Peripheral Blood Stem Cells Group Research Articles

Alemtuzumab, Dual Graft-versus-Host Disease Prophylaxis, and Lower CD3+ T Cell Doses Equalize Rates of Acute and Chronic Graft-versus-Host Disease in Pediatric Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation with Matched Unrelated Donor Peripheral Blood Stem Cells or Bone Marrow Grafts

Data comparing hematopoietic stem cell transplantation (HSCT) using bone marrow (BM) or peripheral blood stem cell (PBSC) grafts in children after alemtuzumab-based conditioning are lacking. We investigated whether in vivo T cell depletion using alemtuzumab could reduce the risk of severe acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) after HSCT with matched unrelated donor (MUD) BM or PBSCs. This retrospective multicenter study included 397 children (BM group, n = 202; PBSC group, n = 195) who underwent first MUD HSCT at 9 pediatric centers in the United Kingdom between 2015 and 2019. The median age at transplantation was 7.0 years (range, .1 to 19.3 years), and the median duration of follow-up was 3.1 years (range, .3 to 7.5 years). The 3-year overall survival was 81% for the entire cohort (BM group, 80%; PBSC group, 81%). The incidence of grade II-IV aGVHD was significantly higher in the PBSC group (31%) compared to the BM group (31% versus 19%; P = .003), with no difference in the incidence of grade III-IV aGVHD (BM, 7%; PBSC, 12%; P = .17). CD3+ T cell dose >5 × 108/kg and the use of PBSCs were independent predictors of grade II-IV aGVHD. When considering CD3+ T cell dose and GVHD prophylaxis, PBSC transplantation with a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) and a CD3+ T cell dose ≤5 × 108/kg had a comparable grade II-IV aGVHD to BM transplantation plus a CNI (20% versus 18%; P = .52). PBSC transplantation was associated with a lower incidence of cGVHD compared to BM transplantation (6% versus 11%; P = .03). Within the limits of this study, we identified a potential strategy to reduce the risk of severe GVHD in pediatric PBSC recipients that includes a combination of in vivo T cell depletion using alemtuzumab and dual GVHD prophylaxis (with a CNI and MMF) and limiting the CD3+ T cell dose to ≤5 × 108/kg.

Bone Marrow Versus Peripheral Blood in HLA-Matched Sibling Transplantation: Does the Stem Cell Source Matter in Severe Aplastic Anemia?

Background Selecting a graft source is critical in HLA-matched sibling donor hematopoietic stem cell transplantation (MSD-HCT) for severe aplastic anemia (SAA). Since graft-versus-host-disease (GVHD) is the major cause of mortality after MSD-HCT, and SAA patients do not need the graft-versus-leukemia effect, the selection of a suitable source of stem cells becomes critical. Although bone marrow (BM) is the preferable stem cell source based on the registry-based studies, mobilized peripheral blood stem cells (PBSC) may offer faster engraftment with rapid immune reconstitution. Moreover, the recent advances in conditioning regimens have significantly reduced transplantation-related complications. Here, we compared the long-term outcomes of BM vs PBSC as a graft source in adult patients with SAA who received MSD-HCT with the reduced intensity conditioning (RIC) regimen. Method We conducted a retrospective analysis of 171 consecutive SAA adult patients who received MSD-HCT with Flu6/Cy2/ATG4 RIC regimen (Flu, 30 mg/m 2 IV for 6 days: Cy, 50 mg/kg IV for 2 days; rabbit ATG, 2.5 mg/kg IV for 4 days) or total nodal irradiation (TNI) of 750 cGy combined with ATG as GVHD prophylaxis (TNI-750/ATG) from March 2002 to March 2021 at Seoul St. Mary's Hospital, Seoul, Korea. BM was the primary graft source, but PBSC was used in donors who refused BM harvest, were unsuitable for general anesthesia, or received TNI-750/ATG conditioning. The primary endpoint of this study was to compare the overall survival (OS), and the secondary endpoints included speed of hematologic recovery, primary or secondary graft failure (GF), and failure-free survival (FFS) between the BM and PBSC group. Results The median patient age in the BM group was 38 years (range, 15 - 59) and 44 years (range, 19 - 64) in the PBSC group (p=0.005). There were no differences of baseline characteristics between the two groups except for a donor-to-recipient sex discrepancy (female to male, BM vs. PBSC; 16.4% vs. 30.9%, p=0.029). The majority of BM group (114/116, 98.2%) received the Flu6/Cy2/ATG4 RIC regimen, while 38.2% (21/55) of PBSC group received TNI-750/ATG for the conditioning (p<0.001). The PBSC contained a median 4.71 (range, 1.22 - 17.03) x 10 6/kg CD34 + cells and 368.82 (range, 25.12 - 1234.70) x 10 6/kg CD3 + cells which were about 1.7-fold (BM 2.80 x 10 6/kg CD34 + cells; range, 0.25 - 10.05) and 10-fold (BM 39.61 x 10 6/kg CD3 + cells; range, 1.34 - 463.68) higher than the BM graft (p<0.001). Consequently, the PBSC group exhibited faster engraftment of neutrophils (median 13 vs. 11 days, p<0.001) and platelets (median 18 vs. 12 days, p=0.012). However, there were no differences in the incidence of secondary GF (19.0% vs. 12.7%, p=0.386) and donor-type aplasia (4.3% vs. 10.9%, p=0.178) between two groups. Furthermore, the incidence of acute grade I-II (8.6% vs. 10.9%, p=0.619) and moderate to severe chronic graft-versus-host disease (GVHD) (3.5% vs. 5.5%, p=0.542) were also not significantly different between two groups. However, the BM group has shown more CMV reactivation (44.0% vs. 24.9%, p=0.005), and higher incidence of respiratory infection (14.7% vs. 3.6%, p=0.037) than those of the PBSC group. The incidences of transplantation-related complications between the BM and PBSC group are summarized in Table. The 10-year OS (93.8% vs. 98.1%, p=0.246) and FFS (65.7% vs. 69.0%, p=0.455) were comparable (Figure). Moreover, there was no significant difference in FFS between BM and PBSC group by potential risk factors of patient and donor age at MSD-HCT, sex incompatibility, ABC mismatch, PNH clone presence, HCT-CI ≥3, infused CD34 + cell count, interval from diagnosis to transplant, prior IST history, heavy transfusion before allo-HCT, or severity of AA. Conclusions Our results suggest that survival outcomes of MSD-HCT showed no difference between BM and PBSC as graft sources, and using PBSC may be an efficient alternative offering faster engraftment without significant difference in graft failure or transplantation-related adverse events such as GVHD, and survival. Current analysis and results were drawn from the Asian population with a fludarabine-based conditioning regimen and therefore, need to validate in the Western population. In addition, well-designed prospective studies in a larger cohort are required to confirm our findings.

The Comparison between BM and PBSC for the Patients with Pre-Transplant Pulmonary Dysfunction in HLA-Matched Allo-HCT: Subgroup Analysis Exploring the Impact Based on HCT Factors

Introduction Pre-transplant pulmonary dysfunction is known as an important risk factor for lung complications and subsequent non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). However, it remains unknown which cell source would be optimal for the patients with pre-transplant pulmonary dysfunction and whether the impact of cell source would differ according to recipient age, donor relation, and conditioning regimens. Therefore, we evaluated the impact of stem cell sources in patients with pre-transplant pulmonary dysfunction and in the subgroups. Patients and methods We performed a retrospective analysis of clinical data on 3374 allo-HCT in Japan between 2016 and 2020 using Japanese registry database. All patients had standard-risk disease and underwent their first allo-HCT from an HLA-matched donor. Their clinical outcomes were compared between peripheral blood stem cells (PBSCs) and bone marrow (BM) grafts individually in two distinct cohorts, namely the Lung-scored (LS) cohort and the normal cohort, based on the presence of lung scores determined by the Hematopoietic Cell Transplantation-specific Comorbidity Index. In addition, we conducted subgroup analyses to explore potential differences in the impact of cell sources on these outcomes according to the recipient age (≥50 or < 50), donor relation (related or unrelated), and conditioning regimens (cyclophosphamide [CY] / total body irradiation [TBI]-based myeloablative conditioning [MAC], busulfan [BU]-based MAC, or reduced-intensity conditioning [RIC]). Results In the LS cohort, the 2-year overall survival (OS) tended to be higher in the BM group than that in the PBSCs group (71.9% vs 61.4%; P = 0.052). However, in the normal cohort, there was no significant difference between both the cell source types (71.6% vs 73.1%; P = 0.13). Multivariate analyses showed that PBSCs were significantly associated with inferior OS in the LS cohort (hazard ratio [HR], 1.60 [95% CI, 1.06-2.42], P = 0.026). On the other hand, cell source type did not significantly affect OS in the normal cohort (HR, 0.94 [95% CI, 0.78-1.14], P = 0.55). We also found that PBSCs were significantly associated with an increased risk of NRM in the LS cohort (HR, 1.90 [95% CI, 1.03-3.52], P = 0.041), while cell source types did not affect NRM in the normal cohort (HR, 0.85 [95% CI, 0.64-1.13], P = 0.26). PBSCs were not identified as a risk factor for relapse in both cohorts. When we focused on the LS cohort alone, the Figure 1 summarized the impact of the use of PBSCs in the subgroups according to age, donor relation, and conditioning regimens. Briefly, the use of PBSCs exhibited a significant adverse impact on OS (HR, 3.07 [95% CI, 1.16-8.11], P = 0.024) in patients younger than 50 years old. For recipients aged 50 years or older, PBSCs were not associated with inferior OS (HR, 1.49 [95% CI, 0.91-2.42], P=0.11), although it tended to be associated with an increased risk of NRM with a borderline significance (HR, 1.94 [95% CI, 0.99-3.78], P = 0.053, Figure 1). Focusing on the subgroup stratified according to their donor relation, the use of PBSCs were not associated with inferior OS or an increased risk of NRM in both allo-HCT groups from a related donor or unrelated donor. Furthermore, focusing on the subgroups stratified according to conditioning regimens, the use of PBSCs had a significantly negative impact on OS in the subgroup with CY/TBI-based MAC (HR, 7.48 [95% CI, 2.87-19.51], P < 0.001). On the other hand, the use of PBSCs had no significant impact on OS or NRM in the subgroups of BU-based MAC or RIC. Regarding relapse incidences, the impacts of the use of PBSCs were not different in any of the individual subgroups. Conclusion The use of PBSCs were associated with inferior survival in the LS cohort, but not in the normal cohort. When we focused on the subgroups of the LS cohort alone, the use of PBSCs were associated with inferior survival in the subgroup of younger recipients or those with CY/TBI-based MAC. These patients in the LS cohort might benefit from the use of BM. These results should be validated in another registry study, and further research would be warranted for the purpose of preventing adverse impact of PBSCs or the optimal cell source selection.

Outcomes after Bone Marrow Versus Peripheral Blood Haploidentical Hematopoietic Stem Cell Transplantation Using Post-Transplant Cyclophosphamide-Based Gvhd Prophylaxis

Background: Patients who do not have a human leukocyte antigen (HLA)-matched donor can undergo hematopoietic stem cell transplantation (HSCT) by utilizing haploidentical (haplo) family donors and post-transplant cyclophosphamide (PTCy) for Graft-versus-host disease (GVHD) prophylaxis. Originally, Haplo transplants utilized a bone marrow (BM) source because of concern of higher incidence of GVHD with peripheral blood stem cells (PBSC) graft. Recent years have seen an increase in PBSC graft utilization. Some published studies have reported comparable survival between the two graft sources. These studies also reported lower rate of chronic GVHD and higher quality of life with BM and a lower relapse rate and faster engraftment with PBSCs. We aimed to investigate the outcomes following BM versus PBSC haplo HSCT using (PT-Cy)-based GVHD prophylaxis. Methods: In this single-center retrospective study, we included all (n=176) adult patients who underwent haplo HSCT from August 2016 to July 2021 and had at least one year of follow-up. Bivariate analyses, using the chi-square and t-test, were performed. Kaplan-Meier and regression analyses were conducted. Data were analyzed using SPSS version 28. Statistical significance was considered at p<0.05. Results: The study included 176 haplo transplants including 65% peripheral blood and 35% bone marrow grafts. The median age was 54 (18-74) years and 68% of recipients were males. Ethnic minorities comprised 30% of recipients. Hematologic diagnoses included myeloid disease (65%), lymphoid disease (29%), and others (6%). 31 % of the patients underwent a Myeloablative transplant. Hematopoietic cell transplantation comorbidity index of 3 or higher was noted in 53% of patients. With a Median follow-up 21 (0-73) months, Overall survival (OS) and disease-free survival (DFS) was not reached in either BM or PBSC haplo HSCT group. 1-year OS of 75% and 74% (p-0.898) and 1-year DFS of 63% and 63% (p-0.994) were noted in BM and PBSC group respectively. In PBSC versus BM haplo recipients, an earlier neutrophil engraftment (17 days vs 18 days, p=0.022) was seen. Similar incidences of grade II-IV acute GVHD (50% vs 51%, p=0.875), relapse (22% vs 26%, p=0.579), non-relapse mortality (NRM, 17% vs 20%, p=0.682), platelet engraftment (28 vs 31 days, p<0.092) and 1- year chronic GVHD (35% vs 38%, p=0.410) were noted. Conclusions: In this study, Haploidentical allogeneic hematopoietic stem cell transplant recipients demonstrated similar rates of overall and disease-free survival, relapse, non-relapse mortality, acute and chronic GVHD, and platelet engraftment regardless of graft source. Neutrophil engraftment was observed one day earlier in peripheral stem cell recipients. This supports the use of either PBSC or Bone marrow as the preferred source of Haploidentical transplants.

Haploidentical Stem Cell Transplantation Had a Lower Incidence of Bronchiolitis Obliterans Syndrome Compared with HLA-Matched Sibling Transplantation for Patients with Hematologic Malignancies: Benefit from ATG?

Background: Haploidenticalstem cell transplantation(HID-SCT) based on antithymocyte globulin (ATG) GVHD prophylaxis had achieved similar incidence of cGVHD with HLA-matched sibling transplantation (MSD-SCT). However, bronchiolitis obliterans syndrome (BOS) serve as pulmonary cGVDH, was rarely compared between HID and MSD transplantation. Methods: One thousand four hundred and five patients with hematologic malignancies underwent SCT were enrolled in this retrospective study. Based on donor type, we divided the patients into three groups: HID, MSD and MUD (match unrelated donor) groups. All patients in HID and MUD group received ATG for GVHD prophylaxis, and the minority of patients in MSD group because of clinical trials. The vast majority of HID-SCT recipients transplanted with mixed grafts (bone marrow plus peripheral blood stem cell), whereas most MSD-SCT and all MUD-SCT recipients received PBSC (peripheral blood stem cell) grafts. The cumulative incidences and risk factors of BOS were analyzed. Results: The 5-year cumulative incidence of BOS was 7.2% in the whole population. HID transplantation had lower 5-year cumulative incidence of BOS than MSD transplantation (4.1% vs 10.0%; p<0.001), and the similar incidence with MUD transplantation (4.1% vs 6.2%; p=0.224). The 5-year cumulative incidence of BOS was lower in ATG group than that in non-ATG group in the whole and MSD population both (4.6% vs 11.2%; p<0.001; and 4.1% vs 11.2%; p=0.042, respectively). The 5-year incidence of BOS in mixed grafts group was also lower than that in PBSC group (4.2% vs 9.1; p=0.001). Multivariate analysis showed that HID, ATG and mixed grafts were protective factors for BOS (OR 0.3; 95%CI, 0.2 to 0.6; p<0.001; OR 0.3; 95%CI, 0.2 to 0.7; p=0.001; OR 0.3; 95%CI, 0.1 to 0.8; p=0.013), and aGVHD and cGVHD were independent risk factors for BOS (OR 2.1; 95%, 1.1 to 4.3; p= 0.035; OR 10.1; 95%CI, 4.0 to 25.0; p<0.001). Conclusions: HID transplantation had a lower incidence of BOS than MSD transplantation, which might be associated with ATG and mixed grafts. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Haploidentical donor stem cell transplantation had a lower incidence of bronchiolitis obliterans syndrome compared with HLA-matched sibling donor transplantation in patients with hematologic malignancies: Benefit from ATG?

Haploidentical donor stem cell transplantation (HID-SCT) based on antithymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis had achieved a similar incidence of chronic graft-versus-host disease (cGVHD) with human leukocyte antigen (HLA)-matched sibling donor stem cell transplantation (MSD-SCT). However, bronchiolitis obliterans syndrome (BOS), which serves as pulmonary cGVHD, was rarely compared between HID and MSD transplantation. One thousand four hundred five patients with hematologic malignancies who underwent allogeneic SCT were enrolled in this retrospective study. Based on donor type, we divided the patients into three groups: HID, MSD, and match unrelated donor (MUD) groups. The cumulative incidences and risk factors of BOS were analyzed. The 5-year cumulative incidence of BOS was 7.2% in the whole population. HID transplantation had a lower 5-year cumulative incidence of BOS than MSD transplantation (4.1% vs. 10.0%, p < 0.001) and a similar incidence with MUD transplantation (4.1% vs. 6.2%, p = 0.224). The 5-year cumulative incidence of BOS was lower in the ATG group than that in the non-ATG group in both the whole and MSD populations (4.6% vs. 11.2%, p < 0.001, and 4.1% vs. 11.2%, p = 0.042, respectively). The 5-year incidence of BOS in mixed grafts [peripheral blood stem cell (PBSC) plus bone marrow] group was also lower than that in the PBSC group (4.2% vs. 9.1, p = 0.001). Multivariate analysis showed that HID, ATG, and mixed grafts were protective factors for BOS [odds ratio (OR) 0.3, 95% CI 0.2-0.6, p < 0.001; OR 0.3, 95% CI 0.2-0.7, p = 0.001; OR 0.3, 95% CI 0.1-0.8, p = 0.013], and acute graft-versus-host disease (aGVHD) and cGVHD were independent risk factors for BOS (OR 2.1, 95% 1.1-4.3, p = 0.035; OR 10.1, 95% CI 4.0-25.0, p < 0.001). HID transplantation had a lower incidence of BOS than MSD transplantation, which might be associated with ATG and mixed grafts.

Addition of Anti-thymocyte Globulin in Allogeneic Stem Cell Transplantation With Peripheral Stem Cells From Matched Unrelated Donors Improves Graft-Versus-Host Disease and Relapse Free Survival

Anti-thymocyte globulin (ATG) is commonly used to prevent graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).To evaluate the impact of ATG as part of the GvHD prophylaxis in our institution, we report the outcome of 415 patients with matched unrelated donors (MUD) transplanted for hematological malignancies with or without ATG from 2005 to 2019 at Oslo University Hospital, Norway. The following groups were compared: (1) 154 patients transplanted with peripheral blood stem cells (PBSC) without ATG 2005-2014. (2) 137 patients transplanted with bone marrow stem cells (BMSC) 2005-2019. (3) 124 patients transplanted with PBSC and ATG (PBSC + ATG) 2014-2019.Three years survival was similar in the groups, 61% following allografting with PBSC, 54% with BMSC, and 59% with PBSC + ATG. Acute GvHD grade III-IV was 14%, 14%, and 7%; chronic GvHD was 81%, 32, and 26%; and extensive cGvHD 44%, 15%, and 6% in the corresponding groups. Both acute and chronic GvHD were significantly reduced in the PBSC + ATG-versus the PBSC group (p < 0.05 and p < 0.001 respectively).Transplant-related mortality (TRM) was 33%, 25%, and 17% (p = 0.18). Graft versus host disease and relapse free survival (GRFS) at 3 years was 43 %, 43%, and 64% in the groups.Adding ATG to the GvHD prophylaxis regimen of MUD allo-HSCT with PBSC resulted in a substantial reduction of both acute and chronic GvHD without compromising the disease control, reflected in a superior 3 years GRFS.

CD34+ Stem Cell Selection and CD3+ T Cell Add-Back from Matched Unrelated Adult Donors in Children with Primary Immunodeficiencies and Hematological Diseases

Less than 25% of children who require hematopoietic stem cell transplantation (HSCT) for primary immunodeficiencies (PIDs) or genetic hematological diseases have an HLA-identical sibling. For them, a matched unrelated donor (MUD), although baring a greater risk of graft failure, delayed engraftment and immune reconstitution, and severe graft-versus-host disease (GvHD), represents a valid alternative. The stem cell source is also important, as unprocessed peripheral blood stem cells (PBSCs) contain 5 to 10 times more T cells than bone marrow (BM)-derived grafts, a major risk especially for small children with PID. A CD34+ positive selection can mitigate HLA compatibility issues, but the resulting CD3+ T cell depletion hampers engraftment and facilitates infections. To mitigate those problems, we decided to add back a certain number of T cells (30×106 cells/kg body weight [BW]) to the positive CD34+ selection derived from MUD BM or PBSCs and report the results in terms of time to engraftment and immune reconstitution, GvHD incidence, infections, and survival. Our aim was to show not only the feasibility and clinical efficacy of this addback but also that PBSC-derived CD34+ selected grafts with calibrated T cell addback would be equivalent to BM-derived grafts. We analyzed retrospectively our single-center cohort of 76 children (median age, 1.9 years) affected by PID (61) and hematological diseases (15) who received a total of 79 MUD HSCTs with CD34+ selection and addback of 30×106 CD3+ cells/kg BW between 2001 and 2019. We used descriptive and analytic statistics (chi-square, Student's t-test, Mann-Whitney U test, as appropriate) and constructed Kaplan-Meier curves using the log-rank test to compare patients grafted with BM or PBSC-derived inocula. The two groups showed no statistically significant differences in terms of age, sex, HLA-mismatch, or amount of CD3+ cells/kg BW added back to the CD34+ selection. However, the latter being higher in the PBSC group (P=.0001). Overall engraftment rate was 96% (73/76) and occurred faster in the PBSC group than in BM recipients: polymorphonuclear cells, 16 versus 21 days (P=.006); platelets, 15 versus 22 days (P=.001). GvHD incidence was low. No acute GvHD was diagnosed in 24 children, whereas grades I, II, III, and IV occurred in 19, 28, five, and three children, respectively (P not significant). Chronic GvHD was seen in only two children. The CD4+ count at six months after HSCT was higher in PBSC recipients as compared to those receiving BM (184 versus 88 CD4+ cells; P=.003). Overall survival for the whole cohort was 80% at 10 years, with no significant difference between the two stem cell sources (P not significant). Viral infections occurred among five of the PBSC grafted children and 14 in the BM group (P not significant), and no patient suffered from post-transplant lymphoproliferative disorder (PTLD). The results we present show that an addback of 30×106 donor CD3+ cells/kg recipient BW to a MUD BM or PBSC-derived CD34+ selection gives promising results in infants and young children undergoing HSCT for PID or hematological diseases. Furthermore, with this manipulation the inherent limits of PBSC-derived grafts can be overcome, allowing both swift engraftment and immune reconstitution without an increase in GvHD, infections, or PTLD.

Bone Marrow Versus Mobilized Peripheral Blood Stem Cells for Non T Depleted Haploidentical Transplantations with Post Transplantation Cyclophosphamide in Acute Lymphoblastic Leukemia: On Behalf of the ALWP of the EBMT

Background: The number of non T depleted haploidentical stem cell transplantations (haplo SCT) with post transplantation cyclophosphamide (PTCy) in adult patients (pts) with acute lymphoblastic leukemia (ALL) is increasing (Shemtov N et al, Leukemia 2019). Although the original haplo SCT with PTCy were performed with bone marrow (BM) grafts, the use of peripheral blood stem cells (PBSC) as the stem cell source may provide some advantages in engraftment and anti-leukemic effect which may be of special importance in ALL. Aim: The goal of this study was to compare BM to PBSC as stem cell source for non-T-cell-depleted haplo SCT with PTCy in adult pts with ALL in first or second complete remission (CR). Methods: The study was based on the haplo SCT with PTCy in adult pts with ALL that met the study inclusion criteria and that were reported to the European Society for Blood and Marrow Transplantation (EBMT) registry from 2010 to 2018. Multivariate analyses (MVA) were performed using the Cox proportional hazard model. Results: A total of 314 pts were reported, 157 of whom received BM and 157 received PBSC as the stem cell source. The median age at transplantation was 37 years (range, 18-68 years) and 36 years (range, 18-73 years), 66% and 62% were males, respectively. Diagnosis was Ph negative B-ALL in 39% and 41% of the pts, Ph positive in 32% and 34 % and T ALL in 29% and 25%, respectively.61% and 65% were in CR1, while 39% and 35% were in CR2. Pts and donor characteristics did not differ between the groups. More pts in the BM group received myeloablative conditioning (MAC), 87% vs 71% in the PBSC group, p&amp;lt;0.0001. The cumulative incidence of engraftment at d60 was higher in the PBSC group compared to BM: 98% vs 93%, respectively p=0.0005. The incidence of 100 days acute(a) and 2y chronic(c) graft vs host disease (GVHD) were not significantly different between the BM and the PBSC graft source; Grade (Gr) II-IV 26% and 36%, III-IV 14% and 14%, total chronic 31% and 36% and extensive 12% in both, respectively. GVHD was the cause of death in 18% of pts receiving PBSC graft in comparison to 13% of those that received BM grafts. In MVA there was a trend for higher incidence of aGVHD II-IV HR 1.52 (0.973-2.38), p=0.065 and cGVHD HR 1.58 (0.995-2.51), p=0.053 in pts receiving PBSC vs BM grafts, respectively. Similarly, there was a trend for higher non relapse mortality (NRM) in the PB vs BM group HR 1.66 (0.99-2.8), p=0.056. There was no difference in relapse incidence (RI) HR 1.23 (0.76-2.0), p=0.416.While, leukemia free survival (LFS), overall survival (OS) and GVHD rel free survival (GRFS) were significantly better in pts receiving BM in comparison to PBSC graft HR 1.43 (1.0-2.03), p=0.047, HR 1.59 (1.08-2.34), p=0.018 and HR 1.42 (1.03-1.95), p=0.03, respectively. Conclusion: In pts with ALL in remission receiving haplo SCT with PTCy, the use of BM versus PBSC grafts resulted in better LFS, OS and GRFS. Disclosures Angelucci: Jazz Pharmaceuticals: Other: Local advisory board; Roche: Other: Local advisory board; Vertex Pharmaceuticals Incorporated, and CRISPR Therapeutics: Other: Partecipation in DMC; BlueBirdBio: Other: Local advisory board; Novartis: Honoraria, Other: Chair Steering Committee TELESTO protocol; Celgene: Honoraria, Other: Partecipation in DMC. Socie:Alexion: Consultancy. Blaise:Molmed: Consultancy, Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Jazz Pharmaceuticals: Honoraria. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

PS1247 EZH2 GAIN-OF-FUNCTION MUTATIONS ARE NOT ASSOCIATED WITH MORE FAVORABLE PROGNOSIS IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA: A PRELIMINARY ANALYSIS ON 590 PATIENTS

Background: 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 available1. While bone marrow (BM) was originally the preferred stem cell source, more recently peripheral blood stem cell (PBSC) is more often used. Some retrospective studies suggest that the risk to develop acute and chronic graft-versus-host-disease (GVHD) is higher with PBSC than BM, while PBSC may reduce the risk of relapse2. Aims: Here we analyzed the effect of stem cell source in 91 HL patients receiving Haplo-SCT with PT-Cy, with the aim to evaluate if the final outcome is modified by the use of PBSC or BM Methods: From April 2009 to January 2017, 91 consecutive patients with poor prognosis HL received a Haplo-SCT with PT-Cy either from a PBSC (n = 38) or BM (n = 53). The two cohorts were similar for most characteristics, but the PBSC group had more patients with an unfavorable hematopoietic stem cell transplant comorbidity index (HCT-CI) score ≥3 (p = 0.002) and had received a non myeloablative conditioning (NMAC; p = 0.001). Results: Cumulative incidence of neutrophil>500/ul at day +30 and of platelet >20000/ul at day +60 were 96% (95% CI: 89–98) and 96% (95% CI: 88–99), respectively, with no significant differences between the PBSC and BM cohorts. With a median follow-up of 22.8 months, there was no difference between PBSC and BM graft in terms of cumulative incidence of grade 2–4 acute GVHD (29% vs 21%, p = 0.3), grade 3–4 acute GVHD (3% vs 4%, p = 0.7) and moderate-severe chronic GVHD (9% vs 7%, p = 0.7). This was also confirmed by multivariate analysis (data not shown). In the whole population, the 2-year overall survival (OS), 2-year progression-free survival (PFS) and 1-year GVHD/relapse free survival (GRFS) rates were 67%, 58% and 58%, respectively. We observed a trend for improved OS (74% vs 62%, p = 0.07) and PFS (62% vs 56%, p = 0.1) for recipients of PBSC relative to BM cells, but pre-transplant disease status was the only significant variable by univariate analysis (Table I). 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) (Table I). Non-relapse mortality was not affected by graft source both by univariate and multivariate analysis, while pre-transplant disease status was the only variable affecting the chance of disease relapse.Summary/Conclusion: Overall these data suggest that PBSC is associated with better outcome, in terms of OS, PFS and GRFS, relative to BM cells as graft source for patients undergoing Haplo-SCT with PT-Cy. In addition, the risk of acute and chronic GVHD is not increased after PBSC relative to BM graft.

PS1246 GRAFT SOURCE AND PRE‐TRANSPLANT DISEASE STATUS ARE THE MAIN VARIABLES AFFECTING THE OUTCOME OF T CELL‐REPLETE HAPLOIDENTICAL TRANSPLANTATION WITH POST‐TRANSPLANT CYCLOPHOSPHAMIDE FOR HODGKIN LYMPHOMA

Background: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 available1. While bone marrow (BM) was originally the preferred stem cell source, more recently peripheral blood stem cell (PBSC) is more often used. Some retrospective studies suggest that the risk to develop acute and chronic graft‐versus‐host‐disease (GVHD) is higher with PBSC than BM, while PBSC may reduce the risk of relapse2.Aims:Here we analyzed the effect of stem cell source in 91 HL patients receiving Haplo‐SCT with PT‐Cy, with the aim to evaluate if the final outcome is modified by the use of PBSC or BMMethods:From April 2009 to January 2017, 91 consecutive patients with poor prognosis HL received a Haplo‐SCT with PT‐Cy either from a PBSC (n = 38) or BM (n = 53). The two cohorts were similar for most characteristics, but the PBSC group had more patients with an unfavorable hematopoietic stem cell transplant comorbidity index (HCT‐CI) score ≥3 (p = 0.002) and had received a non myeloablative conditioning (NMAC; p = 0.001).Results:Cumulative incidence of neutrophil&gt;500/ul at day +30 and of platelet &gt;20000/ul at day +60 were 96% (95% CI: 89–98) and 96% (95% CI: 88–99), respectively, with no significant differences between the PBSC and BM cohorts. With a median follow‐up of 22.8 months, there was no difference between PBSC and BM graft in terms of cumulative incidence of grade 2–4 acute GVHD (29% vs 21%, p = 0.3), grade 3–4 acute GVHD (3% vs 4%, p = 0.7) and moderate‐severe chronic GVHD (9% vs 7%, p = 0.7). This was also confirmed by multivariate analysis (data not shown). In the whole population, the 2‐year overall survival (OS), 2‐year progression‐free survival (PFS) and 1‐year GVHD/relapse free survival (GRFS) rates were 67%, 58% and 58%, respectively. We observed a trend for improved OS (74% vs 62%, p = 0.07) and PFS (62% vs 56%, p = 0.1) for recipients of PBSC relative to BM cells, but pre‐transplant disease status was the only significant variable by univariate analysis (Table I). 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) (Table I). Non‐relapse mortality was not affected by graft source both by univariate and multivariate analysis, while pre‐transplant disease status was the only variable affecting the chance of disease relapse.Summary/Conclusion:Overall these data suggest that PBSC is associated with better outcome, in terms of OS, PFS and GRFS, relative to BM cells as graft source for patients undergoing Haplo‐SCT with PT‐Cy. In addition, the risk of acute and chronic GVHD is not increased after PBSC relative to BM graft.image

Long-term Outcomes of Autologous Peripheral Blood Stem Cell Transplantation in Patients With Cirrhosis

Peripheral blood stem cells (PBSCs) mobilized with colony-stimulating factor can promote liver regeneration and increase liver function in patients with liver diseases. However, thelong-term effects of stem cell treatments on survival and risk of hepatocellular carcinoma (HCC) in patients with cirrhosis have not been determined. We investigated the long-term effects of autologous stem cell transplantation and risk of HCC in patients with cirrhosis. We performed a retrospective analysis of 2 cohorts of patients with decompensated cirrhosis who received transplantations of autologous PBSCs (n= 282) or standard medical treatment (SMT, n= 286) in China from January 1, 2006, through December 31, 2016. Patients were followed up until death or liver transplantation. Mortality data were obtained by case records and confirmed by telephone calls. Survival time was calculated and HCC was confirmed by computed tomography or ultrasound. We used propensity score matching to adjust the differences between the 2 groups. Survival and incidence of HCC were analyzed and Cox proportional hazard regression was used to determine the prognostic factors. After propensity score matching, time of survival was significantly higher in the PBSC group than the SMT group (P= .001). The adjusted rate of 5-year survival was 71.2% in the PBSC group and 52.1% in the SMT group. The overall incidence of HCC did not differ significantly between the PBSC and SMT groups (21.1% vs 20.4%; P= .999). Significant improvement of liver functions was observed at 1 year, 2 years, 3 years, and 5 years after PBSC transplantation compared with the SMT group. In a long-term analysis of patients with decompensated cirrhosis, autologous transplants of PBSCs significantly improved long-term survival compared with a control group. PBSC transplant did not appear to increase the risk of HCC.

Role of Cell Source and Graft Composition in Haploidentical Transplantation Using Post-Transplant Cyclophosphamide

Introduction: Cell source and graft composition are known to have a prognostic role in allogeneic hematopoietic cell transplant (HCT). Currently, there are no data in the setting of haploidentical-HCT with post-transplant cyclophosphamide (PT-Cy).Patients and methods: One-hundred patients undergoing haplo-HCT with PT-Cy from Sept 2011 to Nov 2015 were included in this multicenter retrospective analysis.Bone marrow (BM) was used as graft source in 25 patients and peripheral blood stem cell (PBSC) in 75. The two groups (BM vs PBSC) were similar in terms of age, Disease Risk Index (DRI) and HCT-CI. The only differences were on disease type (lymphoid malignancies 76% vs 57%, p=0.02) and conditioning regimen (myeloablative: 100% versus 30%, p<0.01).Graft cellular subsets analysis was performed by means of flow cytometry (CD34, CD3, CD4, CD8, CD56, CD19, CD38, CD31, CD25, CD45RA, CD95, CD127, CCR4, CCR6, CCR7). Overall Survival (OS) and Progression Free Survival (PFS) were performed with Kaplan-Meier analysis. Acute GVHD, chronic GVHD, Non-Relapse Mortality (NRM) and Relapse Incidence/Progression of disease (RI/POD) were obtained with competing risk analysis.Results: For the whole cohort, neutrophil and platelet engraftment cumulative incidences at day +30 were 97% (95% CI: 91-99) and 64% (95% CI: 53-73), with no differences between BM or PBSC. Grade II-IV and grade III-IV aGVHD cumulative incidences at day +100 were 36% (95% CI: 26-48) and 10% (95%CI: 5-18), respectively. Acute GVHD cumulative incidence was significantly lower for BM grafts [16% (95% CI: 5-33) vs 43% (95% CI: 31-54), p=0.02], but no differences were observed regarding grade III-IV acute GVHD [8% (CI 95%: 1-24) vs 11% (CI 95%: 5-20), p=0.73]. Chronic GVHD cumulative incidence at 18 months was 23% (95%CI: 15-32) with no difference between BM or PBSC. With a median follow up of 16.5 months (range 0.8 - 40.6), the 18-months PFS and OS were 43% (95%CI: 32-54) and 63% (95% CI: 52-73), respectively. NRM and RI/POD at 18 months were 18% (95%CI: 11-26) and 38% (95%CI: 27-49).Multivariable analysis was performed using patient (age, gender, HCT-CI, DRI) and transplant characteristics (donor gender, donor-recipient relation, graft source). A DRI>1 was the only factor associated with higher RI/POD (HR 3.45, 95% CI: 1.4-8.2, p<0.01), lower PFS (HR 2.77, 95%CI: 1.4-5.3, p<0.01), and lower OS (HR 2.33, 95%CI: 1.1-4.9, p=0.02). Graft source did not influence survival outcomes.Graft cell composition analysis was performed separately for BM and PBSC cohorts. For the BM group, univariable analysis showed that CD4 graft count ≥20x10^6/kg was associated with a prolonged PFS [60% (95%CI: 28-81) vs 0%, p<0.01] (fig. 1), a trend toward a decreased NRM [0% vs 27% (95%CI: 5-56), p=0.05] and a prolonged OS [92%(95%CI: 57-99) vs 58% (95%CI:27-80), p=0.05]. Among the CD4 subsets analyzed (activated, central memory, effector, effector memory, memory stem cells, regulatory, Th17), naive T cells ≥8.5x10^6/kg (CD3+/CD8-/CD4+/CCR7+/CD45RA+/CD95-) and recent thymic emigrants ≥6.9x10^6/kg (median) (RTEs, CD4+/CD31+/CD45RA+) were the only phenotypes associated with a better PFS and OS (p=0.02 and p=0.04 respectively). For the PBSC group, CD8 graft count ≥ 75 x10^6/kg (median) was associated with a lower NRM [3% (95%CI: 0-12) vs 16% (95%CI:6-30), p=0.01]. No associations were found regarding graft cell composition and incidence of acute or chronic GVHD for both BM and PBSC groups.Conclusions: In our retrospective analysis, we did not observe significant differences in survival outcomes based on graft source. Patients receiving BM grafts developed fewer grade II-IV aGVHD, but grade III-IV aGVHD incidence was similar between the two groups.For the BM group, a higher CD4 count was predictive of better PFS, TRM and OS, as reported with standard GVHD prophylaxis and matched donors (Waller EK, J Clin Oncol 2014. 32: 2365-2372). Interestingly, of the CD4 population, only naive T cells and RTEs were associated with an improved PFS and OS. A protective effect of CD8 cell count was observed in the PBSC group. This is similar to the non PT-Cy setting where higher CD8 cells are associated with better survival outcomes (Reshef R, J Clin Oncol 2015). These data should be validated in a prospective analysis to guide the choice of cell source in the haplo PT-Cy setting. [Display omitted] DisclosuresCorradini:Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Servier: Honoraria; Gilead: Honoraria; Takeda: Consultancy.

Influence of Stem Cell Source on Outcomes of Allogeneic Reduced-Intensity Conditioning Therapy Transplants Using Haploidentical Related Donors

We compared outcomes for 2 retrospective cohorts of patients undergoing reduced-intensity conditioning (RIC) therapy transplants using haploidentical related donors and post-transplant prophylaxis against graft-versus-host disease (GVHD) with high-dose cyclophosphamide, tacrolimus, and mycophenolate. The first cohort of 13 was transplanted with bone marrow (BM) as the stem cell source, whereas the second cohort of 23 used peripheral blood stem cells (PBSCs) mobilized with granulocyte colony-stimulating factor. The BM cohort received a single 60-mg/kg dose of cyclophosphamide on day +3, whereas the PBSC cohort received 2 doses on days +3 and +4. Patients in the first cohort were slightly older and had a higher proportion of acute myeloid leukemia, but there were no differences in the distribution of Disease Risk Index scores between the 2 groups. Patients in the PBSC group received double the number of CD34+ cells in the stem cell graft. Times to neutrophil and platelet recovery were not different between the 2 groups. Three patients, all in the PBSC group, failed to engraft but recovered with autologous hemopoiesis and survived. The 6-month cumulative incidences of acute GVHD were 55.1% for BM and 48.5% for PBSCs (P = .651), whereas 24-month cumulative rates for chronic GHVD were 28.6% for BM and 32.3% for PBSCs (P = .685). Only 2 patients, both in the BM group, died of nonrelapse causes, both of second cancers. The 2-year cumulative incidences of relapse were 43.9% for BM and 23.5% for PBSCs (P = .286). Overall survival at 2 years was significantly better for PBSC patients (P = .028), at 83.4% versus 52.7% for BM. Relapse-free and event-free survival did not differ significantly between BM and PBSC groups. In this retrospective analysis, we conclude that the use of PBSCs for haploidentical RIC transplants is a feasible strategy, with equivalent rates of acute and chronic GVHD and risk of relapse and low nonrelapse mortality compared with BM.

Effect of Total Nucleated and CD34+ Cell Dose on Outcome after Allogeneic Hematopoietic Stem Cell Transplantation

During more recent years only few studies have analyzed the effect of total nucleated cell (TNC) and CD34+ cell dose in allogeneic hematopoietic stem cell transplantation (HSCT). A single-center analysis included 544 patients, 227 with a sibling donor and 317 with an unrelated donor. Most patients (n = 292) were treated with myeloablative conditioning, whereas the remaining patients (n = 252) received reduced-intensity conditioning. Bone marrow (BM) (n = 121) and peripheral blood stem cell (PBSC) grafts (n = 423) were analyzed separately. Median TNC and CD34+ cell dose was 3.2 × 108/kg versus 11.6 × 108/kg in BM and 3.9 × 106/kg versus 8.1 × 106/kg in PBSC. In the BM group we found a higher TNC and CD34+ cell dose was associated with a faster neutrophil engraftment (P < .001 and P = .02). In the PBSC group we found patients given a very high (≥11 × 106/kg) CD34+ cell dose had decreased rates of survival (P = .001) and increased relapse (P = .02). A high CD34+ cell dose correlated with faster platelet engraftment (P < .01). In HSCT using PBSCs, the CD34+ cell doses should be kept below 11 × 106/kg but over 2.5 × 106/kg.

Peripheral Blood Stem Cells Vs Bone Marrow: Stem Cell Source Comparison for Patients Acute Myeloid Leukemia and Myelodysplastic Syndrome Receiving an Allogeneic Stem Cell Transplantation from a 10/10 Matched Donor. Study from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC)

Introduction: Peripheral blood stem cells (PBSC) are increasingly used for unrelated donor (UD) hematopoietic stem cell transplantation (HSCT). A recent randomized prospective trial did not detect significant survival differences between PBSC and bone marrow (BM) transplantation from a UD. The use of PBSC reduced the risk of graft failure, whereas BM reduced the risk of chronic graft versus host disease (GVHD) (Anasetti & al, NEJM 2012). However, HLA matching was based on HLA-A, HLA-B, HLA-C &HLA-DRB1 (8/8 but also 7/8), some of the patients (pts) received a reduced intensity conditioning regimen (22%) and diseases consisted of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), but also other hematological malignancies. We thus conducted this study to compare mobilized PBSC with BM for matched 10/10 UD HSCT after standard conditioning regimen (MAC) in pts with AML and MDS only.Patients and methods: We included all consecutive pts in France who received a first HSCT for AML or MDS with PBSC or BM from a matched 10/10 UD after a MAC (fractionated total body irradiation (TBI)-Cyclophosphamide(Cy), n=165 or Endoxan-Cy, n=203) between 2000 and 2013. Clinical data were prospectively collected using ProMISe (Project Manager Internet Server), an internet-based data registry system shared by all centers of the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC). HLA typing data were collected from the SFHI (French Society of Histocompatibility and Immunogenetic) and the ABM (French Biomedical Agency). This study is in accordance with Helsinki declaration for clinical research.Results: We included368 adults pts (221 [60%] received BM; 147 [40%] received PBSC). Median follow-up was of 16.5 months [0-156]. The BM and PBSC groups were well balanced with respect to age, diagnosis, disease risk, use of antithymocyte globulins (ATG) (67 [30%] BM and 52 [35%] PBSC recipients,) and cytomegalovirus (CMV) recipient and donor status. PBSC recipients were more likely to be male and received less TBI-based regimen. GVHD prophylaxis mainly combined cyclosporine A (CSA) and methotrexate (MTX) (82%).The median number of nucleated cell dose infused was higher in the PBSC group compared with the BM group: CD34+ cells, 6.96 x10⁶/kg [1.2-37.8] vs 2,78 x10⁶/kg [0.6-89] p<0.01) and total nucleated cells, 9.8 x10⁸/kg [1.3-663] vs 2.3 x10⁸/kg [0.3-305.3] p<0.01).Two hundred and seven (90%) pts engrafted after BM and 144 (99.3%) after PBSC HSCT (p=0.1). Among pts who received PBSC as compared with those who received BM, the median time to neutrophils engraftment (> 0.5 x 109 /L) was 6 days shorter and 8 days shorter to platelets engraftment (>20x109 /L) (p<0.01).The cumulative incidence (CI) for severe acute GVHD III-IV was 21.1% and 16.3% in the PBSC and the BM group, respectively (p=0.18).CI of chronic GVHD was higher after PBSC (47.1% vs 34.3% for BM, p=0.05). By multivariate analysis, the absence of ATG in the conditioning regimen (HR 0.4 95%CI [0.22-0.72] p<0.01) and PBSC as stem cells source (HR 0.6 95%CI [0.34-0.97] p=0.04) were associated with an increased chronic GVHD.At 2-years, the CI of non relapse related mortality (NRM), relapse as well as disease free survival (DFS) and overall survival (OS) were similar between the 2 groups (Table 1).In multivariate analysis, better OS was associated with complete remission (CR) disease status (HR 0.5 95%CI [0.32-0.69] p<0.01) and pts’s age<38.1 years (HR 0.67 95%CI [0.48-0.93] p=0.02) at time of HSCT, and the use of CSA-MTX as GVHD prophylaxis (HR 0.6 95%CI [0.41-0.95] p=0.03).Conclusion: OS, NRM and relapse rates are similar with PBSC and BM after HLA 10/10 matched UD for AML or MDS using MAC, but engraftment is better with PBSC and the CI of chronic GVHD is lower with BM. Better results are obtained for pts <38 years old with a disease in CR at time of HSCT using CSA-MTX as GVHD prophylaxis. The absence of ATG with PBSC was associated with chronic GVHD. This study thus favors the use of ATG in the setting of matched 10/10 PBSC. However, the role of ATG in the context of BM after HLA 10/10 matched UD MAC HSCT remains unclear and warrants further investigation.Table 1:2-year CI of NRM*, relapse, DFS** and OS***ParametersBM % (95% CI)PBSC % (95%CI)p valueNRM23 (20-26)18 (15-21)0.8Relapse30 (27-33)28 (25-31)0.83DFS47.1 (44-51)54.4 (50-58)0.2OS54 .4 (50.8-57.9)60.2 (55.7-64.6)0.31*NRM: non-relapse mortality**DFS: disease free survival***OS: overall survival DisclosuresNo relevant conflicts of interest to declare.

Intracerebral Implantation of Autologous Peripheral Blood Stem Cells in Stroke Patients: A Randomized Phase II Study

In our previous study, intracerebral implantation of peripheral blood stem cells (PBSCs) improved functional outcome in rats with chronic cerebral infarction. Based on this finding, a randomized, single blind controlled study was conducted in 30 patients [PBSC group (n = 15) and control group (n = 15)] with middle cerebral artery infarction confirmed on a T2-weighted MRI 6 months to 5 years after a stroke. Only subjects with neurological deficits of intermediate severity based on the National Institute of Health Stroke Scale (NIHSS; range: 9-20) that had been stable for at least 3 months were enrolled. Those in the PBSC group received subcutaneous G-CSF injections (15 µg/kg/day) for 5 consecutive days, and then stereotaxic implantation of 3-8 × 10(6) CD34(+) immunosorted PBSCs. All 30 patients completed the 12-month follow-up. No serious adverse events were noted during study period. Improvements in stroke scales (NIHSS, ESS, and EMS) and functional outcomes (mRS) from baseline to the end of the 12-month follow-up period were significantly greater in the PBSC than the control group. The fiber numbers asymmetry (FNA) scores based on diffusion tensor image (DTI) tractography were reduced in every PBSC-treated subject, but not in the control group. Reduction in the FNA scores correlated well with the improvement in NIHSS. Furthermore, a positive motor-evoked potential (MEP) response by transcranial magnetic stimulation (TMS) appeared in 9 of the 15 subjects in the PBSC group. This phase II study demonstrated that implantation of autologous CD34(+) PBSC was safe, feasible, and effective in improving functional outcome.

Similar outcomes of peripheral blood stem cells vs. bone marrow for human leukocyte antigen‐matched unrelated donor transplantation in adult patients with acute myeloid leukemia using risk‐adapted graft‐versus‐host disease prophylaxis

In unrelated donor allogeneic stem cell transplantation (URD-SCT), most studies reported that peripheral blood stem cells (PBSC) resulted in higher incidence of acute and/or chronic graft-versus-host disease (GVHD) without survival benefits compared with bone marrow (BM). To overcome these shortcomings of PBSC, we have used a risk-adapted GVHD prophylaxis for patients that received HLA-matched URD-SCT, which was adding low-dose rabbit antithymocyte globulin (Thymoglobulin(®) , 1.25 mg/kg for 2 d) to conditioning in the transplants with PBSC and not BM. To determine whether this strategy is effective, we analyzed 115 adult patients with acute myeloid leukemia who received HLA-matched URD-SCT with PBSC (n = 70) or BM (n = 45) using our risk-adapted GVHD prophylaxis strategy. The PBSC group showed faster neutrophil (11 d vs. 13 d; P < 0.01) and platelet (12 d vs. 18 d; P < 0.01) engraftment compared with the BM group. No difference was observed in the incidence of acute GVHD grade II-IV at 100 d (54.3% vs. 64.4%; P = 0.38) and chronic GVHD at 4 yr (65.1% vs. 60.0%; P = 0.83). Other outcomes including the incidence of relapse (30.8% vs. 31.2%; P = 0.53), non-relapse mortality (13.5% vs. 6.9%; P = 0.24), disease-free survival (55.7% vs. 61.9%; P = 0.68), and overall survival (62.2% vs. 63.2%; P = 0.96) at 4 yr were not significantly different. Our risk-adapted GVHD prophylaxis strategy resulted in similar transplant outcomes including comparable incidence of GVHD between the PBSC and BM groups in HLA-matched URD-SCT.

Bone Marrow (BM) Versus Peripheral Blood Stem Cell (PBSC) For Haploidentical Transplantation With Nonmyeloblative (NMA) Conditioning Regimen and Post Infusion Cyclophosphamide

IntroductionTransplantation from alternative donors has been used since several years for patients with hematological malignancies lacking of HLA identical donors. The Baltimora group pioneered the use of cyclophosphamide (Cy) after haploidentical unmanipulated (BM) stem cells infusion. BM was chosen to reduce the risk of acute and chronic graft versus host disease (GVHD). PBSC could replace BM, fastening engraftment and immunological reconstitution. However, the risk of GVHD could be higher.We retrospectively analyzed a cohort of patients from two institutions, receiving haploidentical transplantation with nonmyeloablative conditioning regimen (NMA) and PSBC or BM, with post-infusion Cy. Patients and MethodsFrom April 2009 to April 2013, 72 patients with poor prognosis hematological malignancies received haploidentical transplantation. Conditioning regimens consisted of Cy 14.5 mg/kg d -5 and -6, fludarabine 30 mg/m2 d-6 to d-2, and low dose TBI (2 Gy) at d-1. GVHD prophylaxis consisted of Cy 50 mg/kg day +3 and +4, tacrolimus (FK, 1 mg total dose, in continuous infusion) until days +180 (Milan cohort) or cyclosporine (CsA, 3 mg/kg) (Marseille cohort) and MMF (15 mg/kg 3 per day) until day +35. FK, CsA and MMF were started at d +5. G-CSF was started at d +5 in all patients. Donors underwent bone marrow harvest under general anesthesia and a total of 4 x 10e8 nuclear cells per kg of recipient was targeted. Unmanipulated bone marrow was used as stem cell support at d0. In Marseille, donors were mobilized using 5 to 6 days of subcutaneous G-CSF (Neupogen®) (10 mcg/kg/day). A minimum of 4 x 10e6 CD34/kg was harvested. ResultsThe median follow-up was 12 months (range: 1-48). For the population as a whole, the median time to ANC more than 0.5 x 10e9/L was 20 days (14-32) and the median time to transfusion-independent platelet (PLT) count was 29 days (14-52). Engraftment results in the two cohorts of patients (BM vs PBSC) were not significantly different [ANC 21 days (14-32) vs 20 days (14-27), and PLT 29 days (16-46) vs 27 days (14-52)]. Overall, aGVHD 2-4 incidence was 27% and cGVHD was 13%. No difference was founded in the two cohorts: aGVHD 2-4 24% vs 33% and cGVHD 11% vs 17%. The 1-year non relapse mortality was 18% overall, and it was not statistically different even if numerically lower in the PBSC group (22% vs 9%). ConclusionThis retrospective study showed that there was not significant differences in terms of hematological reconstitution and both acute and chronic GVHD, using unmanipulated BM and PBSC after NMA conditioning regimen and post-infusion Cy. The 1-year NRM, even if not statistically different, was lower with PBSC. These data warrant confirmation with more patients and longer follow-up. Disclosures:No relevant conflicts of interest to declare.

Mobilized Peripheral Blood Stem Cells Compared with Bone Marrow as the Stem Cell Source for Unrelated Donor Allogeneic Transplantation with Reduced-Intensity Conditioning in Patients with Acute Myeloid Leukemia in Complete Remission: An Analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Reduced-intensity conditioning allogeneic stem cell transplant (RIC-alloSCT) is being increasingly used for patients with acute myelogenous leukemia (AML) with comorbidities. Few published data are currently available regarding for the use of peripheral blood stem cells (PBSCs) compared to bone marrow (BM) in the RIC-alloSCT using unrelated donors (URDs). This retrospective report compared the outcomes of PBSC versus BM RIC-alloSCT. Between 2000 and 2007, 602 patients with AML in complete remission (CR) underwent RIC-alloSCT from URDs with PBSC (508) or BM (94) grafts. Recipient's age was higher in the PBSC versus BM groups 57 (range, 17-77 years) and 51 (range, 17-76 years), respectively (P < .0001). Leukemia features and disease status at RIC-alloSCT were also comparable between the PBSC versus BM groups. Engraftment was achieved in 97% and 96% with BM versus peripheral blood (PB), respectively. Acute graft-versus-host disease (aGVHD) grade >II was significantly higher in the PBSC group: 27% versus 12% in the BM group (P < .002). Similarly, chronic graft-versus-host disease (cGVHD; at 2 years) was somewhat higher in the PBSC group with 43% ± 3% versus 35% ± 6% in the BM group, respectively (P = .04). The 2-year probabilities of leukemia-free survival (LFS) were 46% ± 3% for the PBSC group in comparison to 43% ± 6% for the BM transplant group (P = NS), whereas relapse incidence was significantly higher in the BM versus the PB transplant group: 46% ± 6% versus 32% ± 3%, respectively (P = .014). Non-relapse mortality (NRM) was significantly higher for the PBSC versus the BM group: 28% ± 2% versus 13% ± 4%, respectively (P = .004). In multivariate analysis, after adjustment for differences between both groups, the PBSC group was associated with a higher incidence of aGVHD (grade II-IV; hazard ratio [HR] = 2.33; P = .06), higher NRM (HR = 2.3; P = .015), and a decreased relapse incidence (HR, 0.61; P = .02) with no statistical difference of LFS between the 2 groups (P = .88). In conclusion, our results indicate significantly higher incidence of aGVHD and NRM and a lower incidence of relapse but not statistically different LFS comparing unrelated PBSC to BM grafts after RIC-alloSCT.