Better Engraftment of Single-Unit Unrelated Cord Blood Transplantation in Patients with Acquired Severe Aplastic Anemia Not Respond to IST Using Conditioning Regimen without ATG

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5727-5727
Author(s):  
Wan Xiang ◽  
Baolin Tang ◽  
Huilan Liu ◽  
Xiaoyu Zhu ◽  
Kaidi Song ◽  
...  
Keyword(s):  
Body Weight ◽  
Graft Failure ◽  
Single Unit ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Cell Number ◽  
Blood Transplantation ◽  
Primary Graft Failure ◽  
Total Body ◽  
Unrelated Cord Blood

Background: Previous studies show that the use of single-unit unrelated cord blood transplantation (sUCBT) 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 engraftment after sUCBT. Patients and methods: We retrospectively analyzed the outcomes of 21 Chinese patients with acquired SAA who do not have HLA-matched siblings and do not respond to first-line immunosuppressive therapy with ciclosporin (CSA) and/or anti-thymocyte globulin (ATG) that received sUCBT were included beteween July 2016 and October 2018. Data collected as of June 2019 were analyzed. 6 patients (ATG group) used a conditioning regimen consisting of ATG (rabbit) 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 sUCBT was 11 (5-20) years, median body weight was 34(18-53)kg. Waiting time from diagnosis to transplantation was 427(277-3407)days. The median total nucleated cell number and CD34-positive cell number at infusion were 3.57(2.77-9.36) × 107/kg and 2.5(1.02-3.99) × 105/kg, respectively. Another group (No-ATG) of 15 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 11 (3-42) years, median body weight was 35(13-70)kg. Waiting time from diagnosis to transplantation was 1664(160-2006)days. The median total nucleated cell number and CD34-positive cell number at infusion were 3.63(1.65-9.38)×107/kg and 2.5(0.69-5.61)×105/kg, respectively. CsA and MMF was given to both groups as prophylaxis for graft versus host disease (GVHD). Results: Primary graft failure was observed in 4 out of 6 patients in ATG group. All of these 4 patients received salvage transplantation with haploidentical related donor, 3 patients died after salvage transplantation due to grade IV GVHD in intestinal tract and infection. However, all of 15 patients in the No-ATG group had completely engraftment. The median time to neutrophil engraftment was 18 (13-27) days, platelet engraftment was 32 (17-112) days. 42-day cumulative incidence of engraftment is 100% compared to 33% in ATG group (P=0.008). During follow-up, 2 patients died before 1 year due to renal failure (n=1) and encephalorrhagia (n=1) in the No-ATG group. One-year survival rate is 86.7% in No-ATG group compared to 50% in ATG group (P=0.0598). Conclusion: sUCBT after a FLU-CY-TBI conditioning regimen was an effective and safe option for SAA patients, with better engraftment and survival. 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 sUCBT. Table Disclosures No relevant conflicts of interest to declare.

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.

scholarly journals Randomised controlled trial of conditioning regimen for cord blood transplantation for adult myeloid malignancies comparing high-dose cytarabine/cyclophosphamide/total body irradiation with versus without G-CSF priming: G-CONCORD study protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e040467
Author(s):  
Seitaro Terakura ◽  
Takaaki Konuma ◽  
Masatsugu Tanaka ◽  
Yukiyasu Ozawa ◽  
Makoto Onizuka ◽  
...  
Keyword(s):  
Cord Blood ◽  
Study Protocol ◽  
Total Body Irradiation ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
High Dose ◽  
Blood Transplantation ◽  
Total Body ◽  
Randomised Controlled

IntroductionA better long-term quality of life after umbilical cord blood transplantation (CBT) is observed compared with transplants from other alternative donors, whereas graft failure and relapses after CBT are still major issues. To minimise graft failure and relapse after CBT, intensification of conditioning by the addition of high-dose cytosine arabinoside (CA) and concomitant continuous use of granulocyte-colony stimulating factor (G-CSF) are reported to convey a significantly better survival after CBT in some retrospective studies. To confirm the effect of G-CSF plus CA combination, in addition to the standard conditioning regimen, cyclophosphamide (CY)/total body irradiation (TBI), we design a randomised controlled study comparing CA/CY/TBI with versus without G-CSF priming (G-CSF combined conditioned cord blood transplantation [G-CONCORD] study).Methods and analysisThis is a multicentre, open-label, randomised phase III study that aimed to compare G-CSF+CA/CY/TBI as a conditioning regimen for CBT with CA/CY/TBI. Patients with acute myeloid leukaemia or myelodysplastic syndrome, aged 16–55 years, are eligible. The target sample size is 160 and the registration period is 4 years. The primary endpoint is the 2-year disease-free survival rate after CBT. The secondary endpoints are overall survival, relapse, non-relapse mortality, acute and chronic graft-versus-host disease, engraftment rate, time to neutrophil recovery, short-term adverse events, incidence of infections and causes of death.This study employs a single one-to-one web-based randomisation between the with-G-CSF versus without-G-CSF groups after patient registration. Combination of high-dose CA and CY/TBI in both groups is used for conditioning.Ethics and disseminationThe study protocol was approved by the central review board, Nagoya University Certified Review Board, after the enforcement of the Clinical Trials Act in Japan. The manuscripts presenting data from this study will be submitted for publication in quality peer-reviewed medical journals. Study findings will be disseminated via presentations at national/international conferences and peer-reviewed journals.Trial registration numbersUMIN000029947 and jRCTs041180059.

Reduced-Intensity Unrelated Cord Blood Transplantation for Adult Patients with Severe Aplastic Anemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4408-4408
Author(s):  
Hisashi Yamamoto ◽  
Daisuke Kato ◽  
Naoyuki Uchida ◽  
Kazuya Ishiwata ◽  
Shinsuke Takagi ◽  
...  
Keyword(s):  
Cord Blood ◽  
Aplastic Anemia ◽  
Therapeutic Option ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Cell Number ◽  
Adult Patients ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Reduced Intensity

Abstract Although unrelated cord blood transplantation (UCBT) has become a viable therapeutic option widely applicable for adult patients with hematological diseases, UCBT for severe aplastic anemia (SAA) remains to be controversial due to higher incidence of graft failure (GF) relative to the other stem cell sources. To evaluate the feasibility of UCBT for SAA, we retrospectively analyzed results for 11 adult patients with SAA who received first UCBT after reduced-intensity conditioning regimen (RI-UCBT) in Toranomon Hospital. Median age was 49 years (range, 20–70). Nine of them were non-responders to intensive immunosuppressive therapy and were multiply transfused, and two patients were fulminant type with no neutrophils in peripheral blood at diagnosis. The conditioning regimen consisted of fludarabine 125mg/m2, melphalan 80mg/m2, and 4 Gy of total body irradiation. Graft-versus-host disease prophylaxis was composed of cyclosporine alone (n=2), tacrolimus alone (n=2), and tacrolimus plus mycophenolate mofetil (n=7). Median total nucleated cell number and median CD34+ cell number were 2.65 × 107/kg (range, 1.83–4.39) and 0.70 × 105/kg (range, 0.27–1.52), respectively. Serological HLA disparities were as follows; 6/6 (n=3), 5/6 (n=2), and 4/6 (n=6). Ten of the 11 patients achieved primary neutrophil and platelet engraftment. Median time to an absolute neutrophil count > 0.5×109/liter and an unsupported platelet count > 20×109/liter were 18 days (range, 12–28) and 42.5 days (range, 26–64) respectively. All patients who achieved engraftment resulted in complete hematological recovery with complete donor chimerism, except for one patient who developed late GF at three years after UCBT. All 2 who experienced GF (1: primary GF, 1: late GF) were rescued by second RI-UCBT. Two of the 11 patients died from IPS (n=2), and remaining 9 patients are alive, having survived for 18.7 months (range, 2–71 months). Six out of 7 patients who survived more than 6 months were free from immunosuppressant. The probabilities of overall survival and event-free survival at 2 years after UCBT were 77.8% and 68.2%, respectively. Our results here strongly indicated feasibility and effectiveness of RI-UCBT for adult SAA patients with high engraftment rate and low treatment-related mortality. RI-UCBT could be considered as a viable therapeutic option for those who lack suitable HLA-matched sibling donors and failed immunosuppressive therapy.

Myeloablative Conditioning with Pharmacokinetic-Targeted Intravenous Busulfan and Cyclophosphamide in Unrelated Cord Blood Transplantation for Myeloid Malignancies in Children

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1965-1965
Author(s):  
Henrique Bittencourt ◽  
Marc Ansari ◽  
Mohamed Aziz Rezgui ◽  
Samira Meziani ◽  
Marie-France Vachon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Myeloablative Conditioning ◽  
Platelet Recovery ◽  
Myeloid Malignancies ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
Unrelated Cord Blood

Abstract Abstract 1965 Unrelated cord blood transplantation (UCBT) has been an increasingly used stem cell source in hematopoietic stem cell transplantation for myeloid malignancies in children when a related HLA-identical donor is unavailable. Advantages of UCBT include a less stringent HLA compatibility and prompt availability. Myeloablative regimens for UCBT use a combination of total body irradiation or Busulfan (Bu) with Cyclophosphamide (Cy) or other chemotherapy agent. Intravenous Bu has a more predictable bioavailability comparing with oral Bu. Nevertheless, there is still an important variation in Bu pharmacokinetics (PK) between patients. Dose modification of Bu based on its first-dose PK might decrease the risk of toxicity and graft rejection and increase its antitumoral effect. In order to analyse the role of a myeloablative conditioning regimen of PK-adapted Bu for myeloid malignancies we analyzed 30 consecutive first UCBT performed in children between dec/2000 and aug/2010. Median age at transplant was 6.3(0.6-17.3) years, 18 (60%) were male and median weight was 26.2 (6.9-81.1) kg. There were 18 acute myeloid leukemia (AML) and 12 myelodysplastic syndromes (MDS). Seven, nine, and two patients with AML were transplanted in first remission (CR1), second remission (CR2), or in advanced phase of disease (>CR2 or in relapse), respectively. Twenty-eight patients received a single UCBT. Seven, thirteen, and ten patients received a 6/6, 5/6 and 3–4/6 HLA-matched graft. Median infused nucleated cells (NC) and CD34+ cells were 5.28 × 107/kg and 2.07 × 105/kg of recipient body weight, respectively. Cyclosporin A and steroids were used as graft versus host disease (GvHD) prophylaxis. All patients received anti tymoglobuline. Conditioning regimen consisted of PK-adapted Bu (targeted steady-state concentration - Css - between 600–900 ng/ml) and Cy 200 mg/kg (n=27), Melphalan 135 mg/m2 (n=2) or Cy 120 mg/kg and etoposide 30 mg/kg (n=1). PK data were available for all but one patient. For five patients the initial prescribed dose of Bu was not changed, for two patients initial prescribed dose of Bu was decreased and for 22 patients the initial prescribed dose of Bu was increased (median increase of 24.8% - range: 5.3–56,3 %). Median follow-up was 53 months. Cumulative incidence (CI) of neutrophil (>0.5×109/L) at D+60 and platelet recovery (>50×109/L) at D+150 was 83% and 83%, respectively. Median time to neutrophil and platelet recovery was 20 days and 69 days, respectively. There was a single case of graft failure. CI of acute GVHD grade II-IV at D+180 was 14% (with one case of grade III aGvHD). There were two cases of VOD (one mild and one moderate). Two-years CI of transplant-related mortality (TRM) was 17% (three patients died due to infections and one due to graft failure). CI of relapse at 2 years was 30% (with all relapses occurring within two years of UCBT). Event-free survival (EFS) at 5 years was 53%. EFS for patients with MDS (67%) and AML (45%) were not significantly different (P=0.45). Overall survival (OS) at 5 years was 61%. There was a tendency to a better OS for patients with MDS vs AML (83% vs 49% - P=0.19). For AML, disease status did not influence survival. In conclusion, UCBT for myeloid malignancies is a viable option when a HLA-identical sibling donor is unavailable. PK study for ivBu is important as most patients needed Bu dose adjustment. PK-adapted BU seems to reduce acute toxicity and graft failure. However TRM due to infection and relapse remains a problem. New conditioning regimens associating fludarabine with PK-adapted Bu alongside with modification in GvHD prophylaxis to improve immunological recovery might contribute to further decrease TRM and relapse and improve UCBT results, especially for AML. Disclosures: No relevant conflicts of interest to declare.

Successful Engraftment of Cord Blood Transplantation Following Reduced-Intensity Conditioning Regimen Using Fludarabine and Busulfan for Advanced Hematologic Malignancies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5066-5066
Author(s):  
Yuji Satou ◽  
Toshiro Nagasawa ◽  
Takayuki Azuma ◽  
Yuji Miura ◽  
Tsunehiko Komatsu
Keyword(s):  
Cord Blood ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Chronic Phase ◽  
Hematologic Malignancies ◽  
Blood Transplantation ◽  
Donor Type ◽  
Primary Graft Failure ◽  
Reduced Intensity

Abstract Background: The potential role of reduced-intensity cord blood transplantation (RI-CBT) without total body irradiation (TBI) in adults remains unclear. We investigated the feasibility of RI-CBT using non- TBI regimen for the treatment of patients with advanced hematologic malignancies. Methods: Twenty-three patients (median age, 61, range, 38–74) with advanced hematologic malignancies were enrolled in this study (18 patients in refractory or relapsed phase,5 patients in remission or chronic phase). Conditioning regimen comprised of fludarabine 30 mg/m2 on days −8 to −3, busulfan 4 mg/kg p.o. or 3.2 mg/kg i.v. on days −6 to −5. In one cases. we administered busulfan 3.2mg/kg i.v. on days −6 to −3, because of blastic crisis. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus alone. Engraftment was defined as an absolute neutrophil count > 0.5 x 10E9/l. Primary graft failure was defined as the complete loss of donor-type hematopoiesis without engraftment. Secondary graft failure was defined as the loss of donor-type hematopoiesis after primary engraftment. Median follow-up of surviving patients was 1096 days (range, 53–1207). Primary endpoint was engraftment. All patients provided informed consent in accordance with the requirements of Institutional Review Board. Results: All the patients tolerated the conditioning regimen. Median dose of infused nuclear cells was 2.7x10E7 /kg (range, 1.9–4.6). Twelve patients achieved engraftment at a median of day 20.5 (range, 10–36), but two of them developed secondary graft failure. Complete donor-type chimerism was documented within 30 days of transplant in six patients. Primary graft failure was diagnosed in remaining eleven patients. Six of them, underlying disease progressed despite conditioning regimens. As of August 2007, five patients survived (3 patients in complete remission, one patients relapsed after transplantation, the other one not reached remission). Estimated 1-year overall survival rate was 20.7% (95% confidence interval, 3.0–38.4%). Conclusions: Though the pre-transplant condition of patients were not good, engraftment was obtained with approximately the half patients. This study demonstrated the feasibility of RI-CBT using non-TBI regimen for adult patients with advanced hematological diseases; however, high incidences of disease progression before engraftment was significant problem. RI-CBT may become the choice of treatment for patients with advanced hematologic malignancies that are incurable with conventional treatments.

Sign in / Sign up

Export Citation Format

Share Document