Comparative Outcomes of Reduced-Intensity and Myeloablative Conditioning in Unrelated Cord Blood Transplantation for Adult Standard-Risk Hematological Diseases

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4498-4498
Author(s):  
Aya Nishida ◽  
Hikari Ota ◽  
Kazuya Ishiwata ◽  
Masanori Tsuji ◽  
Hisashi Yamamoto ◽  
...  
Keyword(s):  
Cord Blood ◽  
Relapse Rate ◽  
Cumulative Incidence ◽  
Cord Blood Transplantation ◽  
Myeloablative Conditioning ◽  
Hematological Diseases ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Standard Risk ◽  
Reduced Intensity

Abstract Abstract 4498 Background: Unrelated cord blood transplantation (uCBT) using reduced-intensity conditioning (RIC) is increasingly used for older and medically unfit patients. Data on the efficiency of hematopoietic stem cell transplantation (HCT) after RIC in younger and standard-risk patients are limited relative to myeloablative conditioning (MAC). Objective and method: To compare the outocomes of RIC to MAC in uCBT for adult patients with standard-risk hematological diseases, we retrospectively reviewed medical records of 57 standard risk hematological disease patients who underwent first uCBT at Toranomon Hospital from Jan. 2005 to December.2011. The definition of standard risk disease is severe aplastic anemia (SAA), myelodysplastic syndrome (MDS) in RA, RARS, and RCMD, acute myeloid or lymphoid leukemia (AML, ALL) in complete remission (CR) 1 or 2, chronic myeloid leukemia (CML) in chronic phase, malignant lymphoma (ML) and adult T-cell leukemia (ATL) in CR. RIC and MAC are defined according to previously reported criteria. Result: The median age of the studied patients was 55 years (range; 26–70). Twenty nine of patients received RIC and 28 MAC. Eleven patients of SAA, 7 MDS, 17 AML, 12 ALL, 5 CML, 2 ML, and 3 ATL were included in this study. Median follow-up days of survivors was 299 (11–2522). Cumulative incidence of neutrophil engraftment was 89.2% and the median days of engraftment is 20 days (11–51). Cumulative incidence of grade 2 to 4 acute graft versus host disease (aGVHD) was 42.9%. The 5-year disease-free and overall survival (DFS and OS) rates were 49.1% and 42.6%, respectively. The 5-years OS was comparable between MAC and RIC (RIC= 52.1% versus MAC= 44.2%; P=0.90). The 5-years OS of the elderly patients >54 years (n=27, 47%) were significantly lower than that in the younger patients (n=30, 53%) (35.1% versus 63.7%; P=0.042). The 5-years transplant-related mortality (TRM) was comparable between MAC and RIC (RIC= 35.0% versus MAC= 28.6%; P=0.56). The relapse rate was also comparable in two groups (RIC=11.9% versus MAC=33.6%; P=0.2) Conclusion: This study showed that uCBT with RIC for standard risk disease patients with median age of 55 years old had the similar results as MAC regimens in the 5-years OS, DFS, TRM and relapse rate. Disclosures: No relevant conflicts of interest to declare.

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.

Reduced-Intenisty Unrelated Cord Blood Transplantation for Patients with Advanced Malignant Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5453-5453
Author(s):  
Naoyuki Uchida ◽  
Shigesaburo Miyakoshi ◽  
Tomoko Matsumura ◽  
Koichiro Yuji ◽  
Shinsuke Takagi ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Cord Blood ◽  
Malignant Lymphoma ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Risk Patients ◽  
Unrelated Cord Blood ◽  
Standard Risk ◽  
Reduced Intensity

Abstract Allogeneic stem cell transplantation has been potentially curative approach for advanced malignant lymphoma. Unrelated umbilical cord blood cell has become a viable source of transplantation for those who lack suitable donors, but the outcome of the transplantation with reduced-intensity conditioning has not been clearly defined yet. We have therefore analysed the outcome of the patients with advanced malignant lymphoma who have undergone reduced-intensity unrelated cord blood transplantation (RI-UCBT). Thirty patients (median age, 47 years; range 27–69 years) underwent RI-UCBT with a preparative regimen consisting mainly of fludarabine 125 mg/m2, melphalan 80 mg/m2, and 4 Gy of total body irradiation since June 2002 to June 2005 with a mean follow-up of 353 days (59–621 days). The types of lymphoma included in this study were DLBCL (11 cases), PTCL (5), Hodgkin disease (5), Follicular lymphoma (5), AITL (2), ALCL (1), and nasal NK/T lymphoma (1). All the patients were heavily treated before proceeding to RI-UCBT, including 9 with prior autologous and 1 allogeneic transplantation. The median infused total cell dose was 2.71 x 107/kg (range, 1.76–4.76 x 107/kg). Graft-versus host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Twenty-four patients (80%) achieved primary neutrophil engraftment at a median of 23 days (12–33 days), and 18 (60%) achieved platelet engraftment at a median of 40 days (26–77 days). Fourteen patients (57.1%) developed grade II to IV acute GVHD at a median of 31 days (15–59 days). Five patients subsequently relapsed and all died within 2 years. Fifteen patients died of non-relapse causes such as infection (8), GVHD (3), IP (2), and others (2). Transplant-related mortality (TRM) within 100 days was 54%. The estimated 1-year probability of overall survival was 24% (95%CI: 1–46%). In subgroup analyses, standard risk patients (CR1, CR2, PR1, n=5) showed 80% while high risk (n=25) showed 13% overall survival at 1 year. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack HLA-matched donors. Although the patients in standard risk can expect reasonably good overall survival, the beneficial effect is only limited to small part of the high risk patients. To further improve the outcome, RI-UCBT should be investigated among patients with less advanced diseases in a well-designed clinical trial. Figure Figure

Outcomes after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia. An Eurocord-Netcord Survey.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 304-304 ◽  
Author(s):  
Vanderson Rocha ◽  
Gerard Michel ◽  
Nabil Kabbara ◽  
William Arcese ◽  
Juan Ortega ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cumulative Incidence ◽  
Lymphoblastic Leukemia ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Advanced Phase ◽  
Unrelated Cord Blood

Abstract Unrelated cord blood transplantation (UCBT) is an alternative option to treat children with haematological diseases without an HLA-identical donor. We have analyzed a total of 323 children with ALL receiving an UCBT, from 1994 to 2004 in 99 transplant centres in 24 countries, mostly in Europe. Cumulative incidence with competing risk and KM estimates were used to calculate outcomes. Seventy six children were transplanted in CR1, 136 in CR2 and 111 in more advanced phase of the disease. Among those children poor cytogenetics were observed in 89% of children in 1CR, 33% in 2CR and 42% in advanced phase. Twenty percent of children transplanted in advanced phase had been previously autografted. The median age was 6.5 years at UCBT, median cell dose infused was 4.1x107/kg and the median follow time was 22 months (3–96). The cord blood was HLA identical (6/6) in 12% of the cases, 5/6 in 46%, 4/6 in 39% and 3/6 in 3%. All children received myeloablative conditioning regimen (TBI in 66%) and the majority (67%) received CsA+corticoids as GVHD prophylaxis. Cumulative incidence of neutrophil recovery at day 60, platelets recovery (&gt;20.000) at day 180, acute (grade II–IV) and chronic GVHD were 76±5%, 54±5%, 42±3%, 14±2%, respectively. Overall 2 year-LFS was 36±3%. In a multivariate analysis, only CR1 or CR2 were associated with better LFS (HR=1.8; p&lt;0.0001). Outcomes CR1 (n=76) CR2 (n=136) Advanced (n=111) TRM at day 100 22+/−5% 25+/−4% 34+/−5% Relapse at 2 years 34+/−8% 37+/−5% 48+/−7% LFS at 2 years 42+/−6% 41+/−4% 24+/−4% For those patients transplanted with poor cytogenetics, LFS at 2 years was 32±6% and it was 37% for CR1, 43% for CR2 and 0% for advanced phase of the disease. In conclusion, in these large series of high risk ALL patients, these results show that UCBT should be proposed as alternative source of allogeneic transplantation for children lacking an HLA identical donor, in earlier status of the disease.

Reduced Intensity Conditioning Regimen in Single Unrelated Cord Blood Transplantation in Adults with Hematological Malignant Disorders. An Eurocord-Netcord and SFGM-TC Survey.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3143-3143 ◽  
Author(s):  
Vanderson Rocha ◽  
Bernard Rio ◽  
Federico Garnier ◽  
Marc Renaud ◽  
Anne Sirvent ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Blood Transplantation ◽  
Reduced Intensity Conditioning Regimen ◽  
Conditioning Regimens ◽  
Unrelated Cord Blood ◽  
One Year ◽  
Reduced Intensity

Abstract Results of reduced intensity conditioning regimen (RIC) in unrelated cord blood transplantation (UCBT) have been reported, however more frequently RIC was performed using double cord blood transplants. In order to study risk factors in single RIC-UCBT we have analyzed 65 patients with hematological malignancies (ALL=10, AML=37, Hodking and NHL=10, MDS=4, CML=3, Myeloma =1) transplanted from 1999–2005 and reported to Eurocord and SFGM-TC. The median follow-up was 8 months (3–26) and the median age was 47 years (16–76). At transplant, 49% of the patients had advanced phase of disease and 39% had received a previous autologous transplants. The conditioning regimen varied according diasease and centers: Fludarabine(FLU)+Endoxan (EDX) +TBI (2Gy) was given to 33 patients, FLU+(EDX or Melphalan) in 11, FLU+BU (<8mg/kg) associated or not to other drugs in 13, FLU+TBI(2GY) in 3 and other regimens in 5 patients. ATG/ALG was added in 26% of the cases. GVHD prophylaxis most commonly (55%) consisted of CsA and MMF; 87% received hematopoietic growth factors (<day 8). The median nucleated cell dose infused was 2.4 x107/kg and the graft was HLA identical (6/6) ( HLA A and B low resolution and DRB1 allelic typing) in 3 cases, 5/6 in 15, 4/6 in 37 and 3/6 in 10. Results: Median time to neutrophil recovery (>500/mm3) was 20 days (0–56) and 35 dyas for platelets recovery (>20.000/mm3). At day 60 probability of neutrophil recovery was 87± 7% of the 33 patients who received the Flu+End+TBI conditioning regimen and was 65±10% for patients receiving other regimens (p<0.01). Chimerism analysis was available in 71% of the patients at 3 months and was full donor in 67%, mixed chimerism in 9% and autologous reconstitution in 24%. Grade II aGVHD was observed in 13%, grade III in 7% and grade IV in 7%; the TRM was 45±7% overall, 50±15% in acute leukemia, 30±15% in lymphomas and 27±16% for other diagnoses. The TRM at one year for those receiving <2.4 x 107 TNC/kg was 53±9% and for those receiving >2.4 x107TNC/kg was 39±10% (p=0.07). For patients receiving Flu+End+TBI the TRM at one year was 24±10% and for those receiving other conditioning regimens was 60±9% (p=0.001). DFS at one year for lymphomas was 50±9%, for leukemias was 27±7% and for other diagnoses was zero. When the HLA compatibility was 6/6 or 5/6, DFS at one year was 42±12%, for 4/6 disparities DFS was 27±9% and for 3/6 disparities DFS was zero. DFS was 43±11% for those receiving Flu+End+TBI, and was 16±7% for patients receiving other conditioning regimens (p=0.005). For patients receiving >2.4 x 107TNC/kg the DFS was 31±12% and for patients receiving <2.4 x 107TNC/kg the DFS was 14±8% (p=0.05). In collusion, results of single RIC-UCBT are encouraging; cell dose and HLA remain important factors in this setting. The type of conditioning (Flu+End+TBI) seems to be associated with decreased TRM and better DFS, but a multivariate analysis with a higher number of patients is needed.

Sign in / Sign up

Export Citation Format

Share Document