Comparison of Different TBI Based Conditioning Regimen in Pediatric Haematological Malignancies: A Retrospective Study of 702 Patients from French Registry.
Authors: Maurin C. , Bordigoni P. , Michel G. , Yakouben K. , Gluckman E. , Jouet J.P. , Galambrun C. , Mechinaud F. , Cahn J.Y. , Souillet G. , Vilmer E. , Dalle J.H. 
Published: April 2020

Rational: HSCT is widely used as treatment of poor-risk pediatric hematological malignancies from 80’s. Many different TBI or busulfan based conditioning regimen have been developed. Although many studies have compared TBI vs busulfan, few studies were available for evaluating different TBI based regimen.

Methods: In order to compare efficacy, safety and toxicity of these different TBI based regimen, we realized retrospective study regarding HSCT in pts under 18 years of age from French HSCT registry from 1985 to 2004. P value under 0.05 was considered as statistically significant.

Results: A total of 702 pts were transplanted during this period using 26 different TBI based conditioning regimen but just 4 of them included more than 30 patients: TBI+Cyclophosphamide (R1, n=305), TBI+Cytarabine+Melphalan (R2, n=249), TBI+VP16 (R3, n=35) or TBI+Cyclophosphamide+VP16 (R4, n=30). We exposed here the results of 554 pts given either R1 or R2. Main characteristics and results are summarized in table. Engraftment rates were similar in R1 and R2. Ten years OS was significantly better for R1 vs R2 (57.8+/−4.1% vs 48.8+/−4%, P=0.0008). There were no significant differences for both conditioning regimen regarding the risk of relapse (R1: 35.8+/−3.9% vs R2: 27.6+/−3.9%), the risk of grade III and IV aGVHD (R1: 16.7+/−2.2% vs R2: 20.01+/−2.6%) and the risk of cGVHD (R1: 26.9+/−3.2% vs R2: 32.4+/−5.2%). TRM at 10 years was significantly worse for R2 vs R1 (33+/−3.3% vs 22.8+/−2.8%, P=0.004). The results obtained with TBI+VP16 were similar than those with TBI+Cy where the results from TBI+VP16+Cy were closed to those from TBI+Arac+Melphalan (data not shown).

Discussion and Conclusion: Too many different TBI based conditioning regimen were used. In order to standardize procedures among transplant centers, we would like identify a gold standard. In our study, TBI + Cy appears safer than TBI+Cytarabine+Melphalan as conditioning regimen for pediatric hematological malignancies since OS and TRM were better although same relapse and GVHD rates were obtained.

Main characteristics TBI + Cy (n=305) TBI+Arac+MEL (n=249) TBI: total body irradiation; Cy: cyclophosphamide; Arac: cytarabine; MEL: melphalan % of male 56 62 Median age at diagnosis (years) 11 (0–17.7) 5 (0.8–17.1) Median age at graft (years) 12.5 (0.4–18) 8.5 (1.9–17.8) Median time from diagnosis to graft (months) 8 (2–173.3) 24 (3–151) Diagnosis ALL low risk/high risk 139(46%)/17(6%) 191(77%)/30 (12%) AML low risk/high risk 46(15%)/43(14%) 3(1.2%)/7(2.8%) MDS 12 (4%) 4 (1.6%) CML chronic phase/other (%) 28(9%)/5(1.6%) 2(0.8%)/1(0.4%) Source of Stem Cells Bone marrow 222 (73%) 221 (89%) Peripheral blood 22 (7.3%) 5 (2%) Cord blood 60 (20%) 19 (7.6%) Sibling 145 (47%) 125 (50%) Unrelated 156 (51%) 102 (41%) Matched/Mismatched 69/31% 75/24% Median follow-up (months) 19.8 (0.7–229.5) 13 (0.2–210.9)