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)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2552-2552 ◽  
Author(s):  
Aurélie Ravinet ◽  
Aurélie Cabrespine ◽  
Gerard Socie ◽  
Noel Milpied ◽  
Ibrahim Yakoub-Agha ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
French Society ◽  
Peripheral Blood Stem Cells ◽  
Cell Therapies ◽  
Gvhd Prophylaxis

Abstract 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*** Parameters BM % (95% CI) PBSC % (95%CI) p value NRM 23 (20-26) 18 (15-21) 0.8 Relapse 30 (27-33) 28 (25-31) 0.83 DFS 47.1 (44-51) 54.4 (50-58) 0.2 OS 54 .4 (50.8-57.9) 60.2 (55.7-64.6) 0.31 *NRM: non-relapse mortality **DFS: disease free survival ***OS: overall survival Disclosures No relevant conflicts of interest to declare.

scholarly journals Impact of Antithymocyte Globulins on Patient Outcome after Myeloablative Bone Marrow Stem Cell Transplantation from HLA 10/10-Matched Unrelated Donor: A Report from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1218-1218
Author(s):  
Aurélie Ravinet ◽  
Aurélie Cabrespine ◽  
Gerard Socie ◽  
Ibrahim Yakoub-Agha ◽  
Stephane Vigouroux ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Causes Of Death ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
French Society ◽  
Matched Unrelated Donor ◽  
Cell Therapies

Abstract Background: A recent prospective study (Socie & al Blood 2011) demonstrated that the addition of antithymocyte globulins (ATG) to prophylaxis for graft versus host disease (GVHD) in the setting of standard myeloablative conditioning (MAC) regimen matched unrelated donor (UD) allogeneic stem cell transplantation (HSCT) resulted in a decrease in incidence of chronic GVHD without an increase of relapse or non-relapse mortality. However, stem cell source was mostly peripheral blood stem cells (PBSC) and patients (pts) were compatible at HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1 (eight out of eight alleles). A retrospective study using the same setting (Mohty & al Leukemia 2012) found very similar results with donor/recipient pairs matched at 10 loci (ten out of ten alleles). However, one third of the pts received PBSC as stem cells source and 20% of the pts were transplanted with a mismatch donor (9 out of 10 alleles). We thus conducted this study to assess the impact of ATG in pts with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) transplanted with MAC using bone marrow only (BM) from matched 10/10 UD. Patients and methods: We includedall consecutive pts older than 18 years who received a first HSCT in France for AML or MDS with BM from a matched 10/10 UD after a standard conditioning regimen (fractionated total body irradiation (TBI)-Cyclophosphamide(Cy), n=106 or Endoxan-Cy, n=91) between June 2000 and June 2012. 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). This study was approved by the scientific committee of the SFGM-TC. Results: A total of 197 adult pts met the criteria and were analyzed (165 AML (84%) and 35 MDS). 54 (27%) pts received ATG in the conditioning regimen whereas 143 (73%) did not. Median follow up was of 20.3 months [0.4-156]. Both groups (with or without ATG) were well balanced except for the number of CD34+ cells infused (higher in the ATG group: 3.07x106/kg [0.7-13] vs 2.71x106/kg [0.6-89] for none ATG group (p=0.03)) and GvHD prophylaxis (more likely cyclosporine plus methotrexate with ATG (94%) vs 84% without, p=0.05). The probability of acute GvHD grade II-IV was similar between both groups: 41.3% with ATG vs 49.6% without, p=0.2. Incidence rate of severe acute GVHD grade III-IV at day 100 tended to be lower in the ATG group as compared with the none ATG group (20.3% vs 9.5%, respectively, p=0.052). The cumulative incidence (CI) of chronic GVHD at 2 years was 42% in the ATG group vs 28% in the none ATG group and 37% vs 44% at 4 years, respectively (p=0.18). The probability of extensive chronic GVHD at 2 years was identical between both groups (12% with ATG vs 16% without, p=0.95). 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, advanced disease status was the only parameter associated with decreased DFS (HR 0.37, 95% CI [0.19-0.70], p=0 .02) and OS (HR 0,41, 95% CI [0,24;0,71], p<0.01). During the study, 106 pts died (28 pts (52%) in the ATG group and 78 in the none ATG group (53%)). No difference was observed in terms of cause of death (detailed in Table 2) between the two groups, relapse accounting for half the causes of in both groups (47%). Conclusion:The addition of ATG to MAC regimen in pts with AML or MDS transplanted with BM from matched 10/10 resulted in similar outcomes in terms of NRM, relapse as well as DFS and OS. Despite the limitation due to the retrospective setting of our study, we did not find any obvious benefit for adding ATG to the conditioning regimen in this setting. Prospective studies are needed to firmly answer to this question and notably to better assess a possible benefit in terms of quality of life in the ATG group. Table 1: 2-years cumulative incidence of NRM, relapse, DFS and OS Outcomes ATG group % [95% CI] Non ATG group % [95% CI] p value NRM 21 [15-27] 23 [19-27] 0.90 Relapse 32 [25-39] 31 [27-35] 0.83 DFS 46.9 [39.9-53.9] 46.7[39.7-53.7] 0.98 OS 57.1 [50.2-64] 53[46-60] 0.62 Table 2: main causes of death Causes of death ATG group n,(%) Non ATG group n,(%) Relapse 13 (46.3) 36 (46) GvHD 3 (10.7) 9 (11.5) Infection 2 (7) 12 (15.5) Organ toxicity 5 (18) 11 (14) Secondary neoplasia 1 (3.6) 1 (1.5) Rejection 0 2 (2.5) Unknown 4 (14.4) 7 (9) Disclosures No relevant conflicts of interest to declare.

Fludarabine Based Conditioning for Allogeneic Transplantation in Severe Aplastic Anemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2029-2029
Author(s):  
Mammen Chandy ◽  
Biju George ◽  
Auro Viswabandya ◽  
Vikram Mathews ◽  
Ashish Bajel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Severe Aplastic Anemia ◽  
Peripheral Blood Stem Cells ◽  
Allogeneic Bmt ◽  
Gvhd Prophylaxis ◽  
Blood Stem Cells

Abstract Patients with severe aplastic anemia (SAA) who are multiply transfused or septic have a poor outcome after allogeneic stem cell transplantation. Forty three patients (31 males and 12 females) with SAA underwent allogeneic BMT using a fludarabine based conditioning regimen between 1998 and 2005. The median age was 20 years (range: 4–38) with 11 children and 32 adults. All donors were 6 antigen matched HLA identical sibling or family donors. Co morbidities seen included bacterial sepsis in 15 patients, fungal pneumonia in 4 and a recent intracranial bleed in 5 patients. Seven patients had failed Antithymocyte or antilymphocyte globulin (ATG/ALG) and two patients had failed their first transplant. The median time from diagnosis to transplant was 12 months (range: 2 – 96) and the median transfusions prior to BMT was 28 (range: 2 – 380). Conditioning therapy consisted of: Fludarabine (Flu) 180 mg/m2 over 6d + Busulfan (Bu) 8 mg/kg over 2d + ATG 40 mg/kg/day over 4 d in 17 patients, Flu 180 mg/m2 over 6d + Cyclophosphamide (Cy) 120 mg/kg over 2d ± ATG 40 mg/kg/day over 4d in 17 patients, Flu/TBI/OKT3 in 4, and Cy 120 + Flu 150mg/m2 in 5 patients. Graft versus host disease (GVHD) prophylaxis consisted of Cyclosporine and mini methotrexate. Graft source was peripheral blood stem cells in 39 patients and G-CSF stimulated bone marrow in 4. The median cell dose was 5.2 x 108 MNC/kg (range: 2.1 – 13.6) for PBSC and 5.2 x 108 TNC/kg (range: 3.7 – 6.8) for bone marrow. Five patients expired within the first 10 days due to sepsis. Thirty seven patients engrafted with a mean time to ANC > 500 of 11.6 days (range: 8 – 18) and median platelet engraftment time of 13 days (range: 8 – 32). One patient had primary graft failure and expired on day 64 due to fungal pneumonia despite a second transplant. Acute GVHD was seen in 14 patients (38%) with Grade III–IV GVHD in 4 (10.5%). Chronic GVHD was seen in 10 patients with 6 having limited and 4 with extensive GVHD. Two patients had secondary graft rejection on day + 24 and +60 respectively and expired due to fungal pneumonia. At a median follow up of 17 months (range: 5 – 78); 29 patients (67.7%) are alive and well. Among patients treated with Flu/Bu/ATG, 12/17 (70.5%) are alive and well while the DFS is 82% (14/17) in patients treated with Flu/Cy ± ATG. Comparison with patients conditioned with Cy/ATG during 1990–2004 is given in the table. This comparison suggests that a fludarabine based conditioning regimen may be better, with less rejection, than Cy/ATG for allogeneic BMT in sick patients with SAA who are infected and multiply transfused at the time of BMT. Comparative data Fludarabine Cy/ATG Number 43 26 Rejection 3 (7%) 7 (27%) DFS 29(67.7%) 11 (46%)

Subsets of CD34+ and Engraftment Kinetics in Allogeneic Peripheral Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2954-2954
Author(s):  
Domenico Pastore ◽  
Anna Mestice ◽  
Paola Carluccio ◽  
Tommasina Perrone ◽  
Manuela Leo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Conditioning Regimen ◽  
The Other ◽  
Peripheral Blood Stem Cells ◽  
Gvhd Prophylaxis ◽  
Cd34 Cells

Abstract Engraftment kinetics in allogeneic peripheral blood stem cell transplantation (alloPBSCT) depend on the number and efficiency of the stem cells in the graft, the conditioning regimen and GvHD prophylaxis. Currently, stem cell evaluation is performed by counting CD34+ cells; however, CD34+ cells are a heterogeneous population including the early uncommitted fraction as well as different subsets committed to one or the other lineage; hence, defining the CD34+ subset most predictive of engraftment and its threshold value would be of the utmost importance. This study aimed to identify which graft product subset of CD34+ cells might be the most predictive of early hematopoietic recovery following alloPBSCT. The relationships between the number of “mature” subsets of CD34+ cells (CD34+/CD33+, CD34+/CD38+, CD34+/DR+ and CD34+/CD133) and “immature” subsets of CD34+ cells (CD34+/CD33−, CD34+/CD38−, CD34+/DR− and CD34+/CD133+) and early neutrophil and platelet engraftment were studied in a homogeneous series (for disease, pre-transplant chemotherapy, conditioning regimen GvHD prophylaxis) of 30 acute myeloid leukemia (AML) patients after alloPBSCT from HLA-identical siblings. All patients received the BU-CY regimen consisting of busulfan 4 mg/kg/day for 4 consecutive days followed by cyclophosphamide 60 mg/kg/day for 2 consecutive days; GvHD prophylaxis included cyclosporin and methotrexate. The CD34+ dose infused ranged from 2.9 to 8.8 × 106/Kg (median 4.6); the percentage of immature CD34+ cells was 36% for CD34+/CD33−, 60% for CD34+/CD38−, 5% for CD34+/DR− and 70% for CD34+/CD133+; this translates into a median dose of 1.6 × 106/Kg (range 0.3–5) for CD34+/CD33−, 2.6 × 106/Kg (range 0.1–6.2) for CD34+/CD38−, 0.4 × 106/Kg (range 0.1–2.3) for CD34+/DR− and 0.95 ×106/Kg (range 0.6–2.3) × 106/Kg for CD34+/CD133+. Median time to achieve engraftment of neutrophils and platelets was 13 days (range 10–16) and 15 days (range 13–19), respectively. In our experience the total CD34+/CD133+ cell number was inversely correlated with the days required for recovery of 0.5 × 109/L neutrophils (r = −0.76, p<0.05) and 100 × 109/L platelets (r = −0.71, p<0.05); this correlation was better than the total CD34+ cells dose and neutrophil (r = −0.71, p<0.05) and platelets engraftment (r = −0.68, p = 0.06). No correlation was found between the other CD34+ subsets and neutrophil and platelets engraftment. With regard to the threshold dose for early neutrophil engraftment, all 14 patients who received more than 1 × 106/Kg of CD34+/CD133+ had a neutrophil count higher than 1.0 × 109/L at 12 days. We suggest that a high number of CD34+/CD133+ peripheral blood stem cells may be associated with faster neutrophils and platelets recovery; these findings may help to predict the repopulating capacity of PBSC in patients after allogeneic PBSCT, especially when a relatively low number of CD34+ cells is infused.

scholarly journals Unrelated Alternative Donor Transplants for Severe Acquired Aplastic Anemia: A 12-Year Retrospective Study from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2945-2945
Author(s):  
Raynier Devillier ◽  
Jean-Hugues Dalle ◽  
Laurence Clement ◽  
Noel Milpied ◽  
Patrice Chevallier ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Bone Marrow Transplantation ◽  
Cumulative Incidence ◽  
Marrow Transplantation ◽  
Chronic Gvhd ◽  
Hla Typing ◽  
French Society ◽  
Cell Therapies ◽  
Gvhd Prophylaxis

Abstract In the absence of a matched sibling donor for patients with severe aplastic anemia (SAA), allogeneic hematopoietic stem cell transplantation (Allo-HSCT) from an HLA-matched unrelated donor (UD) is considered after immune suppressive therapy (IST) failure. Outcome after UD Allo-HSCT for SAA has significantly improved in the last 2 decades because of optimization of HLA typing, as well as better conditioning regimens and improved GVHD prophylaxis (Maury Haematologica 2007; Bacigalupo Haematologica 2010). However, the age limit, the impact of extensive HLA typing (12 loci) as well as the best timing for UD Allo-HSCT remain unclear. We thus analyzed all patients in France who received a first Allo-HSCT for idiopathic SAA from a UD between 2000 and 2012. 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). The French national ethics board (CCTIRS) approved this study. Written informed consent was obtained from all patients before Allo-HSCT. One-hundred and thirty-nine consecutive patients (64 male (46%)) were included. Median age was 23 years (range: 1-66). Most patients (81%) received in vivo T-cell depletion using antithymocyte globulins or alemtuzumab. Total body irradiation was used in 64 patients (46%), using low dose in 58 cases (91%). GVHD prophylaxis combined Cyclosporine A and methotrexate in 68% of cases. Respectively 113 (81%) patients and 26 (19%) patients were transplanted using a 10/10 and a 9/10 HLA-matched UD (according to HLA A, B, C, DRB1 and DQB1 allelic matching). Ten patients (7%) experienced primary graft failure. Forty-eight patients developed grade II-IV acute GVHD, leading to a day-100 cumulative incidence of 35%. The cumulative incidence of chronic GVHD was 24% at 4 years (extensive GVHD, 8%) with no specific risk factor identified. With a median follow-up of 51 months, the 4-year overall survival (OS) was 66% for the whole cohort. In multivariate analyses, worst OS was observed for patients transplanted before 2006 (HR=2.45 [1.23-4.88]; p=0.011, Figure 1A), with a CD34+ cell dose < 4 x 106/kg (HR=2.62 [1.31-5.25]; p=0.006), with time from diagnosis to Allo-HSCT > 12 months (HR=2.16 [1.02-4.60]; p=0.046) and who received a 9/10 matched UD (HR=2.27 [1.05-4.91]; p=0.038). Of note, there was a trend for higher mortality in patients older than 40 years of age (HR=1.97 [0.95-4.09]; p=0.069). There was no difference in OS according to conditioning regimen or GVHD prophylaxis. Ninety-eight out of 139 patients had extensive HLA typing on 12 loci (HLA A, B, C, DRB1, DQB1 and DPB1), respectively 82 and 16 patients from the 10/10 and 9/10 HLA-matched groups. Zero, 1 and 2 DPB1 matched alleles were found in 36 (37%), 52 (53%) and 10 (10%) patients, respectively. Of note, we found no difference in 4-year OS according to DPB1 matching among the 82 evaluable 10/10 HLA-matched patients (0 (n=27) vs. 1 or 2 matched DPB1 alleles (n=55): 74% vs. 66%, p=0.466). However, patients transplanted with a 9/10 HLA-matched donor with no matched DPB1 allele reached a significantly lower 4-year OS (0 (n=9) vs. 1 or 2 matched DPB1 alleles (n=7): 22% vs. 86%, p = 0.029, Figure 1B). In conclusion, outcome after UD Allo-HSCT for idiopathic SAA continues to improve with best results seen after 2005. In the presence of a 10/10 matched UD (allelic level), patients less than 40 years of age should be transplanted as quickly as possible if refractory to IST, at least in the first year after the time of diagnosis. Given the excellent OS in the recent period and the particularly low rate of chronic GVHD, Allo-HSCT could be discussed as front line therapy in selected young patients with SAA for whom a 10/10 UD is readily available in the absence of a matched family donor. Moreover, in the absence of a 10/10 HLA-matched UD, Allo-HSCT from a 9/10 HLA-matched UD in the presence of 1 or 2 matched DPB1 alleles is promising and merits further evaluation. Figure 1: A) Overall survival in the 139 patients according to the transplantation period and B) according to DPB1 matching in the patients who received a 9/10 HLA-matched UD Allo-HSCT Figure 1:. A) Overall survival in the 139 patients according to the transplantation period and B) according to DPB1 matching in the patients who received a 9/10 HLA-matched UD Allo-HSCT Disclosures No relevant conflicts of interest to declare.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation Following Reduced-Intensity Conditioning Regimen for Elderly Patients (60 years and older) with Hematological Malignancies Using Unrelated Donors: A Retrospective Study on Behalf of the French Society for Stem Cell Transplantation and Cell Therapies (SFGM-TC)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2472-2472
Author(s):  
Jean El Cheikh ◽  
Patrick Sfumato ◽  
Nathalie Fegueux ◽  
Mohamad Mohty ◽  
Ibrahim Yakoub-Agha ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Hematological Malignancies ◽  
Conditioning Regimen ◽  
French Society ◽  
Hematopoietic Stem ◽  
Cell Therapies ◽  
Gvhd Prophylaxis

Abstract Background: Reduced intensity conditioning (RIC) regimen has allowed the extension of allogeneic hematopoietic stem cell transplantation (allo-HSCT) to a previously unreached population of older patients for whom hematologic malignancies aremore common. The use of unrelated donors (UD) in patients aged of 60 years or more has drastically increased in the past few years. To date, there are only limited data on the feasibility and outcomes of UD allo-HSCT in elderly patients (60 years or more). The purpose of the current study is to describe outcomes in a large cohort of patients aged 60 years or older who received a RIC UD allo-HSCT in recent years. Patients and methods: Between 2008 and 2012, this retrospective multicenter study included 539 consecutive patients aged of 60 years or more (142 aged 65 or more and 9 aged 70 or more) who received a first allo-HSCT for hematological malignancies (351 with myeloid disorders and 188 with lymphoid malignancies) from an UD (HLA matched at HLA-A, -B, -C, -DQ and –DRB1, 10 out of 10 alleles in 95% of cases) after a RIC regimen (Peripheral blood stem cells in 92% of cases) in France. In 85% of the patients, conditioning regimen was fludarabine-based and Graft versus Host Disease (GvHD) prophylaxis consisted of cyclosporine (CSA) plus MMF in 47% of cases and CSA plus methotrexate in 20%. To address the role of age by itself in our population, 2 groups of patients were defined: patients with age at allo-HSCT less than 65 years old ("UD<65 group", n=397) and patients who were aged 65 years or more ("UD ≥ 65 group", n=142). 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). This study was approved by the scientific committee of the SFGM-TC and is in accordance with the declaration of Helsinki for clinical research. Results: Patient characteristics were similar between the 2 groups (UD<65 group and UD ≥ 65 group) for time between diagnosis and allo-HSCT, gender, disease (myeloid versus lymphoid), disease status (complete remission at allo-HSCT versus others), source of stem cells, number of infused total nucleated and CD34 cells, donor age, donor gender, patient/donor sex mismatch, HLA matching, patient/donor CMV (cytomegalovirus) status, the use of antithymocyte globulins (ATG) or TBI-based regimen (2 gray only), and GvHD prophylaxis. Patients in the UD ≥ 65 group received more CD3 cells (p=0.02). The median follow-up was 36 months (range, 0.3-73.5) for UD<65 group and 32 months (range, 0.03-72) for UD≥65 group. During evolution, the cumulative incidence (CI) of grade II–IV acute GvHD was 36% in UD<65 group and 31% in UD≥65 group (p= 0.684) while the CI of chronic GvHD at 2 years was 42% and 35%, respectively (p= 0.334). CI of treatment related mortality (TRM), disease free survival (DFS) and overall survival (OS) were not different between the 2 groups (Table 1). Multivariate analysis for TRM, DFS and OS show that age by itself has no influence. Conclusion: These data suggest equivalence of outcome between UD<65 group and UD≥65 group after RIC UD allo-HCT in this large cohort of elderly patients ( above 60 years old ) with hematological malignancies. Age by itself thus appears not to be a limitation in this particular population of elderly patients. Table 1: 2-year cumulative incidence of TRM, DFS and OS Characteristics TRM DFS OS All patients 29% 42% 49% Patients aged less than 65 years (UD<65 group) 28% 41% 49% Patients aged 65 years or more (UD≥65 group) 33% 47% 51% p value 0.350 0.417 0.809 Disclosures Beguin: Genzyme / Sanofi: Research Funding. Michallet:BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hospira: Consultancy, Honoraria.

Stem Cell Transplantation (SCT) for Acute Myeloid Leukemia (AML): A Single Center in over 25 Years Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5351-5351
Author(s):  
Stella Santarone ◽  
Erminia Di Bartolomeo ◽  
Paolo Di Bartolomeo
Keyword(s):  
Stem Cell ◽  
Multiorgan Failure ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Stem Cell Source ◽  
Short Course ◽  
Gvhd Prophylaxis

Abstract In this study we report the results of SCT in 116 patients (M51, F65) with AML transplanted from HLA identical (n=111) or 1 antigen mismatched (n=5) related donors between 1981 and 2006. The median age was 33 years (1–63). At time of SCT, 76 patients were in CR1, 23 in CR2 and 17 in CR>2 or in relapse. The stem cell source was bone marrow for 94 patients, PBSC for 21 and cord blood for 1. The conditioning regimen was myeloablative for 110 patients (BU CY for 87 and TBI CY for 23) and not-myeloablative for 6 (Thiotepa CY). For GvHD prophylaxis, 30 patients received cyclosporine (CSA) alone and 86 were given CSA and short course methotrexate. All patients engrafted with a median time to achieve 0.5 ×109/L neutrophils and 50×109/L platelets of 20 (10–37) and 22 (11–103) days respectively. One patients lost the graft six months after SCT and was successfully retransplanted. Acute GvHD grade II–IV occurred in 24%. Chronic GvHD occurred in 21% (9% limited, 12% extensive). The overall transplant related mortality (TRM) was 15.5% at 12 months (14,4% in CR1, 8,7% in CR2 and 29% in CR>2 or in relapse). Causes of death were: GvHD in 6 patients, infection in 6, multiorgan failure in 3, renal insufficiency in 1, encephalopathy in 1, pancreatitis in 1. The overall incidence of relapse was 29% (25% in CR1, 26% in CR2, 53% in CR>2). Twelve patients (1 in CR1, 5 in CR2 and 6 in >CR2 or relapse) underwent a second SCT from the same donor after a median interval from the first and second SCT of 456 (203–1946) days. The TRM post-second SCT was 16%. Nine of 12 patients are now living and cured after a median follow-up of 5,4 years (1–16,8). Overall, after a median follow-up of 8.08 (0.3–22) years, 71 out of 116 patients (61%) are living and cured. The 20 years probability of disease free survival is 68% for patients in CR1, 74% for patients in CR2 and 18% for patients in CR>2 or relapse (Fig. 1). In univariate analysis the patient age < 30 years, the BUCY regimen as compared to the TBI regimen and a dose of marrow cells > 3.0 × 108/Kg are associated with a better survival. We conclude that SCT is a curative treatment for patients with AML. In our experience second SCT gives results comparable to those of first transplant. Fig 1. Probability of DFS according to phase of disease at SCT Fig 1. Probability of DFS according to phase of disease at SCT

scholarly journals HLA-Matched Related Donor Hematopoietic Cell Transplantation in Patients with Fanconi Anemia Conditioned with a Combination of Cyclophosphamide and Fludarabine : A Study on Behalf of the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4391-4391 ◽  
Author(s):  
Lina Benajiba ◽  
Clementine Salvado ◽  
Jean-Hugues Dalle ◽  
Charlotte Jubert ◽  
Claire Galambrun ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Graft Failure ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
French Society ◽  
Cell Therapies ◽  
Related Donor ◽  
Grade 3

Abstract Background. Fanconi anemia (FA) is a rare, phenotypically heterogeneous, inherited disorder clinically characterized by congenital abnormalities, progressive bone marrow failure (BMF) and a predisposition to develop malignancies. Hematopoietic stem cell transplantation (HSCT) is the only curative option for FA patients. However, finding the best conditioning regimen is still challenging for clinicians. To reduce toxicities, we used progressively lower doses of cyclophosphamide (CY) for conditioning through non-irradiation based regimens. A reduced conditioning regimen based on CY 60mg/kg alone was proposed by Bomfim et al (BBMT, 2007). Survival rates were excellent but some patients experienced primary (n=1) or late (n=4) graft failure (11% of the patients). Mucositis was a major problem as 25 patients (60%) presented grade 3 / 4 mucositis. The rate of Chronic graft versus host disease (GvHD) was 29%. We hypothesized that tapering the dose of CY to 40mg/Kg and adding fludarabine (FLU) at 90mg/m2 might improve engraftment, decrease GvHD rates and eventually improve overall toxicity in FA patients transplanted with HLA matched siblings. Method. In 2004, the French reference centre for aplastic anemia and the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) recommended to use FLU 90mg/m2 (30mg/m2 days -4, -3, -2) and CY 40mg/kg (10mg/kg days -5, -4, -3, -2) for FA patients transplanted from matched family donor. Indication for transplantation was based on hematological complications (transfusions and/or infections). FA patients with morphologic signs of clonal evolution (myelodysplastic syndrome or acute myeloid leukemia) were excluded. All patients in France who received a first Allo-HSCT for FA from a matched related donor between October 2004 and January 2013 using this approach were analyzed (n=20). Clinical data were prospectively collected using ProMISe (Project Manager Internet Server), an internet-based data registry system shared by all SFGM-TC centres. All patients received uromitexan. Ciclosporin A and micophenolate mofetil were used as GVHD prophylaxis. Six patients received an in vivo T cell depletion using antithymocyte globuline because of local policy at their centre. The guidelines were approved by Saint-Louis hospital ethical committee. Results. The median age at transplant was 9 years (range: 6-19). Stem cell source was bone marrow in 16 cases and matched related cord blood in the remaining transplants. None of the patients received peripheral blood stem cells. All patients had severe or moderate BMF (median hemoglobin: 8.9g/dl, median platelets: 31 103/ul, median neutrophils: 0.88 103/ul) at time of transplant. Two patients had chromosomal abnormalities (47,XX,i(1)(q10)[10]/48,idem,+8[3] and 47,XX,+der(1;3)(q10;q10)[14]/46,XX[6]); however, none of them developed overt myelodysplasia/leukemia before transplant. Patients belonged to complementation groups FANC-A (n=17) and FANC-G (n=2). Transplantation was performed within a median of 30 months from FA diagnosis (range: 7-143). A median of 3.8. 108 nucleated marrow cells were infused (range: 0,65-8,97). Within a median follow up of 2 years (range: 0.2-7.4), overall survival was 95% (figure 1). Only one patient with an atypical form of FA associated with severe immunodeficiency prior to transplant died subsequently due to uncontrolled cerebral toxoplasmosis. Engraftment rate was 100% with a median time to neutrophils and platelets recovery of 16.5 (11-28) and 15 (4-29) days, respectively. No grade 3/4 regimen related toxicity was observed and only 1 patient experienced mucositis (grade 2) using this conditioning regimen. Total acute GvHD grade 3 / 4 was only observed in 3 patients (15%) and chronic GvHD was extensive in 2 patients (10%) and limited in 3 patients (15%). Median alive patients karnofsky scored 100% (range 90 – 100%). No secondary malignancy was observed in our cohort so far. Conclusion. The combination of low dose CY (40mg/Kg) plus FLU (90mg/m2) in HLA-matched donor HSCT in patients with FA resulted in an excellent engraftment rate (100%) with no secondary graft failure, low rates of acute and chronic GvHD, low rates of regimen related toxicity, eventually resulting in an excellent overall survival (95% at 2 years). A longer follow-up in this cohort is needed to confirm such excellent results long-term, namely the continued absence of secondary cancer. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

G-CSF Primed Bone Marrow Is Not Superior to Unprimed Bone Marrow as a Source of Stem Cells in HLA Matched Related Allogeneic SCT for β Thalassaemia Major.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5052-5052
Author(s):  
Reena Rajasekar ◽  
Vikram Mathews ◽  
Kavitha M. Lakshmi ◽  
Auro Viswabandya ◽  
Biju George ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
T Cells ◽  
Survival Curve ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
T Cell Subsets ◽  
Thalassaemia Major ◽  
Class Iii ◽  
Gvhd Prophylaxis

Abstract G-CSF stimulated BM (G-BM) offers a source of stem cells that has been reported to be associated with faster engraftment and decreased risk of GVHD. It is possible that these differences are related to the immunological composition of these grafts. We compared G-BM and unprimed bone marrow as a source of stem cells in 33 consecutive thalassaemia major patients who underwent a matched related allogeneic SCT treated with a similar conditioning and GVHD prophylaxis regimen. Twenty patients received G-BM from HLA matched donors primed with G-CSF 10ug/Kg/day for 2 days prior to BM harvest and the rest received unprimed BM. Lymphocyte subsets and progenitor cells contained in the grafts was assessed using FACSCalibur and monoclonal antibodies directed against B, NK and T cell subsets. The median age of the cohort was 7 years (range: 2–14) and there were 22 (67%) males. All patients received Bu/Cy/ATG as conditioning regimen. Cyclosporine and short course Methotrexate were used as GVHD prophylaxis. 88% of patients achieved sustained engraftment. The mean follow up was 37 months. Patient and graft characteristics were similar in both HSC sources (Table 1). The target cell dose of 3x108 TNC/Kg could be achieved with smaller volume of the graft in the G-BM group. Time to neutrophil engraftment (median: 16 days, p= 0.260) and platelet engraftment (median: 30 Vs 26 days, p= 0.163) was identical in both the groups. The incidence of acute GVHD (grade II–IV, 10% vs. 15%) and chronic GVHD (12% vs. 9%) were similar in both the groups. 9 patients rejected their graft, six (30%) in G-BM and three (23%) in BM. There were 4 transplant-related deaths within the first 100 days (two in each group). Survival curve analysis showed no difference in overall and event free survival between the two groups. In this cohort of patients, G-BM resulted in rates of engraftment, GVHD, rejection and TRM that were similar to those produced by unprimed BM. G-BM as a HSC source may not add selective advantage to patients with thalassaemia major undergoing a matched related allogeneic SCT. Comparison of Graft Source Characteristics BM (n=13) G-BM (n=20) P Age (median years: range) 6 (2–14) 8 (2–13) 0.22 Male (%) 9 (69) 13 (65) 1.00 Lucarelli Class III (%) 5 (39) 9 (45) 0.71 Harvest TNC/mm3 23430±9007 39045±13457 0.000 Harvest Volume 417±173 290±98 0.012 TNC / 10e8/kg 4 (2.9–7.6) 4.8 (2.4–8.8) 0.083 CD34 x 10e6/kg 6.89 (3.3–12.9) 8.3 (1.2–16.4) 0.439 Total CD3 cells x 10e6/kg 45.6 (12.7–120.1) 40.4 (26.2 – 139.8) 0.912 NK cells x 10e6/kg 4.71 (0.9–49.8) 6.7 (0.1–15.2) 0.580 Total B cells x 10e6/kg 19 (0.3 – 47.2) 24.3 (0.8 – 62.2) 0.32 Helper T cells x 10e6/kg 20.8 (7.2 – 48.7) 13.7 (15.4 – 77.8) 0.556 Cytotoxic T cells x 10e6/kg 24.8 (7 – 91) 10.6 (8.8 – 51.2) 0.39

scholarly journals Outcome of Severe Aplastic Anemia Post Allogenic Stem Cell Transplant with Mycophenolate and Calcineurin Inhibitor for Graft Versus Host Disease Prophylaxis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4879-4879
Author(s):  
Omar Albanyan ◽  
Hyejeong Jang ◽  
Seongho Kim ◽  
Andrew Kin ◽  
Asif Alavi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Grade Ii ◽  
Matched Donor

Abstract Introduction: Severe aplastic anemia (SAA) is a rare hematopoietic stem cell disorder characterized by hypocellular marrow and pancytopenia. Multiple factors play an important role in treatment approach include age, comorbidities, degree of pancytopenia and availability of stem cell donor to either immunosuppression irrespective (IST) or allogenic hematopoietic stem cell transplant (alloSCT). The use of nonmyeloablative conditioning regimen has improved the outcomes, however the choice for post-transplant GVHD prophylaxis remain a topic of debate. The use of mycophenolate mofetil (MMF) has been used as an alternative for methotrexate (MTX) as has shown to be associated with lower incidence of mucositis and shorter time to engraftment. Methods: We retrospectively evaluated consecutive adult patients with SAA who underwent alloSCT at Karmanoc Cancer Institute. All patients received fludarabine, cyclophosphamide and antithymocyte globulin for conditioning regimen with calcineurin inhibitors (CNI) and MMF for GVHD prophylaxis. MMF was started at day -3 at 15 mg/kg three times daily and stopped at day +30 in the absence of active GVHD. The primary objectives were to estimate cumulative incidence of acute (aGVHD) and chronic GVHD (cGVHD) and overall survival (OS). Secondary objectives were to evaluate time to engraftment, days of hospitalization and incidence of mucositis. Results: From January 2005 and May 2019, 33 patients with SAA underwent alloSCT. Patient characteristics are detailed in Table 1. Median age was 36 years (range, 18-71). Twenty-seven patients received bone marrow stem cells (82%) and six patients received peripheral blood stem cells (18%). Thirty patients (91%) received 8/8 HLA matched donor and three patients (9%) received 7/8 HLA matched donor. Sixteen patients (48%) received stem cells from sibling donor and 17 patients (52%) received stem cells from unrelated donor. Thirteen patients (39%) had received IST prior to alloSCT, and 20 patients (61%) received upfront alloSCT. For GVHD prophylaxis all patients received MMF and CNI (tacrolimus=32, and cyclosporine=1). Median time from diagnosis to transplant was 15.8 months for patients who received IST prior to alloSCT and 2 months for patients who received upfront alloSCT. Median time to platelet engraftment was 13.5 days and neutrophil engraftment was 12 days, while one patient experienced graft failure. The median number of days for hospital stay were 25 days. Four patients (11%) developed grade I-II mucositis, no grade III-IV mucositis was observed in the first 30 days and 6 patients had CMV reactivation. The 100-day cumulative incidence rate of grade II-IV aGVHD was 21.2% (95% CI, 9.2 - 36.5), grade III-IV aGVHD was 9.1% (2.3-21.9) and 1-year CIR of cGVHD was 21.2% (95% CI, 9.2-36.5). Comparing patients who received IST prior to alloSCT versus upfront alloSCT, the 100-day CIR of grade II-IV aGVHD was 30.8% (95% CI, 8.2 - 56.5) and 15% (95% CI, 3.6 - 34.0), respectively, (Gray p=0.26) and the 3-year CIR of cGVHD was 39.6% (95% CI, 13.1 - 65.5) and 27.8% (95% CI, 9.2 - 50.3), respectively, (Gray p=0.37). Comparing patients who received alloSCT from related versus unrelated donor, 100-day CIR of II-IV aGVHD was 12.5% (95% CI, 1.9 - 33.6) and 29.4% (95% CI, 10.2 - 51.9), respectively, (Gray p=0.26), and the 3-year CIR of cGVHD was 34.2% (95% CI, 11.4 - 58.9) and 29.4% (95% CI, 10.1 - 52.0), respectively (Gray p=0.90). Median follow up of surviving patient was 5 years (95% CI, 3.1-6.8). Three-year OS was 87% (95% CI, 75.7- 99.9) and median OS was not reached. Six patients died by the time of the analysis, one patient died from graft failure (86 days after transplant from 8/8 HLA MUD), two patients died due infectious complications (808 days and 1637 days after transplant), three patients died due to multiorgan failure (215, 297 and 1097 days after transplant). Conclusion: Our data with use of CNI and MMF for GVHD prophylaxis for SAA following alloSCT with nonmyeloablative conditioning regimen showed that the rate of mucositis was low, engraftment time was rapid, and hospitalization was short, while OS, rates of acute and chronic GVDH were comparable to previously published rates with CNI and MTX-based GVHD prophylaxis. Figure 1 Figure 1. Disclosures Modi: Genentech: Research Funding; Seagen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees. Deol: Kite, a Gilead Company: Consultancy.

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