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Peripheral blood stem cell transplantation vs. bone marrow transplantation for aplastic anemia: a systematic review and meta-analysis
Zhang, Z., Zhou, X., Cheng, Z., Hu, Y.
Frontiers in medicine. 2023;10:1289180
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Editor's Choice
Abstract
BACKGROUND Hematopoietic stem cell transplantation (HSCT) is an effective treatment for aplastic anemia. Recently, peripheral blood stem cell transplantation (PBSCT) has gradually replaced traditional bone marrow transplantation (BMT). However, which graft source has a better therapeutic effect and prognosis for aplastic anemia (AA) remains unclear. Therefore, we conducted this systematic review and meta-analysis. METHODS We systematically searched PubMed, EMBASE, and the Cochrane Library without language limitations for studies using PBSCT or BMT for AA. Data were analyzed using the Open Meta-Analyst. RESULTS We identified 17 of 18,749 studies, including seven comparative reports and nine single-arm reports, with a total of 3,516 patients receiving HSCT (1,328 and 2,188 patients received PBSCT and BMT, respectively). The outcomes of the comparative studies showed similar 5-year overall survival [OS; relative risk (RR) = 0.867; 95% confidence interval (CI), 0.747-1.006], similar transplant-related mortality (RR = 1.300; 95%CI, 0.790-2.138), graft failure rate (RR = 0.972; 95%CI, 0.689-1.372) between the PBSCT group and the BMT group, while the PBSCT group had a significantly higher incidence of chronic graft-versus-host disease (GVHD; RR = 1.796; 95% CI, 1.571-2.053) and a higher incidence of grade IV acute GVHD (RR = 1.560; 95% CI, 1.341-1.816) compared to the BMT group. The outcomes of single-arm reports showed similar 3-year OS and incidences of chronic GVHD, acute II-IV GVHD, III-IV GVHD, transplant-related mortality and graft failure rate between PBSCT and BMT. CONCLUSION Before 2010, PBSCT was not superior to BMT in terms of 5-year OS, transplant-related mortality and graft failure rate, but it exhibited a higher risk of both chronic and acute GVHD. After 2010, PBSCT and BMT showed similar 3-year OS, GVHD risks, transplant-related mortality and graft failure rate. PB grafts are more suitable for HSCT of the AA for convenience and pain relief. SYSTEMATIC REVIEW REGISTRATION www.crd.york.ac.uk/PROSPERO/, CRD42023412467.
PICO Summary
Population
Participants with aplastic anaemia enrolled in studies included in systematic review (n=3516, 17 studies: 7 comparative, 10 single arm)
Intervention
Peripheral blood stem cell transplantation (PBSCT group, n=1328)
Comparison
Bone marrow transplantation (BMT group, n=2188)
Outcome
The outcomes of the comparative studies showed similar 5-year overall survival [OS; relative risk (RR) = 0.867; 95% confidence interval (CI), 0.747-1.006], similar transplant-related mortality (RR = 1.300; 95%CI, 0.790-2.138), graft failure rate (RR = 0.972; 95%CI, 0.689-1.372) between the PBSCT group and the BMT group, while the PBSCT group had a significantly higher incidence of chronic graft-versus-host disease (GVHD; RR = 1.796; 95% CI, 1.571-2.053) and a higher incidence of grade IV acute GVHD (RR = 1.560; 95% CI, 1.341-1.816) compared to the BMT group. The outcomes of single-arm reports showed similar 3-year OS and incidences of chronic GVHD, acute II-IV GVHD, III-IV GVHD, transplant-related mortality and graft failure rate between PBSCT and BMT.
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HLA-haploidentical transplantation for relapsed/refractory AML: better LFS with BM than with PBSC in patients ≥ 55 years of age
Baron, F., Labopin, M., Tischer, J., Ciceri, F., Raiola, A. M., Blaise, D., Sica, S., Vydra, J., Fanin, R., Stölzel, F., et al
American journal of hematology. 2022
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Abstract
The best stem cell source for T-cell replete HLA-haploidentical transplantation with post-transplant cyclophosphamide (PTCy) remains to be determined. In this EBMT retrospective study we analyzed the impact of stem cell source on leukemia-free survival (LFS) in adult patients with primary refractory or relapsed acute myeloid leukemia (AML) given grafts from HLA-haploidentical donors with PTCy as graft-versus-host disease (GVHD) prophylaxis. A total of 668 patients (249 bone marrow (BM) and 419 peripheral blood stem cells (PBSC) recipients) met the inclusion criteria. The use of PBSC was associated with a higher incidence of grade II-IV (HR = 1.59, P = 0.029) and grade III-IV (HR = 2.08, P = 0.013) acute GVHD. There was a statistical interaction between patient age and the impact of stem cell source for LFS (P < 0.01). In multivariate Cox models, among patients <55 years, the use of PBSC versus BM resulted in comparable LFS (HR = 0.82, P = 0.2). In contrast, in patients ≥55 years of age, the use of PBSC versus BM was associated with higher non-relapse mortality (NRM) (HR = 1.7, P = 0.01), lower LFS (HR = 1.37, P = 0.026) and lower overall survival (OS) (HR = 1.33, P = 0.044). In conclusions, our data suggest that in patients ≥55 years of age with active AML at HLA-haploidentical transplantation, the use of BM instead of PBSC as stem cell source results in lower NRM and better LFS. In contrast among younger patients, the use of PBSC results in at least a comparable LFS. This article is protected by copyright. All rights reserved.
PICO Summary
Population
Adults with primary refractory or relapsed acute myeloid leukaemia receiving haploidentical transplantation (n=668)
Intervention
Stem cell graft sourced from peripheral blood stem (PBSC, n=419)
Comparison
Stem cell graft sourced from bone marrow (BM, n=249)
Outcome
The use of PBSC was associated with a higher incidence of grade II-IV (HR = 1.59) and grade III-IV (HR = 2.08) acute GVHD. There was a statistical interaction between patient age and the impact of stem cell source for LFS. In multivariate Cox models, among patients <55 years, the use of PBSC versus BM resulted in comparable LFS (HR = 0.82). In contrast, in patients ≥55 years of age, the use of PBSC versus BM was associated with higher non-relapse mortality (NRM) (HR = 1.7), lower LFS (HR = 1.37) and lower overall survival (OS) (HR = 1.33).
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Bone Marrow versus Peripheral Blood Graft for Haploidentical HCT with Post Transplantation Cyclophosphamide
Mehta, R. S., Saliba, R. M., Alsfeld, L. C., Jorgensen, J. L., Wang, S. A., Anderlini, P., Al-Atrash, G., Bashir, Q., Ciurea, S. O., Hosing, C. M., et al
Transplantation and cellular therapy. 2021
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Editor's Choice
Abstract
BACKGROUND In the COVID-19 pandemic era, the numbers of haploidentical hematopoietic cell transplantation (HCT) with peripheral blood (PB) versus bone marrow (BM) grafts increased significantly, which may be associated with adverse outcomes. METHODS We compared outcomes of BM vs PB grafts in patients =18 years with hematological malignancy who underwent T-cell replete haploidentical HCT and graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus and mycophenolate mofetil. FINDINGS Of 264 patients, 180 (68%) received BM and 84 (32%) received PB graft. Median age was 50 years in both groups. Majority (n=199, 75%) received reduced-intensity conditioning. More patients had acute leukemia or myelodysplastic syndrome in BM (n=152, 85%) than PB (n=46, 55%), p<0.01. The median time to neutrophil and platelet engraftment, and incidence of grade II-IV and III-IV acute GVHD (aGVHD) was comparable in both groups. Among grade II-IV aGVHD, steroid-refractory aGVHD (SR-aGVHD) was 9% (95% CI 5-18) in BM vs 32% (95% CI 19-54) in PB; hazard ratio (HR) 3.7, 95% CI 1.5-9.3, p=0.006. Chronic GVHD (cGVHD) was 8% (95% CI 4-13) vs 22% (95% CI 14-36); HR 3.0, 95% CI 1.4-6.6, p=0.005 and systemic therapy-requiring cGVHD was 2.5% (95% CI 1-7) vs 14% (95% CI 7-27), respectively; HR 5.6, 95% CI 1.7-18, p=0.004 at 1 year. PB group had a significantly higher risk of bacterial and viral infections with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, non-relapse mortality, or survival. INTERPRETATION Our data suggest the use of BM over PB graft for haploidentical HCT.
PICO Summary
Population
Adult patients with haematological malignancies undergoing haploidentical transplantation (n=264)
Intervention
Bone marrow graft (n=180)
Comparison
Peripheral blood graft (n=84)
Outcome
Median age was 50 years in both groups. Majority (n=199, 75%) received reduced-intensity conditioning. More patients had acute leukemia or myelodysplastic syndrome in BM (n=152, 85%) than PB (n=46, 55%). The median time to neutrophil and platelet engraftment, and incidence of grade II-IV and III-IV acute GVHD (aGVHD) was comparable in both groups. Among grade II-IV aGVHD, steroid-refractory aGVHD (SR-aGVHD) was 9% (95% CI 5-18) in BM vs 32% (95% CI 19-54) in PB; hazard ratio (HR) 3.7, 95% CI 1.5-9.3. Chronic GVHD (cGVHD) was 8% (95% CI 4-13) vs 22% (95% CI 14-36); HR 3.0, 95% CI 1.4-6.6, and systemic therapy-requiring cGVHD was 2.5% (95% CI 1-7) vs 14% (95% CI 7-27), respectively; HR 5.6, 95% CI 1.7-18 at 1 year. PB group had a significantly higher risk of bacterial and viral infections with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, non-relapse mortality, or survival
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Collection of Peripheral Blood Progenitor Cells in One Day is Associated with Decreased Donor Toxicity compared to Two Days in Unrelated Donors
Hsu, J. W., Shaw, B. E., Kim, S., Logan, B. R., Sees, J. A., Confer, D. L., Pulsipher, M. A., Shah, N., Switzer, G. E., Abidi, M. H., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
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Editor's Choice
Abstract
Peripheral blood stem cells (PBSC) have been increasingly used for allogeneic hematopoietic cell transplantation compared to bone marrow stem cells. Currently, the National Marrow Donor Program (NMDP) policy recommends 5 days of daily filgrastim followed by either 1 or 2 days of apheresis for unrelated donors, depending on collection center choice. To date, there are no studies that compare the differences in donor experience between one and two days of apheresis. We examined 22,348 adult unrelated donor collections in 184 centers from 2006-2016. 20,004 (89.5%) donors had collections on 1 day vs. 2,344 (9.5%) over 2 days. Information on why donors were apheresed in one day vs. two days were not available. Donors who underwent apheresis in 1 day were more likely to be male (67% vs. 46%, p<0.001), younger (age <30 years 48% vs. 36%, p<0.001) and have a higher body weight (83.0 kg vs. 75.9 kg, p<0.001) and BMI (BMI>30: 30% vs. 22%, p<0.001). Successful collection of the requested CD34(+) cell count was achieved on the first day in 82% of one day collections vs 16% of 2-day collections. Despite not administering filgrastim the evening after the first day of collection in patients who underwent 2 days of apheresis, the median concentration of CD34(+) cells/L in the product on the second day of apheresis was higher than the first day (23.8x10(6) CD34(+)/L 1(st) day vs. 28.7x10(6) CD34(+)/L 2(nd) day, p<0.001). Donors collected in one day were less likely to experience citrate toxicity (36% vs 52%, p<0.001), hospitalizations (1% vs 6%, p<0.001), and other side effects related to apheresis (Modified Toxicity Criteria incidence: 20% vs. 26%, p<0.001). Female sex, older age, collection via central lines, and greater BMI were factors associated with greater likelihood for development of toxicity whereas less toxicity was noted in those with higher CD34(+) counts and more blood processed on the first day of collection. We conclude that although unrelated donors can be successfully collected in one or two days, one day apheresis procedures were associated with less overall toxicity and we therefore recommend single day collections, especially if the requested number of cells have been collected in one day.
PICO Summary
Population
Adult unrelated donor collections in 184 centers from 2006-2016, (n=22,348)
Intervention
Peripheral blood stem cell collection over 1 day (n=20,004)
Comparison
Peripheral blood stem cell collection over 2 days (n=2,344)
Outcome
Successful collection of the requested CD34(+) cell count was achieved on the first day in 82% of one day collections vs 16% of 2-day collections. Despite not administering filgrastim the evening after the first day of collection in patients who underwent 2 days of apheresis, the median concentration of CD34(+) cells/L in the product on the second day of apheresis was higher than the first day (23.8x10(6) CD34(+)/L 1(st) day vs. 28.7x10(6) CD34(+)/L 2(nd) day). Donors collected in one day were less likely to experience citrate toxicity (36% vs 52%,), hospitalizations (1% vs 6%), and other side effects related to apheresis (Modified Toxicity Criteria incidence: 20% vs. 26%). Female sex, older age, collection via central lines, and greater BMI were factors associated with greater likelihood for development of toxicity whereas less toxicity was noted in those with higher CD34(+) counts and more blood processed on the first day of collection.
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Peripheral Blood Stem Cells vs Bone Marrow for T Cell-replete Haploidentical Transplantation with Post-transplant Cyclophosphamide in Hodgkin Lymphoma
Mariotti, J., Devillier, R., Bramanti, S., Giordano, L., Sarina, B., Furst, S., Granata, A., Maisano, V., Pagliardini, T., De Philippis, C., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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Editor's Choice
Abstract
Haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) represents a potential curative strategy for patients with Hodgkin lymphoma (HL) when a matched related or unrelated donor is not available. The role of graft source, either bone marrow (BM) or peripheral blood stem cells (PBSC) in this setting was not fully elucidated. We performed a retrospective study on 91 patients with HL in order to compare the outcome after BM (n=53) or PBSC (n=38) transplant. Eighty-nine patients engrafted with no difference between BM and PBSC in terms of median time for neutrophil (20 vs 20 days, p=0.405) and platelet (26 vs 26.5 days, p=0.994) engraftment. With a median follow-up of 40.2 months, 100-days cumulative incidence of grade 2-4 acute graft-versus host disease (GVHD) and grade 3-4 acute GVHD was 24% and 4%, respectively. Graft source was not associated with a different risk of acute GVHD both by univariate and multivariate analysis. Consistently, 1-year cumulative incidence of chronic GVHD was 7% with no differences between the two graft types (p=0.761). Two-year overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM) and GVHD/relapse-free survival (GRFS) were 67%, 58%, 20% and 52%, respectively. By univariate analysis, pre-transplant disease status was the main variable affecting all outcomes. By multivariate analysis, PBSC resulted a protective factor both for OS (HR: 0.29, p=0.006), PFS (HR: 0.38, p=0.001) and GRFS (HR: 0.44, p=0.020). The other independent variables affecting the final outcome were pre-transplant disease status and hematopoietic cell transplant comorbidity index (HCT-CI). In conclusion, when planning a Haplo-SCT with PT-Cy for patients with poor risk HL, graft type is an important variable to take into account when selecting the best available donor.
PICO Summary
Population
Patients with Hodgkin lymphoma (n=91)
Intervention
Haploidentical peripheral blood stem cell transplant (n=38)
Comparison
Haploidentical bone marrow transplant (n=53)
Outcome
Graft source was not associated with a different risk of acute GVHD both by univariate and multivariate analysis. Consistently. By univariate analysis, pre-transplant disease status was the main variable affecting all outcomes. By multivariate analysis, PBSC resulted a protective factor both for OS (HR: 0.29), PFS (HR: 0.38) and GRFS (HR: 0.44).