MRD-Based Therapeutic Decisions in Genetically Defined Subsets of Adolescents and Young Adult Philadelphia-Negative ALL
by
, , , , and
Manuela Tosi
1, 
Orietta Spinelli
1,
Matteo Leoncin
2,
Roberta Cavagna
1,
Chiara Pavoni
1,
Federico Lussana
1,
Tamara Intermesoli
1,
Luca Frison
2,
Giulia Perali
2,
Francesca Carobolante
2,
Piera Viero
2,
Cristina Skert
2,
Alessandro Rambaldi
1,3 and
Renato Bassan
2,* 1
Hematology Unit, Azienda Socio Sanitaria Territoriale (ASST), Ospedale Papa Giovanni XXIII, 24127 Bergamo, Italy
2
Hematology Unit, Azienda Ulss3 Serenissima, Ospedale dell’Angelo, 30174 Venezia-Mestre, Italy
3
Department of Oncology-Hematology, University of Milan, 20122 Milan, Italy
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(9), 2108; https://doi.org/10.3390/cancers13092108
Submission received: 2 April 2021
/
Revised: 21 April 2021
/
Accepted: 22 April 2021
/
Published: 27 April 2021
(This article belongs to the Special Issue Minimal Residual Disease of Cancers)
Simple Summary
In acute lymphoblastic leukemia (ALL), once a complete remission is achieved following induction chemotherapy, the study of submicroscopic minimal residual disease (MRD) represents a highly sensitive tool to assess the efficacy of early chemotherapy courses and predict outcome. Because of the significant therapeutic progress occurred in adolescent and young adult (AYA) ALL, the importance of MRD in this peculiar age setting has grown considerably, to refine individual prognostic scores within different genetic subsets and support specific risk and MRD-oriented programs. The evidence coming from the most recent MRD-based studies and the new therapeutic directions for AYA ALL are critically reviewed according to ALL subset and risk category.
Abstract
In many clinical studies published over the past 20 years, adolescents and young adults (AYA) with Philadelphia chromosome negative acute lymphoblastic leukemia (Ph− ALL) were considered as a rather homogeneous clinico-prognostic group of patients suitable to receive intensive pediatric-like regimens with an improved outcome compared with the use of traditional adult ALL protocols. The AYA group was defined in most studies by an age range of 18–40 years, with some exceptions (up to 45 years). The experience collected in pediatric ALL with the study of post-induction minimal residual disease (MRD) was rapidly duplicated in AYA ALL, making MRD a widely accepted key factor for risk stratification and risk-oriented therapy with or without allogeneic stem cell transplantation and experimental new drugs for patients with MRD detectable after highly intensive chemotherapy. This combined strategy has resulted in long-term survival rates of AYA patients of 60–80%. The present review examines the evidence for MRD-guided therapies in AYA’s Ph− ALL, provides a critical appraisal of current treatment pitfalls and illustrates the ways of achieving further therapeutic improvement according to the massive knowledge recently generated in the field of ALL biology and MRD/risk/subset-specific therapy
