Unrelated Cord Blood Transplantation (UCBT) in Adults with MDS or Secondary Acute Myeloblastic Leukemia (sAML): a Survey On Behalf of Eurocord and CLWP of EBMT.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1198-1198
Author(s):  
Marie Robin ◽  
Guillermo Sanz ◽  
Irina Ionescu ◽  
Bernard Rio ◽  
Anne Sirvent ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Median Time ◽  
Advanced Disease ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Neutrophil Recovery ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Unrelated Cord Blood

Abstract Abstract 1198 Poster Board I-220 Background: Unrelated cord blood transplantation is an alternative option to treat patients with high risk hematologic malignancies in the absence of an HLA identical donor. Results of UCBT in patients with MDS or secondary leukaemia (sAML) have been scarcely published. Method: We performed a survey to identify predictors of outcomes in a large cohort of 108 adults with MDS or sAML reported to Eurocord-Promise data bases (62 centres in 17 countries in Europe) and transplanted with an UCBT from 1998 to 2007. Sixty-seven patients were transplanted for sAML (secondary to MDS in 42 cases) and 41 for MDS. Worst status before UCBT for MDS was RA in 4, RAEB1 in 10, RAEB2 in 14, CMML or RAEBt in 9, unclassified in 4 patients. IPSS classification at transplantation was low, intermediate 1, intermediate 2, high or missing in 8, 12, 7, 6 and 8 patients, respectively. For patients with sAML, 48% were transplanted in CR1 at UCBT. Median age at UCBT was 43 years (from 18 to 72 years). Median time from diagnosis to UCBT was 10 months. Transplant characteristics: 77 patients received a single and 31 a double UCBT. UCB grafts had ≥ 2/6 HLA mismatched in 60 % of cases. Myeloablative conditioning regimen (MAC) was given to 57 patients whereas 51 patients received a reduced intensity conditioning regimen (RIC). GVHD prophylaxis consisted in CSA+MMF in 52, CSA+steroids in 43 and other combinations in 13 patients. Median number of collected nucleated cells was 3.4 for single and 4.6 × 107/kg for double UCBT. Median follow-up was 25 months. Results: cumulative incidence (CI) of neutrophil recovery at day 60 was 82±4% with a median time to achieve more than 500 ANC/mm3 of 23 days. Neutrophil recovery was independently associated with number of CD34+ cells/kg (> 1.1 × 105, Hazard Ratio (HR), 1.79; P= .02) and advanced disease status (intermediate 2 or high MDS and sAML not in CR; HR, 1.92; P= .007). CI of grade II-IV acute GVHD at day 100 and chronic GVHD at 2 years were 26±4% (II n=18, III n=6, IV n =6) and 42%±8, respectively. Two-year non-relapse mortality was significantly higher after MAC (62% vs. 34%, p=0.009). In counterpart, 2-year relapse rate was higher after RIC (14% vs 29%, p=0.02). Two-year DFS and OS were 30 and 34%, respectively. In univariate analysis, among patient-, disease- and transplant- factors studied only patients with high risk disease at maximal pre-transplant stage or transplanted > 18 months after diagnosis had significant poorer DFS (disease risk: 49% vs. 22%; time: 35% vs. 15%). However, in multivariate analysis, the only factor associated with decreased DFS was advanced disease (HR: 2.05; p= .01). Conclusion: These data indicate that UCBT is an acceptable alternative option to treat adults with high risk MDS or sAML without a HLA-matched related or unrelated bone marrow donor. Controlled disease at time of transplantation improves outcome. More investigations are needed to compare these results with outcomes after other stem cell sources from unrelated HSCT donor. Disclosures: No relevant conflicts of interest to declare.

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 (>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<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.

Allogeneic Hematopoietic Cell Transplantation From Combined Haploidentical Family Members and Unrelated Cord Blood (CB) Can Benefit High Risk Patients Lacking HLA-Identical Donors.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3378-3378 ◽  
Author(s):  
Elizabeth Shima Rich ◽  
Andrew Artz ◽  
Theodore Karrison ◽  
Lucy A Godley ◽  
Olatoyosi Odenike ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Median Time ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Bone Marrow Cells ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Blood Transplantation

Abstract Abstract 3378 Poster Board III-266 Introduction: Haploidentical-cord blood transplantation is a promising approach for patients (pts) who lack HLA donors and may improve rates of early engraftment while allowing long term cord blood reconstitution with low rates of GVHD. We enrolled 29 pts (17 AML/MDS, 4 ALL, 3 CML, 4 NHL/HL, 1 severe aplastic anemia) lacking HLA identical donors. The median age was 40 years (range, 4-67), and median weight was 75 kg (range, 14-125). Twenty-two (76%) pts had active disease at time of transplant; 6 had prior autologous transplants. 14 pts were Caucasian; 15 were other race or ethnicity. The haploidentical donor was the mother in 4; father in 3; child in 10; sibling in 10; and half-sibling in 2 cases. The median haploidentical CD34+ dose was 2.51 × 106/kg (range, 1.25-10.95); CD3+ cells were 1.0 × 104/kg (range, 0.3-3.7). Single unrelated CB units were matched by low resolution at HLA-A and B and high-resolution at DRB1, and matched 6/6 in 2 pts; 5/6 in 18 pts; 4/6 in 9 pts. Median cord total nucleated cells equaled 1.93 × 107/kg (range, 1.07-9.36); CD34+ cells were 0.08 × 106/kg (range, 0.03-0.75). The conditioning regimen for 18 pts was fludarabine (Flu) (30 mg/m2 on d-7 through -3), melphalan (Mel) (70 mg/m2 on d -3 and -2), and Thymoglobulin (rATG) (1.5 mg/kg on d-7, -5, -3, -1). Eleven pts received Flu, thiotepa (5 mg/kg on d -7 and -6), total-body irradiation (TBI) (12 Gy lateral opposed fields in 2 Gy fractions BID on d-3 through -1), and rATG. GVHD prophylaxis consisted of tacrolimus (Tac) + methylprednisolone or Tac + mycophenolate. Engraftment: Two pts died early (sepsis, CVA). Three other pts failed to engraft with either haploidentical or CB and died of infection on d36, 43, and 63. One of these had anti-donor HLA antibodies. 24 pts engrafted with a median time to ANC >500/mL of 10 days (range, 9-31) and median time to sustained platelets >20,000/mL of 20 days (range, 15-63). In the majority of pts, early haploidentical engraftment was replaced by durable engraftment of CB by 100 days. However, 3 pts had persistent hematopoiesis associated with only the haploidentical donor, while a fourth pt engrafted with only CB on day 31. Late graft failure and death from sepsis occurred in one of the patients with haploidentical engraftment. In unfractionated peripheral blood or bone marrow cells, median haploidentical chimerism was 95% (range, 0-100) on d14; 76% (range, 0-95) on d30; 6% (range, 0-87) on d100. Median unfractionated cord chimerism was <5% (range, 0-100) on d14; 20% (range, 0-100) on d30; 85% (range, 0-100) on d100. In the CD3+ compartment, median haploidentical chimerism was 95% (range, 0-100) on d14; 86% (range, 0-95) on d30; 6% (range, 0-79) on d100. Median CD3+ cord chimerism was 5% (range, 0-100) on d14; 26% (range, 0-100) on d30; 90% (range, 1-100) on d100. Toxicities and outcome: Other fatal toxicities included VOD (1), EBV-associated PTLD (1), ARDS (1), cardiac arrest (1), intractable seizures (1). Two patients developed TTP and later died of complications related to sepsis. Five pts relapsed of whom 4 have died. Acute GVHD (aGVHD) grade II occurred in 3 pts, one of whom developed the only case of chronic GVHD after failing to continue prograf. No aGVHD grade III-IV was seen. Twelve pts are currently alive; 11 are without disease. The median follow up for survivors is 186 days (range, 16-642). Estimated one year survival is 26% (95%CI, 6-46), and PFS is 19% (1-36). Conclusions: Combined haploidentical and CB transplantation results in early haploidentical engraftment followed by durable CB predominance in a majority of pts. The median times to neutrophil engraftment are considerably shorter - and the range narrower - than with other methods of cord blood transplantation. Early haploidentical engraftment failed in four patients; cord blood engraftment also failed in three of these pts and in three others. Rates of acute and particularly of chronic GVHD are low. Durable remissions can be achieved even in high risk pts regardless of age or remission status at the time of transplant. Disclosures: Rich: Genzyme: Research Funding. Odenike:Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees. van Besien:Genzyme: Research Funding.

Unrelated cord blood transplantation for adult patients with advanced myelodysplastic syndrome

Blood ◽  
2003 ◽  
Vol 101 (12) ◽  
pp. 4711-4713 ◽  
Author(s):  
Jun Ooi ◽  
Tohru Iseki ◽  
Satoshi Takahashi ◽  
Akira Tomonari ◽  
Koji Ishii ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Cord Blood ◽  
Median Time ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Adult Patients ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Unrelated Cord Blood

AbstractWe report the results of unrelated cord blood transplantation (CBT) for 13 adult patients with advanced myelodysplastic syndrome (MDS). The median age was 40 years, the median weight was 51 kg, and the median number of infused nucleated cells was 2.43 × 107/kg. Twelve patients had myeloid reconstitution, and the median time to more than 0.5 × 109/L (5 × 108/L) absolute neutrophil count was 22.5 days. A self-sustained platelet count more than 50 × 109/L was achieved in 11 patients at a median time of 49 days. Acute graft versus host disease (GVHD) occurred in 9 of 12 evaluable patients and chronic GVHD in 8 of 11 evaluable patients. Ten patients are alive and free of disease at between 171 and 1558 days after transplantation. The probability of disease-free survival at 2 years was 76.2%. These results suggest that adult advanced MDS patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT.

scholarly journals Early Engraftment of Unrelated Cord Blood Transplantation in Patients with Acquired Severe Aplastic Anemia Using Conditioning Regimen without Anti-Thymocyte Globulin

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2072-2072
Author(s):  
Wan Xiang ◽  
Huilan Liu ◽  
Baolin Tang ◽  
Xiaoyu Zhu ◽  
Yao Wen ◽  
...  
Keyword(s):  
Cord Blood ◽  
Immunosuppressive Therapy ◽  
Median Time ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Cell Number ◽  
Blood Transplantation ◽  
Primary Graft Failure ◽  
Unrelated Cord Blood

Abstract Background: Previous studies show that the use of unrelated cord blood transplantation (UCBT) for severe aplastic anemia (SAA) has poor outcome because of high incidence of primary graft failure. Effective measures to completely prevent rejection in SAA remain to be identified, but higher cell dose, less HLA disparities and better conditioning regimen are known to improve the outcome. In this study we compare two conditioning regimens to determine which is better to facilitate early engraftment after UCBT. Patients and methods : We retrospectively analyzed the outcomes of 35 Chinese patients with acquired SAA who received UCBT since September 2016. Eighteen patients (ATG group) used a conditioning regimen consisting of ATG (thymoglobulin) 2.5 mg/kg (D-9 to D-7) with fludarabine 30 mg/m2 (D-9 to D-4), cyclophosphamide 60 mg/kg (D-3 to D-2) and total body irradiation (3 Gray) on D-1. Median age at time of UCBT was 9 (4-37) years. The median total nucleated cell number and CD34-positive cell number at infusion were 4.08 (1.74-9.36) × 107/kg and 2.13 (0.67-4.29) × 105/kg, respectively. Another group (No-ATG) of 17 patients used a conditioning regimen without ATG consisting of fludarabine 40 mg/m2 (D-8 to D-4), cyclophosphamide 60 mg/kg (D-3 to D-2) and total body irradiation (4 Gray) on D-1. Median age at time of UCBT was 14 (4-52) years. The median total nucleated cell number and CD34-positive cell number at infusion were 3.5 (1.07-7.87)× 107/kg and 1.7 (0.69-5.27) × 105/kg, respectively. Ciclosporin (CsA) and mycophenolate mofetil (MMF) was given to both groups as prophylaxis for graft versus host disease (GVHD). Results: Neutrophil recovery (>0.5×109/L) was observed in 11 patients of the ATG group and the median time to engraftment was 19 (13-35) days. The median time to platelet recovery (>20 × 109/L) was 40 (24-153) days. Primary graft failure was observed in seven patients. Only 1 out of 17 patients in the No-ATG group had primary graft failure. The median time to neutrophil engraftment was 17 (13-36) days. The median time to platelet engraftment was 31 (17-65) days. During follow-up, 7 patients died before 1 year due to non-engraftment (n=4), infection (n=2) and encephalorrhagia (n=1) in the ATG group. Four patients died in the No-ATG group due to infection (n=3) and IV grade acute GVHD in the skin and the intestinal tract (n=1, induced by discontinuing medicine). Furthermore, conditioning regimen without ATG shows even more superiority in patients refractory to immunosuppressive therapy with ATG and/or CsA (n=8), who had neutrophil engraftment completely within 20 days after cord blood infusion. Conclusi on: UCBT after a FLU-CY-TBI conditioning regimen without ATG for SAA patients is better than that with ATG, especially for patients refractory to immunosuppressive therapy. Pediatric and adult SAA patients who are younger than 50 years old, lack of HLA-matched sibling donor and refractory to immunosuppressive therapy should consider UCBT. Table. Table. Disclosures No relevant conflicts of interest to declare.

Unrelated Cord Blood Transplantation (CBT) for Thalassemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 554-554 ◽  
Author(s):  
Tang-Her Jaing ◽  
Patrick Tan ◽  
Joseph Rosenthal ◽  
Brian Wang ◽  
David Gjertson ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Critical Factor ◽  
Matched Pair ◽  
Curative Therapy ◽  
Unrelated Cord Blood Transplantation ◽  
Cell Dose ◽  
Blood Transplantation ◽  
Unrelated Cord Blood

Abstract CBT is a curative therapy for thalassemia, with cell dosage is a critical factor for CBT. We previously showed that by combining strategies that maximize cell dose-using non-red cell reduced plasma depleted cord blood (PD CB), forego post-thaw wash, and double cord transplantation - promising results may be achieved with unrelated CBT in selected patients. Between 7/91 and 4/06, 45 unrelated CBT were performed after myeloablative therapy (Bu/Cy/ATG in all 33 patients with known regimen) in 36 pediatric patients with transfusion-dependent thalassemia and 2 SCD patients at 14 transplant centers (TC) using 80% PD CB (6 double cords & 1 re-transplant). For the thalassemics, 19 were Lucarelli class 1, 4 class 2, 1 class 3, and 14 status unknown. Median age was 6 yo (range 0.3–20 yo) and median weight was 19 kg (range 8–76 kg). Data was audited. No significant adverse events were observed despite major ABO incompatibility in 9 cases. Unadjusted ANC500, platelet 20K and 50K engraftment with donor chimerism were achieved in 81±7%, 79±8% and 76±8% of the cases, and median times to ANC500 engraftment, platelet 20K and 50K engraftment were at +16.5 (range 11–33), +37 (range 16–133) and +55 (range 26–144 days) days, respectively. 8 patients died including 2 early deaths prior to day +20 and one accidental trauma caused cerebral hemorrhage. All remaining 30 patients are alive, with 25 disease-free and 5 autologous recovery for an 1-Yr OS of 77±7% and DFS at 65±8%. With a mean and median follow up time of 392 and 257 days respectively (range 7–1,760 days), the median day to hospital discharge was day +58 (range 22–137 days). The two experienced TC (>5 cases of CBT for hemoglobinopathy) were compared with less experienced centers, and CBU that were post-thaw washed (14%) were compared with CB that were not washed (86%). Results show potential benefits with TC experience and no post-thaw wash; however, since both experienced centers do not practice post-thaw wash, these two factors cannot be distinguished. Unadjusted ANC500, platelet 20K and 50K engraftment were 87±7%, 86±8% & 86±8% and 1-Yr OS of 87±7% and DFS at 77±9% were achieved for experienced centers not performing post-thaw wash. The role of plasma depletion vs. RBC depletion was also studied by matching age, weight, TNC dose, #HLA matches, conditioning regimen, thalassemia diagnosis, and post-thaw wash between the groups at the 2 experienced TC. Outcome trended towards improvements in engraftment and thalassemia-free survival for PD CB; however, larger numbers and rigorous matched pair analysis are needed for definitive conclusions. Overall, this is the largest known study of unrelated cord blood transplantation for thalassemia and preliminary results show that when cell dose (PD CBU, double cord, and no wash) and other conditions (TC experience and judicious patient selection) are optimal, CBT may be a promising approach for the curative therapy of thalassemia major with unadjusted ANC500, platelet 20K and 50K engraftment rates of 93±7%, 91±8% & 82±8% respectively and 1-Yr OS of 86±9% and DFS at 86±9%.

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