Single Center Experience of Allogenic Hematopoietic Stem Cell Transplantation in 100 Patients with Myelodysplasia: The Impact of Graft-Versus-Host Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5537-5537
Author(s):  
Colombe Saillard ◽  
Raynier Devillier ◽  
Sabine Furst ◽  
Jérome Rey ◽  
Angela Granata ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Donor Type ◽  
The Impact ◽  
Disease Free

Abstract Introduction Allogenic hematopoietic stem cell transplantation (Allo-HSCT) is a curative treatment for patients with myelodysplasia (MDS). However, because of age, MDS patients represent a challenging population for such an intensive treatment. Additionally, the low rate of HLA-identical donor has represented a major limitation in this strategy. Recently, reduced-intensity conditioning (RIC) regimens have made feasible Allo-HSCT in the elderly, although relapse rate might be increased. Additionally, the development of HSCT using alternative donors overcomes HLA-compatibility limitations. Graft-versus-host disease (GVHD) is a major post-transplant event, graft-versus-leukemia effect being counterbalanced by toxicity and impaired quality of life. The aim of this retrospective study was to report outcome of patients with MDS who underwent Allo-HSCT and to study the impact of GVHD. Methods Between 2003 and 2014, 100 consecutive patients presenting with MDS, or MDS-secondary AML, underwent Allo-HSCT in our institution. At diagnosis, 58 patients had ≥ 2 cytopenias. IPPS was low/intermediate-1 in 46% and intermediate-2/high in 54%, R-IPSS was very low/low in 25%, intermediate in 20% and high/very high in 55%. Cytogenetics, according to Disease Risk Index (DRI), was intermediate in 79% and adverse in 21%. Secondary MDS represented 27% of our cohort. Before Allo-HSCT, 42% received 5-Azacytidine, 27% intensive chemotherapy and 9% were transplanted upfront. At the time of Allo-HSCT, the median recipient age was 61 (19-71) years. Median time between diagnosis and Allo-HSCT was 12 months (1-131). After excluding patients transplanted upfront, 31 patients still had ≥5% blasts after treatment. Donors were HLA-matched in 70% (41% related, 29% unrelated), 30% were not HLA-matched (10% unrelated, 7% cord blood, 13% T-repleted haplo-HSCT). Stem cell source was peripheral blood stem cells in 90%. Twelve percent of patients received non-myeloablative (NMA) conditioning regimen, 75% RIC and 13% reduced-toxicity conditioning (RTC) regimens. Post-graft immunosuppression consisted in cyclosporine A (CSA) in 58%, CSA-Mycophenolate Mofetil (MMF) in 15%, CSA-Methotrexate in 14% and CSA-MMF-Cyclophosphamide for haplo-HSCT (13%). Results Median follow-up was 37 months (3-197). The incidence of 3-4 acute GVHD at day 100 was 7% (95% CI = 2-12). The incidence of severe chronic GVHD at 3 years was 19% (95% CI = 11-27). One and 3-year non-relapse mortality (NRM) were 23 and 29% respectively. The cumulative incidence of relapse (CIR) at 1 year and 3 years 24% and 33% respectively. One and 3-year progression-free survival (PFS) were 52% (95% CI = 43-63) and 37% (95% CI = 28-49). One and 3-year overall survival (OS) were 60% (95% CI = 51-71) and 48% (95% CI = 39-60). At one year, 51 patients were alive and disease-free, including 61% (n=31) without immunosuppression. At the end of follow-up, 39 patients were alive and disease-free, including 85% (n=33) without immunosuppression and 77% (n=30) GVHD-free. Time-dependent analysis of GVHD impact (Table 1), adjusted on age, donor-type, DRI and conditioning regimen, revealed that acute GVHD strongly impacts on OS (HR 3.8, 95% IC = 2-7, p<0.01), PFS (HR 3.1, 95% CI = 1.7-5.6, p<0.01) and NRM (HR 12, 95% CI = 5.2-28, p<0.01). Chronic GVHD was statistically significant on CIR (HR 0.16, 95% CI = 0.04-0.7, p=0.02) and NRM (HR 2.8, 95% CI = 1-8, p=0.05). Pre-transplant disease characteristics did not have any impact by univariate analysis. Multivariate analysis did not find any impact of age, donor type, DRI and conditioning regimen in terms of OS, PFS, NRM and CIR. Conclusion Our results suggest that GVHD highly influences outcome, regardless of MDS and Allo-HSCT characteristics. It should be quoted that a significant number of patients are alive, long-term survivors, disease-free and GVHD-free suggesting good quality of life. These results invite defining better strategies of GVHD prevention while retaining disease control magnifying the existing graft-versus-leukemia effect. Table 1. Time-dependent analysis of the impact of acute and chronic GVHD, adjusted on age (< or > 60), donor-type (HLA-matched or not matched), DRI and conditioning regimen (NMA, RIC or RTC). HR 95% CI p Acute GVHD OS PFS NRM CIR 3.8 3.1 12 0.4 2-7 1.7-5.6 5.2-28 0.09-1.7 <0.01 <0.01 <0.01 0.2 Chronic GVHD OS PFS NRM CIR 0.7 0.8 2.8 0.2 0.3-1.5 0.4-1.8 1.01-8 0.04-0.8 0.4 0.6 0.050.02 Disclosures Vey: Celgene: Honoraria; Roche: Honoraria; Janssen: Honoraria.

Second Allogeneic Hematopoietic Stem-Cell Transplantation Using Fludarabine Treosulfan Conditioning Regimen in Patients Previously Treated with Busulfan-Based Regimens; Myeloablation with Acceptable Toxicity.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2255-2255 ◽  
Author(s):  
Avichai Shimoni ◽  
Avital Rand ◽  
Noga Shem-Tov ◽  
Izhar Hardan ◽  
Yulia Volchek ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
High Dose ◽  
Primary Malignancy ◽  
Hematopoietic Stem ◽  
Reduced Toxicity ◽  
Disease Free

Abstract Abstract 2255 Poster Board II-232 The prognosis of patients (pts) with leukemia who relapse after a prior autologous and or allogeneic hematopoietic stem cell transplantation (SCT) is dismal. A second allogeneic SCT can salvage some of these pts but myeloablative conditioning is associated with high rates of non-relapse mortality (NRM) in this setting and a relatively poor outcome. Reduced intensity conditioning allows reduction of NRM following a second SCT, but may be associated with a high relapse rate, mostly when leukemia is not in remission at the time of SCT. Similarly, allogeneic SCT for pts who develop secondary leukemia after a prior autologous SCT for a primary malignancy is associated with similar risks. The combination of fludarabine and treosulfan (FT) has been previously reported as a dose intensive myeloablative regimen with reduced toxicity and effective anti-leukemia capability, but its merit in second SCT is not defined. We explored a regimen consisting of fludarabine (total 150 mg/m2) and treosulfan (total 30-36 gr/m2) with the addition of ATG to recipients of unrelated or mismatched donor SCT, as a conditioning regimen for a second SCT. The study included 17 pts, 10 male, 7 female, median age 58 years (range, 20-70). Patient diagnosis at second SCT was AML (n=11), MDS (n=3), myelofibrosis (n=2) and CML in accelerated phase (n=1). The first transplant was autologous (n=6) or allogeneic (n=11). Autologous SCT was given for AML (n=3, 1 of them APL) or for a primary malignancy (lymphoma - 2, multiple myeloma -1). Second allogeneic SCT was given for relapse after a prior SCT or for secondary AML/MDS in the 3 pts having autologous SCT for lymphoma and myeloma. The Donor for the second SCT was an HLA-match sibling (n=6) or matched unrelated (n=11). In the 11 pts having a second allogeneic SCT after failure of a first allogeneic SCT the donor was the same donor in 3 transplants and a different donor in 8 transplants. The conditioning regimen for the first SCT contained high-dose intravenous busulfan (12.8 mg/kg) in 9 pts and reduced dose busulfan (6.4-9.6 mg/kg) in 5 pts. The three pts with primary lymphoma and myeloma were given BEAM and high-dose melphalan, respectively. The median time between the first and second SCT was 28 months (range, 3-48 months). Only 4 pts were in remission at the time of second SCT. Six pts were chemo-refractory and 7 pts were transplanted in untreated malignancy. Results: 12 pts engrafted with a median time to ANC > 0.5 × 109/L of 12 days (range, 9-38) and for PLT > 20 × 109 of 15 days (range, 11-44). Five pts died prior to engraftment, 3 of infections, 1 of cerebral hemorrhage and 1 of graft failure. There were no deaths related to organ toxicity (e.g. VOD or pneumonitis) and no late deaths due to NRM. Acute GVHD grade II-IV occurred in 2 pts, cumulative incidence 28%. Chronic GVHD occurred in 4 of 8 evaluable pts, cumulative incidence 57%. There were no deaths attributed to acute or chronic GVHD. The cumulative incidence of NRM was 30% (95%CI, 14-62). Three pts relapsed with a cumulative incidence of 25% (95%CI, 9-69). In all, with a median follow-up of 12 months (range, 1-59 months) the estimated 2-year overall and disease-free survival were both 45% (95CI, 17-73). Best results were achieved in the group of 8 pts having a second SCT form a second allogeneic donor; 5 pts are currently disease-free for a median of 18 months (range, 3-38), despite transplantation in advanced phase; 3 refractory to salvage chemotherapy and one in untreated relapse after the first SCT. The estimated 2 year survival in this group was 60%, a promising outcome in this setting. In conclusion, the fludarabine-treosulfan regimen is feasible for a second allogeneic SCT. NRM especially in the early post-transplant period is substantial, but can be expected in a group of heavily pretreated pts, many with active and refractory leukemia. The regimen has a promising anti-leukemia effect in this setting with a low recurrence rate, especially when using a different donor than in the prior transplant. The FT regimen can be considered a reduced toxicity myeloablative regimen that is feasible in pts given a prior transplant including pts previously given myeloablative doses of busulfan. Disclosures: No relevant conflicts of interest to declare.

Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia Using Alemtuzumab and Cyclophosphamide as Conditioning Regimen.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3198-3198
Author(s):  
Fernanda Lodi ◽  
Gustavo Teixeira ◽  
Antonio Vaz Macedo ◽  
Rosana Lamego ◽  
Simone Silva Magalhaes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Median Number ◽  
Off Label Use ◽  
Hematopoietic Stem ◽  
Off Label

Abstract Abstract 3198 Poster Board III-135 Introduction Cyclophosphamide (Cy) with/without antithymocyte globulin (ATG) as conditioning regimen for allogeneic hematopoietic stem cell transplantation (AlloHSCT) is the treatment of choice for young patients with severe aplastic anemia (SAA). In developing countries, and particularly in Brazil, ATG costs limit its use in AlloHSCT for SAA patients. Alternative low-cost regiments, like busulfan (BU) with Cy as conditioning regimen is still associated with a significant rate of rejection, especially in heavily transfused patients, and long-term infertility. Alemtuzumab (Cam) was reported as an alternative to ATG for SAA patients, with similar activity and a lower cost. Material and Methods In order to study the effect of the combination of Cy and Cam, we reviewed all AlloHSCT performed for SAA using this conditioning regimen. Between April 2007 and Mai 2009, fifteen patients with SAA (defined by Camitta criteria) underwent an AlloHSCT in our institution. Median age at transplantation was 25 (range 5-42) years. All but one patient had positive CMV serology. Median number of transfusions was 20 (range 10-67). One patient received a second AlloHSCT due to a late (> 4 years) graft rejection. Patients received an unmanipulated bone marrow (n=11) or peripheral blood (n=4) graft as stem cell source and all but one patient were transplanted with an HLA-identical sibling. Median number of nucleated cell infused was 2.86 (range 1.65-6.50)x10 8/kg. Cyclosporin alone (n=10) or in combination with methotrexate (n=5) was used as GVHD prophylaxis. Results Thirteen out of 15 patients presented neutrophil recovery with a median time to > 0.5×10 9 neutrophil/L of 23 (range 13-30) days. Platelet recovery (> 20×10 9 platelets/L) occurred in thirteen patients with a median time of 16.5 (range 9-45) days. Acute graft versus host disease (GVHD) was observed in just one patient (grade II). None of 12 patients alive 100-days after AlloHSCT presented chronic GVHD. Seven patients presented CMV reactivation. One patient did not engrafted and other presented a late (14 months) rejection. One patient became pregnant after alloHSCT and gave birth to a healthy child. With a median follow-up of 315(range 4-782) days, two patients died and the estimate 1-year overall survival rate is 87%. One patient died due to complications of a CNS bleeding that occurred hours before marrow infusion and the other of GI infection while still on neutropenia. Conclusion Use of cyclophosphamide and alemtuzumab as conditioning regimen is a valid option in SAA patients undertaking AlloHSCT, with significant lower rates of acute and chronic GVHD. Nevertheless, a longer follow-up is required to properly evaluate rejection incidence. Disclosures Off Label Use: Drug: Alemtuzumab Off-label Use: Aplastic Anemia.

Long-Term Follow-up of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Severe Alpastic Anemia After Cyclophosphamide Plus Antithymocyte Globulin Conditioning Regimen,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4090-4090
Author(s):  
Johanna Konopacki ◽  
Raphael Porcher ◽  
Marie Robin ◽  
Sabine Bieri ◽  
Jean Michel Cayuela ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Increased Risk ◽  
Long Term Follow Up

Abstract Abstract 4090 Background: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) from an HLA- identical sibling is the treatment of choice for young patients with acquired severe aplastic anemia (SAA). Due to increased rates of secondary solid cancer in patients with SAA who received an irradiation-based conditioning regimen, we decided 2 decades ago to use the association of Cyclophosphamide (CY) and Antithymocyte globulin (ATG). We report here the long-term follow-up of patients who underwent HSCT from an HLA-identical related donor after this conditioning regimen. Patients and Methods: 61 consecutive patients with SAA who received a first transplantation from June 1991 to February 2010 in our center were included. Patients with Fanconi anemia or other congenital bone marrow failure were excluded. The conditioning regimen consisted in CY (200mg/Kg) and ATG (2.5 mg/kg/day × 5 days). The donors were HLA-identical siblings in 60 cases and family HLA-matched in 1 case. Graft-versus -host disease (GvHD) prophylaxis associated cyclosporine and methotrexate (days 1, 3, 6 and 11). Long-term clinical outcome, immune recovery and quality of life were assessed. Results: The median age was 21 years [range: 4–43], 41 being adults. Median duration of the disease before HSCT was 93 days. Most of the patients had idiopathic aplastic anemia (n=49, 80%). Median time from diagnosis to HSCT was 3 months (range, 1 to 140). All but 2 patients received bone marrow as source of stem cells and all but 2 engrafted (primary graft failure= 3.4%) with a neutrophils count > 0.5 G/L and a platelets count >20 G/L after a median of 23 (range, 19 to 43) and 21 days (range, 10 to 177), respectively. In patients who had achieved neutrophil recovery, no secondary graft failure was observed. Cumulative incidence (CI) of acute grade II-IV GvHD was 23% (95%CI, 13 to 34) and 18 patients developed chronic GvHD (CI: 32%, 95% CI, 20 to 46). In multivariate analysis, a higher number of infused CD3 cells was associated with an increased risk of developing chronic GvHD (p=0.017). With a median follow-up of 73 months (8 to 233), the estimated 6-year overall survival was 87% (95%CI, 78 to 97). At 72 months, the CI of secondary malignancies was 9%, 10 patients developed avascular necrosis (21% CI), 12 patients were diagnosed with endocrine dysfunctions (19% CI) and 5 presented cardiovascular complications (CI of 10%). The CI of bacterial, fungal and viral infections were 25% (95% CI, 15 to 36), 8% (95% CI, 3 to 17) and 61% (95% CI, 46 to 73) at 72 months, respectively. At 2 years post HSCT, the immune reconstitution was normal for CD3, CD8 T-cells, B-cell and NK-cell but still incomplete for CD4 T-cells. A FACT-BMT questionnaire of quality of life (QOL) was sent to all survivors (n= 53) of who 26 accepted to respond to the questionnaire. There was no evidence for a change in QOL perception with time after transplantation. Our data were compared with those obtained from HSCT recipients from a Swiss transplant center (n=125 patients), mainly transplanted for hematological malignancies. The perception of QOL in patients who were transplanted for SAA was similar to the group of patients who were transplanted for other reason than SAA. Conclusions: Our results confirm that HSCT from HLA-identical sibling donors after CY-ATG conditioning regimen is a curative treatment for patients with SAA, with an excellent long-term outcome. We found an increased risk of chronic GvHD associated with the number of infused CD3 cells. Furthermore, we also found non negligible late complications as well as a similar quality of life with patients transplanted for hematological malignancies. Improving long-term health conditions must thus be a priority field for research, exploring the use of new conditioning regimen as well as new GvHD prophylaxis to improve the quality of life post HSCT of such patients. Disclosures: Peffault de Latour: Alexion: Consultancy, Research Funding.

Low Counts of Plasmacytoid Dendritic Cells After Engraftment Are Associated with Higher Early Transplantation-Related Mortality in Patients Receiving Unrelated HSCT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4541-4541
Author(s):  
Matheus Vescovi GonÇalves ◽  
Mihoko Yamamoto ◽  
Vergílio Antônio Rensi Colturato ◽  
Mair Pedro de Souza ◽  
Marcos Mauad ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Stem Cell ◽  
Nk Cells ◽  
Hematopoietic Stem Cell ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Innate Defense ◽  
Common Diagnosis ◽  
The Impact

Abstract Abstract 4541 Background: The heterogeneous status of host immune defenses may influence the risk of infection and graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). In such defense, dendritic cells (DC) which act as specialized antigen-presenting cells that bridge the innate and adaptive immune systems, and NK-cells, responsible for the innate defense against infections and residual tumor cells, are essential cell components. Objectives: To monitor the recovery of different subsets of DC and NK cells after unrelated umbilical cord blood (UCB), bone marrow (BM), and peripheral blood (PBSC) HSCT and to evaluate the impact of the distribution of these cell subsets on the outcome of the transplant. Methods: Overall, 34 patients (median age 13y; range 1–63y) receiving a UCB (n=15), BM (n=14) or PBSC (n=5) unrelated HSCT were studied. The most common diagnosis was acute leukemia (ALL, 12 cases; AML, 10; CML, 5; aplastic anemia, 4; MDS, 2; Hodgkin lymphoma, 1; SCID, 1), a majority of patients were males (56%), and received myeloablative conditioning (MAC) regimens (73%). Antithymocyte globulin (ATG) was used in 38% and total body irraditation (TBI) in 41% of cases. Median time to neutrophil engraftment was 18 days (range: 12–45). T-cell (CD4+, CD8+, CD4−8−, CD4+8+), DC [CD123+ plasmacytoid(p)DC, CD11c+ myeloid(m)DC, and CD16+ monocytoid(mo)DC] and NK cell subsets (CD3−/CD19− 56++16− and 56+16++) were quantified by multiparametric flow cytometry at 7 sequential time points (pre-transplant, at engraftment, and at days 3, 7, 14, 21 and 60 after engraftment). Results: As compared to BM/PBSC, UCB was associated with a delayed neutrophil recovery (28 days vs. 17 days; p=0.01), and a trend to lower counts of all T-, NK- and pDC subsets, particularly for the CD4+ and CD4−/CD8− T-cells during the first 3 weeks after recovery. Conversely, no significant differences were observed between both groups as regards the distribution of mDC and moDC. The use of TBI, MAC or ATG were not associated with the reconstitution of the studied cell subsets. In contrast, patients who died from transplantation-related causes (TRM) had significantly lower counts of pDC and mDC during the first 3 weeks after HSCT. At day 21 after engraftment, the median number of pDC and mDC was 0.9 and 2.0/uL among patients who died from TRM vs. 7.1 (p=.006) and 8.4/uL (p=.01) in the remainder, respectively). Patients presenting grade II-IV acute GVHD also had significantly lower pDC counts at days 14 and 21. There was no significant association of both the hematopoietic stem cell source and the conditioning regimen on the risk of TRM or acute GVHD. Conclusion: Low pDC counts in the first weeks after unrelated HSCT are associated with an increased incidence of GVHD and mortality. The precise mechanisms that might explain the role of pDC on immunity early after HSCT deserve further investigations. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Impact of Age in Allogeneic Stem Cell Transplantation with Thiotepa Busulfan and Fludarabine (TBF) for Myelofibrosis : A Retrospective Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4858-4858
Author(s):  
Federica SORA ◽  
Patrizia Chiusolo ◽  
Sabrina Giammarco ◽  
Idanna Innocenti ◽  
Francesco Autore ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Total Dose ◽  
Cell Transplantation ◽  
Older Patients ◽  
Research Funding ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
The Impact

Abstract Allogeneic hematopoietic stem-cell transplantation (HSCT) currently remains the only curative therapy for intermediate or high risk disease.myelofibrosis (MF). We are reporting 56 patients (pts) who underwent an allogeneic HSCT in our Centre between 2016 and 2020, and assessed factors predictive of outcome. The median age was 59 years (36-72). Most patients (72%) were JAK2+ and had int2-high DIPSS (92%). The conditioning regimen consisted of thiotepa, busulfan , fludarabine (TBF). All pts received thiotepa 10 mg/kg and fludarabine 150 mg/m^2. The dose of busulfan was adjusted considering the age and the comorbidity score. One pt received 3 days of busulfan (total dose 9.6 mg/kg); 47 received 2 days (total dose 6.4 mg/kg) and 8 received one day of busulfan iv (3.2 mg/kg). Donor was an identical sibling in 13 pt, haploidentical in 18, matched unrelated donor (UD) in 18 and a mismatchedUD in 7. Thus we had 31 HLA matched and 25 HLA mismatched grafts. Fortytwo patients received post-transplant cyclophosphamide (PTCy)-based GVHD (Graft versus host disease ) prophylaxis with cyclosporine and mycophenolate mofetil , and 14 patients received a standard GvHD prophylaxis (CSA+MTX+ATG). The 2 year survival (OS) was 73 % and disease free survival (DFS) was 66 % and the cumulative incidence (CI) of TRM was 23% and of relapse 11%. The incidence of acute GvHD grade II-IV was 22% in HLA matched and 50% in HLA mismatched pts (p=0.022), grade III-IV was 6% and 25% respectively (p=0.042) . The incidence of moderate-severe chronic GvHD was 25% in HLA matched and 36% in HLA mismatched grafts (p=0.36). HLA had a major impact on survival : 85% vs 49% survival for matched vs mismatched patients (p=0.01). Patients age &gt;60 years had a major impact on outcome, with a 2 year survival of 51% vs 88% in patients over (n=24) or under 60 years of age (n=32) (p=0.007; the DFS was 46 % and 80% respectively and the CI of TRM was 42% vs 9% (p=0.003). As to the total dose of busulfan, we found 26% TRM in patients receiving busulfan for 2 days (total doe 6.4 mg/kg) (n=47) and 0% in older patients receiving 1 day only (total dose 3.2 mg/kg) (n=8) ; relapse rate was 10% and 20% respectively. In multivariate cox analysis including age, spleen size ,DIPSS score, number of transfusion received and donor type, only HLA matching influenced the incidence of acute GvHD; transfusion burden and age plays a role in NRM and OS; DIPSS predicts relapse . In conclusion: older patients with MF have a high NRM and need to be prepared with a milder conditioning regimen. Disclosures Laurenti: Janssen: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria; BeiGene: Honoraria. Sica: Pfizer: Honoraria.

Novel Conditioning Regimen for Haploidentical Hematopoietic Cell Transplant for Severe Aplastic Anemia in Children

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5651-5651 ◽  
Author(s):  
Hasan Hashem ◽  
Rawad Rihani ◽  
Eman Khattab ◽  
Mayada Abu Shanap ◽  
Abdelghani Tbakhi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Stem Cell Source ◽  
Cell Source

New hematopoietic cell transplant (HCT) approaches are urgently needed for patients with severe aplastic anemia (SAA) who lack an HLA-identical donor. Haploidentical HCT with post transplant cyclophosphamide (PTCy) represent a potential universal available option for almost all children with SAA. We present a novel conditioning regimen for haploidentical HCT in children with SAA in a center where horse ATG is not available. Conditioning regimen consists of rabbit ATG 2.5 mg/kg/day from day -9 to -7, Fludarabine 30 mg/kg/day from day -6 to -2, Cyclophosphamide 14.5 mg/kg/day from day -6 to -5, Thiotepa 5 mg/kg/day from day -4 to -3, and 4 Gy TBI on day -1 in in two fractions. GvHD prophylaxis consist of PTCy 50 mg/kg/day on days +3 and +4 along with Cyclosporine A and Mycophenolate mofetil (MMF) starting on day +5. Four consecutive children with SAA referred to our center for haploidentical HCT starting in 2018. Median age at HCT was 9 years (5-16) with 3 males and 1 female. All patients were heavily transfused with both blood and platelets prior to referral for HCT. Two patients had strong and one had weak positive anti-HLA antibodies (DSAs) and received desensitization with IVIG, Rituximab and plasmapheresis. One patient received buffy coat infusion on day -1 due to persistent strong DSAs despite desensitization. Median CD34+ dose received was 12 x 10e6, and median CD3+ dose was 29 x 10e6. Donors were all same blood group to patients. All patients successfully engrafted neutrophils at median of 13 days (12-14). Platelets engraftment in 3/4 patients at median of 7 days (5-10). All patients received peripheral blood as stem cell source. Three of four patients survived and doing well at last follow up. One patient had toxic death on day +38 due to chemotherapy related toxicity causing multi-organ failure. Chimerism analysis was full donor in all four patients at median follow up time of 11 months (2-12). Patients were sent home at median of 24 days post HCT. None developed grade 2-4 acute GvHD nor chronic GvHD. Acute GvHD of skin grade 1 stage 1 developed in 2 patient and managed with topical steroids. Viral reactivations consisted of CMV viremia and BK hemorrhagic cystitis in all patients, and have all resolved. No post transplant autoimmune complications. Haploidentical HCT with PTCy represents a quick and first line approach in heavily transfused children with SAA. Although yet limited number of patients, this regimen is feasible and appears to be safe. A great advantage of this regimen is the rapid engraftment of both neutrophils and platelets. Moreover, although using peripheral blood as a stem cell source, there was no severe acute or chronic GvHD. Disclosures No relevant conflicts of interest to declare.

Fludarabine/Melphalan Conditioning for Allogeneic Stem Cell Transplantation (SCT) in Elderly Patients with AML/MDS.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5410-5410
Author(s):  
Glen A. Kennedy ◽  
Jason Butler ◽  
Simon Durrant ◽  
Geoff R. Hill ◽  
Robyn Western ◽  
...  
Keyword(s):  
Stem Cell ◽  
Elderly Patients ◽  
Survival Data ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Term Survival ◽  
Phase 2 Trial ◽  
Kaplan Meier

Abstract Aims: To assess the tolerability and efficacy of a reduced-intensity, non-TBI based allogeneic SCT conditioning regimen utilising fludarabine and melphalan (FluMel) in elderly patients with AML /MDS. Methods: Fludarabine (25mg/m2 D-7 to D-3) and melphalan (120mg/m2 D-2) allogeneic SCT was performed as part of a prospective phase 2 trial to assess the tolerability of the preparative regimen across a range of haematological malignancies. For this analysis, all patients aged &gt;50yrs with AML /MDS who underwent FluMel transplantation were retrospectively reviewed. Standard GVHD prophylaxis was cyclosporine + methotrexate (D1–11). Both HLA-matched siblings and volunteer unrelated donors (VUD) were permitted as stem cell donors. Graft source was G-CSF stimulated PBPC; all grafts were T-cell replete. Survival data was calculated utilising the Kaplan-Meier product-limit method. Results: In total 20 patients &gt;50yrs (16M and 4F) had received FluMel allogeneic SCT for AML (n=15) or MDS (n=5). Median age at SCT was 60yrs (range 50 to 67yrs). AML transplants were performed in CR1 (n=5), early 1st relapse (n=3), CR2 (n=3), MDS phase post CR1 (n=2), early 3rd relapse (n=1), and primary refractory disease (n=1); 7/15 AML patients had intermediate risk and 7/15 poor risk cytogenetics (1 no data available). All 5 MDS patients were previously untreated; all had INT-1 risk disease on IPSS. Donors were HLA-matched siblings in 14 cases and VUD in 6. A total of 6 patients have died, including 2 prior to engraftment (1 of hepatic failure and 1 from idiopathic pneumonia syndrome) and 4 after day 75 (relapsed AML 2 cases; acute GVHD 1 case; multi-organ failure 1 case). All 18 patients who survived the initial cytopenic period achieved durable engraftment; 10 (50%) subsequently developed acute GVHD, including grades II-IV in 9 cases (45%) and grades III-IV in 3 (15%). Of the 12 patients with follow-up &gt;3mths post-SCT, 9 (75%) developed chronic GVHD, which was extensive-stage in 8 (67%). At a median follow-up of 2.4 yrs (range 0.1–5.2 yrs), overall and event-free survival at 2 years for the whole cohort are both 66%. Conclusions: Our experience suggests that allogeneic SCT with FluMel conditioning in elderly patients AML /MDS is associated with acceptable treatment-related toxicity and significant long-term survival. Further studies on this transplant approach in older patients are warranted.

Updated Analysis of Hematopoietic Stem Cell Transplantations after Reduced Intensity Conditioning Regimen (RIC HSCT) for Hematological Malignancies from the Société Française de Greffe de Moelle Osseuse et de Thérapie Cellulaire (SFGM-TC) Registry.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 45-45 ◽  
Author(s):  
Mauricette Michallet ◽  
Quoc-Hung Le ◽  
Thomas Prebet ◽  
Mohamad Mohty ◽  
Jean Michel Boiron ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Grade Ii ◽  
The Impact ◽  
Global Population

Abstract This report updates a retrospective study from SFGM-TC registry concerning 738 patients who underwent RIC HSCT for hematological malignancies [280 F, 458 M, median age: 51 years (1–72)] between 1997 and 2004. The diagnosis were 173 AML, 40 ALL, 68 MDS, 152 NHL, 36 HD, 45 CLL, 70 CML, 154 MM; 332 patients have been previously transplanted. At time of conditioning, 261 patients were in CR, 224 in PR and 253 in progressive disease (PD). Peripheral blood stem cells (PBSC) were used in 574 patients and bone marrow in 164 patients from 655 HLA related donors and 83 unrelated donors. As conditioning, 152 patients received fludarabine and TBI (2 grays), 300 patients fludarabine, busulfan and anti-thymocyte globulins (FBS) (ATG 1d: 57, 2 d: 84, 3 d: 58, 4 d: 18, 5 d: 83) and 286 patients an other regimen. As GVHD prophylaxis, 722 patients received a cyclosporine A (CsA) based regimen. After transplant, 252 patients (35%) in the global population developed an acute GVHD ≥ grade II (grades III and IV: 116) and 208 patients (37%) in the PBSCT population (grades III and IV: 100). A chronic GVHD was present in 258 patients (38%) in the global population (115 limited and 143 extensive) and 221 patients (42%) in the PBSCT population (95 limited and 126 extensive). With a median follow-up of 27 months, the 3-year probability of overall survival (OS) and event-free survival (EFS) for the global population was 38% (33–44) and 28%(24–34) and for PBSC SCT patients 39%(33–46) and 32%(27–39) respectively. The 3-year probability of OS varied according to diagnosis (CLL: 62%, NHL:50%, CML:44%, MM:41%, MDS:37%, AML:26%, ALL:20%) and cGVHD (no:28%, yes:61%). The cumulative TRM incidence was 12% at 1 year and 13% at 3 years. A multivariate analysis was performed studying pre and post transplant factors for OS, EFS and GVHD:. Table 1 summarizes all variables showing a significant impact on OS and EFS. Furthermore, analyses showed the impact of one variable on AGVHD and cGVHD for PBSCT population: FBS with ATG 1day vs 2 days [HR:1.56(1.19–2.04) p=0.001, HR:1.50(1.14–1.97) p=0.003]. In conclusion, besides the influence of known factors on OS and EFS after RIC HSCT, this study pointed out, on a large series with a long-term follow-up, the major impact of disease status, acute and chronic GVHD and demonstrated the important role of ATG duration on GVHD incidence. Table 1: Multivariate analyses OS/EFS Variables OS (HR) p EFS (HR) p Conditionning :FBS ATG 1d vs 2 d Global 1.47 (1–2.2) 0,05 NS PBSC 1.6 (1.03–2.49) 0,04 NS FBS ATG 5d vs 2 d PBSC NS 1.13(1.04–1,24) < 0.01 PD vs CR Global 1.22 (1.1–1.32) < 0.01 1.15 (1.07–1.25) < 0.01 PBSC 1.2 (1.1–1,3) < 0.01 1.14 (1.05–1.24) < 0.01 Previous HSCT: yes vs no Global 1.27 (1.02–1,59) 0,04 1.25 (1.01–1.55) 0.04 AGVHD : Grade II vs 0-I PBSC 1.21 (1–1.47) 0,05 NS AGVHD : Grade III-IV vs 0-I Global 1,28 (1,14–1,43) < 0.01 1.12 (1–1.25) 0.04 PBSC 1.3 (1.14–1.47) < 0.01 1.13 (1–1.28) 0.05 cGVHD : yes vs no Global 0.2 (0.14–0.28) < 0.01 0.25 (0.19–0.35) < 0.01 PBSC 0.19 (0.13–0.28) < 0.01 0.25 (0.18–0.34) < 0.01

Reduced Intensity Versus Myelo-Ablative Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation for Blastic Plasmacytoid Dendritic Cell Neoplasm: A Retrospective Study of the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3208-3208 ◽  
Author(s):  
Mathieu Leclerc ◽  
Régis Peffault de Latour ◽  
Mauricette Michallet ◽  
Didier Blaise ◽  
Patrice Chevallier ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Conditioning Regimen ◽  
French Society ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Donor Type ◽  
Conditioning Regimens ◽  
Disease Free

Abstract Introduction Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare form of acute leukemia associated with an overall bad prognosis. Only very few cases have been reported to reach durable remissions thanks to chemotherapy alone. Allogeneic hematopoietic stem cell transplantation (HSCT) using a myelo-ablative conditioning regimen (MAC) has been reported to be the gold standard treatment for BPDCN (Roos-Weil et al, 2013). However, little is known about the place of reduced-intensity/non-myelo-ablative conditioning regimens (RIC/NMA) in this setting. Methods We retrospectively collected from the database of the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) all cases of BPDCN treated with allogeneic HSCT. Immunophenotypes at diagnosis were centrally reviewed in order to confirm diagnosis according to the Garnache-Ottou diagnostic criteria (Garnache-Ottou et al, 2009). Twenty-eight patients had a diagnostic score of 2 or more. The remaining 15 patients all had CD4+ CD56+ disease, but as they were mostly diagnosed before publication of this score, other markers (such as CD123, BDCA-2 and BDCA-4) were not performed routinely at that time, precluding calculation of a score at least equal to 2. Results From February 2003 to January 2014, 43 patients with BPDCN received an allogeneic HSCT in 21 French centers. PatientsÕ characteristics are summarized in table 1. Median age was 57 (range: 20-72), sex ratio (M/F) was 2.1/1 and most patients were in CR1 at time of transplant. Sibling transplantation was performed in 42% of cases. Peripheral blood was the main source of stem cell used in this study (70% of cases). Conditioning regimens were MAC in 18 cases (42%) and RIC/NMA in 25 cases (58%, table 2). Four patients (9%) had engraftment failure or secondary graft rejection, 3 of whom having received cord blood units. All these 4 patients were transplanted again 2 to 17 weeks after the first transplant. After a mean follow-up of 668 days for the entire cohort (1050 days for alive patients), 22 patients (51.2%) were alive, 19 of whom being disease-free (44.2%). Eleven patients had relapsed, at a median of 225 days post-HSCT (range: 74-821 days). Two-year cumulative incidences of relapse (CIR) and non-relapse mortality (NRM) were 25.5% (95% CI = [0.13-0.40]) and 32.8% (95% CI = [0.186-0.479]) respectively (figure 1). At 2 years post-transplant, disease-free survival (DFS) and overall survival (OS) were 44.9% (95% CI = [0.291-0.595]) and 52.2% (95% CI = [0.357-0.664]), respectively. Even though not statistically significant, patients receiving a MAC (n = 18) were less likely to relapse than patients receiving RIC/NMA (2-year CIR = 7.1% and 36% respectively, P = 0.137), but had a higher NRM rate (43.9% versus 26% at 2 years, P = 0.419), resulting in similar 2-year DFS and OS (57.1% versus 38%, P = 0.511 and 57.1% versus 49.7%, P = 0.91). There was a trend for a lower incidence of NRM at 2 years in patients transplanted from a sibling donor versus others (16.7% and 39.9% respectively, P = 0.0505, figure 2), but donor source had no effect on CIR (P = 0.826), DFS (P = 0.194) and OS (P = 0.188). Conclusion In this series of 43 patients with BPDCN, allogeneic HSCT was associated with a good disease control, but NRM was high. In this regard, transplantation from a sibling donor appears to be the best option. RIC/NMA are feasible and may also reduce the incidence of NRM, but at the expense of a higher incidence of relapse. Table 1. Patients' characteristics N 43 Age 57 (20-72) Sex (M/F) 29/14 Time from diagnosis (days) 170 (107-1050) Disease status at HSCT  CR1 34 (79%)  CR2 5 (12%)  No CR 2 (5%)  Unknown 2 (5%) Donor  Sibling 18 (42%)  Unrelated 23 (53%)  Mismatch relative 2 (5%) Cell source  Bone Marrow 7 (16%)  Peripheral Blood 30 (70%)  Cord Blood 6 (14%) Conditioning regimen  MAC 18 (42%)  RIC/NMA 25 (58%) CMV status (D/R)  -/- 18 (42%)  -/+ 9 (21%)  +/- 4 (9%)  +/+ 12 (28%) GVHD prophylaxis  Ciclo/MTX 15 (35%)  Ciclo/MMF 19 (44%)  Ciclo alone 5 (12%)  Other 2 (5%)  Unknown 2 (5%) Table 2. Conditioning regimens MAC 14 Cy/TBI 11  Cy/TBI 12 Gy 9  Cy/TBI 10 Gy 1  Cy/Flu/TBI 12 Gy 1 Bu/Cy 3 RIC/NMA 29 Flu/Bu/ALG 10 Flu/TBI 2 Gy 10  Flu/TBI 2 Gy 5  Cy/Flu/TBI 2 Gy 4  AraC/Flu/TBI 2 Gy 1 Sequential 5  Amsa/AraC/Flu/Cy/Bu/ALG 3  Amsa/AraC/Flu/Cy/TBI 2 Gy/ALG 1  Amsa/AraC/Flu/Bu/ALG 1 Flu/Bu/Thiotepa/ALG 1 Flu/Mel 1 Cy/TBI 8 Gy 1 TLI/ALG 1 Figure 1. Cumulative incidences of relapse and non-relapse mortality Figure 1. Cumulative incidences of relapse and non-relapse mortality Figure 2. Non-relapse mortality according to donor type Figure 2. Non-relapse mortality according to donor type Disclosures No relevant conflicts of interest to declare.

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