scholarly journals Antithymocyte Globulin Improves the Survival of Patients with Myelodysplastic Syndrome Undergoing HLA-Matched Unrelated Donor and Haplo-Identical Donor Transplants

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5851-5851
Author(s):  
Miao Miao ◽  
Hong Wang ◽  
Hong Liu ◽  
Jinyi Zhou ◽  
Tongtong Zhang ◽  
...  
Keyword(s):  
Antithymocyte Globulin ◽  
Median Overall Survival ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
The Past ◽  
Conditioning Regimens ◽  
Matched Sibling

Abstract Background: Significant advances have been achieved in the outcomes of patients with myelodysplastic syndromes (MDS) after both HLA-matched sibling donor transplants (MSDT) and non-MSDT in the past few years, the latter including HLA-matched unrelated donor (MUDT) and haplo-identical donor transplants (HIDT). Methods: We retrospectively analyzed the data of 85 consecutive patients with MDS who received allogeneic HSCT between Dec 2007 and Apr 2014 in our center. These patients comprised 38 (44.7%) who received MSDT, 29 (34.1%) MUDT, and 18 (21.2%) HIDT. Results: The median follow-up was 30.0 months. Over all, the median overall survival (OS) was 60.2 months and the probabilities of OS at the first, second and fifth year were 63%, 57% and 48%, respectively. Median OS post transplant (OSPT) was 57.2 months and the probabilities of OSPT at the first, second and fifth year were 58%, 55% and 48%, respectively. Relapses occurred in 16 patients (18.8%), and the cumulative incidence of relapse at the first, second and third year were 14%, 23% and 27%, respectively. The survival of patients receiving non-MSDT was superior to that of MSDT, median OSPT being 84.0 months and 23.6 months, respectively (P=0.042); And the similar result was observed when we analyzed the OS of patients who underwent non-MSDT or MSDT (median OS: 120 months vs. 27.0 months; P=0.028). We also found that using antithymocyte globulin (ATG) in conditioning regimens significantly improved survival after non-MSDT, with better OS and OSPT (P=0.016 and P=0.025). Furthermore, we compared OS or OSPT of patients who received non-MSDT with ATG (n=38) and MSDT without ATG (n=37). Our results showed that using ATG in conditioning regimen significantly improved survival of non-MSDT, with better OSPT (median OS: 84.0 months vs. 23.0 months; P=0.026) and OS (median OS: 120 months vs. 25.1 months; P=0.016). Conclusions: These data suggest that, non-MSDT could be a valid alternative when MSDT is not available, and ATG may improve the survival of MDS patients after non-MSDT. Disclosures No relevant conflicts of interest to declare.

Antithymocyte Globulin-Based Prophylaxis for Graft Versus Host Disease Compared to Post-Transplant Cyclophosphamide-Based Prophylaxis in Matched Unrelated Donor Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2307-2307
Author(s):  
Sara Redondo Velao ◽  
Mi Kwon ◽  
Diana Champ ◽  
MJ Pascual Cascon ◽  
Pascual Balsalobre ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Cumulative Incidence ◽  
Antithymocyte Globulin ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis

Abstract INTRODUCTION Post-transplant high-dose cyclophosphamide (PTCy) has shown to prevent graft versus host disease (GvHD) after haploidentical allogeneic hematopoietic cell transplantation (HSCT). Although less extended, its use after matched unrelated donor (MUD) HSCT in combination with additional immunosuppression has been encouraging. The aim of this study was to analyze and compare outcomes of antithymocyte globulin based (ATG) versus PTCy-based GvHD prophylaxis in matched unrelated donor HSCT. MATERIAL AND METHODS We retrospectively analyzed 51 MUD (8/8 HLA-matched) transplants performed in two Spanish centers: 25 received ATG-based prophylaxis and were performed from 2010 to 2013, and 26 received PTCy-based prophylaxis and were performed from 2013 to 2016. RESULTS Characteristics of patients and post-HSCT complications are detailed in Table 1. There were no significant differences in age, gender, diagnosis and Disease risk index. For the ATG group, conditioning regimen consisted of fludarabine combined with busulfan (80%) or melphalan (12%), and TBI plus cyclophosphamide (8%). All patients received ATG 2 mg/kg from day -4 to day -2 followed by methotrexate and cyclosporine (CsA). Conditioning regimen for patients from the PTCy group consisted of fludarabine and busulfan (85%) and thiotepa combined with busulfan and fludarabine (15%). GvHD prophylaxis consisted of PTCy 50 mg/kg on days +3 and +4, combined with: CsA plus MMF in 57%, CsA alone in 31%, or tacrolimus plus MMF or sirolimus in 8%, and tacrolimus alone in 4%. With a median follow-up of 58 months for the ATG group and 12 months for the PTCy group, there were no statistically significant differences in overall survival at 18 months (56% vs 85%, p=0.08), in event free survival (56% vs 68%, p=0.5), and in cumulative incidence of relapse (12% vs 18%, p=0.3). Non-relapse mortality at 12 months was significantly higher in the ATG group (32% vs 10%, p = 0.04). The ATG group presented more cases of hepatic toxicity grades I-IV and hemorrhagic cystitis than PTCy group (Table 1). Cumulative incidence of acute GvHD grades II-IV was higher in the ATG group as well as acute GvHD grades III-IV, with no differences in moderate/severe chronic GvHD incidence (Figure A). CONCLUSION In our experience, albeit differences in follow-up and limited number of patients, we conclude that PTCy combined with additional immunosuppression after MUD allogeneic HSCT offers lower rates of acute GvHD together with less toxicity and non-relapse mortality compared to ATG-based prophylaxis. Further analysis including larger series and follow-up are needed to confirm these observations. Disclosures No relevant conflicts of interest to declare.

Comparison of Outcomes After Allogeneic HSCT for Adult Patients with AML in Remission Using in the Conditioning Regimen Either I.V. Busulfex (BU) Plus Cyclophosphamide (Cy) or TBI Plus Cy: An- ALWP-EBMT Survey.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 195-195
Author(s):  
Arnon Nagler ◽  
Myriam Labopin ◽  
Avichai Shimoni ◽  
Liisa Volin ◽  
Donald W. Bunjes ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Post Transplantation ◽  
Allogeneic Hsct ◽  
Reduce Relapse Rate ◽  
Conditioning Regimens ◽  
Wbc Count ◽  
Transplantation Outcomes

Abstract Abstract 195 TBI/CY and oral (p.o) Bu/Cy are the traditional allogeneic HSCT (alloHSCT) myeloablative conditioning regimens for adults with AML with comparable survival and relapse probabilities. Intravenous (i.v.) Bu in contrast to p.o Bu has more predictable pharmacokinetics and a more favorable toxicity profile. Post transplantation outcomes with i.v. Bu/Cy, thus, may be superior to those achieved with TBI/Cy. In order to address these issues, the ALWP of the EBMT performed a survey comparing i.v. Bu/Cy to TBI/Cy as conditioning regimen for adult pts. with AML undergoing alloHSCT. Overall, 603 alloHSCT were analyzed. One hundred pts. underwent alloHSCT with Bu/Cy while 503 with TBI/Cy. Age was 41 (range, 18–57) and 41 (range, 16–61) years and median transplant year was 2004 (2000 – 2005) and 2003 (2000 – 2005) for the Bu/Cy and TBI/Cy groups, respectively. Disease status at alloHSCT were CR1 – 81% vs. 78% and CR2–19% vs. 22% for the Bu/Cy and TBI/Cy groups, respectively. WBC count at diagnosis was 11×109/L and 15×109/L, respectively. Regarding the cytogenetic classification, 10% and 10% were good, 60% and 55% were intermediate and 9% and 6% were poor risk, respectively (data were NA for 21%–26% of pts). Sixty nine percent and 68% of both groups underwent alloHSCT from sibling donors, while 31% and 32% from MUD, respectively. Length of follow up was 37(15–86) and 57 (1–105) months for both groups, respectively. Sixty nine percent and only 41% of the Bu/Cy and TBI/Cy groups received PB, while 31% and 59% received BM grafts, respectively (p<0.0001). Engraftment was similar in the Bu/Cy vs. the TBI/Cy groups, 95% and 96%, respectively. Cumulative incidence of TRM at 2y was 17+4% and 23+2%, respectively (p=0.23). Acute GVHD (II–IV) was also similar between the 2 groups, 28% and 32%, respectively. Two year relapse incidence was 30+5% and 22+2% for Bu/Cy vs. TBI/Cy, respectively (p=0.03) while LFS was comparable 57+5% and 61+2%, respectively (p=0.5). In multivariate analysis Cy/TBI was found to be an independent good prognostic factor for reduce relapse rate (p=0.03, HR-1.67) and there was a trend for higher TRM (p=0.16). Poor prognostic factors for LFS and TRM were age >40y, disease status (CR2 vs. CR1) and MUD vs. Sib. donor. In conclusion, in this retrospective EBMT survey outcomes of alloHSCT in adult pts. with AML in CR using either i.v Bu/Cy or TBI/Cy were comparable. Disclosures: No relevant conflicts of interest to declare.

Matched Unrelated Donor Transplantation Is Curative In Selected Patients with Diffuse Large B Cell Lymphoma: A Report of the Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 363-363 ◽  
Author(s):  
Irit Avivi ◽  
Carmen Canals ◽  
Jian Jian Luan ◽  
Gerald. G. Wulf ◽  
Arnon Nagler ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Conditioning Regimen ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Unrelated Donor ◽  
Refractory Disease ◽  
Matched Unrelated Donor ◽  
Matched Sibling

Abstract Abstract 363 Matched unrelated donor stem cell transplantation (MUD-SCT) has recently become a therapeutic option for patients with B cell diffuse large cell lymphoma (DLBCL) who fail other conventional therapies and do not have a matched sibling donor available. We present retrospective data of 473 DLBCL patients, 285 males and 188 females, aged 18 to 69 years (median 46 years), treated with matched sibling (n=301) or matched unrelated (n=172) SCT between January 2000 and December 2007 and reported to the EBMT registry. Median time from diagnosis to allograft was 25 months (range 2 – 203). Fifty-seven percent of the patients had failed previous autologous SCT, and 12% were transplanted in chemorefractory disease. After a median follow up of 41 months, the estimated 3-year non-relapse mortality (NRM), relapse rate (RR), progression free survival (PFS) and overall survival (OS) for the whole series were 37%, 32%, 31% and 40%, respectively. There were no statistically significant differences in patient age, disease status at transplantation, stem cell source and intensity of conditioning regimen between the Sib and the MUD cohorts (summarized in Table 1).However, a higher number of patients undergoing MUD have already failed an autograft (66% vs 52%, p=0.004), and T cell depleted grafts were more frequently used in the MUD cohort. Acute GvHD occurred in 48% of patients treated with a sib allograft vs 54% in those receiving a MUD (p=n.s). Interestingly, there were no statistically significant differences in NRM and RR between the Sib and the MUD groups (3 yr NRM=38% vs 37%, RR approached 38% vs 34%), resulting in a similar 3-year PFS and OS (32% vs 29% and 42% vs 35%, respectively). Multivariate analysis identified refractory disease (p = 0.001, RR 3.2; CI=1.3-3.5), poor performance status (p = 0.017, RR 1.9; CI=1.1-3.4) and age at transplantation > 50 years (p = 0.015, RR1.5; CI=1.1-2.1) as independent adverse prognostic factors for NRM and time from diagnosis to SCT < 36 months (p = 0.02, RR 1.5; CI=1.1-2.1), a previously failed autologous SCT (p = 0.026, RR .4; CI=1.1-1.9), refractory disease (p = 0.003, RR 2; CI=1.3-3.1), poor performance status (p = 0.0001, RR 3.5; CI=2.1-5.6) and T cell depletion (p = 0.001, RR 2; CI=1.3-2.9) as adverse prognostic factors for RR. A previous autologous SCT, poor performance status and refractory disease at transplantation were found to be significantly associated with a shorter PFS (p=0.04, RR 1.3; CI=1-1.6; p=0.0001, RR 2.4; CI=1.6-3.4; p=0.000,RR 2.1; CI=1.5-2.9, respectively) and refractory disease (p=0.0001, RR 2.2; CI=1.6-3.1) and poor performance status at the time of SCT (p=0.0001, RR 2.5; CI=1.7-3.6) with a shorter OS. Patients allografted from MUD tended to have a slightly increased risk of overall mortality in multivariate analysis, but this was not statistically significant (p=0.06, RR 1.2; CI=0.95-1.6). In conclusion, MUD SCT provides a curative option, not significantly inferior to that obtained with a matched sibling transplant, for selected patients with DLBCL who have failed conventional therapies, including autograft. Similarly, the type of conditioning regimen was not found to have a significant impact on patient outcome. Table 1. Clinical characteristics Sib vs MUD Sib (n = 301) MUD (n= 172) p Age (median, years) 46 45 N.S. Previous ASCT 48% 33% 0.004 Refractory disease 12% 12% N.S. Poor P.S. 13% 7% 0.06 RIC/CC 57%/43% 56%/42% N.S. SC source BM/PB 20%/80% 22%/78% N.S. ATG/ALG 15% 46% <0.001 in vivoüT-cellüdepletion 12% 20% 0.03 ex vivoüT-cellüdepletion 5% 12% 0.03 ASCT. Autologous stem cell transplantation; PS. Performance status; RIC. Reduced intensity conditioning; CC. Conventional conditioning; SC. Stem cell; BM. Bone marrow; PB. Peripheral blood; ATG/ALG. Anti-thymocyte globulin/ALG. Anti-lymphocyte globulin. Disclosures: No relevant conflicts of interest to declare.

Treatment of Relapsed AML and MDS After Allogeneic Stem Cell Transplantation: A Second Transplant From a Different Donor May Be the Most Effective Option

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1963-1963
Author(s):  
Avichai Shimoni ◽  
Noga Shem-Tov ◽  
Yulia Volchek ◽  
Ronit Yerushalmi ◽  
Arnon Nagler
Keyword(s):  
Supportive Care ◽  
Median Time ◽  
Patient Group ◽  
Cumulative Incidence ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Matched Sibling ◽  
Relapsed Disease ◽  
Better Than

Abstract Abstract 1963 Salvage Therapy with Azacitidine Increases therapy for patients (pts) with AML and MDS. However, relapsed disease continues to be the most common reason for treatment failure. There is no standard treatment for relapsed disease after SCT. Treatment options range from supportive care alone to chemotherapy and donor lymphocyte infusion (DLI) and up to a second SCT from the same or a different donor. However, the most effective therapy is controversial and treatment results are often poor. We retrospectively analyzed the outcomes of 475 adult pts with AML (n=378) and MDS (n=97) given allogeneic SCT in a single institution over a 12 year period. The median age of this patient group was 54 years (range, 17–76), 279 men, 196 women. The donor was an HLA-matched sibling (n=246), 1-antigen mismatched related (n=10), or matched unrelated (n=219). Disease status at SCT was early (n=186), intermediate (n=87) or advanced (n=202) by CIBMTR criteria. The conditioning regimen was myeloablative (MAC, n=123), reduced-intensity (n=121) or reduced toxicity MAC (RTC, n=231).With a median follow-up of 40 months (range, 2 months – 12 years), 210 pts are alive, 103 died of non-relapse causes (NRM), 193 relapsed and 162 of them died. The cumulative incidence of relapse was 44% (95%CI, 39–49) and advanced disease at SCT was the only predicting factor for relapse, HR 2.3 (p< 0.001). Pts were given supportive care or low-dose chemotherapy alone (n=70), intensive chemotherapy ± DLI (including SCT from the same donor, n=99) or a second SCT from a different donor (n=24). In all, the median overall survival (OS) was 2.8 months, and the 2-year OS was 12% (95% CI, 7–17%). Among the 24 pts having a second SCT from a different donor, the median age at second SCT was 50 years (19–78). 18 pts were initially given SCT from a matched sibling, 12 were re-transplanted from a second sibling and 6 from an unrelated donor. Six pts were initially transplanted from an unrelated donor and re-transplanted from a different unrelated donor. The initial conditioning regimen was MAC (n=10), RTC (n=11) or RIC (n=3). The second regimen was most often fludarabine and treosulfan (FT, n=14) for those not previously given treosulfan, including all previously MAC recipients. Other regimens were fludarabine and busulfan (n=6) or FLAMSA (n=4). The median time from the first SCT to relapse was 14 months (2 months – 9 years), 6 within 6 months. The median time from first relapse to second SCT was 3 months (range, 1–41 months). 9 pts were in remission at second SCT with prior therapy, 9 were chemo-refractory, and 6 were re-transplanted with no attempts of re-induction. The median follow-up of surviving pts is 16 months (range, 2–74). 22 pts engrafted in a median of 13 days (range, 9–26). 2 pts died early from infections and 2 from GVHD and the cumulative incidence of NRM was 17% (95%CI, 7–42). 11 pts relapsed after second SCT, cumulative incidence 52% (95%CI, 34–79) 8 of them died. The estimated 2-year OS is 40% (95%CI, 16–63) and the 2-year disease-free survival is 31% (95%CI, 11–51). Pts re-transplanted in chemo-sensitive or untreated relapse had a better outcome than those with chemo-refractory relapse, 2 year OS 57% and 13%, respectively (p=0.02). Pts given FT for second SCT also fared better than the other regimens, 2-year OS 63% and 13%, respectively (p=0.02). 2 of 6 pts with relapse less than 6 months after SCT are long-term survivors after second SCT. The outcomes after second SCT seem better than the 12% 2 year OS of the entire relapsing patient group. To minimize the time bias of pts been able to have a second SCT, we compared their outcomes to the subgroup of 68 pts who were alive at least 3 months after relapse and theoretically been able to have a second SCT from a different donor. 14 pts in this subgroup are alive with an estimated 2-year OS of only 15% (95%CI, 4–22, p=0.02). Among these 68 pts, 37 achieved remission with re-induction, and were alive at least 3 months after relapse, and their 2-year OS was 26%, which is also inferior to the 2-year OS of 57% in pts re-transplanted in sensitive or untreated relapse (p=0.05). In conclusion, a second SCT from a different donor is feasible in a subset of pts with AML and MDS relapsing after SCT. Toxicity with the new RTC regimens, such as treosulfan-based is acceptable. This is a promising option for pts able to be successfully re-induced or re-transplanted early with a pre-identified second donor. These observations merit further confirmation in larger studies. Disclosures: No relevant conflicts of interest to declare.

Efficacy and Safety of Unrelated Cord Blood Transplantation in Patients with Acquired Refractory Aplastic Anemia: A Phase II Study on Behalf of Eurocord and the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2671-2671 ◽  
Author(s):  
Régis Peffault de Latour ◽  
Sylvie Chevret ◽  
Charlotte Jubert ◽  
Anne Sirvent ◽  
Claire Galambrun ◽  
...  
Keyword(s):  
Phase Ii ◽  
Research Funding ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Blood Transplantation ◽  
Grade Ii ◽  
One Year

Abstract Background: While therapeutic outcomes in patients (pts) with acquired severe aplastic anemia (SAA) has greatly improved in recent years, results remain poor for pts who are refractory to first-line immunosuppressive therapy (IST) and lack a matched unrelated donor. We conducted a prospective multi-center phase II uncontrolled trial to assess the efficacy and safety of cord blood transplantation (CBT) in refractory SAA pts (NCT 01343953). Patients and methods: Pts with SAA refractory to IST with anti-thymocyte globuline (ATG) and ciclosporin (CsA) were eligible in case of no existing matched unrelated donor but available one or two unrelated CB units containing alone or both together more than 4 x 107/Kg frozen nucleated cells/Kg (no more than 2 out of 6 HLA mismatches allowed between each CB unit and the pts). Pts with isolated bone marrow cytogenetic abnormality (absence of morphologic evidence of myelodysplastic syndrome) were also eligible. The conditioning regimen consisted of fludarabine 30mg/m2 (D-6 to D-3), cyclophosphamide 30mg/kg (D-6 to D-3), ATG (thymoglobulin) 2.5mg/kg at D-3 and D-2 (5mg/Kg total dose) and total body irradiation (2 Gray) on D-2. All pts received one injection of anti-CD20 (150 mg/m2) to prevent EBV reactivation (D+5). CsA was given alone as prophylaxis for graft versus host disease (GVHD). The trial used the Fleming's Single Stage Phase II Design, with sample size computed to demonstrate an improved overall survival (OS) rate at one year from 20% up to 50%, with type I and type II error rates set at 0.05. A minimum sample of 25 pts was required, with a minimum number of 9 pts alive at one year needed to indicate treatment efficacy. Secondary endpoints included cumulative incidences (CumI) of engraftment, acute and chronic GVHD (aGVHD and cGVHD), infections, relapse and late cause of death. Results: 29 pts were included between June 2011 and October 2015. One pt was diagnosed with dyskeratosis congenita and a matched unrelated donor was identified for another pt between inclusion and anticipated date of CBT (exclusion criteria). One pt died before CBT due to a septic shock (D+4 after inclusion). Analyses were conducted in the remaining 26 pts. Median time between SAA diagnosis and CBT was 12 months (interquartile range (IQR) 8.7 to 17.8). All pts received at least one course of IST before CBT (2 courses, n=8). Twenty-three pts received 20 or more transfusions before CBT. BM karyotyping showed 2 pts respectively with monosomy 7 in 4 and 15 mitoses as well as one pt with trisomy 8 in 4 mitoses before CBT. Eight pts (31%) have a PNH clone (median 4.5% [IQR: 3.1-9.7]). Median age at time of CBT was 16 years (IQR 8.25 to 23) and median follow-up is 13.2 months (IQR 4.1 - 23.5). Three out of 26 pts incorrectly received twice the dose of ATG (10mg/Kg total dose) due to protocol violation. Sixteen pts received one CB and 10 received two CB units. Median number of nucleated cells infused was 3.7 x 107/Kg (IQR, 3-4.9) and CD34+ cells infused was 1.4 x 105/Kg (IQR, 1.0-1.9). Myeloid engraftment occurred in 23 pts, with a 60 day-CumI of neutrophil engraftment of 88.5% with full chimerism for all of them. Three pts did not engraft (2 deaths at D71 and D92 and one successful second HSCT). The 100 day-CumI of grade II-IV acute GVHD was 40% (95% CI, 20-60) (8 grade II; 0 grade III; 2 grade IV). Among the 23 pts alive at day 100, five developed cGVHD leading to a one-year CumI of cGVHD at 27% (95% CI, 7-47) (severe cGvHD in 2 pts). During follow-up, 8 pts experienced a total of 18 grade III infections with a 6-month CumI of 32% (95% CI, 13-51). None of the pts presented post-transplant EBV-related lymphoproliferative disorder. Immune reconstitution is shown in Figure 1. Three pts died before 1 year due to non-engraftment (n=2) and infection (n=1, one of those who received twice the dose of ATG). With 23 pts alive at 1 year, the primary objective of the study was thus reached. The one-year treatment related mortality (TRM) was 15% (95%CI, 4-35). One additional pt who had also received twice the dose of ATG died (severe cGvHD) after one year (at 13.6 months), resulting in a 14-month OS of 81% (95%CI, 66-100) (Figure 2). Conclusion: CBT with at least 4 x 107/Kg frozen nucleated cells/Kg after a FLU-CY-TBI-ATG conditioning regimen gave rise to very encouraging results in this particular high risk SAA refractory population. Pediatric and young adult SAA pts who are refractory to first-line IST should now be considered either way for matched unrelated donor or CBT. Disclosures Peffault de Latour: Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria, Research Funding; Amgen: Research Funding.

Long Term Follow up of Two Randomized Trials on Antithymocyte Globulin (ATG) for GVHD Prophylaxis in Unrelated Donor Transplants: Chronic GVHD, Bronchiolitis and Quality of Life.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 438-438
Author(s):  
Andrea Bacigalupo ◽  
Maurizio Vignola ◽  
Teresa Lamparelli ◽  
Paolo Bruzzi ◽  
Stefano Guidi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Antithymocyte Globulin ◽  
Randomized Trials ◽  
Chronic Gvhd ◽  
Prospective Trial ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
One Year

Abstract Background . We have reported that rabbit antithymocyte globulin (ATG Sangstat-Genzyme) prevents acute and chronic graft versus host disease (GvHD) in patients undergoing an unrelated donor transplant (Blood2001; 98 (10): 2942–2947). Patients had entered two consecutive randomized trials: in trial-1, 54 patients were randomized to non-ATG (n=25) or 7.5mg/kg rabbit ATG (n=29). In trial-2, 28 patients were randomized in the non-ATG arm and 27 in the ATG 15mg/kg arm. Aim of the study: to assess the risk of extensive chronic GvHD, bronchiolitis obliterans , quality of life, survival and transplant related mortality (TRM) 4 years later. Patients. Seventy five patients survived 100 days after BMT, and were available for analysis : in trial-1 there were 20 patients per arm, in trial-2 there were respectively 18 and 17 patients. The median follow up was 7.4 years for trial-1 and 5.3 years for trial-2. Each patients was updated and assessed for survival, chronic GvHD, for bronchiolitis , relapse of the original disease and quality of life. Results. Results are given in percentage, in the order non-ATG vs ATG patients. At last follow up chronic GvHD (limited+extensive) was scored in 74% vs 33% respectively for non-ATG and ATG of patients in trial 1 (p=0.01) and in 61% vs 29% in trial-2 (p=0.06): when the two trials are combined cGvHD is scored in 68% vs 31% of non-ATG vs ATG patients (p=0.002). Extensive chronic GvHD was scored in both trials in 35% and 13% of patients (0.03). Bronchiolitis was present at last follow up in trial-1 in 50% vs 0% (p=0.01), and in 33% vs 8% in trial-2 (p=0.1). Combined data show bronchiolitis in 40% vs 4% of non-ATG vs ATG patients (p=0.002). Median timing of bronchiolitis was 1155 days. When patients developed bronchiolitis, the mortality was high (50%). Quality of life was assessed by looking at proportion of patients with Karnowski score of 100% at last follow up: the proportion was 37% vs 91% patients in trial-1 (p=0.02), it was 75% vs 100% patients in trial-2 (p=0.2) and overall in 56% vs 95% of all non-ATG vs ATG patiens (p=0.007). Relapse related deaths were 13% in the non-ATG and 11% in the ATG group. Survival: the actuarial survival at 5 years in trial-1 is 48% vs 53% (non-ATG vs ATG) and in trial-2 30% vs 41%. The actuarial TRM is 48% vs 40%, and in trial-2 it is 62% vs 47% (non-ATG vs ATG patients). Actuarial 5 year TRM in patients surviving one year (late TRM) is 28% vs 4% (p=0.02). Conclusions. This updated analysis of two randomized GITMO trials, confirms with longer follow up, that ATG pre-transplant produces (1) a significant reduction of chronic GvHD (from 68% to 31%) and (2) a significant reduction of extensive chronic GvHD (from 35% to 13%). As a consequence quality of life is significantly improved in ATG patients. This study also shows that ATG reduces the risk of chronic bronchiolitis (from 40% to 4%), and late TRM (beyond one year) (from 28% to 4%). These data give strong support for the inclusion of ATG in the conditioning regimen of unrelated transplants: dosing and timing should be considered (Blood2003; 102 (11); 242a) and could be tested in a prospective trial. This work was supported by Fondazione CARIGE, GENOVA

Genoidentical Donor Versus A, B, Cw, DR, DQ, HLA Allelic-Matched Unrelated Donor for Stem Cell Transplantation in Patients with Standard Risk Haematological Malignancy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 976-976 ◽  
Author(s):  
Ibrahim Yakoub-Agha ◽  
Jean-Michel Boiron ◽  
Mauricette Michallet ◽  
Noel Milpied ◽  
Jean-Henri Bourhis ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Sibling Donor ◽  
Significant Difference ◽  
Matched Sibling ◽  
Standard Risk

Abstract To compare outcome of pts with standard risk hematological malignancy undergoing allogeneic stem cell transplantation (allo-SCT) from either allelic A, B, Cw, DR and DQ HLA-matched unrelated (so called 10/10) or HLA-matched sibling donor, we conducted a prospective study including 12 French BMT centres. Between 01/2000 and 12/2002, 236 consecutive pts were enrolled. Fifty five pts received unrelated allo-SCT (pheno-group) and 181 received genoidentical allo-SCT (geno-group). Conditioning regimen associated TBI and Cy in all pts. Pts who received ATG with conditioning were excluded. GVHD prophylaxis consisted on Cs-A plus MTX. Diagnoses of the underlying disease were, AL (n=175) of whom 47 were in CR > 1; CML (n=43) of whom 4 were with accelerated phase and myelodysplastic syndrome (n=18) of whom 11 with untreated disease. The analyses were performed at the reference date of december 31th 2003. The two groups were comparable in terms of patients’ initial characteristics. However, pts of pheno-group were slightly younger and had more often CML whereas those belonging to geno-group had more often acute leukemia in 1st remission . At the date of analysis, the median follow-up was 955d (373–1398). The overall survival was 63% and 52,5% (p=NS) for geno and pheno-group, respectively. Furthermore, the statistical power was insufficient to demonstrate an equivalence of the two survival curves.. Although, the occurrence of acute GVHD of grade ≥2 was statistically higher in pheno-group (67% vs 52%, p=0.0), there was no significant difference en term of TRM between the two groups (27% vs 33% for geno and pheno-group, respectively). Relapse rates were 20% vs 26% and ultimately EFS (56% vs 52%) for geno and pheno-group. In multivariable analysis, only age (>36 years) and positive-CMV serology of recipient were found to adversely influence EFS. Finally, there was no demonstration of an independent prognostic value of the donor origin on outcome. In conclusion, although, the equivalence was not fully demonstrated between the two groups, these preliminary results of allo-SCT from 10/10 HLA-matched unrelated donor compare favourably to those obtained with HLA-matched sibling donor in patients with standard risk haematological malignancies.

Results of Haematopoietic Stem Cell Transplantation (HSCT) for Hurler’s Syndrome: European Experience 1994–2004.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 402-402 ◽  
Author(s):  
Jaap Jan Boelens ◽  
R. Wynn ◽  
A. O’Mearra ◽  
P. Veys ◽  
M. Cavazzana-Calvo ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Donor Chimerism ◽  
Stem Cell Source ◽  
Cell Source ◽  
Conditioning Regimens ◽  
Hurler’S Syndrome

Abstract Worldwide more than 400 patients with Hurler’s syndrome (HS), characterized by severe neurodegeneration, cardiac disease, skeletal abnormalities and death in early childhood, have undergone allogeneic-HSCT since 1980. Although, long term follow up of successfully transplanted children is very encouraging, the engraftment and survival results are very variable between the various studies, ranging from less than 25% up to more than 85%. We retrospectively analyzed the results of 146 patients transplanted in Europe from 1994–2004, to assess: 1) the effect of conditioning regimen and grafts (-manipulation) used on the “alive and engrafted” rate and 2) the transplantation-related morbidity/mortality. HSCT with a family donor was performed in 52 patients. An unrelated donor was used in 94 patients. The majority of patients received marrow (n=103). The rest received cordblood (n=23) or peripheral blood (n=20). Twenty-eight patients received a T-cell depleted (TCD) graft. Conditioning regimens used were grouped as follows: busulfan-cyclofosfamide 200mg/kg (n=68), busulfan- with high dose cyclofosfamide (either 240mg/kg or 260mg/kg; n=41), fludarabine-based myelo-ablative (n=19) and reduced intensity conditioning regimens (RIC: n=18). Fourteen patients received dose-adjusted busulfan. Engrafted was defined as a donor chimerism of more than 10%, and an alpha-L-iduronidase level of more than the lower limit of normal for the heterozygote individuals (&gt;4.5 nmol/hr/mg). The “alive and engrafted” rate after first transplantation and overall “alive and engrafted” rate after one to three transplantations was 83/146 (57%) and 111/146 (76%), respectively. The median follow up was 39 mth (5–120mths). Multivariate analysis (confounders: age, sex, heterozygote donor, unrelated donor, stem cell source, HLA-disparity, conditioning regimen, TCD and busulfan targeting) on the primary endpoint “alive and engrafted” showed that RIC (RR 13,4: 2,6–67,1) and TCD (RR 5,7: 1,14–28,4) are individual risk factor for graft failure. Busulfan targeting suggests to be an individual protective factor (RR 0,27; 0,04–1,8); 12/14 (86%) were “alive and engrafted” after 1st HSCT. Thirthy three patients received a 2nd graft, of whom 26/33 (82%) are alive and engrafted: 16/21 using the same, 10/12 using a different donor, and 16/19 after myeloabaltive, 10/14 after RIC. Two of the 3rd HSCTs were successful. After 1st HSCT moderate to severe aGvHD (grade ≥2) occurred in 23/146 (16%) patients. Extensive cGvHD was seen in 2/114 (1.4%) patients, only. IPS/DAH was seen in 4/134 (2.3%) patients and VOD in 12/134 (9%) patients. Main cause of death (n=28) was infectious (n=15: mainly viral). Other causes of death: GvHD (n=3), Cardiac ECI (n=2), VOD (n=2), DAH (n=1), unknown (n=1), Hurler (n=4). The majority of the “alive and engrafted” patients have a donor chimerism of &gt;95% (91/111; 82%), 11/111 (9,9%) between 75–95%, 6/111 (5,4%) between 50–75% and 3/111 (2.7%) between 10–50%. In summary, no stem cell source (BM, cordblood and PBSC) is superior and no conditioning regimen used is superior. RIC and TCD results in inferior engraftment rates. Second HSCTs are successful in more than 80%. Relatively low morbidity rates are seen. The engraftment of HSCT for HS can be optimized by avoiding T-cell depletion, RIC and probably by busulfan-targeting.

Similar Outcome of Upfront Unrelated and Matched Sibling Donor Hematopoietic Stem Cell Transplantation in Idiopathic Aplastic Anaemia of Childhood and Adolescence: A Cohort Controlled Study on Behalf of the UK Paediatric BMT WP, of the PD WP and of the SAA WP of the EBMT

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 256-256
Author(s):  
Carlo Dufour ◽  
Marta Pillon ◽  
Elisa Carraro ◽  
Neha Bhatnagar ◽  
Rob Wynn ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Recurrence ◽  
Controlled Study ◽  
Unrelated Donor ◽  
Childhood And Adolescence ◽  
Sibling Donor ◽  
Matched Sibling ◽  
Median Interval

Abstract The classical treatment algorythm of idiopathic severe aplastic anemia (SAA) forsees, if a sibling donor is not available in the family, a first line option represented by immunosuppressive therapy (IST) with ATG and Cyclosporine A (CsA). IST provides a very good survival rate but a fairly high rate of failures (no response, relapse, need for transplant). This is particularly important in childhood and adolescence where faulty hematopoiesis represents a relevant limitation of quality of life. The option of haematopoietic stem cell transplantation (HSCT) from matched unrelated donor (MUD) as front line treatment with no prior failed IST, has never been investigated so far. This study provides for the first time the outcome analysis of 29 consecutive SAA patients who received an upfront unrelated donor HSCT without prior IST, in 9 UK Centres and compares each of these patient with 3 matched controls from the data base of the SAAWP of the EBMT who, in a similar time-span, underwent Matched Sibling Donor (MSD) HSCT. Twenty four patients received HLA-A,-B,-C,-DQ-,-DRB1 matched MUD HSCTs whilst 5 received single antigen/allele Mismatched Unrelated Donor (MMUD) grafts. The conditioning regimen was FCC (Fludarabine, Cyclophosphamide and Alemtuzumab) with the addition of low dose (3cGy) TBI for the MMUD HSCTs. GVHD prophylaxis was with CsA +-Mycophenolate. The primary endpoints were overall survival (OS) and event free survival (EFS). Events were death, disease recurrence, second HSCT, clinical PNH and post-transplant malignancies. Complete remission (CR) was defined as Hb > 10 g/dl, neutrophil count > 1x 109/l and platelet count > 100x109/l. The 87 (3 for each MUD/MMUD HSCT) patients from the EBMT data base who underwent MSD HSCT as first line treatment were matched to the upfront MUD/MMUD cohort by age, gender, time from diagnosis to HSCT and source of stem cells. Their median follow-up was 1.6 years (range 0.01-9.39). In the upfront MUD/MMUD cohort there were 12 males (41%) and 17 females (59%). Median age at HSCT was 8.46 years (range 1.73-19.11), 72% was aged below and 28% above 12 years; median interval from diagnosis to HSCT was 0.39 years (range 0.19-1.35) with 72 % receiving bone marrow and 28% peripheral blood stem cells. The median follow-up was 1.7 years (range 0.19-8.49). The median time to neutrophil recovery (>0.5 x 109/l) was 18 days (range 9-29) and the median time to platelet recovery (>50 x 109/l) was 19 days (range 10-40). The 100 day cumulative incidence (CI) of grade II-IV acute GVHD was 10 ± 6% ; there was only one case of grade III-IV acute GVHD (frequency of 3.5%). The 1 year CI of chronic GVHD was 19 ± 8%. There were 5/29 cases (frequency of 17,2 %), 4 in the MUD and 1 the MMUD subset. Chronic GVHD was limited in all cases and restricted to skin. There were only 2 events in this cohort; one primary graft failure following a HLA-A MMUD HSCT who has now successfully received a second HSCT and one death due to idiopathic pneumonia syndrome. No post-treatment malignancies occurred at last follow-up. The other 27 patients are in CR at last follow-up. The median interval diagnosis-neutrophil recovery was similar in MUD/MMUD (0.39 years; range 0.19-1.35) vs MSD transplants (0,31 years; range 0,1- 0,45) (p=0.93). The 2 year OS was 96%±4% in the upfront MUD/MMUD cohort vs 91%±3% of the MSD cohort (p=0.30). The 2 year EFS was 92%±5% in the upfront cohort vs 87%±4% in MSD (p=0.37) (Fig 1). The 2 year CI of rejection was 4%±4% in the MUD/MMUD vs .1%±1% in the MSD group (p=0.48). This is the first controlled study indicating that in idiopathic SAA of childhood and adolecence upfront MUD/MMUD HSCT using FCC as conditioning regimen, has similar outcome to MSD HSCT. MUD HSCT may be considered a feasible and successful treatment option when children lack a MSD and a MUD is readily available. Figure 1 Figure 1. Comparison of EFS between upfront MUD/MMUD and front-line MSD HSCT. Events were: death, disease recurrence, second HSCT, clinical PNH and post-transplant- malignancies. Table 1 EFS N events 2-yrs Pr (%) (SE) p-value MUD/MMUD 29 2 92 (5) 0.37 MSD 87 11 87 (4) Disclosures Dufour: Pfizer: Consultancy.

Related or Unrelated Donor Results in Similar Outcomes after Hsct; Single Center Experience in Colombia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5512-5512
Author(s):  
Virginia Abello ◽  
Carmen Rosales ◽  
Manuel Rosales ◽  
Javier Figueroa ◽  
Iris Cordoba ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Developed Countries ◽  
Rank Test ◽  
Time Interval ◽  
Unrelated Donor ◽  
Fisher Exact Test ◽  
Late Time ◽  
Single Center

Abstract INTRODUCTION ASTC is the standard treatment in multiple hematologic diseases; unfortunately most patients do not have a compatible family donor, URD ASCT is an alternative to those patients. There is evidence from developed countries that outcomes may be similar regardless the donor, but there is not enough information from Latin America regarding survival after URD ASCT. We compared survival at 1 and 3 years from patients transplanted using related or unrelated donors in a single center in Colombia. MATERIALS AND METHODS Paired analysis was performed comparing one URD ASCT with one or two RD ASCT with similar characteristic in terms of age, diagnosis (AML, ALL, aplasia, CML, MDS), EBMT risk, year of transplant and conditioning regimen. Chi-square or Fisher exact test was used to compare the groups (p<0.05). The survival curves of Kaplan-Meier and log-rank test (p<0.05) were used to estimate the probabilities of one (OS1) and three (OS3) overall survival in different groups according to EMBT score risk. RESULTS 28 URD ASCT were performed between 2011 and 2014, 24 of those (18 matched and 6 missmatched URD ASCT) were paired with 41 RD ASCT. Of those 62% were males, mean age was 33.4 years, 70.8% patients were in early stages, almost 60% had more than 12 months interval between diagnosis and transplant. Most common diagnoses were acute lymphoid leukemia and acute myeloid leukemia. 80% of donors where found through NMDP. No significant differences in sex, age, disease status (early, intermediate, late), time interval from diagnosis to transplantation, and patient-donor sex combination, ranked according to EBMT risk score, were find between the tow groups. Median follow-up was 322 days (range 165-693), for the whole group. There were no significant differences in the OS1 or OS3 between URD o RD ASCT, in different EBMT score groups. Low risk: OS1: URD 86.6% vs RD 75.8%, p = 0.46; OS3: 86.6% vs 68.9%, p = 0.28. High risk OS1 75% vs 63.6%, p=0.92; OS3 75% vs 63.6%, p=0.92. CONCLUSIONS In this cohort of patients, the type of donor had no influence in the outcome measured in terms of OS. This is the first experience with URD ASCT in Colombia; longer follow up of this cohort is needed to confirm this results, but our findings suggest this transplantation modality is a real alternative to patients in our country in need of a transplant without an HLA identical related donor. Disclosures No relevant conflicts of interest to declare.

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