Nonmyeloablative Unrelated Donor Hematopoietic Cell Transplantation to Treat Patients with Poor-Risk, Relapsed, or Refractory Multiple Myeloma

AbstractThe purpose of this study was to determine long-term outcome of unrelated donor nonmyeloablative hematopoietic cell transplantation (HCT) in patients with poor-risk multiple myeloma. A total of 24 patients were enrolled; 17 patients (71%) had chemotherapy-refractory disease, and 14 (58%) experienced disease relapse or progression after previous autologous transplantation. Thirteen patients underwent planned autologous transplantation followed 43–135 days later with unrelated transplantation, whereas 11 proceeded directly to unrelated transplantation. All 24 patients were treated with fludarabine (90 mg/m2) and 2 Gy of total body irradiation before HLA-matched unrelated peripheral blood stem cell transplantation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. The median follow-up was 3 years after allografting. One patient experienced nonfatal graft rejection. The incidences of acute grades II and III and chronic graft-versus-host disease were 54%, 13%, and 75%, respectively. The 3-year nonrelapse mortality (NRM) was 21%. Complete responses were observed in 10 patients (42%); partial responses, in 4 (17%). At 3 years, overall survival (OS) and progression-free survival (PFS) rates were 61% and 33%, respectively. Patients receiving tandem autologous-unrelated transplantation had superior OS and PFS (77% and 51%) compared with patients proceeding directly to unrelated donor transplantation (44% and 11%) (PFS P value = .03). In summary, for patients with poor-risk, relapsed, or refractory multiple myeloma, cytoreductive autologous HCT followed by nonmyeloablative conditioning and unrelated HCT is an effective treatment approach, with low NRM, high complete remission rates, and prolonged disease-free survival

Progress in the treatment of acute myeloid leukemia

Significant progress in understanding the mechanisms leading to the development of acute myeloid leukemia (AML) has led to the identification of numerous molecular abnormalities that may be responsible for leukemogenesis. Over the same period, large trials have established standard regimens combining cytotoxic agents for the treatment of patients with AML. Current research is attempting to better stratify patients by identifying risk factors responsible for resistance, and to discern ways for incorporating newer agents with specific and targeted activity into our standard regimens, Herein the recent developments in the diagnosis and treatment of AML are reviewed

Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies improved outcomes over two decades

We have used a non-myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation for the past 20 years. During that period, changes in clinical practice have been aimed at reducing morbidity and mortality from infections, organ toxicity, and graft-versus-host disease. We hypothesized that improvements in clinical practice led to better transplantation outcomes over time. From 1997-2017, 1,720 patients with hematologic malignancies received low-dose total body irradiation +/- fludarabine or clofarabine before transplantation from HLAmatched sibling or unrelated donors, followed by mycophenolate mofetil and a calcineurin inhibitor +/- sirolimus. We compared outcomes in three cohorts by year of transplantation: 1997-2003 (n=562), 2004-2009 (n =594), and 2010-2017 (n=564). The proportion of patients >= 60 years old increased from 27% in 1997-2003 to 56% in 2010-2017, and with scores from the Hematopoietic Cell Transplantation Comorbidity Index of >= 3 increased from 25% in 1997-2003 to 45% in 2010-2017. Use of unrelated donors increased from 34% in 1997-2003 to 65% in 2010-2017. When outcomes from 2004-2009 and 2010-2017 were compared to 1997-2003, improvements were noted in overall survival (P=0.0001 for 2004-2009 and P <= 0.0001 for 2010-2017), progression-free survival (P=0.002 for 2004-2009 and P<0.0001 for 2010-2017), non-relapse mortality (P<0.0001 for 20042009 and P<0.0001 for 2010-2017), and in rates of grades 2-4 acute and chronic graft-versus-host disease. For patients with hematologic malignancies who underwent transplantation with non-myeloablative conditioning, outcomes have improved during the past two decades