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Hypercalcaemia: an unusual presenting feature of childhood acute lymphoblastic leukaemia

Rajagopal R, Lum SH, Jalaludin MY, Krishnan S, Abdullah WA, Ariffin H

Br J Haematol, 2013 Oct;163(2):147.
PMID: 23961807 DOI: 10.1111/bjh.12500
Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis*
Challenges in surviving childhood leukaemia

Ariffin H

Lancet Haematol, 2019 06;6(6):e288-e289.
PMID: 31078469 DOI: 10.1016/S2352-3026(19)30047-X
Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma*
Physical Inactivity as an Early Sign of Frailty in Young Adult Survivors of Childhood Acute Lymphoblastic Leukemia

Chua LL, Azanan MS, Oh L, Ariffin H

J Pediatr Hematol Oncol, 2023 Jul 01;45(5):e560-e566.
PMID: 36730635 DOI: 10.1097/MPH.0000000000002586

Young adult survivors of childhood leukemia have been reported with increased likelihood of age-related comorbidities compared with the general population. We compared the prevalence of frailty in young adult survivors of childhood acute lymphoblastic leukemia (n=58, median age=23 y, median survival time=18 y) with age-matched and sex-matched controls without history of cancer. Frailty phenotypes were determined using Fried frailty model. Association between frailty status and cardiometabolic conditions, systemic inflammation, and T-cell immunophenotype changes were also examined. Frailty and prefrailty were more common among survivors compared with controls (58.6% vs. 34.5%, P =0.019). Physical inactivity (39.7%) was the most frequently observed frailty criterion among the survivors. Prevalence of cardiometabolic conditions was comparable between the robust and frail/prefrail survivors. Robust survivors had a higher level of T-cell activation than the prefrail/frail survivors ( P <0.05), but no significant difference was observed for systemic inflammatory markers (IL-6 and C-reactive protein) and percentage of terminally differentiated T cells. Signs of frailty, especially physical inactivity, was detected in childhood acute lymphoblastic leukemia survivors early in their third decade of life. Survivors who were prefrail/frail also had altered T-cell activation; however, the role of such changes in T-cell phenotype in the etiology of frailty warrant further investigation.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma*
Fulltext Bone marrow necrosis preceding infantile acute lymphoblastic leukaemia

Eusni RM, Hamidah Hussin N, Zarina AL, Rahman J

Malays J Pathol, 2007 Dec;29(2):113-7.
PMID: 19108404 MyJurnal

We report a case of bone marrow necrosis preceding infantile acute lymphoblastic leukaemia (ALL). Bone marrow necrosis is a rare antemortem event and has been known to be present in many conditions, notably in haematological malignancies like acute lymphoblastic leukaemia. This case was a 6-month-old Chinese boy who was referred to Hospital Universiti Kebangsaan Malaysia for further investigation of pancytopaenia, high-grade fever, bloody diarrhoea and petechial rashes for one week. His first bone marrow aspirate revealed bone marrow necrosis. His clinical condition improved after ten days. However, his full blood picture then revealed the presence of 5% blast cells. His subsequent marrow 2 weeks later revealed acute lymphoblastic leukaemia (FAB-L1) and immunophenotyping showed precursor B acute lymphoblastic leukaemia-null type. He was started on United Kingdom Acute Lymphoblastic leukaemia (UK ALL) Infantile Leukaemia protocol, however, he defaulted treatment after 3 days. Mode of presentation, mechanism of disease and laboratory investigations and outline of treatment will be discussed.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/physiopathology
Chemotherapy induced acute pancreatitis in a child with acute lymphoblastic leukaemia

Menon, B.S., Mohamed, W.M., Majid, N.A., Ariff, A.R.

Malaysian Journal of Paediatrics and Child Health, 1998;10(2):62-64.
MyJurnal

We report a case of chemotherapy induced acute pan-creatitis in a child with acute lymphoblastic leukaemia. L-asparaginase is the most likely incriminating drug.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Surveillance blood counts for early detection of relapse in acute lymphoblastic leukemia

Ariffin H, Lim HL

Pediatr Blood Cancer, 2005 Aug;45(2):229.
PMID: 15768379
Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis*
A four-point clinical criteria distinguishes immune thrombocytopenia from acute lymphoblastic leukaemia

Lum SH, How SJ, Ariffin H, Krishnan S

Med J Malaysia, 2016 02;71(1):28-9.
PMID: 27130741

Immune thrombocytopenia is the most common diagnosis of isolated thrombocytopenia. The dilemma encountered by paediatricians is missing diagnosis of acute leukaemia in children with isolated thrombocytopenia. We demonstrated childhood ITP could be diagnosed using a four point clinical criteria without missing a diagnosis of acute leukaemia. Hence, bone marrow examination is not necessary in children with typical features compatible with ITP prior to steroid therapy. This can encourage paediatricians to choose steroid therapy, which is cheaper and non-blood product, as first line platelet elevating therapy in children with significant haemorrhage.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis*
Fulltext High white cell count at presentation in children with acute lymphoblastic leukaemia

Menon BS, Wan Maziah WM, Jackson N, Jamaluddin N, Narazah MY, Dasgupta A, et al.

Med J Malaysia, 1999 Jun;54(2):283-4.
PMID: 10972046
Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood*
Lymphoblastic lymphoma/leukaemia presenting as perichondritis of the pinna

Indudharan R, Arni T, Myint KK, Jackson N

J Laryngol Otol, 1998 Jun;112(6):592-4.
PMID: 9764308

Extra-nodal non-Hodgkin's lymphoma (NHL) of the pinna has only been reported once in a patient with immunodeficiency. We report an unusual case of lymphoblastic lymphoma in a patient without any immunodeficiency, presenting as an inflammatory lesion of the pinna, which illustrates the need to biopsy any non-healing lesion as soon as possible to ensure that such a treatable malignancy is diagnosed at an early stage.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology*
Hybrid acute leukaemia--a report of 3 cases

Ng SC, Wong TK, Lin HP

Ann Acad Med Singap, 1989 Nov;18(6):721-3.
PMID: 2624424

The simultaneous expression of both lymphoid and myeloid phenotypic features in acute leukaemia is rare. We report 3 cases of biphenotypic hybrid acute leukaemia seen in our institution. All 3 patients achieved remission with treatment for acute lymphoblastic leukaemia but two subsequently relapsed while on treatment. The hybrid acute leukaemias are important areas for further research both for delineation of basic biology and choice of optimal treatment.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology*
Fulltext Utilization of a Mixture Cure Rate Model based on the Generalized Modified Weibull Distribution for the Analysis of Leukemia Patients

Omer ME, Abu Bakar M, Adam M, Mustafa M

Asian Pac J Cancer Prev, 2021 Apr 01;22(4):1045-1053.
PMID: 33906295 DOI: 10.31557/APJCP.2021.22.4.1045

OBJECTIVE: Cure rate models are survival models, commonly applied to model survival data with a cured fraction. In the existence of a cure rate, if the distribution of survival times for susceptible patients is specified, researchers usually prefer cure models to parametric models. Different distributions can be assumed for the survival times, for instance, generalized modified Weibull (GMW), exponentiated Weibull (EW), and log-beta Weibull. The purpose of this study is to select the best distribution for uncured patients' survival times by comparing the mixture cure models based on the GMW distribution and its particular cases.
MATERIALS AND METHODS: A data set of 91 patients with high-risk acute lymphoblastic leukemia (ALL) followed for five years from 1982 to 1987 was chosen for fitting the mixture cure model. We used the maximum likelihood estimation technique via R software 3.6.2 to obtain the estimates for parameters of the proposed model in the existence of cure rate, censored data, and covariates. For the best model choice, the Akaike information criterion (AIC) was implemented.
RESULTS: After comparing different parametric models fitted to the data, including or excluding cure fraction, without covariates, the smallest AIC values were obtained by the EW and the GMW distributions, (953.31/969.35) and (955.84/975.99), respectively. Besides, assuming a mixture cure model based on GMW with covariates, an estimated ratio between cure fractions for allogeneic and autologous bone marrow transplant groups (and its 95% confidence intervals) were 1.42972 (95% CI: 1.18614 - 1.72955).
CONCLUSION: The results of this study reveal that the EW and the GMW distributions are the best choices for the survival times of Leukemia patients.
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Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality*
Fulltext Association of Genetic Ancestry With the Molecular Subtypes and Prognosis of Childhood Acute Lymphoblastic Leukemia

Lee SHR, Antillon-Klussmann F, Pei D, Yang W, Roberts KG, Li Z, et al.

JAMA Oncol, 2022 Mar 01;8(3):354-363.
PMID: 35084434 DOI: 10.1001/jamaoncol.2021.6826

IMPORTANCE: Racial and ethnic disparities persist in the incidence and treatment outcomes of childhood acute lymphoblastic leukemia (ALL). However, there is a paucity of data describing the genetic basis of these disparities, especially in association with modern ALL molecular taxonomy and in the context of contemporary treatment regimens.
OBJECTIVE: To evaluate the association of genetic ancestry with childhood ALL molecular subtypes and outcomes of modern ALL therapy.
DESIGN, SETTING, AND PARTICIPANTS: This multinational, multicenter genetic association study was conducted from March 1, 2000, to November 20, 2020, among 2428 children and adolescents with ALL enrolled in frontline trials from the United States, South East Asia (Singapore and Malaysia), and Latin America (Guatemala), representing diverse populations of European, African, Native American, East Asian, and South Asian descent. Statistical analysis was conducted from February 3, 2020, to April 19, 2021.
MAIN OUTCOMES AND MEASURES: Molecular subtypes of ALL and genetic ancestry were comprehensively characterized by performing RNA sequencing. Associations of genetic ancestries with ALL molecular subtypes and treatment outcomes were then evaluated.
RESULTS: Among the participants in the study, 1340 of 2318 (57.8%) were male, and the mean (SD) age was 7.8 (5.3) years. Of 21 ALL subtypes identified, 8 were associated with ancestry. East Asian ancestry was positively associated with the frequency of somatic DUX4 (odds ratio [OR], 1.30 [95% CI, 1.16-1.45]; P cell ALL (OR, 0.80 [95% CI, 0.71-0.90]; P cell ALL in children of African descent compared with those with a high percentage of Native American ancestry (African: OR, 1.22 [95% CI, 1.07-1.37]; P = .003; Native American: OR, 0.53 [95% CI, 0.40-0.67]; P

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma*
Eosinophilic myocarditis mimicking acute coronary syndrome in a young man with T-lymphoblastic lymphoma and hypereosinophilia

Raffali MAA, Boon Cong B, Muhammad SF, Che Hassan HH

BMJ Case Rep, 2023 Sep 25;16(9).
PMID: 37748814 DOI: 10.1136/bcr-2023-255396

A man in his 20s with underlying chemorefractory primary T-lymphoblastic lymphoma and hypereosinophilia developed acute chest pain in the ward after readmission for disease progression. ECG showed widespread ST depression and serum troponin was markedly elevated. Transthoracic echocardiography showed diffused thrombus deposition with preserved ejection fraction consistent with eosinophilic myocarditis. The patient ultimately succumbed to the disease, after complications with severe hospital-acquired pneumonia.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma*
Relationship between oral health status and hematological values in pediatric leukemic patients: an evaluative survey

Venkataraghavan K, Majithia U, Choudhary P, Trivedi K, Shah S

J Contemp Dent Pract, 2016 Jan-Feb;15(5):614-7.
PMID: 25707835

INTRODUCTION: Leukemia is a malignancy of the bone marrow and constitutes 30% of all childhood cancers. The leukemic condition itself and its therapy cause oral signs and symptoms with significant morbidity.
AIMS AND OBJECTIVES: The aim of this study was to review the oral health status in children with leukemia and relate the gingival and periodontal findings to the changes in their hematological values.
MATERIALS AND METHOD: The oral health status in 47 pediatric leukemic patients in the age group of 6 to 14 years was assessed using the dmft/DMFT index, OHI(S) index and modified gingival index (MGI). Their hematological reports on the day of examination were obtained. The patients were divided into three groups based on the status of treatment. The relation between the platelet count and the WBC count with the MGI score was checked.
RESULTS: The highest dmf and DMF scores were seen in patients who were currently under treatment. Though an inverse relation was seen between the platelet count and the MGI score, a statistically significant value was not obtained.
CONCLUSION: A longitudinal follow-up of patients should be carried out in order to establish a relation between the hematological parameters and the gingival inflammation score

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy
Fulltext S-phase fraction and pro-inflammatory cytokine expressions in acute lymphoblastic leukaemia

Maha A, Cheong SK, Leong CF, Seow HF

Malaysian Journal of Medicine and Health Sciences, 2005;1(1):41-51.

Objective: Despite much progress in treatment strategies, long term survival of adult ALL is still inferior to that in children. The underlying mechanisms for these differences are largely unknown. Intensification of contemporary therapy has also resulted in many children being over-treated. The action of chemotherapeutic drugs used in the treatment of ALL includes cell cycle dependent agents which are effective on cells that are proliferating. Cell proliferation in haemopoietic cells is controlled by cytokines. Thus, we proposed to study the cell cycle profile of ALL cases and also expression of cytokines to determine their role in affecting treatment outcome in the different age groups.
Methods: We determined the S-phase fraction from the cell cycle profile by flowcytometry and tested the expressions of cytokine IL-1beta, IL-6, IL-18, IFN-gamma, TNF-alpha and GM-CSF using RT-PCR in de novo ALL cases.
Results: We found a significantly higher S-phase fraction in samples from children 2-10 years old compared to the older age group (>10 years old) (p=0.001). GM-CSF was found to be expressed in a significantly lower percentage of children compared to adults (p=0.008).
Conclusion: Our results implied that GM-CSF may have induced cell cycle arrests in adult ALL resulting in a lower percentage of S-phase fraction. This may contribute to the poorer prognosis in adult ALL because non-cycling blasts are less sensitive to some chemotherapeutic drugs.
Keywords: ALL, S-phase fraction, GM-CSF, age

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cystic Meningioma Masquerading as a Metastatic Tumor: A Case Report

Ramanathan N, Kamaruddin KA, Othman A, Mustafa F, Awang MS

Malays J Med Sci, 2016 May;23(3):92-4.
PMID: 27418876 MyJurnal

Cystic meningioma is a rare form of intracranial meningioma. Meningiomas are typically solid tumors but may rarely have cystic components. The diagnosis of cystic meningioma is clinically challenging as the finding of multiple intra-axial tumors, including metastatic tumors, is relatively common. We report a case of cystic meningioma initially diagnosed as a metastatic tumor from a recurrence of acute lymphoid leukemia. However, postoperative histopathological examination demonstrated an atypical meningioma.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Fulltext Double Philadelphia chromosome-positive B acute lymphoblastic leukaemia in an elderly patient

Tang YL, Raja Sabudin RZ, Leong CF, Ko CC, Chia WK, Salwati S, et al.

Malays J Pathol, 2015 Dec;37(3):275-9.
PMID: 26712675 MyJurnal

A rare case of double Philadelphia chromosome-positive B Acute lymphoblastic Leukaemia (B-ALL) is reported here. A 60-year-old lady presented with one month history of fever, submandibular lymphadenopathy, loss of appetite and weight loss. Physical examination revealed multiple palpable cervical lymph nodes. Blood film showed leucocytosis with 72% blasts. Bone marrow assessment confirmed a diagnosis of B-ALL with presence of double Philadelphia (Ph) chromosomes. As she was very ill, she was initially treated with an attenuated regimen of induction chemotherapy consisting of rituximab, cyclophosphamide, vincristine and prednisolone (R-CVP) along with intrathecal chemotherapy comprising methotrexate, cytarabine and hydrocortisone. Bone marrow examination post-induction chemotherapy showed >5% blasts. She was subsequently re-induced with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) along with intrathecal chemotherapy, following which she went into complete remission. Consolidation chemotherapy consisting of methotrexate, methylprednisolone, cytarabine, intrathecal chemotherapy and imatinib was subsequently administered followed by maintenance chemotherapy consisting of vincristine, prednisolone and imatinib (IDEAMOP). She developed spontaneous bruises and relapsed four months into her maintenance chemotherapy with 90% blasts in the bone marrow which was treated with fludarabine, cytarabine and granulocyte colony stimulating factor (FLAG). Unfortunately she developed neutropenic sepsis which was complicated by invasive lung aspergillosis. Bone marrow examination post-FLAG showed 80% blasts. Despite aggressive antifungal therapy, her lung infection worsened and she finally succumbed to her illness 13 months after the initial diagnosis. We highlight a rare case of elderly B-ALL with double Ph chromosomes which carries a poor prognosis despite aggressive treatment for the disease and its complications.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
Physical activity of pediatric patients with acute leukemia undergoing induction or consolidation chemotherapy

Tan SY, Poh BK, Chong HX, Ismail MN, Rahman J, Zarina AL, et al.

Leuk. Res., 2013 Jan;37(1):14-20.
PMID: 23099236 DOI: 10.1016/j.leukres.2012.09.005

This study aimed to assess the physical activity levels of pediatric patients with acute leukemia undergoing chemotherapy. Thirty-eight pediatric patients and matched controls, aged 3-12 years old, were measured for weight, height, and other anthropometric parameters. Physical activity was assessed using actical accelerometer and activity log book. Patients recorded significantly lower mean total activity counts (26.2±30.2 cpm vs. 192.2±68.8 cpm; p<0.01) and spent more time in sedentary activities (1301±121 min vs. 1020±101 min; p<0.001) compared to controls. They also achieved fewer 1-5-min bouts of moderate-vigorous physical activity (MVPA) compared to controls (1.50±5.95 vs. 37.38±40.36; p<0.001). In conclusion, patients had lower physical activity level and intensity; and simple exercise intervention programs may be needed to minimize the detrimental effects of prolonged sedentary behaviors.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/physiopathology*
Fulltext Disseminated fusariosis and endogenous fungal endophthalmitis in acute lymphoblastic leukemia following platelet transfusion possibly due to transfusion-related immunomodulation

Kah TA, Yong KC, Rahman RA

BMC Ophthalmol, 2011;11:30.
PMID: 22044440 DOI: 10.1186/1471-2415-11-30

To report a case of disseminated fusariosis with endogenous endophthalmitis in a patient with acute lymphoblastic leukemia. Transfusion-associated immune modulation secondary to platelet transfusion could play an important role in the pathophysiology of this case.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy*
Fulltext Optic nerve involvement as a first manifestation of acute lymphoblastic leukaemia after remission

Peyman M, Hieng TL, Subrayan V

BMJ Case Rep, 2011;2011.
PMID: 22698906 DOI: 10.1136/bcr.11.2010.3517
Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology

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