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Bone marrow versus mobilized peripheral blood stem cell graft in T-cell-replete haploidentical transplantation in acute lymphoblastic leukemia
Nagler, A., Dholaria, B., Labopin, M., Savani, B. N., Angelucci, E., Koc, Y., Arat, M., Pioltelli, P., Sica, S., Gulbas, Z., et al
Leukemia. 2020
Abstract
The ideal stem cell graft source remains unknown in haploidentical haematopietic cell transplantation (haplo-HCT) with posttransplantation cyclophosphamide (PTCy). This study compared outcomes of bone marrow (BM) versus peripheral blood (PB) stem cell graft for haplo-HCT in acute lymphoblastic leukemia (ALL). A total of 314 patients with ALL (BM-157; PB-157) were included in this study. The cumulative incidence of engraftment at day 30 was higher in the PB group compared with BM (93% vs. 88%, p < 0.01). The incidences of acute graft-versus-host disease (GVHD) and chronic GVHD were not significantly different between the study cohorts. In the multivariate analysis, there were tendencies toward a higher incidence of grade II-IV acute GVHD (hazard ratio (HR) = 1.52, p = 0.07), chronic GVHD (HR = 1.58, p = 0.05), and nonrelapse mortality (NRM) (HR = 1.66, p = 0.06) in patients receiving PB versus BM graft, respectively. The use of PB grafts was associated with lower leukemia-free survival (LFS) (HR = 1.43, p = 0.05), overall survival (OS) (HR = 1.59, p = 0.02), and GVHD-free, relapse-free survival (GRFS) (HR = 1.42, p = 0.03) compared with BM grafts. There was no difference in relapse incidence (HR = 1.23, p = 0.41) between the study groups. In conclusion, use of BM graft results in better survival after haplo-HCT with PTCy in patients with ALL, compared with PB stem cell graft.
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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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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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The concentration of total nucleated cells in harvested bone marrow for transplantation has decreased over time
Prokopishyn, N. L., Logan, B. R., Kiefer, D. M., Sees, J. A., Chitphakdithai, P., Ahmed, I. A., Anderlini, P. N., Beitinjaneh, A. M., Bredeson, C., Cerny, J., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Bone Marrow (BM) is an essential hematopoietic stem cell (HSC) source for many allogeneic hematopoietic cell transplant (HCT) recipients, including adult patients (for specific diseases and transplant strategies) and the majority of pediatric transplants. However, since the advent of Granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC), there has been a significant decrease in utilization of BM in transplant patients, predominantly thought to be due to the increased logistical challenges around BM harvesting compared to PBSC, and generally no significant survival advantage of BM or PBSC. The decreased frequency of collection has the potential to impact the quality of BM harvests. In this study, we examined >15,000 BM donations collected at National Marrow Donor Program (NMDP) centers between 1994 and 2016, and revealed a significant decline in the quality of BM products (defined by concentration of total nucleated cells (TNC) - TNC/mL). TNC concentration dropped from 21.8x10(6)/mL in the earliest era (1994-1996) to 18.7 TNC x10(6)/mL in the most recent era (2012-2016) (Means Ratio 0.83, p<0.001). This decline in BM quality was seen despite selection of more donors perceived to be optimal (e.g. younger age and male). Multivariate regression analysis showed that higher volume centers, performing more than 30 collections per era, had better quality harvests with higher concentrations of TNC collected. In conclusion, we show a significant decrease in the quality of BM collections over time and lower volume collection centers had poorer quality harvests. In this analysis we could not elucidate the direct cause for this finding, suggesting that further studies investigating the key factors responsible, as well as exploring the impact on the transplant recipient, are required.
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Peripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia: a report from the ALWP of the EBMT
Savani, B. N., Labopin, M., Blaise, D., Niederwieser, D., Ciceri, F., Ganser, A., Arnold, R., Afanasyev, B., Vigouroux, S., Milpied, N., et al
Haematologica. 2016;101(2):256-62
Abstract
Increasing numbers of patients are receiving reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation. We hypothesized that the use of bone marrow graft might decrease the risk of graft-versus-host disease compared to peripheral blood after reduced intensity conditioning regimens without compromising graft-versus-leukemia effects. Patients who underwent reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation from 2000 to 2012 for acute leukemia, and who were reported to the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation were included in the study. Eight hundred and thirty-seven patients receiving bone marrow grafts were compared with 9011 peripheral blood transplant recipients after reduced intensity conditioning regimen. Median follow up of surviving patients was 27 months. Cumulative incidence of engraftment (neutrophil >0.5x10(9)/L at day 60) was lower in bone marrow recipients: 88% versus 95% (P<0.0001). Grade II to IV acute graft-versus-host disease was lower in bone marrow recipients: 19% versus 24% for peripheral blood (P=0.005). In multivariate analysis, after adjusting for differences between both groups, overall survival [Hazard Ratio (HR) 0.90; P=0.05] and leukemia-free survival (HR 0.88; P=0.01) were higher in patients transplanted with peripheral blood compared to bone marrow grafts. Furthermore, peripheral blood graft was also associated with decreased risk of relapse (HR 0.78; P=0.0001). There was no significant difference in non-relapse mortality between recipients of bone marrow and peripheral blood grafts, and chronic graft-versus-host disease was significantly higher after peripheral blood grafts (HR 1.38; P<0.0001). Despite the limitation of a retrospective registry-based study, we found that peripheral blood grafts after reduced intensity conditioning regimens had better overall and leukemia-free survival than bone marrow grafts. However, there is an increase in chronic graft-versus-host disease after peripheral blood grafts. Long-term follow up is needed to clarify whether chronic graft-versus-host disease might increase the risk of late morbidity and mortality. Copyright© Ferrata Storti Foundation.