Risk analysis of fluctuating hypercalcemia after leukapheresis in cellular therapy.

Optimized management of citrate-induced hypocalcemia is required to provide safe leukapheresis. We prospectively analyzed subjects who underwent leukapheresis for cytotherapy, and evaluated serum ionized (iCa) concentrations before, at the end of, and 1 h after leukapheresis. During leukapheresis, calcium gluconate solution was continuously supplemented intravenously with hourly measurement of iCa. 76 patients including 49 lymphapheresis for chimeric antigen receptor T-cell therapy and 27 stem cell collections were enrolled. Median processing blood volume was 10 L (range, 6-15 L). Fluctuating hypercalcemia, in which the iCa concentration rose above its upper limit 1 h after leukapheresis, was observed in 58 subjects (76.3%). Multivariate analysis revealed that higher ratios of processing blood volume to body weight, more rapid calcium supplementation, and lower iCa concentration at the end of leukapheresis significantly increased elevation of serum iCa concentration by 1 h after leukapheresis. Based on multivariate analyses, we developed a formula and a diagram that accurately estimates serum iCa concentration 1 h post-leukapheresis. This suggests optimal targets for iCa concentration and calcium supplementation rates. In cases with high ratios of processing blood volume to body weight, slowing the rate of blood processing, rather than increasing calcium supplementation should safely alleviate hypocalcemia during leukapheresis without inducing hypercalcemia thereafter.

Risk factors and timing of autologous stem cell transplantation for patients with peripheral T-cell lymphoma.

High-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT) is an option for patients with peripheral T-cell lymphoma (PTCL); however, neither prospective nor retrospective studies support proceeding with ASCT upfront, and the timing of HDC-ASCT remains controversial. We retrospectively analyzed the risk factors for outcomes of 570 patients with PTCL, including PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL), who received ASCT for frontline consolidation (n = 98 and 75, respectively) or alternative therapies after either relapse (n = 112 and 75) or primary induction failure (PIF; n = 127 and 83) between 2000 and 2015. Significant risk factors for overall survival (OS) after upfront ASCT were a ≥ 2 prognostic index for T-cell lymphoma (P < 0.001) and partial response (PR) at ASCT (P = 0.041) in PTCL-NOS patients, and > 60 years of age (P = 0.0028) and PR at ASCT (P = 0.0013) in AITL patients. Performance status of ≥ 2 at ASCT (P < 0.001), receiving ≥ 3 regimens before ASCT (P = 0.018), and PR at ASCT (P = 0.018) in PTCL-NOS patients and > 60 years of age at ASCT (P = 0.0077) in AITL patients were risk factors for OS after ASCT with a chemosensitive PIF status. Strategies that carefully select PTCL patients may allow identification of individuals suitable for ASCT.

Unrelated bone marrow transplantation or immediate umbilical cord blood transplantation for patients with acute myeloid leukemia in first complete remission.

BACKGROUND: While unrelated bone marrow transplantation (UBMT) has been widely used as alternative donor transplantation, the use of umbilical cord blood transplantation (UCBT) is increasing recently. METHODS: We conducted a decision analysis to address which transplantation procedure should be prioritized for younger patients with acute myeloid leukemia (AML) harboring high- or intermediate-risk cytogenetics in first complete remission (CR1), when they lack a matched related donor but have immediate access to a suitable umbilical cord blood unit. Main sources for our analysis comprised the data from three phase III trials for a chemotherapy cohort (n = 907) and the registry data for a transplantation cohort (n = 752). RESULTS: The baseline analysis showed that when the 8/8 match was considered for UBMT, the expected 5-year survival rate was higher for UBMT than for UCBT (58.1% vs. 51.8%). This ranking did not change even when the 7/8 match was considered for UBMT. Sensitivity analysis showed consistent superiority of UBMT over UCBT when the time elapsed between CR1 and UBMT was varied within a plausible range of 3-9 months. CONCLUSIONS: These results suggest that 8/8 or 7/8 UBMT is a better transplantation option than UCBT even after allowing time required for donor coordination.

Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies.

We present a comparative study on 124 patients with hematologic malignancies who had undergone reduced-intensity conditioning and then received a transplant from an HLA-matched related (MRD), an HLA-matched unrelated (MUD), or an HLA-haploidentical related (HAPLO) donor. The conditioning regimen, which consisted of fludarabine, melphalan or busulfan, and alemtuzumab was administered to patients with lymphoid (n = 62) or myeloid disease (n = 62). Mycophenolate mofetil was used as prophylaxis for graft-versus-host disease (GVHD), and 38, 58, and 33 patients received transplants from MRD, MUD, and HAPLO donors, respectively. Only 2 patients experienced primary graft failure (GF) after melphalan-based regimen, whereas 8 of the 17 patients who received a transplant from HAPLO donors experienced a primary GF after busulfan-based regimen. The cumulative incidence of grade III to IV acute GVHD in engrafted patients who had received transplants from MRD, MUD, or HAPLO donors was 3%, 11%, and 27%, respectively, and the 2-year overall survival (OS) rates were 51%, 22%, and 23%, respectively. According to multivariate analysis, transplantation from either MUD or HAPLO donors compared with MRD were adverse factors that affected the OS (P = .006 and P = .002, respectively). In conclusion, the reduced-intensity regimen that included fludarabine, busulfan, or melphalan and alemtuzumab using only mycophenolate mofetil as the GVHD prophylaxis conferred favorable outcomes in the MRD group but lower survival rates in the MUD and HAPLO groups. The busulfan-based regimen led to a high incidence of GF in the HAPLO group, suggesting the need for modification or intensification of immunosuppression.