• Nonmyeloablative, related HLA-haploidentical BMT utilizing high-dose posttransplantation cyclophosphamide has a favorable safety profile.• Risk-stratified relapse and survival outcomes with this approach are comparable to those of HLA-matched BMT.Related HLA-haploidentical blood or marrow transplantation (BMT) with high-dose posttransplantation cyclophosphamide (PTCy) is being increasingly used because of its acceptable safety profile. To better define outcomes of nonmyeloablative (NMA) HLAhaploidentical BMT with PTCy, 372 consecutive adult hematologic malignancy patients who underwent this procedure were retrospectively studied. Risk-stratified outcomes were evaluated using the refined Disease Risk Index (DRI), developed to stratify disease risk across histologies and allogeneic BMT regimens. Patients received uniform conditioning, T-cell-replete allografting, then PTCy, mycophenolate mofetil, and tacrolimus. Six-month probabilities of nonrelapse mortality and severe acute graft-versus-host disease were 8% and 4%. With 4.1-year median follow-up, 3-year probabilities of relapse, progression-free survival (PFS), and overall survival (OS) were 46%, 40%, and 50%, respectively. By refined DRI group, low (n 5 71), intermediate (n 5 241), and high/very high (n 5 60) risk groups had 3-year PFS estimates of 65%, 37%, and 22% (P < .0001), with corresponding 3-year OS estimates of 71%, 48%, and 35% (P 5 .0001). On multivariable analyses, the DRI was statistically significantly associated with relapse, PFS, and OS (each P < .001). This analysis demonstrates that the DRI effectively risk stratifies recipients of NMA HLA-haploidentical BMT with PTCy and also suggests that this transplantation platform yields similar survivals to those seen with HLA-matched BMT. (Blood. 2015;125(19):3024-3031)

This is a pivotal, multicenter, open-label study of moxetumomab pasudotox, a recombinant CD22-targeting immunotoxin, in hairy cell leukemia (HCL), a rare B cell malignancy with high CD22 expression. The study enrolled patients with relapsed/refractory HCL who had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 every 28 days for ≤6 cycles. Blinded independent central review determined disease response and minimal residual disease (MRD) status. Among 80 patients (79% males; median age, 60.0 years), durable complete response (CR) rate was 30%, CR rate was 41%, and objective response rate (CR and partial response) was 75%; 64 patients (80%) achieved hematologic remission. Among complete responders, 27 (85%) achieved MRD negativity by immunohistochemistry. The most frequent adverse events (AEs) were peripheral edema (39%), nausea (35%), fatigue (34%), and headache (33%). Treatment-related serious AEs of hemolytic uremic syndrome (7.5%) and capillary leak syndrome (5%) were reversible and generally manageable with supportive care and treatment discontinuation (6 patients; 7.5%). Moxetumomab pasudotox treatment achieved a high rate of independently assessed durable response and MRD eradication in heavily pretreated patients with HCL, with acceptable tolerability.

Key Points• Posttransplantation cyclophosphamide is effective as sole GVHD prophylaxis for myeloablative HLA-matched-related or -unrelated BMT.• Despite low chronic GVHD with PTCy, relapse and survival are comparable with outcomes reported using other GVHD prophylactic approaches.High-dose, posttransplantation cyclophosphamide (PTCy) reduces severe graft-versushost disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT), but the impact of PTCy on long-term, disease-specific outcomes is unclear. We conducted a retrospective study of 209 consecutive adult patients transplanted for acute myeloid leukemia (AML, n 5 138), myelodysplastic syndrome (n 5 28), or acute lymphoblastic leukemia (ALL, n 5 43) using PTCy as sole GVHD prophylaxis after myeloablative conditioning and HLA-matched-related or -unrelated T-cell-replete allografting. At alloBMT, 30% of patients were not in morphologic complete remission. The cumulative incidences of grades II to IV and III to IV acute GVHD at 100 days and chronic GVHD at 2 years were 45%, 11%, and 13%, respectively. Forty-three percent of patients did not require immunosuppression for any reason beyond PTCy. At 3 years, relapse cumulative incidence was 36%, disease-free survival was 46%, survival free of disease and chronic GVHD was 39%, and overall survival was 58%. Lack of remission at alloBMT, adverse cytogenetics, and low allograft nucleated cell dose were associated with inferior survival for AML patients. Minimal residual disease but not t(9;22) was associated with inferior outcomes for ALL patients. The ability to limit posttransplantation immunosuppression makes PTCy a promising transplantation platform for the integration of postgrafting strategies to prevent relapse. (Blood. 2014;124(25):3817-3827) IntroductionHistorically, graft-versus-host disease (GVHD), particularly chronic GVHD (cGVHD), has been associated with a reduced risk of relapse after allogeneic blood or marrow transplantation (alloBMT).1-3 However, cGVHD is also the leading cause of late nonrelapse mortality (NRM) posttransplantation, contributing to the substantially elevated mortality risk in alloBMT survivors that continues for at least 15 years after transplantation. 4 In this context, the development of effective pharmacologic strategies for preventing cGVHD has proved to be challenging, and an estimated 41% to 60% of patients treated with calcineurin inhibitor (CNI) -based GVHD prophylaxis after HLA-matched-related or -unrelated allografting develop cGVHD.5-7 T-cell depletion (TCD), whether in vivo or in vitro, is effective in reducing cGVHD, but it can be associated with higher rates of infection, posttransplantation lymphoproliferative disorder, NRM, and disease relapse. 8,9 Initially developed as an approach to facilitate HLA-haploidentical alloBMT, high-dose, posttransplantation cyclophosphamide (PTCy) was found to be effective in preventing both acute GVHD (aGVHD) and cGVHD. [10][11][12] Subsequently, the efficacy of PTCy as sole GVHD prophylaxis after myeloablative conditioni...