1.
Immune recovery after in vivo T-cell depletion myeloablative conditioning hematopoietic stem cell transplantation in severe beta-thalassemia children
Qin, F., Shi, L., Li, Q., Zhang, Z., Liu, L., Li, J., Yang, G., Lai, Y.
European journal of haematology. 2019
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Editor's Choice
Abstract
BACKGROUND The clinical outcome of HSCT in those with severe beta-thalassemia (beta-TM) is closely related to post-transplantation immune reconstitution (IR). However, the data on the IR in these settings are scarce. METHODS A prospective analysis of the clinical outcome and IR in 47 children with severe beta-TM who underwent in vivo T-cell depletion myeloablative conditioning and matched sibling donor HSCT was performed. IR, including immune cell subset counts, as well as the generation of new T and B cells assays after HSCT, was measured. RESULTS In the first year after HSCT, bacterial infections, cytomegalovirus (CMV) reactivation were observed in 70.2% and 36.2% of the patients, respectively. In the same period, poor CD4(+) T cell recovery were observed. The B cells recovered within 6 months. NK cells recovered as early as 1 month, but their function was defective. Cord blood and bone marrow (CB+BM) group had slower T cell recovery, and higher B cells and NK cells in comparison to peripheral blood and bone marrow (PB+BM) group. CONCLUSION The high incidence of infection within 1 year after in vivo T-cell depletion myeloablative conditioning HSCT in severe beta-TM was consistent with poor IR. This article is protected by copyright. All rights reserved.
PICO Summary
Population
Children with severe beta-thalassaemia (n=47).
Intervention
In vivo T-cell depletion myeloablative conditioning and matched sibling donor HSCT.
Comparison
None.
Outcome
In the first year after HSCT, bacterial infections, cytomegalovirus (CMV) reactivation were observed in 70.2% and 36.2% of the patients, respectively. In the same period, poor CD4(+) T cell recovery were observed. The B cells recovered within 6 months. NK cells recovered as early as 1 month, but their function was defective. Cord blood and bone marrow (CB+BM) group had slower T cell recovery, and higher B cells and NK cells in comparison to peripheral blood and bone marrow (PB+BM) group.
2.
Allogeneic Transplantation after Myeloablative Rituximab/BEAM +/- Bortezomib for Patients with Relapsed/Refractory Lymphoid Malignancies: 5-Year Follow-up Results
Chamoun, K., Milton, D. R., Ledesma, C., Young, K. H., Jabbour, E. J., Alatrash, G., Anderlini, P., Bashir, Q., Ciurea, S. O., Marin, D., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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Free full text
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Editor's Choice
Abstract
Although bortezomib and rituximab have synergistic activity in patients with lymphoma, and can both attenuate graft-versus-host disease (GVHD), the drugs have not been used together in patients undergoing allogeneic stem-cell transplantation (alloSCT). In this phase 1/2 trial, we assessed the safety and activity of bortezomib added to the rituximab (R) plus BEAM (carmustine, etoposide, cytarabine, melphalan) regimen in patients with relapsed lymphoma undergoing alloSCT. Primary GVHD prophylaxis consisted of tacrolimus and methotrexate. Bortezomib (1 - 1.3 mg/m(2) per dose) was administered intravenously on days -13, -6, -1, and +2. We performed inverse probability weighting analysis to compare GVHD and survival results to a historical control group that received R-BEAM without bortezomib. Thirty-nine patients were assessable for toxic effects and response. The median age was 54 years. The most common diagnosis was diffuse large B-cell lymphoma (41%). Twenty-two patients (56%) and 17 patients (44%) received their transplants from matched related and unrelated matched donors, respectively. The maximum tolerated bortezomib dose was 1 mg/m(2). The weighted cumulative incidences of grade II-IV and grade III or IV acute GVHD were 50% and 34%, respectively; these incidences and survival rates were not significantly different from those of the control group. Median survival has not been reached in patients age ≤50 years and who had a long follow-up time of 60.7 months. The R-BEAM regimen has a survival benefit in lymphoma patients age ≤50 years undergoing alloSCT. The addition of bortezomib has no impact on survival or incidence of GVHD.
PICO Summary
Population
Patients with relapsed lymphoma undergoing allo-SCT
Intervention
Bortezomib added to the rituximab plus BEAM (carmustine, etoposide, cytarabine, melphalan) regimen (n=39)
Comparison
Historical control group that received R-BEAM without bortezomib.
Outcome
The R-BEAM regimen has a survival benefit in lymphoma patients age </=50 years undergoing alloSCT. The addition of bortezomib has no impact on survival or incidence of GVHD.
3.
Myeloablative unrelated cord blood transplantation in adolescents and young adults with acute leukemia
Hayashi, H., Volt, F., Sanz, J., Petersen, E., Dhedin, N., Hough, R., Milpied, N., Angelucci, E., Yakoub-Agha, I., Michallet, M., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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Free full text
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Editor's Choice
Abstract
Outcomes for adolescents and young adults (AYA) with leukemia differ from other age groups but are still underrepresented in clinical research. The aim of this study was to analyze outcomes of umbilical cord blood transplant (UCBT) in AYA with acute leukemia reported to Eurocord/EBMT. Patients (n=504) had acute lymphoblastic (59%) or myeloid leukemia (41%), were aged 15-25 years, and received UCBT after myeloablative conditioning regimens between 2004 and 2016. Primary endpoint was 3-year overall survival (OS). Median follow-up was 3.9 years. Transplant was single in 58% and double UCBT in 42%. Three-year OS was 45% and leukemia free survival (LFS) was 41%. Cumulative incidence functions (CIF) of non-relapse mortality (NRM) and relapse were 31% and 28%, respectively. CIF of acute GVHD grade II-IV at day-100 was 28%. Three-year CIF of chronic GVHD was 25%. In adjusted analysis, better disease status at UCBT (HR 2.74, p <0.001) and more recent UCBT (HR 1.43, p=0.01) were associated with increased OS and a similar effect of these factors was observed on LFS. Contrastingly, the use of ATG had a negative effect in LFS. The risk of acute GVHD grade II-IV increased with the use of double UCBT (HR 1.65, p =0.02) and decreased with more recent transplantation period (HR 0.65, p=0.02) and ATG use (HR 0.55, p =0.01). Outcomes of AYA UCBT improved in more recent years becoming comparable to pediatric results. Demonstrating the feasibility of UCBT in AYA facilitates stem cell source selection and provides the basis for future prospective studies.
PICO Summary
Population
Adolescents and young adults with acute leukaemia (n=504)
Intervention
Unrelated cord blood transplantation after myeloablative conditioning
Comparison
None
Outcome
Three-year overall survival (OS) was 45% and leukemia free survival (LFS) was 41%. Cumulative incidence functions (CIF) of non-relapse mortality (NRM) and relapse were 31% and 28%, respectively. CIF of acute GVHD grade II-IV at day-100 was 28%. Three-year CIF of chronic GVHD was 25%. In adjusted analysis, better disease status at UCBT and more recent UCBT were associated with increased OS and a similar effect of these factors was observed on LFS. Contrastingly, the use of ATG had a negative effect in LFS. The risk of acute GVHD grade II-IV increased with the use of double UCBT and decreased with more recent transplantation period and ATG use.