History Of Prior Transplant Research Articles

2730. Clinically significant cytomegalovirus infection in patients with lymphoma and no prior cellular therapy

Abstract Background Reactivation of cytomegalovirus (CMV) is commonly reported in lymphoma patients who undergo cellular therapy, with often poor outcomes. The risk for CMV reactivation in patients with lymphoma prior to cellular therapy is not well understood. As new alternative immunosuppressive therapies emerge for lymphoma, understanding baseline risk for CMV reactivation is paramount to improve clinical and oncologic outcomes. Our goal was to identify risk factors, and describe outcomes associated with clinically significant CMV infection (CS-CMVi) in lymphoma patients with no prior cellular therapy. Methods We performed a retrospective cohort study for all lymphoma patients who underwent testing for CMV by PCR from blood between 1/2017 and 12/2020. Patients with prior history of transplantation or chimeric antigen receptor therapy were excluded. Patients with and without CS-CMVi were identified for risk factor analysis by univariate analysis. Results A total of 217 lymphoma patients were included in our analysis; CS-CMVi was identified in 41 (19%) patients. When compared to patients without CS-CMVi (control group), lymphoma patients with CS-CMVi were more likely to have history of HIV (5% vs 0%; p= 0.0350), primary central nervous system lymphoma (7% vs 1%; p= 0.0220) and relapsed disease (54% vs 25%; p= 0.0005) (Table 1). CS-CMVi was also more common if testing was done at time of relapse diagnosis (32% vs 10%; p= 0.0007), during work up for infection (98% vs 68%; p < 0.0001) and more often (3 vs 1; p < 0.0001) (table 1). Mortality and remission rates within 1 year of testing were worse in patients with CS-CMVi (table 2 and figure 1). Conclusion CS-CMVi in lymphoma patients is associated with poor outcomes including oncologic outcomes. Further analysis to better define patients with lymphoma at high-risk for CS-CMVi should be studied for future preventative strategies. Disclosures Fareed Khawaja, MBBS, MEDSCAPE: Honoraria|Viracor: Grant/Research Support Roy F. Chemaly, MD/MPH, Eurofins-VViracor: Grant/Research Support|Karius: Advisor/Consultant

Bendamustine Bridging Versus Standard of Care Chemotherapy on Toxicity Profile for Multiple Myeloma Patients Undergoing CAR T Cell Therapy

Introduction Multiple myeloma (MM) remains an incurable malignancy arising from plasma cells, however great promise has been seen with the use of Chimeric Antigen Receptor (CAR) T cells. Autologous CAR-T products require bridging therapy, however little is known about different agents used in this manner. Some studies indicate decrease in disease burden is crucial, while others note an association with higher rates of toxicity and negative effect on survival. As commercial CAR T cell therapy is indicated after failure of at least 4 prior treatments, careful consideration of bridging therapy is crucial, particularly in patients with aggressive and high-risk disease. This study aims to compare the impact of bendamustine to standard of care (SOC) bridging therapy in MM patients undergoing CAR T cell therapy. Methods A single-center retrospective chart review of 19 adult patients with relapsed/refractory multiple myeloma treated with CAR T cells, who also received bridging therapy with either bendamustine (n=9) or SOC/Other (n=10) was conducted at Mount Sinai Hospital. Patient demographic information (gender, race, MM subtype, history of prior transplant) was collected and toxicity profiles (infection, pancytopenia, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS)) were compared. Descriptive statistics were used to analyze demographic characteristics and toxicity profiles between the two cohorts. Results Comparative analysis of demographics showed that both cohorts were predominantly males with IgG MM subtype, and varied in terms of race ( Figure 1a). The Other cohort had a higher proportion of patients with a history of autologous stem cell transplant (ASCT) (70%) compared to the bendamustine group. In the SOC group, two patients developed infections, whereas none were observed in the bendamustine cohort ( Figure 1b). Pancytopenia was observed in both groups, but interestingly, 100% of patients experienced it in the SOC cohort. CRS and ICANS were comparable between the two groups ( Figure 1b). Comparative statistics demonstrated no significant difference between the two groups ( Figure 1c). Conclusion Our study findings indicate that there was no significant difference in toxicity profiles between the two pre-conditioning therapy groups. Given our limited sample size, future studies with a larger are indicated to validate these results.

Factors associated with treatment response to CD19 CAR-T therapy among a large cohort of B cell acute lymphoblastic leukemia.

CD19-targeted chimeric antigen receptor (CAR) T cell therapy has demonstrated striking responses among B cell acute lymphoblastic leukemia (B-ALL), but analyses of potential factors associated with poor response and relapse are lacking. Here, we summarize the long-term follow-up of 254 B-ALL treated with CD19 CAR-T cells from 5 clinical trials (NCT03173417, NCT02546739, and NCT03671460 retrospectively registered on May 23, 2017, March 1, 2018, and September 7, 2018, respectively, at www.clinicaltrials.gov ; ChiCTR-ONC-17012829, and ChiCTR1800016541 retrospectively registered on September 28, 2017, and June 7, 2018, at www.chictr.org.cn ). Our data showed that TP53 mutation, bone marrow blasts > 20%, prior CAR-T/blinatumomab treatment, and severe cytokine release syndrome (CRS) were associated with a lower complete remission (CR) rate while age, extramedullary disease, complex cytogenetics, history of prior transplant, prior courses of chemotherapy, CAR-T cell dose, and manufacturing source of the cellular product did not affect patients' CR rate. Risk factors related to leukemia-free survival (LFS) and overall survival (OS) were history of prior transplant, complex cytogenetics, TP53 mutation, severe CRS, neurotoxicity, and CAR-T therapy without consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT). Age and CAR-T cell dose did not influence LFS and OS. Patients with consolidative allo-HSCT after CAR-T therapy had a superior OS and LFS compared to those who did not. This benefit was also observed in both pediatric and adult patients as well as in patients either in high- or low-risk groups. This large study to identify risk factors of CR, LFS, and OS may help to maximize clinical outcomes of CAR-T therapy. Précis TP53 mutation and BM blasts > 20% are two independent factors associated with the CR rate. Patients with high tumor burden as well as those with bone marrow blasts < 5% can benefit from consolidative allo-HSCT post-CAR-T therapy.

Tailored Rabbit Antithymocyte Globulin Induction Dosing for Kidney Transplantation.

BackgroundRabbit antithymocyte globulin (rATG) is the most widely used kidney transplant induction immunotherapy in the United States. It was recently Food and Drug Administration approved for this indication with typical dose recommendations of 1.5 mg/kg for up to 7 days given via a central line.MethodsWe theorized that reduced rATG dosing when compared with conventional dosing (6-10.5 mg/kg) is safe and effective, leading to development of a risk-stratified treatment protocol. Five-year data from a retrospective cohort of 224 adult kidney transplants (2008-2013) with follow-up through 2015 is presented. Cumulative rATG doses of 3 mg/kg were administered peripherally to nonsensitized living donor recipients, 4.5 mg/kg to nonsensitized deceased donor recipients. A subset of higher immunologic risk recipients (defined as history of prior transplant, panel reactive antibody greater than 20%, or flow cytometry crossmatch positivity) received 6 mg/kg.ResultsThere were no differences in patient or graft survival between the 3 groups. One-year rejection rates in the first 2 groups were 8.3% and 8.8%, respectively, comparable to contemporaneous rates reported to the Scientific Registry of Transplant Recipients. Dose tailoring permitted substantial cost savings estimated at US $1 091 502. Mean length of stay fell by almost 3 days as the protocol was refined. There were no episodes of phlebitis. Infection rates were comparable with those reported to the Scientific Registry of Transplant Recipients.ConclusionsThe novel findings of the current study include peripheral administration, reduced dosing, favorable safety, excellent allograft outcomes, and clear associative data regarding reduced costs and length of stay.

Comparable Progression-Free and Overall Survival Following Transplantation of Single Cord Blood with HLA-Matched Related Donor in Adults with Non-Remission Myeloid Malignancies

<Introduction> Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment for patients with non-remission myeloid malignancies. Although bone marrow (BM) or peripheral blood (PB) from HLA-matched related donor (MRD) have been the first choice of graft when available, true superiority of MRD over others can still be controversial especially for patients with non-remission myeloid malignancies. Cord blood (CB) has emerged as a promising alternative graft and its outcome has been encouraging over periods. Rapid availability is the advantage of MRD and CB over unrelated adult donor, which could fit to patients with non-remission myeloid malignancies who need urgent allo-SCT. So far, few studies are available comparing the outcomes of CB and MRD for adults with non-remission myeloid malignancies.<Methods> We retrospectively reviewed the outcomes of patients with non-remission myeloid malignancies who underwent allo-SCT using CB or MRD at our institute from Jan. 2008 to Dec. 2015 consecutively. Patients who lacked MRD or were unable to find suitable unrelated donor within appropriate periods underwent CB transplantation. Patients who had a prior history of transplantation, were in poor performance status (ECOG PS 3 and greater), had active infections at the time of conditioning, were over 60 years, or received ATG as GVHD prophylaxis were excluded.<Results> One hundred and fifty-nine patients were included in this study. One hundred and thirty-seven patients received single CB, whereas 21 receive PB from MRD and one received both PB and BM from the same MRD. Underlying diagnoses were AML (n=125), MDS-RAEB (n=20), CML (n=11), and MPN (n=3). All patients were not in remission at the start of conditioning regimens including primary induction failure (n=47), first relapse (REL) (n=37), second REL (n=4), and CML-BC/AP after TKI failure (n=11). Fifty-six patients who were diagnosed with AML with MRC or MDS were untreated or only received agents for blast control before transplantation. One hundred and twenty-nine patients were conditioned with MAC regimens, whereas 21 patients received RIC regimens. The median interval from diagnosis to transplant was 162 days (range, 34-2774 days). Recipients of CB and MRD were comparable in terms of median age (50 years in CB, 47 years in MRD), diagnosis, disease status, conditioning regimens, median interval from diagnosis to transplant, and year of transplant. CB recipients received more HLA-mismatched grafts and received a lower number of CD34+ cells, compared to MRD recipients. Median follow-up periods of survivors were 997 days for CB and 1459 days for MRD recipients, respectively. The overall (OS) and progression-free survival (PFS) showed no statistically significant differences between CB and MRD recipients; 3-year OSs of CB and MRD recipients were 47.2% (95% CI, 37.4-56.3%) and 45.5% (24.1-64.6%) (p=0.67), respectively (Figure 1), and 3-year-PFSs of CB and MRD recipients were 40.6% (31.4-49.6%) and 35.6% (15.7-56.2%) (p=0.3), respectively. Cumulative incidence of neutrophil engraftment was almost comparable between CB and MRD recipients (91% vs 100%, p=0.1), although CB recipients showed slower neutrophil recovery (median 21 (12-39) days vs 15 (11-39) days, p<0.01). Lower incidence of relapse was observed in CB recipients (31.5% vs 55.3% at 3 years, p=0.01), whereas CB recipients showed a trend to a higher NRM incidence relative to the MRD recipients, although not statistically significant (27.9% vs 9.1% at 3 years, p=0.19).<Conclusions> Both transplant strategies have shown promising outcomes in patients with non-remission myeloid malignancies. Our analysis also shows that CB is not inferior to MRD as a source of hematopoietic stem cell grafts and may be associated with a lower relapse rate. CB could expand the possible donor pool for patients who need urgent allo-SCT and should be more considered as valuable grafts. [Display omitted] DisclosuresIzutsu:Abbvie: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Janssen Pharmaceutical K.K.: Honoraria; Eisai: Honoraria; Kyowa Hakko Kirin: Honoraria; Chugai Pharmaceutical: Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria; Mundipharma KK: Research Funding.

Collection of Peripheral Blood Stem Cells in Patients with Multiple Myeloma after Stem Cell Transplant: A Single Institution Experience

BackgroundAutologous stem cell transplant is the standard of care for eligible multiple myeloma patients. However, many patients relapse with passage of time. These patients often do not have any or have inadequate numbers of previously harvested stem cells. The question still comes up frequently whether peripheral blood stem cells can be successfully collected from patients with history of prior transplant and what is the best approach. Herein, we report the results from our institution.Patients and MethodsRecords of patients with multiple myeloma who received transplant at our institute between 03/01/12 -07/09/15 dates were reviewed. Recorded data included disease stage, prior transplant and chemotherapies, stem cell mobilization strategies and time to engraftment. Student T-test was performed on reviewed data.ResultsA total number of 21 patients (7 male and 14 female) with multiple myeloma and prior transplant underwent peripheral blood stem cell collection. Median age at diagnosis was 52.1 years (range 36-71 years). Each patient had at least 2 prior rounds of chemotherapy with a median of 4 prior lines of chemotherapies (range 2-6).One patient had a prior history of allotransplant and remainder had at least one prior autotransplant. ISS staging at diagnosis included 5 patients with Stage 1, 2 patients with Stage 2, 5 patients with Stage 3 and stage was not available for 8 patients. One patient had plasma cell leukemia. Disease subtypes included two patients with IgA kappa, one with IgA lambda, nine with IgG kappa, two with IgG lambda, five with kappa light chain, one with lambda light chain and one with non-secretory disease. 33% of patients had high risk cytogenetics at time of stem cell collection.The total number of prior transplants before stem cell collection was 25 with a median of 1 transplant (range 1-2). Median age at the time of collection was 59.3 years (range 43-81). Disease status at time of salvage transplant included complete response in 5 patients, very good partial response in 2, partial response in 9 and stable disease in 5 patients.Filgrastim with plerixafor was used for mobilization in 15 patients, filgrastim, plerixafor and pegfilgrastim in 5 patients and filgrastim with pegfilgrastim in 1 patient. A median number of 3 doses of plerixafor (range 0-5) were used. Median stem cell collection dose was 9.75 X 106/kg CD34 cells (range 3.29-24.8 X 106/kg) and median number of collection days was 3 (range 1-5). All patients received salvage transplants. Engraftment occurred at a median of 12 days (range 10-27). The 21 patients received a total number of 30 transplants after collection with a median of 1 transplant (range 1-2). Prior to collection, D-PACE was administered to 10 patients, VDT-PACE to 2 patients, VCD to 1 patient and growth factors only to 8 patients. 5/8 patients who were mobilized with only growth factors had baseline platelet count of < 130,000. Patients receiving D-PACE had a median collection of 13.55 X 106 cells as compared to 5.70 X 106 cells without it (p<0.004).ConclusionsOur experience shows that collecting peripheral blood stem cells after prior transplantation in patients with multiple myeloma is very feasible even in patients with multiple lines of chemotherapies. Addition of D-PACE as chemo-mobilization strategy has proved to be effective if platelet count is normal at baseline. DisclosuresNo relevant conflicts of interest to declare.

Impact of HLA Haplotype Matching On Engraftment in Reduced Intensity Cord Blood Transplantation.

Abstract 3043 IntroductionHLA-mismatched unrelated cord blood transplantation (UCBT) is feasible and, in retrospective comparative analyses, allows survival rates similar to conventional unrelated HLA-matched adult-derived grafts. Although it is clear that the degree of UCB HLA mismatch in patients has a negative effect on outcomes, the biologic implications of HLA haplotype itself have not been explored for UCBT. In unrelated bone marrow transplantation, an effect of HLA haplotype matching on GVHD has been clarified. (S.Morishima. et al. Blood 2010). This study was conducted to determine the impact of HLA haplotype matching in reduced intensity UCBT. Patients and MethodsTo determine the impact of HLA haplotype matching with outcomes after UCBT, We retrospectively reviewed patients with hematologic malignancies who underwent reduced intensity CBT at Toranomon Hospital from August 2006 and December 2010 consecutively. Patients who had prior history of transplantation, were in poor performance status (ECOG PS >3), had active bacterial or fungal infections at the time of conditioning were excluded. Then, the remaining 164 consecutive patients were reviewed. The most frequently used conditioning regimens were fludarabine, alkylating agent (melphalan or busulfan) with total body irradination (TBI), tacrolimus plus mycophenolate mofetil for GVHD prophylaxis. DNAs of 164 pairs were analysed for HLA-A, -B, and -DRB1 based on High Resolution typing, and we have determined the HLA haplotype based on Japanese common HLA haplotypes referred from the previous reports. ResultsFor A, B, DR based on high resolution typing the following mismatch occurred: no mismatch 3(2%), one mismatch 12(7%), two mismatch 58(35%), three mismatch 60(37%), four mismatch 28(17%), five mismatch 3(2%) in the GvH direction, and: no mismatch 2(1%), one mismatch 16(10%), two mismatch 55(34%), three mismatch 56(34%), four mismatch 32(20), five mismatch 3(2%) in the HvG direction. Then 37 among 164 pairs were defined as the HLA haplotype matched group. The number of total nucleated cells and CD34+ cells were not significantly different between HLA haplotype matched group and non-matched group. The cumulative incidence of neutrophil recovery was higher in HLA haplotype matched group than in non-matched group.( 94.6% vs. 80.3% up to day 60, p=0.0027). Lower incidence of pre-engraftment immune reaction(PIR) and acute GVHD were observed in haplotype matched group (37.8 % vs. 47.9 % up to day 60 post-transplant, P = 0.32), III to IV acute GVHD( 18.9% vs. 27.7% up to day 100 post-transplant, p=0.29). The cumulative incidences of relapse tended to be lower in haplotype matched group than in non-matched group (21.5% vs. 31.5%, P=0.28).Overall survival (OS) was estimated as 36.0 % at 3 years post-transplant. There were no significant differences between mathed and non-matched group in the cumulative incidence of OS (36.8 % vs. 34.3% at 3 years post-transplant, P = 0.84). ConclusionHLA haplotype matching in UCBT was found to have a significant impact on engraftment in this analysis. Disclosures:No relevant conflicts of interest to declare.

Promising Outcome for Patients with AML-MRC Following Cord Blood Transplantation: Is Induction Chemotherapy Before Transplant Necessary?

Abstract 3132▪▪This icon denotes a clinically relevant abstract Introduction:In year 2008 version of WHO classification for myeloid malignancies, a category of AML with myelodysplasia-related changes (AML-MRC) was defined which included both de novo AML with dysplasia and AML secondary to MDS. It is characterized by poor chemosensitivity for which allogeneic transplantation (allo-SCT) has been a viable option to cure. Umbilical cord blood transplantation (UCBT) is a possible treatment strategy that can be performed for those who lack suitable donors due to rapid availability and less stringent HLA matching required. So far, there have been sparse reports available on UCBT for those with AML-MRC. This study was conducted to see the current update in our institute and to see whether the presence of induction chemotherapy before transplant is better for the outcome. Design and Methods:We retrospectively reviewed patients diagnosed as AML-MRC who underwent UCBT at our institute from Mar. 2002 to Mar. 2011 consecutively. Patients who lacked appropriate adult PB/BM donors underwent UCBT. Patients who had prior history of transplantation, were in poor performance status (ECOG PS >3), had active bacterial or fungal infections at the time of conditioning were excluded. Results:Eighty-one patients were included. 52 (64%) were males, and median age was 61 years (range, 17–72). 35 (43%) were de novo AML, and 46 (57%) were AML secondary to MDS. Median time from diagnosis to transplantation was 346 days (range, 42–7997). 39 (48%) did not receive induction chemotherapy before transplant. 76 (94%) were not in remission, 29 (36%) were in high, and 52 (64%) were in very high WPSS risk group, just before transplant. 54 (67%) received reduced-intensity conditionings. 65 received GVHD prophylaxis of tacrolimus-based, while 16 did cyclosporine alone. Median observation time for survivors was 646 days (range 32–2456). Median days of neutrophil recovery (> 500/ul) was 20 days (range, 11–45), and cumulative incidence of engraftment was 76.5 % up to day 50 post-transplant. Cumulative incidences of relapse and non-relapse mortality at 2 years post-transplant were 37.8 % and 33.3 %, respectively. Higher incidence of relapse was observed in those with prior history of MDS in univariate analysis (51.8 % vs. 21.2 % at 2 years post-transplant, P = 0.004), which was the only significant factor associated with higher relapse rate in multivariate analysis (P = 0.020). More NRM was observed in those received transplant early period from 2002 to 2005 vs. those who did from 2006 to 2010 (45.1 % vs. 25.5 % at 2 years post-transplant, P = 0.001), and in those received GVHD prophylaxis using CsA alone vs. others (72.0 % vs. 24.8 % at 2 years post-transplant, P = 0.0002). In multivariate analysis, higher degree of HLA mismatch (2 antigens vs. less than 2) and GVHD prophylaxis using CsA alone were associated with higher incidence of NRM (P = 0.024 and P = 0.00047, respectively). Overall survival (OS) was estimated as 42.1 % at 2 years post-transplant. Better OS was observed in those who received conditioning containing 12.8mg/kg of iv busulfan (60.8% vs. 32.4% at 2 years post-transplant, P = 0.0337), in those received tacrolimus-based GVHD prophylaxis vs CsA alone (47.9 % vs. 17.0 % at 2 years post-transplant, P = 0.0024), and in those received transplant in recent period from 2006 to 2010 vs. those who did from 2002 to 2005 (52.1 % vs. 26.1 % at 2 years post-transplant, P = 0.0248). In multivariate analysis, GVHD prophylaxis using CsA alone and poor WPSS risk category just before transplant were the factors significantly asssociated with poor OS (P < 0.0001 and P = 0.001, respectively). There were no significant differences between presence or absence of prior induction chemotherapy in terms of cumulative incidence of neutrophil recovery (71.4 % vs. 82.1% up to day 50 post-transplant, P = 0.88), relapse (38.0 % vs. 36.1%, P = 0.94), NRM (30.7 % vs. 35.4 %, P = 0.87), and OS (47.7 % vs. 36.2%, P= 0.72) at 2 years post-transplant. Conclusions:These data indicate that CBT is a feasible and promising treatment approach for those with AML-MRC, including elderly patients. More intensive GVHD prophylaxis was beneficial in reducing NRM and improving OS for the population studied. Presence of prior induction chemotherapy before transplant was not associated with higher rate of engraftment or better OS, suggesting tumor reduction before pre-transplant conditioning may not be necessary for successful outcome in our transplant settings. Disclosures:No relevant conflicts of interest to declare.

Comanaging an Organ Transplantation and Melanoma

Objective: To determine malignant melanoma cause-specific and overall survival among patients with melanoma diagnosed after organ transplantation compared with a national sample with malignant melanoma. Design: Retrospective review. Setting: Mayo Clinic sites. Patients: Immunosuppressed organ transplant recipients with malignant melanoma identified from surgical and medical databases at Mayo Clinic (1978-2007), the Organ Procurement and Transplantation Network/United Network for Organ Sharing database (1999-2006), and the Israel Penn International Transplant Tumor Registry (1967-2007). Main Outcome Measures: Prognostic analyses by Breslow thickness and Clark level of overall and melanoma cause-specific survival. Expected survival rates were estimated by applying the age-, sex-, and calendar year–specific survival rates of patients with malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program to the study cohort. Results: Malignant melanoma was diagnosed in 638 patients (724 cases) after transplantation. Breslow thickness was available for 123 patients; Clark level, for 175. Three-year overall survival rates for patients stratified by Breslow thickness (≤0.75, 0.76-1.50, 1.51-3.00, and >3.00 mm) were 88.2%, 80.8%, 51.2%, and 55.3%, respectively, and 3-year cause-specific survival rates (95% confidence intervals) were 97.8% (93.7%-100%), 89.4% (76.5%-100%), 73.2% (53.2%-100%), and 73.9% (56.4%-96.6%), respectively. Three-year cause-specific survival rates (95% confidence intervals) for patients stratified by Clark level (I-IV) were 100%, 97.4% (92.4%-100%), 82.8% (65.3%-100%), and 65.8% (51.8%-83.7%), respectively. For patients with Breslow thickness of 1.51 to 3.00 mm and Clark level III or IV, the cause-specific survival rate in the study sample was significantly different from the expected estimates for patients with the same Breslow thickness or Clark level. Conclusions: Compared with the expected survival rates derived from malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program, immunosuppressed organ transplant recipients with thicker melanomas (ie, with a Clark level of III or IV or a Breslow thickness of 1.51 to 3.00 mm) had a significantly poorer malignant melanoma cause-specific survival rate. The overall survival rate was worse among patients with a prior history of transplantation, regardless of Breslow thickness or Clark level.

Double-Unit Cord Blood Transplantation for Hematological Malignancies in Japan: Multicenter Phase II Study (C-SHOT 0507)

Abstract 3071 Objective:Double-unit cord blood transplantation (dCBT) has been widely applied for patients with less dose single-unit cord blood (sCB) because of a higher engraftment failure. Although several reports have suggested that dCBT may have impact on increasing GVHD incidence and reducing disease relapse, pre-transplant conditioning and GVHD prophylaxis varied too much to read the results. We therefore conducted a prospective multi-center phase II study assessing safety and efficacy of dCBT by using relatively uniform myeloablative conditioning and GVHD prophylaxis in Japan. Methods:From Apr. 2006 to Jan. 2010, patients younger than 55 years with hematological malignancies who lack any adequate unrelated and related donors and without prior history of transplantation were prospectively enrolled. Thirty-nine centers participated following approval by each institutional review board (Trial identifier: UMIN :C000000359, C-SHOT0507). Patients were eligible when there is no single unit with total nucleated cell (TNC) dose of > 2.5 × 107 /kg available, and at least 2 units available that have combined TNC > 2.5 × 107 /kg, with one of each > 1.5 × 107 /kg and the other < 2 × 107 /kg. CB units mismatched at 0–2 antigen in HLA-A, -B, -DR between unit and patient were selected. Preparative regimens were 12 Gy of TBI, Ara-C (12 g/m2) combined with G-CSF, and 120 mg/kg of CY for myeloid diseases, while TBI + CY for lymphoid diseases (S.Takahashi, et al. Blood 109;1322, 2007). GVHD prophylaxis was short term MTX and CsA. Results:Seventy patients were enrolled and 61 patients (AML 29, ALL 17, CML 6, MDS 6, ML 3) received dCBT. Nine patients did not receive dCBT due to disease progression (n=7) and other SCT (n=2). Disease status at dCBT was 27 in standard (CR1, CP1) and 34 in advanced (beyond CR1 or CP1). The median age was 37 years (range; 10–54) and median weight was 70.5kg (50.1–129.8). Median total and CD34+ cell doses (both units combined) at cryopreservation were 3.52 × 107 /kg (2.25 – 4.43) and 1.04 × 105 /kg (0.39 – 2.67), respectively. Median TNCs of larger and smaller unit were 1.90 × 107 /kg (1.47 – 2.48) and 1.60 × 107 /kg (0.74 – 1.97), respectively. Cumulative incidence of neutrophil recovery (NR, >0.5 × 109/L) was 67%(53–77) at day28, and 85%(73–92) at day 50. The median time to NR was day 26 (18–50) and median time to transfusion-independent platelet recovery (>20 × 109/L) was day 53 (32–98). Four died early before day 30 (2 on day8, 1 each on day11 and day 29) and 6 received 2nd transplantation due to engraftment failure (on day30, 33, 37, 42, 50, 54). Among engrafted 51 patients, all 50 patients assessed for chimeric status showed single donor-derived engraftment; 27 were from larger unit and 23 from smaller dose of TNC. Number of TNC of engrafted smaller unit was ranged from 0.74 – 1.96 × 107 /kg, including 6 that were even less than 1.5 × 107 /kg. There is no correlation between unit dominance and the number of TNC, CD34+ cell dose, CFU-GM dose, degrees of HLA/sex/ABO mismatches between units and recipients, and graft viability. Acute GVHD progressed in 33 (65%) of 51 evaluable patients (29% grade II-IV), and chronic GVHD was observed in 18 (36%) of the 50 evaluable patients (18% extensive). Actual EFS, RFS and OS at 1y and 3y was 48%(37–58) and 46%(35–56), 49%(36–61) and 47%(34–59), 57%(44–69) and 54%(40–65), respectively. Median follow-up period of survivors (n=32) are 1226.5days (365–1721). EFS at 1y of standard and advanced status patients was 67%(46–81) and 32%(18–48), respectively (p=0.023). Dose of TNC, CD34 and HLA disparity did not significantly affect on survival. Cumulative incidence of day100-TRM was 26%, and relapse late at 3y was 16.3%. Cause of death were disease progression in 11 and TRM (infection and organ failures) in 18. Discussion:Myeloablative dCBT can be a safe and effective alternative option for those who only have insufficient sCB available (less than 2.5×107/kg of TNC). So far, parameters assessed, such as the engraftment kinetics, survival rate, cumulative incidence of GVHD and relapse in dCBT seem to be comparable to our historical data of sCBT. Determinants of engrafting units after dCBT are still unclear. Disclosures:Off Lavel Use: G-CSF at pre-conditioning for myeloid malignancies is an off-label use in Japan. This study was supported by a Research Grant for Tissue Engineering (H17-014) and a Research Grant for Allergic Disease and Immunology (H20-015) from the Japanese Ministry of Health, Labor and Welfare. Disclosures:Off Label Use: G-CSF at pre-conditioning for myeloid malignancies is an off-label use in Japan. Kato:Research Grant for Tissue Engineering (H17-014) and a Research Grant for Allergic Disease and Immunology (H20-015) from the Japanese Ministry of Health, Labor and Welfare.: Research Funding.

Graft-Versus-Host Disease Prophylaxis Using Tacrolimus + Mycophenolate in Cord Blood Transplantation for Elderly; Impact of Mycophenolate Dosing

Abstract 4563 Introduction:Cord blood transplantation with fludarabine-containing toxicity-reduced conditioning (RT-CBT) has been widely applied to adult patients who have advanced hematologic diseases and are not eligible for conventional conditioning. Severe immune-mediated reactions early after transplant (preengraftment immune reactions, PIR) have been the major cause of early non-relapse mortality particularly for elderly patients. Mycophenolate mofetil (MMF) has been administered since late December 2005 at our institute and was shown to be effective in reducing early toxicity (Transplantation 92:366,2011). However, disease relapse has been the issue hampers successful outcomes, and the optimal GVHD prophylaxis has still not been established. We conducted a retrospective analysis of those who received RT-CBT at our institute using tacrolimus + MMF focusing on the impact of MMF dosing on the outcome. Design and Methods:We retrospectively reviewed patients aged 55 and older who underwent single-unit RT-CBT and GVHD prophylaxis using tacrolimus + MMF consecutively. Median dose of MMF was 33 mg/kg recipient body weight per day, ranging from 13 to 80 mg/kg, divided by 2 or 3 times at each physician's determination. MMF was started on day -1 and continued until neutrophil recovery (>500/μl). Patients who had prior history of transplantation, were in poor performance status (ECOG PS 4 and greater), had active bacterial or fungal infections at the time of conditioning, had diagnosed as multiple myeloma were excluded. Results:From December 2005 to April 2011, 134 patients underwent RT-CBT at our institute. Twenty-seven were excluded due to active infection at the day of transplant or poor performance status, and 107 patients were subjected to the following analysis. The diagnoses included were AML/MDS (n=87), ALL (n=2) CML/MPD (n=4), ML (n=11), and SAA (n=3). Eighty-six (80%) had high risk diseases, and 29 (27%) and 6 (6%) were in ECOG PS 2 and 3, respectively. Cumulative incidence of neutrophil recovery >500/μl were 81 %. Median follow-up time of survivors was 521 days (range, 83 – 1847). Cumulative incidences of non-relapse mortality were 21.4 % and 27.3 % at day 100 and 1 year post-transplant, respectively. Overall survival and event-free survival at 1 year post-transplant were estimated as 47.7 % and 31.7 %, respectively. The patients were subdivided into 2 groups according to MMF dosing (≥30 vs. <30, n = 82 vs. 25) and were compared in terms of the incidence and severity of PIR, neutrophil recovery, NRM, RR, and OS. The cumulative incidence of total PIR was higher in low MMF group compared to high (76.0 % vs. 51.2 %, P=0.009), whereas that of severe-type PIR, defined by the presence of organ dysfunction (described in Transplantation 92:366,2011), was comparable between 2 groups (8.0 % vs. 9.8 %, P=0.83). The incidences of neutrophil recovery (88 % vs 79.3 % at 50 days post-transplant, P=0.10), grade II-IV acute GVHD (61.3 % vs 46.1 % up to day 100, P=0.09), engraftment failure & NRM (40.7 % vs 27.3 % at 1 year P=0.57), HHV6-associated limbic encephalopathy (12.3 % vs 8.6% at day 100 P=0.57), and relapse (37.9% vs 37.2 % at 1 year, P=0.58) were comparable between 2 groups. Overall (34.7 % vs 50.8 %, P = 0.60) and event-free survival (21.4 % vs 34.5 %, P = 0.38) at 1 year post-transplant were also comparable between 2 groups. Cox regression analysis did not find factors significantly affecting OS, PFS, NRM and relapase. Conclusions:These data indicated that lower MMF dosing (<30 mg/kg) does increase the incidence of total PIR, but similarly effective in reducing that of severe form nor NRM as standard dose of MMF (≥ 30 mg/kg), even for elderly population whose majorities were in advanced disease status. Prospective study is warranted to determine the optimal dose of MMF. Disclosures:Off Label Use: Mycophenolate mofetil is used in off-label for GVHD prophylaxis.

Malignant Melanoma in Solid Transplant Recipients

To determine malignant melanoma cause-specific and overall survival among patients with melanoma diagnosed after organ transplantation compared with a national sample with malignant melanoma. Retrospective review. Mayo Clinic sites. Immunosuppressed organ transplant recipients with malignant melanoma identified from surgical and medical databases at Mayo Clinic (1978-2007), the Organ Procurement and Transplantation Network/United Network for Organ Sharing database (1999-2006), and the Israel Penn International Transplant Tumor Registry (1967-2007). Prognostic analyses by Breslow thickness and Clark level of overall and melanoma cause-specific survival. Expected survival rates were estimated by applying the age-, sex-, and calendar year-specific survival rates of patients with malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program to the study cohort. Malignant melanoma was diagnosed in 638 patients (724 cases) after transplantation. Breslow thickness was available for 123 patients; Clark level, for 175. Three-year overall survival rates for patients stratified by Breslow thickness (≤ 0.75, 0.76-1.50, 1.51-3.00, and >3.00 mm) were 88.2%, 80.8%, 51.2%, and 55.3%, respectively, and 3-year cause-specific survival rates (95% confidence intervals) were 97.8% (93.7%-100%), 89.4% (76.5%-100%), 73.2% (53.2%-100%), and 73.9% (56.4%-96.6%), respectively. Three-year cause-specific survival rates (95% confidence intervals) for patients stratified by Clark level (I-IV) were 100%, 97.4% (92.4%-100%), 82.8% (65.3%-100%), and 65.8% (51.8%-83.7%), respectively. For patients with Breslow thickness of 1.51 to 3.00 mm and Clark level III or IV, the cause-specific survival rate in the study sample was significantly different from the expected estimates for patients with the same Breslow thickness or Clark level. Compared with the expected survival rates derived from malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program, immunosuppressed organ transplant recipients with thicker melanomas (ie, with a Clark level of III or IV or a Breslow thickness of 1.51 to 3.00 mm) had a significantly poorer malignant melanoma cause-specific survival rate. The overall survival rate was worse among patients with a prior history of transplantation, regardless of Breslow thickness or Clark level.

Successful Treatment of a Patient With Epstein-Barr Virus–Positive B-Cell Lymphoproliferative Disorder Resembling Post-Transplant Lymphoproliferative Disorder Using Single-Agent Rituximab

Lymphoproliferative disorders that are associated with the Epstein-Barr virus (EBV) are most common after organ and allogeneic bone marrow or stem-cell transplantation. These disorders are rare but can be quite serious. Multiple treatment regimens have been attempted, including the anti-CD20 monoclonal antibody rituximab.1 Nontransplantation-related EBV-positive lymphoproliferative disorders such as age-related EBV-positive diffuse large-cell lymphoma also occur, although less commonly. There is no standard management for these latter disorders.2 We herein describe an elderly patient with no prior history of transplantation or known immunodeficiency who developed a life-threatening lymphoproliferative disorder that was associated with a clonal immunoglobulin gene rearrangement secondary to EBV. The patient was treated successfully with single-agent rituximab.

Comparative Single-Institute Analysis of Cord Blood Transplantation From Unrelated Donors with Related Bone Marrow or Peripheral Blood Stem-Cell Transplants in Elderly Patients with Hematologic Diseases After Reduced Intensity-Conditioning Regimen.

Abstract 2295Poster Board II-272 Introduction:Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning has been widely applied to those who have advanced hematologic diseases and are not eligible for conventional conditioning. Although bone marrow or peripheral blood from related donors (rBM/PB) have been the first choice of graft when available, followed by unrelated adult donor or cord blood (CB), true superiority of rBM/PB over others can still be controversial. Elderly patients have difficulty finding related donors since their siblings are also in their elderly who have higher chance of having co-morbidity relative to younger patients. Rapid availability is the advantage of rBM/PB and CB share over unrelated adult donor, which enabled adapting similar policy of performing transplant possible, especially for elderly patients, given the significantly higher treatment-related mortality for elderly. Design and Methods:We retrospectively reviewed patients aged 55 and older who underwent reduced intensity allogeneic stem-cell transplantation using CB or rBM/PB at our institute from Jan. 2004 to Dec. 2008 consecutively. Patients who were considered for allogeneic transplant and had available 6/6 or 5/6 HLA-matched relatives performed rBM/PB transplants, whereas those who lacked rBM/PB donors underwent CB transplants. Patients who had prior history of transplantation, were in poor performance status (ECOG PS 2 and greater), had active bacterial or fungal infections at the time of conditioning, had diagnosed as multiple myeloma, adult T-cell leukemia, non-malignant diseases were excluded. Results:Two-hundred and thirty-two (171 CB and 60 rBM/PB) RI transplantation were performed from Jan. 2004 to Dec. 2008 at our institute, and 82 (61 CB and 21 rBM/PB) were eventually subjected to the analysis after excluding those who were ineligible according to the above mentioned criteria. The diagnoses included were AML (n=51), MDS (n=9), ALL (n=9) CML/MPD (n=4), and ML (n=9). Fifty-eight (71%) had high risk diseases, and 24 (29%) were in ECOG PS 2. Recipients of CB and rBM/PB were comparable in terms of diagnosis, disease risk (standard vs high), ECOG PS (0-1 vs 2), and year of transplant (2004-2005 vs 2006-2008). The median age for rBM/PB recipients was slightly younger (median 60, range 55-66) than that for CB (median 62, range 55-69, P < .03). CB recipients received more serologically HLA-mismatched grafts (98% vs. 3%, P<.0001), had shorter duration of donor search (median 43 days vs. 148 days, P<.0001), were conditioned more frequently with fludarabine/melphalan/TBI regimen (70% vs. 5%, P<.0001), used more tacrolimus (100% vs. 29%) and less methotrexate (0% vs. 100%, P<.0001) for GVHD prophylaxis, compared to rBM/PB recipients. Median follow-up time of survivors were 766 (25-1769) days for CB and 824 (173-1345) for rBM/PB recipients respectively. CB recipients showed slower neutrophil recovery (median 21 (12-43) days vs. 15 (11-21) days), and lower rate of myeloid engratment (75% vs. 100%, P<.01). The overall (OS) and event-free survival (EFS) at 2 years post-transplant showed no statistically significant differences between CB (OS 29+/-6% and EFS 23+/-6%) and rBM/PB recipients (OS 37+/-12% and EFS 29+/-11%). 23/43 (47%) CB recipients' death was due to non-relapse causes, whereas 9/12 (75%) rBM/PB recipients' death was due to relapse. Cumulative incidences of relapse at 2 years were 44+/-0.5% for CB and 49+/-1.4% for rBM/PB recipients (N.S.). Conclusions:These data suggest that, for elderly patients, comparable results can be expected using CB, which opens more opportunity for elderly patients to undergo allogeneic transplants who generally have difficulty finding healthy related donors compared to younger patients. However, before CB become the first choice of graft, higher rate of engraftment failure and non-relapse mortality, particularly during early period post-transplant, need to be overcome, and, at this moment, rBM/PB is still the optimal graft of choice when available over CB. Disclosures:No relevant conflicts of interest to declare.

Oral Beclomethasone Dipropionate Monotherapy as An Initial Treatment for Stage 1-2 Gastrointestinal Tract Acute Graft-Versus-Host Disease Following Unrelated Cord Blood Transplantation.

Abstract 1153Poster Board I-175 IntroductionSystemic corticosteroid has been used as initial treatment for gastrointestinal tract acute graft-versus-host disease (GI-aGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, the response remains far from satisfactory, and adverse events caused by prolonged immunosuppression are significant problem. Oral beclomethasone dipropionate (BDP) is a topically active corticosteroid with low bioavailability. Although several studies demonstrated that BDP as monotherapy or in combination with systemic corticosteroid is safe and effective for treatment of GI-aGVHD, there has been not much data available regarding this issue in unrelated cord transplantation (UCBT). Design and MethodsThis study was approved by the institutional review board and started since January 2006. BDP was administered as a single agent in patients who developed stage 1-2 GI-aGVHD following UCBT, were able to swallow the drug, and gave written informed consent. BDP was administered orally as one enteric-coated cellulose capsule and an aqueous suspension every 6h for a total daily dose of 8mg. Response was evaluated on days 3, 7, 14, 21, and 28 after the beginning of BDP treatment. Patients who had worsening GI symptoms at day 3, or who had no improvement at day 7 were classified as nonresponders, and systemic corticosteroid was started. ResultsForty patients were included in this analysis from Jan 2006 through April 2009. Median age was 53.5 years (range 22-82). Twenty-eight (70%) had advanced disease (relapse or refractory disease), and 12 (30%) had history of prior transplantation. All but one patient received fludarabine-based preparative regimen. GVHD prophylaxis consisted of tacrolimus plus mycophenolate mofetil in 27, and tacrolimus alone in 13. Single cord blood units, matched at 4/6 in 35, 5/6 in 3, and 6/6 in 2, were infused. GI-aGVHD developed at a median of 32.5 days (range, 8-80 days) post-transplant. Twenty-five (62.5%) had stage 1 and 15 had stage 2 GI-aGVHD. Twenty (50%) had only GI involvement and the others had mild skin involvement. BDP was started at a median of 36 days (range, 8-86 days) post-transplant. Thirty-three (82.5%) responded to BDP treatment. Response occurred at a median of 4 days (range, 2-7 days) after BDP treatment. Response rate was suggestively higher in patients with stage 1 GI-aGVHD (88%) compared with those with stage 2 (73%), although not statistically significant (P=0.1). The median duration of BDP treatment was for 51 days (range, 7-343 days). Three patients progressed and 4 patients did not respond. Twenty-seven (67.5%) developed infectious episodes during BDP treatment; bacterial sepsis in 9, CMV reactivation in 10, CMV gastroenteritis in 2, Fungal pneumonia in 3, and others in 3 patients. Two patients developed symptomatic adrenal insufficiency during BDP treatment, and required systemic steroid hormone replacement. Transplant-related mortality was 15% at 100 days post-transplant. Three patients died due to sepsis associated with GVHD, 2 died from idiopathic pneumonia syndrome, and 1 died from invasive fungal infection. At median follow-up of 475 days (range, 132-1368 days), overall survival at 2 years was 35.7%. Conclusions: In this study, we evaluated the efficacy and safety of BDP as a single agent in a series of patients with stage 1-2 GI-aGVHD following UCBT. The response rate was 82.5%, which compares favorably with previously reported response rate using BDP as monotherapy or in combination with systemic corticosteroid after allogeneic HSCT. Furthermore, BDP treatment was not associated with the increased risk of severe opportunistic infections. We conclude that BDP as a single agent could become an ideal therapeutic approach for stage 1-2 GI-aGVHD following UCBT DisclosuresNo relevant conflicts of interest to declare.

Comparable Barriers to Access to Kidney Transplantation Across National Lines

Comparable Barriers to Access to Kidney Transplantation Across National Lines

Pre-Transplant Conditioning Using Intravenous Busulfan Is a Feasible and Effective Option in Reduced-Intensity Cord Blood Transplantation.

Although cord blood (CB) transplantation with reduced-intensity conditioning (RICBT) has been widely applied to those who lack available related or unrelated donors and are not eligible for conventional conditioning, the optimal pre-transplant conditioning has not been established yet. Intravenous busulfan (ivBu) has been incorporated in conditioning regimens before bone marrow or peripheral blood stem cell transplantation, but the feasibility in cord blood transplantation has been controversial. In order to address this issue, we retrospectively reviewed patients who underwent RICBT including ivBu. Twenty-one patients, who were at ECOG performance status of 2 or less and received RICBT at our institute from June 2007 to April 2008 consecutively, were included in this study. Median age was 56 years (range, 21–71). Seventeen were AML, 3 were ALL, and 1 was MDS RA. All but 2 (MDS RA and ALL in CR2) were not in remission, 5 had CNS involvement, and 9 had history of prior transplantation. Seventeen had HCT-specific comorbidity index score ≥1, including 8 ≥2, and 6 ≥3. Fludarabine phosphate 125–180mg/m2 and ivBu 6.4–12.8mg/kg were used in all patients. All but 2 received additional melphalan (Mel) or total body irradiation (TBI); Mel 80–140mg/m2 for 10, 2–8Gy of TBI for 8, and Mel 40mg/m2 plus 4Gy of TBI for 1. Graft-versus-host disease prophylaxis consisted of tacrolimus plus mycophenolate mofetil in 11, tacrolimus alone in 8, and cyclosporine alone in 1. Single cord blood units, matched at 4/6 in 20 and 5/6 in 1, of 2 x 107/kg of recipient body weight at minimum were infused. Seventeen achieved neutrophil recovery ≥500/μl on day 19 post-transplant at medium (range, 12–30). Among 4 who failed to achieve neutrophil recovery, 2 experienced early disease progression, 1 showed rejection, and 1 died before engraftment due to interstitial pneumonia. All 17 patients who achieved neutrophil engraftment and 1 who died before engraftment showed complete donor-type chimerism on 13 days post-transplant at medium (range, 8–35). Median follow-up time of survivors was 398 days (range, 162–532) post-transplant. Cumulative incidence of non-relapse mortality at day 100 and day 365 post-transplant were both 19%. No VOD/SOS was observed. Disease-free survival and overall survival (OS) at 1 year post-transplant were 40±11% and 61±9%, respectively. Thus, ivBu can be safely administered, and have potential to achieve successful engraftment as well as sufficient disease control, indicating possible benefit of incorporating this drug in pre-transplant conditioning of RICBT. The optimal dosing schedule or combination with other therapeutic modalities needs further investigation in prospective clinical trials.

Factors affecting kidney‐transplant outcome in recipients with lupus nephritis

Factors associated with outcome in renal transplant recipients with lupus nephritis have not been studied. Using the data from the United States Renal Data System of patients transplanted between January 1, 1995 through December 31, 2002 (and followed through December 31, 2003) (n = 2882), we performed a retrospective analysis of factors associated with long-term death-censored graft survival and recipient survival. The number of pretransplant pregnancies incrementally increased the risk of graft failure [hazard ratio (HR) 1.54, p < 0.05] in the entire subgroup of females and in the subgroup of recipients aged 25-35 yr. Recipient and donor age had an association with both the risk of graft failure (HR 0.96, p < 0.001; HR 1.01, p < 0.005) and recipient death (HR 1.04, p < 0.001; HR 1.01, p < 0.05). Greater graft-failure risk accompanied increased recipient weight (HR 1.01, p < 0.001); African Americans compared with whites (HR 1.55, p < 0.001); greater Charlson comorbidity index (HR 1.17, p < 0.05); and greater panel reactive antibody (PRA) levels (HR 1.06, p < 0.001). Pretransplant peritoneal dialysis as the predominant modality had an association with decreased risk of graft failure (HR 0.49, p < 0.001), while prior transplantation was associated with greater risk of graft failure and recipient death (HR 2.29, p < 0.001; HR 3.59, p < 0.001, respectively) compared with hemodialysis (HD). The number of matched human leukocyte antigens (HLA) antigens and living donors (HR 0.92, p < 0.05; HR 0.64, p < 0.001, respectively) was associated with decreased risk of graft failure. Increased risk of graft failure and recipient death was associated with nonuse of calcineurin inhibitors (HR 1.89, p < 0.005; HR 1.80, p < 0.005) and mycophenolic acid (MPA) (including mycophenolate mofetil and MPA) or azathioprine (HR 1.41, p < 0.05; HR 1.66, p < 0.01). Using both cyclosporine and tacrolimus was associated with increased risk of graft failure (HR 2.09, p < 0.05). Using MPA is associated with greater risk of recipient death compared with azathioprine (HR 1.47, p < 0.05). In renal transplant recipients with lupus nephritis, multiple pregnancies, multiple blood transfusions, greater comorbidity index, higher body weight, age and African American race of the donor or recipient, prior history of transplantation, greater PRA levels, lower level of HLA matching, deceased donors, and HD in pretransplant period have an association with increased risk of graft failure. Similarly, higher recipient and donor age, prior transplantations, and higher rate of pretransplant transfusions are associated with greater risk of recipient mortality. Using neither cyclosporine nor tacrolimus or using both (compared with tacrolimus) and neither MPA nor azathioprine (compared with azathioprine) was associated with increased risk of graft failure and recipient death. Using MPA is associated with greater risk of recipient death compared with azathioprine. Testing these results in a prospective study might provide important information for clinical practice.

Caroli's disease and outcomes after liver transplantation

Caroli's disease is a rare autosomal recessive disorder characterized by intrahepatic cystic dilatation of the bile ducts that, when progressive, leads to intrahepatic stones, recurrent cholangitis, portal hypertension, cholangiocarcinoma, and liver failure. Liver transplantation is a promising curative option for advanced Caroli's disease. The aim of this study was to determine the outcomes of liver transplantation in unselected patients with Caroli's disease and recommend an evidence-based therapeutic algorithm for the management of Caroli's disease. Of the 78,124 patients transplanted in the United States between 1987 and 2006, 104 had Caroli's disease; 96 of these underwent liver alone, and 8 underwent combined liver/kidney transplantation. The patient survival and graft survival were analyzed by Kaplan-Meier survival analysis, and risk of death and risk of graft loss were analyzed by Cox proportional hazards regression. The overall 1-, 3-, and 5-year graft (79.9%, 72.4%, and 72.4%) and patient (86.3%, 78.4%, and 77%) survival rates were excellent for patients after liver transplantation. For combined liver/kidney transplantation (n = 8), the 1-year patient survival and graft survival were 100%. Proportional hazards analysis identified Asian ethnicity, elevated bilirubin, requirement of life support or hospitalization prior to transplantation, and a cold ischemia time greater than 12 hours as associated with increased risk of both graft loss and death. A history of prior transplant or prior abdominal surgery was also associated with increased risk of graft loss. In conclusion, liver transplantation is an excellent treatment option for patients with advanced Caroli's disease and should be considered in a timely fashion to prevent worsening complications including refractory cholangitis and cholangiocarcinoma.

Pretransplant peritoneal dialysis and graft thrombosis following pediatric kidney transplantation: a NAPRTCS report.

Graft thrombosis is a common cause of graft failure in pediatric renal transplantation. Several previous studies, including a North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) review of pretransplant dialysis status and graft outcomes, have described a potential correlation of peritoneal dialysis (PD) and graft thrombosis. This issue is of particular concern for pediatric transplant programs as more than 65% of children with end stage renal disease are treated with PD. We reviewed 7247 pediatric renal transplants performed between 1987 and 2001. Thrombosis was the cause of graft loss in 2.7% (199) of all the transplants performed. Among failed transplants, thrombosis was the third most common cause of graft loss in both index (11.6%) and subsequent transplants (14.5%). Thrombosis becomes the most common cause of graft failure (21%, 61/294) if one looks at transplants in the later cohort, from 1996 to 2001. This change is primarily because of a decrease in the incidence of acute rejection. In the PD group, 3.4% of all grafts were lost as a result of thrombosis. This compares with 1.9% in the hemodialysis group, 2.4% in the pre-emptive transplant group, and 4.1% among patients who received both dialysis modalities. There was a statistically significant difference in thrombosis failure risk in the different dialysis groups (p = 0.005) with those who received only peritoneal dialysis having the highest risk. Additional significant risk factors for graft thrombosis included; cadaver donor source (p < 0.001), cold ischemia time >24 h (p < 0.001), history of prior transplant (p < 0.001), donor age <6 yr (p < 0.001), and >5 pretransplant blood transfusions (p = 0.02). Using stepwise proportional hazards modeling, only pretransplant peritoneal dialysis, >24 h cold ischemia time, prior transplant, and donor age <6 yr were simultaneously associated with an increased risk of thrombosis. We conclude that pretransplant PD is associated with an increased risk of graft thrombosis. Special precautions should be undertaken in pediatric renal transplant patients who have received PD, especially infants and young children.