Page 110 - Haematologica Vol. 109 - July 2024

ARTICLE - MUD versus haplo PT-CY stem cell transplantation in children with AML A. Ruggeri et al.
aGVHD and cGVHD were assigned and graded using stan- dard criteria.21, 22 Competing events of aGVHD and cGVHD were relapse and death. Cytogenetics abnormalities were classified according to the genetically defined prognostic stratification of the 2017 European Leukemia Net cytogenetic classification system.1 Neutrophil recovery was defined as the time from HCT to the first of 3 consecutive days with neutrophil counts above 0.5x109/L; platelet recovery was defined as independence from platelet transfusion for at least 7 days with a platelet count of more than >20×109/L. Death and consecutive HCT were competing events.
Statistical analysis
The overall population included 420 MUD and 96 haplo PT- CY. A matched pair analysis was performed to reduce or eliminate confounding factors: the matching included exact match on disease status, cell source and age group at HCT, and nearest match on year of HCT, age at diagnosis, female donor to male recipient, Lansky score and cytomegalovirus match. A maximum of three MUD matched patients was allowed for one haplo PT-CY. There were three controls for 73, two for 12 and one for ten haplo PT-CY. For one haplo PT-CY it was impossible to find a control. Finally, a match could be identified for 253 MUD and 95 haplo PT-CY. Median values with respective interquartile ranges (IQR), were used to express quantitative variables while frequen- cies and percentages were used for categorical variables. On the unmatched population, differences between MUD and haplo PT-CY on quantitative and qualitative variables have been tested using χ2 and Wilcoxon tests respectively. LFS, OS and GRFS were estimated using the Kaplan-Meier estimator. All outcomes with competing events were esti- mated using the cumulative incidence function. Median fol- low-up was estimated using the reverse of the Kaplan-Meier method. All outcomes were censored at last follow-up or at 2 years due to a different follow-up between the groups. Differences in outcomes were tested using a Cox model including a cluster term for each pair. Results are expressed as hazard ratio (HR). Outcomes and HR are presented with their 95% confidence interval (CI). All tests are two-sided with an error rate fixed at 5%. Analyses were done using R statistical software version 4.0.2 (http://www.R-project.org), and matching was performed using the MatchIt package.
Results
Patients and transplant characteristics
Patient and transplant characteristics are summarized in Table 1. Overall, 96 and 420 patients receiving a haplo PT- CY or MUD HCT, respectively, fulfilled the inclusion criteria. Median age at transplant was 9.8 (IQR, 3.0-15.2) years for haplo PT-CY and 7.7 (IQR, 2.8-13.6) years for MUD (P=0.03). Patients in the haplo group were transplanted more recently (median 2018 for haplo vs. 2016 for MUD, P<0.01). In both
groups the majority of patients were in CR1 at transplant (72.9% haplo vs. 70.5% MUD; P=0.63).
Cytogenetic risk at diagnosis was not significantly different in the two groups (good: 21.3% vs. 13.6%, intermediate: 48% vs. 44.3%, poor: 30.7% vs. 42.1% in haplo PT-CY and MUD respectively).
Donors were older in the haplo PT-CY than in the MUD cohort: 35.7 years (IQR, 29.9-42.7) versus 27.7 years (IQR, 23.3-34.2; P<0.01). BM was the most frequently used stem cell source in both groups (65.6% for haplo vs. 63.6% for MUD; P=0.71).
Conditioning regimen was MAC, mainly based on busulfan (Bu), with Bu/fludarabine (66.7%) based in the haplo PT-CY and Bu/CY (28.8%) or Bu/CY/melphalan (38.3%) being the most common in MUD.
Post-HCT immunosuppression consisted mainly of cyc- losporine (CSA) plus mycophenolate mofetil (MMF) in the haplo PT-CY (52.1%) and CSA plus methotrexate (MTX) in the MUD cohort (68.6%).
The baseline characteristics of the matched cohort are described in Table 2.
Engraftment, acute and chronic graft-versus-host disease
The CI of day 60 neutrophils and day 180 platelet recovery for haplo PT-CY was 90.4% (95% CI: 82-95) and 92.2% (95% CI: 82.6-96.6) while for MUD it was 97.1% (95% CI: 93.9-98.6) and 93.8% (95% CI: 89.1-96.4) respectively.
The 100 day grade 2-4 aGVHD was 36.7% (95% CI: 26.8-46.6) for haplo PT-CY and 28.7% (95% CI: 23.2-34.4) for MUD and CI of grade 3-4 aGvHD was 14.4% (95% CI: 8.1-22.5) versus 6.4% (95% CI: 3.8-9.9), respectively.
2-year CI of cGVHD was 22.4% (95% CI: 13.4-32.8) and 18.5% (95% CI: 13.5-24.1) for haplo PT-CY and MUD respectively; 2-year CI of extensive cGVHD was 6.6% (95% CI: 2.4-13.8) and 8.6% (95% CI: 5.3-13) for haplo PT-CY and MUD (Table 3). According to donor type, there were no statistically signifi- cant differences between groups on the incidence of grade 2-4 aGVHD (HR=1.26, 95% CI: 0.84-1.89; P=0.27), cGVHD (HR=1.81, 95% CI: 0.75-4.37; P=0.19) and extensive cGVHD (HR=1.01, 95% CI: 0.25-4.03; P=0.99). The risk of grade 3-4 aGvHD was significantly higher in haplo PT-CY (HR=2.33, 95% CI: 1.18-4.58; P=0.03) (Table 4).
Main outcomes
Results of the punctual estimation of outcomes after matched-pair analysis are summarized in Table 3.
The 2-year CI of RI was 19.5% (95% 11.4-29.2) for haplo PT- CY versus 19.3% (95% CI: 14.4-29.4) for MUD. The 2-year NRM was 11% (95% CI: 5.2-19.1) versus 8% (95% CI: 5-11.9) after haplo PT-CY and MUD respectively.
The 2-year OS was 71.5% (95% CI: 59.1-80.7) and 78.4% (95% CI: 72.2-83.4), the 2-year LFS was 69.5% (95% CI: 57.7-78.6) and 72.7% (95% CI: 66.3-78.1) and the 2-year GRFS was 54.5% (95% CI: 42.5-65) and 60.7% (95% CI: 53.8-66.9) for
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