Page 67 - Haematologica Vol. 107 - September 2022

ARTICLE - Outcome of r/r B-ALL with extramedullary disease S. Kayser et al.
distribution of relapse-free survival and OS.22 OS was cal- culated from the start of INO treatment until last follow- up or death. Relapse-free survival was calculated from achievement of CR after the start of INO treatment until last follow-up or relapse. The confidence interval (CI) estimation for survival curves was based on the cumulative hazard function using the Greenwood formula for variance estima- tion. Log-rank tests were employed to compare survival curves between groups. The effect of allogeneic HSCT on OS as a time-dependent intervening event was tested using the Mantel-Byar method23 for univariable and Andersen-Gill model for multivariable analyses.24 The method of Simon and Makuch was used to estimate survival distributions with respect to time-dependent interventions.25 The indi- viduals at risk were initially all represented in the INO ther- apy group. If patients underwent allogeneic HSCT, they were removed at this time point from the INO therapy group and further followed up within the allogeneic HSCT group. All statistical analyses were performed with the statistical software environment R, version 3.3.1, using the R packages prodlim, version 1.5.7, and survival, version 2.39-5.26
Results
Patients’ characteristics
At the time of r/r ALL with EMD, median white blood cell and platelet counts were 5.9x109/L (range, 0.04-36x109/L) and 110.5x109/L (range, 6-337x109/L), respectively. Fifteen patients (48%) were female; Eastern Cooperative Oncology Group score was ≤2 in 29 patients and 3 in two patients (Table 1). Overall, patients had a median of two EMD mani- festations (range, 1-9). Localization of EMD is shown in Table
Table 1. Patients’ characteristics at the time-point of relapsed/refractory acute lymphoblastic leukemia and extramedullary disease.
2. In addition to EMD, 16 (52%) patients had a relapse in bone marrow.
Genetics
Cytogenetic analysis at the time of r/r ALL with EMD was available for 13 (42%) patients, of whom six had a bone marrow relapse as well. Of the 13 patients with cytogenetic information, six had a normal karyotype, four had a com- plex karyotype (≥3 abnormalities), two had a t(9;22)(q34;q11) and one had an additional X-chromosome. In one patient clonal evolution to a complex karyotype was detected.
Response
Response was not assessed after the first induction cycle in seven (23%) of the 31 patients, including one who died at day 11 of the first INO cycle due to cerebral hemorrhage. Figures 1 and 2 are representative PET-CT images of pa- tients with partial remission (PR) and CR, respectively. CR assessed by PET-CT (CR; including EMD and hematologic/bone marrow CR) after the first INO cycle was achieved in ten of the 24 assessed patients (42%) (Figure 2A, B), nine patients (37.5%) had a PR (Figure 1A, B), two (8%) had stable disease and three (12.5%) showed resis- tant/progressive disease. After two cycles of INO, 17 of 31 patients (55%) achieved CR, nine (29%) achieved PR, one patient (3%) experienced early death and four patients with stable, resistant or progressive disease did not re- ceive further INO treatment (13%). Interestingly, only two patients with PR after the first cycle achieved a CR after the second INO cycle, whereas the other seven patients
Table 2. Localization of extramedullary disease.
Localization of extramedullary disease*
Number
Lymph nodes
15
Gastrointestinal organs
15
Osteolytic lesions
12
Skin lesions
7
Soft tissue
5
Genitals
4
Mediastinal mass
2
Lung/pleural effusion
2
Epidural mass
2
Nasopharyngeal mass
2
Central nervous system with epidural mass
1
Peripheral nerves
1
Vertebral mass
1
Pelvic mass
1
Cardiac involvement
1
Number (31)
%
Female gender
15
48
ECOG status ≤2
3
29 2
94 6
Value
Range
Median age, years
31
19-81
Median WBC x109/L missing
5.9 3
0.04-36
Platelets x109/L missing
110.5 3
6-337
Hemoglobin, g/dL missing
11.5 3
6.6-15.2
Median BM blast cells, % missing
10 2
0-100
ECOG: Eastern Cooperative Oncology Group; WBC: white blood cell count; BM: bone marrow.
*Overall, patients had in median two extramedullary disease mani- festations (range, 1-9). Each localization of extramedullary disease was counted separately; thus, the total number does not add up to the total number of patients.
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