Page 333 - Haematologica Vol. 109 - July 2024

LETTER TO THE EDITOR
Univariate comparisons were performed with χ2 and Fish- er’s exact tests for categorical variables and Mann-Whitney test for continuous variables. Probability of OS was cal- culated using the Kaplan-Meier estimator. Probabilities of CNS relapse and GvHD were estimated using cumulative incidence curves. CNS relapse, death and relapse in oth- er sites were competing events. Concerning GvHD, both death and relapse were considered as competing events. Univariate analyses were performed with the log-rank test for OS and Gray’s test for cumulative incidence estimates. Results were expressed as estimates with a 95% confi- dence interval (95% CI). All tests were two-sided with a type 1 error rate fixed at 0.05. Statistical analyses were performed with SPSS 27.0 and R 4.1.1.
Study inclusion criteria were met by 7,991 patients: 5,724 (71.6%) AML, and 2,267 (28.4%) ALL. Patients were trans- planted between 1996 and 2016.
Median age was 44 years (interquartile range [IQR]: 31.6- 55.4), 6,014 (75.3%) were in first, 1,800 (22.5%) in second, and 177 (2.2%) in third CR. Ninety-one patients of the 7,991 (1.1%) experienced CNS relapse after allo-HSCT; of those, we have information for 88 patients at diagnosis: 4 pa- tients (4.5%) showed initial CNS involvement (see Online Supplementary Table S1 for patients and transplant char- acteristics, and patients with and without CNS relapse). Incidence of CNS relapse was 0.9% (95% CI: 0.7-1.2 ), 1.2% (95% CI: 1-1.5 ) and 1.4% (95% CI: 1.1-1.7 ) at two, five and ten years post allo-HSCT (Figure 1A).
Patients with ALL had higher risk for CNS relapse (1.9% vs. 0.9% in AML at 5 years, P=0.002) (Figure 1B). The risk of developing a CNS relapse after allo-HSCT was higher after 2010 (median time of transplant, P=0.013) (Figure 2A). No other risk factors such as age, donor type, conditioning,
use of total body irradiation, patient or donor sex were identified (Online Supplementary Table S2).
Median age of patients with CNS relapse was 41 years (IQR: 30.8-50.4). Sixty-one patients (67%) were transplanted in CR1, 27 (29.7%) in CR2, and 3 (3.3%) in CR3. Thirty-six (39.6%) showed an isolated CNS relapse, 30 (33%) a combination of CNS and bone marrow (BM) relapse, 23 (25.3%) suffered a CNS relapse secondary to a hematologic relapse, and 2 (2.2%) after a molecular relapse. Of all CNS relapse patients, 72.5% did not show GvHD before the CNS relapse while 27.5% did. Median time from transplant to CNS relapse was 396 days (IQR: 197-737).
Fifty-two patients had AML (57.1%), 39 ALL (42.9%) (see Online Supplementary Table S3 for patients’ and trans- plant characteristics). ALL patients with CNS relapse were younger: 33.3 years versus 46.1 years in AML (P<0.01). Time from transplant to CNS relapse was 401 days in AML (IQR: 247.8-834.2) and 343 days in ALL (IQR: 128.5-665.5) pa- tients (P=0.092). The median follow-up after CNS relapse was 88.3 months.
For 66 patients (72.5%), CNS relapse was the first relapse, 25.3% already had a hematologic relapse, and 2.2% al- ready had a molecular relapse. Cumulative incidence of CNS relapse at five years was 4% (95% CI: 2.2-6.5) for AML CBF patients versus 0.7% (95% CI: 0.5-1) for patients with intermediate or adverse risk AML (P<10-3). All 13 CBF AML patients who relapsed have received cytarabine before transplant; however, we do not have information on exact dosages, neither do we have information on the chemo- therapy regimen in CBF AML patients who did not relapse. Thirty-six AML and 30 ALL patients developed CNS relapse as first relapse post HSCT. Thirty-one (48.6%) achieved CR after the CNS relapse (41.2% CR in AML and 56.7% in ALL,
AB
Figure 1. Central nervous system relapse of the population and by diagnosis. (A) Central nervous system (CNS) relapse in the entire population. (B) CNS relapse by diagnosis. HSCT: hematopoietic stem cell transplantation.
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