Reduced-Intensity Unrelated Cord Blood Transplantation (RICBT) for Elderly Patients with Hematological Malignancies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2349-2349
Author(s):  
Yoshiki Nakae ◽  
Rie Kojima ◽  
Aki Chizuka ◽  
Yuko Osajima ◽  
Toshiyuki Noguchi ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Blood Transplantation ◽  
Kaplan Meier ◽  
Low Incidence ◽  
Unrelated Cord Blood

Abstract Abstract 2349 Introduction: Incidence of hematological malignancies is higher in elderly population. However, standard chemotherapy has not been established and the potential role of RICBT has remained unclear. This study reports the results of RICBT for elderly patients with hematological malignancies, retrospectively. Objective: To investigate the feasibility of RICBT. Primary endpoints were engraftment and overall survival (OS). secondary endpoint was transplant-related mortality (TRM). Patients and Methods: Between Feb.2009 and Jun.2010, 29 patients (median age 70 years, range 58–76) received RICBT for hematological malignancies. Primary diseases were divided into 2 groups; advanced (intermediate and high risk; n=21) or standard (n=8). All cases in 70's were included in the high risk. Median follow up time was 238 days (range 8–464).Conditioning regimen and GVHD prophylaxis consisted of fludarabine, busulfan or cyclophosphamide, and TBI 2Gy with tacrolimus± MTX for <70 years(n=18), fludarabine, busulfan or cyclophospamide, and ATG 7.5mg/kg with cyclosporine ± MTX for >70 years (n=11) and <70 years with comorbidities. Median total transplanted nucleated cells: 3.2 × 10|jE7 cells (2.0–4.8); Median CD34+: 0.4× 10|jE5 cells (0.3–2.9); HLA match: 5/6 (n=1), 4/6 (n=28). Time to event curves were plotted by using the actuarial method of Kaplan-Meier, and differences between curves were analyzed by log-rank tests. Results: Neutrophile (>500/μL) and platelet engraftment (>20,000/μL) were observed in 89.6% (95% CI; 79–100) at day 60 (median; 18.0 days, range; 13–28), and 62.1% at day 100 (median; 36.5 days, range; 17–60), respectively. Neutrophile engraftment was 100% in TBI regimen (median; 18 days, range; 13–28), 75% in ATG regimen (95% CI; 51–100, median; 19 days, range; 16–27)(p=0.04). Platelet engraftment was 77% in TBI regimen, 42% in ATG regimen, respectively (p=0.06). Primary graft failure occurred in 3% of all cases. Cumulative incidence of acute GVHD (II-IV) was 58% (95% CI; 39–78) at day 100 (median; 27.5 days, range; 13–82), 81% (95% CI; 62–100, median; 28 days, range; 17–82) in TBI regimen and 12.5% (95% CI; 0–35, median; 13 days, range; 13) in ATG regimen, respectively (p=0.01). The 1-year estimated OS was 51% (95% CI: 25–77) in all cases, 51% (95% CI: 13–90) in TBI, and 48% (95% CI: 18–77) in ATG, respectively (p=0.08). According to the age, OS was 80% (95% CI: 45–80) in 50's, 53% (95% CI: 20–86) in 60's, and 38% (95% CI: 0–77) in 70's (P=0.0765). Causes of TRM included infections (n=5 including 3 cases in 70's), TMA (n=2). Incidence of TRM at day 100 was 20% (95% CI; 4–35, median; 47 days, range; 8–79), 7% in TBI regimen (95% CI; 0–21, median; 79days), 41% in ATG regimen (95% CI; 9–72, median; 30 days, range; 9–72). Incidence of TRM, according to the age, was 40%,0%, and 52% in 50's,60's, 70's, respectively. Discussion and Conclusion: Because of the high incidence of high risk disease and TRM, despite low incidence of GVHD, RICBT is associated with a low OS in patients over 70 years compared with those who are under 70 years. Eligibility of RICBT needs to be investigated, especially in 70's patients, and further studies are warranted to clarify the safety in elderly patients. Disclosures: No relevant conflicts of interest to declare.

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

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

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

scholarly journals Intensified Myeloablative Unrelated Cord Blood Transplantation for High-Risk or Advanced Hematological Malignancies: Experience at a Single-Institution in China

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1222-1222
Author(s):  
Zimin Sun ◽  
Huilan Liu ◽  
Baolin Tang ◽  
Xiaoyu Zhu ◽  
Wen Yao ◽  
...  
Keyword(s):  
Retrospective Study ◽  
High Risk ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Hematological Malignancies ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Neutrophil Engraftment

Abstract Introduction : Unrelated cord blood transplantation (CBT) is one of the most promising curative treatment modalities for hematological malignancies. But the data was limited in China. This retrospective study evaluated the clinical outcomes of intensified myeloablative unrelated CBT for high-risk or advanced hematological malignancies in our single center. Patients and Methods: From September 2006 to December 2013, Total of 187 high-risk or advanced hematologic malignancies underwent intensified myeloablative unrelated CBT. All CBT patients received a myeloablative conditioning regimen of TBI/Ara-C/CY [total body irradiation (TBI, total 12 Gy, 4 fractions) (d-7, d-6) arabinoside cytarabine (Ara-C) (2.0g/m2 every 12h for 2 days) (d-5, d-4) and cyclophosphamide (CY, 60 mg/kg daily for 2 days) (d-3, d-2)] (age≥14 years or primary induction failure or no remission after relapse), or Fludarabine/BU/CY2 [fludarabine (Flu, 30mg/m2 daily for 4 days) (d-8~ -5), busulfan (0.8mg/kg every 6h for 4 days) (d-7~ -4) and CY (60 mg/kg daily for 2 days) (d-3, d-2)] (For lymphoid malignancies patients with age ＜14 years or prior radiotherapy which would presuppose a high risk of toxicity), or Ara-C/BU/CY2 [ Ara C (2.0g/m2 every 12h for 2 days) (d-9, d-8), (busulfan (0.8mg/kg every 6h for 4 days) (d-7~ -4) and CY (60 mg/kg daily for 2 days) (d-3, d-2)](for myeloid malignancies patients with age < 14 years or prior radiotherapy which would presuppose a high risk of toxicity), and G-CSF was given with 5 ug/kg daily by subcutaneous injection one day prior to Ara-C with 3 days. For GVHD prophylaxis, all patients were given a combination of cyclosporine and short-course mycophenolate mofetil, and no patient received antithymocyte globulin (ATG). Results: Total of 181 patients (97.3%) achieved neutrophil engraftment and platelet engraftment, and the median number of days was 18 days (range 12~37 days) and 37.5days (range 15~112 days), respectively. Total nucleated-cell dose (≥5.2×107 / kg) and total CD34+ cell dose (≥3.8×105 / kg) were the favorable factors predicting for a higher probability of neutrophil engraftment (p =0.012, 0.025). The cumulative incidence of pre-engraftment syndrome (PES) and day-100 grade Ⅱ-Ⅳ acute GVHD was 75.4% (95% CI, 65.2-84.2%) and 28.34% (95% CI, 28.13~28.55%), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute GVHD 100 days after transplantation was 32.6% (95% CI, 42.3-22.8%)in the PES group and 15.2% (95% CI, 8.3-22.6%) in the non-PES group (р=0.016). Multivariate analysis showed that BU/CY2 based conditioning and without PES were significant risk factors for graft failure [RR=2.34 (95% CI, 1.32- 6.12), p =0.015; RR=2.89 (95% CI, 1.25- 6.82), p =0.009]. The median follow-up time was 27（7~89）months. Transplant-related mortality at 180 days and relapse at 3 years after CBT was 24.9% (24.7~25.2%) and 14.7% (14.6~14.9%). Probabilities of 3-year overall survival (OS) and disease-free survival (DFS) were 61.2% (95% CI, 51.3%- 72.3%) and 58.6% (95% CI, 49.5%- 67.9%), respectively. For pediatric patients, 3-year OS and DFS were 66.2% (95% CI, 56.4%- 75.8%) and 64.8% (95% CI, 54.6%- 74.2%); for adult patients, 3-year OS and DFS were 54.5% (95% CI, 45.8%- 63.7%) and 50.3% (95% CI, 41.5%- 60.1%), respectively. Conclusions: To the best of our knowledge, this is the largest clinical study of unrelated CBT reported in China. This retrospective study indicates that intensified myeloablative CBT procedures are associated with significant favorable outcomes in survival advantage in high-risk or advanced hematological malignancies. Disclosures No relevant conflicts of interest to declare.

Reduced-Intensity Unrelated Cord Blood Transplantation (RICBT) for Over 65 Year-Old Elderly Patients with Myeloid Malignancies

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4495-4495
Author(s):  
Aki Chizuka ◽  
Rie Kojima ◽  
Yoshiki Nakae ◽  
Ko Miyamoto ◽  
Kazuko Arai ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Relapse Rate ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Platelet Recovery ◽  
Myeloid Malignancies ◽  
Day Range

Abstract Abstract 4495 <Introduction> Incidence of myeloid malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is higher in elderly population. However, standard chemotherapy has not been established and the potential role of RICBT has remained unclear. This study reports the results of RICBT for elderly patients with myeloid malignancies. <Objective> To investigate the feasibility of RICBT. Primary endpoints were engraftment and overall survival (OS). 2nd endpoints were transplant-related mortality (TRM) and relapse rate. <Patients and Methods> Between Mar.2009 and Jul.2011, 21 patients (median age 70 years, range 65–74) received RICBT for myeloid malignancies (de novo AML; n=7, MDS related; n=14). Primary diseases were divided into 2 groups; advanced (high risk; n=11) or standard (CR1 & 2; n=10). Median follow up 9.5 months (0.3–29).Conditioning regimen was fludarabine 200mg/m2, busulfan, and TBI 2Gy(n=9) or ATG 7.5mg/kg (n=12).Immunosuppresants were tacrolimus± MTX (n=13) or cyclosporine ± MTX (n=8). Median total nucleated cells (TNC): 2.6 × 10^7 cells (2.0–4.8); Median CD34+: 0.4 × 10^5 cells (0.2–2.9); HLA match: 5/6 (n=1), 4/6 (n=20). Time to event curves were plotted by using the actuarial method of Kaplan-Meier, and differences between curves were analyzed by log-rank tests. <Results> Neutrophile (>500/μ L) and platelet recovery (>20,000/μ L) were observed in 86% (95% CI; 82–87) at day 60 (median; 17 day, range; 12–27), 62% (95% CI; 41–83) at day 100 (median; 32 day, range; 41–83), respectively. Neutrophile engraftment was 100% in TBI regimen (median; 16 days, range; 13–20), 79% in ATG regimen (median; 19 days, range; 12–27) (P=0.09). Platelet engraftment was 86% (95% CI; 60–100) in TBI regimen, 42% (95% CI; 14–70) in ATG regimen, respectively (p=0.02). Cumulative incidence of acute GVHD (II-IV) was 33% (95% CI; 13–53) at day 100 (median; 24days, range; 10–82), 73% (95% CI; 17–82, median; 25 days, range; 17–82) in TBI regimen and 14% (95% CI; 0–33, median; 11.5 days, range; 10–13) in ATG regimen, respectively (P=0.02). The 1-year OS was 64% (95% CI; 46–86) in all cases, 71% (95% CI; 38–100) in TBI regimen, 63% (95% CI; 37–89) in ATG regimen, respectively (P=0.55,Figure1). According to the age, OS was 81% (95% CI; 57–100) in 60’s, 45% (95% CI; 14–76) in 70’s, respectively (P=0.04). Causes of TRM included infections (n=2) and late graft failure (n=1), all cases in 70’s and received ATG. Relapse rate was 19% (95% CI; 2–36) in all cases, 43% (95% CI; 6–80) in TBI regimen, and 7% (95% CI; 3–68) in ATG regimen at 500 days, respectively (P=0.06). <Discussion and Conclusion> RICBT with ATG regimen is associated with a high TRM in over 70 year-old high risk patients. However, ATG regimen may conduct low incidence of acute GVHD and relapse rate. Eligibility of RICBT needs to be investigated, especially in over 70 patients, and further studies are warranted to clarify the safety in elderly patients. Disclosures: No relevant conflicts of interest to declare.

Outcomes after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia. An Eurocord-Netcord Survey.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 304-304 ◽  
Author(s):  
Vanderson Rocha ◽  
Gerard Michel ◽  
Nabil Kabbara ◽  
William Arcese ◽  
Juan Ortega ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cumulative Incidence ◽  
Lymphoblastic Leukemia ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Advanced Phase ◽  
Unrelated Cord Blood

Abstract Unrelated cord blood transplantation (UCBT) is an alternative option to treat children with haematological diseases without an HLA-identical donor. We have analyzed a total of 323 children with ALL receiving an UCBT, from 1994 to 2004 in 99 transplant centres in 24 countries, mostly in Europe. Cumulative incidence with competing risk and KM estimates were used to calculate outcomes. Seventy six children were transplanted in CR1, 136 in CR2 and 111 in more advanced phase of the disease. Among those children poor cytogenetics were observed in 89% of children in 1CR, 33% in 2CR and 42% in advanced phase. Twenty percent of children transplanted in advanced phase had been previously autografted. The median age was 6.5 years at UCBT, median cell dose infused was 4.1x107/kg and the median follow time was 22 months (3–96). The cord blood was HLA identical (6/6) in 12% of the cases, 5/6 in 46%, 4/6 in 39% and 3/6 in 3%. All children received myeloablative conditioning regimen (TBI in 66%) and the majority (67%) received CsA+corticoids as GVHD prophylaxis. Cumulative incidence of neutrophil recovery at day 60, platelets recovery (&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.

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.

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.

Reduced Intensity Conditioning Regimen Prior to Unrelated Cord Blood Transplantation In Patients with Acute Myeloid leukemia : Preliminary Analysis of a Prospective Phase II Multicentric Trial on Behalf of Societe Française De Greffe De Moelle Osseuse Et Therapie Cellulaire (SFGM-TC) and Eurocord

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 911-911 ◽  
Author(s):  
Bernard Rio ◽  
Sylvie Chevret ◽  
Stephane Vigouroux ◽  
Patrice Chevallier ◽  
Sabine Furst ◽  
...  
Keyword(s):  
Cord Blood ◽  
De Novo ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Blood Transplantation ◽  
Reduced Intensity Conditioning Regimen ◽  
Prospective Phase ◽  
Grade Ii ◽  
Unrelated Cord Blood

Abstract Abstract 911 Unrelated cord blood transplantation (UCBT) after reduced intensity conditioning regimen (RIC) has extended the use of CB in elderly patients(pts) and those with co-morbidities without an HLA identical donor. To evaluate RIC-UCBT in pts with Acute Myeloid Leukemia (AML), we conducted a prospective phase II multicentric trial in France, whose primary objective was to show a reduction in non-relapse mortality (NRM) from 40% (based on registry data) to 20%. We calculated that at least 76 pts should be enrolled (for controlling type I and type II error rates both at 5%). Inclusion criteria were: 1) de novo and secondary AML, 2) lack of HLA identical unrelated donor (10/10 or 9/10), 3) cord blood units (CBU) with less than 3/6 HLA disparities, 4) a nucleated cell dose before freezing of more than 3×107/Kg within 1 or 2 CBU. The conditioning regimen consisted of cyclophosphamide (50mg/kg) +fludarabine (200mg/m2)+ TBI(2Gy), CsA +MMF as GVHD prophylaxis and GCSF from day +1. Supportive care and infections prophylaxis were given according to the EBMT recommendations. Patients were enrolled in 23 centers from Oct. 2007 to Sept. 2009. This preliminary results include 65 pts, 55% female, median age at diagnosis of 49.7 years (range, 13–65), mostly with de novo AML, extramedullary leukemic involvement of AML in 8%. Cytogenetics was normal in 33 pts (52%), of those 10/33 were FLT3 positive, and abnormal in 48%, including 36% with a complex karyotype and/or abnormality of chr 5, 7, 11 and inv 3. Nine (14%) pts had been previously transplanted. 57% of the pts were transplanted in 1st complete remission (CR1), 40% in CR2 and 3% in non-remission. Median time from diagnosis to transplant was 6.6 months (range, 3.7–24) in pts transplanted in CR1 and was 21 months (range, 5.1–93) for pts transplanted in CR2. Median age was 51 years (14-65), median weight was 65 kg (49-105), 51% were CMV-seropositive. The median follow-up for survivors was 20 months (range 9–30). 51% of the pts had no comorbidity. The Sorror score was 1 in 17%, 2 in 8 and 3 or more in 24%. 60% of the pts received 2 CBU. The median number of nucleated cells (NC) and CD34 infused after thawing were 3.4 x107/kg (0.5-6) and 1.1 x105/kg (0.10-3.1), respectively. Patients transplanted with a single CBU received a median of 2.92 NC x107/kg and of 0.92 CD34 x105/kg. Those transplanted with 2 CBU received 3.5 x107/kg and 1.1 x105/kg, respectively; 3% of the units were HLA matched, 23% 5/6 and 74% 4/6 (HLA defined as low resolution for HLA-A and B and high resolution for HLA-DRB1; the highest HLA disparity between CB and pts was taken into consideration in double CBT). ABO major incompatibility was observed in 40% of the pts (in double CB, the highest incompatibility was considered). Results: Median time to cell recovery was 15 days (95CI: 11–20) for neutrophils and 43 days for platelets. Cumulative incidence (Cum Inc) of neutrophil recovery at day 60 was 86% (95CI: 78–95%); 85% (95CI: 69–99) after 1 CBU and 87% (95CI: 76–98) after 2 CBU (p=ns). Twenty-three pts developed grade II-IV acute(a) GVHD (grade II: n=8; grade III n=14; grade IV n=1); Cum Inc of aGVHD (II-IV) at day 100 was 37% (95CI: 24–47%)(38% (95CI: 20–57) for 1 and 34% (95CI: 19–49) for 2 CBT (p=ns)). At 1 year post-transplant, Cum Inc of chronic GVHD was 13% (95CI: 3–23%) and Cum Inc of NRM was 18% (95CI: 8–28%), with variations according to patient status (20% for pts transplanted in CR1 and 13% for pts transplanted in CR2) or number of CBU (21% for 1 CBU and 16% for 2 CBU). At 1 year, Cum Inc of relapse was 30% (95CI : 19–42%); it was 37% for patients transplanted in CR1 and 19% for patients transplanted in CR2 (p=ns), 32% for those transplanted with one CBU and 29% for those transplanted with 2 CBU (p=ns). At 1 year, overall survival was 60% (95CI: 48–74%) and LFS was 52% (95CI: 41–66%). LFS was 43% (95CI: 29–63%) for pts transplanted in CR1, 68% (95CI: 52–89%) for those transplanted in CR2 (p=0.05). According to number of graft, LFS was 48% (95CI: 31–73%) for those transplanted with 1 CBU and 55% (95CI: 41–74%) for those transplanted with 2 CBU (p=ns). In conclusion, the preliminary results of this prospective trial show the interest of RIC-UCBT in patients with AML without a HLA identical donor. A decreased NRM was observed, based on data with a median follow-up of 20 months. We have observed better LFS in patients transplanted in CR2, probably related to the very high risk group of patients transplanted in CR1. These results will be confirmed in the whole enrolled cohort. 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.

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