Pretransplant Transfusions Research Articles

The Risk of Pretransplant Blood Transfusion for Primary Graft Dysfunction After Lung Transplant

BackgroundPrimary graft dysfunction (PGD) is the leading cause of short- and long-term mortality associated with lung transplantation. The impact of pretransplantation blood transfusions for recipients is not fully elucidated. MethodsThis is a retrospective review of 206 consecutive lung transplantations performed at a single academic center (Northwestern University Feinberg School of Medicine, Chicago, IL) from January 2018 to July 2022. Data on patient characteristics, pretransplantation laboratory values, transfusion requirements, and intraoperative and postoperative outcomes were collected. ResultsPGD grade 3 (PGD 3) occurred in 13.2% of the cohort (n = 28). A total of 33 patients received a blood transfusion within 4 weeks, whereas 21 patients received a blood transfusion a week before their lung transplant. Pretransplantation transfusions were strongly associated with a higher incidence of PGD 3 (48.5% vs 6.9%; P < .001). There was no significant difference in 1-year survival between the pretransplantation transfused group and the nontransfused group (77.7% vs 88.0%; P = .478). The 1year survival was reduced in recipients with PGD 3 compared with recipients without PGD 3 (63.5% vs 89.9%; P = .0012). In univariate analysis, pretransplant and intratransplant predictors of PGD 3 included younger age (P < .01), pretransplant extracorporeal membrane oxygenation (ECMO) use (P < .001), higher lung allocation score (P < .001), coronavirus disease 2019 (COVID-19)–related acute respiratory distress syndrome (P < .01), blood transfusion within 4 weeks (P < .001), longer operative time (P < .001), intratransplant blood transfusion (P < .001), and intratransplant venoarterial ECMO use (P < .001). ConclusionsPretransplantation blood transfusions could be associated with a higher rate of PGD. The findings indicated the potential risks of pretransplantation blood transfusions in lung transplant recipients.

Red Blood Cell Transfusion Prior to Lung Transplantation: Impact on Patient Outcomes.

There is an established association between red blood cell (RBC) transfusion and increased mortality and morbidity in cardiac surgery; however, there is little data demonstrating the influence of blood transfusion while awaiting lung transplantation. Therefore, our study compared the impact of pretransplant RBC transfusion on patient survival and post-transplantation adverse events. Adult lung transplant patient data were extracted retrospectively using the United Network for Organ Sharing thoracic database. Patients were stratified into two groups based on pretransplant transfusion status. In total, 28,217 patients were analyzed in our study (transfused: n = 1,415 and not transfused: n = 26,802). There was an increasing trend in pretransplant transfusion rates from 2006 to 2020. Transfused patients had a higher incidence of adverse events post-transplantation, including dialysis, stroke, and acute organ rejection before discharge. Multivariable survival analysis found an increased mortality risk in patients who required pretransplant transfusion(s) compared to those who did not have a transfusion (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.17-1.41; p < 0.001). There was no significant difference in bronchiolitis obliterans syndrome development between groups (HR: 0.92; 95% CI: 0.82-1.04; p = 0.185). To conclude, our study provides data to suggest that RBC transfusion(s) before lung transplantation are associated with increased patient morbidity and mortality, but have no association with chronic graft rejection development.

Influence of Pretransplant Anemia on Red Blood Cell Transfusions in Myeloma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

Background and Objectives: Anemia during peripheral blood stem cells (PBSCs) transplant is considered a bad prognostic marker. The study aimed to determine whether pretransplant anemia influence peritransplant transfusion requirements in myeloma patients. Methods: Myeloma patients planned for PBSC transplant were stratified based on hemoglobin levels at time of mobilization, PBSC collection, and PBSC infusion. Univariate and multivariate analysis was performed to study the predictors for good mobilization, adequate CD34 yield by apheresis, and red blood cell (RBC) transfusion in the peritransplant period. Results: Of 67 patients, the prevalence of anemia at mobilization, PBSC collection, and PBSC infusion was 37%, 58%, and 70%, respectively. Eighty-five percent had good mobilization with peripheral blood CD34 count of 50 cells/μl (8–123) and 81% had adequate CD34 yield with first apheresis. Thirty-two percent patients received peritransplant RBC transfusion with the median of one unit (range: 0–5). Anemia on the day of infusion did influence the RBC transfusions in the peritransplant period (P = 0.03). Conclusion: One third of myeloma patients require RBC transfusion support in the peritransplant period. We identified pretransplant anemia neither influenced mobilization nor PBSC collection but increased the risk for RBC transfusion in the peritransplant period.

Iron overload during the treatment of acute leukemia: pretransplant transfusion experience.

Background:Recent studies have shown the increased risk of mortality in cases with acute leukemia and iron overload. We aimed to determine the status of iron overload in patients with acute leukemia.Materials & Methods:Patients diagnosed with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) between January 2015 and December 2019 were included in the study.Results:At 6 months, there were statistically more patients with serum ferritin >1000 in the AML group compared to the ALL group (p = 0,011).Conclusion:Iron overload occurs earlier in patients with AML; the difference disappears after 6 months of treatment. It is the correct point to emphasize that iron overload is an important factor of pretransplant morbidity, especially in AML cases.

Pre-transplant Transfusion Burden and Transplant Outcomes, Is there a Case for Earlier Transplant?

Pre-transplant Transfusion Burden and Transplant Outcomes, Is there a Case for Earlier Transplant?

Pre-transplant donor-type red cell transfusion is a safe and effective strategy to reduce isohemagglutinin titers and prevent donor marrow infusion reactions in major ABO-mismatched transplants.

ABO incompatibility is not a barrier to allogeneic stem cell transplant but may result in acute hemolytic reactions. As stem cell product manipulation is cumbersome, we are reporting the effectiveness and safety of donor-type red cell infusion as a method of reducing acute hemolytic reaction while using marrow as stem cell source. In major ABO-mismatched bone marrow transplants, manipulation of marrow product requires expertise and expensive equipment, which may not be readily available to transplant centers in low- and middle-income regions. The aim behind our study is to report a safe and effective strategy to reduce isohemagglutinin titers and prevent donor marrow infusion reactions in major ABO-mismatched transplants. We retrospectively analyzed 303 consecutive allogeneic bone marrow transplants (BMTs) for beta thalassemia major, between August 2015 and March 2020, with either major (n = 41) or bidirectional (n = 14) mismatches. When isohemagglutinin titers were 1:32 or higher, donor-type packed red blood cell was divided into 4 aliquots, irradiated and administered over 4 days at incremental volumes. Patients were observed for hemolytic reaction, and if no reaction, bone marrow was infused without manipulation. Out of 55 patients, 20 received donor-type blood infusion. Twelve patients showed evidence of mild hemolysis. None developed severe hemolytic or anaphylactic reaction. Titers were rechecked in 14 patients and all had reduction in titers, except for one. Our experience demonstrated that donor-type PRBC infusion is safe and effective in preventing acute hemolysis in major ABO-mismatched stem cell transplants even with bone marrow as graft source.

Deferoxamine as a Treatment for Cardiac Siderosis Induced Cardiomyopathy Post Liver Transplantation

Introduction Iron overload cardiomyopathy (CM) occurring after liver transplantation in the absence of preexisting myocardial dysfunction or severe hepatic iron overload (ie hemochromatosis) has been described post-mortem. Cardiac siderosis without primary iron overload syndromes was found to be positively correlated to both higher pretransplant transferrin saturation (TSAT) and transfusion of red blood cells. We report an unusual case of a patient with alcohol-induced cirrhosis and heterozygous C282Y mutation who developed a dilated CM post-liver transplant with confirmed cardiac siderosis treated with IV deferoxamine leading to improvement in cardiac function. Case Report A 47-year-old woman with alcohol-induced cirrhosis underwent liver transplantation with a normal pre-operative cardiac evaluation including a transthoracic echocardiogram (TTE) with left ventricular ejection fraction (LVEF) 55-60%. Pre-operative iron studies showed an iron saturation of 91% with ferritin of 156. Her post-op course was uncomplicated, receiving minimal blood products (4 units of packed red blood cells). Two months later she was hospitalized for dyspnea and large pleural effusions. TTE showed depressed LVEF 17%. A cardiac MRI demonstrated a severely dilated LV indexed to BSA (1.5) with severe myocardial siderosis indicated by decreased T2* of 9-14 ms as well as significant mid-wall myocardial fibrosis. Right heart catheterization demonstrated a normal right atrial pressure, wedge pressure 18 mmHg, mean pulmonary pressure 26 mmHg and Fick cardiac index of 2.02 L/min/m2 for which milrinone was initiated. Endomyocardial biopsy confirmed intramyocardial iron deposition and native liver biopsy had grade 2-3 iron deposition. Etiology of her CM post-transplant was attributed to HFE gene heterozygosity in the setting of cirrhosis with post-transplant iron sensitivity (hepcidin depletion). She was initiated on IV chelation therapy with deferoxamine with follow up CMRI showing improved cardiac siderosis indicated by T2* of 13-17 ms with RV function 41% from 20% and LV function 25% from 17%. She was weaned off milrinone and continued on weekly deferoxamine chelation sessions. Summary This case highlights an unusual cause of cardiac siderosis related cardiomyopathy post-liver transplantation treated with IV iron chelation therapy leading to partial LV/RV recovery.

Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with paroxysmal nocturnal hemoglobinuria.

The safety and efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) remain unclear. Therefore, we retrospectively analyzed the outcomes of 42 adult patients with PNH who underwent allogeneic HSCT using the registry database of the Japan Society for Hematopoietic Cell Transplantation. The median patient age was 32.5years. The number of packed red cell (PRC) transfusions was < 20 times in 19 patients and ≥ 20 times in 16; 7 patients had missing data. Stem cell sources were bone marrow (N = 15) or peripheral blood (N = 13) from a related donor or bone marrow (N = 11) and cord blood (N = 3) from an unrelated donor. The cumulative incidence of neutrophil engraftment at day 40 was 81%. Six patients died before engraftment, and the 6-year overall survival (OS) was 74%. The OS of patients with < 20 pretransplant PRC transfusions was significantly higher than that of patients with ≥ 20 pretransplant PRC transfusions (95% vs. 63%; P < 0.05). Moreover, the OS of patients aged < 30years was significantly higher than that of patients aged ≥ 30years (90% vs. 59%; P < 0.05). Allogeneic HSCT for PNH could provide favorable survival; however, pretransplant transfusion burden and patient age should be considered when deciding the timing of allogeneic HSCT.

Real-world outcomes of stem cell transplantation for severe aplastic anemia: A single-center experience in Northern India.

Stem cell transplantation is the cornerstone of therapy for transplant-eligible patients with severe aplastic anemia. Patients with severe aplastic anemia undergoing stem cell transplantation (including matched haplo-identical related donors) with a standard conditioning regimen and graft-versus-host disease (GVHD) prophylaxis were analyzed. High-risk patients were identified as having undergone >20 pre-transplant transfusions, having febrile neutropenia at the time of transplantation, or having undergone failed immunosuppressive therapy. A total of 111 patients underwent stem cell transplantation, with a median age of 17 years. Seventy-six patients received matched related donor (MRD) transplants, and 35 received haplo-identical donor (HID) transplants. Among all patients, 65.7% were high-risk patients, with a significantly higher proportion among those receiving HID transplants (38% for MRD vs. 83% for HID). Acute GVHD grades 2-4 was observed in 9% of patients, and chronic GVHD in 16.2% of patients. Primary graft rejection was more common in 9.9% of patients (21% for HID, 5% for MRD). The 2-year overall survival and disease-free survival were 67% and 66%, respectively, with better outcomes for MRD and low-risk HID transplants than for high-risk HID transplants. The most common cause of mortality was sepsis-related death (accounting for 27% of the total deaths). Sepsis-related early deaths were significantly more common among high-risk patients who received HID transplants. We conclude that MRDs remain the preferred donor source for allogeneic stem cell transplants in patients with aplastic anemia; however, HIDs can be considered as a life-saving treatment for patients with aplastic anemia.

Assessment of Iron Overload in the Pediatric Allogeneic HSCT Recipient

Background: Owing to improved strategies in pediatric bone marrow transplantation, a larger number of transplanted children are now becoming long term survivors. These post-transplant patients remain at risk for late complications including iron overload, which has the potential to impair quality of life and adversely affect later outcomes. While literature has previously focused on iron overload in the adult sickle cell patient, there has been minimal research into its effect on the pediatric bone marrow transplant recipient. Thus, no current guidelines exist for screening, management or treatment of iron overload in this patient population. Our study focuses specifically on this population and reports the relationship between number of PRBC transfusions and current diagnostic tools.Objectives: To identify the presence or absence of correlation between the number of red blood cell transfusions and indicators of iron overload via two different modalities: ferritin values and the T2* MRI liver iron concentration (Ferriscan).Methods: A retrospective chart review of the allogeneic pediatric bone marrow transplant patients over the past 5 years at a single center (n = 32). Quantitative data obtained which included number of PRBC transfusions, ferritin, and T2* MRI LIC. Correlation analysis subsequently performed between pre-and post-transplant values.Results: There was significant (p < 0.001) moderate correlation (r = 0.62) between the number of pre-transplant PRBC transfusions and the pre-transplant ferritin value. No significant (p >0.1) correlation between the number of pre-transplant PRBC transfusions and the pre-transplant T2* LIC. Also, no significant (p > 0.1) correlation between pre-transplant ferritin and T2* LIC. The total number of PRBC transfusions up to 100 days post-transplant did have significant (p = 0.008) moderate correlation (r= 0.62) with post-transplant ferritin values. There was significant (p = 0.01) strong correlation (r= 0.87) between the total number of PRBC transfusions up to 100 days post-transplant with post-transplant T2*LIC values. No significant correlation (p > 0.1) between post-transplant ferritin and T2* MRI LIC values.Conclusions: In terms of modalities utilized for evaluation of iron overload in the pediatric allogeneic BMT population, no significant correlation exists between ferritin values and T2* MRI liver iron concentration values. While ferritin is an acceptable screening tool the post-transplant T2*MRI LIC is a more accurate diagnostic indicator of transfusion burden. Future studies will be used to explore associated adverse outcomes of patients diagnosed with iron overload. DisclosuresNo relevant conflicts of interest to declare.

Intraoperative red blood cell transfusion, delayed graft function, and infection after kidney transplant: an observational cohort study

Kidney transplant patients are frequently anemic and at risk for red blood cell (RBC) transfusion. Previous studies suggest that pre-transplant RBC transfusion may improve kidney transplant outcomes; however, RBC transfusion is also associated with infection. The purpose of our study was to characterize the relationships between intraoperative RBC transfusion, delayed graft function (DGF), postoperative surgical site infection (SSI), and sepsis. Analysis was performed on a historical cohort of adult kidney transplant patients from a single medical center during a two-year period. Crude odds ratios for DGF, superficial and deep SSI, and sepsis were calculated for transfused patients and multivariate regression was used to control for potential confounders when significant relationships were identified. Four hundred forty-one patients had kidney transplant during the study period; 27.0% had RBC transfusion, 38.8% had DGF, 7.0% had superficial SSI, 7.9% had deep SSI, and 1.8% had sepsis. High dose RBC transfusion was associated with improved graft function, but this was negated after adjusting for confounders (OR = 0.86, 95% CI 0.26 to 2.88). There was no association between RBC transfusion and SSI. RBC transfusion was independently associated with sepsis (OR = 8.98, 95% CI 1.52 to 53.22), but the confidence interval was wide. Intraoperative RBC transfusion during kidney transplant is not associated with improved allograft function or incisional SSI, but is associated with postoperative sepsis. RBCs should not be liberally transfused during kidney transplant surgery to improve graft outcomes.

Age-Dependent Association Between Pre-transplant Blood Transfusion and Outcomes of Pediatric Heart Transplantation.

Avoidance of red blood cell (RBC) transfusions in patients awaiting heart transplantation (HTx) has been suggested to minimize the risk of allosensitization. Although recent studies have suggested that an immature immune system in younger HTx recipients may reduce risks associated with RBC transfusion, the role of age in moderating the influence of transfusion on HTx outcomes remains unclear. We used available data from a national transplant registry to explore whether the association between pre-transplant transfusions and outcomes of pediatric HTx varies by patient age. De-identified data were obtained from the United Network for Organ Sharing registry, including first-time recipients of isolated HTx performed at age 0-17years in 1995-2015. The primary exposure was receiving blood transfusions within 2 weeks prior to HTx. Patient survival after HTx was evaluated using multivariable Cox proportional hazards, where age at transplant was interacted with exposure to pre-transplant transfusion. Age-specific hazard ratios (HRs) of pre-transplant transfusion were plotted across ages at transplant. There were 4883 patients meeting inclusion criteria, of whom 1258 died during follow-up (mean follow-up duration 6 ± 5years). Patients receiving pre-transplant transfusions were distinguished by younger age, higher prevalence of prior cardiac surgery, greater likelihood of being in the intensive care unit, and greater use of left ventricular assist device bridge to transplant. In multivariable analysis, pre-transplant transfusions were associated with increased mortality hazard among infants < 1year of age (HR = 1.46; 95% CI 1.23, 1.74; p < 0.001). For each additional year of age, the excess hazard associated with pre-transplant transfusions decreased by 3% (interaction HR = 0.97; 95% CI 0.98, 0.99; p = 0.003). By age 8, the association between pre-transplant transfusions and post-transplant mortality was no longer statistically significant (HR = 1.15; 95% CI 0.99, 1.32; p = 0.060). Pre-transplant transfusions were associated with increased mortality hazard only among younger children (age < 8years) undergoing HTx. These data support the current practices of transfusion avoidance prior to HTx, particularly in younger patients.

Transfusion with packed red blood cells while awaiting lung transplantation is associated with reduced survival after lung transplantation.

The effect of pretransplant transfusion of red blood cells on survival after lung transplantation (LTx) has not been studied. The UNOS database was queried from 2005 to 2013 to compare survival in recipients receiving a transfusion while on the LTx wait list. Of 12283 adult patients undergoing single or bilateral LTx from May 2005 onwards, 11801 met inclusion criteria, among whom 512 required transfusion while on the LTx wait list. Transfusion was associated with a higher mortality hazard in unadjusted Cox proportional hazards analysis (HR=1.296; 95% CI: 1.124, 1.494; P<.001), and in a multivariable Cox model (HR=1.178; 95% CI: 1.013, 1.369; P=.033) after multiple imputation was used to complete data on covariates. Propensity score matching was used to match transfusion recipients to nonrecipients on the likelihood of having received transfusions on the wait list, calculated from characteristics at the time of listing. Unadjusted Cox regression stratified on the matched pairs also demonstrated an association between transfusion receipt on the wait list and higher post-transplant mortality hazard (HR=1.494; 95% CI: 1.127, 1.979; P=.005). Blood transfusion while on the LTx wait list was associated with diminished patient survival after transplantation.

Factors Associated With Delayed Graft Function and Their Influence on Outcomes of Kidney Transplantation.

One of the main postoperative complications of kidney transplant is delayed graft function (DGF), which means absence of graft function after transplant or the need for dialysis during the first week post procedure. The occurrence of DGF currently in our hospital is high and has been attributed to a combination of many factors. The aim of this study was to evaluate the factors associated to DGF and their influence in the outcome of kidney transplants. Historical cohort of 150 patients transplanted with live or deceased donor kidneys from 2011 to2013. DGF was associated to time in dialysis and the number of recipient pre-transplant transfusions, donors age, serum creatinine level, use of vasoactive drugs in the donor, distance from place of organ retrieval and transplant center, and duration of cold ischemia time. DGF influenced post-transplantation outcome in regard to length of stay in intensive care, length of hospital stay, acute rejection episodes, and higher creatinine levels at discharge. Patients and graft survival were shorter in the DGF group. There are multiple factors related to DGF, the most important being those related to donors, and organ storage. The most important factor related to the recipient was the dialysis vintage. We did not find a correlation between DGF and HLA-compatibility. DGF consequences are important, including worse graft function and survival, as well as impact in recipient morbidity and mortality.

Impact of pretransplant red cell transfusion on outcome after allogeneic stem cell transplantation in adult patients with severe aplastic anemia.

The aim of this study was to evaluate the impact of pretransplant transfusion of packed red cells (PRCs) on outcome after allogeneic stem cell transplantation (SCT) in severe aplastic anemia (SAA). A total of 221 adult SAA patients receiving allogeneic SCT were analyzed. The patients were divided into two groups according to the amount of pretransplant transfusion before SCT: the low transfusion group (⩽32 PRC units, n=164) and the high transfusion group (>32 PRC units, n=57). The incidence of engraftment failure was not different between the two groups. The incidence of acute GvHD (grades II-IV) was higher in the high transfusion group than in the low transfusion group (P=0.04), and the incidences of chronic extensive GVHD were not significantly different (P=0.136). The high transfusion group had higher 5-year transplant-related mortality (TRM) (24.8% vs 6.8%, P<0.001) and lower overall survival (OS) (72.3% vs 91.9%, P<0.001) than those in the low transfusion group. Multivariate analysis revealed that the high transfusion group and unrelated donor type were independent prognostic factors affecting OS. These results indicate that a history of higher pretransplant transfusion of PRCs was associated with increased TRM and decreased OS, suggesting that iron overload had a negative impact on outcome after SCT in SAA.

Impact of Red Blood Cell and Platelet Transfusions at Early after Engraftment on Outcome of Allogeneic Hematopoietic Stem Cell Transplantation

▪Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often associated with comorbidity or mortality, due to graft-versus-host disease (GVHD), opportunistic infections, and regimen-related toxicities. Recently, several studies have shown that pre-transplant red blood cell (RBC) transfusions may increase risks of such allo-HSCT-related complications, possibly due to iron overload caused by pre-transplant RBC transfusions. However, it is unknown how post-transplant RBC and platelet (PLT) transfusions influence the long-term outcome of allo-HSCT. In this study, to clarify impact of RBC and PLT transfusions at early after engraftment of allo-HSCT, we investigated the clinical and laboratory findings and long-term outcomes of 71 recipients of allo-HSCT including 48 bone marrow transplantation and 23 peripheral blood stem cell transplantation who received leukoreduced and irradiated RBC and/or PLT from days 31 to 50, after exclusion of patients who did not achieve complete chimera (>90% donor cells) before day 30 or engraftment (neutrophil count > 0.5 x 109 /L) up to day 35; whose disease relapsed until day 60; and who did not survive until day 100. In these 71 patients, 33 (46.5%) patients received RBC and/or PLT transfusion, while 38 (53.5%) received no transfusion from days 31 to 50. Among groups of those patients who received RBC (RBC-transfused patients), PLT (PLT-transfused patients), and both (RBC/PLT-transfused patients) transfusions, pre-transplant findings, including age, sex, sources, serum ferritin (Ft) levels, conditioning regimens, and blood group and HLA compatibilities were not significantly different. However, even at day 100, significant decreases of both Hb concentrations and platelet counts, but not leukocyte counts, were observed in RBC-transfused patients, PLT-transfused patients, and RBC/PLT-transfused patients (Table 1), although vast majority of them no longer required transfusion after day 50. Moreover, serum Ft and C-reactive protein (CRP) levels were higher at day 100 in RBC-, PLT-, and RBC/PLT-transfused patients versus other patients (Table 1). Risk of clinically significant chronic GVHD (cGVHD) by transfusions of both RBC and PLT from days 31 to 50 did not reach statistical significance [hazard risk (HR) = 2.75, p = 0.06], but cumulative incidence of cGVHD was significantly greater in RBC/PLT-transfused patients compared with other patients (p = 0.03). Risk of cGVHD was also correlated with elevated CRP levels (HR = 3.28, p = 0.02) rather than serum Ft levels (HR = 1.40, p = 0.6) at day 100 in univariable analysis, although multivariable analysis did not show significant differences in CRP levels (p=0.07). Moreover, non-relapse mortality was greater in patients who received RBC transfusion compared other patients (p = 0.02), although overall survival (p=0.1) and cumulative incidence of relapse (p=0.4) were not different. In conclusion, both RBC and PLT transfusions early after engraftment of allo-HSCT may be correlated with following elevations of CRP and serum Ft levels and contribute to adverse long-term outcomes of allo-HSCT with an increase of cGVHD. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Risk Factors for Poor Survival after Hematopoietic Stem Cell Transplantation in Inherited Bone Marrow Failure Syndromes

Introduction: Inherited bone marrow failure syndromes (IBMFS) are characterized by single or multi-lineage cytopenias as well as non-hematologic manifestations. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for the hematological abnormalities. However, high rates of mortality and morbidity from this procedure have been reported in patients with IBMFSs.Objective: The study aim was to investigate the impact of patient, donor and treatment-related variables on the outcome of HSCT in IBMFS patients.Methods: Data of patients who were prospectively enrolled in the Canadian Inherited Marrow Failure Registry (CIMFR) from 2001 to 2012 and underwent HSCT were analyzed. The CIMFR is a population-based multicenter study, which includes all 16 pediatric tertiary care centers across all provinces in Canada. These centers care for >95% of the eligible pediatric IBMFS population in Canada. Descriptive analyses, as well as univariate and multivariate analyses (using a Cox proportional hazards model) were performed to assess the impact of multiple factors on probability of survival following transplant.Results: Among 363 patients enrolled in CIMFR, 65 underwent allogeneic HSCT. Thiry-four patients were male and 30 were female (gender unknown for 1 patient). Median age at diagnosis with IBMFS was 3.0 years (range: prenatal diagnosis to 32.0 years) and median age at HSCT was 6.5 years (range: 0.25-20.1 years). Median follow-up time post-HSCT (time to death or last follow-up) was 2.8 years (range 0.01–15.9 years). Indications for transplant included severe cytopenia (n=44), myelodysplastic syndrome (n=18) acute myeloid leukemia (n=2) and unavailable cause (n=1). Cell type were bone marrow (n=40), cord blood (n=17), peripheral blood (n=5), unknown (n=3). Sixty-two percent of patients (n=40) received cells from an unrelated donor. Seventy-four percent (n=47) of patients had a full HLA-matched donor; 19 of those were related and 28 were unrelated donors. The most common conditioning regimen combined high dose cyclophosphamide, fludarabine and anti-thymocyte globulin (n=17). Incidence of graft failure, acute (grade II-IV) graft versus host disease (GVHD) and chronic GVHD was 14%, 30% and 22%, respectively. Five-year probability of survival for HSCT recipients was 73.4% ± 6.1% (SE). Causes of death included infections (CMV, fungal infections and bacterial), GVHD, lymphoproliferative disorder and congestive heart failure, pulmonary fibrosis, bronchiolitis obliterans. In the univariate analysis, factors significantly associated with increased mortality post-HSCT included ≥20 pre-HSCT platelet transfusions, pre-transplant administration of granulocyte colony-stimulating factor, 1 or more HLA mismatches, donor type (divided into four categories: matched related, partially matched related, matched unrelated, partially matched unrelated) and conditioning regimens combining high doses of cyclophosphamide with fludarabine and anti-thymocyte globulin (while comparing this combination against all others). The former 3 variables remained significant in the multivariate analysis.Conclusion: Number of pre-transplant platelet transfusions, use of granulocyte colony-stimulating factor and one or more donor-recipient HLA mismatches were shown to increase the risk of mortality in patients with IBMFSs undergoing HSCT. Novel strategies are needed to improve outcome in patients with a high risk of HSCT-related complications. DisclosuresNo relevant conflicts of interest to declare.

Effect of Pre-Transplant Red-cell Transfusion Events on Transplant Related Mortality and Overall Survival in Children with Leukemia Undergoing Hematopoietic Stem Cell Transplant

Background: Recent studies have shown that an elevated ferritin level prior to hematopoietic stem cell transplant (HSCT), serving as a surrogate marker of body iron load, is independently associated with transplant related mortality (TRM) and inferior overall survival (OS) in adult oncology patients. Study Design and Methods: We performed a retrospective cohort study of 112 children with leukemia treated at our institution over a 10 year period, and compared TRM and OS after HSCT in those children with and without high red-blood cell (RBC) transfusions. Both groups were similar in regards to age, diagnoses, donor type (matched related, matched unrelated, mismatched related, mismatched unrelated), stem cell source (peripheral blood, umbilical cord, bone marrow), baseline liver, cardiac and renal function, and median follow-up time. However, more children in the low RBC transfusion event cohort had high Karnofsky/Lansky performance scores (83.5% vs 54.5%, p=0.001) and fewer had recurrent leukemia or other forms of advanced disease compared with the children more heavily transfused (41.8% vs 87.9%, p<0.0001). Results: No association was observed between high RBC transfusion exposure and TRM. High RBC transfusion events were associated with lower OS at 5 years in univariate analysis (38% versus 61%, p=0.04); in multivariate analysis, this association was not significant (hazard ratio=1.3, 95% confidence interval 0.7-2.5). Conclusion: Further studies in children are needed to investigate iron overload and HSCT outcomes.

Allogeneic HSCT Patients Receiving More RBC Transfusions Are At Increased Risk For Development Of Grade 2-4 Acute Graft-Versus-Host Disease

BackgroundA critical barrier to progress in allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been a lack in understanding regarding why some transplant recipients of HLA-matched transplant grafts develop severe graft-versus-host disease (GvHD) while other recipients have relapse of their cancer without GvHD. Patients who develop a modest degree of acute and/or chronic GvHD have less relapse and optimal survival after allogeneic BMT. Thus, a mechanistic understanding of regulation of donor T-cell activation after allo-HSCT is needed. Using mouse models, Desmarets et al. have shown that pre-transplant leukoreduced RBC transfusions can cause recipient immunization against minor histocompatibility antigens (miHA) and activation and expansion of recipient T-cells that recognize donor miHA, contributing to rejection of subsequent allo-HSCT (Blood. 2009; 114:2315). Preliminary data from our lab suggest that leukoreduced RBC transfusions given concurrently with allo-HSCT can also increase post-transplant activation and expansion of donor T-cells, an effect which may lead to increased GvHD after transplant. Here, we have conducted a retrospective study of post-transplant RBC transfusions and acute GvHD (aGvHD) in allo-HSCT patients. We hypothesized that increased numbers of transfusions during the 30-day post-transplant period would be correlated with increased severity of aGvHD in these patients. MethodsWe conducted a retrospective analysis of RBC transfusion records and aGvHD data collected for 181 adult allo-HSCT patients who received their transplants at Emory University Hospital (EUH) between 2004 and 2009. Nine patients were excluded who died < 50 days post-transplant without developing aGvHD, since this was too early to determine aGvHD occurrence. Of the remaining 172 patients studied (median age 48 yrs at time of transplant, range 18-72), 88 (49%) were male and 84 (51%) were female. Patients had received either matched related HSCT (n=69, 40%) or matched unrelated HSCT (n=103, 60%) for treatment of SAA (n=7), BAL (n=2), ALL (n=18), AML (n=69), hemolytic anemia (n=2), CLL (n=6), CML (n=8), HD (n=5), MDS (n=23), myelofibrosis (n=6), MM (n=7) or NHL (n=19). For pts who developed aGvHD, the onset time ranged from 1 to 139 days post-transplant, with a median of 30 days. No aGvHD (grade 0) was diagnosed in 58 pts (34%), while 37 pts (21%) developed grade 1 aGvHD and 77 pts (45%) developed grade 2-4 aGvHD. The number of ABO matched, irradiated RBC units transfused 0 - 30 days post-transplant was tallied for each patient, ranging from 0 (no transfusions, n=13, 7.6% of pts) to 26 units, with an average of 5.6 and median of 4 units. All transfusions during this timeframe were administered at EUH. The median follow up time was 22 months post-transplant (range, 1.1 – 96.1 months). ResultsPts were assigned to two groups, those who developed grade 0-1 aGvHD (n=95, 55%) or grade 2-4 aGvHD (n=77, 45%) within 140 days post-transplant. This study did not include analysis of late-onset aGvHD or chronic GvHD past this time point. Patients with grade 2-4 aGvHD had a higher average number of transfusions 0 - 30 days post-transplant compared with patients having grade 0-1 aGvHD (6.5 vs. 4.9 units, p = 0.02). Receiver-operator characteristics (ROC) analysis showed that a cutoff value of > 4 transfusions 0 - 30 days post-transplant had 56% sensitivity and 65% specificity to predict development of grade 2-4 aGvHD. When tested by logistic regression in a multivariate model, this cutoff value had a highly significant correlation with grade 2-4 aGvHD, with an odds ratio of 2.83 and p value = 0.0024. Other covariates including patient age, gender, and type of transplant (related vs. unrelated) were not significantly associated with aGvHD outcome. ConclusionOur retrospective analysis identified a significant positive correlation between the number of post-transplant RBC transfusions and severity of aGvHD after allo-HSCT. Additional studies are planned to determine whether RBC transfusions 0 - 30 days post-transplant stimulate allo-reactive T-cells via allo-antigen presentation or by otherwise promoting inflammation, and if one or both of these mechanisms contribute to increased GvHD. If so, it may be possible to develop strategies for optimization of RBC transfusion practices to reduce the risk of severe aGvHD after allo-HSCT. Disclosures:No relevant conflicts of interest to declare.

An update on the impact of pre-transplant transfusions and allosensitization on time to renal transplant and on allograft survival

BackgroundBlood transfusions have the potential to improve graft survival, induce sensitization, and transmit infections. Current clinical practice is to minimize transfusions in renal transplantation candidates, but it is unclear if the evidence continues to support pre-transplant transfusion avoidance. Changes in the Medicare prospective payment system may increase transfusion rates. Thus there is a need to re-evaluate the literature to improve the management options for renal transplant candidates.MethodsA review applying a systematic approach and conducted using MEDLINE®, Embase®, and the Cochrane Library for English-language publications (timeframe: 01/1984–03/2011) captured 180 studies and data from publically available registries and assessed the impact of transfusions on allosensitization and graft survival, and the impact of allosensitization on graft survival and wait time.ResultsBlood transfusions continued to be a major cause of allosensitization, with allosensitization associated with increased rejection and graft loss, and longer wait times to transplantation. Although older studies showed a beneficial effect of transfusion on graft survival, this benefit has largely disappeared in the post-cyclosporine era due to improved graft outcomes with current practice. Recent data suggested that it may be the donor-specific antibody component of allosensitization that carried the risk to graft outcomes.ConclusionsResults of this review indicated that avoiding transfusions whenever possible is a sound management option that could prevent detrimental effects in patients awaiting kidney transplantation.