Myeloablative Cord Blood Transplantation Research Articles

Refining eligibility criteria of unit selection for myeloablative cord blood transplantation in acute leukemia: Real-world experience of a referral center.

The algorithm for cord blood (CB) unit selection is still somewhat ambiguous. We retrospectively analyzed 620 cases of acute leukemia between 2015 and 2020, who were treated with myeloablative single-unit umbilical CB transplantation (UCBT). We found that, when human leukocyte antigen (HLA) mismatch was ≤3/10, CD34+ cell dosage<0.83 × 105/kg-considerably lower than prevalent guidelines-was permissible without affecting survival. Moreover, synergy between donor killer-cell immunoglobulin-like receptors (KIR) haplotypes-B and donor-recipient HLA-C mismatch protected against relapse-related mortality. We submit that minimum required CD34+ cell dosage can possibly be relaxed to broaden access to UCBT, and donor KIR genotyping should be considered during unit selection.

Individualized Dosage Optimization for Myeloablative Conditioning before Unrelated Cord Blood Transplantation in a Diamond–Blackfan Anemia Patient with Germline RPL11 Mutation: A Case Study

Unrelated cord blood transplantation (CBT) for Diamond–Blackfan anemia (DBA), a systemic ribosomopathy affecting the disposition of conditioning agents, has resulted in outcomes inferior to those by transplantations from matched donors. We report the experience of the pharmacokinetics-guided myeloablative unrelated CBT in a DBA patient with a germline RPL11 mutation. The conditioning consisted of individualized dosing of fludarabine (based on weight and renal function with a target area under the curve (AUC) of 17.5 mg·h/L) and busulfan (based on therapeutic drug monitoring with a target AUC of 90 mg·h/L), as well as dosing and timing of thymoglobulin (based on body weight and pre-dose lymphocyte count to target pre-CBT AUC of 30.7 AU·day/mL and post-CBT AUC of 4.3 AU·day/mL, respectively). The pharmacokinetic measures resulted in a 27.5% reduction in busulfan and a 35% increase in fludarabine, as well as an over three-fold increase in thymoglobulin dosage with the start time changed to day-9 instead of day-2 compared to regular regimens. The transplantation resulted in rapid, complete, and sustained hematopoietic engraftment. The patient is now healthy over 3 years after CBT. A pharmacokinetics-guided individualized dosing strategy for conditioning might be a feasible option to improve the outcomes of DBA patients receiving unrelated myeloablative CBT.

Incidence and Risk Factors for Acute and Chronic Kidney Injury after Adult Cord Blood Transplantation.

Although cord blood transplantation (CBT) extends allograft access, patient comorbidities, chemoradiation, and nephrotoxic medications all contribute to acute kidney injury (AKI) risk. We analyzed AKI in adult myeloablative CBT recipients who underwent transplantation from 2006 to 2017 for hematologic malignancies using cyclosporine A (CSA)/mycophenolate mofetil immunosuppression. Maximum grades of AKI were calculated using Kidney Disease: Improving Global Outcomes (grade 1, 1.5 to <2-fold; grade 2, 2 to <3-fold; or grade 3, ≥3-fold over baseline) definitions. In total, 153 patients (median 51 years [range, 23-65], 114/153 [75%] acute leukemia, 27/153 [18%] African, 88/153 [58%] cytomegalovirus seropositive, median age-adjusted hematopoietic cell comorbidity index 3 [range, 0-9], median pretransplant albumin 4.0 g/dL [range, 2.6-5.2]) underwent transplantation. The day 100 cumulative incidence of grade 1-3 AKI was 83% (95% confidence interval [CI], 77%-89%) (predominantly grade 2, median onset 40 days, range 0 to 96), and grade 2-3 AKI incidence was 54% (95% CI, 46%-62%) (median onset 43 days, range 0 to 96). Mean CSA level preceding AKI onset was high (360 ng/mL, target range 300-350). In multivariate analysis, African ancestry, addition of haploidentical CD34+ cells, low day -7 albumin, critical illness/intensive care admission, and nephrotoxic drug exposure (predominantly CSA and/or foscarnet) were associated with AKI. In a day 100 landmark analysis, 6% of patients with no prior AKI had chronic kidney disease (CKD) at 2 years versus 43% with prior grade 1 and 38% with prior grade 2-3 AKI (overall P= .02). Adult CBT recipients are at significant AKI risk, and AKI is associated with increased risk of CKD. Prevention strategies, early recognition, and prompt intervention are critical to mitigate kidney injury.

No Engraftment Advantage after Single or Double Umbilical Cord Blood Transplant (CBT) with the Addition of a Non-HLA Matched Off-the-Shelf Expanded Cord Blood Unit Compared to Conventional CBT: Results of a Randomized Trial

Background: Based on pilot study data demonstrating safety and excellent survival [Blood 2014 124:46] in acute leukemia patients undergoing myeloablative cord blood transplant (CBT) plus infusion of an off-the-shelf non-HLA matched expanded CB unit (OTS) for bridging hematopoiesis, a randomized trial was conducted to determine whether myeloablative CBT with or without an OTS would confer more rapid neutrophil (ANC) engraftment and therefore a survival advantage. Methods: We conducted a multi-center, randomized controlled phase II trial (RCT) with a primary endpoint of ANC engraftment defined as the first of 2 consecutive days in which neutrophil count ≥ 500 cells/μL. Secondary endpoints included platelet engraftment, overall survival (OS), disease free-survival (DFS), acute/chronic graft-versus-host disease (GVHD), non-relapse mortality (NRM), and relapse. 160 patients were enrolled between February 2013 and June 2018. Patients were randomized to receive either a conventional single or double CBT (SOC group) (n=78) or SOC + OTS (OTS group) (n=82). Unmanipulated CB units had to be at least 4/6 HLA-matched to the patient (intermediate resolution for HLA-A, -B and allele-level for HLA-DRB1) with no HLA matching required for the OTS. Patient disease (AML=68, ALL=77, MDS=7, CML/other=8), disease risk, gender, age, race, ethnicity, CMV serology, performance score and HLA-match were balanced between the two study groups. Patients received conditioning with either FLU 75mg/m2, TBI 13.2 Gy, CY120 mg/kg or with FLU 150mg/m2, TBI 4Gy, CY 50 mg/kg and Thiotepa 10 mg/kg. Cyclosporin and MMF were used for GVHD prophylaxis in all patients (Table 1). Results: The median follow-up of surviving patients was 15 months. Approximately 30% of patients enrolled were &amp;lt;18 years and most patients received the high dose TBI (13.2Gy) regimen (85% in OTS group and 91% in SOC group). The median pre-cryopreserved total nucleated cell dose was 5.4 × 107/kg for both groups while the median pre-cryopreserved CD34 cell dose was 0.30 and 0.28 × 106/kg for the OTS and SOC group, respectively. Patients in the OTS group received an additional median CD34+ cell dose of 10.5x106/kg. Median time to ANC engraftment was similar between the 2 groups, at 20 days (range 7-46) in the OTS group and 19 days (13-51) in the SOC group. Five patients experienced graft failure, 2 in the OTS group and 3 in the SOC group. Similarly, no difference was seen for median time to platelet engraftment [38 days (35-43) vs. 40 days (30-42) for the OTS and the SOC group]. Peripheral blood chimerisms performed weekly (day 7-28) revealed that the initial circulating myelomonocytes present in the peripheral blood of OTS patients at day 7 were nearly all generated from the OTS product. Contribution to engraftment of the OTS graft was transient, and generally undetectable after day 21. All outcomes were similar between the two groups. OS and DFS at 2 years were 70% and 60% vs 61% and 55% for the OTS and the SOC groups, respectively. Cumulative incidence of relapse and NRM at 2 years were 18% and 21% in the OTS group and 21% and 22% in the SOC group. Grade III-IV aGVHD was 16% and 14% for the and the SOC group, respectively. The OTS product was well tolerated, and serious adverse events rates similar between the 2 groups. Patients continue to be followed through 2 years to assess cGVHD, and graft-relapse-free-survival. Conclusion: In this multi-center RCT, no significant difference was observed in the primary or secondary endpoints. Importantly, while the median time to ANC recovery in the OTS group was unchanged (20 days) from our pilot study, the observed time to neutrophil recovery in the SOC group was 7 days quicker than expected based on previously observed outcomes following myeloablative CBT (median 26 days). During the 5 years that this study was open to accrual, the criteria for CB donor selection have improved, now regularly utilizing CD34+ cell content and high-resolution HLA-typing where available, as has the quality of the CB inventory. This RCT highlights that delayed engraftment should no longer be a barrier in the consideration of SOC CBT for patients with hematological malignancies. As expected, and observed consistently following CBT, both groups demonstrated low incidence of severe acute GVHD and relapse at 2 years. Interventions in CBT should focus on improving immune reconstitution and reducing the risk of NRM but must be easily adopted into SOC in order to be adopted clinically. Disclosures Milano: ExCellThera: Research Funding; Amgen: Research Funding. Rezvani:Kaleido: Membership on an entity's Board of Directors or advisory committees, Other: one-time compensation from advisory boards; Nohla Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: one-time compensation from advisory boards; AbbVie: Other: Principal investigator ; U.S. Department of Justice: Other: Expert medical witness; Johnson &amp; Johnson: Employment, Other: Brother is employed. Delaney:Nohla Therapeutics: Employment, Equity Ownership; Biolife Solutions: Membership on an entity's Board of Directors or advisory committees.

Invasive Fungal Disease Following Myeloablative Cord Blood Transplantation for Patients with Hematological Malignancies

Objective: Invasive fungal disease (IFD) is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, limited data is available on its clinical features after cord blood transplantation (CBT) for patients with hematological malignancies. Method: We retrospectively reviewed 63 patients who underwent myeloablative CBT at our institution between July 2013 and June 2019 with a median follow-up of 14 months. Micafungin, Voriconzole or Posaconazole was used for IFD prophylaxis. Results: Eight patients were identified as having an IFD, including 2 with proven IFD, 1 with probable IFD, and 5 with possible IFD. The most common prophylaxis regimen is micafungin (68.2%, 43/63). The incidence rate of IFD in the primary antifungal prophylaxis (PAP) and secondary antifungal prophylaxis (SAP) groups were 11.3% and 25% (P=0.488). The OS of day at +100, six months and +200 in the IFD and No IFD groups were 62.5% vs. 86.9% (P=0.1), 50 % vs.78.2% (P=0.07), and 50% vs.75.9% (P=0.094), respectively. The 3-year probabilities of overall survival (OS) in the IFD and No IFD groups were 50% and 60.5%, respectively (p=0.316). The incidence rate of Non-relapse Mortality in the IFD and No IFD groups were 42.9% and 30%, respectively (p=0.319). Conclusion: Antifungal prophylaxis could help to reduce the incidence of IFD after CBT for patients with hematological malignancies. Figure Disclosures No relevant conflicts of interest to declare.

The Prognostic Impact of Pretransplantation Inflammatory and Nutritional Status in Adult Patients after Myeloablative Single Cord Blood Transplantation

Markers of inflammatory and nutritional status, such as the Controlling Nutritional Status (CONUT) score, Prognostic Nutritional Index, Glasgow Prognostic Score, and C-reactive protein-albumin ratio (CAR) has been demonstrated to be associated with poor prognosis in patients with various cancers. Although the relatively low cell dose of a single cord blood unit restricts the indication for cord blood transplantation (CBT) to pediatric and relatively smaller and lighter adult patients, the impact of malnutrition on outcomes after CBT is unclear. We retrospectively analyzed 165 adult patients who underwent myeloablative single-unit CBT in our institute. In multivariate analysis, a higher CONUT score, which is indicative of poor inflammatory and nutritional status, was significantly associated with poor outcomes, including low neutrophil engraftment and development of extensive chronic graft-versus-host disease. A higher CAR, which is also suggestive of poor inflammatory and nutritional status, was significantly associated with poor neutrophil engraftment and higher overall mortality. Body mass index (BMI) was not associated with transplantation outcomes. These data suggest that poor pretransplantation inflammatory and nutritional status might be a more practical parameter than lower BMI, for predicting transplantation outcomes after single CBT for adults.

Demonstration of Rapid Functional Myeloid Cell Recovery after Infusion of a Universal Donor Ex Vivo Expanded Progenitor Cell Therapy As a Bridging Graft Source

Cord blood transplant (CBT) recipients are known to be at risk for delayed engraftment, resulting in an increased risk of morbidity and mortality post transplant. To overcome delayed engraftment, several groups have developed methods to expand ex vivo cord blood stem/progenitor cells (HSPC) which are under clinical evaluation. The majority of these expansion methods require identification of a patient specific cord blood donor as the source material for expansion, resulting in delays in the time to transplant and inherently carry a risk of product failure. In contrast, we have developed an off-the-shelf, universal donor ex vivo expanded cord blood (CB) derived HSPC product intended for use as a transient graft source which has been demonstrated to significantly reduce the incidence of documented bacterial infections in both transplant and non-transplant settings.1,2 Donor chimerism studies conducted weekly in the first month post transplant confirm that the initial early (days 0-14) myelomonocytic engraftment is derived largely from our universal donor graft. Herein, we now demonstrate that the these rapidly engrafting myelomonocytic cells generated from the universal donor graft source are mature and functionally intact human myeloid cells that can fight infectious organisms.CBT recipients enrolled on a phase II myeloablative CBT trial were included in these ancillary studies in which we evaluated the functional capacity of newly generated myeloid cells in peripheral blood. A flow cytometry-based assay which allowed quantitation of both phagocytosis and O2-dependent killing (oxidative burst) in myeloid cells was used. Strikingly, both monocytes (CD14+) and granulocytes (CD15+) in patients’ blood displayed similar frequencies of phagocytosis and O2-dependent killing of Staphlococcus aureus at day 7 (90.3%±2.2% phagocytosis and 88.9±5.2% O2-dependent killing n=2) when more than 95% of myeloid cells were from the expanded cell product compared to day 14 (69±13.2% phagocytosis and 94±2% O2-dependent killing, n=2) when more than 99% of cells were from a non-manipulated CB unit as a result of immunologic rejection by the T cell replete CB unit. These findings provide strong evidence that de novo generated myeloid cells from expanded HSPCs are as functionally competent as myeloid cells de novo generated from non-expanded CB.To better study the functionional properties of myeloid cells derived in vivo from rapidly repopulating expanded CB HSPCs, we transplanted either 20,000 non-expanded (NE-HSPC) CD34+ CB cells or their expanded progeny (E-HSPC) into sub-lethally irradiated NOD-scid IL2rγnull (NSG) mice. At day 7 after transplantation mice transplanted with E-HSPC showed 40-fold higher human engraftment in the bone marrow than mice transplanted with NE-HSPC (28.3 ± 1% vs 0.7±0.1%, n=3, p<0.001). Remarkably, the monocytes and granulocytes from their bone marrow showed a similar phagocytic potential to that of the monocytes and granulocytes of mice receiving NE-HSPC (60.4±3.2% vs 69.6±3.2%, n=3, p=0.06). Moreover, the frequency of phagocytosis in the myeloid cells isolated from the lungs of mice receiving E-HSPC was 7-fold higher than in the lungs of mice receiving NE-HSPC. It has been well documented that E-HSPC when infused alone, also contribute to long term engraftment in NSG mice, and therefore at 22 weeks after transplantation, the frequency of phagocytosis in monocytes and granulocytes isolated from the bone marrow of mice receiving E-HSPC remained similar to that in the bone marrow of mice receiving NE-HSPC for Staphlococcus aureus (55.1 ±1.9% vs 43.8%±7%, n=5, p=0.15), Escherichia coli (50.8±2% vs 49 ±8.3%, n=5, p=0.83) and Zymosan (43.7%±3 vs 49.9%±9.2%, n=5, p=0.54) indicating the continued generation of functional myeloid cells from long term repopulating cells.We demonstrate for the first time that ex vivo expanded CB HSPCs rapidly give rise to functional myelomonocytic cells in vivo in patients and immunodeficient mice. This study validates that our universal donor off-the-shelf, expanded CB HSPC cell product is a valuable resource for patients undergoing myeloablative CBT, and further warrants its widespread use in a non-transplant setting as a supportive "myeloid bridge" to mitigate treatment-related morbidity and mortality.1. Delaney C. et al. Lancet Haematol. 2016 Jul;3(7):e330-92. Summers C. et al. Blood 2014 124:3860 DisclosuresDelaney:Nohla Therapeutics: Employment.

Myeloablative Cord Blood Transplantation Yields Excellent Disease Free Survival in Patients with Acute Lymphoblastic Leukemia

Background: Allogeneic hematopoietic cell transplantation (HCT) is a potential curative treatment for children and adults with acute lymphoblastic leukemia (ALL). However, relapse occurs in approximately 30% of patients with ALL after HCT, with even worse outcomes in patients with minimal residual disease (MRD) pre-transplant [1]. Lower relapse rates have been reported for patients undergoing cord blood transplantation (CBT) compared to unrelated donor transplant. In the present study we sought not only to evaluate outcomes for ALL patients undergoing a myeloablative CBT, but also to see if the outcomes varied according to MRD status.Methods: Using prospectively collected data, we reviewed 67 consecutive patients with ALL who received a CBT between 2006 and 2016. The conditioning regimens consisted of either TBI (1320 cGy), Cytoxan and Fludarabine (FLU), (n=49) or Treosulfan (Treo), FLU and 200 cGY TBI (n=18). GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil (MMF). Donor units were selected to be at least a 4 out of 6 match to recipient at HLA-A and HLA-B antigens and HLA-DRB allele. Ten-color multiparameter flow cytometry studies on bone marrow aspirates were performed before HCT to determine the presence of MRD. Disease free-survival (DFS) was evaluated using the method of Kaplan and Meier. Probabilities of non-relapse mortality (NRM) and relapse were summarized using cumulative incidence estimates using the appropriate competing risks.Results: Patient characteristics are shown in Table 1. The median age and weight was 22 years (range, 0.6-58 years) and 57 kg (range 8-99 kg), respectively. Thirty-nine patients (58%) were non-Caucasian. At the time of transplant 32 patients (47%) were in first complete remission (CR1), 28 (42%) in CR2 and 7 (11%) in CR≥3. Any level of residual disease was considered MRD-positive (n=22). Fifteen patients (22%) had Ph+ ALL. Nine patients (13%) had a prior allogeneic transplant. The majority of patients (n=48; 72%) received a double-CB graft; the rest received a single-CB graft. In addition, 14 patients (21%) received an ex-vivo-expanded CB unit as part of their graft, combined with an unmanipulated CB unit. Median time to engraftment was 31 days (range, 21-80 days). The overall DFS at 5 years was 74% (CI 95%: 60-83) with no difference between MRD-negative 78% (CI 95%: 61-88) and MRD-positive patients 67% (CI 95%:43-81) (p=0.40) [Figure 1A and 1B]. The overall cumulative incidence of relapse and NRM at 5 years post-transplant was 14% (CI 95%: 5-31) and 12% (95%: 3-26), respectively. The risk of relapse was not significantly higher in MRD-positive compared to MRD-negative (HR 1.80 (95 CI: 0.50-6.51) p=0.36), when adjusting for year of transplant, CMV serostatus, age, and disease risk. The cumulative incidence of acute GVHD grade II-IV and III-IV at day 100 was 86% (CI 95%: 75-92) and 16% (CI 95%: 8-26), respectively.Conclusions: Our data suggest that outcomes in patients with ALL following myeloablative CBT are remarkable with 74% DFS at 5 years and very low rate of relapse. The implication of these results is particularly important for patients from racial and ethnic minorities. Indeed, because mismatches in CB units can be tolerated, it is possible to find suitable donors for nearly all patients, regardless of their race/ethnicity. Furthermore, the risk of relapse was similar between MRD-negative and positive patients, although this requires further study in larger populations given the relatively low number of MRD-positive patients.

Pre-engraftment bloodstream infections in acute leukemia patients undergoing unrelated cord blood transplantation following intensified myeloablative conditioning without ATG.

The aim of this study is to investigate the impact of pre-engraftment bloodstream infections (BSIs) on the outcomes in acute leukemia patients undergoing myeloablative cord blood transplantation (CBT). A total of 226 acute leukemia patients who received unrelated CBT were enrolled in this study, and all these patients received an intensified myeloablative conditioning without ATG. Pre-engraftment BSIs occurred in 72 patients (31.9%), and the median time of onset was 4.5days after cord blood infusion, BSIs of gram-negative bacilli, and gram-positive cocci comprised of 63.8 and 36.2%, respectively. The cumulative incidences of neutrophil and platelet engraftment, acute or chronic graft versus host disease (GVHD) were comparable among the non-BSI, gram-negative bacilli BSI, and gram-positive cocci BSI groups. The cumulative incidence of transplant-related mortality (TRM), relapse, overall survival (OS), and disease-free survival (DFS) was similar between the non-BSI and the BSI groups. For subgroups analysis, TRM was lower in gram-positive cocci BSI patients compared with that of gram-negative bacilli BSI patients (8.3 vs 39.3%) (p = 0.01) (HR = 0.39, p = 0.034), and the 5-year OS was higher in gram-positive cocci BSI cohort (79.1 vs 44.2%) (p = 0.01) (HR = 0.36, p = 0.046). Our study demonstrated that, for acute leukemia patients who received CBT after myeloablative conditioning that omitted ATG, pre-engraftment BSI had no impact on engraftment, GVHD, TRM, relapse, and long-term survival. Due to the fact that gram-negative bacilli BSI was associated with poor outcomes compared with gram-positive cocci BSI, appropriate early empirical antimicrobial management strategies and better supportive care are required to decrease the gram-negative bacilli BSI-related mortality.

Distinct Patterns of Early Hematopoietic Reconstitution in Patients Receiving Notch Expanded Non HLA-Matched Off-the-Shelf Cord Blood Derived Hematopoietic Stem and Progenitor Cells

Introduction: Delayed hematopoietic recovery and increased risk of transplant related mortality (TRM) continue to be major risk factors for patients undergoing myeloablative cord blood transplant (CBT). To overcome this issue, our group has developed methods for the ex vivo expansion of cord blood (CB) derived hematopoietic stem and progenitor cells (HSPCs) using an engineered Delta-1 Notch ligand. This expanded CB HSPC product has now been developed for use as a cryopreserved, universal donor (non-HLA matched), off-the-shelf (OTS) cell therapy to be infused as an adjuvant graft in CBT recipients. We have previously reported the promising clinical outcomes observed after infusion of the expanded OTS cell product after myeloablative CBT for faster neutrophil and platelet recovery, reduced TRM and grade III-IV acute GVHD and higher overall survival rate in comparison to the conventional CBT patients1. Based on these results, a multicenter Phase II randomized clinical trial is now underway. Herein, we sought to identify factors that contributed to the improved outcome in these patients by defining the patterns of early hematopoietic recovery in the peripheral blood of patients during the first four weeks after myeloablative CBT.Method: Between February 2013 and June 2015, 27 patients were enrolled in this study to assess the efficacy of our OTS product as an adjuvant graft to improve hematopoietic reconstitution and reduce regimen related toxicities in recipients of myeloablative CBT. Fourteen of the 27 patients were randomized to receive the OTS product. The frequencies of monocytes, T cells and NK cells (defined as CD14+, CD3+ and CD56+ respectively) within the freshly isolated peripheral blood mononuclear cells were determined by real-time immunophenotyping using multi-color flow cytometry on days 7, 14, 21, and 28 following CBT 2.Results: Strikingly, on day 7 the median absolute number of monocytes was ~100-fold higher in the OTS group as compared to the conventional group (4.7 cells/μL, 95% CI: 2.0 - 13 cells/μL vs 0.04 cells/µL, 95% CI: 0.01- 0.2 cells/μL), however by day 14 the absolute number of monocytes was similar in the two groups. Chimerism studies further confirmed that on day 7 nearly all (95-100%) of the circulating myeloid cells were derived from the OTS graft, whereas on day 14 the CD14 fraction was predominantly from the unmanipulated conventional graft. Furthermore, we anticipated that infusion of a non-HLA matched cell product would induce enhanced alloreactivity of the unmanipulated CB unit in vivo. Thus, we set out to analyze the frequency and composition of the donor derived peripheral blood T cells in both groups. We did not observe any differences in the absolute number of T cells present on day 7, but on day 14, we documented a robust expansion of circulating T cell in OTS patients (median=26 cells/µL, 95% CI: 12 - 50 cells/μL in the OTS group vs 5.4 cells/µL, 95% CI: 1.7 - 12 cells/μL, in the conventional group, p=0.0015). T cell subset analysis revealed that it is CD8+ T cells that are the primary contributor to the observed total T cell burst on day 14, with an absolute median number of 20.2/μL (OTS) vs 1.29/ μL (conventional), CI 95%: 10.7 - 36.6 vs 0.53 - 8.75, p = 0.0003. Additionally, a small, ~3- fold, increase in numbers of CD4+ T cells from day 7 to 14 was seen in the OTS patients but not in the conventional group (p = 0.03), resulting in a significantly lower median day 14 CD4:CD8 ratio in OTS patients than in conventional patients (0.17 vs 1.4, 95% CI: 0.1- 0.5 vs 0.4 - 3.9, p =0.004). Moreover, the analysis of NK cells at any time point and monocytes and T cells on day 21 and 28 did not yield any statistically significant changes in patients in each groupConclusion: Our findings show that patients receiving a non-HLA matched OTS product display a distinct pattern of early immune cell recovery characterized by an early monocyte burst on day 7 as "myeloid bridge" and a CD8 T cell burst on day 14. Better understanding of how these observations could impact the overall clinical outcomes in myeloablative CBT recipients will potentially expand the future applications of the non-HLA matched OTS product. SHAPE \\* MERGEFORMAT1. Milano F. et al. Blood. 2014;124(21):46.2. Li J. et al. Blood. 2014;124(21):3897. [Display omitted] DisclosuresDelaney:Biolife Solutions: Membership on an entity's Board of Directors or advisory committees; medac: Research Funding; Novartis: Other: Chair, DSMB.

Infusion of Ex Vivo Expanded Cord Blood Progenitor Cells Is Associated with Reduced Hospital Days and Utilization of Opiate Infusion and Total Parenteral Nutrition in Patients Receiving Myeloablative Cord Blood Transplantation

Infusion of Ex Vivo Expanded Cord Blood Progenitor Cells Is Associated with Reduced Hospital Days and Utilization of Opiate Infusion and Total Parenteral Nutrition in Patients Receiving Myeloablative Cord Blood Transplantation

Impact of Pre-Transplant Minimal Residual Disease in Patients with AML Undergoing Myeloablative Cord Blood Transplantation

Impact of Pre-Transplant Minimal Residual Disease in Patients with AML Undergoing Myeloablative Cord Blood Transplantation

Infusion of a Non HLA-Matched Off-the-Shelf Ex Vivo Expanded Cord Blood Progenitor Cell Product Following Myeloablative Cord Blood Transplantation Is Safe, Decreases the Time to Hematopoietic Recovery, and Results in Excellent Overall Survival

Background: Myeloablative cord blood transplant (CBT) recipients experience delayed hematopoietic recovery and an increased risk of transplant related mortality (TRM). With the primary goal of generating increased numbers of hematopoietic stem and progenitor cells (HSPC) to supplement a conventional cord blood (CB) graft and thereby enhance engraftment and reduce early TRM, we have developed methods to ex vivo expand CB-derived HSPC in the presence of Notch ligand for 14 days. The product is then harvested and cryopreserved for future clinical use. We have previously reported that infusion of non-HLA matched, off-the-shelf ex vivo expanded CB progenitor cells in patients undergoing myeloablative CBT is safe and associated with faster neutrophil (ANC) recovery. We now present updated outcomes data with a median follow-up of 3.2 years (range 1.9-3.7).Methods: Between September 2010 and August 2012, 15 patients with hematologic malignancies were enrolled in this single center Phase I trial to assess the safety of infusing a non-HLA matched expanded CB HSPC product to augment conventional CBT. Conditioning consisted of Fludarabine (75mg/m2), Cytoxan (120mg/kg) and TBI (13.2 Gy). On the day of transplant, 1 or 2 unmanipulated CB units were infused first followed 4 hours later by infusion of the expanded CB product. Donor(s)/host chimerism studies were performed weekly from day 7 to 28, then at days 80, 180 and 1 year on peripheral blood flow sorted into myeloid and lymphoid fractions. Graft versus host disease (GVHD) prophylaxis consisted of cyclosporine and MMF beginning on day -3. ANC and platelet engraftment were calculated using cumulative incidence rates to accommodate competing risks. Disease-free survival (DFS) was analyzed using Kaplan-Meier estimates.Results: The median age was 21 years (range, 5-45) and weight 59 kg (range, 23-89). Other patient characteristics and median infused cell doses are shown in Table 1. Four patients (26%) received only 1 unmanipulated CB unit along with the expanded graft. All patients engrafted at a median of 19 days (range, 9-31 days), significantly faster than the 25 days (range, 14-45) observed in 41 recipients of two unmanipulated units otherwise treated identically (p=0.01) (Figure 1A).Similar to our initial expansion trial using partially HLA-matched expanded CB cells, early (day 7) myelomonocytic (CD33 and CD14) recovery was almost entirely (98–100%) due to cells arising from the expansion product. Cells derived from the expansion product were no longer detected at day 14 in all but 2 patients. The median time to platelet recovery (>20 x 10^9/L) was 35 days (range 21–45).The cumulative incidence of platelet recovery by day 100 was significantly higher than that observed in our concurrent control group 92% (CI 95%: 59-99) vs. 69% (95%: 51-81), respectively (p=0.005) (Figure 1B). The probability of 3-year DFS was 86% (95% CI, 57-97). No TRM was observed throughout the study period (Figure 1C), although 2 patients relapsed at days 53 and 219 posttransplant and subsequently died after further therapy. All patients presented with grade II acute GVHD at a median time of 32 days (14-86), with no grade III-IV aGVHD observed (Figure 1D). The skin was the most commonly affected organ (n=12). Eight (53%) patients were treated for pre-engraftment syndrome at a median time of 6 days (range 4-9) and five (33%) patients had GVHD after day 100. At 2 years only 2 patients are still on immunosuppressive therapy for mild chronic GVHD.Conclusions: The results of this Phase I safety study demonstrated that infusion of an off-the-shelf non-HLA matched expanded CB HSPC product to augment a CB graft in the myeloablative setting was safe and led to more rapid neutrophil and platelet recovery compared to our concurrent control group. Importantly, no TRM was observed among the 15 patients on this study, with only 2 deaths due to relapsed disease, leading to an excellent OS of 86% at a median follow-up of 3.2 years. Quite interesting is the observation of no grade 3-4 acute GVHD, even with infusion of a non-HLA matched expanded cell product that may induce increased alloreactivity of the unmanipulated CB unit(s). However, in this preliminary pilot study, it appeared that infusion of the non HLA-matched product was associated with less severe acute GVHD. Based on these very promising results, a prospective multicenter randomized trial utilizing this product is underway. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Infusion of Ex Vivo Expanded Cord Blood Progenitor Cells Reduces the Risk of Bacteremia after Myeloablative Cord Blood Transplant

▪Background: Delayed hematopoietic recovery after myeloablative cord blood transplantation (CBT) is associated with higher infection-related morbidity and mortality when compared to recipients of conventional donor grafts. In particular, prolonged neutropenia, related to low cell doses provided by the cord blood (CB) graft, results in higher rates of infection in the first 100 days post-transplant. To overcome this issue, our group has explored ex vivo expansion of CB-derived CD34+ cells in the presence of Notch ligand. We have previously demonstrated that infusion of this expanded progenitor cell product leads to a significant reduction in the time to neutrophil engraftment in the myeloablative CBT setting [Delaney C, et al, Nat Med 2010]. We now hypothesize that faster neutrophil engraftment is associated with lower risk of bloodstream infections in the first 100 days post-transplant in patients receiving ex-vivo expanded progenitors (EXP) compared to patients receiving conventional CBT (CON).Methods: Between April 2006 and June 2014, a total of 93 consecutive patients were enrolled on multicenter studies coordinated by our Institution. Of these 93, 55 (59%) received single (n=9) or double (n=46) unmanipulated CB graft, while 38 (41%) patients received 1 or 2 unmanipulated CB units plus infusion of either a fresh partially HLA-matched (n=23) or a cryopreserved non-HLA matched (n=15) ex-vivo expanded CB unit. All patients received the same conditioning regimen of Fludarabine (75mg/m2), Cytoxan (120mg/kg) and TBI (13.2 Gy) over 8 days. GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. Cox regression model was used to assess the risk of bacterial infection where "failure" was defined as the first occurrence of bloodstream infection within 100 days following CBT.Results: The median patient age was 22 years (range 0.6-45) and 26 (range 3-45) for CON and EXP group respectively (p=0.51); gender, race and CMV serostatus were not different between the 2 groups. Disease distribution was similar in the two groups, with most patients undergoing CBT for AML (n=47), ALL (n=28) and MDS (n=10). Median pre-thaw TNC/kg x107 was 4.97 (range 3.4-16.6) and 11.2 (range 2.7-30.4) for the CON and EXP groups respectively, and pre-thaw CD34 cells/kg x106 was 0.19 for the CON (range 0.04-0.98) and 6.3 for the EXP group (range 0.12-49.7). As expected, time to engraftment was significantly faster for patients receiving the EXP units at 17 days (range 6-41) vs. 25 days in the CON group (range 14-45, p<0.01). Only 1 case of graft failure was observed in the EXP group. The median time to first positive bloodstream infection in the EXP cohort was 36 days (range 3-98) vs. 8 days (range 1-88) in the CON group. The cumulative incidence of bacteremia was significantly lower in the EXP group (n=14) compared to the CON group (n=36) at 37% vs. 65% respectively (p=0.005, Figure 1). The hazard ratio (HR) of bacteremia episodes was significantly lower among patients receiving the expanded cells (HR 0.43; 95% CI 0.23-0.79; p=0.007). Among first documented bacteremic episodes, 5 of 50 (10%) were gram-negative rod bacteremias, all of which were in the CON group.Conclusions: Infections remain a significant risk for morbidity and mortality after myeloablative CBT and are the leading cause of early treatment related mortality. Our data suggest that there was a significant reduction in risk of bacteremia in the first 100 days post myeloablative CBT and a longer time to first infection when patients received ex vivo expanded progenitor cells, either as a partially matched fresh infusion or as an off-the-shelf, non-HLA matched expanded product. Infusion of the expanded cells resulted in reduced time to myeloid engraftment and offered a protective effect against episodes of bacteremia, but the exact mechanisms are presently unknown. It is possible that the expanded cells may home to regions of mucosal injury post TBI and mitigate breakdown thus reducing bacterial translocation. Further research to further define the expanded cells’ mechanism of action with regards to infection reduction is currently underway in animal models. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Intensified Myeloablative Unrelated Cord Blood Transplantation for High-Risk or Advanced Hematological Malignancies: Experience at a Single-Institution in China

Introduction : Unrelated cord blood transplantation (CBT) is one of the most promising curative treatment modalities for hematological malignancies. But the data was limited in China. This retrospective study evaluated the clinical outcomes of intensified myeloablative unrelated CBT for high-risk or advanced hematological malignancies in our single center.Patients and Methods: From September 2006 to December 2013, Total of 187 high-risk or advanced hematologic malignancies underwent intensified myeloablative unrelated CBT. All CBT patients received a myeloablative conditioning regimen of TBI/Ara-C/CY [total body irradiation (TBI, total 12 Gy, 4 fractions) (d-7, d-6) arabinoside cytarabine (Ara-C) (2.0g/m2 every 12h for 2 days) (d-5, d-4) and cyclophosphamide (CY, 60 mg/kg daily for 2 days) (d-3, d-2)] (age≥14 years or primary induction failure or no remission after relapse), or Fludarabine/BU/CY2 [fludarabine (Flu, 30mg/m2 daily for 4 days) (d-8~ -5), busulfan (0.8mg/kg every 6h for 4 days) (d-7~ -4) and CY (60 mg/kg daily for 2 days) (d-3, d-2)] (For lymphoid malignancies patients with age ＜14 years or prior radiotherapy which would presuppose a high risk of toxicity), or Ara-C/BU/CY2 [ Ara C (2.0g/m2 every 12h for 2 days) (d-9, d-8), (busulfan (0.8mg/kg every 6h for 4 days) (d-7~ -4) and CY (60 mg/kg daily for 2 days) (d-3, d-2)](for myeloid malignancies patients with age < 14 years or prior radiotherapy which would presuppose a high risk of toxicity), and G-CSF was given with 5 ug/kg daily by subcutaneous injection one day prior to Ara-C with 3 days. For GVHD prophylaxis, all patients were given a combination of cyclosporine and short-course mycophenolate mofetil, and no patient received antithymocyte globulin (ATG).Results: Total of 181 patients (97.3%) achieved neutrophil engraftment and platelet engraftment, and the median number of days was 18 days (range 12~37 days) and 37.5days (range 15~112 days), respectively. Total nucleated-cell dose (≥5.2×107 / kg) and total CD34+ cell dose (≥3.8×105 / kg) were the favorable factors predicting for a higher probability of neutrophil engraftment (p =0.012, 0.025). The cumulative incidence of pre-engraftment syndrome (PES) and day-100 grade Ⅱ-Ⅳ acute GVHD was 75.4% (95% CI, 65.2-84.2%) and 28.34% (95% CI, 28.13~28.55%), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute GVHD 100 days after transplantation was 32.6% (95% CI, 42.3-22.8%)in the PES group and 15.2% (95% CI, 8.3-22.6%) in the non-PES group (р=0.016). Multivariate analysis showed that BU/CY2 based conditioning and without PES were significant risk factors for graft failure [RR=2.34 (95% CI, 1.32- 6.12), p =0.015; RR=2.89 (95% CI, 1.25- 6.82), p =0.009]. The median follow-up time was 27（7~89）months. Transplant-related mortality at 180 days and relapse at 3 years after CBT was 24.9% (24.7~25.2%) and 14.7% (14.6~14.9%). Probabilities of 3-year overall survival (OS) and disease-free survival (DFS) were 61.2% (95% CI, 51.3%- 72.3%) and 58.6% (95% CI, 49.5%- 67.9%), respectively. For pediatric patients, 3-year OS and DFS were 66.2% (95% CI, 56.4%- 75.8%) and 64.8% (95% CI, 54.6%- 74.2%); for adult patients, 3-year OS and DFS were 54.5% (95% CI, 45.8%- 63.7%) and 50.3% (95% CI, 41.5%- 60.1%), respectively.Conclusions: To the best of our knowledge, this is the largest clinical study of unrelated CBT reported in China. This retrospective study indicates that intensified myeloablative CBT procedures are associated with significant favorable outcomes in survival advantage in high-risk or advanced hematological malignancies. DisclosuresNo relevant conflicts of interest to declare.

Comparable 3-Year Disease-Free Survival Regardless of Anti-Thymocyte Globulin Inclusion in Pediatric Myeloablative Cord Blood Transplantation for Acute Lymphoblastic Leukemia

Background: Cord blood (CB) is routinely used as an alternative stem cell source for the treatment of children with acute leukemia and has been associated with high rates of disease-free survival (DFS). However, one controversial issue in pediatric CB transplantation is the role of anti-thymocyte globulin (ATG) as immunoprophylaxis. While inclusion of ATG in the conditioning may decrease the risk of graft-versus-host disease (GVHD), it could potentially abrogate graft-versus-leukemia effects and increase the risk of opportunistic infections. Thus, we compared outcomes in a uniform group of pediatric patients with acute lymphoblastic leukemia (ALL) who underwent myeloablative CB transplantation with or without ATG.Methods: Patients with ALL in morphologic remission (CR1 n=106, CR2 n=146, CR3 n=45) aged ≤ 20 years transplanted between 01/2007-12/2011 with high-dose total body irradiation-based conditioning and single or double unit CB grafts were eligible for analysis. CB units were 4-6/6 HLA-A,-B at the antigen-level, -DRB1 allele matched to the recipient and had CB unit with cryopreserved total nucleated cell dose of ≥ 2.5 x107/kg/unit. Cox regression models were built to evaluate potential differences in outcome in ATG versus non-ATG CB transplant recipients. The primary endpoint was 3-year DFS.Results: Of 297 patients, 92 received ATG and 205 did not. Age and disease status were similar in each group whereas ATG recipients were less likely to be CMV seropositive and more likely to receive single unit CB grafts. While neutrophil engraftment was similar in each group, the risk of day 100 grade II-IV acute GVHD [30% (95%CI: 21-40) versus 54% (95%CI: 47-61), p = 0.0002] and 3-year chronic GVHD [22% (95% CI: 14-31) versus 43% (95% CI: 36-50), p = 0.0008] were decreased in ATG recipients. However, day 100 grade III-IV aGVHD was comparable: 11% (95%CI: 5-18) in ATG versus 17% (95%CI: 12-23) in non-ATG recipients, p = 0.15]. The 3-year TRM was similar in both groups: 16% (95%CI: 10-25) in ATG versus 17% (95%CI: 13-23) in non-ATG recipients (p = 0.98). Relapse was also similar in ATG and non-ATG recipients: 17% (95%CI: 10-23) versus 27% (95%CI: 21-34, p = 0.12), respectively. In multivariate analysis, negative CMV serostatus was associated with reduced TRM risk [HR 0.55 (95%CI: 0.30-0.98), p = 0.004] whereas remission status CR2 or CR3 significantly increased relapse risk [HR 2.18 (95%CI: 1.22-3.89), p = 0.008], but inclusion of ATG had no effect on either outcome. With a median follow-up of survivors of 36 months (range 5-72), the 3-year DFS was 66% (95%CI: 56-76) and 55% (95%CI: 48-62) in ATG and non-ATG recipients, respectively (p = 0.23, Figure 1). The distribution of causes of death was similar in each group. In multivariate analysis, treatment failure risk was increased in patients transplanted in CR2 or CR3, but the inclusion of ATG had no effect (p = 0.24) (Table 1).Conclusion: Inclusion of ATG in pediatric myeloablative CB transplant for ALL is associated with a decreased risk of grade II-IV acute GVHD and chronic GVHD but not severe grade III-IV acute GVHD. There was no difference in 3-year DFS in each group and multivariate analysis revealed ATG inclusion had no impact upon treatment failure risk. These results indicate that optimization of both ATG and non-ATG conditioning platforms are needed in order to further improve CB transplantation survival in children with ALL. Unanswered questions include the impact of the formulation, dose and timing of ATG administration. These findings cannot be extrapolated for other diagnoses, reduced intensity conditioning, or adults.Table 1Hazard ratio(95% confidence interval)p-valueATG useConditioning without ATG Conditioning with ATG1.00 0.78 (0.52 – 1.18)0.24 Disease statusCR1 CR2, CR31.00 2.01 (1.31 – 3.08)0.001 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Real-Time Immunophenotyping of Peripheral Blood Early Post Myeloablative Cord Blood Transplant Can Identify Patients at Risk for Primary Graft Failure

▪Introduction: Primary graft failure (PGF) is a potentially life threatening complication following hematopoietic cell transplantation. Patients undergoing cord blood transplantation (CBT) are at higher risk for PGF and also experience delayed hematopoietic recovery. The ability to distinguish between PGF and delayed engraftment is critical for correct clinical management. Limited data exists analyzing the kinetics of engraftment of specific circulating cell lineages within 14 days after double CBT (dCBT). Herein, we investigate the potential for real time immunophenotyping (RTIP) of day 7 and day 14 post-transplant peripheral blood (PB) samples as an effective and economically feasible tool to distinguish PGF versus delayed engraftment.Methods: Between Feb 2013 and Jun 2014, 26 patients underwent a myeloablative dCBT at our institute. Heparinized PB samples (30 ml) were obtained from patients on days 7 and 14 post-transplant. PB mononuclear cells (PBMCs) were isolated by density gradient separation and total cell number was counted. RTIP with 9-color flow cytometry was performed at each time point using isolated fresh PBMC.Results: Median time to engraftment was 19 days (range 12-51) in 23 evaluable patients. The remaining 3 patients had no documented hematopoietic recovery by routine daily CBCs. Two patients were declared PGFs when day 21 PB chimerism results demonstrated 100% host T cells followed by confirmation of 0% donor engraftment on day 28. The third patient never had sufficient quantity of circulating cells to obtain RTIP results and died on day 28 with no hematopoietic recovery. Excluding this patient, we were able to quantify the absolute number of PBMC at day 7 (median: 3.1/µl; 95% CI: 2.6-4.6) and day 14 (median: 26/µl; 95% CI: 33-103) in all other patients. There was an increase in the absolute number of PBMC from day 7 to 14 in all patients except the two who experienced PGF. Furthermore, RTIP of day 7 PBMC revealed a predominance of T cells that were donor-derived, while day 14 RTIP of PBMC demonstrated a decreased frequency of T cells and increased frequency of predominantly donor-derived monocytes and NK cells. In contrast to the engrafting patients, the two PGF patients displayed a markedly different pattern in RTIP with minimal evidence of circulating monocytes in the day 14 samples (Fig 1A). Importantly, RTIP demonstrated that day 7 PBMC contained a higher frequency of CD14+CD16- monocytes and CD56brightCD16- NK cells than were infused, suggesting these specific cells were generated de novo and were not representative of cells infused with the graft (data not shown).Correlations between day 7 or day 14 cell subset numbers and time to engraftment were analyzed. The median absolute number of monocytes at day 7 was 0.075/µl (95% CI: 0.03-0.153). Patients with day 7 monocyte counts above the median demonstrated earlier engraftment than patients below the median (17.5 vs 26.5 days; p= 0.011). Using linear regression with engraftment as the variable of interest and the absolute number of day 7 monocytes as the predictor, the coefficient was 0.6 (95% CI: 0.075- 0.78, P=0.025) (Fig 1B). As expected, higher day 14 monocytes also correlated with earlier engraftment. With respect to the NK cell subset, the absolute number of NK cells at day 7 was not significantly correlated with engraftment time, but day 14 NK cell numbers were predictive of engraftment kinetics. The median number of NK cells at day 14 was 2.78/µl (95% CI: 1.87-5.79). Patients with day 14 NK counts above the median had earlier engraftment than those below the median (16 vs 26.5 days; (P=0.0034). The regression coefficient was 0.5 (95% CI, 0.077- 0.77; P=0.024). Finally, although total T cell numbers at day 7 and day 14 had no correlation with engraftment time, the two evaluable PGF patients had a greater inversion of CD4:CD8 ratio (0.038 & 0.058) than others (median: 0.71, 95% CI: 0.22-1.42) at day 14.Conclusions: This study provides the first clear evidence that RTIP of PBMC at days 7 and 14 can detect the kinetics of circulating de novo generated monocytes and NK cells and also reflects the in vivo immune environment in patients following dCBT. Importantly, detecting and measuring specific cell subsets using RTIP permits earlier identification of patients at high risk of graft failure versus patients with delayed engraftment and warrants further development as a clinically feasible diagnostic method to guide clinical intervention. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

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.

Sustained Donor Engraftment in Recipients of Double-Unit Cord Blood Transplantation Is Possible Despite Donor-Specific Human Leukoctye Antigen Antibodies

The impact of human leukocyte antigen (HLA) donor-specific antibodies (DSA) on cord blood (CB) engraftment is controversial. We evaluated the influence of pre-existing HLA-antibodies (HLA-Abs) on engraftment in 82 double-unit CB recipients (median age, 48 years) who underwent transplantation for hematologic malignancies. Of 28 patients (34%) with HLA-Abs, 12 had DSA (median mean fluorescence intensity 5255; range, 1057 to 9453). DSA patients had acute leukemia (n = 11) or myelodysplasia (n = 1) and all received either high-dose or reduced-intensity (but myeloablative) conditioning. After myeloablative CB transplantation (CBT) (n = 67), sustained donor engraftment was observed in 95% without HLA-Abs (median, 23 days), 100% with nonspecific HLA-Abs (median, 23 days), and 92% with DSA (median, 31 days, P = .48). Of 6 patients with HLA-Abs to 1 unit, 3 engrafted with that unit and 3 with the other. Of 6 patients with HLA-Abs against both units, 1 had graft failure despite being 100% donor, and 5 engrafted with 1 unit. Successful donor engraftment is possible in patients with DSA after myeloablative double-unit CBT. Our data suggest potential deleterious effects of DSA can be abrogated in patients with hematologic malignancies.

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.