Unrelated Umbilical Cord Blood Transplantation for Hematological Malignancies Using Fludarabine/BUCY2 Conditioning Regimen

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4572-4572
Author(s):  
Zimin Sun ◽  
Huilan Liu ◽  
Liangquan Geng ◽  
Xingbing Wang ◽  
Kaiyang Ding ◽  
...  
Keyword(s):  
Cord Blood ◽  
Graft Failure ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Median Number ◽  
Myelogenous Leukemia ◽  
Blood Transplantation

Abstract Abstract 4572 Cord blood transplantation (CBT) is largely used to treat patients affected by hematological malignant disorders. Myeloablative TBI-based conditioning appears to provide reliable engraftment after CBT for malignancies. However, the toxicity of TBI limits their widespread use. So far, a standard non-TBI based regimen has not been firmly established. In order to overcome graft failure, we investigated a strategy using Fludarabine (FLU)/BUCY2 regimen in CBT for patients with hematologic malignancies. Seventeen patients(children 16, adult 1) with hematologic malignancies who underwent single-unit CBT used a conditioning regimen comprising FLU 120 ‡r/‡u, intravenous busulfan (BU) 12.8‡r/kg and cyclophosphamide (CY)120 mg/kg (FLU/BUCY2). All patients were given a combination of cyclosporine A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Seventeen patients with acute leukemia (n=13), chronic myelogenous leukemia (n=4) were treated, thirteen of whom were high risk diseases and two were advanced-stage at CBT. Seventeen patients with a median age of 8 years (range,2.5–46 years) and a median weight of 32 kg (range, 12–55 kg)received the median number of nucleated cells and CD34+cells infused were 5.70× 107/kg (range: 3.15–9.60×107/kg) and 3.84× 105/kg (range:1.27–5.24 ×105/kg), respectively. The cumulative incidence of primary donor engraftment was 94% (16 patients); one patient had secondary graft failure. Median time to neutrophil≥0.5×109/L was 17 days (range 12–30) and platelet engraftment (≥20×109/L) was 35 days (range 14–56). Preengraftment syndrome (PES) developed in 71% of the patients at a median of 7days (range: 5–13).9 cases developed acute GVHD (56%), more than grade II in three cases. Two of fourteen patients who survived more than 100 days developed chronic GVHD. 12 cases are alive at a median follow-up of 7 months (range 3~ 11).The probability of overall survival at 100 days and 1 year are 88.2% and 67.9%, respectively. Two cases had extramedullary relapsed. Five cases died of severe GVHD (n=3), pulmonary toxicity (n=1) and secondary graft failure (n=1). Preliminary evidence of the small study suggests successful engraftment and decreasing relapse rate following FLU/BUCY2 regimen for CBT in patients with hematologic malignancies. But it had a tendency towards increasing the incidence of GVHD-related morbidity and mortality. Whether this regimen offers a survival benefit for patients with poor-risk leukemia has to be tested in larger prospective trials. Disclosures: No relevant conflicts of interest to declare.

Phase II Multicenter Study of Busulfan-Fludarabine Conditioning Regimen for cord Blood transplantation in Pediatric Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1928-1928
Author(s):  
Hee Young Ju ◽  
Hyoung Jin Kang ◽  
Ji Won Lee ◽  
Hyery Kim ◽  
Kyung Duk Park ◽  
...  
Keyword(s):  
Cord Blood ◽  
Myeloid Leukemia ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Myeloablative Conditioning ◽  
Once Daily ◽  
Pediatric Acute Myeloid Leukemia ◽  
Blood Transplantation

Abstract Abstract 1928 Introduction. Cord blood transplantation (CBT) has become an alternative transplantation for various diseases. CBT has comparable efficacy with unrelated transplantation, but higher transplantation related mortality (TRM) rate upto 50% in early results has been a major obstacle. To reduce TRM, we studied reduced toxicity myeloablative conditioning regimen with busulfan and fludarabine for CBT in pediatric acute myeloid leukemia (AML) patients. Patients and methods. This study was a phase II prospective multicenter clinical trial (NCT01274195) and 27 patients were enrolled who underwent CBT with upto 2 HLA mismatch cord blood. Conditioning regimen was composed of fludarabine (40 mg/m2 once daily iv on days -8 ∼ -3), busulfan (0.8 mg/kg every 6 hours iv on days -6 ∼ -3) and rabbit thymoglobulin (2.5 mg/kg once daily iv on days -8 ∼ -6). For GVHD prophylaxis, cyclosporine and MMF were used. Results. Nine patients received single unit cord blood, and 18 patients received double unit cord blood. Median dose of nucleated cells and CD34+ cells were 4.23×107/kg (0.5–16.4) and 2.58×105/kg (0.33–6.77), respectively. Primary graft failure developed in 5 patients, and secondary graft failure occurred in 1 patient. Acute and chronic GVHD occurred in 16 patients (59.3%) and 10 patients (37%), respectively. TRM developed in 5 patients (cumulative incidence 22.2%), which included chronic GVHD-associated complication (n=1), post-transplantation lymphoproliferative disease (n=2), pneumonia (n=2), and diastolic cardiomyopathy (n=1). Relapse incidence was 30.9%. The 5-year overall and event-free survival were 46.3% and 40.0%, respectively. Patients who received single unit cord blood showed survival rate of 44.4%, and those who received double unit cord blood showed survival rate of 50%. Univariate analysis revealed that low nucleated cell count (P=0.011), low CD34+ cell count (P=0.002) were independent prognostic factor for survival. Conclusion. Reduced intensity conditioning regimen containing fludarabine and iv busulfan showed lower TRM rate than previous studies with myeloablative conditioning regimens. However graft failure and relapse rate were not satisfactory, and further study for optimization of conditioning regimen is warranted. Disclosures: No relevant conflicts of interest to declare.

A Myeloablative Conditioning Regimen With Fludarabine Demonstrates Good Results In UCBT With Hematologic Malignancies, Especially Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4575-4575
Author(s):  
Juan Tong ◽  
Sun Zimin ◽  
Liu Huilan ◽  
Geng Liangquan ◽  
Zheng Changcheng ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Good Survival ◽  
Myeloablative Conditioning ◽  
Blood Transplantation

Objectives We retrospectively analyzed the safety and efficacy of a myeloablative conditioning regimen without anti-thymocyte globulin (ATG) or total body irradiation (TBI) but with fludarabine (FLU) in unrelated cord blood transplantation (UCBT) for 30 patients with hematologic malignancies. Methods The myeloablative conditioning regimen consisted of FLU, busulfan (BU) and cyclophosphamide (CY). All of the patients received Cyclosporine (CSA) and mycophenolate mofetil (MMF) as graft versus host disease (GVHD) prophylaxis. Results With this conditioning regimen, we achieved high engraftment rates (96.7%) and rapid hematopoietic reconstitution. Acute GVHD occurred in 12 cases of the 29 engraftment patients (41.4%), and 6 cases (20.7%) were of grade III-IV. Chronic GVHD only occurred in 1 of 28 evaluable patients (3.6%). Twenty-three patients (76.7%) became infected, and 3 cases (10.0%) died of severe infections. Cytomegalovirus (CMV) reactivation occurred in 70.0% of the patients, but no CMV diseases were observed, nor did any patients die of CMV infection. The cumulative incidence of relapse (6.7%) was significantly reduced, and none of the acute lymphoblastic leukemia (ALL) patients relapsed. The 3-year overall survival (OS) and event-free survival (EFS) rates were 73.3% and 70.0%, respectively, representing satisfactory survival. The 3-year OS and EFS of the ALL patients was 75.0%. Discussion This conditioning regimen resulted in a high engraftment rate, rapid myeloid reconstruction and a low incidence of infection. Although there were many patients with high-risk disease and disease progression, the regimen resulted in low relapse rates and good survival. None of the ALL patients relapsed after UCBT, indicating that this conditioning regimen could be applied to more patients with ALL. Disclosures: No relevant conflicts of interest to declare.

Unrelated Cord Blood Transplantation in Patients with Hematologic Malignancies in Brazil – A Sociedade Brasileira De Transplantes De Medula Ossea and Eurocord Collaborative Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1211-1211
Author(s):  
Celso Arrais Rodrigues ◽  
Daniela Setubal ◽  
Carmem Bonfim ◽  
Samir Kanaan Nabhan ◽  
Vergílio Antônio Renzi Colturato ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cell Viability ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Hematologic Malignancies ◽  
Median Number ◽  
Myelogenous Leukemia ◽  
Cell Dose ◽  
Blood Transplantation ◽  
Neutrophil Engraftment

Abstract Abstract 1211 Poster Board I-233 Umbilical cord blood transplantation (UCBT) has extended the availability of allogeneic hematopoietic stem cell transplantation to patients without HLA identical donors, mainly for groups of patients with high frequency of rare haplotypes such as the Brazilian population. We evaluated 173 patients who received a single first UCBT in Brazil between with 1993 and 2009 for hematological malignancies from 13 transplant centers. Median age was 8 years (range 1-60) and 58% were male. Sixty-nine patients (40%) had acute lymphoblastic leukemia, 57 (33%) acute myelogenous leukemia, 23 (13%) myelodysplastic syndrome, 18 (10%) chronic myelogenous leukemia and 6 (4%) chronic lymphoid diseases (4 Hodgkin's lymphoma, 1 non-Hodgkin lymphoma and 1 chronic lymphocytic leukemia). Most patients (55%) were transplanted in advanced phases of their diseases. Based on antigen-level HLA-A and -B and allele-level HLA-DRB1 typing, 64 patients (52%) received a cord blood unit with 2 mismatches, 54 (44%) with one mismatch and 5 (4%) received matched units. Conditioning regimen varied according to the disease and the center. Cord blood (CB) units came from CB banks from the USA (n=86), Europe (n=64), and Brazil (n=23). Most patients (94%) received a myeloablative regimen; TBI was used in 86% of cases and ATG/ALG in 82%. Median number of total nucleated cells infused was 4.4×107/kg of recipient weight and the median number of CD34+ cells infused was 1.7×105/kg. Median follow-up time of survivors was 30 months. The cumulative incidence (CI) of neutrophil engraftment at day 60 was 61%, after a median time of 22 days (range 12-55 days) and the CI of platelet engraftment at day 60 was 42%, after a median time of 41 days (range 16-125 days). CI of neutrophil engraftment was only 39% for patients with CML. Nucleated or CD34+ cell dose, number of HLA disparities, bank origin or other patient, disease or transplant-related factors were not associated with engraftment. Techniques of CB thawing, CB unit transportation or cell viability were not analyzed. Only experience of centers (more than 30 UCBT performed) was associated with improved engraftment rate (p=0.05). CI of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 19% and of chronic GVHD only 5% at 3 years. CI of non-relapse related mortality (NRM) was 41%. In a multivariate analysis, factors significantly associated with a higher NRM were patients older than the median age (51% vs. 32% for younger patients, p=0.05), and CD34+ cell dose lower than 1×105/kg (54% vs. 25% P=0.002). At 3 years, the CI of relapse or progression was 20%, and the estimated progression-free survival (PFS) was 36%. In a multivariate analysis, the most important factors associated with a decreased PFS rate were advanced disease status (28% vs. 46% for patients in remission, p=0.001), and a CD34+ cell dose lower than 1×105/kg (21% vs. 42%, p=0.04). At 3 years, estimated overall survival was 41%. In conclusion, UCBT in Brazil seems to be associated with lower engraftment rates as compared to the published experience from other countries. Other factors such as CB unit transportation, CB thawing and cell viability may be analyzed in order to explain the lower engraftment rates. Nevertheless, use of HLA-mismatched UCBT is a valuable alternative for patients with hematologic malignancies in Brazil who lack an HLA-matched related or unrelated donor. UCB units with a higher CD34+ cell count and transplants performed for patients in remission may improve outcomes. Disclosures: No relevant conflicts of interest to declare.

Impact of Early Lymphocyte Recovery On Transplant Outcome After Cord Blood Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3386-3386
Author(s):  
Sara K Tedeschi ◽  
Brian Engelhardt ◽  
Waleed Khalaf ◽  
Janice Tracy ◽  
Jennifer Domm ◽  
...  
Keyword(s):  
Cord Blood ◽  
Nk Cells ◽  
Graft Failure ◽  
Hematological Malignancies ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Rapid Recovery ◽  
Transplant Outcome ◽  
Blood Transplantation

Abstract Abstract 3386 Poster Board III-274 Background: Previous studies have shown that rapid recovery of the absolute lymphocyte count (ALC) is associated with improved transplant outcomes after related and unrelated donor allogeneic stem cell transplantation (allo-SCT). Natural killer (NK) cells are the first lymphocytes to recover after allo-SCT and comprise the majority of peripheral blood lymphocytes after transplantation. Rapid recovery of NK cells at 1 month post allo-SCT has been associated with rapid neutrophil and platelet engraftment and decreased non-relapse mortality. Studies have shown that prolonged T-cell lymphopenia and compensatory expansion of B and NK cells occurs early after cord blood transplantation (CBT). However, no consistent link has been reported between lymphocyte/NK cell recovery and transplant outcome after CBT. Methods: Records from 40 CBT patients at our institution (3/2006-6/2009) were reviewed to determine the impact of lymphocyte recovery on transplant outcome in an IRB-approved study. The ALC was calculated based on the total white cell count and automated differential. Common transplant outcome variables (graft failure, acute and chronic graft versus host disease [GVHD], relapse, non-relapse mortality [NRM] and survival) were studied in relation with ALC at 1, 2, 3 months post-CBT. ALC was analyzed as a continuous variable and also as a dichotomous variable with two distinct groups based on transplant associated outcomes. Results: The majority of patients (n=33, 83%) received CBT for hematological malignancies. The median age was 22 years (range: 0.6-64), and 24 (60%) were male. Disease status at transplantation included 29 (73%) high risk and 8 (20%) standard risk hematological malignancies. Conditioning consisted of myeloablative regimens in 28 (70%) (TBI=21, non-TBI=7). Fifty percent of patients received thymoglobulin with their conditioning regimen. All patients received calcineurin inhibitors and mycophenolate for GVHD prophylaxis. Nineteen patients (48%) received two cord blood units. The median nucleated cell dose was 4.1 × 10 7 cells/kg (range, 2.2-27.3). Five (13%) patients experienced graft failure. Acute GVHD (grade II-IV) occurred in 30 (75%) patients; chronic GVHD occurred in 15 of 31 patients (48%) surviving beyond 100 days. Six (15%) experienced relapse and 9 (23%) died from non-relapse causes. At the time of analysis, 26 patients (65%) were alive with a median follow-up for surviving patients of 422 days (range 51-1256). Patients with ALC<100/μl at 1 month post-CBT showed increased graft failure (4 of 10 vs. 1 of 29; p=0.011). Patients with ALC>150/μl at 1 month post-CBT had decreased NRM (0 vs. 37%±10%, p=0.011) and improved survival (46%± 32% vs. 41%±13%, p=0.013) (Figure 1). There was no impact of ALC at 1, 2, or 3 months post-CBT on relapse or acute or chronic GVHD. There was no relationship between age, type of conditioning regimen, disease risk, number of cord units (one vs. two) or nucleated cell dose on ALC recovery. Conclusion: Our results indicate that ALC 1 month post-CBT is a surrogate marker for engraftment, and that low ALC (<150/μl) identifies an “at-risk” population of patients after CBT. These results point to the importance of developing patient-specific strategies to improve outcomes in those who fail to achieve satisfactory lymphocyte counts in the first month post-CBT. A limitation of this study is the small sample size, and validation in larger prospective multicenter CBT studies is warranted. Disclosures: Jagasia: Genzyme: Research Funding.

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.

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 Treosulfan-based conditioning is feasible and effective for cord blood recipients: a phase 2 multicenter study

2020 ◽  
Vol 4 (14) ◽  
pp. 3302-3310
Author(s):  
Filippo Milano ◽  
Jonathan A. Gutman ◽  
H. Joachim Deeg ◽  
Eneida R. Nemecek ◽  
Joachim Baumgart ◽  
...  
Keyword(s):  
Cord Blood ◽  
Clinical Outcomes ◽  
Hematopoietic Cell Transplantation ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Hematologic Malignancies ◽  
Phase 2 ◽  
Acute Leukemias ◽  
Blood Transplantation

Abstract Although the use of treosulfan (TREO) in conventional donor hematopoietic cell transplantation (HCT) has been extensively evaluated, its use in cord blood transplantation (CBT) for hematologic malignancies has not been reported. Between March 2009 and October 2019, 130 CBT recipients were enrolled in this prospective multicenter phase 2 study. The conditioning regimen consisted of TREO, fludarabine, and a single fraction of 2 Gy total-body irradiation. Cyclosporine and mycophenolate mofetil were used for graft-versus-host disease prophylaxis. The primary end point was incidence of graft failure (GF), and based on risk of GF, patients were classified as low risk (arm 1, n = 66) and high risk (arm 2, n = 64). The median age was 45 years (range, 0.6-65 years). Disease status included acute leukemias in first complete remission (CR; n = 56), in ≥2 CRs (n = 46), and myelodysplastic (n = 25) and myeloproliferative syndromes (n = 3). Thirty-five patients (27%) had received a prior HCT. One hundred twenty-three patients (95%) engrafted, with neutrophil recovery occurring at a median of 19 days for patients on arm 1 and 20 days for patients on arm 2. The 3-year overall survival, relapse-free survival (RFS), transplant-related mortality, and relapse for the combined groups were 66%, 57%, 18%, and 24%, respectively. Among patients who had a prior HCT, RFS at 3 years was 48%. No significant differences in clinical outcomes were seen between the 2 arms. Our results demonstrate that TREO-based conditioning for CBT recipients is safe and effective in promoting CB engraftment with favorable clinical outcomes. This trial was registered at www.clinicaltrials.gov as #NCT00796068.

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.

High Rate of Engraftment and Low Regimen-Related Toxicity Using Fludarabine, Melphalan and Thiotepa Conditioning for Unrelated Donor Cord Blood Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4414-4414
Author(s):  
Stefan O Ciurea ◽  
Partow Kebriaei ◽  
Issa F Khouri ◽  
Muzaffar H. Qazilbash ◽  
Roy B Jones ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Adult Patients ◽  
High Rate ◽  
Unrelated Donor ◽  
Platelet Recovery ◽  
Blood Transplantation

Abstract BACKGROUND: Cord blood transplantation (CBT) represents an alternative source of stem cells for adult patients who lack a matched sibling or unrelated donor. However, the optimal type and intensity of the preparative regimen for patients receiving a CBT is not clear. We hypothesized that a conditioning regimen consisting of fludarabine, melphalan and thiotepa will be associated with an acceptable rate of engraftment and treatmentrelated mortality in patients receiving a CBT. METHODS: 37 patients, median age 31 years (2–57) and a median weight of 73kg, were treated between 8/2003 and 5/2008. All had advanced hematologic malignancies (24 with acute leukemia, 12 with lymphoma and one with CLL) At the time of transplant, 21 pts (57%) were in complete remission (CR) (first CR=20%) and 16 had relapsed/refractory disease. Grafts consisted of double (29 pts) or single (8 pts) CB units. Cytogenetics for patients with acute leukemia were poor in 11, intermediate in 9, good in 1 and unknown in 3 pts. Donor recipient HLA matching was (intermediate resolution class I HLA A and B and high-resolution DRB1): 3/6 (n=1, 1.5%), 4/6 (n=47, 71.2%) and 5/6 (n=18, 27.3%) alleles (n=66 units). Median total nucleated cell count was 1.8×107/kg (range 1–5.8). Nineteen patients received ex-vivo expanded units. The conditioning regimen consisted of melphalan 140 mg/m2 on day -8, thiotepa 10 mg/m2 on day -7, fludarabine 160 mg/m2 over 4 days on days -6, -5, -4, -3, and rabbit ATG 1.25 mg/kg on day -4 and 1.75 mg/kg on day -3 (FMT). Patients with CD 20+ lymphoid malignancies also received rituximab 375mg/m2 on day -9 (n=8, 22%). GVHD prophylaxis was tacrolimus and mini-methotrexate in 23 (62%) and tacrolimus and mycophenolate in 14 pts (38%). RESULTS: 36 patients (97%) were evaluable for engraftment. 1 patient died within 30 days due to progressive leukemia. 34/36 patients (95%) engrafted neutrophils and had hematopoietic recovery with 100% cord blood-derived cells. At day 30, of the 29 patients who received a double CBT, 75% had chimerism derived entirely from one donor while 25% had mixed donors chimerism. Neutrophil recovery to ANC &gt;0.5 × 10e9/l occurred after a median of 21 days (range 6–45) and platelet recovery to &gt;20 × 10e9/l after a median of 37 days (range 26–134, N=24; 67%). 32/37 pts (87%) were in CR after transplant with 16 surviving after a median follow-up of 12.1 months. Thirteen patients (36%) developed gr II–IV aGVHD (gr III–IV aGVHD in 5 patients, 14%), and 13 of 32 patients had cGVHD (40%), with the majority experiencing extensive GVHD. 11 patients (29.7%) relapsed after a median of 7 months post transplant and 12 died of nonrelapse causes. Day-100 treatment-related mortality in this heavily pre-treated population was 10%. Overall, causes of death included disease relapse (n=9), infections (n=6), organ failure (n=3), pulmonary hemorrhage (n=1) and GVHD (n=2). CONCLUSIONS: The FMT regimen was sufficiently immunosuppressive to support high rate of engraftment with acceptable TRM in heavily pre-treated adult patients with advanced hematologic malignancies undergoing CBT. These results support further evaluation of this regimen in CBT.

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.

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