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Improved outcomes for non-myeloablative allo-HCT
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Figure 1. Adjusted cumulative incidence rates of major clinical endpoints by era of transplant. (A) Overall survival, (B) progression-free survival (PFS), (C) non- relapse mortality (NRM), and (D) relapse. Era of transplant: 1997–2003 (black line), 2004–2009 (blue line), and 2010–2017 (red line).
Comparison of endpoints in two most recent transplant eras
Comparisons of clinical endpoints and in the incidences of organ complications and infections in the most recent transplant era (2010–2017) to those in 2004–2009 are shown in the Online Supplementary Tables S2 and S3. OS, PFS, relapse rate, and the rate of grades 2–4 acute GvHD significantly improved in the most recent era as compared to 2004–2009. Over this same time period, significant improvements were also noted in the incidences of gram- negative bacteremias, invasive fungal infections, and in CMV antigenemia and disease.
Discussion
Over the period from 1997–2017, we found marked improvements in OS, PFS, NRM, and in the rates of acute and chronic GvHD after HCT with non-myeloablative conditioning. We also noted a trend toward reduced relapse-related mortality. During this same time period, patient age and burden of comorbidity at the time of HCT increased, higher proportions received grafts from unrelat- ed donors, and AML became the leading indication for HCT, while the numbers of patients with multiple myelo- ma and CML declined. Consistent with these shifts in diagnoses, there was a decrease in patients who under- went HCT after a prior planned autologous transplanta-
tion, which is likely related to the decrease in multiple myeloma as an indication (decreased use of planned tan- dem autologous-allogeneic transplantation),29 and increas- es in prior unsuccessful autologous HCT for non-Hodgkin lymphoma and prior unsuccessful allogeneic HCT for AML. These data underscore the fact that non-myeloabla- tive conditioning has been increasingly recognized as an option for patients with recurrent hematologic malignan- cies after prior HCT with high-intensity conditioning reg- imens.30 Interestingly we did not see an increase in the number of patients with MDS who underwent HCT, despite the increasing recognition of MDS-associated mortality risk and life expectancy benefit of HCT for patients with high-risk MDS.31,32 We suspect that this lack of increase in MDS patients may be due to referral pat- terns from providers who are unaware that HCT is a ther- apeutic option for their MDS patients who are older or medically infirm.
The substantial reduction in NRM, lower risk of relapse seen primarily in the most recent cohort, and modest improvement in relapse-related mortality all contributed to increased overall survival. Contributors to the improve- ment in NRM over time are summarized in Table 4 and include the reductions seen in liver and kidney complica- tions; decreases in incidences of gram-negative bac- teremia, invasive fungal infections, and CMV disease; and reduced rates of acute and chronic GvHD. We speculate that several changes in clinical practice contributed to the
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