AL-06. Influence of allogeneic hematopoietic stem cell transplantation on the treatment outcomes in patients with Ph-positive acute B-lymphoblastic leukaemia

Summary

Hematopoietic stem cell transplantation (HSCT) has improved the results of treatment in patients with hematological malignancies. This option is included in Russian treating protocols of acute B-lymphoblastic leukaemia (B-ALL) from very high-risk group, in particular for Ph-positive variant. The aim of our work was to determine an importance of HSCT after the achieving of CR1 in adult patients with Ph-positive acute B-lymphoblastic leukaemia, to determine risk factors during an execution of program therapy.

Materials and methods

From 2012 to 2022, 68 patients with first identified Ph-positive acute B-lymphoblastic leukaemia were included in retrospective analysis, median age is 35 y.o. (17-72), m/f=29 (43%)/39 (57%). Leukocytosis more than 30×10^9/л was identified in 29 patients (43%). The type of chimeric transcript was identified in 56 patients: р190/р190+р210/р210=33 (59%)/9 (16%)/14 (25%). Patients were treated according to the research protocols RALL–2009+TKI (12 patients); RALL–2012+TKI (26), and RALL–2012m+TKI (24). An approach of low-dose constant chemotherapy was applied for the program therapy (CT), in combination with non-stop usage of imatinib being replaced by dasatinib in cases of lacking molecular remission on the 70th day of the protocol.

Results

Clinical and hematological remission (CR1) was achieved after 1st induction in 67 (98.5%) patients. Molecular complete remission (MolCR) on the 70th day was achieved in 25 patients (37%), dependent on the protocol used: RALL–2009+TKI/RALL–2012+TKI/RALL–2012m+TKI=4 (33%)/13 (50%)/8 (33%). Allo-HSCT was performed in 31 patients (46%) with CR1. The 5-year overall survival (OS) comprised 55%; relapse-free survival (RFS), 35%; mortality, 35%.; early mortality was 3% (n=2). No statistically significant differences were found for OS and RFS, depending on age, treatment protocol, type of chimeric transcript, achievement of MolCR on 70th day. There were statistically significant differences of OS between patients with leukocytosis >30×10^9/l at the onset (32%), versus cases with lower leukocytosis (74%, р=0.024). Four subgroups of patients were discerned during the OS and RFS analysis: CT with or without allo-HSCT in the patients <45 y.o. (“CT+BMT”, “CT”); CT with, or without allo-HSCT over 45 y.o. («CT45+», “CT+BMT45+”). OS levels in all groups did not show significant differences (“CT+BMT” 68% vs “CT” 50% vs “CT45+” 67% vs “CT+BMT45+” 40%). Better RFS was revealed in the “CT45+” group (70%, р=0.016). RFS in “CT+BMT” group (43%) was significantly higher compared to the «CT» group (0%, р=0.005). There weren’t any significant differences between groups “CT45+” (70%) and “CT+BMT45+” (40%), whereas RFS of “CT45+” reached 70%, RFS of “CT+BMT45+” reached 40%. Transplant-related mortality in “CT+BMT” group was 15% (n=4) (sepsis – 3, graft failure – 1), 12% (n=3) of patients died due to relapse of the disease. Transplant-related mortality in “CT+BMT45+” group (n=5) was 60% (graft failure, 1; graft-versus-host disease, 2 cases).

Conclusion

Allo-HSCT in CR1 improves the results of treatment in patients with Ph-positive acute B-lymphoblastic leukaemia due to reduced probability of relapse. There are controversial results of allo-HSCT in patients over 45 y.o. with CR1, due to high transplant-related mortality.

Keywords

Acute B-lymphoblastic leukaemia, Ph-positive, allo-HSCT.