoma in a patient previously treated for childhood acute leukemia including autologous bone marrow transplantation. The prophylactic cranial irradiation and the total body irradiation during autologous bone marrow transplantation may have induced the development of their patient's olfactory neuroblastoma. Although a second primary olfactory neuroblastoma is rare, it should be added to the list of second malignant neoplasmsin the sinonasal region.