scholarly journals Comparison of outcomes after single or double cord blood transplantation in adults with acute leukemia using different types of myeloablative conditioning regimen, a retrospective study on behalf of Eurocord and the Acute Leukemia Working Party of EBMT

Leukemia ◽  
2013 ◽  
Vol 28 (4) ◽  
pp. 779-786 ◽  
Author(s):  
A Ruggeri ◽  
◽  
G Sanz ◽  
H Bittencourt ◽  
J Sanz ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Acute Leukemia ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Working Party ◽  
Myeloablative Conditioning ◽  
Blood Transplantation ◽  
Different Types

Reduced-Intensity Versus Myeloablative Conditioning for Unrelated Cord Blood Transplantation in Adults with Acute Leukemia: A Report from Eurocord, the Acute Leukemia Working Party and the Cord Blood Committee of the Cellular Therapy & Immunobiology Working Party of the European Group for Blood and Marrow Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 155-155
Author(s):  
Frederic Baron ◽  
Ruggeri Annalisa ◽  
Eric Beohou ◽  
Myriam Labopin ◽  
Guillermo Sanz ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cord Blood ◽  
Research Funding ◽  
Cord Blood Transplantation ◽  
Working Party ◽  
Myeloablative Conditioning ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Reduced Intensity

Abstract BACKRGOUND. Non-relapse mortality (NRM) is the first cause of treatment failure after unrelated cord blood transplantation (UCBT) following myeloablative conditioning (MAC). In the last decade, reduced-intensity conditionings (RIC) for UCBT have been developed with the aim of reducing NRM and allowing older patients and those with medical comorbidities to benefit from UCBT. The aim of our retrospective registry study was to compare outcomes of acute leukemia (AL) adult patients given UCBT after either RIC or MAC regimens. Regimens were classified as MAC or RIC based on EBMT criteria. PATIENTS AND METHODS. Data from 1352 adult (> 18 yrs) patients with AL (acute myeloid leukemia [AML; n=894] or acute lymphoblastic leukemia [ALL; n=458]) given a first single or double UCBT from 2004 to 2013 at EBMT-affiliated centers were included in this retrospective study. RESULTS. 518 patients were given UCB after RIC, while 834 patients were administered MAC. The most frequently used conditioning regimens combined either TBI, cyclophosphamide and Flu (TCF regimen, given in 22% of MAC vs 75% of RIC recipients, P<0.001), or thiotepa, Bu and Flu (TBF, given in 32% of MAC vs 6% of RIC recipients, P<0.001). In comparison to MAC recipients, RIC recipients were almost 2 decades older (median age 52.5 vs 33.7 yrs, P<0.001), were more often transplanted for AML (80% vs 57%, P=0.001), received more frequently 2 cord blood units (61 vs 32%, P<0.001), received more frequently units with > or = 2 HLA-mismatches (69% vs 58%, P<0.001), received more TNC (median 3.5x10E7 vs 2.9x10E7, P<0.001), and received less frequently ATG in the conditioning (23% versus 57%). Disease status at UCBT was comparable in both groups (51% of patients in CR1 and 17% >CR). Median follow-up for survivors was 25 months. In univariate analyses, in comparison to patients given MAC, RIC recipients had a similar rate of neutrophil engraftment (89.5 vs 89%, P=0.7), and a similar incidence of grade II-IV acute (34% vs 29%, P=0.1) and chronic (22% vs 26%, P= 0.22) GVHD. In contrast, at 2-yr, RIC recipients had a higher incidence of disease relapse (41 vs 24%, P<0.001) but a lower NRM (19 vs 37%, P<0.001), translating to similar leukemia-free survival (LFS, 40% vs 38%, P=0.6) but better overall survival (OS, 47 vs 42%, P=0.01) than MAC recipients (Figure 1). Further, among ALL patients, the use of TCF regimen (n=159) was associated lower NRM (21 vs 40% at 2-yr, P<0.001), lower relapse incidence (24 vs 34%, P=0.07), and better OS (63 vs 34%, P<0.001) and LFS (55 vs 27%, P<0.001). We performed separate multivariate analyses (MVA) for patients with AML and ALL. In MVA for AML patients, the use of RIC regimen was associated with a higher incidence of relapse (HR=1.6, P=0.005) but a suggestion for lower NRM (HR=0.7, P=0.1) translating to similar OS (HR=1.0, P=0.9) and LFS (HR=1.1, P=0.3). Similarly, in MVA for ALL patients, the use of RIC regimen was associated with a higher incidence of relapse (HR=2.0, P=0.002) but a lower NRM (HR=0.6, P=0.04) translating to similar OS (HR=0.8, P=0.2) and LFS (HR=1.1, P=0.5). Further, interestingly, conditioning with TCF-based regimen was associated with a lower incidence of relapse (HR=0.5, P=0.004) translating into better OS (HR=0.6, P=0.013) and LFS (HR 0.6, P=0.002) in ALL patients in MVA adjusted for conditioning intensity (RIC vs MAC). CONCLUSIONS. These data suggest that LFS and OS might be as good with RIC than with MAC in adults AL patients offered UCBT. These observations could serve as basis for future prospective randomized studies. Figure 1. Unadjusted UCBT outcomes in patients transplanted following RIC versus MAC. Figure 1. Unadjusted UCBT outcomes in patients transplanted following RIC versus MAC. Disclosures Milpied: Celgene: Honoraria, Research Funding. Sierra:Amgen: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Mohty:Janssen: Honoraria; Celgene: Honoraria. Schmid:Neovii: Consultancy; Janssen Cilag: Other: Travel grand.

scholarly journals Outcomes of Graft Failures after Umbilical Cord Blood Transplantation in Acute Leukemia: A Study from Eurocord and the Acute Leukemia Working Party of the EBMT

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 661-661
Author(s):  
Frederic Baron ◽  
Annalisa Ruggeri ◽  
Eric Beohou ◽  
Myriam Labopin ◽  
Mohamad Mohty ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cord Blood ◽  
Graft Failure ◽  
Advanced Disease ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Working Party ◽  
Blood Transplantation ◽  
Haploidentical Transplantation ◽  
Second Transplantation

Abstract Backround & Methods. Approximately 12% of adult patients (pts) receiving umbilical cord blood transplantation (UCBT) as treatment for acute myeloid (AML) or lymphoblastic (ALL) leukemia are reported to experience graft failure (Baron et al., J Hematol Oncol 2015 ; 8 :107). No systematic large study has assessed their outcome thus far. Therefore the acute leukemia working party of the EBMT and EUROCORD performed a multicenter retrospective registry study on adult patients with AML or ALL receiving a first single or double UCBT between 2005 and 2016. Results. The study included 1836 pts. 215 of them (11.7%) had graft failure; 160 with AML and 55 with ALL. Their median age was 43 (range, 18-68) years. 115 pts were male and 100 female. Median year of transplantation was 2010. 67% of the patients were in complete remission (CR) at transplantation, while 33% had advanced disease. Conditioning regimen was myeloablative in 128 pts (60%) and RIC in 87(40%) pts, respectively. ATG was administered in 101 pts. 126 pts received a single UCBT and 49 a double UCBT. Among the 215 pts with graft failure 54 underwent a second allogeneic (n=53) or autologous (n=1) transplantation 16 to 700 (median 62) days after the first UCBT (the 1-year cumulative incidence of second transplantation was 24%). 100-day and 1 year OS in pts not undergoing a second transplantation were 21.9 % (95% CI: 16.3-29.3) and 10.6 % (95% CI: 6.7-16.8), respectively. Among the 53 pts who underwent a second allogeneic transplantation, the second donor was either an unrelated donor (n=34), an HLA-haploidentical (n=17), or an HLA-identical sibling (n=2). Stem cell source consisted of single (n=13) or double (n=13) UCB, PBSC (n=17), BM (n=7), PBSC + UCB (n=3) or PBSC + BM (n=1). Conditioning regimen for the second transplantation was a RIC in 87% of pts. Sustained engraftment was achieved by 33 pts (61%) after the second transplantation. One- and 3-year incidences of relapse, nonrelapse mortality, OS and LFS from second transplantation were 21% and 28%, 47% and 52%, 40% and 23%, and 33% and 21%, respectively. Main causes of death following second transplantation (n=39) included infection (n=14) and leukemia relapse/progression (n=12). In the 17 patients receiving an haploidentical transplantation as second graft 1- and 3-year OS were 51.8 % (95% CI: 32.4-82.7) and 41.4 % (95% CI: 21.8-78.6), respectively. In a multivariate Cox model assessing factors predicting OS in UCBT patients with graft failure, transplantation for advanced disease (HR=2.3; 95% CI : 1.6-3.3, P&lt;0.0001) as well as graft failure after the salvage transplantation (HR=2.8; 95% CI : 1.6-5.0, P=0.0005) were predictive of poor OS while use of RIC conditioning for the first transplantation was associated with a better OS. Conclusions. In this large cohort of adult pts given UCBT as treatment for AML or ALL the incidence graft failure was 12%. A second transplantation could be performed only to a minority (24%) of patients with high, about 50%, TRM but led to a 3-year OS of 23%, rescuing about quater of the pts with graft failure post UCBT. Results were more encouraging in the 17 patients who received a salvage HLA-haploidentical transplantation (3-year OS of 41%). Future attempts should be focused on reducing the high TRM associated with the second transplant while recent progresses in cord blood engineering will likely dramatically decrease the incidence of graft rejction after UCBT. Disclosures Mohty: Sanofi: Honoraria, Speakers Bureau.

High Rate of Engraftment and Low Regimen-Related Toxicity Using Fludarabine, Melphalan and Thiotepa Conditioning for Unrelated Donor Cord Blood Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4414-4414
Author(s):  
Stefan O Ciurea ◽  
Partow Kebriaei ◽  
Issa F Khouri ◽  
Muzaffar H. Qazilbash ◽  
Roy B Jones ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Adult Patients ◽  
High Rate ◽  
Unrelated Donor ◽  
Platelet Recovery ◽  
Blood Transplantation

Abstract BACKGROUND: Cord blood transplantation (CBT) represents an alternative source of stem cells for adult patients who lack a matched sibling or unrelated donor. However, the optimal type and intensity of the preparative regimen for patients receiving a CBT is not clear. We hypothesized that a conditioning regimen consisting of fludarabine, melphalan and thiotepa will be associated with an acceptable rate of engraftment and treatmentrelated mortality in patients receiving a CBT. METHODS: 37 patients, median age 31 years (2–57) and a median weight of 73kg, were treated between 8/2003 and 5/2008. All had advanced hematologic malignancies (24 with acute leukemia, 12 with lymphoma and one with CLL) At the time of transplant, 21 pts (57%) were in complete remission (CR) (first CR=20%) and 16 had relapsed/refractory disease. Grafts consisted of double (29 pts) or single (8 pts) CB units. Cytogenetics for patients with acute leukemia were poor in 11, intermediate in 9, good in 1 and unknown in 3 pts. Donor recipient HLA matching was (intermediate resolution class I HLA A and B and high-resolution DRB1): 3/6 (n=1, 1.5%), 4/6 (n=47, 71.2%) and 5/6 (n=18, 27.3%) alleles (n=66 units). Median total nucleated cell count was 1.8×107/kg (range 1–5.8). Nineteen patients received ex-vivo expanded units. The conditioning regimen consisted of melphalan 140 mg/m2 on day -8, thiotepa 10 mg/m2 on day -7, fludarabine 160 mg/m2 over 4 days on days -6, -5, -4, -3, and rabbit ATG 1.25 mg/kg on day -4 and 1.75 mg/kg on day -3 (FMT). Patients with CD 20+ lymphoid malignancies also received rituximab 375mg/m2 on day -9 (n=8, 22%). GVHD prophylaxis was tacrolimus and mini-methotrexate in 23 (62%) and tacrolimus and mycophenolate in 14 pts (38%). RESULTS: 36 patients (97%) were evaluable for engraftment. 1 patient died within 30 days due to progressive leukemia. 34/36 patients (95%) engrafted neutrophils and had hematopoietic recovery with 100% cord blood-derived cells. At day 30, of the 29 patients who received a double CBT, 75% had chimerism derived entirely from one donor while 25% had mixed donors chimerism. Neutrophil recovery to ANC &gt;0.5 × 10e9/l occurred after a median of 21 days (range 6–45) and platelet recovery to &gt;20 × 10e9/l after a median of 37 days (range 26–134, N=24; 67%). 32/37 pts (87%) were in CR after transplant with 16 surviving after a median follow-up of 12.1 months. Thirteen patients (36%) developed gr II–IV aGVHD (gr III–IV aGVHD in 5 patients, 14%), and 13 of 32 patients had cGVHD (40%), with the majority experiencing extensive GVHD. 11 patients (29.7%) relapsed after a median of 7 months post transplant and 12 died of nonrelapse causes. Day-100 treatment-related mortality in this heavily pre-treated population was 10%. Overall, causes of death included disease relapse (n=9), infections (n=6), organ failure (n=3), pulmonary hemorrhage (n=1) and GVHD (n=2). CONCLUSIONS: The FMT regimen was sufficiently immunosuppressive to support high rate of engraftment with acceptable TRM in heavily pre-treated adult patients with advanced hematologic malignancies undergoing CBT. These results support further evaluation of this regimen in CBT.

Unrelated Cord Blood Transplantation: Comparison After Single Unit Cord Blood Intrabone Injection and Double Unit Cord Blood Transplantation In Patients with Hematological Malignant Disorders. A Eurocord-EBMT Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 223-223 ◽  
Author(s):  
Vanderson Rocha ◽  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Marina Podestà ◽  
Dolores Caballero ◽  
...  
Keyword(s):  
Cord Blood ◽  
Median Time ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Adult Patients ◽  
Myeloablative Conditioning ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
The Impact

Abstract Abstract 223 The use of single cord blood unit for transplantation in adult patients is limited due to the high risk of graft failure and delayed neutrophil and platelet recoveries. The limited hematopoietic progenitors in UCB grafts and their homing after IV injection, have prompted investigators to study the design of delivering CB grafts directly into the bone marrow (BM) space (IBCBT) or to use double cord blood transplantation (dUCBT) to improve engraftment. To evaluate the impact of IBCBT, we made a retrospective based registry comparison with dUCBT performed in the same time period (2006-2010) and reported to Eurocord-EBMT. We included 87 and 149 patients who received either IBCBT or dUCBT, respectively, after a myeloablative conditioning regimen for malignant disorders. IBCBT was performed in 8 EBMT centers whereas dUCBT was performed in 56 EBMT centers. Majority of patients in both groups had acute leukemia. IBCBT patients were older (p<0.001), more frequently received an autologous graft (p<0.001) and had positive CMV serology (p<0.001), and importantly had more advanced disease at transplantation (p=0.04). Median number of infused (after thawing) nucleated cells injected intrabone was 2.5×107/kg and it was 3.9×107/kg in dUCBT (p<0.001). In 72% of both groups, CB grafts were HLA 4/6 (the highest HLA disparity was taken into consideration in dUCBT). Other differences were regarding GVHD prophylaxis that was based on CSA+MMF in 100% of IBCBT and in 62% of dUCBT cases; ATG was used in all IBCBT and 40% of dUCBT. Median follow-up time was 18 months in IBCBT and 17 months in dUCBT. At day 30, cumulative incidence (CI) of neutrophil recovery (ANC >500) was 83% after IBCBT and 63% after dUCBT, and at day 60, it was 90% in both groups; the median time to reach ANC>500 was 23 and 28 days after IBCBT and after dUCBT (p=0.001) respectively. At Day-180 CI of platelets recovery was 81% after IBCBT and 65% after dUCBT (p<0.001) with a median time of 36 days and 49 respectively (p=0.002). At day 100, CI of acute GVHD (II-IV) was 19% and 47% (p<0.001) and chronic GVHD 34% and 37% respectively (p=NS) respectively. Unadjusted 2 years-CI of NRM and RI were 31% and 23% after IBCBT and 35% and 28% after dUCBT, respectively (p=NS). Unadjusted 2 y-DFS estimation was 47% after IBCBT and 37% after dUCBT (p=NS). In multivariate analysis adjusting for statistical differences between 2 groups (such as status of the disease at transplant, age, CMV, previous transplants, GVHD prophylaxis), recipients of IBCBT had improved DFS (HR: 1.64, p=0.035), faster platelet recovery (HR:2.13, p<0.001) and decreased acute GVHD (HR:0.31; p<0.001) compared to dUCBT recipients. We did not find a cut-off value of number of nucleated cells after IBCBT or dUCBT that could be associated with outcomes after both approaches. In conclusion, both strategies have extended the use of CB transplants to adults in need of cord blood transplantation. Therefore, IBCBT is an option to transplant adult patients with single CB units after myeloablative conditioning regimen and may impact the total costs of cord blood transplantation. Based on these results, intra-bone technique may disclose new transplant potentialities also with other HSC sources. Disclosures: No relevant conflicts of interest to declare.

Phase II Multicenter Study of Busulfan-Fludarabine Conditioning Regimen for cord Blood transplantation in Pediatric Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1928-1928
Author(s):  
Hee Young Ju ◽  
Hyoung Jin Kang ◽  
Ji Won Lee ◽  
Hyery Kim ◽  
Kyung Duk Park ◽  
...  
Keyword(s):  
Cord Blood ◽  
Myeloid Leukemia ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Myeloablative Conditioning ◽  
Once Daily ◽  
Pediatric Acute Myeloid Leukemia ◽  
Blood Transplantation

Abstract Abstract 1928 Introduction. Cord blood transplantation (CBT) has become an alternative transplantation for various diseases. CBT has comparable efficacy with unrelated transplantation, but higher transplantation related mortality (TRM) rate upto 50% in early results has been a major obstacle. To reduce TRM, we studied reduced toxicity myeloablative conditioning regimen with busulfan and fludarabine for CBT in pediatric acute myeloid leukemia (AML) patients. Patients and methods. This study was a phase II prospective multicenter clinical trial (NCT01274195) and 27 patients were enrolled who underwent CBT with upto 2 HLA mismatch cord blood. Conditioning regimen was composed of fludarabine (40 mg/m2 once daily iv on days -8 ∼ -3), busulfan (0.8 mg/kg every 6 hours iv on days -6 ∼ -3) and rabbit thymoglobulin (2.5 mg/kg once daily iv on days -8 ∼ -6). For GVHD prophylaxis, cyclosporine and MMF were used. Results. Nine patients received single unit cord blood, and 18 patients received double unit cord blood. Median dose of nucleated cells and CD34+ cells were 4.23×107/kg (0.5–16.4) and 2.58×105/kg (0.33–6.77), respectively. Primary graft failure developed in 5 patients, and secondary graft failure occurred in 1 patient. Acute and chronic GVHD occurred in 16 patients (59.3%) and 10 patients (37%), respectively. TRM developed in 5 patients (cumulative incidence 22.2%), which included chronic GVHD-associated complication (n=1), post-transplantation lymphoproliferative disease (n=2), pneumonia (n=2), and diastolic cardiomyopathy (n=1). Relapse incidence was 30.9%. The 5-year overall and event-free survival were 46.3% and 40.0%, respectively. Patients who received single unit cord blood showed survival rate of 44.4%, and those who received double unit cord blood showed survival rate of 50%. Univariate analysis revealed that low nucleated cell count (P=0.011), low CD34+ cell count (P=0.002) were independent prognostic factor for survival. Conclusion. Reduced intensity conditioning regimen containing fludarabine and iv busulfan showed lower TRM rate than previous studies with myeloablative conditioning regimens. However graft failure and relapse rate were not satisfactory, and further study for optimization of conditioning regimen is warranted. Disclosures: No relevant conflicts of interest to declare.

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