Consecutive Allogeneic Hematopoietic Cell Transplantation Research Articles

Utility of eGVHD App for bedside GVHD assessment in a high-volume BMT center.

Assessing acute and chronic graft-versus-host disease (GVHD) is challenging because there are several classification systems. The European Society for Blood and Marrow Transplantation and the Center for International Bone Marrow Transplantation Registry task force recommends using the eGVHD application (App) to score acute GVHD according to the Mount Sinai Acute GvHD International Consortium (MAGIC) criteria and chronic GVHD according to the National Institutes of Health 2014 criteria. We prospectively used the eGVHD App at each follow-up visit in a large-volume bone-marrow transplant center in India from 2017 to 2021. We retrospectively evaluated the discrepancy in scoring GVHD severity by physicians not using the App from the same patient charts. The App user satisfaction and experience were recorded using the technology acceptance model (TAM) and the Post-Study System Usability Questionnaire (PSSUQ). In 100 consecutive allogeneic hematopoietic cell transplantation recipients, there was more discrepancy in scoring the severity of chronic GVHD (38%) than acute GVHD (9%) without using the App. The median TAM and PSSUQ scores were six (IQR:1) and two (IQR:1), respectively, indicating high perceived usefulness and user satisfaction. The eGVHD App is an excellent learning tool for hematology/BMT fellows and helps manage GVHD in high-volume BMT centers.

Infectious diarrhea after allogeneic hematopoietic cell transplantation assessed by a multiplex polymerase chain reaction assay

ObjectivesTo determine the incidence of infectious diarrhea after allogeneic hematopoietic cell transplantation (HCT) using a multiplex polymerase chain reaction assay and assess risk factors for developing infectious diarrhea. MethodsThis was a single-center retrospective study of 140 consecutive allogeneic HCT recipients. Infectious diarrhea was assessed using a laboratory-developed multiplex polymerase chain reaction the first year after transplantation. ResultsThe incidence rate of infectious diarrhea episodes was 47 per 100 person-years, with the highest rate observed in the pre-engraftment phase. Most episodes were seen as nosocomial infections (38%) and most affected patients (82%) had only one episode of infectious diarrhea. The cumulative incidence of at least one episode of infectious diarrhea was 32% after 1 year. Nonrelapse mortality was higher in transplant recipients with at least one episode of infectious diarrhea (hazard ratio (HR) 2.02, 95% CI = 1.07-3.80). The most frequently observed pathogens were Clostridium difficile, adenovirus, Enteropathogenic Escherichia coli, and Campylobacter jejuni. Patients with acute lower gastrointestinal graft-vs-host disease stage 3 or 4 (HR 3.68, 95% CI = 1.57-8.63) conferred a higher risk for a first infectious diarrhea episode. ConclusionInfectious diarrhea after allogeneic HCT was seen in about one-third of the patients, mostly as nosocomial infection in the pre-engraftment phase.

Predictors of Transplant-Associated Thrombotic Microangiopathy in Patients With Overlap or Chronic Graft-vs-Host-Disease

Recent data suggest that novel biologic agents are associated with increased risk of thrombotic microangiopathy (TMA). Ruxolitinib, an approved treatment for graft-vs-host-disease (GVHD), has been associated with thrombocytopenia of unclear etiology. We investigated factors and outcomes associated with transplant-associated thrombotic microangiopathy (TA-TMA) in patients with GVHD. We retrospectively enrolled consecutive allogeneic hematopoietic cell transplantation recipients with overlap or chronic GVHD at our Joint Accreditation Committee ISCT-Europe & EBMT-accredited unit (January 2016-June 2019). Ruxolitinib has been administered off-label since 2016. Among 160 patients with GVHD, 18 were diagnosed with TA-TMA. TA-TMA developed at a median of 150 posttransplant days (range, 98-3013). Among pre- and posttransplant factors, TA-TMA was associated only with ruxolitinib administration and severe GVHD. Interestingly, these 2 variables did not correlate with each other. In the multivariate analysis, both were independent predictors of TA-TMA. Time-dependent analysis confirmed ruxolitinib's association with TA-TMA. With a follow-up of 38.4 months (4.6-83.9) in surviving patients, 5-year overall survival was 52.9%, independently predicted by TA-TMA, severe acute GVHD, and CD34+ cells infused. Ruxolitinib was not associated with survival outcomes. Our data suggest that ruxolitinib and GVHD severity are associated with TA-TMA. Given the expanding use of ruxolitinib in GVHD and ongoing trials on chronic GVHD, further studies are warranted to confirm these findings.

Myeloablative Hematopoietic Cell Transplantation (HCT) for Low and Intermediate Disease Risk Index Myeloid Malignancies Results in Better Outcomes Compared to Reduced Intensity HCT

The optimal regimen intensity before allogeneic hematopoietic cell transplantation (HCT) remains an unsettled question. The recent Blood and Marrow Transplant Clinical Trial Network BMTCTN 0901 randomized phase III study showed that Myeloablative conditioning (MA) results in better relapse-free survival and a trend towards better overall survival compared to reduced intensity conditioning (RIC). The findings of BMTCTN 0901 though contradicts several prior studies addressing the same question, was limited by the fact that most patients in the RIC received fludarabine/low dose Busulfan and the study was not designed to assess the effect of intensity on patients with different disease risk index (DRI) groups. Acute myeloid leukemia and myelodysplastic syndrome patients with low/intermediate DRI tend to respond well to chemotherapy and can potentially be cured with chemotherapy regimens alone. On the other hand, high and very high risk DRI myeloid malignancies have a high relapse rate and very low rates of success with chemotherapy only approach. We hypothesize that conditioning intensity benefit is limited to patients with low/intermediate risk DRI and no such benefit is seen in the high/very high risk DRI myeloid malignancy patients. To answer this question, we retrospectively analyzed AML/MDS HCT recipients with low/intermediate DRI to assess the impact of conditioning intensity on overall survival (OS), disease free survival (DFS), relapse, and non-relapse mortality (NRM). Survival was calculated using the Kaplan-Meier estimator. Univariate analysis with Gray test and log-rank test will be used for cumulative incidence and survival respectively. Cox regression models were built to study the effect of conditioning intensity adjusted for other significant factors on OS, NRM, DFS, relapse and graft-versus-host disease (GVHD). Conditioning intensity was retained in the cox models and other variables were selected to be included if the P-value was less than 0.05.A total of 232 consecutive allogeneic HCT recipients with low/intermediate DRI myeloid malignancy (AML 170, MDS 60) were included in the analysis with a median follow up of 37 months. Median age was 55 years (18, 75) and 83% were of white race. Patient and transplant related characteristics were as follows: 42% RIC, 11% Myeloablative high dose TBI, 47% non-TBI Myeloablative conditioning; 21% bone marrow graft; 31% matched related donor transplant MRDT, 47% matched unrelated donor transplant MUDT, 22% haploidentical donor HIDT; 49% had hematopoietic cell transplant comorbidity index HCT-CI ≥3 ; donor/recipient female to male 21%; and donor/recipient CMV +/+ 42%, -/- 19%, other 39%. Both MA and RIC groups had similar patient, disease and transplant related characteristics except for a higher percentage of MA recipients received methotrexate as part of their GVHD prophylaxis compared to RIC (78% vs 55%, p<0.001). Recipients of Myeloablative conditioning had better overall survival estimate (3-year 69% vs 57%, p=0.001), DFS (3-year 65% vs 51%, p=0.003) and lower relapse cumulative incidence (3-year 17% vs 32%, p=0.01) but similar NRM (3-year 19% vs 17%, p=0.04) to RIC recipients (figure 1). There was no difference in the cumulative incidence of grade 2-4 acute and moderate-severe GVHD between Myeloablative and RIC groups. Multivariate analysis revealed MA conditioning to be associated with better DFS (HR 0.58, 95% CI 0.39-0.88, p=0.01), lower relapse (HR 0.56, 95% CI 0.32-0.97, p=0.038) and similar NRM (HR1.11, 95% CI 0.54-2.26, p=0.781) compared to RIC. When same analysis was performed for high/very high DRI myeloid malignancy patients (N=247), conditioning intensity had no effect on OS, DFS, Relapse and NRM (P value>0.10 for all).Myeloablative conditioning results in better overall survival and disease control when compared to RIC among AML/MDS patients with low/intermediate DRI risk group. This benefit is not shown among high/very high DRI risk patients. [Display omitted] DisclosuresSolh:Celgene: Speakers Bureau; ADC Therapeutics: Research Funding; Amgen: Speakers Bureau.

Effect of donor type on volume of blood transfusions required after allogeneic hematopoietic cell transplantation.

We reviewed blood product use in 729 consecutive allogeneic hematopoietic cell transplantation (allo-HCT) recipients at our center to assess the volume of red blood cells (RBCs) and platelets required after allo-HCT. The median number of bags required by day 30 was 4 for RBCs (range 0-22) and 9.5 for platelets (0-53). Multivariate analysis showed that related peripheral blood stem cell transplantation (PBSCT) required a significantly lower RBC transfusion volume by day 30 compared to unrelated bone marrow transplantation (UBMT). PBSCT from haplo-identical related donors and cord blood transplantation (CBT) required a significantly greater RBC transfusion volume. For platelet transfusion, related and unrelated PBSCT required a significantly lower volume than UBMT, and CBT a greater volume. Other factors independently associated with greater RBC transfusion volume were male sex, disease status other than complete remission, and major ABO mismatch. For platelet transfusion, these were male sex, disease status, and HCT-specific comorbidity index of 1. Although the burden of blood transfusions may not be the most important factor when choosing a donor type, our findings may provide a foundation for nationwide strategies to prepare blood products and inform aspects of national healthcare expenditures.

571. “Real world” Impact of Letermovir for Prevention of Cytomegalovirus Infection in Hematopoietic-Cell Transplantation

BackgroundLetermovir (LTM) was FDA-approved in 2017 for cytomegalovirus (CMV) prophylaxis in allogeneic hematopoietic cell transplant (HCT) patients. We evaluated the “real-world” impact of LTM in adult HCT recipients at the Mount Sinai Hospital in New York following addition of LTM to our formulary in June 2018.MethodsIn this retrospective study, we compared 31 consecutive allogeneic HCT recipients from June 2018-June 2019 who received LTM prophylaxis from Day +10–100 to 36 consecutive CMV-seropositive patients who underwent allogeneic HCT June 2017-June 2018 and did not receive LTM. Clinical and laboratory data were abstracted from the existing electronic medical record. The primary outcome was development of clinically significant CMV infection (CS-CMV) through 6 months post-HCT, defined as CMV viremia or disease requiring antiviral therapy.ResultsThere were no baseline differences in patient demographics or transplant characteristics between patients who did and did not receive LTM prophylaxis. The median duration of LTM prophylaxis was 96 days (IQR, 66–116). At 6-months post-HCT, the cumulative incidence of CS-CMV was lower in patients receiving LTM prophylaxis vs no prophylaxis (29% vs 61%, respectively; p=0.004, Figure 1). Patients who received LTM developed CS-CMV at a later time post-HCT than those who did not receive prophylaxis (median 160 vs 39 days, respectively; p < 0.01). Among patients with CS-CMV, the median duration of antiviral therapy was 39 vs 70 days in the LTM prophylaxis vs no prophylaxis groups, respectively (p< 0.01). While there was no difference in the incidence of graft-versus-host disease (GVHD), the median time to GVHD diagnosis was longer in the LTM group (63 days vs 27 days in the no prophylaxis group; p=0.02). Between patients who did and did not receive LTM prophylaxis no statistically significant difference was observed, respectively, in incidence of CMV disease (3% vs 14%), hospital re-admission (68% vs 67%), or mortality (26% vs 14%) at 6 months post-HCT.Figure 1.ConclusionWe demonstrated the “real-world” utility of LTM for CMV prevention in HCT recipients. Future studies should further evaluate the impact of LTM on antiviral drug usage, GVHD, and other transplant-related outcomes in this population.Disclosures All Authors: No reported disclosures

Toxoplasmosis as an Early Complication of Allogeneic Hematopoietic Cell Transplantation

Among 419 consecutive allogeneic hematopoietic cell transplant recipients, we observed 17 (4.0%) cases of toxoplasmosis at a median time of day 45 (range, 6 to 322) after transplant. Seven of these 17 cases occurred before day 30 after transplant. Because of the lack of PCR screening and trimethoprim-sulfamethoxazole prophylaxis before engraftment, the diagnosis of toxoplasmosis was late, and 5 of these 7 patients died. Analyzing these cases, early Toxoplasma blood PCR screening, starting from transplant, is crucial.

Risk Factors for 100-Day Readmission after Discharge in Allogeneic Hematopoietic Cell Transplant and Its Clinical Implications

Introduction Hospital readmissions after hematopoietic cell transplant (HCT) carry significant morbidity and mortality in HCT recipients. Herein, we describe a single institution 100-day readmission rate, its risk factors and clinical implications using post-HCT cytoxan as graft vs. host disease (GVHD) prophylaxis. Methods Data on 125 consecutive allogeneic HCT (allo-HCT) patients at Levine Cancer Institute, Charlotte, NC, between March 2014 and May 2018 were reviewed for dates of readmission, reasons for admission, patient demographics, socio-economic status and clinical outcomes. The cohort was divided into 2 groups, readmission vs. no readmission, based on admission to the hospital within 100 days of discharge from index transplantation admission. Study variables were compared between the 2 groups via a descriptive statistical analysis. Fisher's exact test and two-sample t-test were used to calculate P-values for categorical and continuous variables, respectively. Univariate and multivariate logistic regression analysis was used to assess risk factors for readmission. Overall survival (OS) after the initial hospital discharge was evaluated between patients with and without 100-day readmission using the Kaplan-Meier method and log-rank test. The cumulative incidence of non-relapse mortality (NRM) was estimated in a competing risk setting with relapse related death as a competing event. Group comparison of incidences were determined by Gray's test. The effect of readmission on NRM was evaluated in a Cox regression model. Results 52 (41.6%) of 125 allo-HCT patients were readmitted after transplantation admission. Median time to readmission from hospital discharge was 22.5 days (range: 1-96) and median length of stay (LOS) was 12 days (range: 1-70). The most common causes for readmission were infectious complications (57.7%) and GVHD (13.5%). In univariate analysis for 100-day readmission (Table 1), variables such as primary insurance payer, graft cell source, infections and GVHD during index admission, LOS, marital status and ANC recovery did not affect readmission risk, however being non-Caucasian (n=33, 26.4%) had increased odds ratio (OR) of 2.05 (p=0.081). OS was also similar between the 2 groups (P = 0.189). The incidence of NRM for patients with and without readmission was 25.1% and 6.9%, respectively (P = 0.047). Multivariate Cox regression analysis identified 100-day readmission (HR 2.96, 95% CI 1.01-8.71, P = 0.043), and LOS (HR 1.48, 95% CI 1.05-2.10, P = 0.027) as significant risk factors for NRM (Table 2). Conclusions Although readmission after allo-HCT is associated with increased NRM, we could not identify any risk factor for readmission within 100 days of discharge at our institution. We observed increased OR for readmission amongst non-Caucasian race in univariate analyses, but it did not emerge as a significant variable in multivariate analysis.

Transplant-Associated Thrombotic Microangiopathy (TA-TMA): Not a Singular Entity

▪Introduction: Thrombotic microangiopathy (TMA) is a clinical syndrome that can develop after hematopoietic cell transplantation (HCT). Previous studies have been limited to small case series with conflicting results. In this large, single-center longitudinal TA-TMA database, we describe the incidence, etiology, treatment, and outcome of this rare but challenging clinical presentation.Methods: We performed a retrospective cohort analysis of consecutive allogeneic HCT recipient during 2006-2015 at Fred Hutchinson Cancer Research Center. TA-TMA was defined as persistent microangiopathic hemolytic anemia (MAHA) composed of red cell fragmentation, elevated lactate dehydrogenase (LDH), thrombocytopenia, anemia, and lack of coagulopathy (Table 1). We performed a primary search algorithm using “consecutive MAHA” followed by a secondary search algorithm using “suspected hemolysis” to identify all cases from date of transplant until date of death or last follow-up (Table 1). For each suspected case, we further reviewed available patient records to confirm the diagnosis, determine the etiology, treatment, and complication. The most likely etiology was determined by reviewing the clinical events in the 2-week window before the TMA onset. Since 96% of patients were receiving calcineurin inhibitor (CNI), we chose idiopathic/drug as a diagnosis of exclusion if all other causes were excluded. TMA resolution was defined as LDH <1.5x ULN, platelet transfusion independence, and rare or no schistocytes. Continuous and categorical variables were shown as median (interquartile range) and percentage, respectively. Overall survival was depicted with Kaplan-Meier curves, after accounting for delayed entry with left truncation at TMA diagnosis. Cox regression model was built to test the association between TMA resolution as a time-varying covariate and overall survival.Results: Among 2241 consecutive adult allogeneic HCT recipients, 209 patients (9%) met the laboratory criteria of TA-TMA (Table 2) with a median onset time of 62d (35d-93d). One hundred and nine patients (52%) had end-organ damage with either acute kidney injury (AKI) or neurologic deficit. The median follow-up was 181d (92d-478d) and 53 patients (25%) achieved hematologic resolution. Diagnostically, acute GVHD (n=96) represented the largest category and those with GVHD refractory to high dose steroid (n=61) had poor prognosis. Diffuse alveolar hemorrhage (DAH) and idiopathic pneumonia syndrome (IPS) (n=30) also frequently preceded the TMA onset. Finally, despite excluding patients with coagulopathy, non-specific causes of TMA such as disease recurrence (n=20) and systemic infection (n=33) were frequently evident.Overall survival, separated by TMA etiology is shown in Figure 1. Whereas the idiopathic/drug and non-refractory acute GVHD categories approached the survival of non-TMA post-HCT recipients, the other groups had worse prognosis. Regardless of cause, the most common treatment (32%) was CNI cessation or CNI switch (in no particular pattern). We did not observe an association between changes to CNI therapy and TMA resolution (24% vs. 26%, Fisher P 0.80) or overall survival at 6 months (37% vs. 34%, Wald P 0.75). This remained true when each diagnostic category and each CNI drug was separately analyzed. Plasma exchange was rarely performed at our center. Finally, TMA resolution often correlated with improvement of the underlying disorder. The achievement of TMA resolution was associated with significantly improved survival (HR 0.35, P <0.01).Conclusion: Despite meeting the same laboratory definition for persistent MAHA, clinical review revealed heterogeneous disease groups with dissimilar prognostic implications. Our data suggest that TA-TMA is not one disease entity but rather a “final common pathway” for several disorders that likely have different pathophysiologic mechanisms. Instead of empiric treatment with CNI adjustment, we need to identify and understand the underlying causal pathway towards TA-TMA, and to determine if earlier recognition and successful treatment improves patient outcomes. [Display omitted] DisclosuresLee:Kadmon: Other: One-time advisory board member; Amgen: Other: One-time advisory board member; Bristol-Myers-Squibb: Other: One-time advisory board member; Mallinckrodt: Honoraria. Gopal:Seattle Genetics: Consultancy, Research Funding.

Multidrug-resistant organisms in allogeneic hematopoietic cell transplantation.

Multidrug-resistant organisms (MDRO) are a challenge in allogeneic hematopoietic cell transplantation (HCT). However, in the literature there is no comprehensive analysis on MDRO in HCT. In this retrospective, single-center analysis, we appraised prevalence and clinical impact of MDRO in 98 consecutive allogeneic HCT patients. Prior to the conditioning (baseline) and whenever clinically indicated patients underwent a full screening for MDRO (stool and urine cultures, swabs from several body regions). It turned out that 26 patients were colonized by 33 MDRO, either at baseline (n=16) or at any other time until day 100 post-transplantation. Of these 26 patients, eight developed an infection with MDRO, four of them by 4MRGN Pseudomonas aeruginosa, and three of them died MDRO-related. However, there was no significant difference between MDRO-colonized and non-colonized patients regarding overall survival (OS) and non-relapse-mortality (NRM). There was only a trend toward a higher NRM in patients already colonized by MDRO at baseline. This was due to the high NRM in multidrug-resistant P.aeruginosa-colonized patients. In summary, colonization with MDRO other than P.aeruginosa had no negative impact on NRM and OS. Patients colonized by multidrug-resistant P.aeruginosa had a dismal outcome. HCT of these patients should be considered with care. Screening for MDRO in the pretransplant work-up is suggested.

Risk Factors and Outcomes of Invasive Fungal Infections in Allogeneic Hematopoietic Cell Transplant Recipients.

Allogeneic hematopoietic cell transplant (HCT) recipients are at increased risk of invasive fungal infections (IFI), which are associated with a high mortality rate. We evaluated the impact of IFI in allogeneic HCT patients. In total, 541 consecutive allogeneic HCT recipients were included. The cumulative incidence of any IFI and mold infections at 1-year post-HCT was 10 and 7%, respectively. Median times to IFI and mold infection were 200 and 210days, respectively. There was a trend toward fewer IFI and mold infections in the last several years. Both acute graft-versus-host disease (GVHD) (OR 1.83, p=0.05) and corticosteroid duration (OR 1.0, p=0.026) were significantly associated with increased risk of IFI, acute GVHD (OR 2.3, p=0.027) emerged as the most important association with mold infections. Any IFI [HR 4.1 (2.79-6.07), p<0.0001] and mold infections [HR 3.34 (2.1-5.1), p<0.0001] were independently associated with non-relapse mortality (NRM). This association persisted in the setting of both acute and chronic GVHD. Corticosteroid treatment for >90days was also significantly associated with higher NRM [HR 1.9 (1.3-2.6), p<0.0001]. This study highlights the impact of IFI on NRM among HCT patients. The decrease in number of IFI and mold infections over the last several years may reflect the benefit of prophylaxis with mold-active antifungal agents.

Association of socioeconomic status with long-term outcomes in 1-year survivors of allogeneic hematopoietic cell transplantation.

The relationship of socioeconomic status (SES) with long-term outcomes in allogeneic hematopoietic cell transplantation (HCT) survivors has not been well described. We studied the association of SES with the outcomes of 283 consecutive allogeneic HCT recipients transplanted between 2003 and 2012 who had survived for at least 1 year in remission. Median annual household income was estimated using Census tract data and from ZIP code of residence. SES categories were determined by recursive partitioning analysis (low SES (<$51 000/year), N=203; high SES (⩾$51 000/year), N=80). In multivariable analyses, low SES patients had higher risks of all-cause mortality (hazard ratio (HR) 1.98, P=0.012) and non-relapse mortality (NRM) (HR 2.22, P=0.028), but similar risks of relapse mortality (HR 1.01, P=0.97) compared with high SES patients. A trend toward better survival and lower NRM for high SES patients with no chronic GVHD was observed; low SES patients without GVHD had similar survival as patients with chronic GVHD. In allogeneic HCT survivors who survive in remission for at least 1 year, SES is associated with long-term survival that is primarily mediated through higher risks of NRM. More research is needed to understand the mechanisms of health-care disparities and interventions to mitigate them.

Engraftment Syndrome After Allogeneic Hematopoietic Cell Transplantation: Relationship to Acute Gvhd and Impact on Transplant Outcomes

Abstract 3013▪FN2▪This icon denotes a clinically relevant abstract Introduction:The clinical significance of engraftment syndrome (ES) after allogeneic hematopoietic cell transplantation (HCT) is controversial. In order to validate the criteria for ES as described by Spitzer (Bone Marrow Transplant 2001; 27 :893) and to analyze the relationship of ES to acute GVHD (aGVHD), we performed a retrospective review of the incidence of and risk factors for ES and the impact of ES on transplant outcomes in 250 consecutive allogeneic HCT recipients at the MGH between 2000 and 2010. Patients and Methods:After excluding 28 patients with primary graft failure, missing date of engraftment, second or subsequent transplant and syngeneic transplant, 222 patients (128 males, 94 females) with a median age of 53 (range 19–76) yrs were selected for analysis. Underlying diagnoses were AML (32%), NHL/HD (28.8%), MDS (14%) and other (25.2%). 79 patients (35.6%) were in CR, 35 (15.8%) in PR, 65 (29.3%) had refractory disease at the time of transplant, while 43 (19.4%) had either relapsed or progressive disease. Conditioning included either myeloablative (38.3%) or non myeloablative (61.7%) regimens. Donor source was related in 171 (77%) patients (MRD 64.4% vs haploidentical 12.6 %) and unrelated in 51 (23%) patients (MUD 17.6% vs cord blood 5.4%). 71.2% received cyclosporine (CYA) based aGVHD prophylaxis, while 28.8% received non-CYA based prophylaxis. Median time to engraftment was 14 (range 6–65) days. Results:48 of 222 patients (21.6%) met the criteria for ES. Clinical criteria included fever (97.9%), rash (81.3%), weight gain (72.9 %), pulmonary infiltrates (52.1%), elevated creatinine (27.1%), elevated bilirubin (20.8%), transaminitis (20.8 %), and transient encephalopathy (10.4 %). All criteria occurred significantly more commonly in the ES group (p<0.0001 for all except transient encephalopathy, p=0.04). 33 patients (68.8%) with ES received corticosteroids, while 15 patients (31.2%) received only supportive care. 20 (60.6%) of those who received steroids achieved complete resolution of their ES while 11 (33.3%) achieved partial resolution. 2 patients did not respond. With supportive care only, 11 patients (73.3%) achieved complete resolution, while 4 (26.7%) had partial resolution. Using univariable logistic regression analysis, the incidence of ES was not statistically different between the groups according to age, sex, diagnosis, status of the disease at the time of transplant, type of conditioning regimen or the donor type. CYA based aGVHD prophylaxis was associated with a significantly greater risk of developing ES (OR 3.5, 95%CI 1.41–8.71, p=0.007), while transplants after 2006 were associated with a lower risk of ES (OR 0.31, 95%CI 0.16–0.61, p=0.0007). These results are consistent in multivariable analysis: CYA use was associated with a higher risk of developing ES (OR 6.4, 95%CI 1.19–34.4, p=0.03), and transplants after 2006 with a lower risk (OR=0.33, 95% CI 0.14–0.75, p=0.009).16 patients with ES (33.3%) developed early aGVHD within 4 weeks of engraftment vs none who did not develop ES (p <0.0001). The overall rates of aGVHD (47.9% for ES vs 39.1% for non ES, p= 0.32) and of grade 2–4 aGVHD (29.2% vs 23.6%) were not significantly different between the two groups. The incidence of chronic GVHD was also not significantly different between the two groups (42% vs 35%, p=0.24). Although the overall (OS) and progression-free survival (PFS) were shorter in the ES group, the difference was not significant: 2-yr OS and PFS were 45% vs 60% (p=0.1), 33% vs 39% (p=0.09), respectively; HR 1.51 (95%CI 0.97–2.37, p=0.07) for OS, HR 1.44 (95%CI 0.97–2.13, p=0.07) for PFS in multivariable Cox regression analysis. Conclusion:The originally reported clinical criteria that were used to establish a diagnosis of ES (21.6% of patients in this series), were validated in this retrospective analysis of a large cohort of allogeneic HCT recipients receiving diverse conditioning regimens and sources of stem cells. Although predictive for early aGVHD, ES occurred independently of GVHD in more than half of the patients. The reason for the higher incidence of ES in CYA treated patients and patients transplanted before 2006 is unclear and warrants further investigation. A suggestion of inferior OS and PFS in patients who developed ES, apparently independent of GVHD, supports the need to explore early therapeutic intervention to prevent or treat ES. Disclosures:No relevant conflicts of interest to declare.

Observational prospective study of viral infections in children undergoing allogeneic hematopoietic cell transplantation: a 3-year GETMON experience

We studied surveillance, incidence and outcome of viral infections in children undergoing allogeneic hematopoietic cell transplantation (HCT) in the main pediatric transplant units in Spain. We prospectively collected data from first year post-HCT in every consecutive allogeneic HCT performed during 3 years (N = 215): first HCT = 188 and second HCT = 27; median age = 6.6 years (0.1-20.7). Most patients had acute leukemia (N = 137) and 135 recipients (63%) were CMV seropositive. A total of 46 patients underwent cord blood transplant, 133 patients underwent HCT from alternative donors (62%) and 101 patients received anti-thymocyte globulin. Observational time was completed in 137 patients, whereas the remaining 78 died after a median survival time of 99 days (3-352). CMV was monitored in all patients; adenovirus (ADV) and human herpesvirus 6 (HHV-6) were monitored in 101 and 33 patients, respectively. We found 145 viral infections in 103 patients: CMV (n = 42), ADV (n = 32), HHV-6 (n = 7), polyomavirus (n = 20), EBV (n = 6), VZV (n=17) and others (n = 8). CMV infection was significantly higher in seropositive patients (25 vs 7%) (P = 0.02). Extensive chronic GVHD (cGVHD) was significantly associated with an increased rate of viral infections (12 of 16 patients with cGVHD had infections vs 91 of 199 without GVHD) (P = 0.035). In total, 10 patients (4.6%) died of viral infections (CMV = 5, ADV = 3, respiratory = 2). We found a high incidence of viral infection, but mortality was low.

Allogeneic Hematopoietic Cell Transplant for Prolymphocytic Leukemia

The poor prognosis of patients with prolymphocytic leukemia (PLL) has led some clinicians to recommend allogeneic hematopoietic cell transplant (HCT). However, the data to support this approach is limited to case-reports and small case series. We reviewed the database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to determine outcomes after allotransplant for patients with PLL. We identified 47 patients with a median age of 54 years (range: 30-75 years). With a median follow-up of 13 months, progression-free survival (PFS) was 33% (95% confidence interval [CI] 20%-47%) at 1 year. The most common cause of death was relapse or progression in 49%. The cumulative incidence of treatment-related mortality (TRM) at 1-year posttransplant was 28%. The small patient population prohibited prognostic factor analysis, but these data support consideration of allotransplant for PLL. Further study of a larger population of patients is needed to determine which patients are more likely to benefit.

Patterns and kinetics of T-cell chimerism after allo transplant with alemtuzumab-based conditioning: mixed chimerism protects from GVHD, but does not portend disease recurrence

We analyzed the kinetics of CD3 chimerism in 120 consecutive allogeneic hematopoietic cell transplantation (HCT) recipients receiving alemtuzumab-based conditioning. Fifty-two received fludarabine/melphalan, 44 received fludarabine/busulfan, and 24 received clofarabine/melphalan in addition to alemtuzumab. Post-transplant GVHD prophylaxis consisted of tacrolimus. No prophylactic donor lymphocyte infusion or other interventions were used for mixed donor chimerism (MDC). Bone marrow (BM) and/or peripheral blood (PB) samples were obtained at 30 days, 100 days, 180 days, and 1 year following HCT. On Day 30, 15% of assessable patients had MDC in the CD3 compartment. This had increased to 50% by Day 100, and to 63% by Day 180. MDC predicted for a lower risk of acute (p = 0.08) and particularly of chronic GVHD (p = 0.01). MDC was not associated with subsequent relapse or TRM (p = 0.67 and 0.72, respectively). A decline of more than 15% in CD3 chimerism between Day 30 and Day 180 predicted for a 40% risk of subsequent disease recurrence. The observation of MDC after alemtuzumab conditioning does not by itself constitute a risk factor for relapse and should not be used to guide therapeutic intervention. By contrast, declining donor chimerism between Day 30 and Day 180 is associated with a somewhat increased risk of disease recurrence. The high incidence of MDC after alemtuzumab containing conditioning contributes to the low risk of acute and chronic GVHD.