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Oral candidosis in non-Hodgkin's lymphoma: a case report

Siar CH, Ng KH, Rasool S, Ram S, Abdul Jalil A, Ng KP

J Oral Sci, 2003 Sep;45(3):161-4.
PMID: 14650581

Though oral candidosis is an opportunistic fungal infection that commonly affects immunocompromised patients, little is known of its occurrence as a complication of Non-Hodgkin's lymphoma. This paper reports a case of oral candidosis in a 20-year-old Indonesian woman with this lymphoproliferative disease. She presented with acute pseudomembranous candidosis on the dorsum and lateral borders of the tongue, bilateral angular cheilitis and cheilocandidosis. The latter is a rare clinical variant of oral candidosis, and the lesions affecting the vermilion borders presented as an admixture of superficial erosions, ulcers and white plaques. Clinical findings were confirmed with oral smears and swabs that demonstrated the presence of hyphae, pseudohyphae and blastospores, and colonies identified as Candida albicans. A culture from a saline rinse was also positive for multiple candidal colonies. Lip and oral lesions were managed with Nystatin. The lesions regressed with subsequent crusting on the lips, and overall reduction in oral thrush. As Non-Hodgkin's lymphoma is a neoplastic disease that produces a chronic immunosuppressive state, management of its oral complications, including those due to oral candidosis, is considered a long-term indication.

Matched MeSH terms: Lymphoma, Non-Hodgkin/complications*; Lymphoma, Non-Hodgkin/immunology
Fulltext A malignant looking unilateral enlarged tonsil with fungating surface is not always malignant: a case report

A. B. M. Tofazzal Hossain, Shaila Kabir, Charissa Winston, Loo Yizhan, Sadia Choudhury Shimmi, M. Tanveer Hossain Parash, et al.

Malaysian Journal of Medicine and Health Sciences, 2019;15(106):95-95.
MyJurnal

Introduction:A unilateral enlarged tonsil always is a suspicion of carcinoma. Especially if it is with fungating ulcer-ative surface. Neoplasms in unilaterally enlarged tonsil include squamous cell carcinomas and lymphomas. Lym-phomas in oropharynx are not common specially with fungating surface. Usually lymphomas in these areas are Non-Hodgkin’s type. Case description: A 62-year-old woman was admitted in the tertiary level hospital of Kota Kinabalu, Sabah, with the complaint of sore throat, odynophagia and right neck swelling. She was treated as a case of acute tonsillitis by general practitioner without any noticeable improvement. Oral cavity examination revealed a hugely enlarged right tonsil with fungating ulcerative surface and almost obstructing the oropharynx. Trismus was seen which make the examination difficult. A non-tender right upper neck swelling was palpable. All baseline lab-oratory investigations were normal. A contrast-enhanced computed tomography (CECT) showed a heterogeneously enhancing mass at oropharynx compromising the airway, right supraclavicular lymphadenopathy. Histology of biop-sy from right tonsillar mass showed High grade B-cell lymphoma. Chemotherapy was planned. First cycle of chemo-therapy was administered, Patient was discharged home with the complete plan of chemotherapy. Conclusion: This patient was clinically suspicious of carcinoma of palatine tonsil. But later proven as high grade B-cell lymphoma. All unilateral enlarged tonsils are not always carcinoma.

Matched MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell
Extensive intracranial haemorrhage as a complication of acute lymphoblastic leukaemia with hyperleukocytosis

Lim WK, Fong CY, Li L, Foo JC, Yap TY

J Clin Neurosci, 2019 Jun;64:11-14.
PMID: 30948308 DOI: 10.1016/j.jocn.2019.03.056

We report a rare case of distinctive extensive punctate intracranial haemorrhage associated with acute lymphoblastic leukaemia with hyperleukocytosis. A 7-year-old girl presented with hyperleukocytosis (white cell count 788.7 × 109/L; 94% peripheral blasts) and laboratory tumour lysis syndrome. The diagnosis of T-cell acute lymphoblastic leukaemia was established and confirmed by immunophenotyping of peripheral blood and chemotherapy was commenced promptly. On day 3 of treatment, she developed progressive encephalopathy, left sided hemiparesis with left 6th and upper motor neuron 7th cranial nerve palsy. Brain MRI scan showed extensive punctate haemorrhages with perilesional oedema over the frontal, parietal, occipital, temporal, brainstem and cerebellar regions. The lesions were predominantly over the juxtacortical grey matter. She made a full neurological recovery after 3 months. Our report widens the neuroradiological features of intracranial haemorrhage associated with hyperleukocytosis and highlights the importance of prompt chemotherapy in these patients.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
Successful toxicity reduction during delayed intensification in the non-high-risk arm of Malaysia-Singapore Acute Lymphoblastic Leukaemia 2010 study

Oh BLZ, Lee SHR, Foo KM, Chiew KH, Seeto ZZL, Chen ZW, et al.

Eur J Cancer, 2021 01;142:92-101.
PMID: 33246161 DOI: 10.1016/j.ejca.2020.10.010

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.
PATIENTS AND METHODS: 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.
RESULTS: 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

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*
Intracellular vincristine levels in lymphoblasts affect treatment outcome in childhood B-lymphoblastic leukaemia: Ma-Spore ALL 2010 study

Jiang N, Wang L, Xiang X, Li Z, Chiew EKH, Koo YM, et al.

Br J Clin Pharmacol, 2021 Apr;87(4):1990-1999.
PMID: 33037681 DOI: 10.1111/bcp.14596

AIMS: Vincristine (VCR) is a key drug in the successful multidrug chemotherapy for childhood acute lymphoblastic leukaemia (ALL). However, it remains unclear how VCR pharmacokinetics affects its antileukaemic efficacy. The objective of this study is to explore the VCR pharmacokinetic parameters and intracellular VCR levels in an up-front window of Ma-Spore ALL 2010 (MS2010) study.
METHODS: We randomised 429 children with newly diagnosed ALL to 15-minute vs 3-hour infusion for the first dose of VCR to study if prolonging the first dose of VCR infusion improved response. In a subgroup of 115 B-ALL and 20 T-ALL patients, we performed VCR plasma (n = 135 patients) and intracellular (n = 66 patients) pharmacokinetic studies. The correlations between pharmacokinetic parameters and intracellular VCR levels with early treatment response, final outcome and ABCB1 genotypes were analysed.
RESULTS: There was no significant difference between 15-minute and 3-hour infusion schedules in median Day 8 peripheral or bone marrow blast response. Plasma VCR pharmacokinetic parameters did not predict outcome. However, in B-ALL, Day 33 minimal residual disease (MRD) negative patients and patients in continuous complete remission had significantly higher median intracellular VCR24h levels (P = .03 and P = .04, respectively). The median VCR24h intracellular levels were similar among the common genetic subtypes of ALL (P = .4). Patients homozygous for wild-type ABCB1 2677GG had significantly higher median intracellular VCR24h (P = .04) than 2677TT.
CONCLUSION: We showed that in childhood B-ALL, the intracellular VCR24h levels in lymphoblasts affected treatment outcomes. The intracellular VCR24h level was independent of leukaemia subtype but dependent on host ABCB1 G2677T genotype.

Matched MeSH terms: Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Association of ARID5B gene variants with acute lymphoblastic leukemia in Yemeni children

Al-Absi B, Noor SM, Saif-Ali R, Salem SD, Ahmed RH, Razif MF, et al.

Tumour Biol., 2017 Apr;39(4):1010428317697573.
PMID: 28381164 DOI: 10.1177/1010428317697573

Studies have shown an association between ARID5B gene polymorphisms and childhood acute lymphoblastic leukemia. However, the association between ARID5B variants and acute lymphoblastic leukemia among the Arab population still needs to be studied. The aim of this study was to investigate the association between ARID5B variants with acute lymphoblastic leukemia in Yemeni children. A total of 14 ARID5B gene single nucleotide polymorphisms (SNPs) were genotyped in 289 Yemeni children, of whom 136 had acute lymphoblastic leukemia and 153 were controls, using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Using logistic regression adjusted for age and gender, the risks of acute lymphoblastic leukemia were presented as odds ratios and 95% confidence intervals. We found that nine SNPs were associated with acute lymphoblastic leukemia under additive genetic models: rs7073837, rs10740055, rs7089424, rs10821936, rs4506592, rs10994982, rs7896246, rs10821938, and rs7923074. Furthermore, the recessive models revealed that six SNPs were risk factors for acute lymphoblastic leukemia: rs10740055, rs7089424, rs10994982, rs7896246, rs10821938, and rs7923074. The gender-specific impact of these SNPs under the recessive genetic model revealed that SNPs rs10740055, rs10994982, and rs6479779 in females, and rs10821938 and rs7923074 in males were significantly associated with acute lymphoblastic leukemia risk. Under the dominant model, SNPs rs7073837, rs10821936, rs7896246, and rs6479778 in males only showed striking association with acute lymphoblastic leukemia. The additive model revealed that SNPs with significant association with acute lymphoblastic leukemia were rs10821936 (both males and females); rs7073837, rs10740055, rs10994982, and rs4948487 (females only); and rs7089424, rs7896246, rs10821938, and rs7923074 (males only). In addition, the ARID5B haplotype block (CGAACACAA) showed a higher risk for acute lymphoblastic leukemia. The haplotype (CCCGACTGC) was associated with protection against acute lymphoblastic leukemia. In conclusion, our study has shown that ARID5B variants are associated with acute lymphoblastic leukemia in Yemeni children with several gender biases of ARID5B single nucleotide polymorphisms reported.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics*
Fulltext Homonymous Hemianopia: A Rare Presentation of Secondary Central Nervous System Neurolymphomatosis

Awis Qarni F, Tai E, Wh WH, Husin A

Cureus, 2018 May 29;10(5):e2708.
PMID: 30062082 DOI: 10.7759/cureus.2708

Neurolymphomatosis is an atypical complication of non-Hodgkin lymphoma and leukaemia involving infiltration of neurotropic neoplastic cells in the central or peripheral nervous system. A 28-year-old Malay lady with background diffuse large B-cell lymphoma stage IV presented with left homonymous hemianopia associated with cognitive function deterioration. Her best corrected visual acuity was 6/9 in both eyes. Magnetic resonance imaging (MRI) of the brain showed a lesion suggestive of secondary lymphomatous infiltration of the splenium of corpus callosum. The patient underwent chemotherapy, after which repeated MRI showed a reduction in the lesion size. Homonymous hemianopia is a rare presentation of secondary central nervous system neurolymphomatosis. A comprehensive history, physical examination, and radiological imaging are essential to establish the diagnosis in patients presenting with visual field defects.

Matched MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell
CD3-positive plasmablastic lymphoma reported in two cases: A potential diagnostic caveat

Wong YP, Masir N, Chew MX

Indian J Pathol Microbiol, 2021 8 4;64(3):579-583.
PMID: 34341278 DOI: 10.4103/IJPM.IJPM_616_20

Plasmablastic lymphoma (PBL) is a rare aggressive subtype of mature large B cell lymphoma involving almost exclusively the extranodal regions particularly the oral cavity, frequently described in immunocompromised patients. PBL is characterized histologically by diffuse proliferation of large neoplastic cells resembling B immunoblasts or plasmablasts. The diagnosis of PBL can be difficult due to its ambiguous histopathological features mimicking most large cell lymphomas and lacking a distinctive immunophenotypic pattern. They typically lack expression of CD20 and CD79a but may express plasma cell marker, CD138. Aberrant immunoexpression of CD3, a T-cell marker in PBL in the absence of other B-cell markers is exceptionally rare, may potentially lead to incorrect interpretation. Herein, we report a case series of CD3-positive PBL of oral cavity in two individuals, which were initially misdiagnosed as high-grade T-cell lymphomas including extranodal NK/T-cell lymphoma, nasal type. Useful distinguishing clinical settings, histomorphological features, immunohistochemistry and molecular expression profiles of PBL are discussed.

Matched MeSH terms: Plasmablastic Lymphoma/diagnosis*; Plasmablastic Lymphoma/genetics*
Fulltext Comparative aspects of microRNA expression in canine and human cancers

Sahabi K, Selvarajah GT, Abdullah R, Cheah YK, Tan GC

J Vet Sci, 2018 Mar 31;19(2):162-171.
PMID: 28927253 DOI: 10.4142/jvs.2018.19.2.162

MicroRNAs (miRNAs) have important roles in all biological pathways in multicellular organisms. Over 1,400 human miRNAs have been identified, and many are conserved among vertebrates and invertebrates. Regulation of miRNA is the most common mode of post-transcriptional gene regulation. The miRNAs that are involved in the initiation and progression of cancers are termed oncomiRs and several of them have been identified in canine and human cancers. Similarly, several miRNAs have been reported to be down-regulated in cancers of the two species. In this review, current information on the expression and roles of miRNAs in oncogenesis and progression of human and canine cancers, as well the roles miRNAs have in cancer stem cell biology, are highlighted. The potential for the use of miRNAs as therapeutic targets in personalized cancer therapy in domestic dogs and their possible application in human cancer counterparts are also discussed.

Matched MeSH terms: Lymphoma/metabolism; Lymphoma/veterinary
Primary mediastinal large B-cell lymphoma and its mimickers: a rare case report with literature review

Win TT, Kamaludin Z, Husin A

Malays J Pathol, 2016 Aug;38(2):153-7.
PMID: 27568673 MyJurnal

Primary mediastinal large B-cell lymphoma (PMLBL) is an uncommon non-Hodgkin lymphoma with a distinct clinicopathological entity in the WHO classification of lymphoid malignancies. It is known to originate from B-cells of the thymus. It mimics thymic neoplasms and other lymphomas clinically and histopathologically. We reported a 33-year-old obese man who presented with shortness of breath off and on for 4 years. Radiologically, there was a huge anterior mediastinal mass. Tru-cut biopsy was initially diagnosed as type-A thymoma. Histopathological examination of the excised specimen revealed PMLBL with stromal fibrosis and sclerosis which created a diagnostic difficulty. The neoplastic cells varied from medium-sized to large pleomorphic cells, including mononuclear cells with centroblastic and immunoblastic features as well as bi-lobed Reed Sternberg (RS)-like cells and horse-shoe like hallmark cells. Some interlacing spindle cells and epithelioid cells were also present. Immunohistochemically, tumour cells expressed diffuse positivity for LCA, CD20, CD79a, CD23, Bcl2, MUM-1 and heterogenous positivity for CD30 and EMA, and were negative for CD10, CD15 and ALK. Ki67 scoring was very high. Tumour cells infiltrated into peri-thymic fat and pericardium. No malignant cells were detected in the pleural fluid and there was no bone marrow infiltration. The patient showed partial response to 6 cycles of RICE chemotherapy, and was planned for second line chemotherapy using hyper-CVAD regimen followed by autologous stem cell transplantation. This case illustrates the importance of thorough sampling and immunohistochemistry in differentiating PMLBL from its differential diagnoses.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/diagnosis*; Lymphoma, Large B-Cell, Diffuse/pathology
A pioneer experience in Malaysia on In-house Radio-labelling of (131)I-rituximab in the treatment of Non-Hodgkin's Lymphoma and a case report of high dose (131)I-rituximab-BEAM conditioning autologous transplant

Kuan JW, Law CS, Wong XQ, Ko CT, Awang ZH, Chew LP, et al.

Appl Radiat Isot, 2016 Oct;116:13-21.
PMID: 27472826 DOI: 10.1016/j.apradiso.2016.07.016

Radioimmunotherapy is an established treatment modality in Non-Hodgkin's lymphoma. The only two commercially available radioimmunotherapies - (90)Y-ibritumomab tiuxetan is expensive and (131)I-tositumomab has been discontinued from commercial production. In resource limited environment, self-labelling (131)I-rituximab might be the only viable practical option. We reported our pioneer experience in Malaysia on self-labelling (131)I-rituximab, substituting autologous haematopoietic stem cell transplantation (HSCT) and a patient, the first reported case, received high dose (131)I-rituximab (6000MBq/163mCi) combined with BEAM conditioning for autologous HSCT.

Matched MeSH terms: Lymphoma, Non-Hodgkin/pathology*; Lymphoma, Non-Hodgkin/therapy*
Antitumour activity of Sargassum wightii (Greville) extracts against Dalton's ascites lymphoma

Rajan DS, Rajkumar M, Srinivasan R, Harikumar RP, Suresh S, Kumar S

Pak J Biol Sci, 2013 Nov 01;16(21):1336-41.
PMID: 24511743

Seaweeds have been used by mankind as medicine and food for more than 13,000 years. Marine algae are considered to produce a valuable phytoconstituents characterized by a broad spectrum of antitumor activities. The aim of the present study was to explore the effect of different solvent extracts of Sargassum wightii, Greville against Dalton's Ascitic Lymphoma (DAL) in Swiss male albino mice. DAL cells were injected intraperitoneally 1 x10(6) cell to the mice. Two days after cells injection the animals were treated with different solvent extracts of Sargassum wightii at dose of 200 mg kg(-1) for 14 days. 5-fluorouracil (20 mg kg(-1)) was used as reference drug. On day 11, cancer cell number, packed cell volume, decrease in tumour weight of the mice, increase in life span and hematological parameters were evaluated and compared with the same parameters in control. A significant increase in the life span and a decrease in the cancer cell number and tumour weight were noted in the tumour-induced mice after treatment with the extract. The haematological parameters were also normalized by the ethanolic and chloroform extracts in tumour-induced mice. These observations are suggestive of the protective effect of ethanolic extract of Sargassum wightii is comparatively better than other two tested extracts against Dalton's Ascitic Lymphoma (DAL).

Matched MeSH terms: Lymphoma/drug therapy*; Lymphoma/pathology
Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases

Li JF, Dai YT, Lilljebjörn H, Shen SH, Cui BW, Bai L, et al.

Proc Natl Acad Sci U S A, 2018 12 11;115(50):E11711-E11720.
PMID: 30487223 DOI: 10.1073/pnas.1814397115

Most B cell precursor acute lymphoblastic leukemia (BCP ALL) can be classified into known major genetic subtypes, while a substantial proportion of BCP ALL remains poorly characterized in relation to its underlying genomic abnormalities. We therefore initiated a large-scale international study to reanalyze and delineate the transcriptome landscape of 1,223 BCP ALL cases using RNA sequencing. Fourteen BCP ALL gene expression subgroups (G1 to G14) were identified. Apart from extending eight previously described subgroups (G1 to G8 associated with MEF2D fusions, TCF3-PBX1 fusions, ETV6-RUNX1-positive/ETV6-RUNX1-like, DUX4 fusions, ZNF384 fusions, BCR-ABL1/Ph-like, high hyperdiploidy, and KMT2A fusions), we defined six additional gene expression subgroups: G9 was associated with both PAX5 and CRLF2 fusions; G10 and G11 with mutations in PAX5 (p.P80R) and IKZF1 (p.N159Y), respectively; G12 with IGH-CEBPE fusion and mutations in ZEB2 (p.H1038R); and G13 and G14 with TCF3/4-HLF and NUTM1 fusions, respectively. In pediatric BCP ALL, subgroups G2 to G5 and G7 (51 to 65/67 chromosomes) were associated with low-risk, G7 (with ≤50 chromosomes) and G9 were intermediate-risk, whereas G1, G6, and G8 were defined as high-risk subgroups. In adult BCP ALL, G1, G2, G6, and G8 were associated with high risk, while G4, G5, and G7 had relatively favorable outcomes. This large-scale transcriptome sequence analysis of BCP ALL revealed distinct molecular subgroups that reflect discrete pathways of BCP ALL, informing disease classification and prognostic stratification. The combined results strongly advocate that RNA sequencing be introduced into the clinical diagnostic workup of BCP ALL.

Matched MeSH terms: Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/classification*; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics*
Campylobacter jejuni bacteremia in a leukemic child: a nearly missed diagnosis

Ding CH, Wahab AA, Tzar MN, Mokhtar MN, Arunasalam V

Trop Biomed, 2024 Jun 01;41(2):206-208.
PMID: 39154274 DOI: 10.47665/tb.41.2.011

Globally, Campylobacter spp. are responsible for most cases of bacterial gastrointestinal infections in humans and although rare, extraintestinal Campylobacter infections have been described. A 2-yearold neutropenic girl with underlying precursor B-cell acute lymphoblastic leukemia presented with a 3-day history of diarrhea. Her stool culture yielded no enteric bacterial pathogens. However, when her blood culture was flagged as positive for bacterial growth, no colonies could be observed on routine bacteriological isolation media. Nonetheless, gram-negative bacilli with seagull and spiral morphologies were seen when the surface of the isolation media used to subculture her blood was Gram-stained. Bacterial colonies were only visible when a subculture was attempted on a Campylobacter blood-free selective agar medium. The organism was identified as Campylobacter jejuni by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Since the organism was erythromycin-resistant and the patient's age precluded the use of tetracycline and ciprofloxacin, an antibiotic regimen consisting of piperacillin-tazobactam and gentamicin was commenced. Her C. jejuni bacteremia resolved following eight days of antibiotic therapy.

Matched MeSH terms: Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
Ethnic differences in the frequency of subtypes of childhood acute lymphoblastic leukemia: results of the Malaysia-Singapore Leukemia Study Group

Ariffin H, Chen SP, Kwok CS, Quah TC, Lin HP, Yeoh AE

J Pediatr Hematol Oncol, 2007 Jan;29(1):27-31.
PMID: 17230064

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.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma/ethnology*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma/physiopathology
Age, sex, haemoglobin level, and white cell count at diagnosis are important prognostic factors in children with acute lymphoblastic leukemia treated with BFM-type protocol

Ng SM, Lin HP, Ariffin WA, Zainab AK, Lam SK, Chan LL

J Trop Pediatr, 2000 Dec;46(6):338-43.
PMID: 11191144

The presenting features and treatment outcome for 575 Malaysian children (< or = 12 years of age) with newly diagnosed acute lymphoblastic leukemia (ALL), admitted to the University Hospital, Kuala Lumpur, Malaysia between 1 January 1980 and 30 May 1995 were evaluated to determine their prognostic significance. Two-year overall survival was achieved in 67 per cent of all patients and 55 per cent of patients were relapse-free at 2 years. All except 10 patients, with identified French-American-British L3 morphology were treated with the modified Berlin-Frankfurt-Munster 78 treatment protocol. Univariate analyses of failure rate conferred age, sex, white cell count and hemoglobin level as potentially significant prognostic factors. All four presenting features retained their prognostic strength in a multivariate analysis. Race, platelet count, morphological subtype, liver/spleen size, lymphadenopathy, central nervous system and mediastinal mass involvement did not show any significant effect on treatment outcome. The 2-year survival rate was significantly different with regard to age, white cell count and hemoglobin level. However, sex was not significantly related to overall survival. These prognostic factors may have implications on future stratification of risk-adjusted initial treatment in the management of childhood ALL. Our analysis of Malaysian children is similar to what could be predicted based on previous studies in other populations.

Matched MeSH terms: Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*; Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality
DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP-treated diffuse large B-cell lymphomas

Loo SK, Ch'ng ES, Lawrie CH, Muruzabal MA, Gaafar A, Pomposo MP, et al.

Pathology, 2017 Dec;49(7):731-739.
PMID: 29074044 DOI: 10.1016/j.pathol.2017.08.009

DNMT1 is a target of approved anti-cancer drugs including decitabine. However, the prognostic value of DNMT1 protein expression in R-CHOP-treated diffuse large B-cell lymphomas (DLBCLs) remains unexplored. Here we showed that DNMT1 was expressed in the majority of DLBCL cases (n = 209/230, 90.9%) with higher expression in germinal centre B-cell-like (GCB)-DLBCL subtype. Low and negative DNMT1 expression (20% cut-off, n = 33/230, 14.3%) was predictive of worse overall survival (OS; p < 0.001) and progression-free survival (PFS; p < 0.001). Nonetheless, of the 209 DNMT1 positive patients, 33% and 42% did not achieve 5-year OS and PFS, respectively, indicating that DNMT1 positive patients showed considerably heterogeneous outcomes. Moreover, DNMT1 was frequently expressed in mitotic cells and significantly correlated with Ki-67 or BCL6 expression (r = 0.60 or 0.44, respectively; p < 0.001). We demonstrate that DNMT1 is predictive of DLBCL patients' survival, and suggest that DNMT1 could be a DLBCL therapeutic target due to its significant association with Ki-67.

Matched MeSH terms: Lymphoma, Large B-Cell, Diffuse/diagnosis*; Lymphoma, Large B-Cell, Diffuse/drug therapy; Lymphoma, Large B-Cell, Diffuse/metabolism; Lymphoma, Large B-Cell, Diffuse/pathology
Fulltext Computer-assisted quantification of CD3+ T cells in follicular lymphoma

Abas FS, Shana'ah A, Christian B, Hasserjian R, Louissaint A, Pennell M, et al.

Cytometry A, 2017 06;91(6):609-621.
PMID: 28110507 DOI: 10.1002/cyto.a.23049

The advance of high resolution digital scans of pathology slides allowed development of computer based image analysis algorithms that may help pathologists in IHC stains quantification. While very promising, these methods require further refinement before they are implemented in routine clinical setting. Particularly critical is to evaluate algorithm performance in a setting similar to current clinical practice. In this article, we present a pilot study that evaluates the use of a computerized cell quantification method in the clinical estimation of CD3 positive (CD3+) T cells in follicular lymphoma (FL). Our goal is to demonstrate the degree to which computerized quantification is comparable to the practice of estimation by a panel of expert pathologists. The computerized quantification method uses entropy based histogram thresholding to separate brown (CD3+) and blue (CD3-) regions after a color space transformation. A panel of four board-certified hematopathologists evaluated a database of 20 FL images using two different reading methods: visual estimation and manual marking of each CD3+ cell in the images. These image data and the readings provided a reference standard and the range of variability among readers. Sensitivity and specificity measures of the computer's segmentation of CD3+ and CD- T cell are recorded. For all four pathologists, mean sensitivity and specificity measures are 90.97 and 88.38%, respectively. The computerized quantification method agrees more with the manual cell marking as compared to the visual estimations. Statistical comparison between the computerized quantification method and the pathologist readings demonstrated good agreement with correlation coefficient values of 0.81 and 0.96 in terms of Lin's concordance correlation and Spearman's correlation coefficient, respectively. These values are higher than most of those calculated among the pathologists. In the future, the computerized quantification method may be used to investigate the relationship between the overall architectural pattern (i.e., interfollicular vs. follicular) and outcome measures (e.g., overall survival, and time to treatment). © 2017 International Society for Advancement of Cytometry.

Matched MeSH terms: Lymphoma, Follicular/diagnosis*; Lymphoma, Follicular/genetics; Lymphoma, Follicular/pathology; Lymphoma, Follicular/ultrastructure
Fulltext Effect of polymorphisms within methotrexate pathway genes on methotrexate toxicity and plasma levels in adults with hematological malignancies

Suthandiram S, Gan GG, Zain SM, Bee PC, Lian LH, Chang KM, et al.

Pharmacogenomics, 2014 Aug;15(11):1479-94.
PMID: 25303299 DOI: 10.2217/pgs.14.97

Pharmacogenetics of methotrexate (MTX) contributes to interindividual differences in toxicity. We aimed to evaluate the impact of SNPs within the MTX pathway genes on MTX-induced toxicity and MTX plasma levels at 48 h following treatment in Asian adults with acute lymphoblastic leukemia or non-Hodgkin lymphoma.

Matched MeSH terms: Lymphoma, Non-Hodgkin/drug therapy; Lymphoma, Non-Hodgkin/genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
Polymorphisms in methylenetetrahydrofolate reductase gene and risk of non-Hodgkin lymphoma in a multi-ethnic population

Suthandiram S, Gan GG, Zain SM, Haerian BS, Bee PC, Lian LH, et al.

J Hum Genet, 2014 May;59(5):280-7.
PMID: 24646728 DOI: 10.1038/jhg.2014.19

An imbalance in folate metabolism can adversely affect DNA synthesis and methylation systems which can lead to susceptibility to non-Hodgkin lymphoma (NHL). Whether single nucleotide polymorphisms (SNPs) and their haplotypes in the methylenetetrahydrofolate reductase (MTHFR) are associated with NHL, remain inconclusive. We investigated the association between MTHFR C677T and A1298C SNPs and NHL risk in a population which is made up of Malay, Chinese and Indian ethnic subgroups. A total of 372 NHL patients and 722 controls were genotyped using the Sequenom MassARRAY platform. Our results of the pooled subjects failed to demonstrate significant association between the MTHFR C677T and A1298C SNPs with NHL and its subtypes. The results were in agreement with the previous meta-analyses. In the Indian ethnic subgroup however, single locus analysis of MTHFR A1298C appears to confer risk to NHL (Odds ratio (OR) 1.91, 95% confidence interval (95% CI) 1.22-3.00, P=0.006). The risk is almost doubled in homozygous carrier of MTHFR 1298CC (OR 4.03, 95% CI 1.56-10.43, P=0.004). Haplotype analysis revealed higher frequency of CC in the Indian NHL patients compared with controls (OR 1.86, 95% CI 1.18-2.93, P=0.007). There is lack of evidence to suggest an association between MTHFR C677T and A1298C with the risk of NHL in the Malays and Chinese. In the Indians however, the MTHFR A1298C confers risk to NHL. This study suggests ethnicity modifies the relationship between polymorphisms in the folate-metabolizing gene and NHL.

Matched MeSH terms: Lymphoma, Non-Hodgkin/diagnosis; Lymphoma, Non-Hodgkin/genetics*

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