Comparative Single Institute Analysis of Cord Blood Transplantation From Unrelated Donors with Unrelated Bone Marrow or Related Peripheral Blood Stem-Cell Transplants in Adult Patients with Acute Myeloid Leukemia / Myelodysplastic Syndrome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3382-3382
Author(s):  
Kazuhiro Masuoka ◽  
Kazuya Ishiwata ◽  
Masanori Tsuji ◽  
Shinsuke Takagi ◽  
Hisashi Yamamoto ◽  
...  

Abstract Abstract 3382 Poster Board III-270 Recently, unrelated cord blood transplant (UCBT) has been widely applied to those who lack available related or unrelated donors. However, some results in those reports were conflicting, especially for transplantation-related mortality (TRM). The US study demonstrated a poor outcome for TRM in CBT recipients compared with human leukocyte antigen (HLA)–matched bone marrow transplant (BMT) recipients (NEJM. 2004; 351:2265). On the other hand, Takahashi et al showed excellent outcome (TRM 9% and disease free survival, DFS 70%) in CBT (Blood. 2007; 109:1322). Since there has been not much data available regarding this issue, we retrospectively extracted to adult patients with acute myeloid leukemia (AML) / myelodysplastic syndrome (MDS) and analyzed retrospectively the results of 245 recipients who underwent allogeneic stem cell transplantation (allo-SCT). We reviewed medical records of 290 patients with AML/MDS who had received allo-SCT from an unrelated donor between June 2000 and March 2009 at our institute, Tokyo, Japan. Since patients who had previous hematopoietic stem cell transplantations, active serious infection and performance status > 2, were excluded, 45 were subjected to the following analysis. Finally, the study includes 245 recipients of UCB (n = 140), UBM (n = 63), and related mobilized peripheral blood (RPB, n = 42) for de novo AML (n = 132), MDS overt AML (n = 79), refractory anemia (RA, n = 15), and refractory anemia with excess of blasts (RAEB, n = 19). Patient s median age for UCB, UBM, and RPB recipients were 59 (17 - 72), 55 (23 – 70), and 55 (22 – 67), respectively. UCB recipients had more serologically HLA-mismatched grafts (97% vs. 38% vs. 22%, P < .01), were conditioned more frequently with melphalan (75% vs. 27% vs. 20%, P < .01) and with total body irradiation (86% vs. 80% vs. 12%, P < .01 and used more tacrolimus (78% vs. 81% vs. 15%, P < .01) and less methotrexate (0% vs. 98% vs. 85%, P < .01) for graft-versus-host disease (GVHD) prophylaxis. Disease status consisted of standard (CR1 or CR2 of AML and RA, n = 62) and advanced groups(other status, n = 183). UCB recipients had significantly advanced status relative to UBM and RPB recipients (84% vs. 57% vs. 69%, P < .01) at the time of transplantation. Other characteristics such as sex, diagnosis, and body weight were balanced among three groups. Median follow-up time of survivors was 787 days (119 – 2314), 1050 days (244 – 3059), and 1287 days (141 – 3004) for UCB, UBM, and RPB recipients, respectively. The incidence of grade II–IV acute GVHD among evaluable UCB recipients was lower than those of UBM and RPB recipients (32% vs. 54% vs. 59%, P < .01). Similarly, the incidences of chronic GVHD for evaluable UCB, UBM, and RPB recipients were 36%, 69%, and 66%, respectively (P < .01). The estimated overall survival (OS) and DFS rates at 5 years post-transplantation were 36% (95% confidence interval Åm95%CIÅn; 25 - 47%) and 35% (95%CI; 26 - 44%) for UCB, 55% (95%CI; 40 - 69%) and 51% (95%CI; 37 - 64%) for UBM, and 39% (95%CI; 22 - 55%) and 25% (95%CI; 8 - 41%) for RPB (OS, P < .01 and DFS, P < .01). In the standard group, OS and DFS rates were not significantly different in the three groups (OS, UCB 63% vs. UBM 70% vs. RPB 49%, P = .39 and DFS, UCB 63% vs. UBM 70% vs. RPB 39%, P = .10). Similarly, in the advanced group, there were not significantly difference in the three groups (OS, UCB 30% vs. UBM 41% vs. RPB 35%, P = .23 and DFS, UCB 29% vs. UBM 38% vs. RPB 24%, P = .27). Compared with UBM and RPB recipients, UCB recipients had delayed hematopoietic recovery at 60 day (UCB 85% vs. UBM 97% vs. RPB 100%, Hazard ratio ÅmHRÅn= 0.49; 95%CI: 0.40 0.59; P < .01). Five-year estimated TRM and relapse rate (RR) were not significantly different in the three groups (TRM, UCB 34% vs. UBM 29% vs. RPB 50%, P = .39 and RR, UCB 30% vs. UBM 20% vs. RPB 28%, P = .28). < Conclusion> In this analysis, there was no apparent difference in the risks of TRM and RR between the UCB and UBM/RPB recipient groups. OS and DFS in both groups were also comparable among standard and advanced groups. Finally, our clinical results suggest that UCBT could be as safe and effective a stem-cell source as UBMT or RPB transplant for adult AML/MDS patient. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2010-2010
Author(s):  
Kazuhiro Masuoka ◽  
Shigesaburo Miyakoshi ◽  
Kazuya Ishiwata ◽  
Masanori Tsuji ◽  
Shinsuke Takagi ◽  
...  

Abstract &lt;Objectives&gt; Promising results of cord blood transplants from unrelated donors have been reported in adults. To compare of outcomes of bone marrow transplants (BMT, n = 51), and umbilical cord blood transplants (UCBT, n = 110) from unrelated donors in adult patients with acute myeloid leukemia (AML) / myelodysplastic syndrome (MDS), we analyzed retrospectively the results of 161 adult patients with AML and MDS in our hospital. &lt;Patients and Methods&gt; We reviewed medical records of 161 patients with AML/MDS who had received a hematopoietic stem cell transplant from an unrelated donor between August 2000 and April 2007 at Toranomon Hospital, Tokyo, Japan. &lt;Results&gt; Patient’s median age was 55 years (17–71). Diagnoses include de novo AML (n =85), MDS overt AML (n=48), refractory anemia (RA) (n=13), and refractory anemia with excess of blasts (RAEB) (n=15). Disease status consisted of standard (CR1 of AML and RA, n=30) and advanced (other status, n=131). Recipients of UCBT had more advanced disease than recipients of BMT at the time of transplantation (89 percent vs. 65 percent, P&lt;0.001). The median number of nucleated cells that were infused was 0.26×108 per kilogram of the recipient’s body weight for cord blood and 2.5×108 per kilogram for bone marrow (P&lt;0.001). The major difference were higher number in the UCBT group of HLA mismatches (defined by serology for class 1 and molecular typing for DRB1).The donor was HLA mismatched in 96% of UCBT recipients, and in 41% of BMT recipients (P&lt;0.001). Other significant differences were observed in preparative regimens, and graft-versus-host disease (GVHD) prophylaxis. Nonadjusted estimates of 2-year OS and DFS rates were 53% and 48% in the BMT group, and 33% and 25% in the UCBT group (P&lt;0.001). However, 2-year OS and DFS rates in the standard group were not significantly different in the two groups (63% and 63% in the BMT group, and 75% and 58% in the UCBT group; p=0.98 and 0.32). Compared with BMT recipients, UCBT recipients had delayed hematopoietic recovery (Hazard ratio [HR]= 0.52; 95% confidence interval [95CI]: 0.36–0.75; p&lt;0.001), increased 100 day TRM (HR=3.07; 95CI 1.45–6.51; p&lt;0.01) and decreased grade II–IV acute graft-versus-host disease (aGVHD) (HR=0.58; 95CI 0.35–0.96; p=0.03). Two-year relapse rate was not significantly different in the two groups. &lt;Conclusion&gt; We conclude that UCBT from an unrelated donor is a therapeutic option for adult AML/MDS patients who lack an HLA-identical donors. Higher mortality, especially from non-relapse causes, is the biggest problem to be solved to increase the feasibility of this approach.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 401-401
Author(s):  
Yang Jo Chung ◽  
Chul Won Choi ◽  
Christopher Slape ◽  
Terry Fry ◽  
Peter D. Aplan

Abstract The myelodysplastic syndromes (MDSs) are a group of hematologic stem cell disorders characterized by ineffective hematopoiesis and dysplasia. A large number of chromosomal aberrations including deletions, amplifications, inversions, and translocations, some of which involve the NUP98 gene, have been associated with MDS. Recently an MDS mouse model expressing a NUP98-HOXD13 (NHD13) fusion gene was developed, which faithfully recapitulates all of the key features of MDS. Although it is well-established that acute myeloid leukemia (AML) is transplantable, there is no evidence that MDS is a transplantable condition. Therefore, in order to develop evidence for MDS as a hematopoietic stem cell (HSC) disease, we attempted to transfer MDS to normal recipients through bone marrow transplantation (BMT). All the recipients transplanted with bone marrow (BM) cells from NHD13 mice with MDS showed anemia, leukopenia, lymphopenia, and neutropenia when compared to recipients of wild-type (WT) littermates. The homing efficiency of the NHD13 primitive progenitor cells (Lineage negative [Lin−], Sca-1+) was about 2 fold higher than WT, and there was no significant difference in BM cellularity between the recipients of NHD13 and WT BM, indicating that the NHD13 recipients had ineffective hematopoiesis. These phenomena were reproduced in secondary recipients using primary recipients of NHD13 BM as donor mice. In secondary transplantation assays, 3 out of 5 recipients developed acute myeloid leukemia (AML) at 16 weeks post-transplantation. Morphological features of MDS, including nuclear-cytoplasmic asynchrony, binucleate cells, hypersegmented neutrophils, and giant platelets were detected in BM and peripheral blood of NHD13 donor, primary and secondary recipients by cytospin preparations. In competitive repopulation assays, mice transplanted with equal numbers of WT and NHD13 BM cells showed a decreased percentage of NHD13 cells in the peripheral blood, but an increased percentage of NHD13 cells in the BM, again providing evidence of ineffective hematopoiesis of the NHD13 cells. The transplantation of lineage depleted cells from BM has shown that the transplantable cells for MDS reside in the Lin− population of NHD13 BM. These findings demonstrate that MDS can be transferred to healthy recipients by BMT, supporting the concept that MDS originates in a transplantable multilineage hematopoietic stem cell.


Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1866-1868 ◽  
Author(s):  
Hesham M. Amin ◽  
Iman Jilani ◽  
Elihu H. Estey ◽  
Michael J. Keating ◽  
Amanda L. Dey ◽  
...  

AbstractThe hallmark of myelodysplastic syndrome (MDS) is enhanced apoptosis in myeloid, erythroid, and megakaryocytic cells in the bone marrow leading to ineffective hematopoiesis. Recent studies suggested that immunological and microenvironmental factors play a role in the pathophysiology of this disease. We report a significant increase in apoptosis in bone marrow B lymphocytes in MDS as compared to that found in acute myeloid leukemia and healthy controls. Furthermore, we demonstrate that patients with refractory anemia with excess blasts in transformation (RAEB-T) had apoptosis levels in lymphocytes similar to those seen in other subtypes of MDS. Our findings suggest that the alterations in B lymphocytes in the form of increased apoptosis can be seen in MDS and support the concept that immune modulation plays a role in the pathophysiology of MDS.


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