Allogeneic Stem Cell Transplantation Has Limited Benefit in Older Patients with Mixed Phenotype Acute Leukemia (2020)

Mixed phenotype acute leukemia (MPAL) is a high risk leukemia that has markers of both myeloid and lymphoid lineage. The role of hematopoietic stem cell transplantation (alloHSCT) remains uncertain especially in the older population. We sought to evaluate the outcomes of our cohort of MPAL patients who were transplanted, including older adults unfit for MAC compared with the outcomes of patients who were consolidated with chemotherapy only.Methods: 74 patients aged 18 years or older, at the Princess Margaret Cancer Centre between January 1, 2000 and December 31, 2018 were evaluated.Results: Among the 74 MPAL patients included in this study, 59 (79%) received induction. Complete remission (CR) was achieved in 47 (79%) treated patients. 25 of 36(80%) achieved a CR using ALL protocols, while 9 of 23 (39%) achieved a CR using AML protocols. Consolidation treatment post CR was split, with 24(51%) receiving chemotherapy followed by an alloHSCT and 23 (49%) receiving chemotherapy only. In the alloHSCT group, RIC was used in 20 (81%) patients while MAC was used in four younger patients. The median age of the transplant cohort was 50 years with a median OS of 21 months. In the chemotherapy only group, the median age was 57 with a median OS of 18 months.Univariate analysis demonstrated no difference in outcomes in terms of age, induction chemotherapy, donor source, and conditioning intensity. The sole predictor of poor OS on univariate analysis was acute graft versus host disease (aGVHD) with a hazard ratio of 3.3 (95% CI 0.9-11). In total, 12 patients (50%) had aGVHD with a median OS of 16 months. However, when Grade 1/2 and Grade 3/4 aGVHD were compared, median OS was not reached in patients with G1/2, compared with an OS of 11 months in those patients with G3/4 aGVHD. Post-transplant relapses occurred solely in the RIC group and occured early. Although, there were no relapses in the MAC group, the non-relapse mortality (NRM) was 75% compared to 18% in the RIC group.The 3 year OS and relapse free survival (RFS) for the entire cohort was 30% and 32%, respectively. When comparing those who had undergone alloSCT and those who received chemo alone, survival in the two groups were similar with a 3 year OS of 29% vs 32% and the 3 year RFS at 29% and 34%, respectively. Subgroup analysis between the two groups was performed for patients with specific poor prognostic factors (older age, complex cytogenetics, higher WCC, conditioning regimen used), but results showed no significant survival differences.Conclusions: Older patients with MPAL have an inferior prognosis and worse outcomes with alloHSCT compared with those of younger adults or children. Despite the increase in access to alloHSCT and an expanding pool of alternative donors, outcomes with RIC remain similar to consolidation with chemotherapy alone. There may be some evidence to suggest that the graft versus leukemia effect can be harnessed to improve outcomes in selected patients. Mixed phenotype acute leukemia (MPAL) is a high risk leukemia that has markers of both myeloid and lymphoid lineage. The role of hematopoietic stem cell transplantation (alloHSCT) remains uncertain especially in the older population. We sought to evaluate the outcomes of our cohort of MPAL patients who were transplanted, including older adults unfit for MAC compared with the outcomes of patients who were consolidated with chemotherapy only. Methods: 74 patients aged 18 years or older, at the Princess Margaret Cancer Centre between January 1, 2000 and December 31, 2018 were evaluated. Results: Among the 74 MPAL patients included in this study, 59 (79%) received induction. Complete remission (CR) was achieved in 47 (79%) treated patients. 25 of 36(80%) achieved a CR using ALL protocols, while 9 of 23 (39%) achieved a CR using AML protocols. Consolidation treatment post CR was split, with 24(51%) receiving chemotherapy followed by an alloHSCT and 23 (49%) receiving chemotherapy only. In the alloHSCT group, RIC was used in 20 (81%) patients while MAC was used in four younger patients. The median age of the transplant cohort was 50 years with a median OS of 21 months. In the chemotherapy only group, the median age was 57 with a median OS of 18 months. Univariate analysis demonstrated no difference in outcomes in terms of age, induction chemotherapy, donor source, and conditioning intensity. The sole predictor of poor OS on univariate analysis was acute graft versus host disease (aGVHD) with a hazard ratio of 3.3 (95% CI 0.9-11). In total, 12 patients (50%) had aGVHD with a median OS of 16 months. However, when Grade 1/2 and Grade 3/4 aGVHD were compared, median OS was not reached in patients with G1/2, compared with an OS of 11 months in those patients with G3/4 aGVHD. Post-transplant relapses occurred solely in the RIC group and occured early. Although, there were no relapses in the MAC group, the non-relapse mortality (NRM) was 75% compared to 18% in the RIC group. The 3 year OS and relapse free survival (RFS) for the entire cohort was 30% and 32%, respectively. When comparing those who had undergone alloSCT and those who received chemo alone, survival in the two groups were similar with a 3 year OS of 29% vs 32% and the 3 year RFS at 29% and 34%, respectively. Subgroup analysis between the two groups was performed for patients with specific poor prognostic factors (older age, complex cytogenetics, higher WCC, conditioning regimen used), but results showed no significant survival differences. Conclusions: Older patients with MPAL have an inferior prognosis and worse outcomes with alloHSCT compared with those of younger adults or children. Despite the increase in access to alloHSCT and an expanding pool of alternative donors, outcomes with RIC remain similar to consolidation with chemotherapy alone. There may be some evidence to suggest that the graft versus leukemia effect can be harnessed to improve outcomes in selected patients. Figure 1. Table 1.Table 1Characteristics of patients with MPAL Open table in a new tab