scholarly journals Ex Vivo Mesenchymal Precursor Cell–Expanded Cord Blood Transplantation after Reduced-Intensity Conditioning Regimens Improves Time to Neutrophil Recovery

2017 ◽  
Vol 23 (8) ◽  
pp. 1359-1366 ◽  
Author(s):  
Rohtesh S. Mehta ◽  
Rima M. Saliba ◽  
Kai Cao ◽  
Indreshpal Kaur ◽  
Katy Rezvani ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Precursor Cell ◽  
Reduced Intensity Conditioning ◽  
Neutrophil Recovery ◽  
Blood Transplantation ◽  
Conditioning Regimens ◽  
Mesenchymal Precursor Cell ◽  
Mesenchymal Precursor ◽  
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.

Unrelated Cord Blood Transplantation after Reduced Intensity Conditioning (RIC) in Adults with Hematological Malignancy. An EBMT-Eurocord-Netcord, Société Française de Greffe de Moelle et de Thérapie Cellulaire and University of Minnesota Collaborative Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2027-2027
Author(s):  
Vanderson Rocha ◽  
Bernard Rio ◽  
Claudio Brunstein ◽  
Marc Renaud ◽  
Attilio Olivieri ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Disease Status ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Neutrophil Recovery ◽  
Cell Dose ◽  
Blood Transplantation ◽  
Reduced Intensity

Abstract Single center studies have demonstrated promising results in recipients of unrelated umbilical cord blood transplantation (UCBT) treated with a reduced intensity conditioning (RIC). However, little is known about risk factors for outcomes with this strategy. We retrospectively evaluated outcomes after RIC-UCBT in 176 patients with hematological malignancies: 116 had acute leukemia (21 ALL, 77 AML, 18 secAML), 36 lymphoid/plasma-cell diseases (6 Hodgkin, 24 NHL, 4 CLL and 2 Myeloma) and 24 myelodysplastic/myeloproliferative diseases (14 MDS and 10 CML). Median follow-up was 12 months (3–80) and median age 45 years (16–76). At transplant, 51% of patients were in advanced phase of disease and 30% had a previous autologous transplants. The conditioning regimen varied according to disease and centre; however, 95% received Fludarabine (FLU)-containing regimen, 55% being FLU-CY-TBI(2Gy), and ATG/ALG was added in 23%. GVHD prophylaxis consisted most commonly (72%) of CsA+MMF. All received a single UCB unit graft that was HLA identical (6/6) (HLA A and B low resolution and DRB1 allelic typing) in 6%, 5/6 in 27%, 4/6 55% and 3/6 in 11%. The median total nucleated cell dose infused was 2.7 × 107/kg. Median time to neutrophil recovery was 20 days (5–56) and probability of neutrophil recovery was 78±3% at day-60. Chimerism analysis at 3 months was complete in 64%, mixed in 16% and absent (autologous reconstitution) in 19%. In multivariate analysis, cell dose (&lt; vs &gt;2.7 × 107/kg, HR=1.6, p=0.02), HLA compatibility (5–6/6 vs 3–4/6, HR=1.5, p=0.04) and use of FLU+CY+TBI versus other regimens (HR=1.7, p=0.01), were independently associated with neutrophil recovery. At day-100, probability of acute GVHD II–IV was 30% (18% grade II; 6% grade III, 6% grade IV), and no risk factor was associated with its incidence. At 1 year, probability of chronic GVHD was 30%. TRM was 38% at 1 year, being 19% for patients given low dose TBI (&lt;6Gy), vs 61% for those without TBI and 40% for those given a low cell dose (&lt;2.7 × 107/kg), vs 21% for the remainder. In multivariate analysis, both factors were associated with TRM. Probability of relapse at 1 year was 41% and it was associated with disease status and aGVHD (26% in those with and 47% in those without aGVHD, p=0.02). DFS at 1 year was 41% for patients with acute leukaemia, 31% for MDS/CML and 42% for lymphoid/plasma diseases. For those treated with FLU-CY-TBI, DFS was 51% as compared to 28% for those treated with other RICs (p=0.0002). In a multivariate analysis, advanced disease status (HR=1.6, p=0.03) and conditioning regimens other than FLU-CY-TBI (HR=1.9, p=0.004) were associated with decreased DFS. In conclusion, cell dose plays a critical role on engraftment and risk of TRM after UCBT in the RIC setting. Specific RIC regimen, namely FLU-CY-TBI, provides better engraftment, reduced TRM and better DFS. These results support the use of FLU-CY-TBI and UCBT as a strategy for broadening the application of transplant to patients previously excluded on the basis of age, co-morbidities and/or absence of a HLA-matched unrelated donor.

Outcomes After Double Cord Blood Transplantation Compared to Single Cord Blood Transplantation in Adults with Acute Leukemia Given a Reduced Intensity Conditioning Regimen

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 232-232 ◽  
Author(s):  
Vanderson Rocha ◽  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Didier Blaise ◽  
Bernard Rio ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Neutrophil Recovery ◽  
Blood Transplantation ◽  
Reduced Intensity Conditioning Regimen ◽  
Grade Ii ◽  
Reduced Intensity

Abstract Abstract 232 Unrelated cord blood (UCB) is an alternative source of allogeneic hematopoietic stem cell transplantation (HSCT) for adults with acute leukemia lacking a HLA matched donor. Double cord blood unit (dUCBT) has been increasingly used over single CB unit (sUCBT) after reduced intensity conditioning regimen (RIC). Since there is an increased relapse incidence (RI) using RIC-HSCT compared to myeloablative conditioning regimen, we have driven the hypothesis that RI may be decreased and leukemia-free survival (LFS) rate increased after dUCBT compared to sUCBT, due to probably increased graft-versus leukemia (GVL) effect. With this aim, we analyzed 360 adults (>18 years) with ALL (n= 77) or AML (n=238) in CR1 (n=212) and in CR2 (n=148) transplanted with a sUCBT (n=131) or a dUCBT (n=229) after a RIC. Only patients transplanted with a single unit containing more than 2.5×107/kg total nucleated cells (TNC) were included. Patients were transplanted from 2005–2011 in EBMT centers. Comparing the two groups of patients receiving a sUCBT or a dUCBT in CR1, there were no statistical differences according to age, diagnosis (AML or ALL), weight, CMV serostatus, cytogenetics risk, number of HLA incompatibilities. However, dUCBT were performed more recently (2009 vs 2008), the time from CR1 to transplantation was longer (142 days vs 121 days), more frequently transplanted with CY+FLU+TBI2Gy (87% vs 68%), lower frequency of ATG use (21% vs 35%) and finally, dUCBT recipients received higher number of TNC collected (5×107/kg vs 3.9×107/kg) or infused (4×107/kg vs 3.1×107/kg). Median follow-up was 23 months in both groups. Cumulative incidence (CI) of 60 days neutrophil recovery was 82±3% after dUCBT and 76±2% after sUCBT (p=0.86) and frequency of full donor chimerism at day 100, was not statistically different between dUCBT (81%) and sUCBT (86%). At day 100, CI of acute GVHD (grade II-IV) was 35% in both groups, however there was a trend of increased incidence of grade III-IV after sUCBT (19%) compared to dUCBT (10%, p=0.06) but increased incidence of grade II aGVHD after dUCBT (28%) compared to 17% after sUCBT (p=0.05). CI of chronic GvHD at 2 years was 21±4% after dUCBT and it was 12±5% after sUCBT (p=0.15). At 2 years, CI of non relapse mortality (NRM) after dUCBT was 28±4% and it was 30±6% after sUCBT (p=0.87). However, CI of 2y relapse was 21±4% after dUCBT whereas it was 38±2% after sUCBT (p=0.03). In a multivariate analysis adjusting for the differences between the 2 groups, dUCBT was associated with lower incidence of relapse compared to sUCBT (HR=0.74, p=0.01). Therefore, there was an improved 2-y LFS after dUCBT (51±5%) compared to sUCBT (32±3%; p=0.03). This was confirmed in a multivariate analysis (HR=0.64, p=0.04). Concerning patients transplanted in CR2 (n=148), there were no statistically differences of outcomes after dUCBT (n=93) or sUCBT (n=55). At 2y, LFS was 40±6% after dUCBT and 48±3% after sUCBT (p=0.32). In a subgroup analysis of dUCBT (n=118) and sUCBT (n=51) recipients using the same conditioning regimen (CY+FLU+TBI2Gy), 2 y LFS were 54±5% and 33±7% respectively (p=0.05). Conclusion: In this retrospective comparative based registry analysis, in AL patients transplanted in CR1, neutrophil recovery, GVHD and NRM were not statistically different after RIC-dUCBT or RIC-sUCBT, however, dUCBT recipients had decreased relapse incidence and improved LFS. For AL patients transplanted in CR2, there was no benefit of using dUCBT when compared to sUCBT recipients. Disclosures: No relevant conflicts of interest to declare.

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.

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