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. 2022 Oct 12;6(11):e788.
doi: 10.1097/HS9.0000000000000788. eCollection 2022 Nov.

CNS Involvement at Initial Diagnosis and Risk of Relapse After Allogeneic HCT for Acute Lymphoblastic Leukemia in First Complete Remission

Mohamed A Kharfan-Dabaja  1 , Myriam Labopin  2 , Ali Bazarbachi  3 , Urpu Salmenniemi  4 , Stephan Mielke  5 , Patrice Chevallier  6 , Marie Thérèse Rubio  7 , Marie Balsat  8 , Pietro Pioltelli  9 , Anne-Lise Menard  10 , Gerard Socié  11 , Anne Huynh  12 , Nicolaas Schaap  13 , Arancha Bermúdez Rodríguez  14 , Jan J Cornelissen  15 , Ibrahim Yakoub-Agha  16 , Mahmoud Aljurf  17 , Sebastian Giebel  18 , Eolia Brissot  2 , Zina Peric  19 , Arnon Nagler  20   21 , Mohamad Mohty  2   21
Affiliations

CNS Involvement at Initial Diagnosis and Risk of Relapse After Allogeneic HCT for Acute Lymphoblastic Leukemia in First Complete Remission

Mohamed A Kharfan-Dabaja et al. Hemasphere. .

Abstract

Outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adult acute lymphoblastic leukemia (ALL) have improved over time. Studies have shown that total body irradiation (TBI) is the preferable type of myeloablative conditioning (MAC). However, outcomes based on central nervous system (CNS) involvement, namely CNS-positive versus CNS-negative, have not been compared. Here, we evaluated outcomes of 547 patients (CNS-positive = 96, CNS-negative = 451) who were allografted in the first complete remission (CR1) between 2009 and 2019. Primary endpoint was leukemia-free survival (LFS). Median follow-up was not different between the CNS-positive and CNS-negative groups (79 versus 67.2 months, P = 0.58). The CNS-positive group were younger (median age 31.3 versus 39.7 years, P = 0.004) and were allografted more recently (median year 2012 versus 2010, P = 0.003). In both groups, MAC was the preferred approach (82.3% versus 85.6%, P = 0.41). On multivariate analysis, the CNS-positive group had higher incidence of relapse (RI) (hazard ratio [HR] = 1.58 [95% confidence interval (CI) = 1.06-2.35], P = 0.025), but no adverse effect on LFS (HR = 1.38 [95% CI = 0.99-1.92], P = 0.057) or overall survival (OS) (HR = 1.28 [95% CI = 0.89-1.85], P = 0.18). A subgroup multivariate analysis limited to CNS-positive patients showed that a TBI-based MAC regimen resulted in better LFS (HR = 0.43 [95% CI = 0.22-0.83], P = 0.01) and OS (HR = 0.44 [95% CI = 0.21-0.92], P = 0.03) and lower RI (HR = 0.35 [95% CI = 0.15-0.79], P = 0.01). Another subgroup analysis in CNS-negative patients showed that MAC-TBI preparative regimens also showed a lower RI without a benefit in LFS or OS. While a MAC-TBI allo-HCT regimen may not be suitable to all, particularly for older patients with comorbidities, this approach should be considered for patients who are deemed fit and able to tolerate.

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Figures

Figure 1.
Figure 1.
Leukemia-free survival. LFS = leukemia-free survival.
Figure 2.
Figure 2.
Cumulative incidence of relapse. CNS = central nervous system.
Figure 3.
Figure 3.
Leukemia-free survival. Multivariate analysis for patients with CNS involvement. CNS = central nervous system; LFS = leukemia-free survival; TBI-MAC = total body irradiation-myeloablative conditioning.
Figure 4.
Figure 4.
Overall survival. Multivariate analysis for patients with CNS involvement. CNS = central nervous system; OS = overall survival; TBI-MAC = total body irradiation-myeloablative conditioning.
Figure 5.
Figure 5.
Cumulative incidence of relapse. Multivariate analysis for patients with CNS involvement. CNS = central nervous system; TBI-MAC = total body irradiation-myeloablative conditioning.
See this image and copyright information in PMC

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