scholarly journals Post-Transplant Cyclophosphamide Versus Antithymocyte Globulin in Patients with Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplantation from HLA-Identical Sibling Donors: A Retrospective Analysis from the Acute Leukemia Working Party of the EBMT

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 148-148
Author(s):  
Giorgia Battipaglia ◽  
Myriam Labopin ◽  
Rose-Marie Hamladji ◽  
Didier Blaise ◽  
Patrice Chevallier ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cyclosporine A ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
The Other ◽  
Free Survival ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source

Introduction. In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA-identical matched sibling donor (MSD), use of cyclosporine A in association with methotrexate has been the main graft-versus-host disease (GVHD) prophylaxis strategy. Addition of antithymocyte globulin (ATG), especially when using peripheral blood stem cells (PBSC) as source, has also been shown to favor lower rates of chronic GVHD. More recently, use of post-transplant cyclophosphamide (PTCY) in the haploidentical setting resulted in low incidences of both acute and chronic GVHD. Its use has therefore been subsequently reported in other donor settings, including MSD. The aim of our study was to compare GVHD prophylaxis containing either PTCY or ATG in patients diagnosed with acute myeloid leukemia and undergoing allo-HSCT from a MSD. Methods. This was a retrospective study from the EBMT registry. Included were adult patients undergoing their first allo-HSCT during the period 2008-2018 and who were in complete remission at time of allo-HSCT. Results. Globally, 197 and 1,913 patients receiving either PTCY or ATG, respectively, were identified who fulfilled inclusion criteria. Patients in the PTCY group were younger (median age 47 versus 54 years, p<0.01) and had undergone allo-HSCT more recently (median year of allo-HSCT: 2015 versus 2014, p<0.01). Peripheral blood was the more frequently used stem cell source, this being significantly more frequent in the ATG group (95% versus 70%) than in the PTCY group (p<0.01). The conditioning regimen was more frequently myeloablative in the PTCY group (59% versus 48% in the ATG group, p<0.01). Cyclosporine-A alone was the most used systemic immunosuppressive agent associated with either PTCY (22%) or ATG (28%), while 34% and 29% of patients in the ATG group and 7% and 12% in the PTCY group also received either methotrexate or mycophenolate mofetil along with cyclosporine A. No statistical differences were observed for incidence of grade II-IV acute GVHD at 100 days after allo-HSCT, this being 19% versus 17% in the PTCY and ATG groups, respectively (p=0.81). On the other hand, a significantly higher incidence of chronic GVHD at 2 years was observed with the use of PTCY (37% versus 30%, p<0.02) and for extensive chronic GVHD (16% versus 12%, p<0.01) as compared to ATG. There was no impact of conditioning intensity on GVHD incidence. No statistical differences were observed on univariate analysis for all other transplant outcomes, with a leukemia-free survival (LFS) of 55% versus 58%(p=0.75), overall survival (OS) of 64% versus 65% (p=0.61), GVHD-free, relapse-free survival (GRFS) of 44% versus 49% (p=0.19), relapse incidence (RI) of 36% versus 32% (p=0.56) and non-relapse mortality (NRM) of 8% versus 10% (p=0.78). Of note, the cumulative incidences of death due to GVHD were 4.4% and 4% in the PTCY and ATG groups, respectively (p=0.53). Also, there were no differences between the 2 groups for death due to infections: 6% in the PTCY group and 6.3% in the ATG group, respectively (p=0.49). On multivariate analysis, these results were confirmed, with a higher risk of chronic GVHD of any grade (HR=1.41, 95%CI 1.03-1.92; p<0.01) and extensive chronic GVHD (HR=1.68, 95%CI, 1.07-2.62; p<0.01) with PTCY, and no differences with respect to the other outcomes. We also observed that, regardless of the use of PTCY or ATG, use of PBSC was associated with lower RI (HR=0.64, 95% CI 0.46-0.89; p<0.01), higher LFS (HR=0.71, 95% CI 0.53-0.95; p<0.03), and OS (HR=0.72, 95% CI 0.52-0.99; p<0.05). On the other hand, we found no statistical differences in terms of both acute GVHD (HR=0.73, 95%CI, 0.48-1.12; p=0.15) and chronic GVHD (HR=0.83, 95% CI 0.56-1.21; p=0.33) according to stem cell source. These results were also confirmed in a matched-pair analysis. Conclusion. In conclusion, our results highlight that in the HLA-identical sibling setting, the use of ATG provides similar outcomes to those seen with PTCY except for chronic GVHD for which a protective effect of ATG is confirmed as previously reported by different other studies. Disclosures Blaise: Sanofi: Honoraria; Molmed: Consultancy, Honoraria; Pierre Fabre medicaments: Honoraria; Jazz Pharmaceuticals: Honoraria. Chevallier:Incyte: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria; Daiichi Sankyo: Honoraria. Socie:Alexion: Consultancy. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

scholarly journals Family Mismatched Donor Transplantation for Myelofibrosis: A Retrospective Analysis of the EBMT Chronic Leukaemia Working Party

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4655-4655 ◽  
Author(s):  
Kavita Raj ◽  
Eduardo Olavarria ◽  
Diderik-Jan Eikema ◽  
Liesbeth C de Wreede ◽  
Linda Koster ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cumulative Incidence ◽  
Graft Failure ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source ◽  
Mismatched Donor

Abstract Background: Allogeneic stem cell transplantation is a treatment option for patients with advanced myelofibrosis. Problems encountered include an increased risk of delayed or poor engraftment and in the mismatched unrelated donor setting a higher rate of GVHD and particularly poor outcomes. As for other indications for allogeneic stem cell transplants, patients for whom either a matched sibling or matched unrelated donor is not available are considered for either a double umbilical cord blood, a mismatched unrelated donor or haploidentical stem cell transplant. Data on the latter option are limited and we reviewed registry data on all family mismatched donor transplants performed between 2001 and 2015 and reported to the EBMT registry. Results: Records retrieved 69 patients with myelofibrosis transplanted between November 2001 and November 2015. 44 (64%) were male. 50 (74%) had primary myelofibrosis,18 (27%) had secondary myelofibrosis (6 from ET, 5 from PRV and 7 others) and unknown 1(2%). Of 25 patients for whom the JAK2 V617F mutation status was known, 15 (22%) harboured the mutation. Patient Karnofsky performance status was > 70% in 98%. Of the mismatched family donors, 47 (68%) were male and 22 (31%) female. Donors were HLA mismatched at 1 locus in 12 (17%) and 2 or more loci in 48 (69%). Donor-recipient serology combinations were CMV -/- in 8 (12%), +/- in 4 (6%), -/+ in 15 (22%) and +/+ in 34 (49%) missing 8 (12%). Bone marrow was the stem cell source in 34 (49%) and peripheral blood in 35 (51%). The median total nucleated cell count (TNC) infused was 7.5x108/kg (range 2.3-21x108/kg) from data available in 17 patients. The median CD34+ cell dose was 6.9x106/kg (range 1.9-18.18x106/kg) from data available in 19 patients. Conditioning was myeloablative in 48 (70%) and RIC in 21 (30%) The conditioning regimes were varied but the predominant ones were Fludarabine, Busulphan, ATG (FBATG) and Thiotepa, Busulphan, Fludarabine (TBF). TBI was administered in 8 (12%) and in vivo T cell depletion in 22 (32%), ex-vivo T cell depletion in 5 (7%) patients. GVHD prophylaxis varied with post transplant Cyclophosphamide administered in 34/67 (49%) and ATG in 19/67 patients (28%). Neutrophil engraftment was established in 53 (82%) at a median of 20 days (range 11-83). Primary graft failure occurred in 8 (12%) and secondary graft failure in 4 (6%). This occurred at a median of 12 months (range 4.5-35 months). Eleven of these patients had a second allograft at a mean interval of 6.4 months. Responses to the first allograft (censoring for patients who had a second allograft) with data available in 45 patients, showed that complete remission was achieved in 35 patients (78%), 6 (13%) were never in CR and 4 (9%) were not evaluable. The cumulative incidence of grade II-IV acute GvHD at 100 days was 12% (95% CI 4-21%) and for grade III-IV acute GvHD at 100 days it was 5% (95% CI 3-11%). Data for chronic GVHD was valid in 49 patients. The cumulative incidence of chronic GvHD at 2 years was 62% (95% CI 47-76%). The cumulative incidence of limited cGvHD was 45% (95% CI 31-59%) whereas the cumulative incidence of extensive cGvHD was 10% (95% CI 2-19%). The median follow up was 24 months (95% CI 13-35 months). The 2-year OS was 51% (95% CI 37-76%) and the 5-year OS was 38% (95% CI 21-55%). The 2-year RFS was 44% (95% CI 30-59%) and the 5-year RFS was 31% (95% CI 15-48%). The 2 year cumulative incidence of relapse was 14% (95% CI 5-24%). The 2 year NRM was 41% (95% CI 28-55%), which increased to 54% (95% CI 37-72%) at 5 years. The main causes of death were infection (16, 24%), GVHD (7, 10%) organ damage or failure (3, 5%), relapse/disease progression (1, 2%) and secondary malignancy or PTLD (1, 2%). On univariate analysis there was no significant effect of recipient gender, donor gender, degree of HLA mismatch 1 vs >1 Ag MM, CMV matching between donor and recipient, primary or secondary MF, disease stage at transplant (chronic versus advanced phase), conditioning intensity, conditioning regimen, GVHD prophylaxis with ATG or post transplant cyclophosphamide or stem cell source on overall survival. Conclusion: Concerns regarding engraftment and secondary graft failure have excluded patients with myelofibrosis from clinical trials of mismatched related donor transplant. The data suggest that engraftment is feasible, and PFS and OS can be attained with limited severe chronic GVHD with family mismatched donors in this setting. Disclosures Ciceri: MolMed SpA: Consultancy.

Post Transplant Cyclophosphamide (PTCy) with Anti-Thymocyte Globulin (ATG) Effectively Reduces the Severe (Grade III-IV) Acute Graft-Versus-Host Disease (GVHD) When Compared to ATG Alone in Matched Unrelated Donor (MUD) Allogeneic Hematopoietic Cell Transplants

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3430-3430 ◽  
Author(s):  
Uday Deotare ◽  
David Loach ◽  
Fotios V. Michelis ◽  
Dennis D. Kim ◽  
Santhosh Thyagu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Historical Cohort ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source ◽  
Grade Iii ◽  
Severe Grade

Abstract Introduction: Acute Graft-versus-Host Disease (aGVHD) is a frequent complication of Allogeneic Hematopoietic cell transplants (allo-HCT). It can be lethal with increased morbidity and mortality and can occur in upto 40-50% of allo-HCT. Various agents such as calcineurin inhibitors, anti-metabolites and anti T cell antibodies, have been variably used for GVHD prophylaxis. Use of Post-transplant Cyclophosphamide (PTCy) has recently been used extensively in haplo-identical transplant setting with promising results, but has mainly been used in patients with BM as a stem cell source. In those patients receiving PBSC as a stem cell source, PTCy alone could reduce the risk of acute and chronic GVHD significantly. Anti-Thymocyte Globulin (ATG) has been associated with decrease in chronic but not acute GVHD. As most of our patients use PBSC as a graft source, we hypothesized that combination of ATG and PTCy can reduce the incidence of both acute and chronic GVHD. Since we had also used ATG for GVHD prophylaxis in a historical cohort, we compared the results of this approach with the current GVHD prophylaxis regimen. Methods: A total of 28 patients with hematological malignancies, who had an unrelated donor underwent allo-HCT at our center from 1 Oct 2015 to 31 Mar 2016. After interim analysis, when increased non-hematological toxicity was observed with myeloablative conditioning, all patients subsequently received reduced intensity conditioning. Peripheral blood was used as a stem cell source in all patients. The GVHD prophylaxis consisted of a combination of ATG-PTCy-CsA, with rabbit ATG administered on Days -3 (0.5 mg/Kg), -2 (2 mg/Kg) and -1 (2 mg/Kg), PTCy at dose of 50 mg/kg on Days +3 and +4 and CsA from Day+5 onwards. Filgrastim was used from day +7 onwards for 13 patients. Emphasis was given to incidence of acute GVHD, especially Steroid Refractory (SR-GVHD). Results: Out of total of 28 patients, aGVHD was seen in 6 (21.4%) patients, five of which had skin involvement (Grade I- II) and one suspected liver involvement (Grade III), all of which responded rapidly to steroids with no cases of SR-GVHD. Secondary graft failure and EBV reactivations; each were seen in 10% of cases. Primary disease relapse was seen in 3 patients, two of which had minimal residual disease prior to transplantation. These results were then compared to the historical cohort of 27 patients who received a combination of ATG-CsA plus Mycophenolate Mofetil (MMf) (Table 1). The incidence of acute GVHD was 26% vs 22% (p=0.99), with severe Grade III-IV aGVHD of 4% vs 20% (p=0.085) in the ATG-PTCy-CsA and ATG-CsA-MMf cohorts, respectively; both were statistically not signifcant. There were five patients with SR-GVHD in the ATG-CsA-MMf cohort and none in the current GVHD prophylaxis arm. In the historical cohort, the main cause of death in 7 out of 11 patients was severe GVHD as compared to 1 out of 9 in the ATG-PTCy-CsA cohort. Conclusions: Combination of ATG-PTCy-CsA is an effective strategy to reduce aGVHD; especially severe Grade III-IV and doesnot increase the risk of SR-GVHD, in unrelated donor transplants as compared to ATG-CsA-MMf. However, a long term follow up is needed to assess relapse and cGVHD. Disclosures No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation (allo-SCT) in 192 Acute Myeloid Leukemias (AML): A Single Center Experience From 1982 to 2010

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4498-4498
Author(s):  
Carmen Montes-Gaisan ◽  
Jorge Monge ◽  
Clara Martin ◽  
Zurie Diez ◽  
Johny Alberto Hinostroza ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Multivariable Analysis ◽  
The Other ◽  
Univariable Analysis ◽  
Stem Cell Source ◽  
Significant Difference ◽  
Cell Source

Abstract Abstract 4498 Background: Giving the fact that allo- SCT currently offers patients with high risk AML the best chance of cure, we`ve aimed to investigate the outcome of AML patients who have undergone allo-SCT in our center, considered as one of spanish reference hospital in SCT, and the parameters that have been able to influence in relapse rate (RR), overall survival (OS) and relapse free survival (RFS). Methods: Retrospective study in 192 AML patients who have undergone allo-SCT between 1982 and 2010. The analysis has been performed in 171 patients (85 male and 86 female) by excluding 21 acute promyelocitic leukemias (APL): 65 patients until 1999 and 106 since 2000. Median age was 37 1874 and median lecocyte count, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(13400/\hbox{ L }\frac{470}{250000}\) \end{document}. 82 were de novo AML and 87 were in morfologic complete remission (70 in first CR). 14 patients had received a previous SCT. Cytogenetic risk was as follows: 55 intermediate, 34 high and 11 low. Conditioning regimen was ablative in 162 patients: CyTBI (36), BuCy (31), BuFlu (30) and others (3). 130 patients (76) underwent a related allo-SCT (95 of them were matched) and 41 patients (24), an unrelated allo-SCT (64 of them were matched). Stem cell source was bone marrow (BM) in 146 patients (85) and only 3 patients received umbilical cord (UC). Graft versus host disease (GvHD) prophilaxis was based on Ciclosporine in 150 patients (88). Median time from last treatment was 73 days 12268. Results: The median follow-up of this study was 61 months 1317. OS at 1, 3 and 5 years were 57, 44 and 40. RFS at 1, 3 and 5 years were 62, 50 and 45. Early mortality (before day 100) was 26 (43 until 1999 and 15 since 2000, p0,0001): 18 patients because of infections, 10 because of toxicity, 9 because of disease and 7 because of EICH. Late mortality was 27 (more than the half because of relapse, with no significant difference between 19881999 and 20002010). Cumulative relapse incidence at 5 years was 35, with a median time of relapse of 4 months. Secondary malignancies incidence was 5. Multivariable analysis showed that Transplantation Related Mortality (TRM) was influenced by: year of allo-SCT (OS at 5 years of 49 if 20002010 vs 28 if 19821999, p0,0001), late engraftment (p0,002) and severe acute GvHD (OS at 5 years of 45 if no evidence/grade I-II vs 25 if grade III-IV, p0,071). The other important parameters which lost its univariable analysis significance were donor type, recipient age and conditioning regimen. No difference was found in case of HLA and ABO discordance or donor/recipient CMV status. Multivariable analysis also showed that RR and RFS at 5 years was influenced by: disease status at allo-SCT (50 if 1CR vs 0 if 2CR/PR/refractory disease, p0,002), chronic GvHD (67 if present vs 41 if absent, p0,035) and leucocyte count at diagnosis (54 if 20000/ L vs 37 if 20000/ L, p0,038). The other important parameters which lost its univariable analysis significance were cytogenetic risk, initial induction response and positive minimal residual disease (MRD) before allo-SCT. No diference was found in case of ethiologic classification or stem cell source. Conclusions: Allo-SCT is a curative procedure in AML patients (global RFS of 50 at 3 years), specially when disease is under control and patient develops chronic GvHD. In the last decade, there have been important improvements in the procedure which have led to a significant decrease in TRM, and consequently, a significant increase in OS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The 17-Gene Leukemic Stemess Score Can Predict Treatment Outcomes Following Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3299-3299
Author(s):  
Dennis Dong Hwan Kim ◽  
Taehyung Kim ◽  
Tracy Murphy ◽  
Steven M Chan ◽  
Mark D. Minden ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Allogeneic Hct ◽  
Gvhd Prophylaxis ◽  
Acute Myeloid

Introduction: A 17-gene stemness score (LSC17 score) had been reported to determine the risk of therapy resistance in acute myeloid leukemia (Nature 2016), and this was replicated successfully in 5 independent cohorts (n=908). When the patients were stratified according to the median value of the LSC17 score, allogeneic hematopoietic stem cell transplantation (HCT) did not affect overall survival (OS) from initial diagnosis for either high- or low-score patients (p=0.2 for high and p=0.06 for low LSC17 score groups). In the present study, we aimed to further perform a subgroup analysis confined to the patients receiving allogeneic HCT and determine whether the LSC17 score at leukemia diagnosis was associated with treatment outcomes including OS, leukemia-free survival (LFS), non-relapse mortality (NRM), relapse incidence (RI), and acute/chronic GVHD following allogeneic HCT. Methods and patients: Out of 452 patients with available LSC17 scores, 123 patients were included into the final analysis who received allogeneic HCT using matched (n=104, 84.6%) or mismatched/haploidentical donors (n=19, 15.4%). 80 patients were from the previous study (Nature 2016), while 43 patients were a prospectively accrued cohort during 2016-2018. Patients and transplant characteristics were: male/female (n=61/62); median age, 51 (17-73); CR status prior to HCT, CR1 (n=93, 75.6%), CR2 (n=30, 24.4%); Conditioning regimen, reduced intensity/myeloablative conditioning (n=59, 48.0% vs n=64, 52.0%); GVHD prophylaxis using post-transplant cyclophosphamide (PTCy; n=45, 36.6%) or T cell depletion (n=62, 50.4%); Cytogenetic risk, favorable (n=10, 8.1%), intermediate (n=70, 56.9%), adverse (n=26, 21.1%), inconclusive or not done (n=17, 13.8%). The LSC17 score for each patient was measured in a diagnostic sample using a NanoString assay and compared to the high/low threshold of a reference AML cohort (Ng et al, Nature 2016 and unpublished data). Transplant outcomes were compared according to the LSC17 risk group for OS, LFS, NRM and RI. Univariate and multivariate analyses were conducted for OS and LFS using Cox's proportional hazard model or for NRM and RI using Fine-Gray model, respectively. The following variables were included in the model: the LSC17 score group (high vs low LSC17 score), chronic GVHD, CR status (CR2 vs CR1), Cytogenetic risk (adverse vs favorable/intermediate/inconclusive), GVHD prophylaxis (PTCy vs others, T-cell depletion vs others), Age (above 60 vs others), donor type (mismatched/haploidentical vs matched donors). Results: With a median follow-up duration of 22 months among survivors after HCT, 23 patients experienced relapse (n=23, 18.7%) while 63 deaths (51.2%) were noted. Out of 123 patients, 58 (47.1%) had a low LSC17 score and 65 (52.9%) had a high LSC17 score. There was no difference in the distribution of LSC17 scores between the group who received HCT (n=123; 0.479±0.026) vs not (n=229; 0.456±0.019; p=0.491). LFS survival was significantly better in the low LSC17 score group (51.5 vs 32.4% for 2-year LFS rate, p=0.0219), and there was a trend to higher OS rate in the low LSC17 group (48.1%) compared to the high LSC17 group at 2 years (34.2%, p=0.09). Furthermore, patients with a low LSC17 score had a significantly lower RI (14.9% vs 27.3% for 2-year relapse incidence, p=0.028). There is no difference of NRM between the groups (37.2% vs 38.2% at 2 years, p=0.647). Multivariate analysis confirmed that the high LSC17 score group was associated with worse LFS (HR 1.874 [1.080-3.249], p=0.025). However, it was not confirmed with respect to OS or relapse incidence. As expected, it was not associated with NRM. Conclusion: A low 17-gene stemness score is associated with better leukemia-free survival and lower relapse incidence after allogeneic HCT, and is suggested to be associated with OS. The high LSC17 score group may be considered for novel therapeutic strategies to reduce the risk of relapse after allogeneic HCT. Figure Disclosures Chan: Celgene: Honoraria, Research Funding; AbbVie Pharmaceuticals: Research Funding; Agios: Honoraria. Minden:Trillium Therapetuics: Other: licensing agreement. Michelis:CSL Behring: Other: Financial Support. Mattsson:Gilead: Honoraria; Celgene: Honoraria; Therakos: Honoraria. Wang:Pfizer AG Switzerland: Honoraria, Other: Travel and accommodation; Pfizer International: Honoraria, Other: Travel and accommodation; Trilium therapeutics: Other: licensing agreement, Research Funding; NanoString: Other: Travel and accommodation.

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.

Clinical Outcomes of Cord Blood Transplantation from Unrelated Donors Comparable with Marrow or Blood Transplantation from Related Donors in Adults: A Single Institute Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 306-306
Author(s):  
Satoshi Takahashi ◽  
Jun Ooi ◽  
Akira Tomonari ◽  
Takaaki Konuma ◽  
Kenji Fukuno ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Blood Transplantation ◽  
Stem Cell Source ◽  
Cell Source ◽  
Unrelated Donors

Abstract We previously reported some promising results of cord blood transplantation (CBT) compared with bone marrow transplantation (BMT) from unrelated donors in terms of graft-versus-host disease (GVHD), transplant-related mortality (TRM), and disease-free survival (DFS) in our institute (Blood104: 3813, 2004). If the patient was eligible for allogeneic transplantation without any related donors, we performed CBT immediately, rather than waiting for the results of an unrelated marrow donor search. This might be one of the reasons for our favorable CBT results in adults compared with most previously published studies. We studied the clinical outcomes of 163 adults with hematological malignancies who received unrelated CBT (n=92), or BMT or peripheral blood stem cell transplantation (PBSCT) from related donors (n=71, 55 BMT and 16 PBSCT) between January 1997 and February 2005. All patients received myeloablative regimens including 12 Gy of total body irradiation and almost the same supportive care. We analyzed the hematopoietic recovery, rates of GVHD, risks of TRM and relapse, and DFS using Cox proportional hazards models. The age, sex, cytomegalovirus serological status, time from diagnosis to transplantation, and GVHD prophylaxis regimens were not significantly different between both groups. Overall rates of high-risk patients in the CBT and in BMT/PBSCT groups were 58% and 63%, respectively. Human leukocyte antigen (HLA) was scored serologically for HLA-A and B and genetically for DRB1 alleles. There were no complete matches in CBT and 54 (76%) matched grafts in BMT/PBSCT. Median numbers of leukocytes and CD34+ progenitor cells before freezing of cord blood grafts were 2.4x107/kg and 0.9x105/kg, respectively. Median follow-up was 27 months for CBT and 50 months for BMT/PBSCT. Significant delays in neutrophil and platelet engraftment rates occurred after CBT; however, overall myeloid engraftment rates were almost the same for both grafts (94% in CBT and 98% in BMT/PBSCT). The cumulative incidences of grades II to IV acute GVHD, of grades III and IV acute GVHD, and of requiring steroids for treating acute GVHD among CBT recipients were 58%, 8%, and 18%, respectively. Those among BMT/PBSCT recipients were 58%, 19%, and 38%, respectively. Chronic GVHD affected 68 of 75 CBT and 49 of 60 BMT/PBSCT evaluable recipients. Twenty-two CBT and 30 BMT recipients developed extensive GVHD. The 1-year cumulative incidence of TRM, the 3-year cumulative incidence of relapse, and the 3-year probability of DFS in CBT recipients were 9%, 18%, and 71%, compared with 13%, 26%, and 60% in BMT/PBSCT recipients. Multivariate analysis demonstrated no apparent difference in those outcomes between both groups. Taken together, engraftment speed was slower and severe acute GVHD and extensive chronic GVHD tended to be lower in CBT recipients compared with BMT/PBSCT recipients; however TRM, relapse and DFS were comparable in both groups. These data suggest that cord blood from unrelated donors could be as safe and effective a stem cell source as bone marrow or mobilized peripheral blood from related donors for adults when it is used as a primary unrelated stem cell source.

A Comparison of Stem Cell Source in Recipients of T-Cell Depleted Myeloablative Transplants for Leukaemia: No Difference in Mortality Using BM or PBSC.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 46-46
Author(s):  
B.E. Shaw ◽  
Nigel H. Russell ◽  
A. Pagliuca ◽  
J. Apperley ◽  
G. Cook ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Increased Risk ◽  
Significant Difference ◽  
Cell Source ◽  
The Impact

Abstract The use of GSCF-mobilised Peripheral Blood Stem Cells (PBSC) for unrelated donor (UD) transplantation has increased dramatically since 2000. The association of PBSC with more rapid engraftment and with an increase in chronic Graft versus Host Disease (GvHD), compared to bone marrow (BM) has been reported in a number of studies. More recently the use of PBSC has been associated with an increase in transplant related mortality (TRM) and decrease in survival (OS) in T-cell replete transplants. We sought to analyse the impact of PBSC compared to BM in a cohort of UD transplant recipients, where T-cell depleting agents (in-vivo campath in >90%) were included in the transplant conditioning. The study included 145 patients transplanted between January 2000 and March 2006: CML- 35 in 1CP; acute leukaemia (AML in 61, ALL in 49)-110 in CR1 or 2. All had myeloablative conditioning regimens and received grafts with 9–10/10 matched HLA alleles. 86 patients received BM and 59 PBSC. There were no associations between the stem cell source and any transplant variable (including disease and stage). There was a trend to an increased use of PBSC in patients with a single antigen mismatch (p=0.052). All evaluable patients achieved neutrophil engraftment, with a significantly faster time to engraft in recipients of PBSC compared to BM (16 vs 20 days; p=0.0003). The incidence of acute GvHD was 46% (grade I in 50%, II in 41%, III in 8%, IV in 2%). This was significantly higher in recipients of PBSC (60%) compared to BM (36%; p=0.006), however there was no increase in either II/IV (p=0.69) or III/IV (p=0.18) disease in PBSC recipients. In univariate analysis, the presence of a single HLA mismatch (p=0.026) was the only other variable to be associated with an increase in acute GvHD. In a logistic regression model including both these variables, the use of PBSC remained significantly associated with an increase in aGvHD (OR=2.3; 95% CI 1.1,4.7;p=0.020). The TRM was 14%, 27% and 39% at 100 days, 1 and 5 years respectively. At none of these time points was the stem cell source associated with a significant difference in TRM. The 5-year incidence of chronic GvHD was 58% (BM 55%, PBSC 60%; NS), extensive disease in one third, and of relapse was 61% (BM 60%, PBSC 62%; NS). The 5-years OS was 41% with a median follow-up of 3.4 years (0.5–7.1). This was 44% using PBSC and 40% using BM (NS). In conclusion, although we observed an increase in acute GVHD with PBSC this was only of grade 1 disease. We found no association between the use of PBSC and an increased risk of chronic GVHD or of a worse transplant outcome, when compared to BM, in recipients of T-cell depleted myeloablative transplants for leukaemia.

Outcome After 9/10 Mismatched Unrelated Donor or Cord Blood Cells Allogeneic Stem Cell Transplantation (allo-SCT) in the Setting of Reduced-Intensity Conditioning (RIC)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 956-956
Author(s):  
Florent Malard ◽  
Sabine Furst ◽  
Marion Loirat ◽  
Patrice Chevallier ◽  
Jean El-Cheikh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Blood Cells ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Group Versus ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Cell Source ◽  
Unrelated Donors ◽  
Cord Blood Cells

Abstract Abstract 956 Background. Unrelated umbilical cord blood cells (UCB) have emerged as an alternative stem cell source for allo-SCT in patients who lack a matched-related or unrelated donor (MUD). Several studies found a similar outcome between HLA 4–6/6 matched UCB and HLA 8/8 matched and 7/8 mismatched unrelated donors, mainly in the setting of standard myeloablative conditioning. However, currently it is more common practice in many centres to search for 10/10 or 9/10 MUD or for double UCB. Thus far, no study focussed on the comparison of outcome of patients who received double UCB allo-SCT versus allo-SCT using 9/10 mismatched donors. With this background, this retrospective analysis assessed outcome after allo-SCT using double UCB cells or 9/10 mismatched donors in the setting of a RIC regimen. Patients and Methods. This analysis was performed in a series of 152 consecutive adult patients treated for hematological malignancies in 2 centers adopting similar transplant procedures. 85 patients were males (56%) and the median age at time of allo-SCT was 53 years (range, 16–69). Diagnoses included 59 AML (39%), 21 MDS/MPN (14%), 42 NHL (28%), 5 Hodgkin diseases (3%), 18 ALL (12%) and 7 Myelomas (5%). 35 patients (23%) had standard risk disease and 117 patients (77%) presented with high risk disease. Conditioning regimen consisted of fludarabine, cyclophosphamide and low dose TBI for 108 patients (71%), fludarabine and busulfan for 35 patients (23%); and other regimens in the remaining 9 patients (6%). 50 patients (33%) received antithymocyte globulin. The donor was double UCB in 110 cases (“dUCB” group) and 9/10 mismatched unrelated in 42 cases (“9/10” group). During the study period, both participating centers adopted the same strategy for donor search and choice: in the absence of matched-related siblings or 10/10 MUD, 9/10 donors were searched. UCB cells were used if no 9/10 donor could be identified within a reasonable time frame (usually 2–3 months after search initiation). Results. With a median follow-up of 30.3 months (range, 6–72.4), the Kaplan-Meier estimate of overall survival (OS) at 2 years was comparable between both groups [52% (95%CI, 42–61%) in the dUCB group versus 48% (95%CI, 32–62%) in the 9/10 group, P=0.55]. The cumulative incidence of NRM was 26% in the dUCB group versus 24% in the 9/10 group (P=0.95). Grade 3–4 acute GVHD and extensive chronic GVHD incidences were 20% versus 21.4% (P=0.83), and 6% versus 21% (P=0.02), in the dUCB group versus the 9/10 group, respectively. The cumulative incidence of relapse was 34% in the dUCB group versus 38% in the 9/10 group (P=0.63). Finally, the estimate of progression-free survival (PFS) at 2 years was 43% (95%CI, 34–52%) in the dUCB group versus 38% (95%CI, 23–53%) in the 9/10 group (P=0.55). In multivariable analysis including the most important parameters associated with outcome (patient's age at transplantation, patient's sex, diagnosis, disease status at transplantation, use of ATG, GVHD prophylaxis), the stem cell source (dUCB versus 9/10) did not have any significant impact on OS (HR=0.92 (95% CI, 0.41–2.08); P=0.86) Conclusion. These data suggest that dUCB is likely a valid alternative graft source compared to 9/10 mismatched unrelated donors in the setting of RIC allo-SCT since both donor types showed similar results in terms of OS, PFS, disease relapse, and acute GVHD incidence. However, the significantly lower incidence of extensive chronic GVHD in the dUCB group is an important and major finding, highlighting the need for a prospective randomized study in this field. Disclosures: No relevant conflicts of interest to declare.

Hematopoietic Stem Cell Transplantation after Reduced Intensity Conditioning in Acute Myeloid Leukemia Patients Older Than 40 Years.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5074-5074
Author(s):  
Cynthia Huisman ◽  
Ellen Meijer ◽  
Eefke J. Petersen ◽  
Henk M. Lokhorst ◽  
Leo F. Verdonck
Keyword(s):  
Stem Cell ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Free

Abstract Reduced intensity conditioning (RIC) protocols are increasingly used for allogeneic hematopoietic stem cell transplantation (HSCT) in elderly patients. We retrospectively analyzed the outcome of RIC HSCT in a homogeneous group of acute myeloid leukemia (AML) patients over the age of 40. Forty-three AML or high-risk myelodysplastic syndrome patients were treated with a fludarabine and low dose total body irradiation (TBI) based regimen, followed by a full peripheral stem cell graft. Antithymocyte globulin was given to matched unrelated recipients (34%) before infusion of fludarabine. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin and mycophenolate mofetil. All but 2 AML patients were in complete remission at the time of transplantation. Seventy-six percent of patients had a poor risk profile. Hematologic recovery was fast and primary graft failure occurred in one patient. Two patients with active disease at the time of HSCT experienced ongoing relapse. Infections were diagnosed in 9 patients (21%) and 6 patients (14%) were treated for CMV reactivation. Sixty percent of patients developed acute GVHD, which was grade 2 in 40% and grade 3 in 12%. Chronic GVHD occurred in 33% of patients. The incidence and severity of both acute and chronic GVHD was similar in patients with related and unrelated donors (P = 0.84 and 0.74, respectively). Treatment-related mortality (TRM) was low (9%), total nonrelapse mortality was 19%. After a median follow-up of 571 days, 16 patients (37%) experienced relapse. One-year progression-free and overall survival were 61% and 67%, respectively. Median disease-free survival has not been reached yet (> 58 months) and median overall survival was 31 months (Fig 1 and 2, respectively). Poor risk AML was significantly associated with disease-free survival in multivariate analysis (P = 0.02). Age > 60 years, gender, donor type, timing of RIC HSCT (upfront or after relapse) and acute GVHD were not identified as prognostic factors. In conclusion, fludarabine plus low-dose TBI-based RIC HSCT is effective in AML patients over the age of 40 without active disease at the time of transplant and is associated with low TRM. Figure Figure Figure Figure

A Comparison of Stem Cell Source in Adult and Paediatric Recipients of T-Cell Depleted Myeloablative Transplants for Standard Risk Leukaemia: No Difference in Mortality Using BM or PBSC.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1205-1205
Author(s):  
Bronwen E Shaw ◽  
Jane Apperley ◽  
Nigel H. Russell ◽  
Charles F. Craddock ◽  
Effie Liakopoulou ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Stem Cell Source ◽  
Significant Difference ◽  
Cell Source ◽  
Standard Risk

Abstract Abstract 1205 Poster Board I-227 The use of GSCF-mobilised Peripheral Blood Stem Cells (PBSC) for unrelated donor (UD) transplantation has increased dramatically since 2000. The association of PBSC with more rapid engraftment and with an increase in chronic Graft versus Host Disease (GvHD), compared to bone marrow (BM) has been reported in a number of studies. More recently the use of PBSC has been associated with an increase in non relapse mortality (NRM) and decrease in survival (OS) in T-cell replete transplants. We have previously reported outcome data in 145 patients who received an unrelated donor transplant for leukaemia. In that study we reported an increase in mild acute GvHD using PBSC, but no other significant differences in outcome. We have now doubled the cohort and report our findings on 320 patients here. In this group all of the patients received pre-transplant serotherapy (Alemtuzumab = 306, ATG = 14) as part of myeloablative conditioning prior to an HLA-matched UD allograft. Patients were transplanted between January 2000 and August 2007: CML in 1CP (n=102) and acute leukaemia in CR1/2 (AML in 105, ALL in 144). 190 patients received BM and 130 PBSC. The median age of the recipients was 28.9 years (10months - 58years). There was no significant difference in age between those receiving BM or PBSC.98% and 96% of patients receiving PBSC and BM achieved neutrophil engraftment (NS), with a significantly faster time to engraftment in recipients of PBSC compared to BM (14 vs 20 days; p<0.001). The incidence of acute GvHD was significantly higher in recipients of PBSC (64%) compared to BM (51%; p=0.022), however there was no increase in grade III/IV (p=0.420) disease in PBSC recipients. The incidence of chronic GvHD at 6 years was 61% in the BM recipients and 55% in the PBSC recipients (NS), with no difference in the incidence of extensive disease. The 5-years OS was 55% in BM recipients, with a median follow-up of 59 months, compared to 54% in PBSC recipients at a median follow-up of 38 months (NS). The incidence of neither disease relapse nor NRM was significantly different between groups (relapse at 5 years: BM 44%, PBSC 36%; p=0.112, and NRM at 5 years: BM 22%, PBSC 24%; p=0.751). In view of the fact that there were more CML patients in the BM group and more AML patients who received PBSC (the distribution of ALL patients was similar) (p=0.051), we performed a subgroup analysis. The pattern of results for each outcome, dependant on the use of BM or PBSC, in patients with CML and those with acute leukaemia were similar to those reported in the group overall. In conclusion, we have confirmed the results of our previous smaller study, showing the only significant difference in clinical outcome between PBSC and BM to be a higher incidence in the occurrence (but not grade) of acute GvHD. We found no association between the use of PBSC and an increased risk of chronic GVHD or of a worse transplant outcome, when compared to BM. We suggest that either stem cell source can be used with a similar outcome in adult and paediatric recipients of T-cell depleted allografts for standard risk leukaemia. Disclosures: Apperley: Novartis: Consultancy, Honoraria.

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