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Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry
Lacan, C., Lambert, J., Forcade, E., Robin, M., Chevallier, P., Loron, S., Bulabois, CÉ, Orvain, C., Ceballos, P., Daguindau, E., et al
Journal of hematology & oncology. 2024;17(1):2
Abstract
The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis. In total population, grade II-IV and III-IV acute GVHD (aGVHD) were lower with BM than with PB. Grade III-IV aGVHD was lower with BM than with PB + ATG. All outcomes were similar in PB and PB + ATG groups. Then, in total population, adding ATG does not benefit the procedure. In acute leukemia, myelodysplastic syndrome and myeloproliferative syndrome (AL-MDS-MPS) subgroup receiving non-myeloablative conditioning, risk of relapse was twice greater with BM than with PB (51 vs. 22%, respectively). Conversely, risk of aGVHD was greater with PB (38% for aGVHD II-IV; 16% for aGVHD III-IV) than with BM (28% for aGVHD II-IV; 8% for aGVHD III-IV). In this subgroup with intensified conditioning regimen, risk of relapse became similar with PB and BM but risk of aGVHD III-IV remained higher with PB than with BM graft (HR = 2.0; range [1.17-3.43], p = 0.012).
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2.
Allogeneic transplantation of bone marrow versus peripheral blood stem cells from HLA-identical relatives in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukemia: a propensity score analysis of a nationwide database
Itonaga, H., Miyazaki, Y., Aoki, K., Shingai, N., Ozawa, Y., Fukuda, T., Kataoka, K., Kawakita, T., Ueda, Y., Ara, T., et al
Annals of hematology. 2023
Abstract
Bone marrow (BM) and granulocyte colony-stimulating factor-mobilized peripheral blood stem cells (PBSC) are used as grafts from HLA-identical-related donors for adults with myelodysplastic syndrome (MDS). To assess the impact of graft sources on post-transplant outcomes in MDS patients, we conducted a retrospective analysis of a nationwide database. A total of 247 and 280 patients underwent transplantation with BM and PBSC, respectively. The inverse probability of treatment weighting (IPTW) methods revealed that overall survival (OS) was comparable between BM and PBSC (P = .129), but PBSC transplantation was associated with worse graft-versus-host disease (GVHD)-free/relapse-free survival (GRFS) (hazard rate [HR], 1.24; 95% confidence intervals [CIs], 1.00-1.53; P = 0.049) and chronic GVHD-free and relapse-free survival (CRFS) (HR, 1.29; 95% CIs, 1.13-1.73; P = 0.002) than BM transplantation. In the propensity score matched cohort (BM, n = 216; PBSC, n = 216), no significant differences were observed in OS and relapse; 3-year OS rates were 64.7% and 60.0% (P = 0.107), while 3-year relapse rates were 27.1% and 23.5% (P = 0.255) in BM and PBSC, respectively. Three-year GRFS rates (36.6% vs. 29.2%; P = 0.006), CRFS rate (37.7% vs. 32.5%; P = 0.003), and non-relapse mortality rates (13.9% vs. 21.1%; P = 0.020) were better in BM than in PBSC. The present study showed that BM transplantation provides a comparable survival benefit with PBSC transplantation and did not identify an enhanced graft-versus-MDS effect to reduce the incidence of relapse in PBSC transplantation.
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Impact of stem cell selection between bone marrow and peripheral blood stem cells for unrelated hematopoietic stem cell transplantation for hematologic malignancies: on behalf of the Donor/Source Working Group of the Japanese Society for Transplantation and Cellular Therapy
Hayashi, H., Iwasaki, M., Nakasone, H., Tanoshima, R., Shimabukuro, M., Takeda, W., Nishida, T., Kako, S., Fujiwara, S. I., Katayama, Y., et al
Cytotherapy. 2023
Abstract
BACKGROUND AIMS This study aimed to comprehensively assess the impact of stem cell selection between bone marrow (BM) and peripheral blood (PB) in unrelated hematopoietic stem cell transplantation (HSCT) for hematological malignancies. Our objective was to identify specific factors associated with better transplant outcomes. METHODS A retrospective analysis was conducted using data from the Japanese HSCT registry. Inclusion criteria were patients aged 0-70 years who underwent their first unrelated HSCT with BM or PB, with an 8/8 or 7/8 allele HLA match for hematological malignancies between 2010 and 2020. RESULTS Among 10 295 patients, no significant difference was observed in overall survival, relapse, graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) or non-relapse mortality between the groups. Patients who received PB showed no clear difference in acute GVHD but had a greater rate of chronic GVHD, resulting in poor chronic GVHD-free, relapse-free survival (CRFS). Subgroup analyses highlighted the importance of patient-specific factors in source selection. Patients with non-Hodgkin lymphoma and a greater hematopoietic cell transplantation-comorbidity index showed better CRFS and GRFS when BM was the preferred source. Similar trends were observed among patients with standard-risk disease for CRFS. However, no such trends were evident among patients aged 0-24 years, indicating that both sources are viable choices for young patients. CONCLUSIONS This real-world retrospective analysis showed similar basic outcomes for BM and PB in an unrelated setting. The results support that BM may still be preferred over PB, especially when the long-term quality of life is a major concern. A consideration of individual factors can further optimize transplant success. Further research is warranted to explore the long-term implications of stem cell source selection.
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G-CSF-Primed Peripheral Blood Stem Cell Haploidentical Transplantation Could Achieve Satisfactory Clinical Outcomes for Acute Leukemia Patients in the First Complete Remission: A Registered Study
Ma, Y. R., Zhang, X., Xu, L., Wang, Y., Yan, C., Chen, H., Chen, Y., Han, W., Wang, F., Wang, J., et al
Frontiers in oncology. 2021;11:631625
Abstract
G-CSF-mobilized peripheral blood (G-PB) harvest is the predominant graft for identical sibling donor and unrelated donor allogeneic hematopoietic stem cell transplantation (HSCT) recipients, but it was controversial in haploidentical related donor (HID) HSCT. In this registry study, we aimed to identify the efficacy of HID G-PB HSCT (HID-PBSCT) for acute leukemia (AL) patients in first complete remission (CR1). Also, we reported the outcomes for the use of G-PB grafts in comparison with the combination of G-BM and G-PB grafts in HID HSCT recipients. Sixty-seven AL patients in CR1 who received HID-PBSCT were recruited at Institute of Hematology, Peking University. Patients who received haploidentical HSCT using the combination of G-BM and G-PB harvests in the same period were enrolled as controls (n=392). The median time from HSCT to neutrophil and platelet engraftment was 12 days (range, 9-19 days) and 12 days (range, 8-171 days), respectively. The 28-day cumulative incidence of neutrophil and platelet engraftment after HSCT was 98.5% and 95.5%, respectively. The cumulative incidences of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) were 29.9% (95%CI 18.8-40.9%) and 7.5% (95%CI 1.1-13.8%), respectively. The cumulative incidences of total and moderate-severe chronic GVHD were 54.9% (95%CI 40.9-68.8%) and 17.4% (95%CI 6.7-28.0%), respectively. The cumulative incidences of relapse and non-relapse mortality were 13.9% (95%CI 5.4-22.5%) and 3.4% (95%CI 0-8.1%), respectively. The probabilities of overall survival (OS) and leukemia-free survival (LFS) were 84.7% (95%CI 74.7-94.7%) and 82.7% (95%CI 73.3-92.1%) respectively. Compared with the HID HSCT recipients using the combination of G-BM and G-PB grafts, the engraftments of neutrophil and platelet were both significantly faster for the G-PB group, and the other clinical outcomes were all comparable between the groups. In multivariate analysis, graft types did not influence the clinical outcomes. Overall, for the patients with AL CR1, G-PB graft could be considered an acceptable graft for HID HSCT recipients. This study was registered at https://clinicaltrials.gov as NCT03756675.
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5.
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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6.
BM is preferred over PBSCs in transplantation from an HLA-matched related female donor to a male recipient
Nakasone, H., Kawamura, K., Yakushijin, K., Shinohara, A., Tanaka, M., Ohashi, K., Ota, S., Uchida, N., Fukuda, T., Nakamae, H., et al
Blood advances. 2019;3(11):1750-1760
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Abstract
The use of granulocyte colony-stimulating factor-mobilized peripheral blood stem cells (PBSCs) and sex-mismatched hematopoietic cell transplantation (HCT), especially with female donors and male recipients (FtoM), is known to be associated with an increased risk of chronic graft-versus-host disease (GVHD) compared with transplantation with bone marrow (BM). This raises the question of whether the use of PBSCs in FtoM HCT might affect allogeneic responses, resulting in fatal complications. Using a Japanese transplantation registry database, we analyzed 1132 patients (FtoM, n = 315; MtoF, n = 260; sex-matched, n = 557) with standard-risk diseases who underwent HCT with an HLA-matched related donor without in vivo T-cell depletion between 2013 and 2016. The impact of PBSC vs BM on transplantation outcomes was separately assessed in FtoM, MtoF, and sex-matched HCT. Overall survival (OS) and nonrelapse mortality (NRM) at 2 years post-HCT were significantly worse in patients with PBSCs vs those with BM in FtoM HCT (2-year OS, 76% vs 62%; P = .0084; 2-year NRM, 10% vs 21%; P = .0078); no differences were observed for MtoF or sex-matched HCT. Multivariate analyses confirmed the adverse impact of PBSCs in FtoM HCT (hazard ratio [HR] for OS, 1.91; P = .025; HR for NRM, 3.70; P = .0065). In FtoM HCT, patients with PBSCs frequently experienced fatal GVHD and organ failure. In conclusion, the use of PBSCs in FtoM HCT was associated with an increased risk of NRM in the early phase, resulting in inferior survival. This suggests that, when we use female-related donors for male patients in HCT, BM may result in better outcomes than PBSCs.
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Short-term clinical outcomes after HLA 1-locus mismatched uPBSCT are similar to that after HLA-matched uPBSCT and uBMT
Fuji, S., Miyamura, K., Kanda, Y., Fukuda, T., Kobayashi, T., Ozawa, Y., Iwato, K., Uchida, N., Eto, T., Ashida, T., et al
International journal of hematology. 2019
Abstract
In Japan, use of unrelated peripheral blood stem cell transplantation (uPBSCT) from HLA-mismatched unrelated donors has recently been approved. We compared outcomes between HLA-matched and 1-locus mismatched uPBSCT, as well as the impact of HLA disparity in uPBSCT and in unrelated bone marrow transplantation (uBMT). In total, 5862 uBMT recipients and 234 uPBSCT recipients were included. In terms of HLA allele disparity, 185 uPBSCT patients (79.1%) had no HLA mismatch, and 49 (20.9%) had 1-locus mismatch; in comparison, 3585 uBMT patients (61.2%) had no HLA mismatch, and 2277 (38.8%) had 1-locus mismatch. The impact of 1-locus mismatch as compared with match in uPBSCT was not significantly higher than in uBMT [hazard ratio (HR) = 1.02 and 1.27 for grade III-IV acute graft-versus-host disease, HR = 0.98 and 1.14 for non-relapse mortality, and HR = 0.87 and 1.06 for overall survival, respectively]. In conclusion, the impact of single-locus mismatch on short-term outcomes was comparable in uPBSCT and uBMT. Larger studies with longer follow-up are needed to assess long-term outcomes.
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Peripheral Blood versus Bone Marrow from Unrelated Donors: Bone Marrow allografts have improved Long-term Overall and Graft-versus-Host Disease, Relapse-Free Survival
Alousi, A., Wang, T., Hemmer, M. T., Spellman, S. R., Arora, M., Couriel, D. R., Pidala, J., Anderlini, P. N., Boyiadzis, M., Bredeson, C. N., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
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Abstract
BACKGROUND Peripheral Blood (PB) or Bone Marrow (BM) from unrelated donors can serve as a graft source for hematopoietic cell transplantation. Currently, PB is most commonly used in roughly 80% of adult recipients. Determining the long-term impact of graft source on outcomes would inform this decision. METHODS Data collected by the Center for International Blood and Marrow Transplant Research (CIBMTR) from 5,200 adult recipients of a first transplant from a 8/8 or 7/8- human-leukocyte antigen matched unrelated donor for treatment of acute leukemia, chronic myeloid leukemia or myelodysplastic syndrome between the years of 2001-2011 were analyzed to determine the impact of graft source on Graft-versus-Host Disease (GVHD), Relapse-Free Survival (GRFS) defined as freedom from grade III/IV acute GVHD, chronic GVHD requiring immunosuppressive therapy, relapse, or death and overall survival. RESULTS GRFS at 2-years was superior in recipients of BM 16% (95% confidence interval [CI] 14-18) when compared to PB 10% (95% CI, 8-11) (p-value <0*0001)in the 8/8 human-leukocyte antigen -matched cohort and 7/8-matched cohort 11% (95% CI, 8-14) vs. 5% (95% CI, 4-7) (p-value 0*001). With 8/8 matched unrelated donors, overall survival at 5 years was superior in recipients of BM (43%; 95% CI, 40-46) vs. PB (38%; 95% CI 36-40), p =0*014. Inferior survival at 5 years in the PB cohort was attributable to a higher frequency of deaths while in remission when compared to BM recipients. For recipients of 7/8-matched grafts, survival at 5 years were similar BM and PB recipients (32 vs. 29%, p=0*329). CONCLUSION BM grafts results in improved long-term GRFS and overall survival in recipients of matched unrelated donor transplants and should be considered the unrelated allograft of choice, when available, for adults with acute leukemia, chronic myeloid leukemia and myelodysplastic syndrome.
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More chronic GvHD and non-relapse mortality after peripheral blood stem cell compared with bone marrow in hematopoietic transplantation for paediatric acute lymphoblastic leukemia: a retrospective study on behalf of the EBMT Paediatric Diseases Working Party
Simonin, M., Dalissier, A., Labopin, M., Willasch, A., Zecca, M., Mouhab, A., Chybicka, A., Balduzzi, A., Volin, L., Peters, C., et al
Bone Marrow Transplantation. 2017;52(7):1071-1073
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Identification of a 10/10 matched donor for patients with an uncommon haplotype is unlikely
Olson, J. A., Gibbens, Y., Tram, K., Kempenich, J., Novakovich, J., Buck, K., Dehn, J.
Immune Response Genetics. 2017;89(2):77-81
Abstract
BACKGROUND Despite over 6 million subjects contributing to the National Marrow Donor Program human leukocyte antigen (HLA) haplotype frequency reference data (HFD), haplotypes cannot be predicted from the HLA assignments of some patients searching for an unrelated donor (URD) in the Be The Match Registry. We aimed to determine the incidence of these patient searches and whether haplotypes lacking from the HFD can be found among the low-resolution typed URD pool. MATERIALS AND METHODS New NMDP searches with uncommon patient haplotypes (UPH), defined as a lack of haplotype pairs in any single ethnic group in the HFD based upon HLA-A~C~B~DRB1~DQB1, were identified. Each search had up to 20 potential 10/10 or 8/8 URDs typed to determine the likelihood of an allele match. RESULTS The incidence of patient searches without haplotype pairs in a single ethnic group in the HFD was 1.2% (N=144 out of 12,172) and a majority of these patients (117; 81%) had one uncommon haplotype previously uncharacterized in the HFD. Non-White patients had the highest incidence of UPH. Importantly, no patients with UPH had a 10/10 URD identified. The transplant rate among UPH patients was 15%, and a majority of these patients utilized cord blood units as their transplant stem cell source. CONCLUSION Therefore, the HLA HFD that informs the HapLogic matching algorithm is thorough as UPH patient searches were infrequent. Since such patients are highly unlikely to have a fully 10/10 matched URD identified, this study supports the identification of alternative stem cell sources including cord blood or a mismatched URD early in the search process. Copyright © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.