Retrospective Evaluation of Patients Who Underwent Allogeneic Stem Cell Transplantation for Bone Marrow Failure

Year 2023, , 262 - 270, 29.10.2023

Tuba Ersal , Vildan Ozkocaman

https://doi.org/10.46310/tjim.1359793

Abstract

Background: Bone marrow failure is a disease that develops due to different etiologies. Aplastic anaemia (AA) and hypocellular myelodysplastic syndrome (HMDS) are the most common bone marrow failure disorders. Treatment options include supportive therapy, immunosuppressive therapy, and allogeneic hematopoietic stem cell transplantation (allo-HCT). Allo-HCT is the only curative treatment option. This study aimed to retrospectively evaluate the demographic characteristics, treatment, and transplantation results of patients who underwent Allo-HCT for bone marrow failure.
Material and Methods: This single-centre retrospective study enrolled 11 patients (9 with severe AA and 2 with HMDS) who underwent allo-HCT for bone marrow failure. The patients' records until 17.08.2023 were analysed. Age, gender, diagnosis, donor age and gender, type of transplantation, pre-transplant ferritin levels, time to transplantation, volume of infused product, number of CD34+ cells in the infused product, post-transplant engraftment times, discharge time, transplant-related complications, post-transplant follow-up and overall survival times were obtained.
Results: Eleven patients underwent 12 allo-HCTs for bone marrow failure. Seven patients were male, and four were female. The median age was 40, and seven patients were ≥40 years old at the time of transplantation. Eleven transplants were performed from HLA fully matched siblings and one from a 9/10 matched sibling donor. Bone marrow was used as a stem cell source in 8 transplants and peripheral blood in 4 transplants. The conditioning regimen was fludarabine/cyclophosphamide/anti-thymocyte globulin in all patients. The median time from diagnosis to transplantation was five months. The median time for neutrophil engraftment was 23 days. The median platelet >20.000/mm3 engraftment time was 16 days. A statistically significant positive correlation was found between ferritin levels and platelet >20.000/mm3 engraftment (days) (r=0.653, p=0.040) and platelet >50.000/mm3 engraftment (days) (r=0.720, p=0.029). There was a statistically significant negative correlation between the number of infused CD34 positive cells (10⁶/kg) and platelet >50.000/mm3 engraftment (days) (r=-0.670, p=0.024). Patients were discharged in a median of 23 days. Acute graft versus host disease (GvHD) was observed in one patient, while chronic GvHD was not observed in any patient. The median overall survival time was 48 months, and the median post-transplant follow-up was 37 months. Secondary malignancy and MDS were not detected in any patient during the follow-up period. All 11 patients who underwent Allo-HCT from a matched sibling donor are alive and continue to have a complete hematological response. There was no increase in mortality and morbidity in patients aged 40 years and older.
Conclusions: In patients with severe AA and high-risk HMDS without comorbidities between the ages of 40 and 50, allo-HCT should be considered as first-line treatment in the presence of an HLA-matched sibling donor.

Keywords

Acquired severe aplastic anemia, bone marrow failure, myelodysplastic syndrome, allogeneic stem cell transplantation

References

• Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC; British Society for Standards in Haematology. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016 Jan;172(2):187-207. doi: 10.1111/bjh.13853. Erratum in: Br J Haematol. 2016 Nov;175(3):546.
• Bacigalupo A. How I treat acquired aplastic anemia. Blood. 2017 Mar 16;129(11):1428-36. doi: 10.1182/blood-2016-08-693481.
• Tichelli A, Marsh JC. Treatment of aplastic anaemia in elderly patients aged >60 years. Bone Marrow Transplant. 2013 Feb;48(2):180-2. doi: 10.1038/bmt.2012.224.
• Rice C, Eikema DJ, Marsh JCW, Knol C, Hebert K, Putter H, Peterson E, Deeg HJ, Halkes S, Pidala J, Anderlini P, Tischer J, Kroger N, McDonald A, Antin JH, Schaap NP, Hallek M, Einsele H, Mathews V, Kapoor N, Boelens JJ, Mufti GJ, Potter V, Pefault de la Tour R, Eapen M, Dufour C. Allogeneic hematopoietic cell transplantation in patients aged 50 years or older with severe aplastic anemia. Biol Blood Marrow Transplant. 2019 Mar;25(3):488-95. doi: 10.1016/j.bbmt.2018.08.029.
• Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405. Blood. 2016 Jul 21;128(3):462-463. doi: 10.1182/blood-2016-06-721662.
• Karantanos T, DeZern AE. Biology and clinical management of hypoplastic MDS: MDS as a bone marrow failure syndrome. Best Pract Res Clin Haematol. 2021 Jun;34(2):101280. doi: 10.1016/j.beha.2021.101280.
• Flowers ME, Kansu E, Sullivan KM. Pathophysiology and treatment of graft-versus-host disease. Hematol Oncol Clin North Am. 1999 Oct;13(5):1091-112, viii-ix. doi: 10.1016/s0889-8588(05)70111-8.
• Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.
• Zhang Y, Huo J, Liu L, Shen Y, Chen J, Zhang T, Chen X, Pang A, Yang D, Zhang R, Ma Q, Zhai W, He Y, Wei J, Jiang E, Han M, Zheng Y, Feng S. Comparison of hematopoietic stem cell transplantation outcomes using matched sibling donors, haploidentical donors, and immunosuppressive therapy for patients with acquired aplastic anemia. Front Immunol. 2022 Feb 1;13:837335. doi: 10.3389/fimmu.2022.837335.
• Schrezenmeier H, Passweg JR, Marsh JC, Bacigalupo A, Bredeson CN, Bullorsky E, Camitta BM, Champlin RE, Gale RP, Fuhrer M, Klein JP, Locasciulli A, Oneto R, Schattenberg AV, Socie G, Eapen M. Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia. Blood. 2007 Aug 15;110(4):1397-400. doi: 10.1182/blood-2007-03-081596.
• Bacigalupo A, Socié G, Schrezenmeier H, Tichelli A, Locasciulli A, Fuehrer M, Risitano AM, Dufour C, Passweg JR, Oneto R, Aljurf M, Flynn C, Mialou V, Hamladji RM, Marsh JC; Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation (WPSAA-EBMT). Bone marrow versus peripheral blood as the stem cell source for sibling transplants in acquired aplastic anemia: survival advantage for bone marrow in all age groups. Haematologica. 2012 Aug;97(8):1142-8. doi: 10.3324/haematol.2011.054841.
• Sangiolo D, Storb R, Deeg HJ, Flowers ME, Martin PJ, Sandmaier BM, Kiem HP, Nash RA, Doney K, Leisenring WM, Georges GE. Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age. Biol Blood Marrow Transplant. 2010 Oct;16(10):1411-8. doi: 10.1016/j.bbmt.2010.04.005.
• Wilfred G, Ong TC, Sh Shahnaz SAK, Wah HK, Carlo ES, Jameela S, Mui Tan S. Allogeneic hematopoietic stem cell transplantation in severe aplastic anemia: A single centre experience in Malaysia. Blood Cell Ther. 2022 Apr 8;5(2):45-53. doi: 10.31547/bct-2021-018.
• Gallo S, Woolfrey AE, Burroughs LM, Storer BE, Flowers ME, Hari P, Pulsipher MA, Heimfeld S, Kiem HP, Sandmaier BM, Storb R. Marrow grafts from HLA-identical siblings for severe aplastic anemia: does limiting the number of transplanted marrow cells reduce the risk of chronic GvHD? Bone Marrow Transplant. 2016 Dec;51(12):1573-8. doi: 10.1038/bmt.2016.198.
• Ciurea SO, de Lima M, Cano P, Korbling M, Giralt S, Shpall EJ, Wang X, Thall PF, Champlin RE, Fernandez-Vina M. High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation. Transplantation. 2009 Oct 27;88(8):1019-24. doi: 10.1097/TP.0b013e3181b9d710.
• Huang LF, Li L, Jia JS, Yang Y, Lin SY, Meng FK, Zhang DH, He GS. Frontline therapy options for adults with newly diagnosed severe aplastic anemia: Intensive immunosuppressive therapy plus eltrombopag or matched sibling donor hematopoietic stem cell transplantation? Transplant Cell Ther. 2022 Sep;28(9):586.e1-586.e7. doi: 10.1016/j.jtct.2022.05.027.
• Storb R, Prentice RL, Sullivan KM, Shulman HM, Deeg HJ, Doney KC, Buckner CD, Clift RA, Witherspoon RP, Appelbaum FA, Sanders JE, Stewart PS, Thomas ED. Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings. Ann Intern Med. 1983 Apr;98(4):461-6. doi: 10.7326/0003-4819-98-4-461.
• Chang YJ, Xu LP, Liu DH, Liu KY, Han W, Chen YH, Yu-Wang, Chen H, Wang JZ, Zhang XH, Zhao XY, Huang XJ. Platelet engraftment in patients with hematologic malignancies following unmanipulated haploidentical blood and marrow transplantation: effects of CD34+ cell dose and disease status. Biol Blood Marrow Transplant. 2009 May;15(5):632-8. doi: 10.1016/j.bbmt.2009.02.001.
• Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Alyea EP, Soiffer RJ, Antin JH. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood. 2007 May 15;109(10):4586-8. doi: 10.1182/blood-2006-10-054924.
• Platzbecker U, Ehninger G, Bornhäuser M. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem-cell transplantation. Blood. 2007 Oct 15;110(8):3083; author reply 3083-4. doi: 10.1182/blood-2007-05-089839.
• Pulsipher MA, Lehmann LE, Bertuch AA, Sasa G, Olson T, Nakano T, Gilio A, Burroughs LM, Lipton JM, Huang JN, Dickerson K, Bertaina A, Zhuang C, Malsch M, Fleming M, Weller E, Shimamura A, Williams DA. A study assessing the feasibility of randomization of pediatric and young adult patients between matched unrelated donor bone marrow transplantation and immune-suppressive therapy for newly diagnosed severe aplastic anemia: A joint pilot trial of the North American Pediatric Aplastic Anemia Consortium and the Pediatric Transplantation and Cellular Therapy Consortium. Pediatr Blood Cancer. 2020 Oct;67(10):e28444. doi: 10.1002/pbc.28444.