Donor lymphocyte infusions and second transplantation as salvage treatment for relapsed myelofibrosis after reduced-intensity allografting

Thirty myelofibrosis patients (21 males, nine females) with relapse (n = 27) or graft-rejection (n = 3) after dose-reduced allografting underwent a salvage strategy including donor lymphocyte infusions (DLIs) and/or second allogeneic haematopoietic stem cell transplantation (HSCT). Twenty-six patients received a median number of three (range, 1-5) DLIs in a dose-escalated mode starting with a median dose of 1·2 × 10⁶ (range, 0·003-8 × 10⁶) up to median dose of 40 × 10⁶ T-cells/kg (range, 10-130 × 10⁶). 10/26 patients (39%) achieved complete response (CR) to DLIs. Acute (grade II-IV) and chronic graft-versus-host (GvHD) disease occurred in 12% and 36% cases. Thirteen non-responders to DLI and four patients who did not receive DLI due to graft-rejection or acute transformation of the blast phase underwent a second allogeneic HSCT from alternative (n = 15) or the same (n = 2) donor. One patient (6%) experienced primary graft-failure and died. Acute (II-IV) and chronic GvHD were observed in 47% and 46% of patients. Overall responses after second HSCT were seen in 12/15 patients (80%: CR: n = 9, partial response: n = 3). The 1-year cumulative incidence of non-relapse mortality for recipients of a second allograft was 6%, and the cumulative incidence of relapse was 24%. After a median follow-up of 27 months, the 2-year overall survival and progression-free survival for all 30 patients was 70% and 67%, respectively. In conclusion, our two-step strategy, including DLI and second HSCT for non-responding or ineligible patients, is an effective and well-tolerated salvage approach for patients relapsing after reduced-intensity allograft after myelofibrosis.