Double Cord Blood Transplantation for Patients with High Risk Hematological Diseases: Delayed Immune Recovery and High Incidence of Infections.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2923-2923 ◽  
Author(s):  
Vanderson Rocha ◽  
Adrienne Madureira ◽  
Marie Robin ◽  
Marievonick Carmagnat ◽  
Juliana F. Fernandes ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Nk Cells ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Immune Recovery ◽  
Blood Transplantation ◽  
High Incidence

Abstract The possibility to perform double cord blood transplantation (dCBT) has extended its use in adults with high risk hematological disease; however there is no data on immune recovery and report on infections complications. We have performed a phase II study on 16 dCBT from 2004 to 2006. Ten patients had high risk malignant disorders (ALL=1, AML+MDS=6, CML=3) and 6 high risk of rejection (SAA=4, PNH=1 and Fanconi Anemia=1). Among those patients, 4 (25%) received a dBCT as a rescue of previous non-engrafted transplants (2 SAA, 1 AML and 1 CML). Analyses of T, B and NK cells phenotype were performed once a month during the first 3 months and ever two months until 12 months. The median age was 21 years (11–42), the median weight 63 kg (30–90) and the median follow-up was 6 months (3–18). Conditioning regimen varied according to disease (myeloablative) or second transplant (reduced intensity), all but two patients have received ATG. GVHD prophylaxis consisted in CsA + steroids in 12 patients and associated to MMF in 4. Results: 2 patients did not engraft (both with SAA), one patient relapsed 8 days after dCBT, and 12 patients engrafted at a median of 23 days (14–42). Chimerism available in 12 patients before day 100 showed both CB units in 7 patients. After day 100, in 8 evaluable patients, 3 patients had evidence of both CB units engraftement. Acute GVHD was observed in 5 patients (grade II in 4 and grade III in 1) and chronic GVHD in 7 out of 12 at risk. During the first 100 days, 9 CMV reactivations were diagnosed; 4 HSV (resistant to acyclovir); 3 HHV6 infections; 3 EBV reactivations; 2 adenovirus diseases, 4 VRS infections, 2 septicaemias, 3 fungal infections, 1 disseminated toxoplasmosis. After day 100, we observed 4 CMV reactivations, 1 CMV disease, 1 HSV, 1 adenovirus disease and 1 EBV-PTLD. Important lymphopenia was observed in all patients (median of 259mm3 at 3 months (n=14); 389 at 6 months (n=13) and 480 at 12 months (n=8). Median numbers of CD3/CD4 at 3, 6 and 12 months were: 8, 15 and 46 mm3 respectively; of NK cells 203, 249 and 115mm3, and of B cells were 0, 0 and 110 mm3, respectively. At 6 months overall survival was 58±14% and event-free survival was 52±14%. Six patients died: 2 of relapse and 4 from infections. Three out of 4 patients have been rescued of previous non-engraftment and are alive and well (4–18 months). In conclusion, despite the short follow-up dBCT seems to be an option to treat patients with high risk diseases and without a suitable compatible HLA donor. High incidence of infections and delayed immune recovery are major problems after dCBT.

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.

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.

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 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.

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.

scholarly journals Adult cord blood transplant results in comparable overall survival and improved GRFS vs matched related transplant

2020 ◽  
Vol 4 (10) ◽  
pp. 2227-2235
Author(s):  
Prashant Sharma ◽  
Enkhtsetseg Purev ◽  
Bradley Haverkos ◽  
Daniel A. Pollyea ◽  
Evan Cherry ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Blood Transplantation ◽  
Cord Blood Transplant ◽  
Conditioning Regimens ◽  
Related Donor

Abstract We compared outcomes among adult matched related donor (MRD) patients undergoing peripheral blood stem cell transplantation and adult patients undergoing double unit cord blood transplantation (CBT) at our center between 2010 and 2017. A total of 190 CBT patients were compared with 123 MRD patients. Median follow-up was 896 days (range, 169-3350) among surviving CBT patients and 1262 days (range, 249-3327) among surviving MRD patients. Comparing all CBT with all MRD patients, overall survival (OS) was comparable (P = .61) and graft-versus-host disease (GVHD) relapse-free survival (GRFS) was significantly improved among CBT patients (P = .0056), primarily because of decreased moderate to severe chronic GVHD following CBT (P &lt; .0001; hazard ratio [HR], 3.99; 95% confidence interval [CI], 2.26-7.04). Among patients undergoing our most commonly used MRD and umbilical cord blood (CB) myeloablative regimens, OS was comparable (P = .136) and GRFS was significantly improved among CBT patients (P = .006). Cumulative incidence of relapse trended toward decreased in the CBT group (P = .075; HR, 1.85; CI 0.94-3.67), whereas transplant-related mortality (TRM) was comparable (P = .55; HR, 0.75; CI, 0.29-1.95). Among patients undergoing our most commonly used nonmyeloablative regimens, OS and GRFS were comparable (P = .158 and P = .697). Cumulative incidence of both relapse and TRM were comparable (P = .32; HR, 1.35; CI, 0.75-2.5 for relapse and P = .14; HR, 0.482; CI, 0.18-1.23 for TRM). Our outcomes support the efficacy of CBT and suggest that among patients able to tolerate more intensive conditioning regimens at high risk for relapse, CB may be the preferred donor source.

Clinical Outcome of Cord Blood Transplantation by Age with Units Shipped from Tokyo Cord Blood Bank.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5178-5178
Author(s):  
Tokiko Nagamura-Inoue ◽  
Cui Yan ◽  
Hideki Kodo ◽  
Hideo Mugishima ◽  
Michiko Sugo ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Group Iii ◽  
High Risk Patients ◽  
Blood Transplantation ◽  
Group I ◽  
Risk Patients ◽  
Group Ii

Abstract Recently, cord blood transplantation (CBT) for adult is rapidly increasing in number, Especially for the patients over 50 years of age. By the end of 2003, 224 units were shipped for the patients Group I: <15 y.o. 39%, Group II: 15~50 y.o.40% and Group III :> 50 y.o.21%. We analyzed 152 patients with hematological malignancies including ALL, AML, CML, MDS, malignant lymphoma, myeloma and neuroblastoma reported from CBT center in the world by the end of 2003. Patients and Methods:Group I included 58 patients with 13 standard risk and 45 high risk patients and showed mean±SD of age; 5.3 ±4.1y.o.,BW; 20.5±13.4kg, CB volume at collection; 91.6±27.1ml, NC; 5.5±3.3x107/kg, CFC; 8.6±6.4x104/kg, CD34; 1.5±1.1x105/kg, Group II: 64 cases with 25 standard and 39 high risk patients and age; 30.6±10.3y.o., BW; 51.9±9.5kg, CB volume at collection;116.6±27.7ml, NC;2.6±0.7x107/kg, CFC;5.2±2.6x104/kg and CD34;0.8±0.5x105/kg, Group III: 30 cases with 9 standard and 21 high risk patients and age; 54.1±3.3y.o., BW;55.9±11.0kg, CB vol.at collection;118.8±24.7ml NC;2.4±0.4x107/kg, CFC;4.8±1.9x104/kg and CD34;0.8±0.4x105/kg. The patients who underwent CBT for graft failure (GF) of prior transplant were excluded. Conditioning regimen in Group I demonstrated 54 patients with full regimen and 4 with reduced intensity regimen (RIST); in Group II, 62 patients with full regimen and 2 RIST; and in Group III, 14 cases full regimen and 15 cases RIST. Results: Cumulative myeloid engraftment was seen 67.2% in Group I, 73.4% in Group II and 46.7% in Group III (*Group II vs. Group III: P<0.05). Overall survival /EFS on day 100 showed 73.4%/59.4% in Group I, 74.0%/58.6% in Group II and 43.3%/34.5% in Group III (*Group III vs. others: P<0.05). In Group III, the survival rate indicated 42.8% in full regimen group and 13.3% in RIST group at 1year after CBT. In Group I, four patients died of GF, 13 of relapse, 11 of Transplantation related disease (TRD); in Group II, 5 patients died of GF, 8 of TRD, 10 of relapse. In Group III, four patients died of TRD, 3 of GF and 3 of relapse in full regimen, while in RIST, six patients died of TRD, 1 of relapse and 1 of acute GVHD. Conclusion: The application of CBT has been expanded to the elderly patients (>50 y.o.), although the conditioning regimen and the special medical care for the complications in the early pahse after UCBT has remained to be discussed.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document