The relationship of bone marrow fibrosis at diagnosis with prognosis and survival in childhood acute lymphoblastic leukemia

Yıl 2023, Cilt: 9 Sayı: 2, 375 - 383, 04.03.2023

Çiğdem Özdemir Yeter Düzenli Kar Nilgün Eroğlu Hilal Susam Şen Yiğit Şenol İbrahim Eker

https://doi.org/10.18621/eurj.1244314

Öz

Objectives: Our aim in this study is to investigate the effect of fibrosis at diagnosis on treatment and survival in childhood acute lymphoblastic leukemia (ALL).

Methods: This study is retrospective. We evaluated the relationship between patients' age, white blood cell count at diagnosis, morphological blast percentage and flow cytometric blast percentage at diagnosis, day 15^th and day 33^th, absolute blast count in peripheral smear on day 8^th, and the degree of fibrosis in bone marrow biopsy at diagnosis in 36 pediatric patients. The fibrosis degree in biopsy on the thirty-third day after induction therapy was measured.

Results: Twenty-eight (77.8%) cases were diagnosed B-ALL and 8 T-ALL (22.2%). There was no statistically significant difference between the groups with and without fibrosis in terms of any parameter measured at the time of diagnosis, 8^th day, 15^th day, and 33^th day. No significant difference was found between the groups according to overall survival (OS): the mean OS was 50.22 ± 5.44 months in the fibrosis group and 49.70 ± 3.96 months in the non-fibrosis group (p = 0.557).

Conclusions: There is a high detection rate of bone marrow fibrosis in ALL pediatric cases at the time of diagnosis. Nevertheless, fibrosis does not affect survival.

Anahtar Kelimeler

Leukemia, fibrosis, bone marrow, childhood, lymphoblastic, microenvironment

Kaynakça

• 1. Kato M, Manabe A. Treatment and biology of pediatric acute lymphoblastic leukemia. Pediatr Int 2018;60:4-12.
• 2. Brown P, Inaba H, Annesley C, Beck J, Colace S, Dallas M, et al. Pediatric acute lymphoblastic leukemia, version 2.2020, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2020;18:81-112.
• 3. Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 2012;21:309-22.
• 4. Bissell MJ, Radisky D. Putting tumours in context. Nat Rev Cancer 2001;1:46-54.
• 5. Bader JE, Voss K, Rathmell JC. Targeting metabolism to improve the tumor microenvironment for cancer immunotherapy. Mol Cell 2020;78:1019-33.
• 6. Wu Z, Chen R, Wu L, Zou L, Ding F, Wang M, et al. Bone marrow fibrosis at diagnosis predicts survival for primary acute myeloid leukemia. Clin Transl Oncol 2017;19:1462-8.
• 7. Hughes AM, Kuek V, Kotecha RS, Cheung LC. The bone marrow microenvironment in B-cell development and malignancy. Cancers (Basel) 2022;14:2049.
• 8. Chen J, Hendriks M, Chatzis A, Ramasamy SK, Kusumbe AP. Bone vasculature and bone marrow vascular niches in health and disease. J Bone Miner Res 2020;35:2103-20.
• 9. Visnjic D, Kalajzic Z, Rowe DW, Katavic V, Lorenzo J, Aguila HL. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood 2004;103:3258-64.
• 10. Mansour A, Anginot A, Mancini SJ, Schiff C, Carle GF, Wakkach A, et al. Osteoclast activity modulates B-cell development in the bone marrow. Cell Res 2011;21:1102-15.
• 11. Żelechowska P, Brzezińska-Błaszczyk E, Kusowska A, Kozłowska E. The role of adipokines in the modulation of lymphoid lineage cell development and activity: an overview. Obes Rev 2020;21:e13055.
• 12. Hasselbalch HC. The role of cytokines in the initiation and progression of myelofibrosis. Cytokine Growth Factor Rev 2013;24:133-45.
• 13. Norén-Nyström U, Roos G, Bergh A, Botling J, Lönnerholm G, Porwit A, et al. Bone marrow fibrosis in childhood acute lymphoblastic leukemia correlates to biological factors, treatment response and outcome. Leukemia 2008;22:504-10.
• 14. Nguyen T-V, Melville A, Nath S, Story C, Howell S, Sutton R, et al. Bone marrow recovery by morphometry during induction chemotherapy for acute lymphoblastic leukemia in children. PloS One 2015;10:e0126233.
• 15. Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica 2005;90:1128-32.
• 16. Campbell M, Castillo L, Riccheri C, Janic D, Jazbec J, Kaiserova E, et al. A Randomized Trial of the I-BFM-SG for the Management of Childhood non-B Acute Lymphoblastic Leukemia. ALL IC-BFM, August 2009.
• 17. Leeuw JA, Koudstaal J, Wiersema-Buist J, Kamps WA, Timens W. Bone histomorphometry in children with newly diagnosed acute lymphoblastic leukemia. Pediatr Res 2003;54:814-8.
• 18. Nath SV, Nicholson I, Tapp H, Zola H, Zannettino AC, Revesz T. Reticulin fibres anchor leukaemic blasts in the marrow of patients with acute lymphoblastic leukaemia. Med Hypotheses 2011;77:333-5.
• 19. Døsen-Dahl G, Munthe E, Nygren MK, Stubberud H, Hystad ME, Rian E. Bone marrow stroma cells regulate TIEG1 expression in acute lymphoblastic leukemia cells: role of TGFbeta/BMP-6 and TIEG1 in chemotherapy escape. Int J Cancer 2008;123:2759-66.
• 20. Cooke A, Montante-Montes D, Zúñiga-Tamayo D, Rivera M, Bourlon C, Aguayo Á, et al. Bone marrow fibrosis as prognostic marker in adult patients with acute lymphoblastic leukemia. J Hematopathol 2019;12:75-84.
• 21. Wallis JP, Reid MM. Bone marrow fibrosis in childhood acute lymphoblastic leukaemia. J Clin Pathol 1989;42:1253-4.
• 22. Hann IM, Evans DI, Marsden HB, Jones PM, Palmer MK. Bone marrow fibrosis in acute lymphoblastic leukaemia of childhood. J Clin Pathol 1978;31:313-5.
• 23. Bharos, A, AJ de Jong, Nicholas Manton, N Venn, Colin Story, G Hodge, et al. Bone marrow fibrosis and vascular density lack prognostic significance in childhood acute lymphoblastic leukaemia. Leukemia 2010;24:1537-8.
• 24. Norén-Nyström U, Roos G, Bergh A, Forestier E. Prognostic impact of vascular density and fibrosis in the bone marrow of children with high-risk acute lymphoblastic leukemia. Leukemia 2005;19:1998-2001.
• 25. Abou Dalle I, Nassif S, Bazarbachi A. Acute promyelocytic leukemia with increased bone marrow reticulin fibrosis: description of three cases and review of the literature. Hematol Oncol Stem Cell Ther 2018;11:99-104.
• 26. Ayyanar P, Kar R, Dubashi B, Basu D. Post-chemotherapy changes in bone marrow in acute leukemia with emphasis on detection of residual disease by immunohistochemistry. Cureus 2021;13:e20175.