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Indications for allogeneic hematopoietic cell transplantation for adults with Philadelphia-chromosome negative acute lymphoblastic leukemia in first complete remission: all about MRD?

Bone Marrow Transplantation volume 54, pages 3–5 (2019)Cite this article

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Allogeneic hematopoietic cell transplantation (HCT) consolidation has an established record of curing acute lymphoblastic leukemia (ALL) in a subset of adult patients. Historically, the majority of adults with ALL were deemed high-risk, and thus, allogeneic HCT was offered more broadly as a consolidation in suitable candidates at a time when effective salvage regimens for relapsed ALL were lacking. Allogeneic HCT was particularly recommended to consolidate high-risk adult ALL defined based on traditional risk factors such as cytogenetics, older age, and elevated initial white blood cell count. Several prospective studies were conducted that utilized biological randomization to examine the benefit of allogeneic HCT in adults with ALL who attained first complete remission (CR1). The majority of these studies illustrated superiority of HCT over chemotherapy consolidation in reducing leukemia relapse, and several of those studies even demonstrated survival advantage with the transplantation approach [1,2,3]. Nevertheless, who attains the most benefit from early allogeneic HCT was and still remains a matter of debate.

More recently, the management of adult ALL has witnessed changes at an unprecedented pace, and this may impact and alter the indications for allogeneic HCT for adults with Philadelphia-chromosome negative (Ph−) ALL in CR1. Hence, the role of allogeneic HCT consolidation must be re-examined in the context of some key advances in ALL management. First, contemporary pediatric-inspired regimens have been safely administered to fit adults at least until 50 years of age [4,5,6,7], and these regimens have yielded long-term outcomes that appear similar to results of allogeneic HCT consolidation in CR1 [8]. Secondly, the introduction of minimal residual disease (MRD) monitoring, a sensitive and reliable biological marker of leukemia chemosensitivity has refined the management of ALL with frontline regimens [4, 9, 10]. The routine application of MRD has led to better stratifying ALL patients as well as identifying patients who have better chances of cure with chemotherapy only approach. Thus, MRD has emerged as a very powerful and dynamic prognostic tool that has to a large extent replaced traditional risk factors in guiding the decision to transplant. Finally, classifying ALL using next-generation sequencing approaches in addition to cytogenetics has led to discovery of high-risk genomic features that were previously undefined and has refined our ability to identify new high-risk prognostic subgroups that would previously have been considered standard-risk. The key example is ALL with Philadelphia-like (Ph-like) gene signature, a high-risk subset that responds poorly to traditional chemotherapy regimens and may require novel treatment approaches possibly in conjunction with allogeneic HCT for cure [11].

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References

  1. Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008;111:1827–33.

    Article  CAS  Google Scholar 

  2. Cornelissen JJ, van der Holt B, Verhoef GE, van’t Veer MB, van Oers MH, Schouten HC, et al. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison. Blood. 2009;113:1375–82.

    Article  CAS  Google Scholar 

  3. Thomas X, Boiron JM, Huguet F, e Dombret H, Bradstock K, Vey N, et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004;22:4075–86.

    Article  CAS  Google Scholar 

  4. Stock W, Luger SM, Advani AS, Geyer S, Harvey RC, Mullighan CG, et al. Favorable outcomes for older adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL): early results of US intergroup trial C10403. Blood. 2014;124:796.

    Google Scholar 

  5. DeAngelo DJ, Stevenson KE, Dahlberg SE, Silverman LB, Couban S, Supko JG, et al. Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia. Leukemia. 2015;29:526–34.

    Article  CAS  Google Scholar 

  6. Douer D, Aldoss I, Lunning MA, Burke PW, Ramezani L, Mark L, et al. Pharmacokinetics-based integration of multiple doses of intravenous pegaspargase in a pediatric regimen for adults with newly diagnosed acute lymphoblastic leukemia. J Clin Oncol. 2014;32:905–11.

    Article  CAS  Google Scholar 

  7. Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol. 2009;27:911–8.

    Article  CAS  Google Scholar 

  8. Seftel MD, Neuberg D, Zhang MJ, Wang HL, Ballen KK, Bergeron J, et al. Pediatric-inspired therapy compared to allografting for Philadelphia chromosome-negative adult ALL in first complete remission. Am J Hematol. 2016;91:322–9.

    Article  Google Scholar 

  9. Gokbuget N, Kneba M, Raff T, Trautmann H, Bartram CR, Arnold R, et al. Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood. 2012;120:1868–76.

    Article  Google Scholar 

  10. Ribera JM, Oriol A, Morgades M, Montesinos P, Sarrà J, González-Campos J, et al. Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial. J Clin Oncol. 2014;32:1595–604.

    Article  CAS  Google Scholar 

  11. Roberts KG, Gu Z, Payne-Turner D, McCastlain K, Harvey RC, Chen IM, et al. High frequency and poor outcome of philadelphia chromosome-like acute lymphoblastic leukemia in adults. J Clin Oncol. 2017;35:394–401.

    Article  Google Scholar 

  12. Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375:740–53.

    Article  CAS  Google Scholar 

  13. Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376:836–47.

    Article  CAS  Google Scholar 

  14. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–48.

    Article  CAS  Google Scholar 

  15. Giebel S, Marks DI, Boissel N, Baron F, Chiaretti S, Ciceri F, et al. Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2018.

  16. Bar M, Wood BL, Radich JP, Doney KC, Woolfrey AE, Delaney C, et al. Impact of minimal residual disease, detected by flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia. Leuk Res Treat. 2014;2014:421723.

    Google Scholar 

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  1. Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA, USA

    Ibrahim Aldoss & Vinod Pullarkat

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  1. Ibrahim Aldoss
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Correspondence to Ibrahim Aldoss.

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Aldoss, I., Pullarkat, V. Indications for allogeneic hematopoietic cell transplantation for adults with Philadelphia-chromosome negative acute lymphoblastic leukemia in first complete remission: all about MRD?. Bone Marrow Transplant 54, 3–5 (2019). https://doi.org/10.1038/s41409-018-0398-8

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