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• TBF conditioning for PT-Cy haplo-SCT allows high antileukemic activity. • The platform is safe and effective for AML CR1 patients. • High NRM counterbalance benefits disease control for advanced AML patients. Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) is an alternative treatment for acute myeloid leukemia (AML) patients who lack HLA-matched donors. Relapse after haplo-SCT remains a major concern, especially after nonmyeloablative conditioning regimens. Promising results were reported for TBF-based conditioning regimens (thiotepa, busulfan, and fludarabine) in patients transplanted from different categories of donors and for various disease types but not specifically in PT-Cy haplo-SCT for AML. Here we evaluate the outcome of 100 AML patients who received haplo-SCT with PT-Cy after TBF conditioning regimens (reduced-intensity conditioning, n = 77; myeloablative conditioning, n = 23) in 2 transplant programs. Cumulative incidences of grades III to IV acute and moderate or severe chronic graft-versus-host disease (GVHD) were 7% and 14%, respectively. NRM at 2 years was 28%, significantly influenced by disease status at haplo-SCT (first complete response [CR1] versus advanced AML: 16% versus 38%, P =.016) but not by conditioning intensity or age. The cumulative incidences of relapse at 2 years were 17% and 24% in CR1 and advanced AML, respectively (not significant). Progression-free survival, overall survival, and GVHD and relapse-free survival at 2 years were 67%, 71%, and 49% in CR1 patients, respectively, whereas comparative values in patients with advanced disease were 37%, 41%, and 32%. Our study suggests that TBF conditioning for PT-Cy haplo-SCT is safe and effective for AML patients in CR1. In patients with more advanced disease, the relatively low incidence of relapse seems counterbalanced by a high nonrelapse mortality, underlining the need for alternative strategies to decrease relapse risk, without increasing the intensity of conditioning regimen. [ABSTRACT FROM AUTHOR]

Advanced hematologic malignancies have a higher incidence in older patients and very often lack effective treatments. Allo-HSCT represents the only potential curative option for most of hematologic malignancies. However, 2 main limitations limited this development for a long period of time in older patients. High rates of fatal non-relapse morbidities have been progressively decreased using reduced toxicity conditioning approaches. This allowed pushing up the age limit of patients considered for transplant. The search for a donor has been also a high limitation in older population, due to the lower incidence of matched sibling donors in this population. The development of allo-HSCT from a familial Haplo donor after a reduced intensity (RIC) or non-myeloablative conditioning (NMAC) has allowed for the recent development of allo-HSCT in older population. Here we analyzed a cohort of 111 consecutive patients aged of 65 years or older transplanted from a haplo donor in a single institution from 2013 to 2018. During this period of time, the search for a one-mismatch haplotype donor (Haplo) has been progressively introduced in our program, the upper limit age for transplant progressively increased and more advanced diseases. Patient characteristics: Median age: 69,3 (65-78) years; Male patients: 64%; Acute leukemia (AL): 34%; Myelodysplastic/myeloproliferative syndromes (MDS/MPS): 45%; Chronic Leukemia: 2%; Lymphoma: 18%; others: 3%. High or very high risk disease index (DRI): 44%. Donor characteristics: median age: 39,2 (22-68); Male gender: 61%; sibling donor: 17%; offspring donor: 83%. Non Myeloablative/ Reduced toxicity conditioning: 51%/49%; All patients received PTCY. PT Immunosuppression included CSA and MMF. Median follow-up: 20 (3-78) months; ANC recovery in 96%: 19 (10-44) days; untransfused platelet recovery above 20 in 75%: 17 (7-56) days. In evaluable patients for aGVHD: No: 59%; Grade 1: 7%; Grade 2: 16%; Grade 3: 11%; Grade 4: 5%; 85% patients were evaluable for cGVHD: No: 62%; limited: 13%; Moderate/severe:25%; 32 patients (25%) patients died from non-relapse mortality at a median of 116 days (13-1373); 16 patients relapsed/progressed at a median of 5,6 (1-63) months. Two year overall and disease-free survivals are respectively of 58% (95% CI: 6.35-7.04) and 54% (95% CI: 7.17-7.55). the only predictive factor was disease risk. Overall these data show that allo haplo HSCT is a valid option in older patients with high-risk malignancies. To improve results we performed from 2015 in patients older than 65 years systematic and combined evaluation of comorbidities score, performance status and geriatric assessment (instrumental activity of daily living (AIDL); vulnerability assessment) that will be presented in the meeting for this population. [ABSTRACT FROM AUTHOR]

• Nonmyeloablative haploidentical stem cell transplantation for advanced lymphomas is highly feasible with low incidence of nonrelapse mortality. • It provides a strong graft-versus-lymphoma effect for both Hodgkin and non-Hodgkin lymphoma, with low incidence of relapse when performed in partial or complete remission. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a valid option in patients with refractory lymphomas. HLA haploidentical stem cell transplantation (haplo-SCT) expanded the accessibility to allogeneic hematopoietic cell transplantation. The aims of study were to retrospectively assess the toxicity and efficacy of haplo-SCT using nonmyeloablative conditioning in patients with advanced lymphoma. In total, 147 patients with advanced lymphoma at 2 partner institutions were included. Patients received a uniform nonmyeloablative conditioning regimen and graft-versus-host disease (GVHD) prophylaxis. The primary endpoints were progression-free survival (PFS), overall survival (OS), GVHD, nonrelapse mortality, and GVHD, relapse-free survival (GRFS). Median follow-up was 39 months (range, 6 to 114 months). The median age was 46 years (range, 19 to 71 years). Sixty-five percent of patients were in complete remission (CR) at transplantation. Cumulative incidence of grade II to IV acute GVHD was 30% (95% confidence interval [Cl], 23% to 38%). Two-year cumulative incidence of all grades of chronic GVHD was 13% (95% CI, 8% to 20%). Two-year cumulative incidence of disease relapse was 19% (95% CI, 14% to 27%), with a higher incidence in patients not being in CR at allo-HCT (CR versus not CR: 12% versus 33%, P =.006). Two-year PFS, OS, and GRFS were 66% (95% CI, 59-75), 73% (95% CI, 66-81), and 56% (95% CI, 48-65), respectively. Haplo-SCT with post-transplantation cyclophosphamide may be considered a valid option for patients with aggressive lymphoma and deserves further evaluation. [ABSTRACT FROM AUTHOR]

• PBSC graft is associated with reduced mortality relative to BM cells for patients with HL undergoing haplo-SCT with PT-Cy. • Acute and chronic GVHD did not differ between PBSC and BM grafts. • A lower number of patients receiving PBSC haplo-SCT died because of disease relapse relative to BM graft. Haploidentical stem cell transplantation (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) represents a potential curative strategy for patients with Hodgkin lymphoma (HL) when a matched related or unrelated donor is not available. The role of graft source, either bone marrow (BM) or peripheral blood stem cells (PBSCs), in this setting has not been fully elucidated. We performed a retrospective study on 91 patients with HL to compare the outcome after BM (n = 53) or PBSC (n = 38) transplant. Eighty-nine patients engrafted with no difference between BM and PBSCs in terms of median time for neutrophil (20 versus 20 days, P =.405) and platelet (26 versus 26.5 days, P =.994) engraftment. With a median follow-up of 40.2 months, 100-day cumulative incidences of grades II to IV acute graft-versus host disease (GVHD) and grades II to IV acute GVHD were 24% and 4%, respectively. Graft source was not associated with a different risk of acute GVHD both by univariate and multivariate analyses. Consistently, 1-year cumulative incidence of chronic GVHD was 7% with no differences between the 2 graft types (P =.761). Two-year rates of overall survival (OS), progression-free survival (PFS), nonrelapse mortality, and GVHD/relapse-free survival (GRFS) were 67%, 58%, 20%, and 52%, respectively. By univariate analysis, pretransplant disease status was the main variable affecting all outcomes. By multivariate analysis, PBSCs resulted in a protective factor for OS (hazard ratio [HR],.29; P =.006), PFS (HR,.38; P =.001), and GRFS (HR,.44; P =.020). The other independent variables affecting the final outcome were pretransplant disease status and hematopoietic cell transplant–specific comorbidity index. In conclusion, when planning a haplo-SCT with PT-Cy for patients with poor-risk HL, graft type is an important variable to take into account when selecting the best available donor. [ABSTRACT FROM AUTHOR]

Haploidentical related donor (HRD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) was developed as a valid option for the treatment of acute myeloid leukemia (AML) in the absence of a matched donor. However, many investigators are reluctant to consider the use of this alternative in elderly patients, anticipating high morbidity. Here, we report a single-center comparison of HRD versus matched sibling donor (MSD) and unrelated donor (UD) allo-HSCT for patients with AML aged ≥60 years. Ninety-four patients (MSD: n = 31; UD: n = 30; HRD: n = 33) were analyzed. The median age was 65 (range, 60 to 73) years. We observed a higher cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) after UD allo-HSCT (MSD versus UD versus HRD: 3% versus 33% versus 6%, respectively; P  = .006). Two-year cumulative incidence of moderate or severe chronic GVHD was 17%, 27%, and 16% in the MSD, UD, and HRD groups, respectively ( P  = .487). No difference was observed in the 2-year cumulative incidence of relapse or nonrelapse mortality (NRM) (relapse: MSD versus UD versus HRD: 32% versus 25% versus 25%, respectively; P  = .411; NRM: MSD versus UD versus HRD: 19% versus 27% versus 24%, respectively; P  = .709). At 2 years, progression-free survival, overall survival, and GVHD- and relapse-free survival were 48%, 50%, and 39%, respectively, in the MSD group; 48%, 51%, and 23%, respectively, in the UD group; and 50%, 52%, and 32%, respectively, in the HRD group, without statistically significant differences between the groups. We conclude that HRD allo-HSCT is highly feasible and no less efficient than MSD or UD allo-HSCT in patients with AML aged ≥60 years. Thus, the absence of a HLA-identical donor should not limit the consideration of allo-HSCT for the treatment of AML. [ABSTRACT FROM AUTHOR]