Mariana Nassif Kerbauy

Background: Elderly patients are increasingly being offered allogeneic hematopoietic cell transplantation (HCT), and several strategies have been developed to meet their needs. The objective of the current study was to report the feasibility of a reduced-intensity busulfan/fludarabine conditioning regimen with total marrow irradiation in older patients. Methods: This single-center study included 28 patients aged 60–77 years with a median follow-up of 34 months. Results: Overall survival at 2 years was 46%, relapse rate was 30%, and non-relapse mortality was 23%, yielding a progression-free survival of 46%. Rates of grades II-IV acute GVHD, III-IV acute GVHD, and chronic GVHD were 47%, 8%, and 19%, respectively. Only one patient did not achieve neutrophil engraftment. Three patients experienced sinusoidal obstruction syndrome, and all recovered. Causes of death included disease progression ( n = 10), infection ( n = 5, including one COVID-19 case), and acute myocardial infarction ( n = 1). Conclusion: Our results demonstrate the feasibility of an intensified, total marrow irradiation-based conditioning regimen in an elderly cohort, primarily comprising transplants from alternative donors for high-risk diseases. Non-relapse mortality was very low, given the patients’ profile, and compares favorably with others reports reduced-intensity regimen with total body irradiation in older patients. Future studies should compare it to the standard reduced-intensity and non-myeloablative regimens.

Chimeric antigen receptor T-cells (CAR T cells) are genetically modified cellular immunotherapies approved for standard of care treatment of patients with lymphoma and leukemia worldwide. Here we report the initial activity in Brazilian centers through the collaboration between the Brazilian Cellular Therapy and Bone Marrow Transplant Society (SBTMO) and Center for International Blood and Marrow Transplant Research (CIBMTR). A total of 38 patients who received CAR T cells between 2020 and 2023. The median age was 47 years (range 4-77). Indications include Non-Hodgkin Lymphoma (NHL; 26 cases; 68%), Acute Lymphoblastic Leukemia (ALL; 9 cases; 24%), and Multiple Myeloma (MM; 3 cases; 8%). 84% (75% - 24 NHL cases and 25% - 8 ALL cases) were commercial. This report demonstrates the initial implementation of CAR T cells in Brazil among centers that report to the SBTMO/CIBMTR. This infrastructure will assist in further capturing the activity, assessing the outcomes, and complying with regulatory requirements.

Introduction: Triple‐ and quad‐refractory multiple myeloma patients usually have an aggressive course and a poor prognosis. Available therapeutic options are scarce.Methods: The objective of the current study was to evaluate responses and toxicities of VDTPACE or mCBAD with hematopoietic stem‐cell support as a bridge to subsequent therapies in patients with refractory/relapsed multiple myeloma.Results: Thirteen patients were included (11 mCBAD, 2 VDTPACE), and 21 cycles of chemotherapy with hematopoietic stem‐cell support were delivered. Mean number of previous therapies was 4.8. Stem cells were infused on a median day 9.9 after chemotherapy. Mean time to neutrophil recovery was 18.2 days in patients receiving the first cycle and 15.9 following subsequent cycles. Before therapy, most patients were in PD (77%), PR (15%), or VGPR (8%). Following treatment, the best responses achieved were PR (46%), VGPR (46%), and CR (8%). Median overall and progression‐free survivals were 17 and 9 months. There has been no case of non‐relapse mortality. In the 21 cycles, the main complications were infectious.Conclusion: Intensive chemotherapy can decrease disease burden in patients with relapsed/refractory MM, and stem‐cell support can successfully decrease toxicities and treatment‐related mortality associated with these regimens and may be a good bridging option.

Total body irradiation (TBI) has been an essential component of the conditioning regimen in hematopoietic cell transplantation for many years. However, higher doses of TBI reduce disease relapse at the expense of more significant toxicities. Therefore, total marrow irradiation and total marrow and lymphoid irradiation have been developed to deliver organ-sparing targeted radiotherapy. Data from different studies show that TMI and TMLI can be safely administered in escalating doses in association with different chemotherapy conditioning regimen protocols, in situations with unmet needs, such as multiple myeloma, high-risk hematologic malignancies, relapsed or refractory leukemias, and elderly or frail patients, with low rates of transplant-related mortality. We reviewed the literature on applying TMI and TMLI techniques in autologous and allogeneic hematopoietic stem cell transplantation in different clinical situations.