NUDT15 gene polymorphism related to mercaptopurine intolerance in Taiwan Chinese children with acute lymphoblastic leukemia.

A recent study identified a variant of the NUDT15 gene (rs116855232 C>T) associated with intolerance to thiopurine in Korean patients with Crohn's disease. This study prompted us to substantiate the finding in a Taiwanese population. Four hundred and four children with acute lymphoblastic leukemia (ALL), and 100 adults with chronic immune thrombocytopenic purpura or localized lymphoma having normal bone marrow were examined. Two candidate gene approaches, pyrosequencing for NUDT15 and TaqMan assay for thiopurine methyltransferase (TPMT) genotyping (rs1142345 A>G), were performed. We showed a risk allele frequency of NUDT15 of 11.6% in children with ALL and 15.5% in adults. By contrast, the risk allele frequency of TPMT was only 1.6% in children with ALL and 0.5% in adults. The high frequency of risk variant for NUDT15, but not the very low frequency of risk variant for TPMT, was closely associated with the intolerance to mercaptopurine in children with ALL in Taiwan, contrast to that of European descent. In regard to NUDT15 polymorphism, the maximal tolerable daily doses of mercaptopurine in homozygotes, heterozygotes and wild-type groups were 9.4 mg m-2, 30.7 mg m-2 and 44.1 mg m-2, respectively. The outcomes did not differ significantly among the different genotypes.

Evaluation of readmission in children receiving allogeneic hematopoietic stem cell transplantation: an institutional experience.

BACKGROUND: Use of unrelated cord blood (UCB) has become increasingly popular as a stem cell source, given the rapid availability and decreased potential of graft-versus-host disease. We sought to ascertain whether the use of UCB transplantation for pediatric patients changed the rates of unscheduled readmission. METHODS: We analyzed the rate, causes, and evolution of hospitalization among patients receiving UCB versus matched sibling bone marrow. A retrospective analysis of the data from 54 patients who received a matched sibling hematopoietic stem cell transplantation (HSCT; n = 25; 46.3%) versus an unrelated cord blood transplantation (CBT; n = 29; 53.7%) was performed on subjects treated between 1998 and 2006. Patients who died before discharge (n = 4) were excluded from the readmission analysis. RESULTS: A total of 50 patients were recruited for the analyses. Their median age was 6.7 years (range = 0.2-17 years). The median duration of hospitalization was 18 days shorter in the sibling HSCT group than in the unrelated CBT group. There were 89 readmissions in 25 patients (50%): 49 readmissions (55%) in the related HSCT and 40 (45%) in the unrelated CBT cohorts. Forty-two percent of readmissions were due to infections. Mortality following transplantation in 10 patients (19%) included sepsis (n = 3), intracranial hemorrhage (n = 1), pulmonary hemorrhage (n =1), and relapse (n = 5). Seven patients received HSCT from HLA-identical sibling donors and three from a cord blood donor. CONCLUSION: For both groups, infection was the most common reason for readmission followed by graft failure and extramedullary relapse. Although the median hospital stay was shorter in the sibling donor group, some uncertainty exists as to whether the increased risk for readmission was related to proportionally more malignancies or to the severity of the illness. After HSCT, there was a frequent use of hospital resources: 46% of patients were hospitalized for a median of 11 days. The resulting health expenses seem to be useful, since 81% of subjects survived at 36-month follow-up.

Transplantation of unrelated donor umbilical cord blood utilizing double-unit grafts for five teenagers with transfusion-dependent thalassemia.

To augment graft cell dose, we evaluated the safety of the combined transplantation of two partially HLA-matched umbilical cord blood (UCB) units. Five patients with transfusion-dependent thalassemia, median age 11.1 years (range 10-13.1), received 2 UCB units after myeloablative conditioning. Cord blood units were a 4/6-HLA-match or better with the recipient, and contained a minimum combined pre-freeze CD34 cell dose of 3.0 x 10(5)/kg. All patients engrafted at a median of 15 days (range 12-19). Four patients with durable trilineage engraftment showed acute grade I-III GVHD; none developed extensive chronic GVHD until the date of last contact. The median times to red blood cell transfusion independence and platelet engraftment were 32 and 49 days after transplant, respectively. With a median follow-up of 18.5 months (range 11-32), four patients transplanted with UCB from two different partially HLA-matched donors were transfusion-independent. Therefore, transfusion of two partially HLA-matched UCB units is safe, and may overcome the cell-dose barrier that limits the use of UCB in long-term recipients of multiple transfusions for thalassemia.

Improved treatment results for childhood acute myeloid leukemia in Taiwan.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.

CEBPalpha mutations in childhood acute myeloid leukemia.

CEBPalpha: mutations have been described in adult acute myeloid leukemia (AML) and conferred a favorable prognosis. However, CEBPalpha mutation has not been reported in children. We investigated 117 children with de novo AML using DNA PCR assay followed by sequencing for each PCR product. CEBPalpha mutations were detected in seven patients, four had FAB M2, two M1 and one M4. CEBPalpha mutations only occurred in patients with intermediate cytogenetics and not in 56 children with AML1-ETO, CBFbeta-MYH11, PML-RARalpha or MLL rearrangements. Five patients had mutations occurred in both N-terminal part and basic-leucine zipper (bZIP) domain, one had an N-terminal frameshift mutation and the remaining one had an inframe insertion in the bZIP domain. Cloning analysis on five samples carrying more than one mutations demonstrated one homozygous combined mutations and four heterozygous biallelic mutations. Four of seven CEBPalpha mutation(+) patients had cooperating mutations with FLT3-ITD or N-ras mutations compared to 27 in 109 CEBPalpha mutation(-) patients. Our results showed that CEBPalpha mutations occurred in 6% of childhood AML and most exhibited combined mutations in both N-terminal part and bZIP domain.

FLT3-TKD mutation in childhood acute myeloid leukemia.

Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human hematologic malignancies. An internal tandem duplication (ITD) of the juxtamembrane domain-coding sequence of the FLT3 gene (FLT3-ITD) is found in 20-25% of adult acute myeloid leukemia (AML) and at a lower frequency in childhood AML. FLT3-ITD is associated with leukocytosis and a poor prognosis, especially in patients with normal karyotype. Recently, there have been three reports on point mutations at codon 835 of the FLT3 gene (D835 mutations) in adult AML. These mutations are located in the activation loop of the second tyrosine kinase domain (TKD) of FLT3 (FLT3-TKD). The clinical and prognostic relevance of the TKD mutations is less clear. To the best of our knowledge, there has been no report to describe FLT3-TKD mutations in childhood AML. In this pediatric series, FLT3-TKD mutations occurred in three of 91 patients (3.3%), an incidence significantly lower than that of FLT3-ITD (14 of 91 patients, 15.4%) in the same cohort of patients. None of them had both FLT3-TKD and FLT3-ITD mutations. Sequence analysis showed one each of D835 Y, D835 V, and D835 H. Of the three patients carrying FLT3-TKD, two had AML-M3 with one each of L- and V-type PML-RARalpha, and another one had AML-M2 with AML1-ETO. None of our patients with FLT3-TKD had leukocytosis at diagnosis. At bone marrow relapse, one of the four patients examined acquired FLT3-ITD mutation and none gained FLT3-TKD mutation.

Unexpected mortality from the use of E. coli L-asparaginase during remission induction therapy for childhood acute lymphoblastic leukemia: a report from the Taiwan Pediatric Oncology Group.

The relative efficacy and toxicity of E. coli L-asparaginase and epidoxorubicin used in remission induction therapy for childhood acute lymphoblastic leukemia (ALL) were assessed in a randomized trial conducted in Taiwan. All patients had standard-risk ALL, defined as a leukocyte count <10 x 10(9)/l and were aged between 1 and 2 or 7 and 10 years, or a leukocyte count <50 x 10(9)/l and were aged between 2 and 7 years, without evidence of a T cell or mature B cell immunophenotype, central nervous system leukemia or expression of two or more myeloid-associated antigens. Ninety-three patients were randomized to receive E. coli L-asparaginase at 10,000 IU/m2 thrice weekly for nine doses and 108 to receive epidoxorubicin at 20 mg/m2 weekly for two doses during remission induction with daily prednisolone, weekly vincristine and, on day 22, a dose of etoposide plus cytarabine. Patients treated with L-asparaginase had a significantly higher rate of fatal infection with or without hemorrhage than did those who received epidoxorubicin during remission induction (six of 93 vs none of 108, P = 0.009), resulting in a lower rate of complete remission in the former group (93.6 vs 99.1%, P = 0.05). In addition, patients treated with L-asparaginase had a higher frequency of hyperglycemia and hypoalbuminemia. The overall rate of event-free survival was lower in patients treated with L-asparaginase than in other patients (P = 0.06); estimated 3-year rates were 72% (95% confidence interval, 55-89%) and 87.2% (78-96%), respectively. We conclude that L-asparaginase (Leunase) given at 10,000 IU/m2 for nine doses was poorly tolerated and resulted in excessive toxicity, both through its effects as a single agent and possibly through potentiation of etoposide.

Correlation of membrane lipid peroxidation with oxidation of hemoglobin variants: possibly related to the rates of hemin release.

Experiments were performed to delineate the biochemical mechanism of hemoglobin (Hb)-catalyzed lipid peroxidation in human red blood cells (RBCs). Using a modified Langmuir trough lipid monolayer technique, we found that oxidized Hb induced an increase in lipid monolayer surface pressure, suggesting that oxidized Hb readily releases its heme moiety into the lipid monolayer. To confirm our interpretation that oxidized Hb readily releases its heme moiety, we monitored the fluorescence of Hb tryptophan upon oxidation of Hb. We found an increase in Hb fluorescence in the aqueous phase of our monolayer system after the addition of H2O2. The increase in fluorescence should reflect the departure of heme from globin due to a decrease in fluorescent quenching effect by the heme moiety. The rate of increase in lipid monolayer surface pressure upon Hb oxidation differed from Hb to Hb with an order of Hb E > F > S > A. The ability of various Hbs to affect lipid peroxidation in the RBC membrane, as monitored by the parinaric acid oxidation technique, followed this same order. In addition, hemin was shown to be a more potent catalyst of lipid peroxidation in RBC membrane than nonheme irons.

Impaired production of nitric oxide, superoxide, and hydrogen peroxide in glucose 6-phosphate-dehydrogenase-deficient granulocytes.

Since the generation of superoxide and hydrogen peroxide by NADPH oxidase and nitric oxide (NO) by NO synthase (NOS) in granulocytes is NADPH-dependent, we investigated the production of NO, superoxide and H2O2 in glucose 6-phosphate dehydrogenase (G6PD)-deficient human granulocytes. Our results showed that upon stimulation with either 5 microg/ml of lipopolysaccharide (LPS) or 10 microM of phorbol 12-myristate 13-acetate (PMA), the production of nitrite in normal granulocytes was elevated, 252 +/- 135% and 239 +/- 72%, respectively, compared to the resting stage. In contrast, G6PD-deficient granulocytes did not produce more nitrite upon stimulation with either LPS or PMA compared to the resting stage. Western blot analysis indicated a normal expression pattern of inducible NOS in G6PD-deficient granulocytes. In addition, the production of H2O2 and superoxide was also significantly impaired in G6PD-deficient granulocytes compared to control cells. These data demonstrate that G6PD deficiency causes an impairment in the production of NO, superoxide and H2O2.

Hemin-induced membrane sulfhydryl oxidation: possible involvement of thiyl radicals.

Sublytic levels (microM) of hemin destabilized RBC membrane as indicated by ghost fragmentation pattern using a laser viscodiffractometer. Furthermore, electron microscopic study shows that 5 microM of hemin induced echinocytic transformation whereas higher hemin concentration (40 microM) induced spherocytic transformation. In addition, hemin oxidized sulfhydryl groups in a dose dependent fashion and Electron Spin Resonance study suggests that such oxidation may involve a thiyl radical. Moreover, sulfhydryl compounds enhanced hemin-induced lipid peroxidation. Desferroxamine could prevent hemin-induced sulfhydryl oxidation as well as hemin-induced decrease in membrane stability. In contrast, vitamin E could effectively prevent hemin-induced lipid peroxidation but could not prevent hemin-mediated membrane destabilization.

Enhanced susceptibility of erythrocytes deficient in glucose-6-phosphate dehydrogenase to alloxan/glutathione-induced decrease in red cell deformability.

It has been hypothesized that enhanced oxidant sensitivity of glucose-6-phosphate dehydrogenase (G6PD) deficient red cells(RBCs) is the underlying mechanism for drug- or chemical-induced hemolytic crises in G6PD-deficiency. To further test this hypothesis, we used an alloxan-glutathione system to mimic oxidative stress and see how oxidative damage might affect RBC deformability. RBC deformability, a major determinant of RBC survival in vivo, was monitored by a laser viscodiffractometer. Under our experimental conditions, GSH alone had very little effect on the deformability of either normal or G6PD-deficient RBCs. In contrast, alloxan alone induced a small but significant decrease in the deformability of either normal or G6PD-deficient RBCs. Interestingly, alloxan and GSH together induced a further decrease in the deformability of either normal or G6PD-deficient RBCs. The decrease in deformability in G6PD-deficient RBCs was much more profound than in normal RBCs. In addition, an alloxan-vitamin C system produced a similar deleterious effect on RBC deformability as that produced by the alloxan-GSH system. Appreciable amount of hydroxyl radicals was generated by both alloxan-GSH and alloxan-vitamin C systems as evidenced by the production of hydroxylated products of salicylate which was used as a radical trap. Moreover, salicylate could ameliorate the deleterious effect of the alloxan system on the deformability of RBCs. Taken together, our results demonstrated that G6PD-deficient RBCs were particularly susceptible to oxidant-induced damage leading to a dramatic decrease in their deformability and thus provided strong support for the hypothesis that enhanced oxidant sensitivity of G6PD-deficient RBCs is the underlying mechanism for accelerated destruction of these RBCs in vivo.

Enhanced vesiculation exacerbates complement-dependent hemolysis in glucose-6-phosphate dehydrogenase deficient red blood cells.

Glucose-6-phosphate dehydrogenase (G6PD) deficient red blood cells (RBCs) are known to be more susceptible to oxidant-induced hemolysis. Erythrocytes from G6PD-deficient individuals are significantly more susceptible to Ca(2+)-induced vesiculation than normal control cells. The enhanced susceptibility of G6PD-deficient RBCs to Ca(2+)-induced vesiculation is not due to ATP depletion. The remnant G6PD-deficient RBCs following vesiculation are more sensitive to complement-mediated hemolysis than control normal RBCs. A strong positive correlation exists between the level of Ca(2+)-induced vesiculation and the extent of complement mediated hemolysis.

Successfully treated sulphasalazine-induced fulminant hepatic failure, thrombocytopenia and erythroid hypoplasia with intravenous immunoglobulin.

We report the simultaneous development of fulminant hepatic failure, thrombocytopenia and erythroid hypoplasia in a child treated with sulphasalazine. A 12-year-old girl with juvenile rheumatoid arthritis developed fulminant hepatic failure, thrombocytopenia and erythroid hypoplasia, which was confirmed by liver histology and bone marrow examination, 2 weeks after initiation of sulphasalazine therapy. The patient recovered after administration of high doses of intravenous immunoglobulin. This is the first reported case of the concurrent development of these complications associated with sulphasalazine hypersensitivity. The use of intravenous immunoglobulin may have helped in the treatment of this rare adverse effect of sulphasalazine.

Prenatally detected tumor mass in the adrenal gland.

BACKGROUND/PURPOSE: Screening programs using urinary vanillylmandelic acid have detected neuroblastomas in early infancy with some success. With the widespread use of ultrasonography in modern obstetric practice, use of ultrasonography to screen for fetal neuroblastoma seems to be reasonable and practical. METHODS: Seven fetuses had suprarenal masses detected by maternal ultrasound scan at 32 to 37 weeks' gestation between 1993 and 1998. They were delivered normally if the pregnancy was uncomplicated, especially if it was without maternal preeclampsia or fetal hydrops. Each mass was further confirmed by ultrasound scan, computed tomography, or magnetic resonance imaging in the neonatal period. Tumor excision was performed at the age of 6 to 38 days of life. RESULTS: The size of the masses measured ranged from 2.0x2.0 cm to 4.5x4.5 cm. The diagnosis was adrenal hemorrhage in 1 neonate, Evan's stage I neuroblastoma in 3, and stage IV-S neuroblastoma in 3. All of the specimens with a diagnosis of neuroblastoma showed a favorable histology by the Shimada classification system. Infants with stage I disease were treated with tumor excision only, and they had survived without disease by 14, 18, and 25 months of follow-up. One infant with stage IV-S neuroblastoma was treated further with minimal chemotherapy and has survived without disease at the 66-month follow-up examination. Another child with stage IV-S neuroblastoma has survived with local recurrence and increasing liver metastasis and was still on chemotherapy at the 2-month follow-up examination. The third child with stage IV-S disease presented with massive hepatomegaly and bone marrow involvement, and disseminated intravascular coagulopathy had developed. The patient died on the 5th day of life without surgical intervention. CONCLUSIONS: The increasing use of obstetric ultrasonography has made the prenatal screening of neuroblastomas possible. The prognosis of infants with a suprarenal mass may be improved with this early detection and early surgical intervention.

Leukemia cutis as the initial manifestation of acute nonlymphocytic leukemia in a young child.

A 15-month-old boy was well except for asymptomatic, erythematous, wheal-like papuloplaques, macules, and nodules on his face and four extremities. It was misdiagnosed by a pediatrician and treated as urticaria for six months. Later, he was sent to our hospital for evaluation of prolonged fever. Acute nonlymphocytic leukemia (M5) with leukemia cutis was diagnosed by results of hematologic examination and examination of a skin biopsy specimen. After one course of chemotherapy, all of the skin lesions completely resolved and had not recurred. Five months after acute nonlymphocytic leukemia was diagnosed, bone marrow relapse and central nervous system involvement were noted.

[Hematological data analysis in children with thalassemia trait or hemoglobin H disease in Taiwan].

In the past several years, we have collected 91 cases diagnosed as beta-thalassemia trait, 94 cases as alpha-thalassemia trait and 43 cases as hemoglobin H disease. The ages ranged from 6 months to 15 years. The hematological data were analyzed. We calculated the mean +/- SD for each item of the erythrocyte indices (RBC, Hgb, Hct, MCV, MCH, MCHC, +/- RDW) and the Hb electrophoretic results (Hb A, Hb A2, Hb F, Hb H & Bart's) in each group, and tabulated them. Then, comparisons were made between beta and alpha-thalassemia traits or between the thalassemia trait and hemoglobin H disease. We found that each of the mean values for Hgb, Hct, MCV and MCH for children with the beta-thalassemia trait was significantly lower than that for children with the alpha-thalassemia trait. The mean MCV value of the beta-thalassemia trait group was 60.7 +/- 3.4 fl, and 87% of the MCV values in this group ranged from 55 to 65 fl. The mean MCV value for the alpha-thalassemia trait group was 63.3 +/- 3.3 fl, and 56% of the MCV values in this group ranged from 60-65 fl. The MCV values for all of the 185 children studied with either the beta- or alpha-thalassemia trait ranged from 54 to 71 fl, and were far below the normal ranges for MCV values for each age-specific group. The mean percentage of deviation of MCV from normal was greater than that of Hgb in both the beta- and alpha-thalassemia trait groups. A comparison of those with beta-thalassemia trait 6 years old and under and those over 6 years showed that both the mean values of RBC and Hgb were higher in the older subgroup, while the mean MCV values did not show any significant differences between these 2 subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Hodgkin's disease in children: a review of 21 cases.

The clinical data of 21 children with Hodgkin's disease were retrospectively analyzed to identify their characteristics. Our patients were exclusively boys, ranging in age from 2 years and 9 months to 13 years and 9 months (median 7 years and 10 months). A diagnosis could not be made until after the 2nd to 4th biopsy attempt in 9 patients, with a median time lapse of 5 months from initial biopsy. The primary manifestation was generally nodal enlargement, but also included idiopathic cholestasis and Coombs' positive hemolytic anemia. The disease stages of the patients at diagnosis were 2 stage I; 5 stage II; 10 stage III; 1 stage IV; and 3 not determined. The histologic subtypes were 12 nodular sclerosis, 5 mixed cellularity and 4 lymphocyte predominance. Nine patients had "B" symptoms. Seventy-one percent were associated with anemia and the majority were microcytic. There was a high prevalence of advanced disease (61%). The therapy plan was affected by treatment philosophy at the time, availability of anticancer drugs and the family's attitude toward primary treatment. The patients were initially treated with either radiotherapy alone, chemotherapy alone or combined modality regimens. Five patients were lost within 3 months of diagnosis. The remaining 16 patients were followed, with the longest duration being 9.5 years. Two patients died: 4 were lost after 5-12 months of follow-up, (2 with disease, 2 with no evidence of disease); and the remaining 10 were still being followed (from 2 months to 9 1/2 years). Among those still being followed, 6 of them had discontinued their therapy 8 months to 4 years 5 months earlier and none of them had evidence of tumor recurrence.

Early-onset sepsis in children with acute lymphoblastic leukemia.

The presence of early-onset sepsis significantly affects the prognosis of childhood acute lymphoblastic leukemia (ALL). We retrospectively analyzed all the septic episodes that occurred within 30 days of diagnosis of ALL from January 1978 to June 1994. Within the study period, 51 early septic episodes occurred in 45 patients. This accounted for 36.2% of the total number of septic episodes (141) that occurred during this period. The rate of early-onset sepsis in childhood ALL was 11.3% (45/397). The patients ages ranged from 11 months to 14.7 years. Fortyeight episodes of sepsis were caused by single organisms and three were polymicrobic. Pseudomanas aeruginosa was the most common isolate, followed closely by Staphylococcus aureus, Escherichia coli, Streptococcus spp and Salmonella spp. The case fatality rate of early-onset sepsis was 35.6% (16/45). The average time between diagnosis and death was 5.2 days (median, 1 d). Sepsis caused by P. aeruginosa had the highest mortality, with a case fatality rate of 72.7% (8/11), followed by polymicrobial infections (66.7%, 2/3) and candidemia (66.7%, 2/3). In the adolescent age group, initial white blood cell count < 2.0 x 10(9)/L, and depressed immunoglobulin level (especially IgA) were risk factors for a fatal outcome. During the study period, which covered 16.5 years, the incidence of Gram-positive cocci, especially Streptococcus spp, increased significantly and the overall outcome associated with early-onset sepsis improved.

Herpes zoster in infancy after intrauterine exposure to varicella zoster virus: report of two cases.

Herpes zoster occurs very rarely in infancy. We report two infants who developed zoster-like lesions at three and seven months of age. They had no history of chickenpox after birth. Both mothers acquired varicella infection during their sixth month of pregnancy. The crops of vesicular rashes appeared in right L1-3 dermatomes in one patient and left V3, C2 dermatomes in the other. Laboratory findings demonstrated a four-fold rise in varicella zoster virus (VZV) IgG antibody in one patient and positive VZV IgM antibody in the other. Both infants received acyclovir treatment and the skin lesions healed rapidly without sequela. In infancy, herpes zoster may be the primary clinical manifestation of reactivation of latent VZV infection acquired transplacentally during intrauterine life.

Childhood acute nonlymphocytic leukemia in 88 patients.

In this study, 88 newly diagnosed children with acute nonlymphocytic leukemia (ANLL) were retrospectively analyzed for their treatment outcome. The patients included 51 boys and 37 girls, aged from four months to 14 years 11 months (median, seven years one month). The treatment consisted of chemotherapy using protocols which were standard at the time of diagnosis (1978-1991). Cerebrospinal fluid was not routinely examined. Fever with neutropenia was treated with empiric combination antibiotics, and anemia and thrombocytopenia were treated with blood components. Non-compliance was frequent; it was estimated that only 35.6% of all patients followed the given instructions. For the overall group (n = 57), 50.9% achieved confirmed complete remission. Median remission duration was five months and survival time was 11 months. The probability of continuous remission at 24 months was 20.9%. For the compliant group (n = 31), 51.6% attained complete remission, with a median remission duration of 14 months. The probability of continuous remission at 24 months was 44.5%, and the median survival time was six months. Early death occurred in 21.1% of all patients, 38.7% of compliant patients and 85.7% of acute promyelocytic leukemia patients. This study demonstrates how supportive treatment, socioeconomic factors and chemotherapy interact and affect the treatment outcome of ANLL in children.