Hematopoietic Stem Cell Transplantation In Relapsed ALK + Anaplastic Large Cell Lymphoma Of Children and adolescent : A Study On Behalf Of The Sfce and SFGM-TC
Authors: Strullu Marion , Thomas Caroline , Raus Nicole , Paillard Catherine , Bertrand Yves , Jubert Charlotte , De La Tour Regis Peffaut , Lutz Patrick , Dalle Jean-Hugues , Lamant Laurence , Michel Gerard , Brugieres Laurence 
Published: October 2019

Abstract

Introduction
Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for the treatment of relapsed anaplastic large cell lymphoma (ALCL) in children. To date, few pediatric reports have assessed its efficiency and tolerance. While processing the evaluation of new targeted drugs, the impact of HSCT have to be precised in this population.

Patients and methods
We retrospectively analyzed the data all patients (n=34, median age 7.4y [1.1-17]) registered in the SFGM-TC database, who underwent a HSCT for the treatment of an ALCL ALK+ between 1993 and 2011. Central histology review was carried out for 29/34 patients. Most of patients were treated in specific french protocols (HM, n=4 and ALCL99, n=27). Indications of HSCT were based on the european group EICNHL recommandations for 14 patients : on-therapy relapse (n=1) and CD3 positivity (n=13). For 14 other patients, the decision of HSCT relied on one or several of the following criteria : leukemic form (n=6), post autologous transplantation relapse (n=5) and medullar positivity of the NPM1-ALK fusion transcript at relapse (n=7). In the 6 last patients, none risk factor was identifed. At transplant, 26 patients (65%) were in complete remission (CR) (CR1 n=1, CR2 n=18, CR3 n=4, CR4 n=3) whereas 8 (23,5%) had a detectable disease. Five patients had an history of previous autologous transplantation while 1 patient received 2 subsequent HSCT. Of the 35 HSCT performed, donors were HLA-matched related in 11 cases, mismatched related n=1, matched unrelated n=9 and mismatch unrelated n=14 (including 10 cord blood units). Conditionning regimens were mostly myelo-abaltive (n=30) with the use of a total body irradiation of 12 Gy in 26 patients.

Results
Engraftment was observed in 32 patients (median time for neutrophil recovery : 22d [9-44]).With a median follow up of 2.9y [0,1-11,8], 2-year (2y) overall and event-free survivals were respectively 69,6%+-8% and 58,1%+-9%. Cumulative incidences of relapse and non-relapse mortality were 17,8%+-6% and 24,2%+-7% respectively. Six patients (including 3 without CR at transplant) relapsed (median time 108 days [35-235]). Prolounged CR was obtained in 4/6 patients after donor lymphocytes injection (n=1) or Vinblastine-corticosteroid treatment (n=3, with a follow-up of 6y, 2y and 8 months). Twenty-five patients (73.5%) presented an acute GVHD and 5 (14.7%) a chronic GVHD. Eventually, 10 patients died, including 8 of transplant toxicity (5 out of the 8 had been allografted before 2003).

Conclusion
This report shows that HSCT is an efficient treatment in pediatric patients with high risk relapse of ALK+ ALCL. However, the high level of treatment-related mortality rises the question of the place of alternative treatments as Vinblastine, ALK or CD30 inhibitors in place of HSCT. When allograft is required, the use of reduced-intensity conditionning could be help reduce toxicity in these heavily pre-treated patients.

Disclosures:
No relevant conflicts of interest to declare.