Independent risk factors and long-term outcomes for acute kidney injury in pediatric patients undergoing hematopoietic stem cell transplantation: a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) remains a frequent complication in children undergoing hematopoietic stem cell transplantation (HSCT) and an independent risk factor of the patient's survival and a prognostic factor of progression to chronic kidney disease (CKD). However, the causes of these complications are diverse, usually overlapping, and less well understood. METHODS: This retrospective analysis was performed in 43 patients (28 boys, 15 girls; median age, 5.5 years) undergoing HSCT between April 2006 and March 2019. The main outcome was the development of AKI defined according to the Pediatric Risk, Injury, Failure, Loss, End-stage Renal Disease (pRIFLE) criteria as ≥ 25% decrease in estimated creatinine clearance. The secondary outcome was the development of CKD after a 2-year follow-up. RESULTS: AKI developed in 21 patients (49%) within 100 days after HSCT. After adjusting for possible confounders, posttransplant AKI was associated with matched unrelated donor (MUD) (HR, 6.26; P = 0.042), but not total body irradiation (TBI). Of 37 patients who were able to follow-up for 2 years, 7 patients died, but none had reached CKD during the 2 years after transplantation. CONCLUSIONS: Posttransplant AKI was strongly associated with HSCT from MUD. Although the incidence of AKI was high in our cohort, that of posttransplant CKD was lower than reported previously in adults. TBI dose reduced, GVHD minimized, and infection prevented are required to avoid late renal dysfunction after HSCT in children since their combinations may contribute to the occurrence of AKI.

[Lymphomas in immunocompromised patients]. / Lymphomes de l'immunodéprimé.

Immunosuppression is a well known risk factor for the development of lymphoid pathologies. The classification of these neoplasias is becoming more precise and complex, some features being common to all immunocompromised patients, primarily the important influence of Epstein-Barr virus. Whatever the origin of the immunodepression, these lymphoid proliferations are very heterogeneous, constituting a wide range between polymorphic aspects and clearly lymphomatous morphologies indistinguishable from those observed in immunocompetent subjects. It is important to detect precisely these different categories of proliferation within each group of immunosuppression, to better individualize the prognosis and the management of patients.

Prostate Cancer Outcomes Following Solid-Organ Transplantation: A SEER-Medicare Analysis.

BACKGROUND: Immunosuppressive regimens associated with organ transplantation increase the risk of developing cancer. Transplant candidates and recipients with prostate cancer are often treated, even if low-risk features would ordinarily justify active surveillance. METHODS: Using SEER-Medicare, we identified 163 676 men aged 66 years and older diagnosed with nonmetastatic prostate cancer. History of solid organ transplant was identified using diagnosis or procedure codes. A propensity score-matched cohort was identified by matching transplanted men to nontransplanted controls by age, race, region, year, T-stage, grade, comorbidity, and cancer therapy. Fine-Gray competing risk models assessed associations between transplant status and prostate cancer-specific mortality (PCSM) and overall mortality (OM). RESULTS: We identified 620 men (0.4%) with transplant up to 10 years before (n = 320) or 5 years after (n = 300) prostate cancer diagnosis and matched them to 3100 men. At 10 years, OM was 55.7% and PCSM was 6.0% in the transplant cohort compared with 42.4% (P < .001) and 7.6% (P = .70) in the nontransplant cohort, respectively. Adjusted models showed no difference in PCSM for transplanted men (hazard ratio = 0.88, 95% confidence interval = 0.61 to 1.27, P = .70) or differences by prostate cancer therapy. Among 334 transplanted men with T1-2N0, well or moderately differentiated "low-risk" prostate cancer, PCSM was similar for treated and untreated men (hazard ratio = 0.92, 95% confidence interval = 0.47 to 1.81). CONCLUSIONS: Among men aged 66 years and older with prostate cancer, an organ transplant is associated with higher OM but no observable difference in PCSM. These findings suggest men with prostate cancer and previous or future organ transplantation should be managed per usual standards of care, including consideration of active surveillance for low-risk cancer characteristics.

Comparison of frontline treatment with intensive immunosuppression therapy and HLA-haploidentical hematopoietic stem cell transplantation for young patients with severe aplastic anemia - A meta analysis.

AIM: To compare the survivals and treatment related complications between immunosuppression therapy (IST) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) on children and young adults with severe aplastic anemia (SAA) in East Asia during the last 10 years. METHODS: After looking through Pubmed, Embase, Web of Science and Wanfang Data, a total of 491 patients from 7 retrospective studies conducted in East-Asia were included for meta-analysis based on Stata program. Publication bias was measured by Begger and Egger tests. 1/3/5/10 years overall survivals (OS), failure free survivals (FFS), incidence rates of adverse events and their 95% confidence intervals (CI) were pooled and compared. RESULTS: There was no difference of 1/3/5/10 years OS between IST group and haplo-HSCT group, but the 1/3/5/10 years FFS were significantly better in haplo-HSCT group compared with IST group (p < 0.01). However, higher incidence of infections was observed in haplo-HSCT group compared with IST group (76% versus 45%, p < 0.001). The pooled estimates for acute graft versus host disease (aGVHD) and chronic graft versus host disease (cGVHD) were 54% (95% Cl, 43%～64%) and 43% (95% CI, 18%～68%), respectively for haplo-HSCT group. Among them 38% (95%CI, 22%～54%) was grade III aGVHD and 11% (95% Cl, 0%～22%) was grade III-IV aGVHD. Death causes included severe infection, bleeding in IST group and infection, GVHD in haplo-HSCT group. CONCLUSIONS: The long-term survivals were similar for young patients with SAA who received IST or haplo-HSCT as the frontline treatment. The haplo-HSCT group showed a better FFS, on the other hand, had higher incidence of infection and GVHD.

An overview of letermovir: a cytomegalovirus prophylactic option.

Introduction: Human cytomegalovirus (HCMV) or human herpesvirus 5 (HHV-5) is a ß-herpesvirus that causes widespread infection in nearly all members of the human population worldwide. Its persistence in humans after primary infection in a latent phase as well as a partial non-protective immune response is the basis for repeated re-activation/re-infection episodes occurring both in immunocompetent and immunocompromised subjects. In the latter patient populations, which include hematopoietic stem cell transplant (HSCT) recipients, HCMV reactivation episodes may be particularly severe, leading to both systemic and end-organ diseases. Since the 90s, at least four antiviral drugs targeting the DNA polymerase complex have been developed for the prevention and treatment of HCMV infections in transplant recipients, used as first-line (ganciclovir and valganciclovir) and second-line therapy (foscarnet and cidofovir). However, due to their toxicity and drug-resistance induction, new drugs with different targets were needed. Areas covered: In 2017, a new drug named letermovir (LTV), which targets the HCMV DNA terminase complex, was licensed for prophylaxis of HCMV infections in HSCT recipients. This is the focus of this review. Expert opinion: LTV safety and efficacy are promising. However, long-term adverse events and the emergence of drug-resistant HCMV strains must be investigated in extended clinical trials prior to drawing final conclusions.

Survivors' knowledge of their diagnosis, treatment and possible late adverse effects after autologous stem cell transplantation for lymphoma.

Purpose: Lymphoma survivors after high dose therapy with autologous stem cell therapy (HD-ASCT) are at high risk for late adverse effects (AEs). Information patients receive and collect throughout their cancer trajectory about diagnosis, treatment schedule and risks of AEs may influence attitudes and health-related behavior in the years after treatment. The purpose of this study was to explore level of knowledge in lymphoma survivors after HD-ASCT at a median of 12 years after primary diagnosis. Material and methods: From a national study on the effects of HD-ASCT for lymphomas, 269 survivors met for an outpatient examination, including a structured interview addressing knowledge about diagnosis and treatment. Survivors were also asked whether they knew and/or had experienced certain common late AEs. Numbers of recognized and experienced late AEs were presented as sum scores. Factors associated with the level of knowledge of late AEs were analyzed by linear regression analysis. Results: Eighty-one percent of the survivors knew their diagnosis, 99% knew the components of HD-ASCT and 97% correctly recalled having had radiotherapy. Ninety percent reported awareness of late AEs, but the level of knowledge and personal experience with specified AEs varied. Thirty-five percent of survivors stated to have received follow-up for late AEs. In multivariable analysis younger age at diagnosis, having received mediastinal radiotherapy, higher mental health related quality of life, a higher number of self-experienced late AEs and having received follow-up care for late AEs were significantly associated with a higher level of knowledge of AEs. Conclusion: The majority of lymphoma survivors treated with HD-ASCT correctly recalled diagnosis and treatment, while knowledge of late AEs varied. Our findings point to information deficits in survivors at older age and with lower mental health related quality of life. They indicate benefit of follow-up to enhance education on late AEs in lymphoma survivors.

Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission.

HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy-based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease-donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy-based Haplo-HCT vs MSD using calcineurin inhibitor-based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.

Haploidentical vs haplo-cord transplant in adults under 60 years receiving fludarabine and melphalan conditioning.

Haplo-identical transplant with posttransplant cyclophosphamide (haplo) and umbilical cord blood transplant supported by third-party CD34 cells (haplo-cord) are competing approaches to alternative donor transplant. We compared, in adults younger than age 60 years, the outcomes of 170 haplo at 1 institution with that of 137 haplo-cord at 2 other institutions. All received reduced intensity conditioning with fludarabine and melphalan ± total body irradiation. GVHD prophylaxis for haplo consisted of cyclophosphamide, tacrolimus, and mycophenolate, whereas haplo-cord received antithymocyte globulin, tacrolimus, and mycophenolate. Haplo transplant used mostly bone marrow, and peripheral blood stem cells were used in haplo-cord transplants. Haplo-cord were older and had more advanced disease. Haplo-cord hastened median time to neutrophil (11 vs 18 days, P = .001) and platelet recovery (22 vs 25 days, P = .03). At 4 years, overall survival (OS) was 50% for haplo-cord vs 49% for haplo. Progression-free survival (PFS) was 40% for haplo-cord vs 45% for haplo. In multivariate analysis, the disease risk index was significant for OS (hazard ratio, 1.8; 95% confidence interval, 1.48-2.17; P = .00) and PFS. Total body irradiation was associated with decreased recurrence and improved PFS, age >40 with increased nonrelapse mortality. The type of transplant had no effect on OS, PFS, relapse, or nonrelapse mortality. Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) by day 100 was 16% after haplo-cord vs 33% after haplo (P < .0001), but grade 3-4 GVHD was similar. Chronic GVHD at 1 year was 4% after haplo-cord vs 16% after haplo (P < .0001). Haplo or haplo-cord results in similar and encouraging outcomes. Haplo-cord is associated with more rapid neutrophil and platelet recovery and lower acute and chronic GVHD. Institutional review board authorization for this retrospective study was obtained at each institution. Some patients participated in trials registered at www.clinicaltrials.gov as #NCT01810588 and NCT01050946.

Impact of conditioning intensity on outcomes of haploidentical stem cell transplantation for patients with acute myeloid leukemia 45 years of age and over.

BACKGROUND: T cell-replete haploidentical stem cell transplantation (haplo-SCT) is a valid therapeutic option for adult patients with high-risk acute myeloid leukemia (AML) lacking an HLA-matched sibling or unrelated donor. METHOD: We retrospectively analyzed the outcomes of 912 AML patients ≥45 years of age who had undergone haplo-SCT with either myeloablative conditioning (MAC; n = 373) or reduced intensity conditioning (RIC; n = 539) regimens. RESULTS: The median follow-up was 31.1 and 25.7 months for MAC and RIC, respectively. The incidence of relapse and nonrelapse mortality (NRM) were 25.1% versus 28.7% and 31.0% versus 30.3% for MAC and RIC, respectively; 2-year leukemia-free survival (LFS) was 43.9% for MAC versus 41.0% for RIC. In multivariate analysis, the use of MAC versus RIC was not associated with a difference in the outcomes. Results were confirmed in the propensity score-weighted analysis. Disease status and performance status at transplantation were associated with outcomes. Notably, the use of posttransplantation cyclophosphamide was associated with reduced acute graft-versus-host disease (aGVHD) stage III-IV, and NRM and increased overall survival, LFS, and GVHD-free, relapse-free survival. The use of mobilized peripheral blood stem cells was associated with an increased risk of stage II-IV aGVHD. CONCLUSION: No differences were found between MAC and RIC regimens for haplo-SCT in adults with AML who were ≥45 years of age. The type of GVHD prophylaxis, disease status, and performance status were the major predictors of transplantation outcome. These results may serve as the background for randomized study comparing RIC versus MAC for haplo-SCT in adults with AML.

Scoring System Based on Post-Transplant Complications in Patients after Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome: A Study from the SFGM-TC.

PURPOSE: We developed a prognostic scoring system to evaluate the prognosis of myelodysplastic syndrome (MDS) patients surviving more than 100 days allogeneic hematopoietic cell transplantation after (allo-HCT). PATIENTS AND METHODS: We performed a landmark analysis on a derivation cohort of 393 cases to identify prognostic factors for 3-year overall survival. Potential predictor variables included demographic and clinical data, transplantation modalities and early post-transplant complications. The scoring system was tested against a validation cohort which included 391 patients. RESULTS: Complications occurring before day 100 such as relapse [HR = 6.7; 95%CI, 4.5-10.0] (4 points), lack of platelet recovery [HR, 3.6; 95%CI, 2.2-5.8] (2 points), grade-II acute GVHD [HR = 1.7; 95%CI, 1.2-2.5] (1 point) and grade-III/IV [HR = 2.6; 95%CI, 1.8 -3.8] (2 points) were the only independent predictors of 3-year OS. The 3-year OS associated with low (0), intermediate (1-3) and high (≥4) risk scores was respectively 70%, 46% and 6%. The model performed consistently in both cohorts, with good calibration. CONCLUSION: This post-transplant scoring system is a powerful predictor of outcome after allo-HCT for MDS, and can provide useful guidance for clinicians. Additional studies are required to evaluate this scoring system for other hematologic malignancies.

Reduced-Intensity Conditioning Regimens, Prior Chronic Lymphocytic Leukemia, and Graft-Versus-Host Disease Are Associated with Higher Rates of Skin Cancer after Allogeneic Hematopoietic Stem Cell Transplantation.

To assess incidence and risk factors for skin cancer associated with allogeneic hematopoietic stem cell transplantation, we evaluated 1,974 adult allogeneic hematopoietic stem cell transplantation patients from Beth Israel Deaconess Medical Center and Dana-Farber Cancer Institute who received transplants between January 1995 and July 2013 for hematologic malignancy and survived at least 100 days. Median age was 51.1 years, and median follow-up time was 3 years. Overall, 119 patients had 221 skin cancers. The incidences of squamous cell carcinomas (incidence rate ratio = 9.8; 95% confidence interval = 7.7-12.3), basal cell carcinomas (incidence rate ratio = 2.5; 95% confidence interval = 1.9-3.2), and melanoma (standardized incidence ratio = 3.3; 95% confidence interval = 1.7-5.9) were elevated in our cohort. In multivariable models, risk factors for squamous cell carcinomas were increased age (P < 0.0001), chronic lymphocytic leukemia (P = 0.02), and chronic graft-versus-host disease (P = 0.0002). Risk factors for basal cell carcinomas were chronic lymphocytic leukemia (P = 0.003), reduced-intensity conditioning (P = 0.02), acute graft-versus-host disease (P = 0.03), and chronic graft-versus-host disease (P = 0.003). To our knowledge, previously unreported risk factors in this contemporary cohort include prior CLL for squamous cell carcinoma and basal cell carcinoma and reduced-intensity conditioning for basal cell carcinoma. This study also supports chronic graft-versus-host disease as a risk factor for nonmelanoma skin cancer, particularly squamous cell carcinoma.

Effects of post-remission chemotherapy before allo-HSCT for acute myeloid leukemia during first complete remission: a meta-analysis.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is most frequently used to treat acute myeloid leukemia (AML). Whether patients should routinely receive consolidation chemotherapy before proceeding to transplant after achieving first complete remission (CR1) has been a subject of debate. We performed a systematic review and meta-analysis of studies examining the impact of post-remission chemotherapy before allo-HSCT in patients with AML in CR1. Six studies including 1659 patients were included in the meta-analysis. The pooled hazard ratio (HR) for overall survival was 0.9 (95% confidence interval [CI] 0.77-1.05, P = 0.182), and the pooled HR for leukemia-free survival was 0.87 (95% CI 0.75-1.0, P = 0.07). No survival advantage was observed for post-remission chemotherapy before reduced-intensity conditioning or myeloablative conditioning (MAC) allo-HSCT for AML in CR1. The pooled relative risk for relapse incidence (RI) was 1.02 (95% CI 0.82-1.28, P = 0.834). Post-remission chemotherapy before allo-HSCT did not significantly affect the RI in patients with AML in CR1. The analyses revealed no significant benefit of post-remission consolidation chemotherapy in patients who received allo-HSCT. We recommend proceeding to allo-HSCT as soon as CR1 is attained.

Relapse and survival after transplantation for complex karyotype acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and the University of Texas MD Anderson Cancer Center.

BACKGROUND: Despite recent advances in allogeneic hematopoietic stem cell transplantation (AHSCT), the outcome of patients who have acute myeloid leukemia (AML) with a complex karyotype (CK) remains poor. The objective of this study was to identify prognostic factors associated with post-transplantation survival in a large cohort of patients with CK AML. METHODS: In total, data on 1342 consecutively patients who underwent transplantation for CK (≥3 chromosomal abnormalities) AML were provided by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation and from the University of Texas MD Anderson Cancer Center database were included in the analysis. The median patient age was 52 years. The donors were human leukocyte antigen-matched related donors (N = 749), matched unrelated donors (N = 513), and mismatched unrelated donors (N = 80). RESULTS: Relapse was the main cause of treatment failure. Overall, 51% of patients relapsed, 17.6% died of treatment-related mortality, and 31.3% survived leukemia-free. In multivariate analysis, the factors associated with an increased risk of relapse were age (>40 years; hazard ratio [HR], 1.1 per 10 years; P = .02), secondary AML (HR, 1.35; P = .01), active disease at transplantation (HR, 1.98; P < .001), and deletion/monosomy 5 (HR, 1.5; P < .001); whereas age (HR, 1.15 per 10 years; P < .001), secondary AML (HR, 1.36; P = .001), active disease at transplantation (HR, 1.99; P < .001), deletion/monosomy 5 (HR, 1.24; P = .008), and deletion/monosomy 7 (HR, 1.44; P < .001) predicted for leukemia-free survival. CONCLUSIONS: Disease relapse remains the most common cause of treatment failure for patients with CK AML after transplantation. Novel approaches to decrease the relapse rate and improve survival are needed in these patients. Cancer 2018;124:2134-41. © 2018 American Cancer Society.

Decision tree analysis to stratify risk of de novo non-melanoma skin cancer following liver transplantation.

PURPOSE: Non-melanoma skin cancer (NMSC) is the most common de novo malignancy in liver transplant (LT) recipients; it behaves more aggressively and it increases mortality. We used decision tree analysis to develop a tool to stratify and quantify risk of NMSC in LT recipients. METHODS: We performed Cox regression analysis to identify which predictive variables to enter into the decision tree analysis. Data were from the Organ Procurement Transplant Network (OPTN) STAR files of September 2016 (n = 102984). RESULTS: NMSC developed in 4556 of the 105984 recipients, a mean of 5.6 years after transplant. The 5/10/20-year rates of NMSC were 2.9/6.3/13.5%, respectively. Cox regression identified male gender, Caucasian race, age, body mass index (BMI) at LT, and sirolimus use as key predictive or protective factors for NMSC. These factors were entered into a decision tree analysis. The final tree stratified non-Caucasians as low risk (0.8%), and Caucasian males > 47 years, BMI < 40 who did not receive sirolimus, as high risk (7.3% cumulative incidence of NMSC). The predictions in the derivation set were almost identical to those in the validation set (r2 = 0.971, p < 0.0001). Cumulative incidence of NMSC in low, moderate and high risk groups at 5/10/20 year was 0.5/1.2/3.3, 2.1/4.8/11.7 and 5.6/11.6/23.1% (p < 0.0001). CONCLUSIONS: The decision tree model accurately stratifies the risk of developing NMSC in the long-term after LT.

Adrenal Insufficiency in Corticosteroids Use: Systematic Review and Meta-Analysis.

OBJECTIVE: We aimed to estimate pooled percentages of patients with adrenal insufficiency after treatment with corticosteroids for various conditions in a meta-analysis. Secondly, we aimed to stratify the results by route of administration, disease, treatment dose, and duration. METHODS: We searched seven electronic databases (PubMed, MEDLINE, EMBASE, COCHRANE, CENTRAL, Web of Science, and CINAHL/Academic Search Premier) in February 2014 to identify potentially relevant studies. Original articles testing adult corticosteroid users for adrenal insufficiency were eligible. RESULTS: We included 74 articles with a total of 3753 participants. Stratified by administration form, percentages of patients with adrenal insufficiency ranged from 4.2% for nasal administration (95% confidence interval [CI], 0.5-28.9) to 52.2% for intra-articular administration (95% CI, 40.5-63.6). Stratified by disease, percentages ranged from 6.8% for asthma with inhalation corticosteroids only (95% CI, 3.8-12.0) to 60.0% for hematological malignancies (95% CI, 38.0-78.6). The risk also varied according to dose from 2.4% (95% CI, 0.6-9.3) (low dose) to 21.5% (95% CI, 12.0-35.5) (high dose), and according to treatment duration from 1.4% (95% CI, 0.3-7.4) (<28 d) to 27.4% (95% CI, 17.7-39.8) (>1 year) in asthma patients. CONCLUSIONS: 1) Adrenal insufficiency after discontinuation of glucocorticoid occurs frequently; 2) there is no administration form, dosing, treatment duration, or underlying disease for which adrenal insufficiency can be excluded with certainty, although higher dose and longer use give the highest risk; 3) the threshold to test corticosteroid users for adrenal insufficiency should be low in clinical practice, especially for those patients with nonspecific symptoms after cessation.

Normothermic ex vivo allograft blood perfusion in clinical heart transplantation.

BACKGROUND: Cold ischemia associated with cold static storage is an independent risk factor for primary allograft failure and survival of patients after orthotopic heart transplantation. The effects of normothermic ex vivo allograft blood perfusion on outcomes after orthotopic heart transplantation compared to cold static storage have been studied. METHODS: In this prospective, nonrandomized, single-institutional clinical study, normothermic ex vivo allograft blood perfusion has been performed using an organ care system (OCS) (TransMedics, Andover, MA, USA). Included were consecutive adult transplantation patients who received an orthotopic heart transplantation (oHTx) without a history of any organ transplantation, in the absence of a congenital heart disorder as an underlying disease and not being in need of a combined heart-lung transplantation. Furthermore, patients with fixed pulmonary hypertension, ventilator dependency, chronic renal failure, or panel reactive antibodies >20% and positive T-cell cross-matching were excluded. Inclusion criteria for donor hearts was age of <55 years, systolic blood pressure >85 mmHg at the time of final heart assessment under moderate inotropic support, heart rate of <120 bpm at the time of explantation, and left ventricular ejection fraction >40% assessed by an transcutaneous echo/Doppler study with the absence of gross wall motion abnormalities, absence of left ventricular hypertrophy, and absence of valve abnormalities. Donor hearts which were conventionally cold stored with histidine-tryptophan-ketoglutarate solution (Custodiol; Koehler Chemie, Ansbach, Germany) constituted the control group. The primary end point was the recipients' survival at 30 days and 1 and 2 years after their heart transplantation. Secondary end points were primary and chronic allograft failure, noncardiac complications, and length of hospital stay. RESULTS: Over a 2-year period (January 2006 to July 2008), 159 adult cardiac allografts were transplanted. Twenty-nine were assigned for normothermic ex vivo allograft blood perfusion and 130 for cold static storage with HTK solution. Cumulative survival rates at 30 days and 1 and 2 years were 96%, 89%, and 89%, respectively, whereas in the cold static storage group survival after oHTx was 95%, 81%, and 79%. Primary graft failure was less frequent in the recipients of an oHTx who received a donor heart which had been preserved with normothermic ex vivo allograft blood perfusion using an OCS (6.89% versus 15.3%; P = .20). Episodes of severe acute rejection (23% versus 17.2%; P = .73), as well as, cases of acute renal failure requiring haemodialysis (25.3% versus 10%; P = .05) were more frequent diagnosed among recipients of a donor heart which had been preserved using the cold static storage. The length of hospital stay did not differ (26 days versus 28 days; P = .80) in both groups. CONCLUSIONS: Normothermic ex vivo allograft blood perfusion in adult clinical orthotopic heart transplantation contributes to better outcomes after transplantation in regard to recipient survival, incidence of primary graft dysfunction, and incidence of acute rejection.

Post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation: a single-center experience.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is a rare and serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or solid organ transplantation. MATERIAL/METHODS: We conducted a retrospective analysis of the occurrence of post-transplant lymphoproliferative disease in allo-HSCT recipients over 12 years in a single center in China. A total of 343 patients received allo-HSCT. The conditioning therapy consisted of a busulfan/cyclophosphamide-based regimen, a fludarabine/cyclophosphamide-based regimen, or total-body irradiation and cyclophosphamide. In transplantations from unrelated donors and haplo-identical donors, patients also received antithymocyte globulin (ATG) or thymoglobulin as part of the conditioning. RESULTS: Five of the 343 patients (1.46%) were diagnosed with PTLD and all 5 were given ATG as part of conditioning. Among these 5 patients, 4 had lymphoid neoplasm before transplantation. EBV-positivity was confirmed in 4 patients. All 5 PTLD patients received reduction of immunosuppression (RI) as fundamental therapy. At follow-up on April 1, 2013, 1 patient had survived for 2 years and 1 had survived for 9 years. The correlation of PTLD with ATG and underlying diseases were examined by statistical analysis using the chi-squared test or Fisher's exact test (P=0.011 and 0.025, respectively). CONCLUSIONS: Although only 1.46% of patients progressed to PTLD associated with ATG and underlying diseases, the mortality was still high. Moreover, RI can be an effective therapy for PTLD patients, but other approaches should be further explored.

Prevalence of hematopoietic cell transplant survivors in the United States.

Advances in hematopoietic cell transplantation (HCT) have led to an increasing number of transplant survivors. To adequately support their healthcare needs, there is a need to know the prevalence of HCT survivors. We used data on 170,628 recipients of autologous and allogeneic HCT reported to the Center for International Blood and Marrow Transplant Research from 1968 to 2009 to estimate the current and future number of HCT survivors in the United States. Stacked cohort simulation models were used to estimate the number of HCT survivors in the United States in 2009 and to make projections for HCT survivors by the year 2030. There were 108,900 (range, 100,500 to 115,200) HCT survivors in the United States in 2009. This included 67,000 autologous HCT and 41,900 allogeneic HCT survivors. The number of HCT survivors is estimated to increase by 2.5 times by the year 2020 (242,000 survivors) and 5 times by the year 2030 (502,000 survivors). By 2030, the age at transplant will be < 18 years for 14% of all survivors (n = 64,000), 18 to 59 years for 61% survivors (n = 276,000), and 60 years and older for 25% of survivors (n = 113,000). In coming decades, a large number of individuals will be HCT survivors. Transplant center providers, hematologists, oncologists, primary care physicians, and other specialty providers will need to be familiar with the unique and complex health issues faced by this population.

2013 report from the Center for International Blood and Marrow Transplant Research (CIBMTR): current uses and outcomes of hematopoietic cell transplants for blood and bone marrow disorders.

Data reported herein indicate increasing use of hematopoietic cell transplants for persons with blood and bone marrow disorders. Recent trends include increasing use of alternative donors including human leukocyte antigen (HLA)-matched unrelated persons and HLA-matched umbilical cord blood cells, increasing use of blood cell rather than bone marrow grafts, and increasing use of reduced-intensity pretransplant conditioning regimens. Many of these shifts are driven by logistical considerations such as the need for donors in persons without an HLA-identical sibling or expanding use of allotransplants to older persons. Many changes in transplant practices are not supported by results of large randomized trials. More data are needed to critically-assess the impact of these changes.