scholarly journals Comparable Outcomes Among Adult Patients Allotransplanted for Myelodysplastic Syndrome Using Haploidentical, Matched Unrelated or Matched Sibling Donors: A Single-Center Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4914-4914
Author(s):  
Alice Garnier ◽  
Maxime Jullien ◽  
Thierry Guillaume ◽  
Pierre Peterlin ◽  
Amandine Le Bourgeois ◽  
...  
Keyword(s):  
Stem Cells ◽  
Myelodysplastic Syndrome ◽  
Peripheral Blood ◽  
Risk Index ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
Matched Sibling

Abstract Introduction: Allogeneic stem cell transplantation (allo-SCT) remains the only curative option for patients with myelodysplastic syndrome (MDS). If recent data have shown encouraging results with haploidentical (haplo) donors in this context, no comparison with allo-SCT using other source of graft (matched sibling [MSD] or unrelated [MUD] donors) has been reported so far. Methods: We retrospectively considered 102 consecutive adults transplanted for MDS between March 2010 and August 2020 in our Department, comparing outcomes between those receiving a graft from a MSD, a MUD or a haplo-donor. Results : Thirty-three, 48 and 21 patients respectively received a graft from a MSD, MUD or haplo donor. Peripheral blood stem cells (PBSC) were the source of graft for all patients. The median age of the whole cohort was 63 years old (range: 20-74) and the median follow-up was 23 months (range: 0-125). The three groups shared similar characteristics (gender, type of MDS, disease status, disease risk index, CMV status, ABO compatibility, peripheral blood stem cells graft count, conditioning regimen) except median recipient age which was younger in matched patients ( 61 vs 65 MUD vs 65 Haplo, p=0,04) and median donor age which was older in matched transplant ( 61 vs 34 MUD vs 42 Haplo, p< 0,001) (Table 1). With a median follow-up of 46,4 months, the 4-year OS (Figure 1) was comparable between the three groups (haplo: 60.1 % ± 11,0 % , MSD: 59,0 % ±9,4 % and MUD: 61.2 % ± 7,2 %, p = 0.88) as well as the 4-year DFS (Figure 2) (55.9 % ± 11,1 % vs 51,2 % ±9,2 % vs 59.6 % ± 7,2 %, p = 0.78) and the cumulative incidence (CI) of NRM (34.6 % ±12,4 % , 15,4% ± 6,4% and 23.8 % ± 6,4 %, p = 0.21). Also, the 4-year CI of acute grade 3-4 GVHD (14,3% vs 15,2% vs 20,8%, p=0.79) and of moderate/severe chronic GVHD (14,3% vs 24.2% vs 27,1%, p=0.56) were not significantly different. The 4-year GRFS seemed better with haplo (Figure 3) but this was not statistically significant (56,1 % ± 11,0% vs 28,1% ±9,2 % vs 32,8 % ± 7,4%,p=0 .41). Conclusions: These data suggest that haplo-identical donors represent a valid alternative in MDS patients lacking a MSD or a MUD for allo-SCT. Figure 1 Figure 1. Disclosures Moreau: Oncopeptides: Honoraria; Amgen: Honoraria; Celgene BMS: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria.

scholarly journals Transplantation of allogeneic CD34+ peripheral blood stem cells in patients with advanced hematologic malignancy

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4132-4138 ◽  
Author(s):  
WI Bensinger ◽  
CD Buckner ◽  
K Shannon-Dorcy ◽  
S Rowley ◽  
FR Appelbaum ◽  
...  
Keyword(s):  
Stem Cells ◽  
Body Weight ◽  
Peripheral Blood ◽  
Hematologic Malignancy ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Hematologic Malignancies ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Sixteen patients with advanced hematologic malignancies were transplanted with HLA-identical allogeneic peripheral blood stem cells (PBSCs) that were selected for CD34+ cells by an avidin-biotin immunoadsorption technique. The median age of patients was 48 years (range, 37 to 67). Patients received 12.0 or 13.2 Gy of total body irradiation followed by 120 mg/kg of cyclophosphamide. Normal donors received 16 mg/kg of granulocyte-colony stimulating factor on days 1 to 6 followed by PBSC harvests on days 4 to 7. PBSC harvests were processed each day on a single avidin-blotin column containing an antibody to the CD34 antigen and processed cells were infused without cryopreservation daily for 4 consecutive days. Prophylaxis against graft-versus-host disease (GVHD) consisted of cyclosporine alone for 5 patients and CSA plus methotrexate for 11 patients. A median of 18.64 (6.74 to 34.97) x 10(8) CD34+ cells/kg patient body weight were collected from each donor. A median of 8.96 (2.62 to 17.34) x 10(8) CD34+ cells/kg patient body weight were recovered after avidin-biotin adsorption which represented a median CD34+ cell yield of 53% (18% to 77%) with a median purity of 62% (34% to 82%). There was a reduction in CD3+ cells from a median of 557.26 (227.73 to 677.77) x 106/kg to 0.73 x 10(4)/kg (0.40 to 3.65), in CD4+ cells from 351.72 (194.47 to 520.11) x 10(6)/kg to 0.40 (0.15 to 1.03) x 10(4)/kg and in CD8+ cells from 169.74 (53.34 to 325.83) x 10(6)/ kg to 0.32 (0.12 to 2.71) x 10(4)/kg representing a median 2.8 (2.19 to 3.14) log reduction in T cells. One patient died of infection on day 3 posttransplant and was unevaluable for recovery of neutrophils. The median day to recovery of 500 neutrophils/mL was 15 (8 to 26) in the remaining 15 patients. Six of 16 patients falled to achieve a platelet count of 20,000/mL before death on days 3 to 97 of transplant-related complications. The median day to achieving platelets of 20,000 mL in the remaining 10 patients was 11 (7 to 31). Eight of 16 patients (50%) died between 3 and 97 days posttransplant, 7 of transplant-related causes, and 1 of progressive disease. Grade 2–4 acute GVHD occurred in 12 out of 14 (86%) and grades 3–4 in 6 out of 14 (43%) evaluable patients. Six of 8 evaluable patients developed clinical chronic GVHD and 1 developed subclinical chronic GVHD. Bone marrow and/or peripheral blood chimerism studies in 12 evaluable patients showed 97% to 100% donor type in 11 patients with 1 patient in relapse showing 40% donor cells 60 to 90 days posttransplant. Four of 16 patients (25%) are alive and disease-free 312 to 576 days after transplant. There were no episodes of graft failure or rejection. This study shows that allogeneic transplantation using CD34+ selected PBSC results in prompt and sustained engraftment. CD34+ selection, as employed in this preliminary study, however, resulted in an apparently higher rate of acute and chronic GVHD. However, The sample size is quite small and precludes a more definitive conclusion regarding GVHD.

scholarly journals Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor [see comments]

Blood ◽  
1995 ◽  
Vol 85 (6) ◽  
pp. 1655-1658 ◽  
Author(s):  
WI Bensinger ◽  
CH Weaver ◽  
FR Appelbaum ◽  
S Rowley ◽  
T Demirer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Chromosome Analysis ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
Stimulating Factor

Peripheral blood stem cells (PBSCs) are widely used in autologous transplantation because of ease of collection and rapid hematopoietic reconstitution. However, PBSCs have rarely been used for allogeneic transplantation because of concerns about donor toxicities from cytokine administration and the theoretical increased risk of graft- versus-host-disease (GVHD) from the large number of T cells infused. Eight patients with advanced malignancies received allogeneic PBSC transplants from genotypically HLA-identical sibling donors. All donors received 5 days of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 16 micrograms/kg/day) subcutaneously and were leukapheresed for 2 days. After treatment of the patient with total body irradiation and cyclophosphamide (n = 7) or etoposide, thiotepa, and cyclophosphamide (n = 1), PBSCs were infused immediately after collection and without modification. All patients received cyclosporine and either methotrexate (n = 6) or prednisone (n = 2) for GVHD prophylaxis, rhG-CSF was well tolerated with mild bone pain requiring acetaminophen occurring in two donors. All patients engrafted and in seven hematopoietic recovery was rapid, with 500 neutrophils/microL achieved by day 18 and 20,000 platelets/microL by day 12. Complete donor engraftment was documented by Y chromosome analysis in all four sex-mismatched donor-recipient pairs tested and by DNA analysis in two sex-matched pairs. One patient died on day 18 of veno-occlusive disease of the liver with engraftment but before chromosome analysis could be performed (results are pending in 1 patient). A second patient died of fungal infection 78 days after transplant. Grade 2 acute GVHD occurred in two patients and grade 3 GVHD occurred in one patient. One patient is 301 days from transplant in remission with chronic GVHD; the remaining five patients are alive and disease free 67 to 112 days after transplantation. Preliminary results indicate that allogeneic PBSCs mobilized by rhG-CSF can provide rapid hematologic recovery without an appreciably greater incidence of acute GVHD than would be expected with marrow. Further follow-up is required to determine the incidence of chronic GVHD and any potential beneficial effects on relapse after transplant.

Platelet-Derived Microparticles Accelerate Engraftment of Peripheral Blood Stem Cells in Human Allogeneic Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3035-3035
Author(s):  
Christiane de Rop ◽  
Jan Priesack ◽  
Andreas Tiede ◽  
Arne Trummer
Keyword(s):  
Stem Cells ◽  
Cell Count ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Positive Control ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
The Impact

Abstract While the procoagulant activity of platelet derived microparticles (PMP) has been widely accepted, knowledge regarding their immunological and adhesive qualities is still limited. It has been shown that murine BM cells covered with PMP engrafted lethally irradiated mice significantly faster than those not covered, indicating that PMPs play an important role in the homing of peripheral blood stem cells (PBSC). Here we studied the impact of PMP on engraftment in human allogeneic PBSC transplants for patients with hematological malignancies. PBSC samples were collected in buffered citrate from transplantation bags after infusion of transplants into patients with hematological malignancies (AML = 5, ALL = 1). Conditioning regimens included busulfan/cyclophosphamide (Bu/Cy), anti-CD66b-radioimmunotherapy (RIT)/Bu/Cy, and reduced intensity regimens with fludarabin/busulfan (Flu/Bu) and FLAMSA. Platelet-poor plasma (PPP) was prepared (1500g for 20min), immediately shock-frozen in liquid nitrogen and stored at −80°C. For further analysis PPP’s were carefully thawed at room temperature (RT). 90μl of PPP was stained with 5μl of CD41-PE and CD62P-FITC each for 15min at RT in the dark (IgG1-FITC and -PE served as negative controls, TRAP-6 (10μM) stimulated whole blood processed in same way as samples as positive control). To stop staining 900μl PBS/BSA 2% was added and 500μl of this solution were transferred into BD Trucount tubes by reverse pipetting giving a final concentration of 100 beads/μl. Samples were analyzed immediately using Coulter FC500 flow cytometer with CXP software. As expected the CD34 cell count (mean=5.1x106/kg body weight, SD=2.0x106/kg) showed a significant correlation (p=0.0197, Pearson r=−0.83) with the time to engraftment (mean=15.7days, SD=2.0d). The amount of CD62P positive microparticles (mean=423/μl, SD=119/μl) and the conditioning regimen showed no significant correlation with CD34 cell count or time to engraftment with leucocytes >1000/μl. In contrast, CD41-PMP count (mean=1223/μl, SD=857μl) correlated significantly with the CD34 cell count (p=0.0086, Pearson r=0.92) and the time to engraftment (p=0.0039, Pearson r = −0.95). Therefore, PBSCT contain significant amounts of PMP which are most likely generated during apheresis. Preliminary results show a stronger correlation with time to engraftment than does CD34 cell count. We conclude that PMP may accelerate engraftment of PBSC in humans. However, this function seems unrelated to P-Selectin expression. Therefore, further studies aiming to identify other adhesion molecules involved in PMP-mediated engraftment of PBSCT are warranted.

Cryopreservation of Peripheral Blood Stem Cells From Matched Related and Unrelated Donors Is Associated with Delayed Neutrophil and Platelet Engraftment but Does Not Influence Relapse-Free Survival

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2998-2998
Author(s):  
Patrick G Medd ◽  
Sandeep Nagra ◽  
Daniel Hollyman ◽  
Charles F. Craddock ◽  
Ram Malladi
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Lymphoid Malignancy ◽  
Relapse Free Survival ◽  
Peripheral Blood Stem Cells ◽  
Free Survival ◽  
Blood Stem Cells ◽  
Neutrophil Engraftment

Abstract Abstract 2998 Cryopreservation of peripheral blood stem cells (PBSC) for allogeneic transplantation (allo-SCT) has potential advantages including ensuring an adequate stem cell dose is available prior to commencing transplant conditioning and allowing more flexible transplant scheduling. Concerns that cryopreservation may impair engraftment have, however, limited its use. In addition, no published series have examined cryopreservation of matched unrelated donor (MUD) PBSC. In this study, we assessed engraftment and survival following allo-SCT using cryopreserved PBSC. Seventy-six allo-SCT using cryopreserved PBSC were assessed: 57 from HLA matched family donors and 19 from MUD where HLA allelic match was 10/10 (n=14) or 9/10 (n=5). Transplants were performed between 2004 and 2010. Indications for allo-SCT were myeloid malignancy (n=50) or lymphoid malignancy (n=26). Disease was early phase in 51 (67.1%) and late phase in 25 (32.9%) patients. Conditioning was myeloablative (MAC) in 27 and reduced intensity (RIC) in 49 patients, 49 patients received in vivo T cell depletion with alemtuzumab or anti-thymocyte globulin. Median follow-up (FU) of survivors was 41 months. Comparison was made against a broadly matched control group comprising 79 allo-SCT using fresh PBSC. Cumulative incidence of neutrophil engraftment to >0.5 × 109/L at day 14 was (95% confidence interval (CI)) 73.3% (61.–82) vs 92.3% (83.4–96.5) for cryopreserved vs fresh PBSC respectively. Neutrophil engraftment was significantly delayed (P=0.00031, Log-rank test) in the cryopreserved group but neutrophil engraftment at day 30 was identical at 99% in both groups. Platelet (plt) engraftment to >50 × 109/L at day 14 was 27.6% (18.8–38.1) vs 58.9% (47.1–69) for cryopreserved vs fresh PBSC respectively, P<0.0001. Cumulative incidence of plt engraftment at day 30 was 72.3% (60.3–81.2) vs 96.2% (87.4–98.9) for cyropreserved and fresh PBSC respectively. In multivariate analysis delayed neutrophil engraftment was associated with cryopreservation (hazard ratio (HR)=1.59, 95% CI 1.2–2.13, P=0.0014), MAC (HR=1.67, 95%CI 1.22–2.3, P=0.0015) and lymphoid malignancy (HR=1.49, 95% CI 1.11–2, P=0.0077). Delayed plt engraftment was associated with cryopreservation (HR=2.17, 95% CI 1.49–3.13, P<0.0001) and related donor transplant (HR=1.46, 95% CI 1.05–2, P=0.025). Eight patients, 6 in the cryopreserved and 2 in the fresh PBSC group required CD34 selected PBSC ‘top-up’ for primary engraftment failure, 5 of whom (4 cryopreserved, 1 fresh) were alive at last follow-up. One patient in the fresh and none in the cryopreserved PBSC group experienced late secondary graft failure. Relapse-free survival at 2 years was 40.7% (30.4–54.4) vs 50.2% (39.6–63.6) P=0.42 for cryopreserved vs fresh PBSC respectively. There were no significant differences in relapse incidence, transplant-related mortality, incidence of grades II-IV acute graft-vs-host disease or extensive chronic GvHD between cryopreserved and fresh PBSC. Whilst cryopreservation of PBSC for allo-SCT in both matched related and MUD allo-SCT is associated with significantly delayed neutrophil and platelet engraftment, only delayed platelet engraftment is likely to be of clinical significance. Survival was comparable to allo-SCT using fresh PBSC. In lieu of evidence from prospective trials, PBSC cryopreservation should be considered as an option in selected patients for whom its benefits outweigh the risks of delayed engraftment. Disclosures: Craddock: Celgene: Honoraria, Research Funding.

Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Multiple Myeloma (MM): Long Term Follow-up in a Single Centre Series

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4398-4398
Author(s):  
Malek Benakli ◽  
Redhouane Ahmednacer ◽  
Amina Talbi ◽  
Farih Mehdid ◽  
Rachida Belhadj ◽  
...  
Keyword(s):  
Complete Remission ◽  
Median Time ◽  
Acute Gvhd ◽  
Late Onset ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Peripheral Blood Stem Cells ◽  
Heavily Pretreated ◽  
Blood Stem Cells

Abstract Background: RIC allo-SCT has been proposed as a strategy for retaining the graft versus myeloma effect of allo-SCT while decreasing transplant related mortality (TRM). Here, we retrospectively studied a series of 15 patients (pts) with MM treated by RIC allo-SCT. Patients and methods: Between April 2001 and December 2007, 15 pts with MM underwent RIC allo-SCT with an HLA-identical sibling donor. Initially, 8 pts had MM with Ig G, one IgA, 2 light chains, 3 non-secretory and one undetermined. Three pts were stage II and 12 stages III. At time of allo-SCT, 6 pts were in complete remission and 9 in refractory/progressive disease (2 received prior autologous transplants). Median age was 48 years (range, 38–60) and the sex-ratio (M/F) 1,5. Median time from diagnosis to RIC allo-SCT was 18 (range, 6–76) months. The conditioning regimen included Fludarabine 150mg/m2 and Melphalan 140mg/m2. GVHD prophylaxis consisted of association cyclosporine (cSA) and mycophenolate (MMF). All pts received G-CSF mobilised peripheral blood stem cells, with a median CD34+ cell count: 4,5.106/kg (range, 1.92–13). Results: Neutropenia occurred in all pts and the median duration of aplasia was 8 (range, 5–14) days. Only 3 pts (20 %) required red blood cells transfusions and 12 pts (80 %) needed platelets transfusions. Acute GVHD was observed in 6 cases (40 %) including 4 cases of grade II–IV. Eight pts (72 %) had chronic GVHD, of whom 5 with an extensive form. Three pts (20 %) had CMV reactivation at a median time 91 (range, 53–158) days after transplantation. Four pts (26 %) had late onset relapse at a median time of 826 (range, 248–1370) days. TRM was 33 % at one year after RIC allo-SCT. With a median follow-up of 50 (range 14–86) months, 5 pts (33 %) are still alive in complete remission with full donor chimerism. Ten pts (66 %) died (2 early severe infections, 3 acute GVHD, 3 after relapse, one myocardial infarction, and one public highway accident). Overall and progression-free survivals at 7 years are 37,5 % and 31,2 % respectively. Conclusion: This study suggests that RIC allo-SCT is a potential therapy for relapsed MM. However, TRM and relapse remain a matter of concern, likely due to the inclusion of refractory and heavily pretreated pts with many comorbid conditions. Future protocols, should aim for better patient selection, focussing on those pts in first chemosensitive relapse.

scholarly journals Allografting in patients with severe, refractory aplastic anemia using peripheral blood stem cells and a fludarabine-based conditioning regimen: The Mexican experience

2006 ◽  
Vol 81 (3) ◽  
pp. 157-161 ◽  
Author(s):  
David Gómez-Almaguer ◽  
Jorge Vela-Ojeda ◽  
José C. Jaime-Pérez ◽  
César H. Gutiérrez-Aguirre ◽  
Olga G. Cantú-Rodríguez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Aplastic Anemia ◽  
Peripheral Blood ◽  
Conditioning Regimen ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells

Reduced Intensity Allogeneic Stem Cell Transplantation in Patients with Myelodysplastic Syndrome: Does the Conditioning Matter?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4924-4924
Author(s):  
Louis Terriou ◽  
Zina Chir ◽  
Helene Esperou ◽  
Jean-Michel Boiron ◽  
Jean-Paul Vernant ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Chronic Gvhd ◽  
Immunosuppressive Treatment ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
The Impact ◽  
Reduced Intensity

Abstract Allogeneic transplantation following a reduced-intensity conditioning (RIC) has emerged as an alternative to myeloablative transplantation in pts with myelodysplastic syndrome (MDS). Given the uncertainty regarding the most appropriate conditioning regimen, SFGM-TC conducted a retrospective multicenter study in the attempt to evaluate the impact of conditioning on pts’ outcome. The record of 61 pts (37 males) with MDS who received a RIC were reviewed. The median age was 55 years (range: 18–70). According to the FAB classification, 11 pts had RA at diagnosis, of whom one had progressed to REAB and one to AML before transplantation. Thirty two pts had REAB at diagnosis, of whom 2 had progressed to REAB-T and 7 to AML before transplantation. Twelve pts had REAB-T at diagnosis and 6 CMML, of whom 8 progressed to AML before transplantation. The median time from diagnosis to RIC was 12 months (6–129). Conditioning consisted of Fludarabin (Flu) plus busulfan (FB; n=29), Flu plus 2-Gy TBI (F-TBI; n=20) and idarubicin plus aracytine and Flu (FlagIda; n=12). Donors were HLA-identical siblings (n=52) and HLA-matched unrelated (n=9). All pts received peripheral blood stem cells. The median of CD34+ infused cell dose was 5 x 106/kg (0.5–17.3). The median follow-up was 44.7 months (21–85). Estimated 3-year overall survival (OS), progression free survival (PFS), relapse and transplant-relapse mortality (TRM) were 35%, 27%, 66% and 30%, respectively. Neither of the 3 conditioning regimens used (FB, F-TBI and FlagIda) had impact on patients’ outcome. In multivariable analyses, while acute III/IV grade GVHD development was the only factor found to adversely influencing OS (HR=3.6; 95% CI: 1.1–12.2), chronic GVHD development was the only favourably influencing PFS and relapse ratios (HR=0.3; 95% CI: 0.1–0.7 and HR=0.2; 95% CI: 0.1–0.6, respectively). TRM was adversely influenced by male sex of recipient (HR=9.2; 95% CI: 1.5–66.6). RIC is an effective treatment in MDS patients irrespective of conditioning type. While acute III/IV grade GVHD appeared to be detrimental, the benefit effect of chronic GVHD was to be bound to GVL effect as demonstrated by the improvement of PFS and relapse rates in patients who developed chronic GVHD. This study shows no impact of conditioning in pts’ outcomes. New approaches with focus on immunosuppressive treatment are needed to enhance the GVL effect with an acceptable risk of GVHD.

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