Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913

Chiaretti, Sabina; Messina, Monica; Starza, Irene Della; Piciocchi, Alfonso; Cafforio, Luciana; Cavalli, Marzia; Taherinasab, Akram; Ansuinelli, Michela; Elia, Loredana; Petroni, Guglielmo Albertini; Starza, Roberta La; Canichella, Martina; Lauretti, Alessia; Puzzolo, Maria Ctristina; Pierini, Valentina; Santoro, Alessandra; Spinelli, Orietta; Apicella, Valerio; Capria, Saveria; Raimondo, Francesco Di; Fabritiis, Paolo de; Papayannidis, Cristina; Candoni, Anna; Cairoli, Roberto; Cerrano, Marco; Fracchiolla, Nicola; Mattei, Daniele; Cattaneo, Chiara; Vitale, Antonella; Crea, Enrico; Fazi, Paola; Mecucci, Cristina; Rambaldi, Alessandro; Guarini, Anna; Bassan, Renato; Foà, Robin

doi:10.3324/haematol.2020.247973

Cited by 57 publications

(59 citation statements)

References 37 publications

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“…[66] [Figure 1]. A similar trend has been found in B-ALL specifically, with the highest incidence seen in Hispanics/Latinos and the lowest in Blacks [94] . Among older adults, ALL incidence again predominates among Hispanics/Latinos [5] .…”

Section: Incidence Of All Is Highest In Hispanics/latinossupporting

confidence: 66%

Disparities in acute lymphoblastic leukemia risk and survival across the lifespan in the United States of America

Xu¹,

Feng²,

Smith³

2021

jtgg

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Acute lymphoblastic leukemia (ALL) is the most common childhood cancer but is less frequent in adolescents and young adults (AYAs) and is rare among older adults. The 5-year survival of ALL is above 90% in children, but drops significantly in AYAs, and over half of ALL-related deaths occur in older adults. In addition to diagnosis age, the race/ethnicity of patients consistently shows association with ALL incidence and outcomes. Here, we review the racial/ethnic disparities in ALL incidence and outcomes, discuss how these vary across the age spectrum, and examine the potential causes of these disparities. In the United States, the incidence of ALL is highest in Hispanics/Latinos and lowest in Black individuals across all age groups. ALL incidence is rising fastest in Hispanics/Latinos, especially in AYAs. In addition, survival is worse in Hispanic/Latino or Black ALL patients compared to those who are non-Hispanic White. Different molecular subtypes of ALL show heterogeneities in incidence rates and survival outcomes across age groups and race/ethnicity. Several ALL risk variants are associated with genetic ancestry, and demonstrate different risk allele frequencies and/or effect sizes across populations. Moreover, non-genetic factors including socioeconomic status, access to care, and environmental exposures all likely influence the disparities in ALL risk and survival. Further studies are needed to investigate the potential joint effects and interactions of genetic and environmental risk factors. Improving survival in Hispanic/Latino and Black patients with ALL requires advances in precision medicine approaches, improved access

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Section: Incidence Of All Is Highest In Hispanics/latinossupporting

confidence: 66%

Disparities in acute lymphoblastic leukemia risk and survival across the lifespan in the United States of America

Xu¹,

Feng²,

Smith³

2021

jtgg

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“…A 44‐year‐old man diagnosed in March 2018 with early T‐precursor ALL was treated according to an intensive paediatric‐like protocol, 9 achieving complete remission (CR) but not MRD‐negative status. After total body irradiation‐based myeloablative allo‐SCT from his haploidentical sister, bone marrow (BM) MRD became negative, but reappeared three months later.…”

Section: Figurementioning

confidence: 99%

Immunomodulatory and clinical effects of daratumumab in T‐cell acute lymphoblastic leukaemia

et al. 2020

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The described cases point to the difficulties in distinguishing manifestations related to RA from those of SCD in patients with joint complaints, independently of the genotype or severity of complications of SCD. It is strongly advised to keep in mind the possibility of RA coexistence when the clinical course of the painful crisis in SCD patients does not follow the expected trajectory. The prompt use of agents which target the underlying pathophysiology of RA remains the best option for the prevention of potential damage in these patients, who usually present with comorbidities due to SCD.

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“…This study reported 100% complete remissions even for Ph-like ALL, although with a short duration, lower number of molecular remissions and a higher rate of early relapses, confirming the negative prognostic impact on survival of the Ph-like ALL subtype in intensively treated older adults [ 17 ]. A similar prevalence (~20%) and poor clinical outcome were observed in patients enrolled in different GIMEMA (Gruppo Italiano Malattie EMatologiche dell’Adulto) clinical trials [ 18 ], where patients with Ph-like ALL had a lower rate of complete remissions and a worse event free survival compared with non Ph-like ALL cases [ 18 , 19 ].…”

Section: Clinical Features Of Ph-like Allmentioning

confidence: 74%

Genetic Alterations and Therapeutic Targeting of Philadelphia-Like Acute Lymphoblastic Leukemia

Iacobucci

Roberts

2021

Genes

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Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subgroup of B-cell precursor ALL which by gene expression analysis clusters with Philadelphia-positive ALL although lacking the pathognomonic BCR-ABL1 oncoprotein. Its prevalence increases with age and similar to BCR-ABL1-positive ALL, Ph-like ALL is characterized by IKZF1 or other B-lymphoid transcription factor gene deletions and by poor outcome to conventional therapeutic approaches. Genetic alterations are highly heterogenous across patients and include gene fusions, sequence mutations, DNA copy number changes and cryptic rearrangements. These lesions drive constitutively active cytokine receptor and kinase signaling pathways which deregulate ABL1 or JAK signaling and more rarely other kinase-driven pathways. The presence of activated kinase alterations and cytokine receptors has led to the incorporation of targeted therapy to the chemotherapy backbone which has improved treatment outcome for this high-risk subtype. More recently, retrospective studies have shown the efficacy of immunotherapies including both antibody drug-conjugates and chimeric antigen receptor T cell therapy and as they are not dependent on a specific genetic alteration, it is likely their use will increase in prospective clinical trials. This review summarizes the genomic landscape, clinical features, diagnostic assays, and novel therapeutic approaches for patients with Ph-like ALL.

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Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913

Abstract: Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913

Cited by 57 publications

References 37 publications

Disparities in acute lymphoblastic leukemia risk and survival across the lifespan in the United States of America

Disparities in acute lymphoblastic leukemia risk and survival across the lifespan in the United States of America

Immunomodulatory and clinical effects of daratumumab in T‐cell acute lymphoblastic leukaemia

Genetic Alterations and Therapeutic Targeting of Philadelphia-Like Acute Lymphoblastic Leukemia

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