Outcomes Of Cord Blood Transplantation Research Articles

Impact of sex incompatibility on the outcome of single-unit cord blood transplantation for adult patients with hematological malignancies

Donor-recipient sex incompatibility has been associated with transplant outcomes in allogeneic hematopoietic SCT. Such outcomes might be because mHA encoded by Y chromosome genes could be immunological targets for allogeneic T cells and B cells to induce GVHD, GVL effect and graft failure. However, its effect on the outcome of cord blood transplantation (CBT) is yet to be clarified. We retrospectively analyzed 191 adult patients who received single-unit CBT after myeloablative conditioning for malignant disease in our institute. In multivariate analysis, male recipients with female donors had a higher incidence of extensive chronic GVHD (hazard ratio (HR) 2.97, P=0.02), and female recipients with male donors had a lower incidence of platelet engraftment (HR 0.56, P=0.02) compared with female recipients with female donors as the reference. Nevertheless, there was no increase in mortality following sex-incompatible CBT. These data suggested that donor-recipient sex compatibility does not have a significant impact on survival after myeloablative CBT for hematological malignancies.

Frequent Human Herpesvirus-6 Viremia But Low Incidence of Encephalitis in Double-Unit Cord Blood Recipients Transplanted Without Antithymocyte Globulin

Cord blood transplantation (CBT) is a known risk factor for human herpesvirus-6 (HHV-6) infection. We analyzed the nature of HHV-6 infections in 125 double-unit CBT recipients (median age, 42 years) transplanted for hematologic malignancies with calcineurin inhibitor/mycophenolate mofetil prophylaxis and no antithymocyte globulin. One hundred seventeen patients (94%) reactivated HHV-6 by quantitative plasma PCR (median peak, 7600 copies/mL; range, 100 to 160,000) at a median of 20 days (range, 10 to 59) after transplantation. HHV-6 encephalitis occurred in 2 patients (1.6%), of whom 1 died and 1 recovered with therapy. No association was found between high-level HHV-6 viremia (≥10,000 or ≥25,000 copies/mL) and age, diagnosis, conditioning intensity, or dominant unit characteristics or between high-level viremia and transplant outcomes (engraftment, cytomegalovirus reactivation, day 100 grades II to IV acute graft-versus-host disease, day 100 transplant-related mortality, or 1-year disease-free survival). HHV-6 therapy delayed the onset of cytomegalovirus reactivation. Interestingly, HHV-6 resolution was observed in untreated patients, and resolution of viremia correlated with absolute lymphocyte count recovery. We observed a low incidence of encephalitis and no association with CBT outcomes. Our data suggest therapy in uncomplicated viremia may not be warranted. However, further investigation of the risk-to-benefit of HHV-6 viremia treatment and standardization of PCR testing is required.

Effect of ABO Blood Group Incompatibility on the Outcome of Single-Unit Cord Blood Transplantation after Myeloablative Conditioning

ABO blood group incompatibility between donor and recipient has been associated with poor transplant outcomes in allogeneic hematopoietic stem cell transplantation. However, its effect on the outcome of cord blood transplantation (CBT) has yet to be clarified. We retrospectively analyzed 191 adult patients who received single-unit CBT after myeloablative conditioning for malignant disease in our institute. Major mismatch showed a significantly lower incidence of platelet engraftment compared with ABO match as a reference (hazard ratio, .57; P = .01). Nevertheless, there was no increase in graft-versus-host disease, transplant-related mortality, and overall mortality after ABO-incompatible CBT. These data suggested that donor–recipient ABO incompatibility does not have a significant impact on outcome after myeloablative CBT for hematological malignancies.

Alternative Donor Hematopoietic Transplantation For Patients Older Than 50 Years With AML In First Complete Remission: Unrelated Donor and Umbilical Cord Blood Transplantation Outcomes

Post-remission allogeneic transplantation is increasingly used for treatment of the high-risk acute myeloid leukemia (AML) affecting older adults. We analyzed 740 adults over age 50 with AML in first complete remission (CR1) to compare the effectiveness of volunteer unrelated donor (URD) and umbilical cord blood (UCB) graft sources in providing a successful transplant. For prospective cases reported (2005-2010) to the Center for International Blood and Marrow Transplant Research and Eurocord, we evaluated 8/8 HLA allele matched (at HLA-A, -B, -C, -DRB1) n=441; 7/8 matched URD n=94 and UCB n=205 for the outcomes of engraftment, treatment related (non-relapse) mortality (TRM), relapse, leukemia free survival (LFS) and overall survival (OS) using the cumulative incidence and Kaplan-Meier estimators and multivariate Cox regression modeling. Patient age (median 58, range 50-75), gender and CMV serostatus were similar across the treatment groups. However, UCB recipients were less likely to achieve CR within 8 weeks, more likely to report Intermediate and unfavorable risk cytogenetics, more likely to receive reduced-intensity conditioning compared to myeloablative conditioning regimens, and receive cyclosporin rather than tacrolimus-based GVHD prophylaxis.After a median follow-up of 50, 61 and 37 months in 8/8 URD, 7/8 URD and UCB grafts, neutrophil and platelet recovery was slower in UCB compared to URD recipients; the day-42 incidence of neutrophil recovery in UCB recipients was 85% compared to 98% and 92% in 8/8 and 7/8 URD recipients. While there were no significant differences in rates of grade II to IV acute GVHD (35%, 36% and 44% in UCB, 8/8 URD and 7/8 URD recipients respectively), the 3-year incidence of chronic GVHD was significantly lower in UCB recipients (28% compared to 53% and 59% in 8/8 and 7/8 URD recipients. Compared to 8/8 URD transplants, multivariate analysis confirmed higher TRM after transplantation of UCB grafts, but only in the first 3 months (HR 2.83, p<0.0001) with similar risks thereafter (HR 1.00, p=0.99). Compared to 8/8 URD transplants, TRM was higher after 7/8 URD transplants (HR 1.73, p=0.005). There were no significant differences in relapse risks between the three groups; compared to 8/8 URD transplants, relapse risks after UCB and 7/8 URD transplants were HR 1.15, p=0.36 and HR 0.86, p=0.47, respectively. These hazards yielded higher adjusted 3-year LFS after 8/8 URD (39% [95% CI 34%-43%]) compared to 7/8 URD (34% [95% CI 24%-43%]) and UCB transplants (28% [95% CI 22%-35%]), p=0.015) and adjusted 3-year OS of 43% (95% CI 38%-48%), 37% (95% CI 27%-46%) and 30% (95% CI 23%-37%), respectively (p=0.003). Relapse risks were greater in patients with intermediate or unfavorable risk cytogenetics, independent of graft type and leukemia-free and overall survival were also worse in patients with unfavorable risk cytogenetics and in patients over age 60. For the older population with AML, allotransplantation in CR1 can provide extended leukemia-free survival for 30%-43% of patients using any of these graft sources. While 8/8 URD transplants are preferred for patients who can promptly obtain a well-matched URD, for ethnic or racial minorities, UCB grafts provide a meaningful chance of extended LFS, even though nearly all UCB grafts are HLA mismatched.Additionally, the rapid availability of UCB provides effective therapy for older patients with expected short initial remissions: settings where ongoing consolidation therapy has not been effective in limiting risks of relapse. Later TRM and relapse rates were similar, lower risks of chronic GVHD and the need for long-term immunosuppression and its morbidities may be of particular value for these older patients. These encouraging results suggest that allotransplantation need not be withheld from older patients and for clinically suitable AML patients, can produce extended and even curative long-term survival. Disclosures: GluckmanCord use: Honoraria; gamida: Honoraria.

Effects of KIR ligand incompatibility on clinical outcomes of umbilical cord blood transplantation without ATG for acute leukemia in complete remission

To clarify the effect of killer cell immunoglobulin-like receptor (KIR) ligand incompatibility on outcomes of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients in complete remission after single cord blood transplantation (CBT), we assessed the outcomes of CBT registered in the Japan Society for Hematopoietic Cell Transplantation (JSHCT) database. A total of 643 acute leukemia (357 AML and 286 ALL) patient and donor pairs were categorized according to their KIR ligand incompatibility by determining whether or not they expressed HLA-C, Bw4 or A3/A11 by DNA typing. A total of 128 patient–donor pairs were KIR ligand-incompatible in the graft-versus-host (GVH) direction and 139 patient–donor pairs were incompatible in the host-versus-graft (HVG) direction. Univariate and multivariate analyses showed no significant differences between the KIR ligand-incompatible and compatible groups in the GVH direction for both AML and ALL patients of overall survival, disease-free survival, relapse incidence, non-relapse mortality and acute GVH disease. However, KIR incompatibility in the HVG direction ameliorated engraftment in ALL patients (hazard ratio 0.66, 95% confidence interval 0.47–0.91, P=0.013). Therefore, there were no effects of KIR ligand incompatibility in the GVH direction on single CBT outcomes for acute leukemia patients without anti-thymocyte globulin use. However, it is necessary to pay attention to KIR incompatibility in the HVG direction for engraftment.

Cord blood transplantation for the treatment of acute leukemia

Objective This review discussed the available data on treatment outcomes of cord blood transplantation (CBT) for acute leukemia. Data sources The data cited in this review were obtained from articles listed in Medline and Pubmed. Study selection We reviewed the articles of clinical results from various registries and institutions, as well as our experiences with CBT in children, adolescents and adults. Results This research has clearly shown that cord blood (CB) has several unique characteristics resulting in distinct advantage and disadvantages when compared to transplantation with unrelated donor bone marrow or peripheral blood stem cells. The field of CBT has advanced from investigating its safety and feasibility to addressing more specific issues such as accelerating engraftment, extending access, and examining outcomes in specific subgroups of patients. Many approaches have been investigated in the attempt to improve engraftment and survival. Variable factors have been identified, such as factors related to donor choice (human leukocyte antigen (HLA) compatibility, cell dose, and others) and transplantation (conditioning and graft-versus-host disease prophylaxis regimen). Data support that CB should be considered a reasonable option in those that do not have HLA matched sibling donor and for those in whom the time to transplant is critical. Conclusions CB is a reasonable alternative to unrelated donor bone marrow or peripheral blood progenitor cells for transplantation. Recently developed strategies aimed at improving hematopoietic recovery and reducing early transplantation-related mortality could further improve treatment outcomes of CBT for patients with acute leukemia.

Association Between Mycophenolic Acid (MPA) Total Serum Trough Levels and Toxicity and Efficacy Outcomes in Cord Blood Transplantation (CBT) Recipients

Association Between Mycophenolic Acid (MPA) Total Serum Trough Levels and Toxicity and Efficacy Outcomes in Cord Blood Transplantation (CBT) Recipients

A proposal for improvement in the utilization rate of banked cord blood

A proposal for improvement in the utilization rate of banked cord blood

Acute kidney injury after myeloablative cord blood transplantation in adults: the efficacy of strict monitoring of vancomycin serum trough concentrations

Acute kidney injury (AKI) is a common medical complication after myeloablative allogeneic stem cell transplantation (SCT). We have previously performed a retrospective analysis of AKI after cord blood transplantation (CBT) in adults, and found that the maximum of vancomycin (VCM) trough levels were significantly higher in patients with AKI. Following these results, we have monitored VCM serum trough concentrations more strictly, to not exceed 10.0mg/L, since 2008. In this report, we performed an analysis of AKI in a new group of 38 adult patients with hematological malignancies treated with unrelated CBT after myeloablative conditioning between January 2008 and July 2011. Cumulative incidence of AKI at day 100 after CBT was 34% (95% confidence interval 19-50). The median of the maximum value of VCM trough was 8.8 (4.5-12.2) mg/L. In multivariate analysis, no factor was associated with the incidence of AKI. No transplant-related mortality was observed. The probability of disease-free survival at 2years was 83%. These findings suggest that strict monitoring of VCM serum trough concentrations has a beneficial effect on outcomes of CBT.

Impact of donor-specific anti-HLA antibodies on graft failure and survival after reduced intensity conditioning-unrelated cord blood transplantation: a Eurocord, Societe Francophone d'Histocompatibilite et d'Immunogenetique (SFHI) and Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) analysis

Graft failure is a major complication after unrelated cord blood transplantation. Presence of HLA-antibodies before cord blood transplantation may impact graft failure. To analyze the effect of anti-HLA antibodies on unrelated cord blood transplantation outcomes, we analyzed 294 unrelated cord blood transplant recipients after reduced intensity conditioning regimen. The majority of the patients (82%) were transplanted for malignancies, 60% with double-unrelated cord blood transplant, 63% were HLA mismatched. Retrospectively, pre-unrelated cord blood transplant serum was tested for HLA-Ab using Luminex™ platform. Results were interpreted as mean fluorescence intensity (MFI) against donor-specific mismatch. Among 62 recipients (23%) who had anti-HLA antibodies before unrelated cord blood transplant, 14 patients had donor specific anti-HLA antibodies (DSA) (7 were donor-specific anti-HLA antibodies for single unrelated cord blood transplant and 7 for double unrelated cord blood transplant). Donor specific anti-HLA antibodies threshold ranged from 1620-17629 of mean fluorescence intensity (MFI). Cumulative incidence of Day-60 neutrophil engraftment was 76%: 44% for recipients with donor specific anti-HLA antibodies and 81% in those without donor specific anti-HLA antibodies (P=0.006). The cumulative incidence of 1-year transplant related mortality was 46% in patients with donor specific anti-HLA antibodies and 32% in those without antibodies (P=0.06). The presence of donor specific anti-HLA antibodies was associated with a trend for decreased survival rate (42% vs. 29%; P=0.07). Donor specific anti-HLA antibody in recipients of unrelated cord blood transplant is associated with graft failure and decreased survival. Patient's screening for donor specific anti-HLA antibodies before unrelated cord blood transplantation is recommended before choosing an HLA mismatched cord blood unit. Whenever possible it is important to avoid selecting a unit for which the patient has donor specific anti-HLA antibodies.

Reconstitution of maturating and regulatory lymphocyte subsets after cord blood and BMT in children

Some clinical characteristics of cord blood transplantation (CBT) might be explained by specificities in the reconstitution of immune subsets differing by their maturation stage or their implication in GVHD, tolerance or immune responses against tumor or infectious agents. Here, we compare the immune reconstitution of several of these subsets after CBT and BMT. B-cell count recovery was faster after CBT. There was no difference in the recovery of CD4(+) and CD8(+) cell counts. There was no difference either in the frequency of several subsets: CD45RO(+) memory, and CD45RA(+) naïve cells within the CD4(+) T-cell compartment, CD27(+) among B cells, CD56(bright), NKG2A(+), and KIR(+) cells among natural killer (NK) cells, CD25(+)FOXP3(+) regulatory T cells and invariant NKT cells. The proportion of the thymic naïve CD31(+)CD45RA(+)CD4(+) T cells was lower after CBT at 6 months post-transplant, and was still below normal at 1 year in both groups. NK-cell expansion was more sustained after CBT, with fewer double-negative NKG2A(-)KIR(-) hyporesponsive cells and more double-positive NKG2A(+)KIR(+) hyper-responsive NK cells. These results, therefore, indicate that further research to improve CBT outcome should try to improve thymopoieisis and take advantage of the sustained NK-cell reconstitution.

Impact of anti-HLA antibodies on allogeneic hematopoietic stem cell transplantation outcomes after reduced-intensity conditioning regimens

Anti-human leukocyte antigen (HLA) antibodies are associated with several complications in solid organ transplantations, but their impact after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not yet well defined. To evaluate the relevance of anti-HLA antibodies, we have retrospectively analyzed 107 peripheral blood allo-HSCTs after reduced-intensity conditioning regimen between 2005 and 2010. Acute myeloid leukemia and multiple myeloma were the most frequent malignancies in the cohort. The detection of anti-HLA antibodies was systematically performed in all patients before transplantation. Anti-HLA antibodies were present in 24 patients (22%). There was no significant impact of anti-HLA antibodies on engraftment, incidence of relapse, and incidence of acute graft-vs-host disease. The presence of anti-HLA antibodies was associated with significantly worse overall survival (p = 0.006) and event-free survival (p = 0.024) after stratification on sex. The 3-year probability of overall survival was 34% without anti-HLA antibodies and 16% in their presence. Patients with anti-HLA antibodies had a higher transplant-related mortality associated with life-threatening vascular complications. Our study supports that anti-HLA antibodies should be tested and considered as an important impacting factor for transplantation outcomes after reduced-intensity conditioning allo-HSCT. We recommend its consideration before allo-HSCT in the donor-recipient selection parameters.

Single-unit umbilical cord blood transplantation from unrelated donors in patients with hematological malignancy using busulfan, thiotepa, fludarabine and ATG as myeloablative conditioning regimen

Attempts to optimize outcomes in cord blood transplantation (CBT) by using new conditioning regimens and standardization of cord blood unit selection are warranted. In all, 88 patients (18 children and 70 adults) with hematological malignancy from nine Spanish institutions underwent a single-unit CBT after an i.v. BU-based myeloablative conditioning regimen. All evaluable patients except one engrafted. The overall cumulative incidence (CI) of myeloid engraftment was 94% at a median time of 19 days. In multivariate analysis, nonadvanced disease stage was the only factor with a favorable impact on myeloid engraftment. The CI of acute GVHD grades II-IV and chronic extensive GVHD were 24% each. The CI of nonrelapse mortality at 100 days, 180 days and 5 years was 14, 23 and 44%, respectively. The 5-year CI of relapse was 18%, whereas disease-free survival (DFS) was 46%, 39% and 11% for patients transplanted in early, intermediate and advanced stages of the disease, respectively. Our study shows high rates of engraftment with fast neutrophil recovery in patients undergoing single-unit CBT using a BU-based conditioning regimen. Long-term DFS can be achieved in a substantial number of patients with high-risk hematological malignancies, particularly when transplanted in an early stage of the disease.

Expansion of T-cells from the cord blood graft as a predictive tool for complications and outcome of cord blood transplantation

We have previously successfully expanded functional T-cells in vitro from cord blood grafts used for clinical transplantation, with the aim of creating donor lymphocyte infusions to treat e.g. malignant relapse. Here we show that the T-cell expansion in addition might work as a prognostic tool for complications after transplantation. We used multi-color flow cytometry to correlate in vitro phenotypical and functional data from 33 expansions to clinical outcome post-transplantation. Higher levels of CD69+ activated T-cells in the expansion were associated with prolonged survival of the patient. In addition, we found a correlation between T-cell expansions containing relatively high levels of effector memory T-cells and graft vs. host disease and relapse. Our data suggest that expansions of cord blood T-cells from the graft might not only be used as donor lymphocyte infusions, but also as in vitro indicators that could give essential information on how to manage cord blood transplanted patients.

Expansion of T-Cells from the Cord Blood Graft as a Predictive Tool for Complications and Outcome of Cord Blood Transplantation

We have previously successfully expanded functional T-cells in vitro from cord blood grafts used for clinical transplantation, with the aim of creating donor lymphocyte infusions to treat e.g. malignant relapse. Here we show that the T-cell expansion in addition might work as a prognostic tool for complications after transplantation. We used multi-color flow cytometry to correlate in vitro phenotypical and functional data from 33 expansions to clinical outcome post-transplantation. Higher levels of CD69+ activated T-cells in the expansion were associated with prolonged survival of the patient. In addition, we found a correlation between T-cell expansions containing relatively high levels of effector memory T-cells and graft vs. host disease and relapse. Our data suggest that expansions of cord blood T-cells from the graft might not only be used as donor lymphocyte infusions, but also as in vitro indicators that could give essential information on how to manage cord blood transplanted patients.

Humoral HLA sensitization matters in CBT outcome

In this issue of Blood, Cutler and colleagues present evidence that donor-specific anti-HLA antibodies are associated with graft failure in double umbilical cord blood transplantation (CBT).1 Engraftment of donor cells is the first important step in successful transplantation and, until recently, the causes of engraftment failure remained elusive.

Analysis of 120 pediatric patients with nonmalignant disorders transplanted using unrelated plasma‐depleted or ‐reduced cord blood

Unrelated cord blood (CB) is an important stem cell source for unrelated hematopoietic cell transplantation (HCT) of patients with nonmalignant disorders. Processing methods to prepare red blood cell-reduced CB units incur significant nucleated cell loss. In contrast, plasma depletion or reduction (PDR) processing of CB units entails the removal of only a portion of the plasma with minimal nucleated cell loss. However, there are relatively limited data regarding outcomes of CB transplants using units processed by PDR. A Center for International Blood and Marrow Transplant Research (CIBMTR)-audited analysis was performed on 120 pediatric patients with nonmalignant disorders transplanted between November 2001 and January 2008 at 29 US and 17 international centers using PDR CB units from two CB banks. Transplant characteristics were as follows: median age, 3.5 years (range, 0.1-14 years); median patient weight, 15 kg (range, 4-61 kg); 58% male; HLA matches (intermediate-resolution HLA-A and HLA-B and high-resolution HLA-DRB1) of the units used in these patients six of six in 26, five of six in 48, four of six in 47, and three of six or two of six in 6; median prefreeze total nucleated cell dose, 10.5×10(7)/kg; median prefreeze CD34+ dose, 3.7×10(5)/kg; and nonmyeloablative regimen in 24%. The median times to myeloid and platelet engraftment were 21 and 49 days, respectively. The cumulative incidence of reported Grade II to IV acute graft-versus-host disease (aGVHD) was 38±5%, and 19±4% had Grade III to IV aGVHD. The Kaplan-Meier estimates of 3-year transplant-related mortality, overall survival, and disease-free survival were 20±4, 79±4, and 70±6%, respectively. These data demonstrate the effectiveness of PDR CB units for HCT.

Impact of Bone Marrow Hematogones on Umbilical Cord Blood Transplantation Outcomes in Patients with Acute Myeloid Leukemia

Early after umbilical cord blood transplantation, patients show marked differences in bone marrow (BM) hematogone percentages. Little is known about whether these differences are clinically relevant. We hypothesized that early recovery of hematogones may be associated with improved transplantation outcomes. BM aspirates were assessed from 88 patients with acute myeloid leukemia by two independent reviewers at day 21 and 100 after umbilical cord blood transplantation. Interobserver variability for BM hematogone percentages at these time points showed correlation coefficients of 0.83 and 0.98, respectively (P ≤ .01 for both). A high percentage of hematogones at day 21 was associated with less acute graft-versus-host disease grade 3 to 4 (P = .01). At day 100, a high percentage of BM hematogones was associated with improved overall survival (P = .02) and lower treatment-related mortality (P ≤ .01). This study shows that BM hematogone percentages may be useful prognostic indicators in patients with acute myeloid leukemia after umbilical cord blood transplantation and should be routinely reported in BM differential counts.

Comparison of Unrelated Cord Blood Transplantation and HLA-Mismatched Unrelated Bone Marrow Transplantation for Adults with Leukemia

Recent advances in unrelated cord blood transplantation (UCBT) and high-resolution typing of human leukocyte antigen (HLA) from an unrelated donor have increased choices in alternative donor/stem cell source selection. We assessed HLA-mismatched locus-specific comparison of the outcomes of 351 single-unit UCB and 1,028 unrelated bone marrow (UBM) adult recipients 16 years old or older at the time of transplantation who received first stem cell transplantation with myeloablative conditioning for acute leukemia or myelodysplastic syndromes. With adjusted analyses, HLA 0 to 2 mismatched UCBT showed similar overall mortality (relative risk [RR] = 0.85, 95% confidence interval [CI], 0.68-1.06; P = .149) compared with that of single-HLA-DRB1-mismatched UBMT. UCBT showed inferior neutrophil recovery (RR = 0.50, 95% CI, 0.42-0.60; P < .001), lower risk of acute graft-versus-host disease (RR = 0.55, 95% CI, 0.42-0.72; P < .001), and lower risk of transplantation-related mortality (RR = 0.68, 95% CI, 0.50-0.92; P = .011) compared with single-HLA-DRB1-mismatched UBMT. No significant difference was observed for risk of relapse (RR = 1.28, 95% CI, 0.93-1.76; P = .125). HLA 0 to 2 antigen-mismatched UCBT is a reasonable second alternative donor/stem cell source with a survival outcome similar to that of single-HLA-DRB1-mismatched or other 7 of 8 UBMT.

Intrabone Marrow Transplantation of Unwashed Cord Blood Using Reduced-Intensity Conditioning Treatment: A Phase I Study

The outcome of cord blood transplantation following reduced-intensity conditioning is suboptimal because of fatal infection triggered by prolonged neutropenia and graft-versus-host disease (GVHD) in addition to graft rejection. Intrabone marrow injection (IBMI) may improve the outcome by providing better hematopoietic engraftment and less GVHD. We therefore evaluated IBMI safety in reduced-intensity stem cell transplantation. Furthermore, we used unwashed cord blood to avoid stem cell loss. Ten patients (median age = 61 years old) were enrolled. Cord blood cells were thawed at the bedside and injected into 4 iliac bone sites (2 at each hemipelvis). The procedure was well tolerated with no injection-related complications. Nine patients achieved donor engraftment. The median time to neutrophil recovery (>0.5 × 10(9)/L) was 17 days, and platelet recovery was achieved in 8 patients. Early full donor chimerism was achieved (median of 15 and 20 days in T cells and myeloid cells, respectively). Three of 9 evaluable patients developed grade II to III GVHD, and 5 of 10 patients died of treatment-related toxicities. The probability of survival at 1 year was 46.7%. IBMI of unwashed cord blood following reduced-intensity conditioning is safe, well tolerated, and may lead to an increased donor engraftment rate.