Abstract Introduction Myelofibrosis (MF), both primary myelofibrosis (PMF) and post essential thrombocytosis/polycythemia vera myelofibrosis (post ET/PV-MF), are chronic myeloproliferative neoplasms that are incurable with standard medical therapy. The only potential curative therapeutic modality remains allogeneic stem cell transplant (ASCT), but the optimum conditioning regimen has yet to be defined and may vary due to pre-ASCT factors such as age, donor source, and comorbidities. In the past, traditional myeloablative (MA) regimens have proven toxic. Reduced intensity conditioning (RIC) regimens have generally become the accepted standard of care for patients with PMF or Post PV/ET MF in need of ASCT, but with the potential for increase in relapse especially for high risk disease. The optimal conditioning regimen has yet to be defined. The regimen of Fludarabine, BCNU, and melphalan (FBM) is considered a reduced toxicity regimen that may afford the benefit of reduction in relapse without increase in toxicity and may “bridge the gap” between MA and RIC especially in older patients. Patients with MF have high inflammatory cytokine levels which may act as mediators of MF symptom burden and may further aggravate mediators of acute GVHD, which is one of the most frequent and severe complications of ASCT. Selection of conditioning regimen and GVHD prophylaxis are keys to MF transplant outcomes. We report here the results of 16 patients who received conditioning with FBM with rATG (FBM-A) with PMF and post PV/ET MF. Methods We conducted a retrospective review of all patients from October 2009 to November 2012 with PMF or post ET/PV-MF who underwent an ASCT with FBM-A. Patient demographic and transplant data were analyzed from a comprehensive database. The use of such data for reporting purpose was approved by the Mayo Clinic Arizona Institutional Review Board. Overall survival was estimated using Kaplan-Meier. Results There were 16 patients analyzed who had PMF or post PV/ET MF or overlap syndromes. The median follow-up of surviving patients is 20.4 months (range 8 months – 46 months). The median age was 60 (range 47-68 yrs) with 56% of patients being ≥ 60yrs. There were 8 males and 8 females. The JAK2 V617F mutation was present in 64% of patients. 86% were high risk according to the DIPSS system with 14% being intermediate-2 risk. None of the patients underwent splenectomy prior to transplant. The median HCT-CI score was 1.5 with 6 (38%) of the patients having an HCT-CMI ≥3. Donors were related in 10 patients (8 matched, 2 mismatched at 1 antigen) and unrelated in 6 (matched, n=3, 1-antigen mismatch, n=3). GVHD prophylaxis consisted of tacrolimus, MMF, and ATG 2.5 – 5.0 mg/kg. The cumulative incidence of acute GVHD grades III-IV was 15.3% at 6 months, and the cumulative incidence of NIH-defined moderate-to-severe chronic GVHD was 25% at 2 years. No patient has relapsed, and no patient has developed graft failure. There have been 4 deaths, 3 from GVHD, and 1 from infection. Among the 3 patients who died from GVHD, all were unrelated donor transplants, and 2 were mismatched unrelated transplants. The 2-year Kaplan-Meier estimate of overall survival (OS) is 72% (95% CI, 45 – 91%). The cumulative incidence of TRM was 12.6% (95% CI 3.9%-34%) at 1 year. Conclusion The reduced-toxicity regimen of FBM-A in PMF, Post ET/PV MF and overlap syndromes appear to provide the benefit of an ablative regimen with the tolerance of a RIC. The 2-year overall survival of 72% in our series is encouraging in an older population of predominantly high-risk patients. Treatment failure was related predominately to GVHD, which continues to be a significant obstacle to better long-term outcomes, especially in unrelated and mismatched patients. Reduced toxicity ASCT conditioning regimens in the setting of MF warrant further investigation. Disclosures: Reeder: Celgene: Research Funding; Novartis: Research Funding; Millenium: Research Funding.

Optimal sampling interval, sample source and technique to detect impending relapse after hematopoietic cell transplantation (HCT) is not well-defined. For most myeloid malignancies (except CML) donor chimerisms, peripheral blood parameters, and bone marrow cytomorphology are the main options for disease detection post-HCT. The role of molecular markers is still evolving. The aim of our study is to evaluate the usefulness of 3 monthly bone marrow (BM) evaluations for the first year after HCT using these techniques in predicting relapse.

Abstract Background The prognosis for AML or MDS patients (pts) with monosomal karyotype (MK) is dismal. Although a benefit for allogeneic hematopoietic cell transplantation (allo-HCT) compared to chemotherapy or autologous HCT has been demonstrated in young (≤ 60) pts (Cornelissen, 2012), the curative potential of allo-HCT in older (≥ 60) pts with monosomal karyotype AML/MDS is not known. Patients and methods In this retrospective review, we analyzed outcomes for 69 AML (n = 49) or MDS (n = 20) pts ≥ 60 who underwent allo-HCT at Mayo Clinic Arizona between 2005 and 2013, based on cytogenetic grouping as follows: cytogenetically normal (CN, n = 23), cytogenetically abnormal but not MK (CA, n = 32), and MK (n = 14). Monosomal karyotype was defined (Breems, 2008) as a karyotype with at least two autosomal monosomies or a single autosomal monosomy in combination with at least one structural abnormality. Univariate and multivariate statistical analyses were performed to evaluate the impact of these 3 cytogenetic groupings on outcome (primary endpoint progression-free survival). The median age for all pts was 66 (60-76), and median follow-up for surviving pts was 22 months (range 70 days – 7.1 years). Thirty-seven pts had high-risk disease (MDS > 5% blasts or AML not in CR), while 32 were considered standard risk (MDS <5% blasts or AML in CR). The majority of pts had good performance status (KPS ≥ 90% in 66), but 34 pts (49%) had an HCT-CI score of ≥ 3. Conditioning was myeloablative (Bu-Cy) in 4, reduced toxicity FBM (Fludarabine, BCNU, Melphalan) in 36, and RIC/NMA in 29. Donors were matched related in 18, matched unrelated in 36, and mismatched unrelated in 15. GVHD prophylaxis included tacrolimus in all pts combined with mycophenolate mofetil (37) or methotrexate (32); 49 pts received in-vivo T-cell depletion with rabbit anti-thymocyte globulin (rATG, Thymoglobulin, Genzyme, Cambridge, MA). Results The Kaplan-Meier estimate of progression-free survival (PFS) at 2 yrs was 59% (CN), 39% (CA), and 1.5% (MK); P = 0.004 (Fig. 1). The cumulative incidence of relapse at 2 yrs (with death without relapse as a competing risk) was 34% (CN), 25% (CA), and 94% (MK); P= 0.009). In a Cox proportional hazards analysis adjusted for age (≤ 66 vs. > 66), risk status (standard vs. high), conditioning (myeloablative [Bu-Cy + FBM] vs. RIC/NMA), use of ATG (yes/no), donor type (unrelated vs. related), and HCT-CI (0-2 vs. ≥ 3), the only factor predictive for inferior PFS was cytogenetic status (MK vs. CN, HR 4.64 [95% CI, 1.7 – 13]; P = 0.003); (MK vs. CA, HR 2.4 [95% CI 0.97 – 5.9]; P = .057). Conclusions Standard allo-HCT in AML or MDS pts ≥ 60 with a monosomal karyotype appears to have limited curative potential. Although larger studies will be required to confirm our results, novel transplant approaches or post-transplant strategies to prevent relapse should be a focus of future studies in this incurable pt population. Disclosures: Reeder: Novartis: Research Funding; Celgene: Research Funding; Millennium: Research Funding.

With the growing diversity in race and ethnicity of the American population, there is a need to characterize the disparities in access and outcomes of hematopoietic cell transplantation (HCT) for the racial and ethnic minorities. This single center study examined the association of ethnicity/ race with outcomes after HCT. Clinical information of 301 adult patients who underwent single allogeneic HCT for a hematological disorder at Mayo Clinic in Arizona from 11/03 to 06/12 was obtained from the institutional database and retrospective chart review. Information about ethnicity was self-reported by patients. Median follow-up was 20 months (range 3-106 months). Overall survival was compared between the racial/ ethnic groups using Cox regression while adjusting for other clinical factors. The study included 224 white patients (75%) and 77 ethnic minority patients (25%). Non-whites/ Hispanics were younger at HCT (median age 40 vs. 56, P = .001). Use of myeloablative conditioning (61% vs. 31%, P < .001) and related donors (50% vs. 35%, P = .01) was more common in Non-whites/ Hispanics. There were no differences in disease diagnosis and risk, gender distribution and HCT- comorbidity index between the two groups. More Non-whites/Hispanics were unemployed (51% vs. 25%; P < .001). No statistically significant differences in the incidence of post-transplant complications including infections, veno-occlusive disease, grade II-IV acute and NIH chronic GVHD were seen between the two groups. Cumulative incidence of relapse at 5 years was higher in Non-whites/ Hispanics (33% vs. 22%; P = .03). Though the univariate analysis showed no differences in overall survival (5 year OS: 52% for Whites vs. 50% for Non-whites/Hispanics; P = .44), a higher risk for mortality was seen in the multivariate analysis for ethnic minorities as compared to the white patients. (Table) Higher risk of mortality from HCT in the ethnic minorities underscores the need for better understanding of the factors responsible for differential outcomes and continued efforts to eliminate disparities in access and outcomes of HCT.TableMultivariate analysis for overall survival after HCTVariableHazard ratio95% CIP valueRace Ethnicity White1.0 Non-white/ Hispanic1.721.03 to 2.870.04Age <501.0 ≥ 501.600.95 to 2.700.07Disease Lymphoma1.0 Leukemia/ MDS1.180.58 to 2.420.64 Others1.360.42 to 4.410.6Disease risk Low1.0 Intermediate1.240.66 to 2.350.5 High2.361.39 to 4.000.001Donor Related1.0 Unrelated1.450.94 to 2.220.08Conditioning Reduced intensity1.0 Myeloablative1.390.85 to 2.30.19Karnofsky performance score 1001.0 <1002.921.82 to 4.69< .001HCT-CI score1.080.97 to 1.190.13CMV status D-/R-1.0 Others1.50.85 to 2.640.16Employment status Employed1.0 Unemployed1.030.63 to 1.690.9 Retired1.440.84 to 2.480.18 Open table in a new tab

Introduction Allogeneic hematopoietic stem cell transplant (HCT) patients are at risk for having a low Vitamin D (VD) level. VD level has been correlated with cancer incidence, pulmonary disease and infection. VD also has immunomodulatory properties and reports suggest that a low VD level increases the incidence of chronic GVHD and may impact mortality in HCT. HCT morbidity and mortality is attributed to infection, organ system toxicity, GVHD and recurrent disease. Identifying a correctable factor that would reduce the occurrence or severity of these complications would be beneficial. It is possible that VD may have significant effect on outcome after HCT due to its described properties. Normal VD level may infer better outcome for HCT patients by improving response in or preventing infection, protecting organ function, decreasing risk of relapse and/or decrease incidence or severity of GVHD. We hypothesize that there is a relationship between VD level and morbidity and mortality after HCT. We therefore studied VD levels pre- and post-HCT to determine if there was an impact of VD level on these outcomes. Patients and Methods Two hundred and fifty patients underwent myeloblative or non-myeloablative HCT between 3/12/2009 and 10/29/2012 at our institution. Baseline demographic data, disease characteristics, transplant variables and outcomes data were obtained from the transplant database. These data were supplemented by retrospective chart review for VD levels prior to transplant, at day 100 and 1 year post-HCT. Data were collected through day 100 for occurrence of infection and admissions to the ICU. Categories for VD level included normal (≥30 ng/ml) or abnormal (<30 ng/ml). Patient characteristics were compared using the Chi-square test or Wilcoxon rank sum test. The logrank test was used to compare the survival curves between groups, and the Cox proportional hazard model was used to measure the association between outcomes (mortality, relapse, acute or chronic GVHD) and VD level. Results Of the 250 patients undergoing HCT VD level was performed on 180 (72%) patients pre-HCT, 149 (60%) patients at day 100 post-HCT and 81 (32%) patients at 1 year post-HCT. The rate of acute or chronic GVHD was not significantly associated with VD level pre or post-HCT. Overall infection risk was not significant pre or post-HCT but when sorted by type of infection bacterial infection (p=0.01), radiologic evidence of pulmonary nodules/consolidation (p=0.03), and ICU admissions (p=0.0313) within the first 100 days post-transplant were significantly increased in patients who had a low VD level at day 100 post -HCT. Pre-HCT and 1 year post-HCT VD level did not impact mortality or relapse but there was a significant increase in one year mortality (p=0.02, HR = 5.99) and relapse (p = 0.03, HR=9.47) in patients who had a low VD level at day 100 post-HCT. ![Figure 1][1] Figure 1 Mortality at 1 Year by Day 100 Post-HCT by VD Level ![Figure 2][1] Figure 2 Relapse at 1 Year by day 100 Post-HCT VD Level ![Figure 3][1] Figure 3 Bacterial Infection, Lung Infection and ICU Admissions by Day 100 Post-HCT VD Level Discussion This study shows that VD may play a significant role in bacterial infection, pulmonary infection, ICU admission, mortality and relapse after HCT. Those patients with a low VD level at day 100 post-HCT had significantly worse outcomes for relapse and mortality. Those patients with a low VD level at day 100 post-HCT had a higher incidence of lung infection, bacterial infection and admission to the ICU. In contrast to previous studies, we found no correlation between VD level and incidence of acute or chronic GVHD. This study is one of the largest reported and the first to our knowledge that reports decreased risk of certain types of infection (bacterial and lung), mortality and relapse in those with an adequate VD level receiving HCT. It is possible that supplementation of VD to keep levels ≥30 would reduce these complications of HCT. Future prospective study of VD is warranted. Finding a low cost and easy to administer therapy (such as VD replacement) that would reduce morbidity, mortality and relapse in the HCT population is needed. Disclosures: Reeder: Celgene: Research Funding; Novartis: Research Funding; Millenium: Research Funding. [1]: pending:yes

Background Steroid-refractory (SR) acute graft-versus host disease (aGVHD) is a serious complication of allogeneic HCT, for which there is no established standard treatment. Both ECP and cytokine inhibitors such as Infliximab have apparent single agent activity in the therapy of SR aGVHD, but there are no published data that address the efficacy of combination anticytokine therapy and ECP in this setting. We report here results in 18 adult patients (pts) with grade III or IV SR aGVHD who were treated with concurrent Infliximab and ECP. Patients All pts underwent allogeneic HCT (first transplant, n=15, second transplant, n=3) for a hematologic malignancy at Mayo Clinic Arizona between March 2012 and May 2013. The median age was 61 (range 22-70), and the median follow-up of 6 surviving pts is 263 days (range 79-433). Donors were related in 3, matched unrelated in 8, and mismatched unrelated in 7. GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil in 13 pts and tacrolimus/methotrexate in 5; in addition, 17 pts received in vivo T-cell depletion with Thymoglobulin 2.5 – 7.5 mg/kg. All pts developed grades III-IV aGVHD at a median day 27 post-transplant (range 10-107) and failed to respond to a course of high-dose corticosteroids (methylprednisolone or equivalent 2 mg/kg daily) for at least 5 days. Treatment Regimen At diagnosis of SR aGVHD, pts were scheduled to receive weekly Infliximab 10 mg/kg (maximum 4 doses), concurrent with ECP performed twice or thrice weekly for one month, followed by a pre-specified taper schedule (anticipated total treatment duration of 6-9 months). To minimize infectious risk and morbidity, corticosteroids were tapered rapidly after the start of Infliximab/ECP therapy. Results Thirteen pts (72%) responded to the Infliximab/ECP combination; complete response (CR; resolution of all GVHD symptoms for at least 30 days and able to discontinue corticosteroids) was observed in 6 pts (33%), and partial response (PR; improvement in GVHD symptoms, partial taper of corticosteroids, and no additional agent for at least 30 days) in 7 pts (39%). At the time of this report, 6 pts are alive, and the Kaplan-Meier estimate of one-year survival is 22.5 % (95% CI, 8.8%-47%). Only pts who achieved CR had good outcomes (5/6 surviving and clinically well); among 13 pts with PR (7) or no response/progression (6) to Infliximab/ECP, 12 have died and one is day 79 post transplant and remains on ECP and low-dose prednisone. Eleven of the 12 deaths were related to GVHD or complications of its treatment (infection, multi-organ failure). Conclusions In this retrospective study of adult pts with severe (grade III/IV) SR aGVHD, treatment with 4 doses of weekly Infliximab and concurrent ECP resulted in an overall response rate of 72%, with one-third of pts achieving CR; the regimen was well-tolerated and facilitated early taper and rapid discontinuance of corticosteroids. Unfortunately, the overall survival of 22.5% at one year does not appear superior to other single agent or combination therapies reported in the literature, or to historical data from our program. Although a small percentage of pts appear to be long-term survivors, the majority of pts succumb to complications of progressive GVHD or infection. Given poor results with available therapies, and the dismal prognosis of pts with SR aGVHD, future research should focus on better preventative strategies for this devastating complication of allogeneic HCT. Disclosures: No relevant conflicts of interest to declare.

Metastatic breast cancer remains a major treatment challenge. The use of high-dose chemotherapy (HDCT) with rescue by autologous mobilized peripheral blood (MPB) is controversial, in part because of contamination of MPB by circulating tumor cells. CD34(+)Thy-1(+) selected hematopoietic stem cells (HSC) represent a graft source with a greater than 250,000-fold reduction in cancer cells. Here, we present the long-term outcome of a pilot study to determine feasibility and engraftment using HDCT and purified HSC in patients with metastatic breast cancer. Twenty-two patients who had been treated with standard chemotherapy were enrolled into a phase I/II trial between December 1996 and February 1998, and underwent HDCT followed by rescue with CD34(+)Thy-1(+) HSC isolated from autologous MPB. More than 12 years after the end of the study, 23% (5 of 22) of HSC recipients are alive, and 18% (4 of 22) are free of recurrence with normal hematopoietic function. Median progression-free survival (PFS) was 16 months, and median overall survival (OS) was 60 months. Retrospective comparison with 74 patients transplanted between February 1995 and June 1999 with the identical HDCT regimen but rescue with unmanipulated MPB indicated that 9% of patients are alive, and 7% are without disease. Median PFS was 10 months, and median OS was 28 months. In conclusion, cancer-depleted HSC following HDCT resulted in better than expected 12- to 14-year PFS and OS in a cohort of metastatic breast cancer patients. These data prompt us to look once again at purified HSC transplantation in a protocol powered to test for efficacy in advanced-stage breast cancer patients.

The anti-cytomegalovirus (CMV) activity and safety of oral maribavir in CMV-seropositive allogeneic stem-cell transplant recipients were evaluated in a randomized, double-blind, placebo-controlled, dose-ranging study. After engraftment, 111 patients were randomized to receive CMV prophylaxis with maribavir (100 mg twice daily, 400 mg once daily, or 400 mg twice daily) or placebo. Within the first 100 days after transplantation, the incidence of CMV infection based on CMV pp65 antigenemia was lower in each of the respective maribavir groups (15%, P = .046; 19%, P = .116; 15%, P = .053) compared with placebo (39%). Similarly, the incidence of CMV infection based on plasma CMV DNA was lower in each of the respective maribavir groups (7%, P = .001; 11%, P = .007; 19%, P = .038) compared with placebo (46%). Anti-CMV therapy was also used less often in patients receiving each respective dose of maribavir (15%, P = .001; 30%, P = .051; 15%, P = .002) compared with placebo (57%). There were 3 cases of CMV disease in placebo patients but none in the maribavir patients. Adverse events, mostly taste disturbance, nausea, and vomiting, were more frequent with maribavir. Maribavir had no adverse effect on neutrophil or platelet counts. These results show that maribavir can reduce the incidence of CMV infection and, unlike ganciclovir, does not cause myelosuppression.

Metastatic renal cell carcinoma (RCC) is a disease that is resistant to conventional systemic therapy. Nonmyeloablative allogeneic stem cell transplant has activity in patients with metastatic RCC. This approach has been used in related donor transplantation but there are limited data on outcomes in the setting of unrelated donor (URD) transplantation. This phase II trial assessed the efficacy, safety, and responses in 16 patients, 10 related and 6 URD transplants after a reduced intensity conditioning regimen and stem cell transplant as a treatment for metastatic RCC. Sixteen patients received a conditioning consisting of either fludarabine, cyclophosphamide (n=11) or fludarabine, total body irradiation (n=5) followed by transplantation from an HLA-matched sibling donor or a unrelated HLA-donor. Cyclosporine and mycophenolate mofetil were administered as posttransplant immunosuppression. Patients were monitored for engraftment by short tandem repeat for myeloid and lymphoid lineages and clinical response was assessed by serial imaging. All patients achieved donor chimerism, 7 patients developed acute, grades 2 to 3, graft-versus-host disease. Chronic graft-versus-host disease occurred in 6 patients and transplant-related mortality was 12%. Of the 10 related donors, 1 obtained a complete response, 3 had a partial response, and 3 had stable disease. In the 6 patients who underwent URD transplant, 1 obtained a complete response and 1 patient had stable disease. These results suggest that similar outcomes are possible where either related or URD were used as the stem cell source in reduced intensity stem cell transplant for metastatic RCC.

Abstract Cytomegalovirus (CMV) remains a major threat to recipients of allogeneic stem cell transplants (SCT). Potential toxicities of currently available anti-CMV agents complicate their use in this population. Maribavir (MBV) is an oral antiviral drug with a unique mechanism of action against CMV and a promising safety profile in early clinical studies. This randomized, double-blind, multicenter, dose-ranging study enrolled adult CMV-seropositive recipients of allogeneic SCT. After engraftment, patients were randomized to receive CMV prophylaxis with placebo or MBV at one of three doses for up to 12 weeks. CMV surveillance was performed weekly with both CMV pp65 antigenemia and plasma CMV DNA PCR assays. If CMV was detected, study drug was stopped and preemptive anti-CMV therapy started as per standard practice at each center. A total of 111 patients were enrolled (median age 47 years; 70% myeloablative SCT; 53% related donor). Incidence of CMV infection or disease in the first 100 days post-SCT are shown in the table. The safety profile of maribavir was favorable in this patient population; most adverse events occurred at similar rates in placebo and MBV groups. There was no adverse impact of MBV on neutrophil counts or other laboratory or ECG parameters. Consistent with prior clinical studies, the most notable events that appeared to be associated with MBV were mild-moderate taste disturbance, nausea, and diarrhea. In conclusion, maribavir prophylaxis reduced the rate of CMV infection compared to placebo, with a favorable safety profile in this complex patient population. Phase 3 studies of maribavir in stem cell and solid organ transplant recipients are being planned. Placebo MBV 100 mg BID MBV 400 mg QD MBV 400 mg BID N evaluable 28 27 27 26 p values represent comparison to placebo (stratified by myeloablative or nonmyeloablative SCT) CMV infection or disease based on: pp65 antigenemia 11 (39%) 4 (15%) 5 (19%) 4 (15%) p=0.046 p=0.116 p=0.053 plasma CMV DNA PCR 13 (46%) 2 (7%) 3 (11%) 5 (19%) p=0.001 p=0.007 p=0.038 Use of preemptive anti-CMV Rx 16 (57%) 4 (15%) 8 (30%) 4 (15%) p=0.001 p=0.051 p=0.002 CMV disease only 3 (11%) 0 0 0 p=0.089 p=0.084 p=0.091

Most umbilical cord blood (UCB) transplant studies indicate that the minimum nucleated cell dose needed for adequate engraftment is > 2 x 107 cells/kg, which eliminates most adults. Using a novel, post-thaw cell manipulation without washing, we explored the notion that the minimum ‘safe' transplant cell dose/kg could be lowered to 1 x 107/kg, which would permit most adults to be transplanted. Washing UCB cells post-thaw before transplantation is a common practice, but is associated with a modest, non-specific cell loss. Our method utilizes rapid thawing at 37°C followed by a slow, progressive dilution to a final DMSO concentration of 1% over 10 minutes with a 10% Dextran, 8% human albumin solution, without washing and with subsequent infusion over 15 minutes. To date 27 adults who did not have a matched sibling (5/6, 6/6) or unrelated (8/8) matched donor have been transplanted using cells processed by this method. Their median age was 42 (22–58) and their median weight was 84 (49–109) kg. Of the group, 18 (67%) had an active refractory hematologic disorder, and only 1 was in CR1 (AML with monosomy 7), and 11 (41%) had failed a prior ablative transplant. HLA matching (serologic for class I, and allele for class II) was 4/6 in 14, 5/6 in 11, and 6/6 in 2. Preparative regimens were ATG plus Cy/TBI in 14, Busulfan/cyclophosphamide in 3 or high dose BCNU-based in 10. GVHD prophylaxis consisted of tacrolimus (Day −2 to Day + 100) and steroids (D + 7 to day +80). Median cell doses infused were: nucleated cells: 1.47 x 107/kg and CD34: 0.48 x 105/kg; 22 (82%) received a nucleated cell dose < 2 x 107/kg. Median post-thaw cell recovery and viability were 97% and 97.5% respectively. Survivals at 100 days and 1 year were 76% (95% CI = 59 – 93)and 44 % (95% CI = 22 – 67) respectively. Median nucleated cell dose infused for the 1+ year survivors was 1.32 x 107/kg with all but one transplanted with < 2 x 107 cells/kg. There were 4 early deaths, early on in the trial at day +5, +13, +17 and +22, all in patients with refractory disease, due to sepsis. The median time to neutrophil engraftment (> 500/μl) was 19 days (range = 11–38 days) and time to platelet engraftment (> 20,000/μl) was 45 days (18–114+); however 2 patients died at day + 33 (VOD) and +114 (fungal pneumonia complicating refractory acute GVHD) without platelet recovery. Acute GVHD was seen in 56% (30% grade III/IV); chronic GVHD was seen in 57%. Within the limited cell dose range used, increasing nucleated cell and CD34 doses, as well as HLA match and disease stage were not predictive of survival or ANC engraftment in univariate analyses. In summary, our survivals are similar to those seen when blood, marrow or UCB stem cells with higher minimum cell dose thresholds are used as the transplant source in similar patients. Using a non-wash post-thaw procedure for our 27 transplants, few viable cells are lost allowing successful UCB transplantation at nucleated cell doses < 2 x 107/kg in adults who do not have a living HLA-matched related or unrelated donor and who otherwise have no option for potentially curative therapy.