The Use of Double-Unit Umbilical Cord Blood Transplantation In Adults with Hematologic Disease.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4579-4579
Author(s):  
Xiao Ma ◽  
Wu Depei ◽  
Aining Sun
Keyword(s):  
Survival Rate ◽  
Cord Blood ◽  
Umbilical Cord Blood ◽  
Cord Blood Transplantation ◽  
Disease Free Survival ◽  
Umbilical Cord Blood Transplantation ◽  
Hematologic Disease ◽  
Free Survival ◽  
Blood Transplantation ◽  
Disease Free

Abstract Abstract 4579 Objective: In this study, we explored the efficiency and toxicity of 38 cases of double-unit umbilical cord blood transplantation (CBT) in adults with hematologic disease. Methods: The tolerance; transplant related complications; survival rate and disease free survival rate were observed and analyzed. A nonmyeloablative conditioning regimen included cyclophosphamide, fludarabine and 2Gy TBI. Cyclosporine combined mycophenolate mofetil and ATG were used to prevent graft versus host disease (GVHD). Results: All these 38 patients tolerated the therapy well while two patients had graft failure. Severe acute GVHD was presented in 6 patients. Chronic GVHD was occurred in 16 patients. Fatal infection complications were occurred in 5 patients (including CMV idiopathic pneumonia in 2 patients) and 4 patients relapsed after transplantation. Neutrophil engraftment obtained on day +17 and platelet reconstitution occurred on day +42 on median. In the follow-up duration of 17 months on median, the expected 2-year relapse mortality was 17.95%; non-relapse mortality was 25.90%; overall survival was 60.80%, and disease free survival was 52.11%. Compare with 39 cases of haplo-identical HSCT in our department, significant delays in engraftment and lower severe GVHD occurred after CBT. There was no apparent difference between the risk of relapse and DFS in both groups. Conclusion: The use of double-unit CBT after reduced intensive conditioning therapy in adults with hematologic disease is an effective and safe treatment. Fatal infection and relapse are the main reasons of failure. Disclosures: No relevant conflicts of interest to declare.

Adult Umbilical Cord Blood Transplantation Following Non-Myeloablative Conditioning; Impact of Increased Cell Dose and 200cGy TBI on Engraftment and Survival.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5399-5399 ◽  
Author(s):  
Mitchell Horwitz ◽  
David Rizzieri ◽  
Gwynn D. Long ◽  
Cristina Gasparetto ◽  
Ashley Morris ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Cord Blood Transplantation ◽  
Disease Free Survival ◽  
Free Survival ◽  
Cell Dose ◽  
Blood Transplantation ◽  
Disease Free

Abstract Reliable engraftment following transplantation of partially matched umbilical cord blood is dependent upon adequate immunosuppression and myelosuppression. The lowest intensity conditioning regimen that will provide reliable cord blood engraftment in adult patients has not been determined. 26 adult patients with a contraindication for myeloablative marrow conditioning due to advanced age or comorbidities, underwent non-myeloablative umbilical cord blood transplantation for hematologic malignancies. The first 13 patients (Cohort 1) were conditioned with Fludarabine 120mg/m2, Cyclophosphamide 2g/m2 and horse Antithymocyte globulin 90mg/kg. Cyclosporine and Mycophenolate Mofetil was administered for GvHD prophylaxis. The median cell nucleated dose was 2.1 × 107/kg and median follow-up is 60 months (Chao 2004 BBMT 10:569). After protocol revision, 200 cGy total body irradiation was added to the regimen described above. In addition, the minimum nucleated cell dose provided from up to two cord blood units was increased to 3 × 107/kg (Cohort 2). With a median follow-up of 12 months, we now report the outcome of cohort 2. Fourteen patients with AML CR1 (2), CR≥2 (5), CML (1), MDS/AML (1), MDS (4), or Follicular Lymphoma (1) and a median age of 54 (range 21–72) were transplanted. Eight patients required dual cord blood grafts to achieve the minimum cell dose. All grafts were at least 4/6 HLA matches (antigen level class I, allele level class II) with the patient, and with each other (dual cord blood grafts). The median cryopreserved and infused nucleated cell dose was 3.6 × 107/kg and 3.5 × 107/kg respectively. Two patients were not evaluable for engraftment due to early toxic death. Two patients experienced primary graft failure. Acute GvHD (grade II skin) was observed in 2 patients. Limited chronic GvHD developed in 2 patients. Parainfluenza type 3 sinusitis and pneumonitis caused significant morbidity in 5 patients. Day 100 treatment-related mortality occurred in 4 patients (30%) due to; infection (2), hemorrhage (2). Relapse occurred in 5 patients (36%). The estimated one year overall and disease-free survival is 25% and 17%, respectively. T-cell recovery was slow. The median CD4 count/ul for engrafted patients was 44 (range 4–516) and 61(range 2–237) at 3 and 6 months following transplantation, respectively. The median CD8 count/ul was 7 (range 0–359) and 108 (range 0–728) at 3 and 6 months following transplantation, respectively. A comparison of results from the two cohorts is presented in the table. The addition of 200cGy and increasing the cell dose facilitated by dual cord blood transplantation doubled the chance for sustained donor engraftment. Improved engraftment was accompanied by increased treatment-related morbidity and mortality, erasing the potential for improved disease-free survival. Disease relapse, in part due to slow immune recovery resulting in impaired anti-tumor response, was the other major impediment to successful outcome. Techniques focused on enhancing immune recovery would significantly improve outcomes of adult cord blood transplantation. Comparison of Cohort 1 vs Cohort 2 Evaluable Patients Med. Nuc Cell Dose/kg D100 TRM(%) Sustained Donor Engraftment (%)† Disease-Free Survival(%)† †estimated (1yr) *P=0.08 **P=NS Flu / Cy / ATG (Cohort 1) 13 2.1 × 107 15 41 15 Flu/Cy/ATG/200cGy(Cohort 2) 12 3.5 × 107 30 83* 17**

An International Multi-Institutional Study of Double Cord Blood Transplantation in a Racially Diverse Population.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2017-2017
Author(s):  
Karen Ballen ◽  
Brian Wang ◽  
Joseph Rosenthal ◽  
Auayporn Nademanee ◽  
Chatchada Karanes ◽  
...  
Keyword(s):  
Cord Blood ◽  
Multivariate Analyses ◽  
Cord Blood Transplantation ◽  
Disease Free Survival ◽  
Racially Diverse ◽  
P Values ◽  
Free Survival ◽  
Cell Dose ◽  
Blood Transplantation ◽  
Disease Free

Abstract Cord blood (CB) is an alternative stem cell source for patients, but single CB products may not contain sufficient cell dose for cord blood transplantation (CBT) of adults. Double cord blood transplantation (DCBT) has been used to increase the cell dose, but the majority of reported patients have been Caucasian. We conducted a retrospective analysis of 89 consecutive DCBT recipients who received at least one CB product from the StemCyte CB banks. The median age was 20 years (range 1–63), with 58% over age 18, and the median weight was 60 kg (range 11–137), with 70% ≥ 50 kg. Diagnoses were: 29 ALL, 23 AML, 10 Thalassemia, 6 CML, 5 MDS, 4 AA, 3 lymphoma, and 9 others. 33% had IBMTR advanced disease status, 28% intermediate, 18% early, and 21% unknown status for the leukemia/lymphoma/MDS cases. 70% of the recipients with known race were non-Caucasian (NC) with 35 Asians (A), 24 Caucasians (C), 9 African Americans, 8 Hispanics, 3 Native Americans, 10 others. Patients were treated with a variety of conditioning regimens (33% reduced intensity) at 39 U.S. and international centers on 4 continents with 37% at non-US centers. Thirty-seven patients (42%) received both units as plasma depleted cord blood products. CB product characteristics were as follows: median pre-freeze TNC dose 3.8×107/kg, median pre-freeze CD34+ dose 1.4×105/kg. The median time to neutrophil (ANC500) engraftment was 21.5 days and the median time to platelet (Plt) 20K and 50K engraftment were 42 and 59 days respectively. Kaplan-Meier (KM) estimates of 100-day transplant related mortality (TRM), 1-year overall (OS) and disease free survival (DFS) were 37±6%, 50±6%, and 37±6% respectively. Causes of death include infection (26%), relapse (23%), multi-organ failure (16%), GvHD (2%), and other (33%). Engraftment correlated with cell dose and disease risk status in univariate analysis. Survival correlated with higher pre-freeze TNC dose (p=.03), higher pre-freeze CD34+ dose (p=.04), and non-washed CB (p=.01). Survival, disease-free survival, ANC 500, plt 20K, and 50K engraftment, and TRM were not different between C and NC or between A and Non-Asians (NA) in multivariate analyses. 1-year OS for C and NC patients were 48% and 54% respectively (p=.24), with DFS of 35% and 40% (p=.32), respectively. In conclusion, this multi-centered international study shows that 1) DCBT can be performed effectively on a racially diverse patient population, 2) Survival and other outcome measures were similar between C and NC or between A and NA patients in multivariate analyses, 3) Cell dose remains important for engraftment even with DCBT. ANC500 Plt 20K 1 Yr Relapse 100-Day & 1-Yr TRM 1-Yr OS 1-Yr DFS * W = Washed CB, NW = Unwashed, CI = Cumulative Incidence; P-values from multivariate Cox Regression model adjusting for recipient weight, malignancy, and # of StemCyte units involved in DCBT. % & Median Days to Engraftment CI 83±7 KM 90±4 21.5 days CI 57±7 KM 78±7 42days 31±7 21±4 37±6 50±6 37±6 P-values* C vs. NC (W) .34 .86 .86 .87 .92 .86 C vs. NC (NW) .06 .59 .90 .35 .72 .92 A vs. NA (W) .43 .15 .80 .33 .13 .66 A vs. NA (NW) .69 .37 .75 .70 .30 .30

A Clinical Study on Double-Unit Umbilical Cord Blood Transplantation in Adults with Hematologic Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4486-4486
Author(s):  
Xiao Ma ◽  
Wu Depei ◽  
Aining Sun
Keyword(s):  
Survival Rate ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Hematologic Disease ◽  
Free Survival ◽  
Fatal Infection ◽  
Disease Free

Abstract Abstract 4486 Objective: In this study, we explored the efficiency and toxicity of 46 cases of double-unit CBT in adults with hematologic disease. Methods: The tolerance; transplant related complications; survival rate and disease free survival rate were observed and analyzed. A nonmyeloablative conditioning regimen included cyclophosphamide, fludarabine and 2Gy TBI. Cyclosporine combined mycophenolate mofetil and ATG were used to prevent graft versus host disease (GVHD). Results: All these 46 patients tolerated the therapy well while four patients had graft failure. Severe acute GVHD was presented in 6 patients. Chronic GVHD was occurred in 18 patients. Fatal infection complications were occurred in 7 patients (including CMV idiopathic pneumonia in 2 patients) and 5 patients relapsed after transplantation. Neutrophil engraftment obtained on day +17 and platelet reconstitution occurred on day +42 on median. In the follow-up duration of 29 months on median, the expected 3-year relapse mortality was 16.7%; non-relapse mortality was 26.1%; overall survival was 57.7%, and disease free survival was 48.2%. Conclusion: The use of double-unit CBT after reduced intensive conditioning therapy in adults with hematologic disease is an effective and safe treatment. Fatal infection and relapse are the main reasons of failure. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cord Blood Transplantation Is an Effective Treatment Option in Patients with Myelodysplastic and Myeloproliferative Syndromes

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2048-2048
Author(s):  
Laura Roberts ◽  
Rachel B. Salit ◽  
Lauren Longo ◽  
Elisabetta Xue ◽  
Corinne Summers ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Disease Free Survival ◽  
High Risk Population ◽  
Free Survival ◽  
Blood Transplantation ◽  
Disease Free ◽  
Very High

Background: Few registry studies have investigated the use of cord blood transplantation (CBT) for treatment of patients with myelodysplastic syndrome (MDS) and myeloproliferative disorders (MPN). To date, the outcomes reported have been not encouraging with excess of graft failures [1] and poor disease-free survival (DFS) [2]. The major obstacle to the success of CBT in this high-risk population has been related to the high rate of non-relapse mortality (NRM) due to the delayed time to engraftment. In this single-center study we retrospectively investigated clinical outcomes in patients with MDS and MPN undergoing a CBT. Methods: We reviewed clinical outcomes in 65 consecutive patients with either MDS (n=42) or MPN (n=23) who received a CBT at our institution between 2006 and 2018. The conditioning regimens used consisted of Cyclophosphamide (CY), Fludarabine (FLU), and total body irradiation (TBI) 13.2 Gy (n=16); Treosulfan, FLU, and TBI 2 Gy (n=26); Busulfan, CY, and FLU (n=6); or CY, FLU, and TBI (2 to 4 Gy) (n=17). All patients received Cyclosporine and Mycophenolate Mofetil for graft-versus-host disease (GVHD) prophylaxis. Cord blood units were HLA-typed at the antigen level for HLA-A and B, and high resolution for HLA-DRB1. Disease risk was classified as low to intermediate (n=37) and high to very high (n=28). Cytogenetics risk at diagnosis was favorable, intermediate and unfavorable in 11 (17%), 33 (51%) and 21 (32%) patients, respectively. Among patients with MDS, the R-IPSS score was low in 6 (14%), intermediate in 18 (43%), high in 8 (19%), and very-high in 10 (24%). Engraftment, relapse, NRM, and acute GVHD were calculated using cumulative incidence estimates adjusting for the appropriate competing risks. DFS and overall survival (OS) were assessed using the Kaplan-Meier method. Results: Patient characteristics are shown in Table 1. Median follow-up was 4.2 years (range, 0.5-12). The median age and weight were 46 years (range, 1-71) and 71 kg (range, 10-116). Six (9%) patients had failed a prior HCT. 56 (86%) patients received 2 cord blood units to achieve the required cryopreserved cell dose. The median cell doses infused were 2.6 x 107 (range, 1.4-15) TNC/kg and 0.12 x 106 (range, 0.02-0.78) CD34+ cells/kg. Neutrophils (>500 for 3 days) and platelet (>20x109/L for 7 days transfusion free) engraftment occurred at a median time of 20 days (range, 6-89) and 35 days (range, 13-85), respectively. There were only 4 (6%) cases of primary graft failure, 2 of which were patients with MDS and 2 patients with MPN, and no cases of secondary graft failures. 76% of MDS patients and 52% of MPN patients achieved platelet engraftment by day 100. OS at 3 years was 60% (95% Confidence Interval, CI: 47-71) and specifically was 63% (95% CI: 47-76) for MDS patients and 55% (95% CI: 32-73) for MPN patients. Disease free survival at 3 years was 54% (95% CI: 41-66) with a cumulative incidence of relapse of 21% (95% CI: 11-32). The cumulative incidence of NRM at day 100 and at 3 years were 9% (95% CI: 4-17) and 25% (95% CI: 15-36), respectively. No differences in DFS, relapse incidence, and NRM were seen between MDS and MPN patients (Table 2). The cumulative incidence of acute GVHD grade II-IV and III-IV were 74% (95% CI: 61-82) and 21% (95% CI: 12-32), respectively. Seventeen (26%) patients developed late acute GVHD at a median time of 186 days (range, 101-379), and 10 (15%) had overlap syndrome. Twenty-three (35%) patients were diagnosed with classical chronic GVHD: 18 (27%) with mild, 3 (5%) with moderate, and only two (3%) with severe grade. Conclusions: The results presented herein demonstrate that in patients with MDS and MPN undergoing CBT sustained engraftment was achievable without excessive graft failures. The rates of OS and DFS at 3 years were extremely encouraging and similar to what was observed after matched related and unrelated donors' transplants. [3,4]. Overall, our data suggest that CBT should be considered as a valid option for this high-risk population in case of lack of conventional donors. Disclosures Delaney: Biolife Solutions: Membership on an entity's Board of Directors or advisory committees; Nohla Therapeutics: Employment, Equity Ownership. Milano:ExCellThera: Research Funding; Amgen: Research Funding.

Sign in / Sign up

Export Citation Format

Share Document