Reduced Intensity Umbilical Cord Blood Transplantation(RI-UCBT) in Adult Patients with Graft Failure or Relapse after First Allogeneic Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5121-5121
Author(s):  
Kazuhiro Masuoka ◽  
Koichiro Yuji ◽  
Yuji Miura ◽  
Tomohiro Myojo ◽  
Daisuke Kato ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Disease Relapse ◽  
Blood Transplantation ◽  
Reduced Intensity ◽  
Neutrophil Engraftment

Abstract Background: Graft failure, graft rejection, or disease relapse post allogeneic hematopoietic stem cell transplantation(HSCT) is life-threatening and serious complication that necessitate consideration for a second transplantation. Graft failure has been more frequently reported in patients with aplastic anemia with T-cell depletion of the graft, in cord blood transplants, or when unrelated or HLA-mismatched related donors were used. In second allogeneic stem cell transplant setting, current questions include suitable stem cell source, additional conditioning, immunosuppression, and the use of a different donor, still remain unknown. We performed a feasibility study of reduced intensity umbilical cord blood transplantation (RI-UCBT) in adult patients with graft failure or disease relapse after first allogeneic transplantation. Patients and Methods: Nine patients (median age, 53 years; range 17–68) with advanced hematological diseases [AML (n=4), ALL (n=2), MDS (n=2), ATL (n=1)] who showed relapse or graft failure after first allogeneic transplantation underwent RI-UCBT with single cord blood unit at Toranomon Hospital between May 2003 and February 2004. Eight cases were in non-CR at transplant. A median time from first to second transplant was 226 days (range 31–475). The median number of mononuclear cells transfused was 2.3 x 107 /kg (range 1.8–3.5). HLA disparities were as follows; 5/6 in two cases, 4/6 in seven cases. Conditioning regimen mainly consisted of fludarabine 25 mg/m2 on days -7 to −3, melphalan 40mg/m2 (n=8) or busulfan 4mg/kg(n=1) day −3 to −2, and 4 Gy total body irradiation on day −1. Graft-versus-host disease (GVHD) prophylaxis was composed of ciclosporin alone (n=6) and tacrolimus alone (n=3). Results: All of them achieved primary neutrophil engraftment (>500/μL) after a median of 22 days (range, 15–32) and achievement of donor T-cell chimerism was confirmed. Four cases developed grade II-IV GVHD, and one case developed limited chronic GVHD. Of all the nine cases received RI-UCBT, seven died from relapse (n=4), sepsis (n=2), and TMA (n=1). Two survived without relapse for +232 and +81 days, respectively. Discussion: Although the number of patients is small and the follow-up period is short, our results corroborate that RI-UCBT for graft failure or relapse post first transplant is tolerated and may be worth considering for further evaluation. Neutrophil engraftment was achieved, however, disease relapse rate and treatment-related mortality is high. The management of disease status and development of ideal conditioning regimen will be the focus of future investigation.

Outcome Of Unrelated Umbilical Cord Blood Transplantation For Children With Osteopetrosis: An Eurocord and Inborn Errors Working Party (IEWP)-EBMT Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2100-2100 ◽  
Author(s):  
Robert Chiesa ◽  
Annalisa Ruggeri ◽  
Marco Zecca ◽  
Franco Locatelli ◽  
Marta Gonzalez-Vincent ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Cell Dose ◽  
Blood Transplantation

Abstract Osteopetrosis (OP) is a genetic disease characterized by increased bone density due to osteoclast dysfunction, leading to life-threatening multi-systemic complications in early childhood. Haematopoietic stem cell transplantation (HSCT) is the only curative approach for most children with OP and can effectively prevent serious complications such as blindness, bone fractures, hydrocephalus and cranial nerve compression. Since timing of transplant is critical in OP, umbilical cord blood is an attractive stem cell source, due to its prompt availability. We analysed the outcomes of unrelated umbilical cord blood transplantation (UCBT) in 45 children with osteopetrosis transplanted in EBMT centers between 1996 and 2012, using data reported to Eurocord. Median age at UCBT was 6 months (1.1 month - 7.4 years). Donor-recipient pairs were matched at HLA-A and -B (antigen level) and DRB1 (allelic level) in 14 or HLA mismatched at 1 (n= 23) or 2 (n= 7) loci. Information on conditioning regimen was available for 42 patients; it was myeloablative (mostly busulfan-based) in 40 children and reduced intensity in 2 patients. GvHD prophylaxis consisted mainly of cyclosporine combined with either prednisolone (n= 20), or methotrexate (n=6), or mycophenolate mofetil (n=3). Anti thymocyte globulin (ATG) or alemtuzumab was given to 37/40 patients. Median number of infused total nucleated cell (TNC) and CD34+ was 13x107/kg and 3.4x105/kg, respectively. Median follow-up for survivors was 44 (range 4-144) months. Neutrophil recovery with donor chimerism was documented in 27/45 patients; 19/25 evaluable patients presented full donor engraftment, while 6 children presented mixed donor chimerism. Median time to neutrophil recovery was 20 (range 10-60) days. Eighteen patients experienced graft failure and 3/18 are alive at last follow up. Information on treatment post-graft failure was available 7/18 children: 6 patients underwent a second HSCT and 3 of them survived. Stem cell dose was associated with a trend for a better probability of donor engraftment: the cumulative incidence of donor engraftment was 46% in patients who received a CD34+ cell dose<2 x 105/kg, versus 71% in children receiving a CD34+ cell dose ≥2x105/kg (p = 0.09). Eleven patients developed grade II-IV acute graft-versus-host disease (aGvHD: n=6 grade II, n=4 grade III, n=1 grade IV) and 5 patients chronic GVHD (cGvHD: n=3 limited, n=2 extensive). Overall survival (OS) at 3 years was 45+8%. Twenty-four patients died after UCBT due to: infections (n=13), acute respiratory distress syndrome (n=2), veno occlusive disease (VOD), (n=2) hemorrhage (n=2), or other causes (n=5). VOD was observed in 7/26 evaluable patients. Stem cell dose and HLA disparity were the only predictors of superior outcome in univariate analysis. The 3-year probability of OS was 50% in patients who received grafts with a CD34+ cell dose >2x105/kg versus 0% in children receiving grafts with a CD34+ cell dose < 2x105/kg (p=0.001). According to HLA disparities, 3-year probability OS was 54% versus 58% versus 0% in patients receiving a 6/6, 5/6 and 4/6 HLA-mismatched graft, respectively (p=0.01). Interestingly, 4/4 children receiving a treosulfan-based myeloablative regimen achieved donor engraftment and 3 children are alive at last follow up. These data suggest that transplantation of unrelated UCB is a valid alternative for children with OP without a matched sibling or a suitable matched unrelated adult donor. The use of CB units mismatched at >1 HLA locus should be avoided due to worse survival. The incidence of primary graft failure was high and therefore the optimization of the conditioning regimen and/or the use of CB units containing a high TNC and CD34+ cell dose must be considered in this setting. The use of treosulfan-based conditioning regimens is worth further investigation, as well as the use of defibrotide prophylaxis to reduce the risk of VOD in this population of high risk patients. 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.

Impact of Myeloablative and Reduced Intensity Conditioning On Outcomes After Unrelated Cord Blood Transplantation for Adults with Acute Lymphoblastic Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3117-3117
Author(s):  
Luciana Tucunduva ◽  
Annalisa Ruggeri ◽  
Guillermo Sanz ◽  
Sabine Furst ◽  
Bernard Rio ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Lymphoblastic Leukemia ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Reduced Intensity Conditioning ◽  
Blood Transplantation ◽  
Conditioning Regimens ◽  
Reduced Intensity

Abstract Abstract 3117 Allogeneic hematopoietic stem cell transplantation is the only curative option for high risk or relapsed acute lymphoblastic leukemia (ALL) in adults. In the absence of an HLA identical sibling donor, HLA matched adult donor or HLA mismatched cord blood are alternative sources of stem cell to treat those patients. However, very few data on the outcomes after umbilical cord blood transplantation (UCBT) for adult ALL using myeloablative or reduced intensity conditioning regimens have been reported. With this aim, we conducted a retrospective survey on the outcomes after UCBT for adult ALL and a more specific analysis for patients with cytogenetic data transplanted in remission with either a myeloablative (MAC) or reduced intensity conditioning regimen (RIC). From 1996 to 2011, 433 adult patients (pts) received a UCBT for ALL. Overall 2-year LFS was 37% for pts in first complete remission (CR1) (n=199), 32% for CR2 (n=138) and 9% for advanced disease (n=96). Complete cytogenetic information at diagnosis was available for 316 pts, of those 251 pts were transplanted in CR1 (63%, n=157) or in CR2 (37%, n=132). Median age at UCBT was 33 years (18 to 66 years) and 76% of the pts (n=191) had an abnormal karyotype at diagnosis. Pts were analyzed according to the presence of t(9;22) as Ph+ (n=115) and Ph- (n=136). Double CBT was performed in 109 pts (43%) and the median total nucleated cell dose at freezing was 4.02×107/kg. Most pts received CBU with one (30%, n=74) or two (56%, n=136) HLA disparities. A myeloablative (MAC) conditioning was given to 177 pts (70%) and 73 (30%) received a reduced intensity conditioning (RIC). Overall 2-year leukemia- free survival (LFS) was 36±3%; 37% for Ph- and 35% for Ph+ pts (p=0.74). On multivariate analysis, 3 factors were associated with improved LFS: age <44 years (HR: 0.6, p=0.004), CR1 at transplant (HR: 0.6, p=0.005) and use of RIC (HR: 0.6, p=0.015). Since the outcomes were different according to disease status and conditioning intensity, a subgroup analysis was performed. Results are shown in Table 1. In pts transplanted with MAC (n=177), most frequent conditioning regimens were Cy-TBI (27%) and Bu+Flu+Thio (25%). Median follow-up (FU) was 26 and 35 months for those in CR1 (n=107) and CR2 (n=70), respectively. Cumulative incidence (CI) of 60-day neutrophil recovery was 87% for pts in CR1 and 83% for those in CR2; acute GVHD was 43% and 37%, respectively. Two-year CI of NRM was 41% for CR1 and 49% for CR2 and 2-year RI was 24% for CR1 and 22% for CR2. Two-year LFS was 35% for CR1 and 30% for CR2. No factor was found to be associated with LFS, relapse nor NRM. One-hundred and four pts died, 81 of transplant-related causes (79%, n=46 for CR1 and 74% n=35, for CR2), mainly due to infections (53% n=24 for CR1 and 38% n=12 for CR2). In pts transplanted with RIC (n=94), Cy+Flu+TBI regimen was used in 74% (n=54). Median FU was 31 and 34 months and median age was 50 and 39 years for those in CR1 (n=49) and CR2 (n=24), respectively. At 2 years, CI of NRM was 22% for CR1 and 17% for CR2. Two-year RI was 30% and 47%, respectively. Two-year LFS was 49% for CR1 and 36% for CR2. For pts in CR1, univariate analysis showed that younger age (< 50 years) was associated with improved LFS (62% × 36%, p=0.042) and lower NRM. Eighteen patients died, 6 of relapse and 12 of transplant-related causes. All patients who died from NRM were 50 years or older. UCBT is an option to treat high risk and relapsed adult ALL. Pts transplanted with MAC had an LFS comparable with that reported with other stem cell sources, but strategies to reduce toxicity are still needed, especially for pts in CR2. Results with RIC are encouraging and may be considered in younger pts. Importantly, in this large series outcomes after UCBT for Ph+ ALL were not statistically different from those compared to Ph-. Table 1. Outcomes according to disease status at UCBT and conditioning regimen MAC RIC CR1 (n=107) CR2 (n=70) CR1 (n=49) CR2 (n=24) LFS (2y) 35 ± 5% 30 ± 6% 49 ± 7% 36 ± 10% Relapse (2y) 24 ± 4% 22 ± 5% 30 ± 7% 47 ± 11% NRM (2y) 41 ± 5% 49 ± 6% 22 ± 6% 17 ± 8% 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.

scholarly journals Graft failure following reduced-intensity cord blood transplantation for adult patients

2006 ◽  
Vol 132 (1) ◽  
pp. 36-41 ◽  
Author(s):  
Hiroto Narimatsu ◽  
Masahiro Kami ◽  
Shigesaburo Miyakoshi ◽  
Naoko Murashige ◽  
Koichiro Yuji ◽  
...  
Keyword(s):  
Cord Blood ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Adult Patients ◽  
Blood Transplantation ◽  
Reduced Intensity

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