Page 132 - 2019_10 resto del Mondo_web

Ferrata Storti Foundation
Haematologica 2019 Volume 104(10):2028-2039
Acute Lymphoblastic Leukemia
A systematic literature review and meta- analysis of minimal residual disease as a prognostic indicator in adult B-cell acute lymphoblastic leukemia
Renato Bassan,1 Monika Brüggemann,2 Hoi-Shen Radcliffe,3 Elizabeth Hartfield,4 Georg Kreuzbauer5 and Sally Wetten3
1Complex Operative Unit of Haematology, dell'Angelo Hospital and Santissimi Giovanni
2
and Paolo Hospital, Mestre and Venice, Italy; Department of Medicine II, Schleswig-
Holstein University Hospital, Kiel, Germany; 3Amgen Ltd, Uxbridge, UK; 4Oxford PharmaGenesis, Oxford, UK and 5Amgen (Europe) GmbH, Zug, Switzerland
ABSTRACT
Minimal (or ‘measurable’) residual disease in acute lymphoblastic leukemia appears to be a prognostic indicator, with potential value in informing individualized treatment decisions. Complete understanding of the strength of the association between minimal residual disease and long-term outcomes is, however, lacking. A systematic litera- ture review and meta-analysis were performed to elucidate the clinical sig- nificance of minimal residual disease with respect to relapse-free survival and overall survival in precursor B-cell acute lymphoblastic leukemia. A total of 23 articles and abstracts, most published between 2012 and 2016, were identified for inclusion in the primary meta-analysis. Typically, patients were in their first complete remission at the time of minimal resid- ual disease assessment; in two studies, all patients were in their second, or later, complete remission. The primary analysis revealed improved relapse- free survival across all studies for patients who achieved minimal residual disease negativity (random effects hazard ratio, 2.34; 95% confidence inter- val, 1.91–2.86). Improved overall survival for patients who achieved mini- mal residual disease negativity was also observed (hazard ratio, 2.19; 95% confidence interval, 1.63–2.94). There was no observed difference in the impact of minimal residual disease status in subgroups based on disease stage, minimal residual disease sensitivity threshold level, Philadelphia chromosome status, histological phenotype, risk group, minimal residual disease testing location, minimal residual disease timing after induction, or minimal residual disease detection method. Despite heterogeneity in study design and patient populations between the contributing studies, these data provide a compelling argument for minimal residual disease as a clinical tool for assessing prognosis and guiding treatment decisions in precursor B- cell acute lymphoblastic leukemia.
Introduction
Acute lymphoblastic leukemia (ALL) is a heterogeneous disease that derives from lymphoid cell populations.1 Precursor B-cell ALL (B-ALL) is the most com- mon immunological subtype,2 and the most common genetic abnormality in B- ALL is the Philadelphia chromosome (Ph-positive ALL), found in approximately one-quarter of adult patients.3 Genetic or molecular profiling can be used to char- acterize disease prognosis, predict response to therapy, and inform treatment deci- sions.4,5
The mainstay of treatment for patients with newly diagnosed B-ALL has histor- ically involved induction chemotherapy, followed by consolidation and mainte- nance chemotherapies; allogeneic hematopoietic stem cell transplantation (HSCT) is recommended following consolidation in selected high-risk groups.6 However,
Correspondence:
RENATO BASSAN
renato.bassan@aulss3.veneto.it
Received: July 2, 2018. Accepted: March 14, 2019. Pre-published: March 19, 2019.
doi:10.3324/haematol.2018.201053
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/10/2028
©2019 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
2028
haematologica | 2019; 104(10)
ARTICLE