scholarly journals Comparison of Conditioning Regimens with or without Antithymocyte Globulin for Unrelated Cord Blood Transplantation in Children with High-Risk or Advanced Hematological Malignancies

2015 ◽  
Vol 21 (4) ◽  
pp. 707-712 ◽  
Author(s):  
Changcheng Zheng ◽  
Zuo Luan ◽  
Jianpei Fang ◽  
Xin Sun ◽  
Jing Chen ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Antithymocyte Globulin ◽  
Hematological Malignancies ◽  
Cord Blood Transplantation ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Conditioning Regimens ◽  
Unrelated Cord Blood

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.

Impact Of Rabbit Anti-Thymocyte Globulin-Containing Reduced-Intensity Conditioning Regimens On Outcomes Of Adults Undergoing Unrelated Cord Blood Transplantation For Hematological Malignancies

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 412-412 ◽  
Author(s):  
Laurent B Pascal ◽  
Luciana Tucunduva ◽  
Annalisa Ruggeri ◽  
Didier Blaise ◽  
Mohamad Mohty ◽  
...  
Keyword(s):  
Cord Blood ◽  
Total Dose ◽  
Hematological Malignancies ◽  
Advanced Disease ◽  
Cord Blood Transplantation ◽  
Disease Status ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Reduced Intensity

Abstract To assess the impact of antithymocyte globulins (ATG), on patients' outcome after unrelated cord blood transplantation (UCBT) following a reduced-intensity regimen (RIC), we conducted a retrospective registry-based analysis on 661 adults with hematological malignancies who underwent unrelated single (s) or double (d) UCBT following RIC with the TBI/cyclophosphamide/fludarabine regimen (TCF) between 2004 and 2011 in EBMT centers. Participating centers were asked to provide additional information on type, timing and total dose of ATG used. Diagnosis was AML/ALL in 51%, MDS/CML in 19% and lymphoid malignancies in 30%; 28% of patients were transplanted in early disease status, 28% in intermediate and 44% in advanced disease. Thirty percent of patients had a previous autologous transplantation. Single UCBT was used in 226 (34%) patients, while 435 (66%) were transplanted with dUCBT. HLA matching was defined as low resolution for HLA-A and HLA-B, and high resolution for HLA-DRB1, and for dUCBT, the highest degree of HLA incompatibility was considered. Therefore, most of the HLA incompatibilities were 4/6 (n=435, 72%). Median number of collected total nucleated and CD34+ cells were 4.4x107/kg and 1.6x105/kg, respectively. All patients received TCF, with TBI 2Gy (86%), TBI 4Gy (12%) and TBI 6Gy (2%). Rabitt ATG (rATG) was used as part of RIC in 82 patients (12.4%) with a median total dose of rATG (Fresenius®) of 20mg/kg (5-60) and rATG (Genzyme®) of 8mg/kg (5-15). GVHD prophylaxis consisted of cyclosporine A (CsA)+ mycophenolate mofetil (MMF) in 91%, Csa alone±other in 9%. The median follow-up was 36.3 months. When compared to patients not receiving rATG-TCF, patients given rATG-TCF had more MDS/CML (30% vs 20%, p<0.01), were transplanted more recently (p=0.02) and there was a trend of being transplanted with more advanced disease (53% vs 43%, p=0.06). Table below shows overall outcomes for 661 patients and univariate analysis for outcomes by the use of rATG-TCF. Type and dose of rATG were not associated with any outcomes. Multivariate (MV) models for outcomes were built adjusting for the differences between 2 groups of rATG-TCF (yes and no) and other risk factors that impact outcomes (patients's age>51 years, positive CMV serology, MDS/CML, advanced disease status, year of transplant, HLA 4/6 and ABO incompatibility). In the final MV models, use of rATG was associated with decreased incidence of aGVHD (HR=0.31, 95%, CI=0.17-0.55, p<0.0001), higher incidence of NRM (HR=1.68, 95% CI=1.16-2.43, p=0.0009) and decreased OS (HR=1.69, 95% CI=1.19-2.415, p=0.003), however it was not associated with engraftment, chronic GVHD and relapse. In rATG-RIC-group, the main cause of death was transplantation related in 51% of cases. Death related to infections was 72% in the rATG-RIC group compared to 39% in the non rATG group. In conclusion, in this retrospective and multicentre analysis, use of rATG as part of TCF regimen, was associated with decreased incidence of acute GVHD, however with increased NRM and decreased OS, probably related to the higher incidence of infections. Despite the retrospective design of our study, we suggest that in UCBT for adults with hematological malignancies given a TCF regimen, systematic use of rATG might be a matter of concern. In addition, timing and dose of rATG are still open questions and only randomized studies may address this issue. Disclosures: Yakoub-Agha: Genzyme: Honoraria, Research Funding.

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