exudates and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Studies had shown that genetic polymorphism plays a significant role in the pharmacokinetics and pharmacodynamics variation of high dose methotrexate (MTX), 5000 mg/m

Topics: Genotype; Malaysia; Methotrexate; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Polymorphism, Genetic; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Purpose Although IKZF1 deletion ( IKZF1

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Female; Humans; Ikaros Transcription Factor; Incidence; Infant; Malaysia; Male; Neoplasm Recurrence, Local; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Singapore

To improve treatment outcome for childhood acute lymphoblastic leukemia (ALL), we designed the Malaysia-Singapore ALL 2003 study with treatment stratification based on presenting clinical and genetic features and minimal residual disease (MRD) levels measured by polymerase chain reaction targeting a single antigen-receptor gene rearrangement.. Five hundred fifty-six patients received risk-adapted therapy with a modified Berlin-Frankfurt-Münster-ALL treatment. High-risk ALL was defined by MRD ≥ 1 × 10(-3) at week 12 and/or poor prednisolone response, BCR-ABL1, MLL gene rearrangements, hypodiploid less than 45 chromosomes, or induction failure; standard-risk ALL was defined by MRD ≤ 1 × 10(-4) at weeks 5 and 12 and no extramedullary involvement or high-risk features. Intermediate-risk ALL included all remaining patients.. Patients who lacked high-risk presenting features (85.7%) received remission induction therapy with dexamethasone, vincristine, and asparaginase, without anthracyclines. Six-year event-free survival (EFS) was 80.6% ± 3.5%; overall survival was 88.4% ± 3.1%. Standard-risk patients (n = 172; 31%) received significantly deintensified subsequent therapy without compromising EFS (93.2% ± 4.1%). High-risk patients (n = 101; 18%) had the worst EFS (51.8% ± 10%); EFS was 83.6% ± 4.9% in intermediate-risk patients (n = 283; 51%).. Our results demonstrate significant progress over previous trials in the region. Three-drug remission-induction therapy combined with MRD-based risk stratification to identify poor responders is an effective strategy for childhood ALL.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Child; Child, Preschool; Disease-Free Survival; Female; Humans; Infant; Infant, Newborn; Malaysia; Male; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Singapore; Treatment Outcome

Childhood acute lymphoblastic leukemia (ALL) is clinically heterogeneous with prognostically and biologically distinct subtypes. Although racial differences in frequency of different types of childhood ALL have been reported, many are confounded by selected or limited population samples. The Malaysia-Singapore (MA-SPORE) Leukemia Study Group provided a unique platform for the study of the frequency of major subgroups of childhood ALL in a large cohort of unselected multiethnic Asian children. Screening for the prognostically important chromosome abnormalities (TEL-AML1, BCR-ABL, E2A-PBX1, and MLL) using multiplex reverse-transcription polymerase chain reaction was performed on 299 consecutive patients with ALL at 3 study centers (236 de novo, 63 at relapse), with the ethnic composition predominantly Chinese (51.8%) and Malay (34.8%). Reverse-transcription polymerase chain reaction was successful in 278 (93%) of cases screened. The commonest fusion transcript was TEL-AML1 (19.1%) followed by BCR-ABL (7.8%), MLL rearrangements (4.2%), and E2A-PBX1 (3.1%). Chinese have a significantly lower frequency of TEL-AML1 (13.3% in de novo patients) compared with Malays (22.2%) and Indians (21.7%) (P=0.04). Malays have a lower frequency of T-ALL (6.2%) compared with the Chinese and Indians (9.8%). Both Malays (7.4%) and Chinese (5.0%) have significantly higher frequency of BCR-ABL compared with the Indian population (P<0.05) despite a similar median age at presentation. Our study suggests that there are indeed significant and important racial differences in the frequency of subtypes of childhood ALL. Comprehensive subgrouping of childhood ALL may reveal interesting population frequency differences of the various subtypes, their risk factors and hopefully, its etiology.

Topics: Adolescent; Asian People; Child; Child, Preschool; Chromosome Aberrations; Female; Humans; Infant; Infant, Newborn; Malaysia; Male; Neoplasm Proteins; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Risk Factors; Singapore

Reports on the outcome of treatment in ALL in Asian (non-Caucasian) adults have been few, and published results compare very unfavourably with results of treatment from 'Western' centres. Seventy-four newly diagnosed Malaysian patients with ALL between the ages of 15 and 69 were treated from 1986 to 1990. The clinical features and prognostic factors were similar to those reported in 'Western' series. The chemotherapy protocol utilized was adapted from the one used by Hoelzer et al in the multicentre German study. The complete remission rate was 73%. The probability of continuous complete remission at 5 years was 29% with a median duration of remission of 15 months. This compares with Hoelzer's initial results of 77% CR rate and 35% CCR at 5 years. Patients with an initial white cell count of less than 30 x 10(9)/l at presentation were found to have a significantly better disease-free survival than those with a count of more than 30 x 10(9)/l (35 vs 22%, P = 0.026, univariate analysis). There was no difference in leukaemia-free survival according to age, sex, ethnic group, or immunophenotype. These results show that the use of moderately intensive chemotherapy protocols in Asian (non-Caucasian) patients achieves similar results to those used in Caucasians. We also showed that the difficulties in 'curing' approximately 70% of adult patient with ALL are universal.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asia; Asparaginase; Cytarabine; Daunorubicin; Dexamethasone; Doxorubicin; Ethnicity; Female; Follow-Up Studies; Germany; Humans; Malaysia; Male; Methotrexate; Methylprednisolone; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisolone; Probability; Racial Groups; Survival Rate; Time Factors; Treatment Outcome; Vincristine

To investigate whether, for children with favorable-risk B-cell precursor ALL (BCP-ALL), an anthracycline-free protocol is noninferior to a modified Berlin-Frankfurt-Muenster ALL-IC2002 protocol, which includes 120 mg/m. Three hundred sixty-nine children with favorable-risk BCP-ALL (age 1-9 years, no extramedullary disease, and no high-risk genetics) who cleared minimal residual disease (≤0.01%) at the end of remission induction were enrolled into Ma-Spore (MS) ALL trials. One hundred sixty-seven standard-risk (SR) patients (34% of Malaysia-Singapore ALL 2003 study [MS2003]) were treated with the MS2003-SR protocol and received 120 mg/m. The 6-year EFS of MS2003-SR and MS2010-SR (anthracycline-free) cohorts was 95.2% ± 1.7% and 96.5% ± 1.5%, respectively (. In comparison with MS2003-SR, the anthracycline-free MS2010-SR protocol is not inferior and was less toxic as treatment for favorable-risk childhood BCP-ALL.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Disease-Free Survival; Humans; Infant; Malaysia; Neoplasm Recurrence, Local; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Singapore; Treatment Outcome

Life-threatening infections significantly impact the care of children undergoing therapy for acute lymphoblastic leukemia (ALL) who are at risk of severe sepsis due to both host and treatment factors. Our aim was to develop a life-threatening infection risk prediction model that would allow remote rapid triage of patients to reduce time to first dose of antibiotics and sepsis-related mortality.. A retrospective analysis of 2068 fever episodes during ALL therapy was used for model building and subsequent internal validation.. Three hundred and seventy-seven patients were treated for ALL in two institutions with comparable critical and supportive care resources. A total of 55 patients accounted for 71 admissions to the critical care unit for sepsis that led to eight septic deaths during a 16-year study period. A retrospective analysis of risk factors for sepsis enabled us to build a model focused on 13 variables that discriminated admissions requiring critical care well: area under the receiver operating characteristic curve of .82; 95% CI .76-.87, p<.001, and Brier score of .033. Significant univariate predictors included neutropenia, presence of symptoms of abdominal pain, diarrhea, fever during induction or steroid-based phases, and the lack of any localizing source of infection at time of presentation.. We have developed a risk prediction model that can reliably identify ALL patients undergoing treatment who are at a higher risk of life-threatening sepsis. Clinical applicability can potentially be extended to low-middle income settings, and its utility should be further studied in real-world settings.

Topics: Anti-Bacterial Agents; Child; Clinical Trials as Topic; Fever; Humans; Malaysia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Sepsis; Singapore

In non-high-risk (non-HR) patients, the Malaysia-Singapore Acute Lymphoblastic Leukaemia 2003 (MS2003) study achieved good outcomes. However, its delayed-intensification (DI) phase, comprising repeated blocks of protocol III (2003-PIII), was toxic and caused significant treatment delays. The successor MS2010 study attempted to lower DI toxicity by replacing myelosuppressive drugs (doxorubicin, cytarabine) with vincristine and asparaginase.. We analysed 1748 admissions for fever in 315 Singapore children with non-HR acute lymphoblastic leukaemia (ALL) (MS2003, n = 183; MS2010, n = 132), comprising 76% of the total cohort (n = 413), to study the impact of these changes.. The new 2010-PVa which has no doxorubicin, was associated with significantly fewer hospitalisations due to fever (0.08 versus 0.30 admissions per block [A/blk], p < 0.001), as than 2003-PIIIa. Similarly in 2010-PIIIb and PVb, where one block of cytarabine was replaced by two doses of vincristine, admissions for fever were also fewer (0.47 versus 0.74 A/blk, p < 0.001) than in 2003-PIIIb. However, the addition of single doses of vincristine and asparaginase in 2010-PIIIa, even with a mandatory seven-day rest, led to more hospitalisations (0.45 A/blk, p < 0.001), increased risk of bacteraemia (relative-risk (RR) = 7.66, p = 0.005) and critical-care admissions (RR = 4.31, p = 0.13). Despite this, overall treatment-related mortality decreased from 2.7% to 0.8%. Taken together, the reduced phase delays allowed earlier completion of the intensive phase of treatment (standard risk: 38.1 versus 49.4 weeks, p < 0.001; intermediate risk: 50.9 versus 58.8 weeks, p < 0.001), while maintaining excellent 10-year event-free survival of 95.4% and overall survival of 96.2%.. In non-HR ALL, replacing doxorubicin/cytarabine with vincristine/asparaginase during some DI blocks is effective in reducing toxicity without compromising outcomes.. NCT0289464.

Topics: Child; Child, Preschool; Female; History, 21st Century; Humans; Infant; Malaysia; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Singapore

Vincristine, an essential component of childhood acute lymphoblastic leukaemia (ALL) therapeutic protocols, is associated with dose-dependent neurotoxicity, but its long-term morbidity in treated children has not been clearly elucidated. The aim of this study is to determine the prevalence of vincristine-induced peripheral neuropathy (VIPN) among Malaysian childhood ALL survivors and its impact on motor function and quality of life.. Survivors of childhood ALL aged 4-18 years who had completed chemotherapy for 2 years or more were evaluated for VIPN using both the clinical Total Neuropathy Score (cTNS) and nerve conduction studies. Motor function and quality of life of the survivors were assessed via the Bruininks-Oseretsky Test of Motor Proficiency Brief Form, Second Edition (BOT-2 Brief Form) and the Paediatric Quality of Life version 4.0 Generic Core Scales (PedsQL4.0) questionnaire, respectively.. One hundred and one survivors with a duration of follow-up ranging from 2.0 to 10.3 years were recruited. Twenty-seven (26.7%) had abnormal cTNS scores and 69 (68.3%) had electrophysiological evidence of neuropathy. Of these, 16 (15.8%) had combined clinical and electrophysiological neuropathy (VIPN). Those previously treated on the intermediate- or high-risk treatment stratification arms had a higher risk of developing VIPN (67.3 vs. 32.7%; odds ratio [OR]: 9.06, 95% confidence interval [CI]: 1.14-71.86; P = 0.014). Survivors with VIPN had significantly lower quality of life scores in the physical (P = 0.024) and social domains (P = 0.039) compared with peers without VIPN, but no association with poorer motor function was observed.. Sixteen percent of ALL survivors had VIPN. VIPN should be increasingly recognised as a late effect of chemotherapy, as it significantly affects physical and social function quality of life.

Topics: Adolescent; Antineoplastic Agents, Phytogenic; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Malaysia; Male; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prevalence; Survivors; Vincristine

To determine the behavioural impact of chemotherapy in survivors of acute lymphoblastic leukaemia (ALL) treated with chemotherapy only and to identify treatment-related or sociodemography-related factors that might be associated with behavioural outcome.. We examined 57 survivors of childhood ALL, who were off treatment for at least 2 years and were in remission, aged 4-18 years, and 221 unrelated healthy controls. The Child Behaviour Checklist (CBCL) parent report was used either in English or in Bahasa Malaysia (the national language of Malaysia) to assess the behavioural outcome.. Childhood ALL survivors had significantly higher scores on externalising behaviour on the CBCL parent report than did controls. Higher problem scores were found in ALL survivors with single parents on 'total problems' (P = 0.03) and subscales 'withdrawn' (P = 0.03), 'social problems' (P < 0.01) and 'delinquent behaviour' (P = 0.03) than in survivors with married parents. Significant associations were seen between a lower education level of the father and the variables representing internalising (withdrawn, anxious/depressed) and externalising (aggressive behaviour). We observed trends on higher scores in all scales in ALL survivors with single parents than in controls with single parents or with fathers with low education level, especially primary education only.. Malaysian childhood ALL survivors had a significantly increased risk for externalising behavioural problems, and there was a trend towards increased risk of problems in many other behavioural scales. Understanding the sociocultural dimension of patients' health is important to be able to design the most appropriate remedy for problem behaviours detected in this multi-ethnic population.

Topics: Adolescent; Aggression; Antineoplastic Agents; Anxiety; Case-Control Studies; Child; Child Behavior; Child Behavior Disorders; Child, Preschool; Depression; Educational Status; Fathers; Female; Humans; Malaysia; Male; Parents; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Single Parent; Surveys and Questionnaires; Survivors

Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA 94C>A) contribute to variable responses, including fatal adverse effects, among subjects treated with 6-mercaptopurine (6-MP). Our objectives were to investigate the distribution of specific TPMT and ITPA genotypes in healthy subjects and patients with acute lymphoblastic leukaemia (ALL) from the three main ethnic groups (Malays, Chinese and Indians) in Malaysia and the association of the polymorphisms with adverse effects of 6-MP.. Patients with ALL and healthy controls were recruited and genotyped for genetic variants of TPMT and ITPA 94C>A. The relationship between genotypes and clinical outcomes was investigated.. Acute lymphoblastic leukaemia patients with allele ITPA 94A were more likely to develop fever and liver toxicity with 6-MP. The prevalence of TPMT variants was low and this makes it unlikely that testing for them would be useful in our populations. Only patients heterozygous for TPMT*3C were detected.. Our results suggest that ITPA 94C>A testing, but not TPMT testing, may help in minimizing the adverse effects of 6-MP in Malaysian patients. However, whether this is true in clinical practice requires a larger study and formal randomized controlled evaluation.

Topics: Adolescent; Antimetabolites, Antineoplastic; Case-Control Studies; Child; Child, Preschool; Ethnicity; Female; Genotype; Humans; Infant; Inosine Triphosphatase; Malaysia; Male; Mercaptopurine; Methyltransferases; Polymorphism, Genetic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrophosphatases; Young Adult

To study genetic epidemiology of childhood acute lymphoblastic leukemia (ALL) in the Chinese and Malays, we investigated 10 polymorphisms encoding carcinogen- or folate-metabolism and transport. Sex-adjusted analysis showed NQO1 609CT significantly protects against ALL, whilst MTHFR 677CT confers marginal protection. Interestingly, we observed that NQO1 609CT and MTHFR 1298 C-allele have greater genetic impact in boys than in girls. The combination of SLC19A1 80GA heterozygosity and 3'-TYMS -6bp/-6bp homozygous deletion is associated with reduced ALL risk in Malay boys. Our study has suggested the importance of gender and race in modulating ALL susceptibility via the folate metabolic pathway.

Topics: Adolescent; Asian People; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Genotype; Humans; Infant; Infant, Newborn; Malaysia; Male; Polymorphism, Single Nucleotide; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Sex Characteristics; Singapore; Young Adult

Eighty-eight multi-ethnic Malaysian pediatric acute lymphoblastic leukemia (ALL) patients were screened for the TEL-AML1 rearrangement by reverse transcription-polymerase chain reaction (RT-PCR). Fluorescence in situ hybridization (FISH) was used as an independent screen for 30 cases and to confirm RT-PCR positive cases. Seventeen patients, or 19%, were found to be t(12;21) positive. Ethnically the group comprised 12 Malays, 4 Chinese, and 1 Indian. All patients, including 1 with an unusual blast cell morphology who suffered an early relapse and death, were characteristic TEL-AML1 cases in cell count, age, ALL subset classification, and fusion transcript expressed. This study shows that in Malaysia, TEL-AML1 is found in the same distinct ALL subset and at a similar frequency as in other diverse childhood ALL cohorts.

Topics: Bone Marrow; Child; Child, Preschool; China; Core Binding Factor Alpha 2 Subunit; Ethnicity; Female; Gene Rearrangement; Humans; Immunophenotyping; India; Malaysia; Male; Oncogene Proteins, Fusion; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Reverse Transcriptase Polymerase Chain Reaction

Topics: Blood Cell Count; Child; Cost-Benefit Analysis; Humans; Malaysia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Treatment Outcome

The aim of this study was to determine the incidence and outcome of herpes zoster hospitalised children with cancer in Kota Baru. It was a retrospective review from January 1994 to December 1998. The diagnosis of herpes zoster was a clinical one. Herpes zoster was diagnosed in 10 of 188 (5%) children with malignancy. The most common malignancy was leukaemia. Nine children were treated with acyclovir. No child developed visceral dissemination and there were no deaths.

Topics: Acyclovir; Antiviral Agents; Burkitt Lymphoma; Child; Child, Preschool; Female; Herpes Zoster; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Malaysia; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Treatment Outcome