Allogeneic Transplant Patients Research Articles

Intersecting Worlds of Transfusion and Transplantation Medicine: An International Symposium Organized by the Canadian Blood Services Centre for Innovation.

The principal theme of the symposium was centered on how the world of regenerative medicine intersects with that of transfusion medicine, with a particular focus on hematopoietic stem cells (HSCs) and stem cell therapies. The symposium highlighted several exciting developments and identified areas where additional research is needed. A revised map of human hematopoietic hierarchy was presented based on the functional and phenotypic analysis of thousands of single stem and progenitor cells from adult bone marrow and fetal liver. These analyses revealed that multipotency is largely restricted to the HSC and multipotent progenitor compartments in adult bone marrow where most progenitors are unipotent, whereas fetal liver contains a large number of distinct oligopotent progenitors. Furthermore, unlike adult bone marrow, multipotency is extended in the downstream progenitors in the hierarchy in the fetal liver stage. Production of platelets ex vivo from HSCs is emerging as a potentially viable option because of advances in culture techniques that combine cytokine mixtures, small molecules, and shear stress. However, limited HSC expansion and low platelet yield from culture-derived megakaryocytes remain problematic. Evidence was presented to support stricter guidelines for transfusion of platelets and red blood cells practices in allogeneic HSC transplant patients, although evidence is often extrapolated from general indications. Basic principles of human leukocyte antigen testing in HSC transplant were described, emphasizing the need for a national (and global) stem cell donor registry. Ongoing research is aimed at improving cellular cryopreservation including the establishment of a new thawing protocol that improves viability of umbilical cord blood CD34+ cells. Umbilical cord blood transplantation practices have also been improved; recent studies suggest noninferior outcomes when patients are transplanted with umbilical cord blood vs a matched adult donor. Finally, mesenchymal stem cell infusion is an example of a cellular therapy useful for immunomodulation. Preclinical trials suggest that mesenchymal stem cells may be effective in managing sepsis. In conclusion, practices and research surrounding HSCs are continuing to evolve rapidly as new information is obtained.

Vaccination in oncology practice and predictors.

Despite, vaccination is a highly effective and widely recommended for prevention of certain infections, vaccination coverage is very low. The purposes of this study were to evaluate the attitudes of medical oncologists towards vaccination and to identify predictors of intention to recommend vaccination in patients with cancer. A structured questionnaire is formed to evaluate the daily practice of vaccination. Turkish medical oncologists were invited to this study via email, SMS, or phone call. Questionnaire was filled out and the data were stored in an online survey platform. Two hundred seventy-three medical oncologists participated in the survey. Influenza, Pneumococcus, and hepatitis B were the most commonly recommended vaccines (87.1, 72.8, 67.0%, respectively). Patients with lung cancer, lymphoma and breast cancer were the main malignancies that medical oncologists suggest vaccination (68.1, 68.1, 24.6%, respectively). The most common times for vaccination were during remission/follow-up period (68.4%) or before beginning chemotherapy (64.1%). Only 23.4% of the physicians thought that their recommendation for vaccination was efficient and adequate. Lack of time and lack of knowledge or experience about vaccination are the most common limitations. There is a positive correlation between experience in the field and evaluating patients for vaccination (r=0.390, p<0.001); on the other hand, there is negative correlation between number of patients seen per day and evaluating patients for vaccination (r=-0.080, p=0.18). Experience with autologous or allogeneic bone marrow transplant patients is related with more tendency to evaluate patients for vaccination (p<0.001). Degree of experience in oncology especially in bone marrow transplant units and total number of patients seen per day are important predictors of vaccination practice in oncology. The frequency of recommendation increases with degree of experience, knowledge, and visit time per patient.

46 - Treatment of Adenovirus (AdV) Infection in Allogeneic Hematopoietic Cell Transplant (allo HCT) Patients (pts) with Brincidofovir: Final 36 Week Results from the Advise Trial

46 - Treatment of Adenovirus (AdV) Infection in Allogeneic Hematopoietic Cell Transplant (allo HCT) Patients (pts) with Brincidofovir: Final 36 Week Results from the Advise Trial

416 - Stratification of Allogeneic Hematopoietic Cell Transplant Patients by Risk of Developing Veno-Occlusive Disease: A Model for Assigning a Risk Score

416 - Stratification of Allogeneic Hematopoietic Cell Transplant Patients by Risk of Developing Veno-Occlusive Disease: A Model for Assigning a Risk Score

353 - Increased Immune Suppression is Associated with Worse Overall Survival in Allogeneic Hematopoietic Cell Transplant Patients Receiving Reduced Intensity Continuous Infusion Busulfan

353 - Increased Immune Suppression is Associated with Worse Overall Survival in Allogeneic Hematopoietic Cell Transplant Patients Receiving Reduced Intensity Continuous Infusion Busulfan

Risk factors for treatment failure after allogeneic transplantation of patients with CLL: a report from the European Society for Blood and Marrow Transplantation.

For young patients with high-risk CLL, BTK-/PI3K-inhibitors or allogeneic stem cell transplantation (alloHCT) are considered. Patients with a low risk of non-relapse mortality (NRM) but a high risk of failure of targeted therapy may benefit most from alloHCT. We performed Cox regression analyses to identify risk factors for 2-year NRM and 5-year event-free survival (using EFS as a surrogate for long-term disease control) in a large, updated EBMT registry cohort (n= 694). For the whole cohort, 2-year NRM was 28% and 5-year EFS 37%. Higher age, lower performance status, unrelated donor type and unfavorable sex-mismatch had a significant adverse impact on 2-year NRM. Two-year NRM was calculated for good- and poor-risk reference patients. Predicted 2-year-NRM was 11 and 12% for male and female good-risk patients compared with 42 and 33% for male and female poor-risk patients. For 5-year EFS, age, performance status, prior autologous HCT, remission status and sex-mismatch had a significant impact, whereas del(17p) did not. The model-based prediction of 5-year EFS was 55% and 64%, respectively, for male and female good-risk patients. Good-risk transplant candidates with high-risk CLL and limited prognosis either on or after failure of targeted therapy should still be considered for alloHCT.

Malignant lymphoma of adolescents and young adults: from the viewpoint of pediatricians.

Since adolescents and young adults (AYAs) with lymphoma began to be treated by pediatric hematologists and hematology physicians, few data have been collected regarding lymphoma in this generation of patients in Japan. We analyzed the number of pediatric hospitals that have treated hematological AYA patients. In half of the pediatric facilities, patients >15 years of age had been treated, and 40% of those facilities treated >1 AYA every year. A past lymphoma study by the Japanese Pediatric Leukemia/Lymphoma Study Group included some AYA patients. However, only the B-NHL03 study analyzed the difference between children and AYAs. In that study, 25 AYAs (7.8%) were treated among all 321 study patients. The 5-year overall survival rates of patients aged <10, 10-14, >14 years, were 88.7%, 87.0%, and 79.3%, respectively. However, this difference was not statistically significant because of the less number of patients. We analyzed data of stem cell transplantation in patients with non-Hodgkin lymphoma (NHL). Of the allogeneic transplant patients, children and AYAs did not significantly differ in treatment results. However, the 5-year transplant-related mortality after autologous transplantation was significantly higher in children than in AYAs. In NHL patients, the survival rate of AYAs after transplantation was not inferior to that of children.

Influences of FLU/BU and FLU/MEL on incidence and severity of oral mucositis among allogeneic hematopoietic stem cell transplantation patients.

In the present study, we compared the incidence and severity of oral mucositis among patients undergoing allogeneic hematopoietic stem cell transplantation after fludarabine-based regimens with busulfan 12.8 mg/kg (FB12.8), with busulfan less than or equal to 9.6 mg/kg (FB9.6), and with melphalan 140 mg/m2 (FM). The incidence of oral mucositis after FB12.8 was the highest among these 3 groups. After FM, all of the patients had developed oral mucositis by day 7. The mean disease duration of oral mucositis after FB12.8 was 13.5 days, whereas the mean disease duration after FM was 24.9 days, and was significantly prolonged as compared to that after FB12.8 (p=0.0009). The incidence of severe oral mucositis (grade 3) after FM was significantly higher than that after FB12.8 (p=0.03). As stated above, although the incidence of oral mucositis after FB12.8 was higher than that after FM, oral mucositis after FB12.8 showed improvement relatively quickly without deterioration. In contrast, the higher incidence of severe oral mucositis and the delay in resolution of mucositis after FM were remarkable.

Preclinical Development of a Cord Blood (CB)-Derived Hematopoietic Stem Cell (HSC) Product for Allogeneic Transplantation in Patients with Hematological Malignancies

Umbilical CB is an established source of HSC for allogeneic transplantation in patients lacking HLA-matched donors. The major limitation of CB transplantation is the relatively low number HSCs within a single CB unit (CBU) resulting in delayed engraftment, infections and ultimately increased mortality. Because of this, double CBU transplantation has been used to reach the required cell doses but this approach has not led to an improved overall outcome and often results in an increased rate of GVHD. These findings have prompted the development of ex vivo expansion strategies to increase the number of HSCs, so that a single CBU can be transplanted. Most of these techniques, however, result in enrichment of short term marrow repopulating cells (ST-RC) at the expense of long term (LT)-RC which may impact durable long term engraftment. In addition, they require 2-3 weeks of culture which complicates the timing of transplant and increases the risk of contamination. Our laboratory has developed a novel approach to expand the numbers of functional HSCs, by transiently influencing the epigenetic determinants of HSCs self-renewal. A 7-day treatment of CB CD34+ cells with valproic acid (VPA) results in a dramatic increase in the number of HSCs capable of durable hematopoietic engraftment in animal model recipients (Chaurasia et al. JCI, 2014). Here we report the pre-clinical development of a VPA-expanded HSC product for utilization in the treatment of patients with hematological malignancies. In the place of using freshly collected CBU as starting sources of CD34+ cells, we validated, optimized and scaled-up the expansion procedure utilizing cryopreserved CBU procured from FDA-licensed Cord Blood Banks and clinically relevant GMP reagents and materials. CBUs from 5 different donors were subjected to thawing followed by positive CD34+ cell selection using a Miltenyi CliniMACS Prodigy®. The total number of nucleated cells (TNC), CD34+ cells, viability, clonogenic potential (i.e. CFU number) and the frequency of various HSC sub-classes were determined post-thawing after which each CBU was subjected to CD34+ cell selection. CD34+ cells counts varied between 1.6 and 13.6x106 (mean of 4.5x106/CBU) and had a purity ranging from 69.2-82.8%. CD34+ cells were treated with cytokines for 16-18h, followed by addition of VPA and ex vivo expansion for 7 days. The generated cell product was characterized phenotypically and functionally and the results were compared to the unmanipulated CBU (uCBU) (Table 1). First, the expanded grafts had greater than 90% viability (range 91.4 to 97%) as compared to 68.2% in the uCBUs after thawing. The average number of CD34+ cells generated was 494.8x106 CD34+ cells (i.e. 126-fold greater than uCBU) which is the equivalent of 61.8x105/Kg/ body weight from a single CBU for an 80 kg individual. The fraction of CD34+ cells, which represented over 60% of the expanded graft, was further assessed for the presence ST-RC, intermediate-term (IT)-RC and LT-RC defined phenotypically as CD34+/CD45RA-/CD90-/CD49f-, CD34+/CD45RA-/CD90+/CD49f-, and CD34+/CD45RA-/CD90+/CD49f+, respectively. The average numbers of each of these HSC sub-classes per expanded CBU were 64, 217 and 265 fold higher than their respective numbers found in the uCBUs. Notably, the expanded grafts contained the equivalent of 22.38x105 IT-RC/kg and 16.98x105 LT-RC/kg where as uCBUs contained only 0.1x105 IT-RC/kg and 0.06x105 LT-RC/kg. Considering the ability of these HSC sub-classes to contribute to intermediate and long term hematopoietic engraftment, their presence in such high number gives the VPA-expanded grafts improved potential to lead to durable hematopoietic and immune reconstitution after transplantation. In addition, the expanded graft has a phenotype which would also be anticipated to lead to rapid hematopoietic recovery since lineage committed precursors (i.e. CD33+, CD15+, CD235a+ and CD41+ cells) represented 35-45% of its composition. Finally, as compared to uCBUs, the expanded HSC product contained 20 times more assayable CFUs consisting predominately of CFU-GEMM which are capable of contributing to multilineage engraftment. In summary, we report the generation of an ex vivo expanded CB HSCs product highly enriched in primitive HSCs sub-classes and which is currently being developed for a Phase I clinical trial for allogeneic CB transplantation in patients with hematological malignancies. [Display omitted] DisclosuresBhardwaj:Parker Institute of Cancer Immunotherapy: Membership on an entity's Board of Directors or advisory committees; Checkpoint Sciences: Membership on an entity's Board of Directors or advisory committees.

Age up to 75 Years Does Not Influence the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome

Introduction: Patients with AML and MDS who are age 60 or above represent a discrete group of patients with a different disease biology compared to younger patients. These patients are often not offered allogeneic hematopoietic stem cell transplant (HSCT) as a curative intent because of concern of increased nonrelapse mortality (NRM) and poor overall survival (OS). Hence, the information on transplant outcomes among this population is very limited. Recently with the use of better supportive care measures and reduced intensity preparative regimens, patients greater than 60 are often recommended to proceed to transplant. This study evaluates our single center experience of allogeneic transplantation in patients with MDS and AML aged 60 and older.Patients and Methods: We retrospectively evaluated 60 years or older consecutive patients with AML and MDS who underwent allogeneic HSCT between January 2005 and December 2014. The primary objectives of our study were to determine NRM, relapse, relapse free survival (RFS) and OS at 1 year following transplant. The secondary objectives were to estimate cumulative incidence of acute (aGVHD) and chronic GVHD (cGVHD) at 1 year, length of stay and readmission rate in the first 100 days following transplant.Results: Between January 2005 and December 2014, 159 patients underwent allogeneic HSCT with the median age of 64 (range, 60-75) years and median follow-up duration for OS of 3.34 (95% CI, 2.51-3.87) years. Increasing number of patients were transplanted in recent years, i.e., 67% patients between 2010-2014 compared to 33% between 2005-2009. One hundred three patients (65%) had AML and 56 patients (35%) had MDS. Forty-nine patients (31%) received full intensity regimen and 110 patients (69%) received reduced intensity regimen. Fifty-two patients (33%) underwent allogeneic related transplant and 107 patients (67%) had allogeneic unrelated transplant. Thymoglobulin based GVHD prophylaxis was given in 77 patients (48%) whereas non-thymoglobulin based GVHD prophylaxis was given in 82 patients (52%). The median day to neutrophil and platelet engraftment was 11 (range, 7-22) days and 16 (range, 0-675) days, respectively. Graft failure occurred in 3 patients. At 1-year follow-up, the cumulative incidence of grade II-IV aGVHD was 39.7% (95% CI, 32.0-47.2%), grade III-IV aGVHD was 20.8% (95% CI, 14.9-27.5%) and cGVHD was 54.1% (95% CI, 46.0-61.5%). The cumulative incidence of chronic extensive GVHD was 39.8% (95% CI, 32.1-47.4%). Blood stream infection, cytomegalovirus reactivation, Epstein-Barr virus reactivation, C. difficile diarrhea occurred in 44%, 35%, 22% and 26% of patients, respectively. At 1-year follow-up, NRM was 25.3% (95% CI, 18.8-32.3%), RFS was 53.3% (95% CI, 46.1-61.7%), relapse rate was 21.4% (95% CI, 15.4-28.1%) and OS was 56.4% (95% CI, 49.2-54.7%). The median day of hospitalization following transplant was 26 (range, 19-112) days and almost half (52%) of patients were readmitted in the first 100 days following transplant. Leukemia recurrence was the most common cause of death. Multivariable analysis demonstrated high disease risk index to be the independent predictor of poor RFS, OS and higher relapse rate (p<0.03), whereas non-thymoglobulin based GVHD prophylaxis, higher comorbidity index (≥3) and MDS were found to be associated with higher NRM (p<0.03). Most importantly, age did not shown to have any effect on relapse rate, OS, RFS, or NRM.Conclusion: Our results indicate that allogeneic HSCT is well tolerated and had acceptable NRM, and OS among this group. Hence, older age alone should not be considered a contraindication to HSCT. [Display omitted] [Display omitted] [Display omitted] DisclosuresDeol:Jazz Pharmaceuticals: Consultancy.

Response to Proteosome Inhibitors and Immunomodulatory Drugs before and after Allogeneic Transplantation in Patients with Multiple Myeloma: A Long Term Follow up Study

Introduction: Allogeneic haematopoietic stem cell transplantation (alloHCT) is a potentially curative approach for patients (pts) with multiple myeloma (MM). The high transplant related mortality (TRM) rate with myeloablative conditioning has resulted in a shift to reduced intensity conditioning regimens (RIC). However, most MM pts who receive an alloRIC ultimately relapse and their treatment remains a challenge. Since alloHCT can modify the biology of the disease, including the immune environment, responses after alloHCT to rescue therapies previously used before alloHCT could be improved. Our main objective was to evaluate the efficacy of regimens including new drugs in MM pts relapsing after alloHCT comparing the efficacy achieved before and after alloHCT.Material and Methods: We report a retrospective multicenter analysis of 126 consecutive pts that underwent alloHCT for MM from 2010 to 2013 at 8 Spanish centers.Results: Baseline pts and transplant characteristics are shown in Table I. The median of prior therapies prior to alloHCT was 3 (1-9), 83% had received previous autologous HCT and 26% had high risk cytogenetic. 71 (56%) and 48 pts (38%) had been treated with regimens containing proteasome inhibitors (PI) and immunomodulatory drugs (IMIDs) before transplantation, respectively. Disease status at transplant was complete remission (CR) in 16 (13%) pts, partial response (PR) or very good PR in 86 (68%) and 24 (18.5%) had relapsed/progressive disease. 35 pts (28%) had active extramedullary disease at transplant. The majority of pts received peripheral blood HCT (90%), RIC (90%) with fludarabine plus melphalan based conditioning regimen (61%) and calcineurin inhibitor plus MTX as GVHD prophylaxis (68%). 19% receiving allo-HCT from an unrelated donor (91% 10/10 HLA matched).All pts engrafted. Grade II-IV acute GVHD occurred in 54% pts (grade IV 8%) and chronic GVHD in 45% (moderate 15%, severe 12%). TRM within the first 100 days after transplant was 6% (overall TRM 28%). 60% pts improved their pre-transplant response, with an overall response rate of 74% (56% CR). After a median follow-up of 92 months for pts alive (22-197), the OS was 51 and 43% at 2 and 5 years respectively.75 pts (59.5%) relapsed after alloHCT, 57 of them with extramedullary involvement. Median time to relapse was 8 months post-transplant (1-141). The cumulative incidence of relapse was 79% at 3 years. Median OS after relapse was 22 months (8-33).Seventeen out of 75 pts who relapsed received IP both in the pre-transplant and in the post-transplant period. Sixteen pts out of 17 who received IP achieved at least PR pre-transplant while 10 out of these 16 pts responded again to PI post-HCT. Moreover, 1 patient reached a deeper response (CR) post as compared to pre alloHCT (PR) and 1 patient who was refractory pre-alloHCT did respond post-alloHCT. In addition, 6 out of 7 pts who did not respond to IP post-transplant reached stable disease with time to progression (TTP) lasting 4 to 12 months.Twelve out of 75 pts who relapsed received IMIDs both pre and post-alloHCT. Ten pts out of 12 who received IMID pre-alloHCT achieved at least PR, and 8 out of these 10 pts responded again to IMIDs post-alloHCT. Moreover, 1 patient who had been refractory to IMIDs in the pre-transplant period reached CR after alloHCT. In addition, 2 out of 4 pts who were refractory to IMIDs in the post-transplant period reached stable disease with TTP of 8 to 13 months.Remarkably, among pts who respond both in the pre and the post-transplant period to IP or IMIDs, the time to response (TTR) and time to progression (TTP) was similar despite the regimens used in the pre-transplant setting were more aggressive (TTR 3 vs 3.5 and TTP 9 vs 7 months before and after alloHCT for IP, and TTR 4 both before and after alloHCT and TTP 10 vs 9.5 months before and after alloHCT for IMIDs).All but 2 pts received first generation IP pre and post-alloHCT (two pts received carfilzomib) and all but 5 received first generation IMIDs (5 pts were treated with pomalidomide).Conclusions: MM pts relapsing after alloHCT should be considered candidates to receive new drugs, as they can achieve response rates at least in a similar proportion and durability to those observed in the pre-transplant setting. This finding is in contrast to the usual course of the disease outside the alloHCT setting, where response rates and TTP decreases with consecutive lines of treatment. DisclosuresMateos:Janssen: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria.

Prognostic Impact of Blood Count Recovery Based Complete Remission Prior to Allogeneic Transplantation in Patients with Acute Leukemia

Background: Morphologic complete remission (CR) is the gold standard for assessing response in acute leukemia. Patients who achieve CR with incomplete count recovery (CRi) in acute myeloid leukemia typically have inferior overall survival and lower event free survival (Walter et al, JCO 2010 and Chen et al, JCO 2015). Incomplete hematologic recovery is likely not an independent risk factor for inferior outcome but possibly correlates with adverse disease characteristics such as high risk cytogenetics or minimal residual disease post therapy. Furthermore, remission status prior to allogeneic stem cell transplantation (SCT) is an important predictor of post-transplant outcome. However, the prognostic role hematologic recovery carries prior to allogeneic transplantation for acute leukemia is not known.Aim: To study the impact of CRi with corresponding impact on relapse incidence (RI), non-relapse mortality (NRM) and overall survival (OS) in allogeneic SCT for acute leukemia.Methods: Patients with acute myeloid or lymphoid leukemia who received allogeneic SCT at our institution between 2010-2015 were identified. All clinical and pathologic data were retrospectively extracted. All patients were deemed in morphologic remission at the time of transplant without evidence of active disease. CR and CRi were defined in accordance to previous international working group definitions. Categorical and continuous variables were analyzed using Pearson's chi-squared and Wilcoxon / Kruskal-Wallis, respectively. Survival estimates were calculated using the Kaplan-Meier and log-rank test. RI was estimated accounting NRM on a competing event analysis using Grey's model.Methods: Patients with acute myeloid or lymphoid leukemia who received allogeneic SCT at our institution between 2010-2015 were identified. All clinical and pathologic data were retrospectively extracted. All patients were deemed in morphologic remission at the time of transplant without evidence of active disease. CR and CRi were defined in accordance to previous international working group definitions. Categorical and continuous variables were analyzed using Pearson's chi-squared and Wilcoxon / Kruskal-Wallis, respectively. Survival estimates were calculated using the Kaplan-Meier and log-rank test. RI was estimated accounting NRM on a competing event analysis using Grey's model.Results:A. Baseline characteristics: A total of 68 patients were identified. A total of 36 were in CR while 32 were in CRi. Baseline patient, disease and transplant characteristics stratified by group are shown (Table 1). Importantly, there were no significant differences between the cohorts with regards to gender, disease status at SCT, intensity of conditioning regimen, use of total body irradiation (TBI), HLA and ABO matching.B. Transplant outcomes: Median follow up of the entire cohort was 13.6 (2-64.9) months. During which 2-year rates of RI, NRM and OS were 42.4, 12.8% and 63.9%, respectively. Stratified by count recovery, the 2-year rates of RI for CR and CRi were 36.2 vs. 43.1, respectively (p = 0.39). 2-year NRM for CR and CRi were 21.7% vs. 11%, respectively (p = 0.1). 2-year OS for CR and CRi were 59% vs. 61.8%, respectively (p = 0.58).Conclusion: We observed comparable post-transplant outcomes between CR and CRi. This suggests that in contrast to acute myeloid leukemia, SCT had a role in mitigating the negative prognostic implication of CRi. These results could have implications as physicians may not need to postpone SCT to await hematologic recovery. This important question should be further validated in a larger cohort of patients. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Biologic vs physiologic age in the transplant candidate.

Hematopoietic cell transplantation (HCT) remains a cornerstone of treatment of many hematologic malignancies but transplant-associated morbidity and mortality limit application to older patients. Biologic or chronologic age barriers to HCT have fallen, because patients in their 8th decade of life comprise the group with the greatest rise in transplant use over the past decade. Evaluating physiologic age or general health in older transplant candidates requires a systematic approach inclusive of functional and comorbidity assessment, which typically is accomplished through geriatric assessment (GA). GA incorporates measures of comorbidity, function, nutrition, social support, and other health-related domains to better describe physiologic age. Older allogeneic transplant patients have a surprisingly high prevalence of vulnerabilities by GA prior to transplant, and significant comorbidity or functional limitations heighten the risks of transplant-related mortality. Ultimately, incorporation of physiologic age can improve estimates of nondisease life expectancy, prognostic survival after HCT, and inform HCT candidacy. Future research on the optimal tools to characterize physiologic age and appropriate interventions in the context of transplant are needed.

Treatment of Adenovirus (AdV) Infection in Allogeneic Hematopoietic Cell Transplant (HCT) Patients (pts) with Brincidofovir: 24 Week Interim Results from the AdVise Trial

Treatment of Adenovirus (AdV) Infection in Allogeneic Hematopoietic Cell Transplant (HCT) Patients (pts) with Brincidofovir: 24 Week Interim Results from the AdVise Trial

1485P - Medical oncologists' attitudes towards vaccination in oncology practice

Despite of vaccination is a highly effective way of preventing certain infections and widely recommended in patients' with cancer, vaccination rate are not high enough. The purpose of this study was to evaluate the attitude of medical oncologists towards vaccination in their daily practice and predictors of vaccination practice in oncology. A structured questionnaire is formed to evaluate the daily practice of vaccination. Medical oncologists actively working in Turkey were invited to study by emails, SMS messages and direct phone calls. Questionnaires were filled and the data were stored with an online survey platform 273 medical oncologists participated the survey. Influenza, Pneumococcus and hepatitis B were the most commonly recommended vaccines (87.1%, 72.8%, 67.0%, respectively) in daily practice. Lung, lymphoma and breast cancer are the pathologies to which medical oncologists give priority while recommending vaccination (68.1%, 68.1%, 24.6%, respectively. Participants prefer to recommend vaccination to patients in remission/follow-up (68.4%) or before starting therapy 64.1%. Patients' age and comorbidities were not related with rate of vaccination. Only 23.4% of the participants thought that their recommendations on vaccination were efficient and satisfying. Lack of time during outpatient clinic visit and lack of knowledge or experience about vaccination are the most common limitations during recommending vaccination. There is a positive correlation between experience in the field and evaluating patients for vaccination (r = 0.390, p < 0.001), on the other hand, there is negative correlation between number of patients daily cared and evaluating patients for vaccination (r= -0.080, p = 0.18). Experience with autologous or allogeneic bone marrow transplant patients is related with more tendency to evaluate patients for vaccination (p < 0.001). Status of experience in oncology, especially in bone marrow transplant units and total number of patients exposed daily are important predictors of vaccination practice in oncology. Similar with the data in other fields, there is also a huge heterogeneity in medical oncologists' attitude towards vaccination.

Comparing the ratio of mean red blood cell transfusion episode rate of 1 unit versus 2 units in hematopoietic stem cell transplant patients.

Two units of red blood cells (RBCs) were typically transfused with each transfusion among hematopoietic stem cell transplant (HSCT) patients. Concerns regarding this practice are increased morbidity, mortality, hospital-acquired infections, length of stay (LOS), and transfusion-related complications. This study compared outcomes of transfusing 1unit of RBCs per transfusion episode to 2units of RBCs per episode among HSCT patients. A retrospective record review was used to evaluate a practice change of transfusing 1 RBC unit per episode among autologous and allogeneic HSCT patients. Primary endpoints included: 1) mean number of RBC transfusion episodes during the hospital stay, 2) mean number of RBC units transfused adjusted by LOS, and 3) mean LOS. Among autologous patients, the ratio of mean rate of transfusion episodes for transfusing 1unit versus 2units per transfusion was 1.24, with a one-tailed 95% upper limit of 1.42. With a noninferiority upper bound of 1.50, using 1unit per transfusion episode was noninferior to 2units per transfusion episode (p=0.011). Among allogeneic HSCT patients, the ratio of mean transfusion episode rate was 1.26 with a one-tailed 95% upper limit of 1.52, which was slightly above the 1.50 noninferiority bound (p=0.061). A single-unit transfusion policy was not inferior to the 2-unit policy for autologous HSCT patients and trended toward noninferiority for allogeneic transplant patients. The mean volume of blood per LOS was lower for the 1-unit practice for both groups. The gains from the practice change may outweigh the risks of not changing.

A Review of Radiation-Induced Coagulopathy and New Findings to Support Potential Prevention Strategies and Treatments.

Results from our recent studies have led to the novel hypothesis that radiation-induced coagulopathy (RIC) and associated hemorrhage occurring as part of the acute radiation syndrome (ARS) is a major cause of death resulting from radiation exposure in large mammals, including humans. This article contains information related to RIC, as well as potential strategies for the prevention and treatment of RIC. In addition, new findings are reported here on the occurrence of RIC biomarkers in humans exposed to radiation. To determine whether irradiated humans have RIC biomarkers, blood samples were obtained from radiotherapy patients who received treatment for different types of malignancies. Blood samples from allogeneic hematopoietic cell transplantation (allo-HCT) patients obtained before, during and after irradiation indicated that exposure led to prolonged clot formation times, increased levels of thrombin-antithrombin III (TAT) complex and increased circulating nucleosome/histone (cNH) levels, which suggest potential coagulopathies in the allo-HCT patients. Since these allo-HCT patients received chemotherapy prior to radiotherapy, it is possible that the chemical agents could have influenced the observed results. Frozen plasma samples from radiotherapy patients with prostate, lung and breast cancer were also obtained for analyses of cNH levels. The results indicated that some of these patients had very high cNH blood levels. Analysis of cNH levels in plasma samples from irradiated ferrets also indicated increased cNH levels compared to preirradiation baseline levels. The results from irradiated animals and some radiotherapy patients suggest the possibility that anti-histone antibodies, which block the toxic effects of elevated cNH levels in the blood, might be useful as therapeutic agents for adverse biological radiation-induced effects. The detection of increased levels of cNH in some radiotherapy patient blood samples demonstrates its potential as a biomarker for diagnosing and/or predicting the propensity for developing coagulopathies/hemorrhage, offering possible treatment options with personalized medicine therapies for cancer patients.

Allogeneic transplantation is not superior to chemotherapy in most patients over 40years of age with Philadelphia-negative acute lymphoblastic leukemia in first remission.

Survival of patients ≥40years of age with Philadelphia-negative acute lymphoblastic leukemia (ALL) remains poor with current therapeutic approaches. It is unknown whether allogeneic hematopoietic stem-cell transplantation (HSCT) in first remission confers a survival benefit compared to a chemotherapy-only approach. We retrospectively compared the outcome of patients >40years treated with HSCT or chemotherapy alone in first remission (n=40 in each cohort). Three-year overall survival (OS) and disease-free survival (DFS) were not significantly different between the chemotherapy-only and HSCT groups (OS, 46% [31-68] vs. 40% [27-59], P=0.35; DFS, 31% [18-52] vs. 40% [27-59], P=0.98). The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 61% [41-76] and 9% [2-21] for the chemotherapy-only group and 28% [15-43] and 32% [17-47] for the transplant group (CIR, P=0.011; NRM, P=0.014). Allogeneic transplantation for patients ≥40years with Ph-negative ALL in first remission is associated with a lower CIR, but this benefit is offset by considerable NRM as compared with chemotherapy-only approach. HSCT may be beneficial in patients with high-risk disease features. Am. J. Hematol. 91:793-799, 2016. © 2016 Wiley Periodicals, Inc.

Clinical and Economic Consequences Associated with Cytomegalovirus Infection Among Allogeneic Hematopoietic Cell Transplant Patients

Clinical and Economic Consequences Associated with Cytomegalovirus Infection Among Allogeneic Hematopoietic Cell Transplant Patients

Allogeneic Transplantation for Patients With Advanced Myelofibrosis: Splenomegaly and High Serum LDH are Adverse Risk Factors for Successful Engraftment

Thirty consecutive patients underwent hematopoietic stem cell transplantation for myelofibrosis (MF) at our institution. The median age at the time of transplant was 49 (range, 18-68) years, 74% of patients had advanced Dynamic International Prognostic Scoring System (DIPSS) scores, and 83% received reduced-intensity conditioning. With a long follow-up of our patients, we analyzed disease and transplant variables that contributed to engraftment and outcomes. Neutrophil engraftment was achieved in 27 patients (90%) at a median time of 15 (range, 10-44) days, and 19 patients (63%) achieved platelet recovery at a median time of 18 (range, 8-100) days. Splenomegaly was associated with poor neutrophil engraftment (subdistributional hazard ratio [SHR], 0.42; 95% confidence interval [CI], 0.21-0.83; P= .01) and platelet engraftment (SHR, 0.18; 95% CI, 0.07-0.48; P<.001). Increased levels of lactate dehydrogenase (LDH) was associated with poor platelet engraftment (SHR, 0.39; 95% CI, 0.16-0.94; P= .04). The median follow-up for surviving patients was 49 (range, 3-155) months. The 1-year cumulative incidence of nonrelapse mortality (NRM) and relapse were respectively, 57% (95% CI, 29%-76%) and 25% (95% CI, 7%-48%). Increased levels of LDH was associated with high NRM (SHR, 2.82; 95% CI, 1.08-7.35; P=.03). The 4-year overall survival (OS) and relapse-free survival (RFS) were 44% (95% CI, 29%-67%) and 37% (95% CI, 23%-61%), respectively. In the multivariable model, splenomegaly and Eastern Cooperative Oncology Group (ECOG) performance status (PS) > 1 were associated with worse OS (hazard ratio [HR], 5.40; 95% CI, 1.19-24.56); P= .03) and RFS (HR, 3.78; 95% CI, 1.01-14.06; P< .05), respectively. ECOG PS > 1 was also associated with worse RFS (HR, 5.00; 95% CI, 1.31-19.14; P= .02). In this patient group with advanced disease, DIPPS score, Lille score, Janus-Associated Kinase V617F (JAK2 V617F) mutation status, and donor type did not predict transplant outcome. We confirm curative potential, but high NRM of allogeneic transplant for advanced MF.