Survival and causes of death in children diagnosed with cancer in Iceland 1981-2006

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn Skoða/Opna(view/open)OBJECTIVE: Of children diagnosed with cancer, approximately one fourth die of the disease or disease related complications. The aim of this study was to investigate survival and causes of death in children with cancer in Iceland. METHODS: This study is retrospective; population based and includes all children, less than 18 years of age, diagnosed with cancer in Iceland from 1981 to 2006. Information was extracted from the Icelandic Cancer Registry, patients hospital records and data from Statistics Iceland. RESULTS: Of 279 children diagnosed with cancer in the research period 215 were alive at the end of 2008. The overall 5-year survival was 81.2% and 10-year survival was 76.7%. There was not a significant survival difference with respect to age at diagnosis, year of diagnosis, gender or geographical residence. The small cohort size could be the explanation. Eleven individuals developed secondary neoplasm, eight of whom died. Sixteen of the 64 nonsurvivors were treated with curative intent until death, 12 of them died of therapy related complications. CONCLUSIONS: Survival rate in childhood cancer in Iceland is comparable to other Western countries. As previously reported, prognosis of patients with secondary neoplasm is unfavorable. Therapy related complications are the most common cause of death in patients treated with curative intent.Inngangur: Um fjórðungur barna sem greinist með krabbamein deyr vegna sjúkdóms síns eða meðferðartengdra fylgikvilla. Tilgangur rannsóknarinnar var að kanna lifun og dánarorsakir barna sem greinst hafa með krabbamein á Íslandi. Aðferðir: Rannsóknin var afturskyggn, lýðgrunduð og náði til allra einstaklinga yngri en 18 ára sem greindust með krabbamein á Íslandi frá upphafi árs 1981 til loka ársins 2006. Upplýsingum var safnað frá Krabbameinsskrá Íslands, sjúkraskrám og Hagstofu Íslands. Niðurstöður: Á rannsóknartímabilinu greindust 279 börn með krabbamein á Íslandi. Af þeim voru 215 á lífi í lok árs 2008. Á tímabilinu var fimm ára lifun 81,2% og 10 ára lifun 76,7%. Ekki var marktækur munur á lifun milli kynja, greiningartímabila, aldurs eða búsetu. Gæti það skýrst af smæð þýðisins. Lifun var mismunandi eftir krabbameinstegundum. Ellefu einstaklingar greindust síðar með meðferðartengd krabbamein, átta þeirra létust. Sextán þeirra 64 sem létust voru í læknandi meðferð fram að andláti. Var dánarorsök meðferðartengdir fylgikvillar hjá 12 úr þeim hópi. Ályktun: Horfur barna og unglinga á Íslandi með krabbamein eru sambærilegar við önnur vestræn ríki. Horfur eru mun verri í meðferðartengdum krabbameinum samanborið við frumkrabbamein. Meðferðartengdir fylgikvillar eru algengasta dánarorsök ef krabbameinsmeðferð er gefin með læknanlegum tilgangi

Childhood cancer in Iceland 1981-2006

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn Skoða/Opna(view/open)BACKGROUND: Childhood cancer is the second most common cause of death in children. The aim of this study was to gather epidemiological information on childhood cancer in Iceland. METHODS: The study was population based and included all children younger than 18 years of age, diagnosed with cancer in Iceland from 1981 to 2006. Information was extracted from the Icelandic Cancer Registry and patient hospital records. RESULTS: During the study period 288 cancer cases were diagnosed in 279 children, 10 cases were secondary neoplasms. Age standardized incidence was 16.1 per 100.000 (95% CI 13,6-18,6) for boys and 12.8 per 100.000 (95% CI 10,5-15,0) for girls. There was no significant difference in the incidence rate between the first and second half of the study period. For children aged 0-14 years, the age standardized incidence was 13.6 per 100.000. The incidence was highest in the 0-4 year age group (17.3 per 100.000) and in the 15-17 year age group (19.6 per 100.000). Brain tumors (27.1%) and leukemia (25.0%) were the most common cancer groups diagnosed. Lymphoid leukemia was the most common cancer type (17.9%) and astrocytoma (13.1%) came second. CONCLUSIONS: The incidence of childhood cancer in Iceland is similar to other Western countries. Long-term follow-up is very important in childhood cancer survivors.Inngangur: Krabbamein er næst algengasta dánarorsök barna á eftir slysum. Tilgangur rann-sóknarinnar var að kanna nýgengi krabbameina hjá börnum á Íslandi.
 Aðferðir: Rannsóknin var lýðgrunduð og náði til allra <18 ára sem greindust með krabbamein á Íslandi frá upphafi árs 1981 til ársloka 2006. Upplýsingum var safnað frá Krabbameinsskrá Íslands og úr sjúkraskrám.
 Niðurstöður: Alls greindust 288 krabbameinstilfelli á tímabilinu hjá 279 börnum. Í 10 tilvikum var um meðferðartengd krabbamein að ræða. Árlegt aldursstaðlað nýgengi hjá drengjum var 16,1 af 100.000 (95% CI; 13,6-18,6) en hjá stúlkum 12,8 af 100.000 (95% CI; 10,5-15,0) en ekki var marktækur munur á nýgengi milli fyrri og seinni hluta rannsóknartímabilsins. Fyrir aldursbilið 0-14 ára var árlegt aldursstaðlað nýgengi 13,6 af 100.000. Miðtaugakerfisæxli og hvítblæði voru samanlagt 52,1% allra krabbameinstilvika. Algengasta grein-ingin var bráða eitilfrumuhvítblæði (17,9%) og stjarnfrumnaæxli (13,1%) næstalgengust. Nýgeng-ið var hæst hjá aldursbilunum 0-4 ára (17,3 af 100.00) og 15-17 ára (19,6 af 100.000). Tíu börn voru með þekkta meðfædda áhættuþætti.
 Ályktun: Nýgengi krabbameina hjá börnum á Íslandi er sambærilegt við nágrannalöndin. Mikilvægt er að fylgja vel eftir börnum sem gengið hafa í gegnum krabbameinsmeðferð og þeim sem hafa þekkta meðfædda áhættuþætti.


Late and long-term effects of leukaemia treatment in childhood

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenIntroduction: The treatment of childhood leukemia has improved substantially over the last decades and now 65-75% of the patients recover. With increasing number of survivors it is important to know the long-term and late effects of leukemia and leukaemia treatment. Patients: Of the 31 children diagnosed with leukemia in Iceland from 1981 to 1990, twenty were enrolled in the study. Average age at enrollment was16 years and 8 months (16:8) and average time since treatment ended was 8:3. Methods: The study was carried out at the Children's Hospital at the University Hospital Iceland where patients were examined and data was gathered on height, weight, hearing, cognitive functions, bloodvalues, immunoglobulins and renal, endocrine, heart, liver and respiratory functions. Results: The children studied were on average 0.48 standard deviations below target height and their body-mass index was higher at the time of study than at diagnosis. Two children had obvious obstructive lung disease. No abnormalities were found in complete blood count nor heart, liver or kidney functions. Two patients were found to have impaired hearing not attributable to acoustic trauma. In some cases abnormal values were found in immunoglobulin classes and 12 patients had decreased serum IgG2. Six needed remedial reading lessons. Three patients needed hormone replacement therapy. Discussion: Minor impact on height and weight was found but the effects on lungs and hearing were inconclusive. Despite markedly decreased serum IgG2 the patients were not more prone to infections. The most obvious effects were on the endocrine system and performance at school. We conclude that the sequelae of childhood leukemia treatment in Iceland are significant and long-lasting, underlining the necessity of a careful long-term follow-up.Inngangur: Fyrir 30 árum var hvítblæði í flestum tilvikum banvænn sjúkdómur í börnum. Síðan þá hefur árangur meðferðar batnað til muna og nú ná 65-75% bata. Mikilvægt er því að þekkja langtímaáhrif hvítblæðis og hvítblæðismeðferðar. Sjúklingar: Þrjátíu og eitt barn greindist með hvítblæði á árunum 1981-1990 og náði rannsóknin til 20 þeirra. Meðalaldur við rannsókn var 16 ár og átta mánuðir (16:8) og meðaltími frá meðferðarlokum var 8:3. Aðferðir: Rannsóknin fór fram á Barnaspítala Hringsins og Heyrnar- og Talmeinastöð Íslands. Upplýsingum var safnað um hæð, þyngd, heyrn, árangur í skóla, blóðhag, mótefni og starfsemi innkirtla, nýrna, hjarta, lifrar og lungna. Niðurstöður: Sjúklingarnir reyndust að meðaltali 0,48 staðalfrávikum undir áætlaðri markhæð. Fimm voru yfir kjörþyngd þegar rannsókn fór fram en enginn við greiningu. Styttingarbrot vinstra slegils allra þeirra sem mældir voru var innan eðlilegra marka. Tveir höfðu greinilega loftvegaþrengingu. Tveir höfðu skerta heyrn sem ekki var hægt að skýra sem hávaðaskemmd. Nokkur frávik voru á aðal mótefnaflokkum og í 12 einstaklingum var IgG2 lækkað. Sex höfðu þurft lestrarsérkennslu í skóla. Þrír þurfa á hormónameðferð að halda. Engin teljandi óregla fannst á blóðhag eða starfsemi hjarta, lifrar eða nýrna. Umræður: Áhrif á hæð og þyngd eru merkjanleg en eru þó ekki klínískt markverð fyrir hópinn. Áhrif á innkirtlastarfsemi og árangur í skóla eru greinilegust. Þrátt fyrir umtalsverða lækkun á sumum mótefnaflokkum er sjúkingunum ekki hættara við sýkingum. Erfitt reyndist að meta áhrif á lungu og heyrn. Þessar niðurstöður eru sambærilegar við erlendar rannsóknir og sýna að nauðsynlegt er að fylgja börnum sem læknast hafa af hvítblæði markvisst eftir í langan tíma

Central nervous system tumours in Icelandic children; diagnoses, treatment results and late effects

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenObjective: Tumours in the central nervous system are the second most common malignant diseases in children. With improved treatment, the number of survivors is increasing. Therefore, better knowledge of the long-term effects of the disease and the therapy is needed. The aim of the current study was to find the incidence of central nervous system tumours in Iceland, evaluate the treatment results and study the long-term effects on the individuals. Material and methods: Data on diagnosis and treatment as well as demographic data were gathered from hospital records from the Reykjavik City Hospital and The University Hospital and operating lists at the Department of Neurosurgery were reviewed. On survivors, physical examination was carried out, blood tests and urine-analysis were done and hearing was tested. Social adaptation, school performance, memory, concentration and general well being were studied by a questionnaire. Results: In the years 1970-1995, 57 children, aged 16 and younger, were diagnosed in Iceland with central nervous system tumours, 30 girls and 27 boys. Two children with brain metastases were excluded. Of the 55 individuals, 38 are alive today, 19 girls and 19 boys. Seventeen children had astrocytoma, grade 1 or 2 and seven had astrocytoma of grade 3 or 4. Seven children had medulloblastoma, other tumours were less common. Four patients with benign tumours in the spine were excluded from the study; three are living abroad and three refused participation. Therefore, 28 patients were included in the further study, 15 males and 13 females. The mean age at diagnoses was 7 years and 8 months (7:8) (median 6:7 years, span 0:0-15:11), the mean age at study was 21:4 years (median 20:2 years, span 7:6-39:9) and the mean time from diagnosis until study was 12:8 years (median 11:5 years, span 2:5-26:3). The mean standard deviation score for height (SDS) was -0.63 at the time of study, five of the patients had SDS below two. Five individuals need hormone replacement therapy and one patient has scoliosis. Three patients have disabilities; two of those are incapable of activities of daily life. Three patients have hearing impairment; one of them is also blind. Of five patients who had seizures when diagnosed, two still have convulsions. Of 28 patients, twelve (43%) had learning difficulties in school and ten (36%) needed remedial teaching. Conclusions: The incidence of central nervous tumours in Icelandic children is comparable to what has been reported in other countries. The results of the treatment are similar to what has been found in the other Nordic countries which maybe better than in other countries. The most prominent long-term effects among the survivors are endocrine dysfunctions and specific learning disabilities. Other, severe long-term complications are rare but have considerable effect on the individuals. We emphazise that organised, long-term follow-up is essential for these individuals, paying special attention to learning difficulties and endocrine dysfunction.Inngangur: Æxli í miðtaugakerfi er annar algengasti illkynja sjúkdómurinn í börnum, næst á eftir hvítblæði. Árangur meðferðar hefur farið stöðugt batnandi og því eykst mikilvægi þess að greina möguleg langtímaáhrif og síðkomna fylgikvilla meðferðar. Tilgangur rannsóknarinnar var að finna heildarfjölda sjúklinga á Íslandi, greiningu þeirra og árangur meðferðar og kanna síðkomna fylgikvilla og langtímaáhrif meðferðar á eftirlifandi einstaklinga. Aðferðir: Sjúklingar voru fundnir með leit í sjúkraskrám á Sjúkrahúsi Reykjavíkur og Landspítalanum auk þess sem farið var yfir aðgerðarbækur á SHR. Upplýsingar um sjúkdóminn, greiningu og meðferð var safnað. Allir þátttakendur í rannsókninni komu í viðtal og skoðun, heyrnarmælingu, blóð- og þvagrannsóknir. Spurningalisti varðandi félagslega aðlögun, skólagöngu, minni, einbeitingu og líðan var einnig lagður fyrir þátttakendur. Niðurstöður: Á árunum 1970-1995 greindust 57 börn á Íslandi yngri en 16 ára með æxli í miðtaugakerfi, 30 stelpur og 27 strákar. Tveir sjúklingar með meinvörp í heila voru útilokaðir frá frekari uppvinnslu. Nú eru 38 þessara einstaklinga á lífi, 19 konur og 19 karlar. Sautján sjúklingar höfðu astrocytoma af gráðu 1 eða 2 en sjö sjúklingar astrocytoma af gráðu 3 eða 4. Sjö sjúklingar höfðu greinst með medulloblastoma, aðrar tegundir voru sjaldgæfari. Fjórir sjúklingar með góðkynja æxli í mænu voru útilokaðir frá rannsókn. Þrír búa erlendis og þrír neituðu þátttöku. Því tóku 28 einstaklingar þátt í rannsókninni, 15 karlmenn og 13 konur. Aldur við greiningu var að meðaltali sjö ár og átta mánuðir (7:8) (miðgildi 6:7 ár, bil 0:0-15:11), meðalaldur við rannsókn var 21:4 ár (miðgildi 20:2 ár, bil 7:6-39:9) og meðaltími frá greiningu að rannsókn var 12:8 ár (miðgildi 11:5 ár, bil 2:5-26:3). Hæð þátttakenda við rannsókn var að meðaltali -0,63 staðalfráviksskor (standard deviation score; SDS), fimm þátttakendur eru með -2 eða minna í staðalfráviksskori. Fimm einstaklingar fá hormónameðferð vegna vanstarfsemi innkirtla í kjölfar meðferðar. Einn einstaklingur hefur hryggskekkju sem rekja má til meðferðar. Þrír einstaklingar hafa verulega skerta hreyfifærni sem rekja má til sjúkdómsins og/eða meðferðar og þar af eru tveir ófærir um athafnir daglegs lífs. Þrír einstaklingar eru heyrnarskertir, þar af er einn einnig blindur. Af fimm sjúklingum sem höfðu krampa sem einkenni um sjúkdóminn fá tveir enn krampa. Af 28 sjúklingum áttu 12 (43%) við sérstaka námsörðugleika að stríða í grunnskóla og tíu (36%) fengu stuðningskennslu. Umræður: Tíðni heila- og mænuæxla virðist sú sama hér og þekkist annars staðar. Árangur meðferðar virðist svipaður og á hinum Norðurlöndunum sem er oft betri en í öðrum löndum. Þau langtímaáhrif sem eru mest áberandi hjá einstaklingum sem lifað hafa æxli í miðtaugakerfi í æsku eru vanstarfsemi innkirtla og sértækir námsörðugleikar. Aðrir alvarlegir fylgikvillar eru ekki algengir en skerða þó lífsgæði einstaklingsins. Nauðsynlegt er að bjóða upp á skipulagt og markvisst eftirlit með þessum sjúklingum að meðferð lokinni með áherslu á að greina námsörðugleika og starfstruflanir í innkirtlum

Bacteremia in children with tumors or malignant diseases 1991-2000

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenIntroduction: Ten to twelve children with tumors or malignant diseases are diagnosed annually in Iceland. Cancer treatment can cause severe immune suppression, which makes the patients susceptible to serious infections. The aim of the current study was to evaluate sepsis in children with tumors or haematological malignancies, describe the types of bacteria cultured and their antibiotic susceptibilities, and collect information on associated risk factors. Materials and methods: This was a retrospective study on all children 0-15 years of age in Iceland who were diagnosed with a tumor or malignant disease between 1991 and 2000. Information was gathered on diagnosis, treatment, blood cultures, blood tests, antibiotic use, presence of foreign bodies (such as CVC) and survival. Results: Hundred-and-eighteen children were diagnosed with cancer or benign central nervous system (CNS) tumors in Iceland during the period 1991-2000. Central nervous system tumors were most common (N=28, 23.7%), leukemia (N=21, 17.8%) and lymphoma (N=17, 14%) were the second and third. The mean age at diagnosis was 5.9 years. Sufficient data was found in the hospital records on 99 children who were included in the study. Five hundred and twenty two blood cultures were drawn from 51 of the 99 children during the period. The mean number of blood cultures per patient was 14.8 for children with leukemia, but 2.6 for children with solid tumors. Of all blood cultures, 63.6% were from a central venous catheter or a Port-A Catheter , 5% from a peripheral site, but 30% were undisclosed. Of the 522 blood cultures, 90 grew bacteria (17.2%). Coagulase-negative staphylococci were isolated from 53 blood cultures (60%) and Staphylococcus aureus from 12 (13%). Positive cultures were regarded as a definite or possible infection in 47 blood cultures (52%), contamination in 17 (18.9% ), but uncertain in 26 (27.7%). Over 60 percent of the blood cultures (N=302) were drawn when a child was neutropenic (ANCInngangur: Árlega greinast 10-12 börn með æxli og illkynja sjúkdóma á Íslandi. Meðferð við illkynja sjúkdómum eykur hættu á alvarlegum sýkingum sem mikilvægt er að bregðast rétt við. Markmið rannsóknarinnar var að meta blóðsýkingar í börnum með æxli og illkynja sjúkdóma, þar með talið einstakar bakteríur og sýklalyfjanæmi þeirra. Áhættuþættir voru einnig kannaðir. Efniviður og aðferðir: Rannsóknin var aftur-skyggn og var rannsóknarþýðið öll börn á aldrinum 0-15 ára greind með illkynja sjúkdóm eða æxli á árunum 1991-2000 á Barnaspítala Hringsins. Upplýsingum var safnað um greiningu, meðferð, blóðræktanir, blóðgildi og fleira, svo sem sýklalyfjanotkun, aðskotahluti og afdrif. Niðurstöður: Alls greindust 118 börn með illkynja sjúkdóm eða æxli á tímabilinu. Æxli í miðtaugakerfi (MTK) voru algengust (N=28, 23,7%), þá hvítblæði (N=21, 17,8%) og eitlakrabbamein (N=17, 14%). Meðalaldur barna við greiningu var 5,9 ár. Upplýsingar úr sjúkraskrám voru fullnægjandi fyrir 99 börn. Af þeim var 51 barn blóðræktað. Fjöldi blóðræktana var 522. Meðalfjöldi blóðræktana var 14,8 hjá börnum með hvítblæði, en 2,6 hjá börnum með föst æxli. Blóðræktanir voru teknar úr holæðalegg eða lyfjabrunni í 63,6%, 5,4% úr útbláæð en 31% tilfella voru ótilgreind. Af 522 ræktunum voru 90 jákvæðar (17,2%). Algengasta bakterían var kóagúlasa-neikvæður stafýlókokkur (KNS) (N=53, 60%), en Staphylococcus aureus næstalgengastur (N=12, 13,3%). Jákvæð ræktun var talin tengjast líklegri eða sannaðri sýkingu í 47 tilfellum (52%), mengun í 17 (18,9%) en óvíst var með 26 ræktanir (27,7%). Barn hafði daufkyrningafæð (ANC ?1,0 *109/L) við 302 blóðræktanir (61,4%). Meðallengd daufkyrningafæðar var 9,0 dagar. C-reative protein (CRP) var að meðaltali 63,9 mg/L við blóðræktun og meðalhiti var 38,8 °C. Í 183 tilfellum var barn á sýklalyfjum við blóðræktun (35,1%). Rannsóknarniðurstöður barna með jákvæða blóðræktun voru ekki frábrugðnar öðrum. Ályktanir: Sýkingar af völdum Gram-jákvæðra baktería, sérstaklega KNS, eru nú mun algengari en Gram-neikvæðra baktería. Hluti jákvæðra ræktana getur þó verið mengun. Blóðrannsóknir virðast hafa lítið forspárgildi um niðurstöður blóðræktana. Ekkert barn lést úr blóðsýkingu af völdum baktería á tímabilinu. Reynslusýklalyfjameðferð hérlendis virðist enn árangursrík

Gemtuzumab ozogamicin as postconsolidation therapy does not prevent relapse in children with AML: results from NOPHO-AML 2004.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.There are no data on the role of postconsolidation therapy with gemtuzumab ozogamicin (GO; Mylotarg) in children with acute myeloid leukemia (AML). The NOPHO-AML 2004 protocol studied postconsolidation randomization to GO or no further therapy. GO was administered at 5 mg/m(2) and repeated after 3 weeks. We randomized 120 patients; 59 to receive GO. Survival was analyzed on an intention-to-treat basis. The median follow-up for patients who were alive was 4.2 years. Children who received GO showed modest elevation of transaminase and bilirubin without signs of veno-occlusive disease. Severe neutropenia followed 95% and febrile neutropenia 40% of the GO courses. Only a moderate decline in platelet count and a minor decrease in hemoglobin occurred. Relapse occurred in 24 and 25 of those randomized to GO or no further therapy. The median time to relapse was 16 months versus 10 months (nonsignificant). The 5-year event-free survival and overall survival was 55% versus 51% and 74% versus 80% in those randomized to receive GO or no further therapy, respectively. Results were similar in all subgroups. In conclusion, GO therapy postconsolidation as given in this trial was well tolerated, showed a nonsignificant delay in time to relapse, but did not change the rate of relapse or survival (clinicaltrials.gov identifier NCT00476541).Swedish Childhood Cancer Foundation Danish Childhood Cancer Foundation Karen Elise Jensen Foundation Wyet

DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML)

Pediatric acute myeloid leukemia (AML) is a heterogeneous disease composed of clinically relevant subtypes defined by recurrent cytogenetic aberrations. The majority of the aberrations used in risk grouping for treatment decisions are extensively studied, but still a large proportion of pediatric AML patients remain cytogenetically undefined and would therefore benefit from additional molecular investigation. As aberrant epigenetic regulation has been widely observed during leukemogenesis, we hypothesized that DNA methylation signatures could be used to predict molecular subtypes and identify signatures with prognostic impact in AML. To study genome-wide DNA methylation, we analyzed 123 diagnostic and 19 relapse AML samples on Illumina 450k DNA methylation arrays. We designed and validated DNA methylation-based classifiers for AML cytogenetic subtype, resulting in an overall test accuracy of 91%. Furthermore, we identified methylation signatures associated with outcome in t(8;21)/RUNX1-RUNX1T1, normal karyotype, and MLL/KMT2A-rearranged subgroups (p < 0.01). Overall, these results further underscore the clinical value of DNA methylation analysis in AML

DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML)

Pediatric acute myeloid leukemia (AML) is a heterogeneous disease composed of clinically relevant subtypes defined by recurrent cytogenetic aberrations. The majority of the aberrations used in risk grouping for treatment decisions are extensively studied, but still a large proportion of pediatric AML patients remain cytogenetically undefined and would therefore benefit from additional molecular investigation. As aberrant epigenetic regulation has been widely observed during leukemogenesis, we hypothesized that DNA methylation signatures could be used to predict molecular subtypes and identify signatures with prognostic impact in AML. To study genome-wide DNA methylation, we analyzed 123 diagnostic and 19 relapse AML samples on Illumina 450k DNA methylation arrays. We designed and validated DNA methylation-based classifiers for AML cytogenetic subtype, resulting in an overall test accuracy of 91%. Furthermore, we identified methylation signatures associated with outcome in t(8;21)/RUNX1-RUNX1T1, normal karyotype, and MLL/KMT2A-rearranged subgroups (p < 0.01). Overall, these results further underscore the clinical value of DNA methylation analysis in AML

Changes in body mass index during treatment of childhood acute lymphoblastic leukemia with the Nordic ALL2008 protocol

Funding Information: Christina Egnell is supported by funding from the Swedish Childhood Cancer Foundation (Barncancerfonden, grant numbers TJ2018‐0093; PR2019‐0075; TJ2019‐0048). This work is part of the Danish nation‐wide research program Childhood Oncology Network Targeting Research, Organisation & Life expectancy (CONTROL) and supported by the Danish Cancer Society (R‐257‐A14720) and the Danish Childhood Cancer Foundation (2019‐5934 and 2020‐5769). Publisher Copyright: © 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.Objectives: Children with acute lymphoblastic leukemia (ALL) have a tendency to gain weight during treatment. As overweight and obesity associate with health problems, prophylactic interventions are warranted. Therefore, it is important to identify the children most prone to gain weight. Methods: Patients aged 2.0–17.9 years at ALL diagnosis were identified from the NOPHO ALL2008 registry. Registry data was complemented with height and weight at the end of therapy from questionnaires. Body mass index (BMI) was classified according to international age- and sex-adjusted International Obesity Task Force BMI cut-offs. BMI values were transformed into standard deviation scores (SDS) to calculate the difference in BMISDS during treatment. Results: Data on BMI change were available for 765 children. Overweight and obesity doubled during treatment: 9.7% were overweight and 2.1% obese at diagnosis and 21.8% and 5.4% at the end of therapy, respectively. The mean BMISDS change was +0.64. Younger (2.0–5.9 years) and healthy weight children were most prone to become overweight (mean change in BMI SDS +0.85 and + 0.65, respectively). Conclusions: Younger children (2.0–5.9 years) with healthy weight at diagnosis were most prone to becoming overweight and therefore are an important group to target while considering interventions.Peer reviewe

Fusion transcript analysis reveals slower response kinetics than multiparameter flow cytometry in childhood acute myeloid leukaemia

Funding Information: We thank the employees at the Department of Clinical Chemistry at Sahlgrenska University Hospital, Haemodiagnostic Laboratory at the Aarhus University Hospital, and Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet for sample collection, processing and analyses. Publisher Copyright: © 2022 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.Introduction: Analysis of measurable residual disease (MRD) is increasingly being implemented in the clinical care of children and adults with acute myeloid leukaemia (AML). However, MRD methodologies differ and discordances in results lead to difficulties in interpretation and clinical decision-making. The aim of this study was to compare results from reverse transcription quantitative polymerase chain reaction (RT-qPCR) and multiparameter flow cytometry (MFC) in childhood AML and describe the kinetics of residual leukaemic burden during induction treatment. Methods: In 15 children who were treated in the NOPHO-AML 2004 trial and had fusion transcripts quantified by RT-qPCR, we compared MFC with RT-qPCR for analysis of MRD during (day 15) and after induction therapy. Eight children had RUNX1::RUNX1T1, one CBFB::MYH11 and six KMT2A::MLLT3. Results: When ≥0.1% was used as cut-off for positivity, 10 of 22 samples were discordant. The majority (9/10) were MRD positive with RT-qPCR but MRD negative with MFC, and several such cases showed the presence of mature myeloid cells. Fusion transcript expression was verified in mature cells as well as in CD34 expressing cells sorted from diagnostic samples. Conclusions: Measurement with RT-qPCR suggests slower response kinetics than indicated from MFC, presumably due to the presence of mature cells expressing fusion transcript. The prognostic impact of early measurements with RT-qPCR remains to be determined.Peer reviewe