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Higher TBI dose improves NMA conditioning HCT for MDS or MPN
Chimerism analysis
In Arm A, the day 28 median donor chimerism levels were 68% for CD3 and 100% for CD33, and the day 84 levels were 79% and 100%, respectively. In Arm B, for patients who received TBI at dose Levels-1 or 2 (300 cGy or 400 cGy), the day 28 median donor chimerism levels were 84% for CD3 and 77% for CD33, and the day 84 levels were 85% and 100%, respectively. For patients who received TBI at dose Level-3 (450 cGy) in Arm B, the day 28 median donor chimerism levels were 82% for CD3 and 100% for CD33, and the day 84 levels were 81% and 100%, respectively.
Hematopoietic cell transplantation failure and relapse
In Arm A, 4 out of 36 patients given TBI at 300 cGy had HCT-failure before day 200, three due to progression and one to graft rejection, with a cumulative incidence of 11%. The escalation rule in this arm was not reached so all patients received dose Level-1 with TBI at 300 cGy. In Arm B, 12 patients received dose Level-1 with TBI at 300 cGy and 5 had HCT-failure, all due to progression, triggering the TBI dose escalation rule. The next five patients received dose Level-2 TBI (400 cGy) and three experienced HCT-fail- ure, all due to progression, triggering again the dose escala- tion rule. The cumulative incidence of HCT-failure for dose Level-1 and dose Level-2 combined was 47%. The subse- quent 24 patients received dose Level-3 with TBI at 450 cGy and only two experienced HCT-failure before 200 days, with a cumulative incidence of 9%. The patients’ characteristics and outcomes for the high-risk patients enrolled on Arm B (separated by TBI dose) are shown in Online Supplementary Table S1 (Table 2 and Figure 3A and E).
The cumulative incidences of progression in Arm A at one year, two years, and five years was 17%, 19%, and 22%, respectively. Patients who received TBI at dose Levels-1 or 2 (300 cGy or 400 cGy) had cumulative inci- dences of progression at one year, two years, and five years of 53%, 53% and 53%, respectively. Patients who received TBI at dose Level-3 (450 cGy) in Arm B had cumulative incidences of progression at one year, two years, and five years of 24%, 24% and 32%, respectively.
Graft-versus-host disease
The cumulative incidences of grades II-IV and grade
III-IV acute GvHD at day 100 were 58% and 13%, respectively. The cumulative incidences of chronic GvHD at one year and two years were 38% and 45%, respectively: one, 21, and eight patients developed mild, moderate, and severe chronic GvHD, respectively. No statistically significant differences were seen between each arm with regards to incidence of acute or chronic GvHD (cumulative incidences in each arm are shown in Table 2) (Figure 4).
Non-relapse mortality
The cumulative incidences of NRM in Arm A at one year, two years, and five years were 17%, 22%, and 43%, respectively. Patients who received TBI at dose Levels-1 or 2 (300 cGy or 400 cGy) had cumulative incidences of NRM at one year, two years, and five years of 29%, 35%, and 35%, respectively. Patients in Arm B who received TBI at dose Level-3 (450 cGy) had cumulative incidences of NRM at one year, two years, and five years of 31%, 43%, and 51%, respectively (Table 2 and Figure 3D).
Figure 2. Outline of treatment plan involving conditioning regimens and graft-versus-host disease (GvHD) prophylaxis. FLU: fludarabine; TBI: total body irradiation; HCT: hematopoietic cell transplantation; MRD: HLA-matched related donor; URD: HLA-matched unrelated donor; MMF: mycophenolate mofetil; CSP: cyclosporine; cGy: centigray; hrs: hours.
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