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Higher TBI dose improves NMA conditioning HCT for MDS or MPN
the TBI dose from the originally used 200 cGy could improve the outcome of HCT in the NMA setting, there- by reducing the risk of disease progression in patients who are not considered candidates for myeloablative condi- tioning.
In agreement with this hypothesis, we showed improvement in outcome by raising the TBI dose from 200 cGy to 300 cGy in our cohort of low-risk patients (MDS-SLD, MDS-MLD, MDS-RS, MDS-U and MPN). Similarly, the day 200 failure rate for high-risk patients (MDS-EB-1/CMML) was reduced to 9% when TBI was raised to 450 cGy while the lower TBI doses of 300 cGy
and 400 cGy failed to improve results. We achieved the primary objective of reducing transplant failure to less than 20% by day 200, which resulted in PFS at two years of 58% in the low-risk group and 33% in the high-risk group. NRM was not significantly increased after escalat- ing TBI to 300 cGy, but 450 cGy TBI led to toxicity with a resultant NRM of 43% at two years after HCT. Limitations of the current study include the slow accrual over ten years. While donor selection and GvHD prophy- laxis remained unchanged during this interval, and there were no major changes in antimicrobial treatments, radio- logical techniques and ancillary therapies, incremental
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Figure 3. Patients enrolled in Arm A receiving 300 cGy total body irradiation (TBI) and patients enrolled in Arm B receiving 450 cGy TBI had reduced day 200 hematopoietic cell transplantation (HCT) failure. Transplant outcomes by Arm and TBI dose: (A) HCT-failure, (B) overall survival, (C) progression-free survival (PFS), (D) non-relapse mortality (NRM), and (E) relapse incidence.
haematologica | 2019; 104(6)
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