Unrelated Cord Blood Cell Transplantation for Acquired Severe Aplastic Anemia: The Report from the Japan Cord Blood Bank Network.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2020-2020
Author(s):  
Seiji Kojima ◽  
Ayami Yoshimi ◽  
Shuichi Taniguchi ◽  
Junichi Hara ◽  
Toshimitsu Matsui ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Aplastic Anemia ◽  
Cumulative Incidence ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Severe Aplastic Anemia ◽  
Bone Marrow Donor ◽  
Grade Ii ◽  
Unrelated Cord Blood

Abstract Treatment approaches for patients with severe aplastic anemia (SAA), who failed immunosuppressive therapy and lack a bone marrow donor remains a great challenge. Unrelated cord blood transplantation (UCBT) has not been recommended for SAA because of historical poor outcome with high rate of engraftment failure. To evaluate the current feasibility of UCBT in SAA, we retrospectively analyzed the outcomes of 31 patients (median age 28 years old; ranged 0.9–72.3 years old) with SAA, who received UCBT as the first graft between 1998 and 2006 in Japan. Median disease duration before UCBT was 337 day (31–5063 days). By serology, HLA loci were matched in 4 recipient-donor pairs and mismatched (1–2 loci) in 27 patients. A minimum cell count of 2 × 107 nucleated cells/kg body weight was infused in all patients. Engraftment was observed in 17 of 24 evaluable patients. The median times to achieve a neutrophil count ≥ 0.5 × 109/l and a platelet count ≥ 50 × 109/l were 19 days (range 12–35 days) and 59 days (range 39–145 days), respectively. The results of chimerism analysis were available in 9 of them and all of them showed complete donor chimerism (>99%) except one with autologous recovery. Late rejection was seen in one patient. Acute GVHD (≥ grade II) was observed in 5 of 18 evaluable patients (grade II; n=4, grade III; n=1) (cumulative incidence =17.1%) and chronic GVHD was observed in 4 of 14 evaluable patients (extensive: n=1, limited: n=3) (cumulative incidence =19.7%). Currently, 13 patients are alive, having survived for median 22.5 months (ranged 3 to 77 months) after UCBT (overall survival at 2 years=40%). Causes of death of 18 patients were following: graft failure (n=7), bacterial/fungal infections (n=3), hepatic veno-occlusive disease (n=3), and others (n=5). The conditioning regimen appeared to be the most important factor for the outcome and low dose total body irradiation (2–4 Gy) + fludarabine (90–250/ mg/m2) and cyclophosphamide (50–100 mg/kg or 2250/mg/m2) (n=5) gave the best outcome with 80% of survival. The GVHD prophylaxis with single agent (cyclosporine or tacrolimus) related with a better engraftment rate than 2 or more agents (84.4% vs 47.3%, p=0.02). These results suggest that UCBT can be a salvage treatment for patients without a bone marrow donor and warrant further evaluation in prospective studies. Optimization of conditioning regimen will improve the engraftment and outcome of UCBT.

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 (>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<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.

Unrelated Cord Blood Does Not Increase An Overall Risk Of Invasive Fungal Infections Compared To Unrelated Bone Marrow: A Single Center Retrospective Analysis For 749 Recipients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4541-4541 ◽  
Author(s):  
Yuki Asano-Mori ◽  
Hideki Araoka ◽  
Muneyoshi Kimura ◽  
Daisuke Kaji ◽  
Hikari Ota ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Fungal Infections ◽  
Chronic Gvhd ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Systemic Corticosteroids ◽  
Grade Ii ◽  
Unrelated Cord Blood

Background Invasive fungal infections (IFIs) are of great concern after allogeneic hematopoietic stem cell transplantation (HSCT), the risk of which is considered to be particularly prominent among cord blood transplantation (CBT) recipients. Patients and Methods We retrospectively analysed the records of 749 adult patients who underwent CBT or unrelated bone marrow transplantation (uBMT) for the first time at the Toranomon Hospital between 2002 and 2012, and who had neither prior history nor suspicious findings of IFIs. As prophylaxis for IFIs, fluconazole (FLCZ) or itraconazole (ITCZ) capsules were conventionally used until around 2006, which were then changed to newer mold-active agents including ITCZ oral solution, voriconazole or micafungin after their approval in Japan, the choice of which was subjected to physician's discretion. Results Engraftment achieved in 418 CBT patients and 198 uBMT patients with a significantly longer neutropenic period in CBT patients (median 20 days vs 18 days, P<0.001), whereas 37 patients underwent re-transplantation and 96 died before engraftment. The incidences of grade II-IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD were significantly less frequent after CBT compared to uBMT (40% vs 54% and 17% vs 46%, both P<0.001). Systemic corticosteroids at ≥0.5mg/kg/day was given in fewer CBT patients compared to uBMT patients (59% vs 66%, P=0.07). The median durations of immunosuppressants and antifungal prophylaxis were significantly shorter in CBT patients compared to uBMT patients (118 days vs 302 days and 315 days vs 491 days, both P<0.001). As prophylaxis for IFIs, 194 CBT patients and 91 uBMT patients received FLCZ/ITCZ capsules, while 341 CBT patients and 123 uBMT patients received newer mold-active agents. Seventy-nine patients (57 in CBT and 22 in uBMT) developed IFIs with a cumulative incidence of 12.2%, at a median of 27 (1-1646) days after HSCT. About 60% of the patients developed IFIs by day 50 and the percentage reached more than 90% until 1 year. The median onset was significantly earlier in CBT patients compared to uBMT patients (day 19 vs day 61, P=0.007). The cumulative incidence of IFIs was significantly higher in CBT patients compared to uBMT patients during 50 days after HSCT (7.9% vs 3.8%, P=0.04), but became significantly lower thereafter until 1 year (2.7% vs 6.9%, P=0.02), and an overall incidence was almost similar between the 2 groups (12.6% vs 11.6%, P=0.58) (Figure 1). Four patients had 2 infectious episodes caused by different fungal species, and a total of 83 infectious episodes were documented. Eighty-one cases were breakthrough infection during antifungal prophylaxis (FLCZ/ITCZ capsules in 28, and newer mold-active agents in 53). Invasive aspergillosis (IA) was the most common, accounting for 67.9% (proven in 11, probable in 46), followed by invasive candidiasis (IC), (19.3%; candidemia in 15, encephalitis in 1). Although the incidences of IA and IC were comparable between CBT and uBMT patients, relatively rare type of IFIs caused by Trichosporon (4 cases), Mucor (2 cases) and Rodotorula (1 case) exclusively occurred in CBT patients, except one case of Fusarium infection in a patient who relapsed after uBMT. Grade II-IV acute GVHD, extensive chronic GVHD and systemic corticosteroids at ≥0.5mg/kg/day were identified as significant risk factors of IFIs for both groups (HR 1.89, P=0.01, HR 4.16, P=0.006, and HR 1.83, P=0.02). However, the impact of all these were not apparent in CBT patients (HR 1.59, P=0.16, HR 2.18, P=0.29 and HR 1.48, P=0.22), in contrast with the powerful impact in uBMT patients (HR 2.51, P=0.049, HR 10.23, P=0.03 and HR 2.87, P=0.03). Although the cessation of antifungal prophylaxis significantly increased the risk of IFIs in uBMT patients (HR 5.95, P=0.01), it showed no impact in CBT patients (HR 0.87, P=0.89). IFIs were main causes of death in 21 patients, which significantly affected non-relapse mortality in both CBT and uBMT patients (HR 3.93 and HR 6.08, both P<0.001). Conclusion Unrelated cord blood did not increase an overall incidence of IFIs, because higher risk in the early post-transplant period was counterbalanced by the dramatically decreased risk due to lower frequencies of GVHD and its treatment in the later period. Particular attention might be required to the early-onset IFIs due to fungi other than Aspergillus or Candida species, in order to further decrease the risk of IFIs after CBT. Disclosures: No relevant conflicts of interest to declare.

Reduced-Intensity Unrelated Cord Blood Transplantation for Adult Patients with Severe Aplastic Anemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4408-4408
Author(s):  
Hisashi Yamamoto ◽  
Daisuke Kato ◽  
Naoyuki Uchida ◽  
Kazuya Ishiwata ◽  
Shinsuke Takagi ◽  
...  
Keyword(s):  
Cord Blood ◽  
Aplastic Anemia ◽  
Therapeutic Option ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Cell Number ◽  
Adult Patients ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Reduced Intensity

Abstract Although unrelated cord blood transplantation (UCBT) has become a viable therapeutic option widely applicable for adult patients with hematological diseases, UCBT for severe aplastic anemia (SAA) remains to be controversial due to higher incidence of graft failure (GF) relative to the other stem cell sources. To evaluate the feasibility of UCBT for SAA, we retrospectively analyzed results for 11 adult patients with SAA who received first UCBT after reduced-intensity conditioning regimen (RI-UCBT) in Toranomon Hospital. Median age was 49 years (range, 20–70). Nine of them were non-responders to intensive immunosuppressive therapy and were multiply transfused, and two patients were fulminant type with no neutrophils in peripheral blood at diagnosis. The conditioning regimen consisted of fludarabine 125mg/m2, melphalan 80mg/m2, and 4 Gy of total body irradiation. Graft-versus-host disease prophylaxis was composed of cyclosporine alone (n=2), tacrolimus alone (n=2), and tacrolimus plus mycophenolate mofetil (n=7). Median total nucleated cell number and median CD34+ cell number were 2.65 × 107/kg (range, 1.83–4.39) and 0.70 × 105/kg (range, 0.27–1.52), respectively. Serological HLA disparities were as follows; 6/6 (n=3), 5/6 (n=2), and 4/6 (n=6). Ten of the 11 patients achieved primary neutrophil and platelet engraftment. Median time to an absolute neutrophil count &gt; 0.5×109/liter and an unsupported platelet count &gt; 20×109/liter were 18 days (range, 12–28) and 42.5 days (range, 26–64) respectively. All patients who achieved engraftment resulted in complete hematological recovery with complete donor chimerism, except for one patient who developed late GF at three years after UCBT. All 2 who experienced GF (1: primary GF, 1: late GF) were rescued by second RI-UCBT. Two of the 11 patients died from IPS (n=2), and remaining 9 patients are alive, having survived for 18.7 months (range, 2–71 months). Six out of 7 patients who survived more than 6 months were free from immunosuppressant. The probabilities of overall survival and event-free survival at 2 years after UCBT were 77.8% and 68.2%, respectively. Our results here strongly indicated feasibility and effectiveness of RI-UCBT for adult SAA patients with high engraftment rate and low treatment-related mortality. RI-UCBT could be considered as a viable therapeutic option for those who lack suitable HLA-matched sibling donors and failed immunosuppressive therapy.

Successful sustained engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with severe aplastic anemia

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3240-3242 ◽  
Author(s):  
Hisashi Yamamoto ◽  
Daisuke Kato ◽  
Naoyuki Uchida ◽  
Kazuya Ishiwata ◽  
Hideki Araoka ◽  
...  
Keyword(s):  
Cord Blood ◽  
Aplastic Anemia ◽  
Umbilical Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Cell Number ◽  
Severe Aplastic Anemia ◽  
Umbilical Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Reduced Intensity

Abstract We retrospectively analyzed 12 consecutive adult severe aplastic anemia patients who received unrelated umbilical cord blood transplantation after a reduced-intensity conditioning regimen (RI-UCBT). The conditioning regimen consisted of 125 mg/m2 fludarabine, 80 mg/m2 melphalan, and 4 Gy of total body irradiation. The median infused total nucleated cell number and CD34+ cell number were 2.50 × 107/kg and 0.76 × 105/kg, respectively. Eleven of the 12 patients achieved primary neutrophil and platelet engraftment. All patients who achieved engraftment had complete hematologic recovery with complete donor chimerism, except for one patient who developed late graft failure 3 years after RI-UCBT. Two of the 12 patients died of idiopathic pneumonia syndrome, and the remaining 10 patients are alive, having survived for a median of 36 months. Our encouraging results indicate that RI-UCBT may become a viable therapeutic option for adult severe aplastic anemia patients who lack suitable human leukocyte antigen-matched donors and fail immunosuppressive therapy.

scholarly journals Unrelated Cord Blood Transplantation for Severe Aplastic Anemia

2008 ◽  
Vol 14 (9) ◽  
pp. 1057-1063 ◽  
Author(s):  
Ayami Yoshimi ◽  
Seiji Kojima ◽  
Shuichi Taniguchi ◽  
Junichi Hara ◽  
Toshimitsu Matsui ◽  
...  
Keyword(s):  
Cord Blood ◽  
Aplastic Anemia ◽  
Cord Blood Transplantation ◽  
Severe Aplastic Anemia ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Unrelated Cord Blood
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