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Published in: Journal of Hematopathology 2/2019

01-06-2019 | Acute Lymphoblastic Leukemia | Original Article

Bone marrow fibrosis as prognostic marker in adult patients with acute lymphoblastic leukemia

Authors: Ana Cooke, Daniel Montante-Montes, Diego Zúñiga-Tamayo, Mauricio Rivera, Christianne Bourlon, Álvaro Aguayo, Roberta Demichelis-Gómez

Published in: Journal of Hematopathology | Issue 2/2019

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Abstract

The role of bone marrow (BM) fibrosis on outcomes of children with acute lymphoblastic leukemia (ALL) has been described with inconsistent results. In adults, there is no information regarding its significance. The aim of this study was to describe the prognostic impact of BM fibrosis in this group of patients. We included 88 biopsies of 44 adult patients. Reticulin and Masson trichrome stains were performed. Fibrosis was graded by modified Bauermeister scale and volume of reticulin/collagen fibers, both methods had good correlation. Survival analyses were performed regarding (1) the presence or not of significant fibrosis at diagnosis, (2) the reduction or not of fibrosis post-treatment, and (3) the amount of fibrosis at diagnosis combined with the depth of the reduction post-treatment. Sixty-six percent of the patients had significant fibrosis at diagnosis (Bauermeister ≥ grade 2) and 45% achieved a significant reduction (≥ 50% volume of reticulin/collagen fibers) post-treatment. The presence of fibrosis at diagnosis had no clear impact on outcomes; however, a significant reduction of the fibrosis post-treatment in patients with standard-risk ALL was correlated with longer RFS (19.1 months vs 10.6 months, p = .022) and OS (54.4 months vs 16.4 months, p = .033). Patients who had fibrosis at diagnosis combined with a deep reduction post-treatment had a better RFS and OS compared with those who did not have fibrosis at diagnosis regardless of its reduction or those who did not achieve a deep reduction. To our knowledge, this is the first study to describe an impact of BM fibrosis reduction post-treatment in adult patients with ALL.
Literature
1.
go back to reference Howlader N, Noone A, Krapcho M, et al. (2017) SEER cancer statistics review, 1975-2014, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2014/, based on November 2016 SEER data submission, posted to the SEER web site, April Http://SeerCancerGov/Csr/1975_2014/. 2017:1-101. Accessed November 2017 Howlader N, Noone A, Krapcho M, et al. (2017) SEER cancer statistics review, 1975-2014, National Cancer Institute. Bethesda, MD, http://​seer.​cancer.​gov/​csr/​1975_​2014/​, based on November 2016 SEER data submission, posted to the SEER web site, April Http://SeerCancerGov/Csr/1975_2014/. 2017:1-101. Accessed November 2017
5.
go back to reference Crespo-Solis E, Espinosa-Bautista K, Alvarado-Ibarra M, Rozen-Fuller E, Pérez-Rocha F, Nava-Gómez C, Ortiz-Zepeda M, Álvarez-Vera JL, Ramos-Peñafiel CO, Meillón-García LA, Rodríguez-Rodríguez S, Pomerantz-Okon A, Turrubiates-Hernández FJ, Demichelis-Gómez R (2018) Retrospective study of adults with acute lymphoid leukemia in Mexico City: first report of the working Group of Acute Leukemia (GTLA). Cancer Med 7(6):2423–2433. https://doi.org/10.1002/cam4.15132017. CrossRefPubMedPubMedCentral Crespo-Solis E, Espinosa-Bautista K, Alvarado-Ibarra M, Rozen-Fuller E, Pérez-Rocha F, Nava-Gómez C, Ortiz-Zepeda M, Álvarez-Vera JL, Ramos-Peñafiel CO, Meillón-García LA, Rodríguez-Rodríguez S, Pomerantz-Okon A, Turrubiates-Hernández FJ, Demichelis-Gómez R (2018) Retrospective study of adults with acute lymphoid leukemia in Mexico City: first report of the working Group of Acute Leukemia (GTLA). Cancer Med 7(6):2423–2433. https://​doi.​org/​10.​1002/​cam4.​15132017.​ CrossRefPubMedPubMedCentral
7.
go back to reference Hann IM, Evans DI, Marsden HB, Jones PM, Palmer MK (1978) Bone marrow fibrosis in acute lymphoblastic leukaemia of childhood. J Clin Pathol 31(4):313–315CrossRefPubMedPubMedCentral Hann IM, Evans DI, Marsden HB, Jones PM, Palmer MK (1978) Bone marrow fibrosis in acute lymphoblastic leukaemia of childhood. J Clin Pathol 31(4):313–315CrossRefPubMedPubMedCentral
8.
go back to reference Perez-Atayde AR, Sallan SE, Tedrow U, Connors S, Allred E, Folkman J (1997) Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am J Pathol 150(3):815–821PubMedPubMedCentral Perez-Atayde AR, Sallan SE, Tedrow U, Connors S, Allred E, Folkman J (1997) Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. Am J Pathol 150(3):815–821PubMedPubMedCentral
11.
go back to reference Belurkar S, Nepali PB, Manandhar B, Manohar C (2015) Evaluation of post chemotherapy bone marrow changes in acute Leukaemia. Int J Sci Res Publ 5(1):2250–3153 www.ijsrp.org Belurkar S, Nepali PB, Manandhar B, Manohar C (2015) Evaluation of post chemotherapy bone marrow changes in acute Leukaemia. Int J Sci Res Publ 5(1):2250–3153 www.​ijsrp.​org
21.
go back to reference Kantarjian HM, O’Brien S, Smith TL et al (2000) Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 18(3):547–561CrossRefPubMed Kantarjian HM, O’Brien S, Smith TL et al (2000) Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 18(3):547–561CrossRefPubMed
22.
go back to reference Arteaga-Ortiz L, Buitrón-Santiago N, Rosas-López A, Rosas-Arzate G, Armengolt-Jiménez A, Aguayo A, López-Karpovitch X, Crespo-Solís E (2008) Experiencia del INCMNSZ en pacientes adultos con leucemia linfoide aguda. Cohorte 2003-2007 con esquemas de tratamiento Hiper-CVAD y Protocolo 0195. Rev Investig Clin 60(6):459–469 Arteaga-Ortiz L, Buitrón-Santiago N, Rosas-López A, Rosas-Arzate G, Armengolt-Jiménez A, Aguayo A, López-Karpovitch X, Crespo-Solís E (2008) Experiencia del INCMNSZ en pacientes adultos con leucemia linfoide aguda. Cohorte 2003-2007 con esquemas de tratamiento Hiper-CVAD y Protocolo 0195. Rev Investig Clin 60(6):459–469
24.
go back to reference NCCN Guidelines Version 2.2016 Acute lymphoblastic leukemia. NCCN Guidelines Version 2.2016 Acute lymphoblastic leukemia.
31.
go back to reference Aguayo A, Kantarjian H, Manshouri T, Gidel C, Estey E, Thomas D, Koller C, Estrov Z, O'Brien S, Keating M, Freireich E, Albitar M (2000) Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood. 96(6):2240–2245PubMed Aguayo A, Kantarjian H, Manshouri T, Gidel C, Estey E, Thomas D, Koller C, Estrov Z, O'Brien S, Keating M, Freireich E, Albitar M (2000) Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood. 96(6):2240–2245PubMed
35.
go back to reference Herold T, Schneider S, Metzeler KH, Neumann M, Hartmann L, Roberts KG, Konstandin NP, Greif PA, Bräundl K, Ksienzyk B, Huk N, Schneider I, Zellmeier E, Jurinovic V, Mansmann U, Hiddemann W, Mullighan CG, Bohlander SK, Spiekermann K, Hoelzer D, Brüggemann M, Baldus CD, Dreyling M, Gökbuget N (2017 Jan) Adults with Philadelphia chromosome – like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis. Haematologica. 102(1):130–138. https://doi.org/10.3324/haematol.2015.136366 CrossRefPubMedPubMedCentral Herold T, Schneider S, Metzeler KH, Neumann M, Hartmann L, Roberts KG, Konstandin NP, Greif PA, Bräundl K, Ksienzyk B, Huk N, Schneider I, Zellmeier E, Jurinovic V, Mansmann U, Hiddemann W, Mullighan CG, Bohlander SK, Spiekermann K, Hoelzer D, Brüggemann M, Baldus CD, Dreyling M, Gökbuget N (2017 Jan) Adults with Philadelphia chromosome – like acute lymphoblastic leukemia frequently have IGH-CRLF2 and JAK2 mutations, persistence of minimal residual disease and poor prognosis. Haematologica. 102(1):130–138. https://​doi.​org/​10.​3324/​haematol.​2015.​136366 CrossRefPubMedPubMedCentral
36.
go back to reference Thiele J, Kvasnicka HM, Facchetti F, Franco V, Van Der WJ, Orazi A (2005) European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 90:1128–1132PubMed Thiele J, Kvasnicka HM, Facchetti F, Franco V, Van Der WJ, Orazi A (2005) European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 90:1128–1132PubMed
Metadata
Title
Bone marrow fibrosis as prognostic marker in adult patients with acute lymphoblastic leukemia
Authors
Ana Cooke
Daniel Montante-Montes
Diego Zúñiga-Tamayo
Mauricio Rivera
Christianne Bourlon
Álvaro Aguayo
Roberta Demichelis-Gómez
Publication date
01-06-2019
Publisher
Springer Berlin Heidelberg
Published in
Journal of Hematopathology / Issue 2/2019
Print ISSN: 1868-9256
Electronic ISSN: 1865-5785
DOI
https://doi.org/10.1007/s12308-019-00353-z

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