1.
Protective effect of HLA-DPB1 mismatch remains valid in reduced-intensity conditioning unrelated donor hematopoietic cell transplantation
Malki, M. M. A., Gendzekhadze, K., Stiller, T., Mokhtari, S., Karanes, C., Parker, P., Snyder, D., Forman, S. J., Nakamura, R., Nademanee, A.
Bone marrow transplantation. 2019
Abstract
A mismatch at HLA-DPB1 locus is associated with higher acute GVHD and lower relapse rate after myeloablative (MAC) allogeneic hematopoietic cell transplantation (alloHCT). Also, in MAC setting, mismatch permissiveness and expression level impact alloHCT outcomes. However, in reduced intensity conditioning (RIC), DP mismatch effect on transplant outcomes is unknown. We retrospectively evaluated DP mismatch influence (number, permissiveness, and expression) on HCT outcomes in 310 patients with high-resolution typing (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1), who underwent RIC HCT. By multivariable analysis, 11/12 had better overall survival (OS) and relapse vs. 12/12 (HR = 1.61 and 2.02; p = 0.04 and 0.01, respectively) and better OS vs. 10/12 (HR = 1.68; p = 0.02). Within the 11/12, nonpermissive (NoPR) mismatch was associated with higher risk of grade II-IV acute GVHD (HR = 1.97; p = 0.005) and nonrelapse mortality (HR = 2.13; p = 0.02) vs. permissive (PR). Grouping 11/12 based on the DP expression conferred higher mortality (HR = 3.78; p = 0.003) when low expressers received a graft from high expressers (AG) vs. low expressers (AA). Better OS was achieved in PR 11/12, when expression was low in patient and donor (AA) vs. all other combinations. Therefore, in RIC HCT, a single-DP mismatch has a protective role, especially in permissive setting, when donor and recipient are low expressers.
2.
Melphalan-Based Reduced Intensity Conditioning is Associated with Favorable Disease Control and Acceptable Toxicities in Patients Older Than 70 with Hematologic Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Al Malki, M. M., Nathwani, N., Yang, D., Armenian, S., Dadwal, S., Salman, J., Mokhtari, S., Cao, T., Sandhu, K., Rouse, M., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
Allogeneic hematopoietic stem cell transplantation (AlloHCT) is offered increasingly to elderly patients with hematologic malignancies. However, outcome data in those who are 70 years or older are limited, and no standard conditioning regimen has been established for this population. In this retrospective study, we evaluated the outcome of 53 consecutive patients aged 70 years and older who underwent AlloHCT with melphalan (Mel)-based reduced-intensity conditioning (RIC) at City of Hope. Engraftment was prompt, with median time to neutrophil engraftment of 15 days. More than 95% of patients achieved complete donor chimerism within 6 weeks from HCT, consistent with "semi-ablative" nature of this regimen. With a median follow up of 31.1 months, the 2-year overall survival (OS), progression-free survival (PFS), and non-relapse mortality (NRM) were 68.9%, 63.8%, and 17.0%, respectively. Cumulative Incidence (CI) of relapse at 1- and 2-years were 17.0% and 19.3%, respectively. 100-day CI of grade II-IV acute GVHD was 37.7% (grade III-IV: 18.9%), and 2-year CI of chronic GVHD was 61.9% (45.9% extensive). The only significant predictor for poor OS was high/very high disease risk index (DRI). Transplant-related complication/morbidities observed here did not differ from the commonly expected in younger patients treated with RIC. In conclusion; AlloHCT with Mel-based conditioning regimen is associated with acceptable toxicities and NRM, lower incidence of relapse and favorable OS and PFS in patients with 70 years of age or older.