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. 2022 Sep 13;6(17):4936-4948.
doi: 10.1182/bloodadvances.2022007597.

Outcomes of allogeneic hematopoietic cell transplantation in adults with fusions associated with Ph-like ALL

Ibrahim Aldoss  1 , Dongyun Yang  2 , Vanina Tomasian  3 , Sally Mokhtari  4 , Ryan Jackson  3 , Zhaohui Gu  2 , Milhan Telatar  3 , Hooi Yew  3 , Monzr M Al Malki  1 , Amandeep Salhotra  1 , Samer Khaled  1 , Haris Ali  1 , Ahmed Aribi  1 , Karamjeet S Sandhu  1 , Matthew Mei  1 , Shukaib Arslan  1 , Paul Koller  1 , Andrew Artz  1 , Patricia Aoun  3 , Dongqing Gu  3 , David Snyder  1 , Forrest M Stewart  1 , Peter Curtin  1 , Anthony S Stein  1 , Raju Pillai  3 , Guido Marcucci  1 , Stephen J Forman  1 , Vinod Pullarkat  1 , Ryotaro Nakamura  1 , Michelle Afkhami  3
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Outcomes of allogeneic hematopoietic cell transplantation in adults with fusions associated with Ph-like ALL

Ibrahim Aldoss et al. Blood Adv. .

Abstract

Allogenic hematopoietic cell transplantation (alloHCT) is a well-established curative modality for acute lymphoblastic leukemia (ALL), yet large amounts of data describing alloHCT outcomes in Philadelphia (Ph)-like ALL are lacking. We retrospectively analyzed archived DNA samples from consecutive adults with B-cell Ph-negative ALL who underwent alloHCT in complete remission (CR) (n = 127) at our center between 2006 and 2020. Identification of fusions associated with Ph-like ALL was performed using cumulative results from RNA-seq, conventional cytogenetics, fluorescence in situ hybridization, and whole genome array studies. Fusions associated with Ph-like ALL were detected in 56 (44%) patients, of whom 38 were carrying CRLF2r. Compared with other non-Ph-like ALL (n = 71), patients with fusions associated with Ph-like ALL were more frequently Hispanic (P = .008), were less likely to carry high-risk cytogenetics (P < .001), and were more likely to receive blinatumomab prior to HCT (P = .019). With the median followup of 3.5 years, patients with Ph-like ALL fusions had comparable posttransplant outcomes compared with other B-cell ALL: 3-year relapse-free survival (RFS) (41% vs 44%; P = .36), overall survival (OS) (51% vs 50%; P = .59), and relapse (37% vs 31%; P = .47). In multivariable analysis, age (P = .023), disease status at the time of transplant (P < .001), and donor type (P = .015) influenced OS. RFS (primary endpoint) was significantly influenced by disease status (P < .001) and conditioning regimen intensity (P = .014). In conclusion, our data suggest that alloHCT consolidation results in similarly favorable survival outcomes in adult patients with Ph-like fusions and other high-risk B-cell ALL.

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Figures

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Graphical abstract
Figure 1.
Figure 1.
Flow diagram of the study design.
Figure 2.
Figure 2.
Genomic classification. (A) Flow diagram of the final comprehensive genomic classification. (B) Pie chart showing the frequency of genomic alterations in adults with Ph-like ALL.
Figure 3.
Figure 3.
Kaplan-Meier curves for survival outcomes at 3 years after HCT. (A) OS and RFS for all patients. (B) Comparison of RFS in patients with and without Ph-like ALL. (C) Comparison of OS in patients with and without Ph-like ALL.
Figure 4.
Figure 4.
Kaplan-Meier curves. (A) Relapse and NRM for all patients. (B) Comparison of relapse in patients with and without Ph-like ALL. (C) Comparison of NRM in patients with and without Ph-like ALL.
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