Abstract
Therapy related acute leukemia consists of a unique subset of acute leukemia with an increased frequency of high risk cytogenetic and molecular abnormalities, dismal response to therapy, higher relapse rates and poor overall survival. Therapy related acute myeloid leukemia (t-AML) is a better defined disease entity than therapy related acute lymphoid leukemia (t-ALL). However, in recent times, t-ALL is also being increasingly recognized and extensively studied. Therapy related acute myeloid leukemia is usually classified together with therapy related myelodysplastic syndrome. However, the management of these two diseases maybe different regarding needs of induction chemotherapy and eligibility for upfront allogeneic hematopoietic stem cell transplantation (Allo HSCT). There is also evidence regarding differences in prognosis and outcomes between these two entities. Allo HSCT offers a potential for cure in t-AML and t-ALL. However, existing literature on the same is confounded by inclusion of t-MDS and secondary acute leukemias. Here we review the current evidence on the outcomes and predictors of outcomes of Allo HSCT in the management of therapy related acute leukemias. We also shed light into the under-representation of therapy related leukemias in clinical trials. This stresses the need for prospective trials incorporating measurable residual disease monitoring and sequential next generation sequencing based genomic data for accurate prognostication and management of therapy related acute leukemia.
Similar content being viewed by others
References
Vardiman JW (2008) Therapy-related myeloid neoplasms. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues 127–129
Morton LM, Dores GM, Tucker MA, Kim CJ, Onel K, Gilbert ES, Fraumeni JF Jr et al (2013) Evolving risk of therapy-related acute myeloid leukemia following cancer. Blood 121(15):2996–3004. https://doi.org/10.1182/blood-2012-08-448068
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM et al (2016) The 2016 revision to the World Health Organization classification of myeloid. Blood 127(20):2391–2405. https://doi.org/10.1182/blood-2016-03-643544
Bagg A (2011) Therapy-associated lymphoid proliferations. Adv Anat Pathol 18(3):199–205. https://doi.org/10.1097/PAP.0b013e31821698ef
Abdulwahab A, Sykes J, Kamel-Reid S, Chang H, Brandwein JM (2012) Therapy-related acute lymphoblastic leukemia is more frequent than previously. Cancer 118(16):3962–3967. https://doi.org/10.1002/cncr.26735
Rosenberg AS, Brunson A, Paulus JK, Tuscano J, Wun T, Keegan THM et al (2017) Secondary acute lymphoblastic leukemia is a distinct clinical entity with. Blood Cancer J 7(9):e605. https://doi.org/10.1038/bcj.2017.81
Leone G, Mele L, Pulsoni A, Equitani F, Pagano L. The incidence of secondary leukemias (0390–6078 (Print))
Borthakur G, Estey AE. Therapy-related acute myelogenous leukemia and myelodysplastic syndrome (1523–3790 (Print))
Schoch C, Kern W, Schnittger S, Hiddemann W, Haferlach T (2004) Karyotype is an independent prognostic parameter in therapy-related acute myeloid. Leukemia 18(1):120–125
Saygin C, Kishtagari A, Cassaday RD, Reizine N, Yurkiewicz I, Liedtke M et al (2019) Therapy-related acute lymphoblastic leukemia is a distinct entity with adverse. Blood Adv 3(24):4228–4237. https://doi.org/10.1182/bloodadvances.2019000925
Kyle RA, Pierre RV, Bayrd ED (1970) Multiple myeloma and acute myelomonocytic leukemia. N Engl J Med 283(21):1121–1125
Pui CH, Behm FG, Raimondi SC, Dodge RK, George SL, Rivera GK, Mirro J Jr et al (1989) Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia. N Engl J Med 321(3):136–142
Bacher U, Haferlach C, Alpermann T, Schnittger S, Kern W, Haferlach T (2013) Patients with therapy-related myelodysplastic syndromes and acute myeloid. Leuk Lymphoma 54(3):639–642. https://doi.org/10.3109/10428194.2012.717275
Singh ZN, Huo D, Anastasi J, Smith SM, Karrison T, Le Beau MM, Larson RA et al (2007) Therapy-related myelodysplastic syndrome: morphologic subclassification may not. Am J Clin Pathol 127(2):197–205
Mauritzson N, Albin M, Rylander L, Billstrom R, Ahlgren T, Mikoczy Z, Bjork J et al (2002) Pooled analysis of clinical and cytogenetic features in treatment-related and de. Leukemia 16(12):2366–2378
Ok CY, Patel KP, Garcia-Manero G, Routbort MJ, Fu B, Tang G et al (2015) Mutational profiling of therapy-related myelodysplastic syndromes and acute. Leuk Res 39(3):348–354. https://doi.org/10.1016/j.leukres.2014.12.006
Shih AH, Chung SS, Dolezal EK, Zhang S-J, Abdel-Wahab OI, Park CY, Nimer SD et al (2013) Mutational analysis of therapy-related myelodysplastic syndromes and acute. Haematologica 98(6):908–912. https://doi.org/10.3324/haematol.2012.076729
Litzow MR, Tarima S, Perez WS, Bolwell BJ, Cairo MS, Camitta BM, Cutler CS et al. Allogeneic transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia (1528–0020 (Electronic))
Kroger N, Brand R, van Biezen A, Zander A, Dierlamm J, Niederwieser D, Devergie A et al (2009) Risk factors for therapy-related myelodysplastic syndrome and acute myeloid. Haematologica 94(4):542–549. https://doi.org/10.3324/haematol.2008.000927
Nampoothiri RV, Law AD, Chen C, Lam W, Al-Shaibani Z, Loach D et al (2020) Predictors of outcomes in adult patients with therapy related acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplant—twenty year experience from a tertiary care centre. Biol Blood Marrow Transplant 26(Supplement 3):S107–S108
Granfeldt Ostgard LS, Medeiros BC, Sengelov H, Norgaard M, Andersen MK, Dufva IH et al (2015) Epidemiology and clinical significance of secondary and therapy-related acute. J Clin Oncol 33(31):3641–3649. https://doi.org/10.1200/JCO.2014.60.0890
Larson RA (2012) Cytogenetics, not just previous therapy, determines the course of therapy-related. J Clin Oncol 30(19):2300–2302. https://doi.org/10.1200/JCO.2011.41.1215
Yakoub-Agha I, de La Salmoniere P, Ribaud P, Sutton L, Wattel E, Kuentz M, Jouet JP et al. Allogeneic bone marrow transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia: a long-term study of 70 patients-report of the French society of bone marrow transplantation (0732–183X (Print))
Anderson JE, Gooley TA, Schoch G, Anasetti C, Bensinger WI, Clift RA, Hansen JA et al (1997) Stem cell transplantation for secondary acute myeloid leukemia: evaluation of. Blood 89(7):2578–2585
Kayser S, Dohner K, Krauter J, Kohne C-H, Horst HA, Held G, von Lilienfeld-Toal M et al (2011) The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853. Blood 117(7):2137–2145. https://doi.org/10.1182/blood-2010-08-301713
Styczynski J, Tridello G, Koster L, Iacobelli S, van Biezen A, van der Werf S et al (2020) Death after hematopoietic stem cell transplantation: changes over calendar year. Bone Marrow Transplant 55(1):126–136. https://doi.org/10.1038/s41409-019-0624-z
Chang C, Storer BE, Scott BL, Scott BL, Bryant EM, Shulman HM, Flowers ME, Sandmaier BM et al (2007) Hematopoietic cell transplantation in patients with myelodysplastic syndrome or. Blood 110(4):1379–1387
Fianchi L, Pagano L, Piciocchi A, Candoni A, Gaidano G, Breccia M, Criscuolo M et al. Characteristics and outcome of therapy-related myeloid neoplasms: report from the Italian network on secondary leukemias (1096–8652 (Electronic))
de Witte T, Hermans J, Vossen J, Bacigalupo A, Meloni G, Jacobsen N, Ruutu T et al (2000) Haematopoietic stem cell transplantation for patients with myelo-dysplastic. Br J Haematol 110(3):620–630
Queralt Salas MA, Prem SA, Atenafu EG, Datt Law AA, Lam W, Al-Shaibani Z et al (2020) Dual T-cell depletion with ATG and PTCy for peripheral blood reduced intensity. Bone Marrow Transplant. https://doi.org/10.1038/s41409-020-0813-9
Borate UA, Norris BA, Statler AA, Fu R, Bucy T, Sekeres MA (2019) Representation of therapy-related myelodysplastic syndrome in clinical trials. Blood Adv 3(18):2738–2747. https://doi.org/10.1182/bloodadvances.2019000293
Ishizawa S, Slovak ML, Popplewell L, Bedell V, Wrede JE, Carter NH, Carter NH, Snyder DS et al (2003) High frequency of pro-B acute lymphoblastic leukemia in adults with secondary. Leukemia 17(6):1091–1095
Pagano L, Pulsoni A, Tosti ME, Annino L, Mele A, Camera A, Martino B et al (1999) Acute lymphoblastic leukaemia occurring as second malignancy: report of the GIMEMA archive of adult acute leukaemia. Br J Haematol 106(4):1037–1040
Ganzel C, Devlin S, Douer D, Rowe JM, Stein EM, Tallman MS (2015) Secondary acute lymphoblastic leukaemia is constitutional and probably not related to prior therapy. Br J Haematol 170(1):50–55. https://doi.org/10.1111/bjh.13386
Giri S, Chi M, Johnson B, McCormick D, Jamy O, Bhatt VR et al (2015) Secondary acute lymphoblastic leukemia is an independent predictor of poor. Leuk Res. 39(12):1342–6. https://doi.org/10.1016/j.leukres.2015.09.011
Ribera JM (2018) Therapy-related acute lymphoblastic leukemia. Haematologica 103(10):1581–1583. https://doi.org/10.3324/haematol.2018.200311
Aldoss I, Dagis A, Palmer J, Forman S, Pullarkat V (2015) Therapy-related ALL: cytogenetic features and hematopoietic cell transplantation. Bone Marrow Transplant 50(5):746–748. https://doi.org/10.1038/bmt.2015.8
Tang G, Zuo Z, Thomas DA, Lin P, Liu D, Hu Y, Kantarjian HM et al (2012) Precursor B-acute lymphoblastic leukemia occurring in patients with a history of prior malignancies: is it therapy-related? Haematologica 97(6):919–925. https://doi.org/10.3324/haematol.2011.057752
Aldoss I, Stiller T, Tsai NC, Song JY, Cao T, Bandara NA et al (2018) Therapy-related acute lymphoblastic leukemia has distinct clinical and cytogenetic features compared to de novo acute lymphoblastic leukemia, but outcomes are comparable in transplanted patients. Haematologica 103(10):1662–1668. https://doi.org/10.3324/haematol.2018.193599
Pedersen-Bjergaard J, Philip P (1991) Balanced translocations involving chromosome bands 11q23 and 21q22 are highly characteristic of myelodysplasia and leukemia following therapy with cytostatic agents targeting at DNA-topoisomerase II. Blood 78(4):1147–1148
Super HJ, McCabe NR, Thirman MJ, Larson RA, Le Beau MM, Pedersen-Bjergaard J, Philip P et al (1993) Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA-topoisomerase II. Blood 82(12):3705–3711
Vasudevan Nampoothiri R, Law AD, Lam W, Chen C, Al-Shaibani Z, Loach D et al (2020) Outcomes of therapy-related acute lymphoblastic leukemia in adults after allogeneic stem cell transplantation. Eur J Haematol 105(1):24–29. https://doi.org/10.1111/ejh.13403
Pagana L, Pulsoni A, Tosti ME, Avvisati G, Mele L, Mele M, Martino B et al (2001) Clinical and biological features of acute myeloid leukaemia occurring as second malignancy: GIMEMA archive of adult acute leukaemia. Br J Haematol 112(1):109–117
Shivakumar R, Tan W, Wilding GE, Wang ES, Wetzler M (2008) Biologic features and treatment outcome of secondary acute lymphoblastic leukemia—a review of 101 cases. Ann Oncol 19(9):1634–8. https://doi.org/10.1093/annonc/mdn182
Kelleher N, Gallardo D, Gonzalez-Campos J, Hernandez-Rivas JM, Montesinos P, Sarra J et al (2016) Incidence, clinical and biological characteristics and outcome of secondary acute lymphoblastic leukemia after solid organ or hematologic malignancy. Leuk Lymphoma 57(1):86–91. https://doi.org/10.3109/10428194.2015.1040013
Acknowledgements
The authors would like to acknowledge the contribution of Dr. Shikha Malhotra M.D. for her contribution towards editing the manuscript.
Funding
No funding source.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest to disclose.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Vasudevan Nampoothiri, R., Viswabandya, A. Allogeneic Hematopoietic Stem Cell Transplantation in Therapy Related Acute Leukemia. Indian J Hematol Blood Transfus 37, 521–527 (2021). https://doi.org/10.1007/s12288-020-01334-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12288-020-01334-4