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Norén-Nyström, Ulrika
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Publications (10 of 19) Show all publications
Wolthers, B. O., Mogensen, P. R., Frandsen, T. L., Abrahamsson, J., Behrendtz, M., Heyman, M., . . . Schmiegelow, K. (2019). Insulin-dependent diabetes: a chronic complication to acute pancreatitis in childhood acute lymphoblastic leukemia. Pediatric Blood & Cancer, 66(1), Article ID e27437.
Open this publication in new window or tab >>Insulin-dependent diabetes: a chronic complication to acute pancreatitis in childhood acute lymphoblastic leukemia
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2019 (English)In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 66, no 1, article id e27437Article in journal (Refereed) Published
Abstract [en]

Pancreatitis is a frequent toxicity to acute lymphoblastic leukemia (ALL) treatment, significantly associated with asparaginase use, and may be followed by severe complications such as acute hyperglycaemia, need for mechanical ventilation, pseudocysts, and death. Here, we provide novel data on seven patients diagnosed with diabetes after pancreatitis and still requiring insulin treatment after a median follow-up of 4.2 years (range: 1.7-9.2). We describe the clinical course of pancreatitis and illustrate the association between pancreatic pseudocysts, older age, and development of insulin-dependent diabetes. Together, this study documents the persisting burden of pancreatitis in childhood ALL and underlines the need for plasma glucose level monitoring.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2019
Keywords
acute lymphoblastic leukemia, diabetes, pancreatitis, toxicity
National Category
Pediatrics Gastroenterology and Hepatology
Identifiers
urn:nbn:se:umu:diva-154024 (URN)10.1002/pbc.27437 (DOI)000450821000024 ()30216644 (PubMedID)
Funder
Novo Nordisk
Available from: 2018-12-20 Created: 2018-12-20 Last updated: 2018-12-20Bibliographically approved
Espersen, A. D., Noren-Nyström, U., Abrahamsson, J., Ha, S.-Y., Pronk, C. J., Jahnukainen, K., . . . Hasle, H. (2018). Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is associated with infancy and trisomy 19: data from Nordic Society for Pediatric Hematology and Oncology (NOPHO-AML) and review of the literature. Genes, Chromosomes and Cancer, 57(7), 359-365
Open this publication in new window or tab >>Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is associated with infancy and trisomy 19: data from Nordic Society for Pediatric Hematology and Oncology (NOPHO-AML) and review of the literature
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2018 (English)In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 57, no 7, p. 359-365Article in journal (Refereed) Published
Abstract [en]

The t(7;12)(q36;p13) (MNX1/ETV6) is not included in the WHO classification but has been described in up to 30% of acute myeloid leukemia (AML) in children <2 years and associated with a poor prognosis. We present the clinical and cytogenetics characteristics of AML cases with t(7;12)(p36;p13). A literature review identified 35 patients with this translocation, published between 2000 and 2015. Outcome data were available in 22 cases. The NOPHO-AML (Nordic Society for Pediatric Hematology and Oncology) database contained 651 patients with AML from 1993 to 2014 and seven (1.1%) had the translocation. The t(7;12) was only present in patients <2 years of age (median age 6 months) but none was diagnosed as newborn. These patients constituted 4.3% of the patients <2 years of age. There was a strong association with trisomy 19 (literature: 86%, NOPHO: 100%) and +8 (literature: 19%, NOPHO: 14%). Seventeen of 22 patients from the literature with t(7;12) and four of seven patients from the NOPHO database suffered from relapse. The patients with t(7;12) had a 3-year event free survival of 24% (literature) vs. 43% (NOPHO) and a 3-year overall survival of 42% (literature) vs. 100% (NOPHO). None of the NOPHO patients was treated with hematopoietic stem cell transplantation (HSCT) in first complete remission. Relapse was frequent but the salvage rate using HSCT was high. We conclude that t(7;12)(q36;13) is a unique subgroup of childhood AML with presentation before 2 years of age with most cases being associated with +19.

Keywords
acute leukemia, AML, cytogenetics, pediatric, t(7;12)(q36;p13)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-147395 (URN)10.1002/gcc.22538 (DOI)29569294 (PubMedID)
Available from: 2018-05-03 Created: 2018-05-03 Last updated: 2018-06-14Bibliographically approved
Hammer, A. S., Juul-Dam, K., Sandahl, J. D., Abrahamsson, J., Balwierz, W., Guilmatre, A., . . . Kjeldsen, E. (2018). Hypodiploidy in Childhood Acute Myeloid Leukemia: A Retrospective Cohort Study within the International Berlin-Frankfurt-Munster Study Group. Paper presented at 60th Annual Meeting of the American-Society-of-Hematology (ASH), 1-4 December, 2018, San Diego, California, USA. Blood, 132
Open this publication in new window or tab >>Hypodiploidy in Childhood Acute Myeloid Leukemia: A Retrospective Cohort Study within the International Berlin-Frankfurt-Munster Study Group
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2018 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 132Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
American Society of Hematology, 2018
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-157236 (URN)10.1182/blood-2018-99-109988 (DOI)000454837604137 ()
Conference
60th Annual Meeting of the American-Society-of-Hematology (ASH), 1-4 December, 2018, San Diego, California, USA
Note

Supplement 1

Meeting abstract 1466

Available from: 2019-03-20 Created: 2019-03-20 Last updated: 2019-03-20Bibliographically approved
Olsson, L., Lundin-Ström, K. B., Castor, A., Behrendtz, M., Biloglav, A., Norén-Nyström, U., . . . Johansson, B. (2018). Improved cytogenetic characterization and risk stratification of pediatric acute lymphoblastic leukemia using single nucleotide polymorphism array analysis: A single center experience of 296 cases. Genes, Chromosomes and Cancer, 57(11), 604-607
Open this publication in new window or tab >>Improved cytogenetic characterization and risk stratification of pediatric acute lymphoblastic leukemia using single nucleotide polymorphism array analysis: A single center experience of 296 cases
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2018 (English)In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 57, no 11, p. 604-607Article in journal (Refereed) Published
Abstract [en]

Single nucleotide polymorphism array (SNP‐A) analyses are increasingly being introduced in routine genetic diagnostics of acute lymphoblastic leukemia (ALL). Despite this, only few studies that have compared the diagnostic value of SNP‐A with conventional chromosome banding have been published. We here report such a comparison of 296 ALL cases, the largest series to date. Only genomic imbalances >5 Mb and microdeletions targeting the BTG1, CDKN2A/B, EBF1, ERG, ETV6, IKZF1, PAX5, and RB1 genes and the pseudoautosomal region 1 (PAR1) were ascertained, in agreement with recent guidelines. Of 36 T‐cell ALL cases, the karyotypes of 24 cases (67%) were revised by SNP‐A analyses that either revealed additional imbalances >5 Mb or better characterized the changes found by G‐banding. Of 260 B‐cell precursor (BCP) ALL cases, SNP‐A analyses identified additional copy number alterations, including the above‐mentioned microdeletions, or better characterized the imbalances found by G‐banding in 236 (91%) cases. Furthermore, the cytogenetic subtype classification of 41/260 (16%) BCP ALL cases was revised based on the SNP‐A findings. Of the subtype revisions, 12/41 (29%) had clinical implications as regards risk stratifying cytogenetic groups or genotype‐specific minimal residual disease stratification. We conclude that SNP‐A analyses dramatically improve the cytogenetic characterization of both T‐cell and BCP ALL and also provide important information pertinent to risk stratification of BCP ALL.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
array analysis, clinical genetic diagnostics, pediatric acute lymphoblastic leukemia, single nucleotide polymorphism
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-153118 (URN)10.1002/gcc.22664 (DOI)000447757100009 ()30203896 (PubMedID)2-s2.0-85053404815 (Scopus ID)
Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2018-11-12Bibliographically approved
Toft, N., Birgens, H., Abrahamsson, J., Griskevicius, L., Hallböök, H., Heyman, M., . . . Schmiegelow, K. (2018). Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia. Leukemia, 32(3), 606-615
Open this publication in new window or tab >>Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia
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2018 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 32, no 3, p. 606-615Article in journal (Refereed) Published
Abstract [en]

Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P = 0.53). Event-free survival rates (pEFS(5y)) were 89 +/- 1% (A), 80 +/- 3% (B) and 74 +/- 4% (C) with significant differences only for non-high risk groups. Except for thrombosis, pancreatitis and osteonecrosis, the risk of 19 specified toxicities was not enhanced by age above 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:umu:diva-146231 (URN)10.1038/leu.2017.265 (DOI)000427041900004 ()28819280 (PubMedID)
Available from: 2018-04-09 Created: 2018-04-09 Last updated: 2018-06-09Bibliographically approved
Stukenborg, J.-B. -., Alves-Lopes, J. P., Kurek, M., Albalushi, H., Reda, A., Keros, V., . . . Jahnukainen, K. (2018). Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy. Human Reproduction, 33(9), 1677-1683
Open this publication in new window or tab >>Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy
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2018 (English)In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 33, no 9, p. 1677-1683Article in journal (Refereed) Published
Abstract [en]

STUDY QUESTION: Does chemotherapy exposure (with or without alkylating agents) or primary diagnosis affect spermatogonial quantity in human prepubertal testicular tissue? SUMMARY ANSWER: Spermatogonial quantity is significantly reduced in testes of prepubertal boys treated with alkylating agent therapies or with hydroxyurea for sickle cell disease. WHAT IS KNOWN ALREADY: Cryopreservation of spermatogonial stem cells, followed by transplantation into the testis after treatment, is a proposed clinical option for fertility restoration in children. The key clinical consideration behind this approach is a sufficient quantity of healthy cryopreserved spermatogonia. However, since most boys with malignancies start therapy with agents that are not potentially sterilizing, they will have already received some chemotherapy before testicular tissue cryopreservation is considered. STUDY DESIGN, SIZE, DURATION: We examined histological sections of prepubertal testicular tissue to elucidate whether chemotherapy exposure or primary diagnosis affects spermatogonial quantity. Quantity of spermatogonia per transverse tubular cross-section (S/T) was assessed in relation to treatment characteristics and normative reference values in histological sections of paraffin embedded testicular tissue samples collected from 32 consecutive boy patients (aged 6.3 +/- 3.8 [mean +/- SD] years) between 2014 and 2017, as part of the NORDFERTIL study, and in 14 control samples (from boys aged 5.6 +/- 5.0 [mean +/- SD] years) from an internal biobank. PARTICIPANTS/MATERIALS, SETTING, METHODS: Prepubertal boys in Sweden, Finland and Iceland who were facing treatments associated with a very high risk of infertility, were offered the experimental procedure of testicular cryopreservation. Exclusion criteria were testicular volumes > 10 ml and high bleeding or infection risk. There were 18 patients with a diagnosis of malignancy and 14 patients a nonmalignant diagnosis. While 20 patients had the testicular biopsy performed 1-45 days after chemotherapy, 12 patients had not received any chemotherapy. In addition, 14 testicular tissue samples of patients with no reported testicular pathology, obtained from the internal biobank of the Department of Pathology at Karolinska University Hospital, were included as control samples in addition to reference values obtained from a recently published meta-analysis. The quantity of spermatogonia was assessed by both morphological and immunohistochemical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The main finding was a significant reduction in spermatogonial cell counts in boys treated with alkylating agents or with hydroxyurea for sickle cell disease. The mean S/T values in boys exposed to alkylating agents (0.2 +/- 0.3, n = 6) or in boys with sickle cell disease and exposed to hydroxyurea (0.3 +/- 0.6, n = 6) were significantly lower (P = 0.003 and P = 0.008, respectively) than in a group exposed to non-alkylating agents or in biobank control samples (1.7 +/- 1.0, n = 8 and 4.1 +/- 4.6, n = 14, respectively). The mean S/T values of the testicular tissue samples included in the biobank control group and the patient group exposed to nonalkylating agents were within recently published normative reference values. LIMITATIONS, REASONS FOR CAUTION: Normal testicular tissue samples included in this study were obtained from the internal biobank of Karolinska University Hospital. Samples were considered normal and included in the study if no testicular pathology was reported in the analysed samples. However, detailed information regarding previous medical treatments and testicular volumes of patients included in this biobank were not available. WIDER IMPLICATIONS OF THE FINDINGS: This study summarizes, for the first time, spermatogonial quantity in a prepubertal patient cohort just before and after potentially sterilizing treatments. Boys facing cancer and cytotoxic therapies are regarded as the major group who will benefit from novel fertility preservation techniques. There are no previous reports correlating spermatogonial quantity to cumulative exposure to alkylating agents and anthracyclines (non-alkylating agents) and no information about the timing of cytotoxic exposures among this particular patient cohort. For prepubertal boys in whom fertility preservation is indicated, testicular tissue should be obtained before initiation of chemotherapy with alkylating agents, whilst for those with sickle cell disease and treated with hydroxyurea, this approach to fertility preservation may not be feasible. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from The Swedish Childhood Cancer Foundation (PR2016-0124; TJ2016-0093; PR2015-0073, TJ2015-0046) (J.-B.S. and K.J.), the Jane and Dan Olssons Foundation (2016-33) (J.-B.S.), the Finnish Cancer Society (K.J.), the Foundation for Paediatric Research (J.-B.S.), Kronprinsessan Lovisas Forening For Barnasjukvard/Stiftelsen Axel Tielmans Minnesfond, Samariten Foundation (J.-B.S.), the Vare Foundation for Paediatric Cancer Research (K.J.) and the Swedish Research Council (2012-6352) (O.S.). R.T.M. was supported by a Wellcome Trust Fellowship (09822). J.P.A.-L. and M.K. were supported by the ITN Marie Curie program 'Growsperm' (EU-FP7-PEOPLE-2013-ITN 603568). The authors declare no conflicts of interest.

Place, publisher, year, edition, pages
Oxford University Press, 2018
Keywords
fertility preservation, childhood cancer, sickle cell disease, alkylating agents, spermatogonial quantity
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-154859 (URN)10.1093/humrep/dey240 (DOI)000452615200011 ()30052981 (PubMedID)2-s2.0-85054967057 (Scopus ID)
Funder
Swedish Childhood Cancer FoundationSwedish Research Council, 2012-6352Wellcome trust, 09822
Available from: 2019-01-04 Created: 2019-01-04 Last updated: 2019-01-04Bibliographically approved
Karlsson, L., Forestier, E., Hasle, H., Jahnukainen, K., Jonsson, O. G., Lausen, B., . . . Abrahamsson, J. (2017). Outcome after intensive reinduction therapy and allogeneic stem cell transplant in paediatric relapsed acute myeloid leukaemia. British Journal of Haematology, 178(4), 592-602
Open this publication in new window or tab >>Outcome after intensive reinduction therapy and allogeneic stem cell transplant in paediatric relapsed acute myeloid leukaemia
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2017 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 178, no 4, p. 592-602Article in journal (Refereed) Published
Abstract [en]

Given that 30-40% of children with acute myeloid leukaemia (AML) relapse after primary therapy it is important to define prognostic factors and identify optimal therapy. From 1993 to 2012, 543 children from the Nordic countries were treated according to two consecutive protocols: 208 children relapsed. The influence of disease characteristics, first line treatment, relapse therapy and duration of first remission on outcome was analysed. Second complete remission (CR2) was achieved in 146 (70%) patients. Estimated 5-year overall survival (OS5y) was 39 +/- 4% for the whole group and 43 +/- 4% for the 190 patients given re-induction therapy, of whom 76% received regimens that included fludarabine, cytarabine (FLA) +/- anthracyclines, 18% received Nordic Society for Paediatric Haematology and Oncology (NOPHO) upfront blocks and 5% received other regimens. Late relapse >= 1 year from diagnosis, no allogeneic stem cell transplantation (SCT) in first remission and core binding factor AML were independent favourable prognostic factors for survival. For the 128 children (124 in CR2) that received SCT as consolidation therapy after relapse, OS5y was 61 +/- 5%. Four of 19 children (21%) survived without receiving SCT as part of relapse therapy. Our data show that intensive re-induction followed by SCT can give cure rates of 40% in children with relapsed AML.

Place, publisher, year, edition, pages
WILEY, 2017
Keywords
acute myeloid leukaemia, relapsed, childhood, allogenic stem cell transplant, survival
National Category
Hematology Pediatrics
Identifiers
urn:nbn:se:umu:diva-138591 (URN)10.1111/bjh.14720 (DOI)000406911500013 ()28439893 (PubMedID)
Available from: 2017-09-21 Created: 2017-09-21 Last updated: 2018-06-09Bibliographically approved
Toft, N., Birgens, H., Abrahamsson, J., Griskevicius, L., Hallbook, H., Heyman, M., . . . Schmiegelow, K. (2016). ADULTS AND CHILDREN (1-45 YEARS) WITH PH-NEGATIVE ALL HAVE ALMOST IDENTICAL OUTCOME IN RISK-STRATIFIED ANALYSIS OF NOPHO ALL2008. Paper presented at 21st Congress of the European-Hematology-Association, JUN 09-12, 2016, Copenhagen, DENMARK. Haematologica, 101, 35-35
Open this publication in new window or tab >>ADULTS AND CHILDREN (1-45 YEARS) WITH PH-NEGATIVE ALL HAVE ALMOST IDENTICAL OUTCOME IN RISK-STRATIFIED ANALYSIS OF NOPHO ALL2008
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2016 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 35-35Article in journal, Meeting abstract (Other academic) Published
National Category
Hematology
Identifiers
urn:nbn:se:umu:diva-124687 (URN)000379484600075 ()
External cooperation:
Conference
21st Congress of the European-Hematology-Association, JUN 09-12, 2016, Copenhagen, DENMARK
Available from: 2016-09-12 Created: 2016-08-22 Last updated: 2018-06-07Bibliographically approved
Borssén, M., Haider, Z., Landfors, M., Norén-Nyström, U., Schmiegelow, K., Åsberg, A. E., . . . Degerman, S. (2016). DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia. Pediatric Blood & Cancer, 63(7), 1185-1192
Open this publication in new window or tab >>DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia
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2016 (English)In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 63, no 7, p. 1185-1192Article in journal (Refereed) Published
Abstract [en]

Background. Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Procedure. Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Results. Two distinct CpG island methylator phenotype (CIMP) groups were identified. Patients with a CIMP-negative profile had an inferior response to treatment compared to CIMP-positive patients (3-year cumulative incidence of relapse (CIR3y) rate: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high-risk T-ALL patients (MRD >= 0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ regarding ETP phenotype, but the CIMP-negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP-positive group. Conclusions. CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making.

Keywords
childhood leukemia, DNA methylation, MRD, prognosis, T-ALL, WBC
National Category
Cancer and Oncology Hematology Pediatrics
Identifiers
urn:nbn:se:umu:diva-124837 (URN)10.1002/pbc.25958 (DOI)000380105400008 ()26928953 (PubMedID)
Available from: 2016-10-03 Created: 2016-08-26 Last updated: 2019-05-10Bibliographically approved
Ranta, S., Nilsson, F., Harila-Saari, A., Saft, L., Tani, E., Söderhall, S., . . . Heyman, M. (2015). Detection of Central Nervous System Involvement in Childhood Acute Lymphoblastic Leukemia by Cytomorphology and Flow Cytometry of the Cerebrospinal Fluid. Pediatric Blood & Cancer, 62(6), 951-956
Open this publication in new window or tab >>Detection of Central Nervous System Involvement in Childhood Acute Lymphoblastic Leukemia by Cytomorphology and Flow Cytometry of the Cerebrospinal Fluid
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2015 (English)In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 62, no 6, p. 951-956Article in journal (Refereed) Published
Abstract [en]

Background: Therapy directed at the central nervous system (CNS) is an essential part of the treatment for childhood acute lymphoblastic leukemia (ALL). The current evaluation of CNS involvement based on cytomorphological examination of the cerebrospinal fluid (CSF) alone is not as sensitive with low cell counts as flow cytometric immunophenotyping (FCI) of the CSF. However, the importance of low CSF blasts counts at diagnosis is uncertain. We sought to determine the significance of FCI in relation to conventional morphological examination.

Procedure: We retrospectively compared FCI of the CSF with cytomorphology at diagnosis or relapse of childhood ALL. All patients were diagnosed 2000–2012 in Stockholm or Umeå, Sweden. Clinical data were collected from medical records and the Nordic leukemia registry. Treatment assignment was based on morphological examination only.

Results: The cohort was comprised of 214 patients with ALL. CSF involvement was detected by both methods in 20 patients, in 17 by FCI alone, and in one patient by cytomorphology alone. The relapse rate was higher for patients with negative cytology but positive FCI compared to those without CNS involvement using both methods. The difference was especially marked in the current protocol. However, none of the patients with negative CSF cytology but positive FCI had a CNS relapse.

Conclusions: FCI of the CSF increased the detection rate of CNS involvement of ALL approximately two times compared to cytomorphology. Patients with low-level CNS involvement may benefit from additional intensified systemic or CNS-directed therapy, but larger studies are needed. 

Keywords
cerebrospinal fluid, cytology, flow cytometric immunophenotyping, leukemia
National Category
Pediatrics Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-103183 (URN)10.1002/pbc.25363 (DOI)000353231500006 ()25545289 (PubMedID)
Available from: 2015-06-30 Created: 2015-05-18 Last updated: 2018-06-07Bibliographically approved
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