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Cancer immunotherapies are associated with remarkable therapeutic response rates but also with unique and severe toxicities, which potentially result in rapid deterioration in health. The number of clinical applications for novel immune effector-cell therapies, including chimeric antigen receptor (CAR)-expressing cells, and other immunotherapies, such as immune-checkpoint inhibitors, is increasing. In this Consensus Statement, members of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Cell Transplantation-Cancer Immunotherapy (HCT-CI) Subgroup, Paediatric Diseases Working Party (PDWP) of the European Society of Blood and Marrow Transplantation (EBMT), Supportive Care Committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) and MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program collaborated to provide updated comprehensive recommendations for the care of children, adolescents and young adults receiving cancer immunotherapies. With these recommendations, we address emerging toxicity mitigation strategies, we advocate for the characterization of baseline organ function according to age and discipline-specific criteria, we recommend early critical care assessment when indicated, with consideration of reversibility of underlying pathology (instead of organ failure scores) to guide critical care interventions, and we call for researchers, regulatory agencies and sponsors to support and facilitate early inclusion of young patients with cancer in well-designed clinical trials.

A 23-month old female with hypoplastic myelodysplastic syndrome underwent allogenic hematopoietic cell transplantation (HCT), complicated by development of acute exotropia. Bilateral chorioretinal scars and a ring enhancing brain lesion were identified in further workup. Disseminated toxoplasmosis post-allogeneic HCT was subsequently confirmed by serologic and polymerase chain reaction testing results.

Sinusoidal obstructive syndrome, also known as hepatic veno-occlusive disease, is a potentially life-threatening complication that occurs in children undergoing haemopoietic stem-cell transplantation (HSCT). Differences in the incidence of genetic predisposition and clinical presentation of sinusoidal obstructive syndrome between children and adults have rendered the historical Baltimore and Seattle diagnostic criteria insufficient for children. In 2017, the European Society for Blood and Marrow Transplantation (EBMT) proposed the first paediatric diagnostic and severity grading guidelines for sinusoidal obstructive syndrome, intended for implementation across European centres. However, universally accepted paediatric criteria are needed to ensure prompt diagnosis, definitive treatment, and improved outcomes for children, adolescents, and young adults with sinusoidal obstructive syndrome, and to facilitate international clinical research collaboration. We convened an international panel of multidisciplinary experts including physicians with expertise in HSCT, paediatric intensive care, nephrology, hepatology, radiology, pathology, and transfusion medicine; HSCT advanced-practice providers and medical trainees; pharmacists; and translational and basic science researchers from the Pediatric Acute Lung Injury and Sepsis Investigators Network, the EBMT, the Pediatric Blood and Marrow Transplant Consortia, and several other institutions with extensive experience in sinusoidal obstructive syndrome. Panellists convened at The University of Texas, MD Anderson Cancer Center (Houston, TX, USA) in February, 2019, to evaluate the available evidence. In this expert position statement paper, we provide consensus recommendations for the international implementation of guidelines for the diagnosis, severity grading, and treatment of sinusoidal obstructive syndrome among children, adolescents, and young adults. We endorse universal adoption of paediatric diagnostic guidelines for sinusoidal obstruction syndrome as proposed by the EBMT, and provide implementation guidance for standardisation across centres; we have further proposed adjunctive use of age-appropriate organ-specific toxicity criteria for severity grading and provided prophylaxis and treatment considerations among children and adolescent and young adult patients. Key recommendations include: (1) liver biopsy, portal venous wedge pressure, and reversal of portal venous flow on Doppler ultrasonography should not be used for the routine diagnosis of sinusoidal obstructive syndrome in children, adolescents, and young adults; (2) platelet refractoriness can be defined as a corrected count increment of less than 5000-7500 following at least two sequential ABO-compatible fresh platelet transfusions; (3) hepatomegaly is best defined as an absolute increase of at least 1 cm in liver length at the midclavicular line; and if a baseline measurement is not available, hepatomegaly can be defined as greater than 2 SDs above normal for age; and (4) the presence and volume of ascites can be categorised as mild (minimal fluid by liver, spleen, or pelvis), moderate (1 cm fluid), or severe (fluid in all three regions with1 cm fluid in at least two regions).

Background Immunosuppressive prophylaxis is usually given to decrease the development of acute graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Belatacept is a Cytotoxic T-lymphocyte-associated protein 4, blocking agent, an immunosuppressive agent used for organ rejection prevention in adult renal transplant recipients. Methods We describe two children in whom belatacept was successfully used for GvHD prophylaxis. Case 1 was noncompliant with prior immunosuppressive therapy for aplastic anemia, and Case 2 developed severe thrombotic microangiopathy (TMA) precluding the use of calcineurin inhibitors (CNI) or mTOR inhibitors. Results and conclusion Belatacept was found to be a safe alternative in preventing GvHD in 2 patients in whom traditional prophylactic therapies were not possible to use.

Vitamin D not only plays an important role in bone metabolism but is also involved in multiple immune-mediated processes in the body which may be adversely affected in those with low levels. Most pediatric studies evaluating the association of vitamin D in patients undergoing allogeneic HSCT are single-center studies. We present the results of retrospective study at 5 centers across the United States in pediatric patients undergoing allogeneic HSCT. (VDD) and (VDI) were defined by vitamin D levels of

Pediatric HSCT patients endure complicated treatment regimens, lifestyle modifications, and a lifetime of long-term follow-up. Treatment adherence in this population is understudied and prevalence unknown. Providers (physicians and advanced practice nurses) in this study completed an online-structured questionnaire about definition, assessment, and perceived rates of adherence. Researchers' extracted 187 statements from participants' responses. The majority (n = 12, 71%) of providers reported adherence as a primary concern in outpatient HSCT. The major concern for providers was the potential of non-adherence to negatively affect outcomes. Providers also shared clinical examples of non-adherence. This study contributes to a better understanding of providers' perceptions of adherence within pediatric HSCT. Additional research is needed to describe, define, and improve adherence in pediatric HSCT to ultimately improve outcomes and quality of life for this vulnerable population.

In 2017, an autologous chimeric antigen receptor (CAR) T cell therapy indicated for children and young adults with relapsed and/or refractory CD19+ acute lymphoblastic leukaemia became the first gene therapy to be approved in the USA. This innovative form of cellular immunotherapy has been associated with remarkable response rates but is also associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration. Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care. Herein, authors representing the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Stem Cell Transplantation (HSCT) Subgroup and the MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program have collaborated to provide comprehensive consensus guidelines on the care of children receiving CAR T cell therapy., Chimeric antigen receptor (CAR) T cell therapies have impressive activity in the treatment of cancer but are associated with potentially fatal toxicities. In light of the approval of CAR T cell therapy for paediatric patients, a panel of experts from the Hematopoietic Stem Cell Transplantation (HSCT) Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, the CAR T Cell Therapy-Associated Toxicity (CARTOX) Program at The University of Texas MD Anderson Cancer Center, and several other institutions have developed consensus guidelines for the use and management of these treatments in paediatric patients, which are presented herein.

Hematopoietic cell transplant (HCT) is associated with a proinflammatory, procoagulant environment that places recipients at increased risk of venous thromboembolism (VTE). Although the incidence of VTE in adult HCT recipients has been extensively studied, similar data for children are lacking. We conducted a multicenter retrospective study to analyze the prevalence of VTE and associated risk factors in a large cohort of patients who underwent HCT at tertiary care US children's hospitals. The Pediatric Health Information System database, a large administrative database that contains clinical and resource utilization data from 49 freestanding children's hospitals in the United States, was used to extract data. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify HCT recipients, VTE events, post-HCT complications, and associated risk factors up to 1 year post-transplant. Data on patients who received HCT from January 2010 through September 2014 were collected. A total of 4158 unique patients mean ± standard deviation age at transplant admit, 8.8 ± 6.5 years; range, birth to 33.4 years) were identified. After HCT 290 subjects (6.9%) developed VTE. VTE prevalence was greater in patients aged ≥ 13 versus13 years (8.54% versus 6.33%; P = .01) and in recipients of allogeneic versus autologous grafts (7.7% versus 5%; P ≤ .01). VTE was associated with prolonged median duration of hospitalization (81 versus 54 days; P ≤.01) and increased 1-year mortality (13.9% versus 5.9%; P ≤ .01). Infections and presence of any graft-versus-host disease (GVHD) were significantly associated with VTE occurrence in recipients of allogenic grafts. Prevalence of VTE in patients who underwent HCT at pediatric tertiary care hospitals is about 7%. Age ≥ 13 years and allogeneic grafts were significant pre-HCT VTE risk factors, with GVHD and infections seen more frequently in patients with VTE.

Very young children undergoing hematopoietic cell transplantation (HCT) are a unique and vulnerable population. We analyzed outcomes of 717 patients from 117 centers who survived relapse free for year after allogeneic myeloablative HCT for hematologic malignancy at = 1 organ toxicity/late effect >1 year after HCT. The most frequent late effects included growth hormone deficiency/growth disturbance (10-year cumulative incidence, 23%; 95% CI, 19% to 28%), cataracts (18%; 95% CI, 15% to 22%), hypothyroidism (13%; 95% CI, 10% to 16%), gonadal dysfunction/infertility requiring hormone replacement (3%; 95% CI, 2% to 5%), and stroke/seizure (3%; 95% CI, 2% to 5%). Subsequent malignancy was reported in 3.6%. In multivariable analysis, total body irradiation (TBI) was predictive of increased risk of cataracts (HR, 17.2; 95% CI, 7.4 to 39.8; P

Vitamin D deficiency (VDD) has been linked to multiple autoimmune disorders because of its importance in self-tolerance and effect on multiple immune system cells. A few studies have shown that patients with VDD may have increased risk of GvHD, CMV infection and decreased overall survival after HSCT, conversely, a study from Brazil showed no such correlations. To better identify the role of vitamin D in children undergoing HSCT, we present the results of a retrospective multicenter study. Records of patients who underwent allogeneic HSCT from January 1, 2012 until June 2017 were reviewed. VDD and insufficiency was defined by vitamin D levels of ≤20 ng/mL and 21-30 ng/mL, respectively. A total of 316 patients were enrolled on the study, of these 276 had at least 1 vitamin D level (pre or post HSCT) and 192 patients had two levels (pre and post HSCT). Patient characteristics and survival graphs are shown in Table 1, Figure 1 and 2 respectively. Severe chronic GvHD was more commonly seen in patients with VDD (p=0.0237). There was no correlation of VDD with the rate of infections (viral, bacterial or fungal), length of hospitalization, neutrophil engraftment, graft failure, or acute GvHD; there were more relapses in patients with normal Vitamin D levels. This retrospective study found that patients with VDD have a slightly higher incidence of severe chronic GvHD, which may explain the lower relapse rate in the VDD group, higher relapse rate in those with normal vitamin D levels but no correlation with all other patient outcomes after HSCT. A small sample size, variability in the accuracy of the assay used to test for vitamin D levels may be some of the limitations. A larger prospective study is needed to help understand the role of vitamin D in children undergoing allogeneic HSCT.

Hepatic veno-occlusive disease (VOD), or sinusoidal obstruction syndrome, is a potentially fatal complication, which occurs in 7–27% of children undergoing hematopoietic stem cell transplantation. In this article, we review commonly accepted diagnostic criteria, atypical diagnostic features as well as preventative and treatment measures associated with VOD. Reversal of portal venous flow by Doppler ultrasound is often a late finding; many patients with anicteric VOD may never develop hyperbilirubinemia, and yet perish from severe VOD. Transjugular liver biopsy is usually not available and/or is often avoided. Prophylactic therapies with ursodeoxycholic acid, heparin and defibrotide are discussed. Supportive care with fluid restriction and diuretic therapy, analgesia, blood and platelet transfusions, paracentesis as well as other pulmonary and renal therapies remain imperative to superior outcomes. Specific therapy with thrombolytics such as defibrotide and recombinant tissue plasminogen activator is discussed and a classification of severity of VOD is proposed.

Pre-existing endothelial dysfunction and vascular injury sustained during allogeneic hematopoietic stem cell transplantation (HCT) increases risk for endothelial injury-related complications like posterior reversible encephalopathy (PRES) and transplant-associated thrombotic microangiopathy (TA-TMA) in patients with sickle cell disease (SCD). Herein, we report two SCD HCT recipients in whom PRES-related symptoms resolved only after eculizumab therapy was initiated for underlying TA-TMA. Case 1 25-year-old male with SCD developed PRES-related seizures and headaches on Day+30 following matched sibling donor bone marrow transplant (BMT) and reduced-intensity conditioning (RIC) with fludarabine/melphalan/alemtuzumab and graft-versus-host disease (GvHD) prophylaxis with tacrolimus and methotrexate (MTX). Symptoms initially resolved after discontinuing tacrolimus. However, on Day+60, he presented with hypertension (HTN), status epilepticus, and right intracranial hemorrhage. Despite adequate HTN control and maximal anti-epileptic therapy, his symptoms persisted. Two weeks later, laboratory testing confirmed TA-TMA. Both PRES and TA-TMA symptoms and signs resolved after five weeks of eculizumab therapy (Figure 1). Case 2 Eight-year-old female with SCD underwent 10/10 matched unrelated BMT following RIC with fludarabine/melphalan/thiotepa/alemtuzumab and MTX/tacrolimus/abatacept for GvHD prophylaxis. She developed altered mental status, seizures, and HTN and Day+74 MRI brain confirmed PRES. Her symptoms also persisted despite tacrolimus cessation and effective HTN control. One week later, laboratory testing confirmed TA-TMA. Complete resolution of neurological symptoms occurred after three weeks of eculizumab therapy. (Figure 2). Conclusion Our cases highlight maintaining a high level of clinical suspicion for TA-TMA in SCD patients presenting with PRES post-HCT and consideration for eculizumab therapy in such patients.

For patients with DBA who are transfusion dependent, HSCT is the only cure. Chronic transfusions can lead to cirrhosis secondary to iron overload, making them poor candidates for myeloablative HSCT. RIC regimens are associated with lower morbidity and mortality compared to myeloablative regimens, but use of RIC in DBA has been limited. Here we present a 14-yr-old girl with DBA and multiple comorbidities including liver cirrhosis, who underwent MUD HSCT utilizing a RIC regimen that is novel to this condition. She tolerated the regimen well, and at 21 months, she remains transfusion independent with chimerisms at 99%.

Veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). Patients with VOD are often critically ill and require close collaboration between transplant physicians and intensivists. We surveyed members of a consortium of pediatric intensive care unit (PICU) and transplant physicians to assess variability in the self-reported approach to the diagnosis and management of VOD. An internet-based self-administered survey was sent to pediatric HSCT and PICU providers from September 2014 to February 2015. The survey contained questions relating to the diagnosis and treatment of VOD. The response rate was 41% of 382 providers surveyed. We found significant variability in the diagnostic and management approaches to VOD in children. Even though ultrasound is not part of the diagnostic criteria, providers reported using reversal of portal venous flow seen on abdominal ultrasound in addition to Seattle criteria (70%) or Baltimore criteria to make the diagnosis of VOD. Almost 40% of respondents did not diagnose VOD in anicteric patients (bilirubin2 mg/dL). Most providers (75%) initiated treatment with defibrotide at the time of diagnosis, but 14%, 7%, and 6% of the providers waited for reversal of portal venous flow, renal dysfunction, or pulmonary dysfunction, respectively, to develop before initiating therapy. Only 50% of the providers restricted fluids to 75% of the daily maintenance, whereas 21% did not restrict fluids at all. Albumin with diuretics was used by 95% of respondents. Platelets counts were maintained at 20,000 to 50,000/mm(3) and 10,000 to 20,000/mm(3) by 64% and 20% of the respondents, respectively. Paracentesis was generally initiated in the setting of oliguria or hypoxia, and nearly 50% of the providers used continuous drainage to gravity, whereas the remainder used an intermittent drainage approach. Nearly 73% of the transplant providers used VOD prophylaxis, whereas the remainder did not use any medications for VOD prophylaxis. There was also considerable variation in the management strategies among the transplant and critical care providers. We conclude that there is considerable self-reported variability in the diagnosis and management of VOD in children. The practice variations reported in this study should encourage the development of standard practice guidelines, which will be helpful in improving the outcome of this potentially fatal complication.

Hepatic veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Untreated hepatic VOD/SOS with multi-organ failure (MOF) is associated with >80% mortality. Defibrotide has shown promising efficacy treating hepatic VOD/SOS with MOF in phase 2 studies. This phase 3 study investigated safety and efficacy of defibrotide in patients with established hepatic VOD/SOS and advanced MOF. Patients (n = 102) given defibrotide 25 mg/kg per day were compared with 32 historical controls identified out of 6867 medical charts of HSCT patients by blinded independent reviewers. Baseline characteristics between groups were well balanced. The primary endpoint was survival at day +100 post-HSCT; observed rates equaled 38.2% in the defibrotide group and 25% in the controls (23% estimated difference; 95.1% confidence interval [CI], 5.2-40.8;P= .0109, using a propensity-adjusted analysis). Observed day +100 complete response (CR) rates equaled 25.5% for defibrotide and 12.5% for controls (19% difference using similar methodology; 95.1% CI, 3.5-34.6;P= .0160). Defibrotide was generally well tolerated with manageable toxicity. Related adverse events (AEs) included hemorrhage or hypotension; incidence of common hemorrhagic AEs (including pulmonary alveolar [11.8% and 15.6%] and gastrointestinal bleeding [7.8% and 9.4%]) was similar between the defibrotide and control groups, respectively. Defibrotide was associated with significant improvement in day +100 survival and CR rate. The historical-control methodology offers a novel, meaningful approach for phase 3 evaluation of orphan diseases associated with high mortality. This trial was registered at www.clinicaltrials.gov as #.

MS and endocrine dysfunction(s) are common well-recognized complications after HSCT. We retrospectively analyzed our data on 160 patients with a median age at transplant of five yr (0.3-23), who had been followed for a median of seven yr (range 3-18) at Nationwide Children's Hospital after transplant. Dyslipidemia and MS were seen in 13% and 7.5% patients, respectively, and 58% of these patients were

Background Hematopoietic cell transplant (HCT) may be a risk factor for morbidity and mortality from respiratory syncytial virus (RSV). Previous studies have been limited by small sample size. We took a multicenter approach with the goal of better understanding the epidemiology, risk factors, treatment, morbidity, and mortality associated with RSV infections among children with HCT in the United States. Methods A retrospective, multicenter, cohort study of pediatric HCT recipients were diagnosed with RSV infection between January 2010 and December 2014. Results Of the 1522 HCT, 47 (3%) patients were diagnosed with RSV. Of those with RSV, 9 (19.1%) were admitted to the pediatric intensive care unit (PICU), 6 (12.8%) received invasive mechanical ventilation, and 1 died. Prophylactic palivizumab was uncommon. All who required critical care received ribavirin vs 7.3% of those who did not (P = .004). Cobacterial infections were found in 16 patients and were not associated with the need for critical care. We examined potential risk factors for severity of RSV disease. In those who received invasive ventilation, 100% had one of the preidentified risk factors. Half of those requiring mechanical ventilation were diagnosed with RSV during their conditioning for transplant as opposed to only 2.4% of those that did not require invasive mechanical ventilation (P = .005). Conclusions In this multicenter cohort, RSV was not common in children following HCT. Few children infected with RSV required critical care and mortality was low. Those diagnosed with RSV during conditioning for transplant were at higher risk for invasive mechanical ventilation.

Anti-seizure prophylaxis is routinely utilized during busulfan administration for HSCT. We evaluated the feasibility and efficacy of levetiracetam in children undergoing HSCT. A total of 28 children and young adults received levetiracetam during HSCT and the outcomes and costs were compared to a historical, but similar cohort of 25 patients who had received fosphenytoin. Levetiracetam was well tolerated and was efficacious in preventing seizures. Cost of drug, administration, and monitoring were also similar among the two groups. Due to non-induction of the hepatic cytochrome P450 enzymes, levetiracetam may lead to better dose assurance of busulfan in targeted dose regimens for HSCT.

Allogeneic HCT is curative for SCN; however, a standard conditioning regimen or intensity has not been established. We describe a patient with SCN associated with c.1A>G (M1V) mutation in ELANE gene resulting in refractoriness to G-CSF, who received reduced-intensity HCT and developed secondary graft failure requiring a second myeloablative HCT. This case suggests that M1V mutation confers a poor G-CSF response and HCT using the best available donor is beneficial.

Matched sibling donor hematopoietic stem cell transplantation is the standard of care for severe aplastic anemia, with an overall survival of 80% to 90%. Only 60% to 70% of patients respond to treatment with immunosuppressive therapy. The main life threatening complications are infections, graft failure, and graft versus host disease. A 10-year-old patient with severe aplastic anemia underwent matched sibling donor hematopoietic stem cell transplantation, but developed sudden onset of fatal multiorgan failure on day +12. The cause of death was found only after autopsy.

CAMT is a bone marrow failure syndrome that usually presents with isolated thrombocytopenia soon after birth. HSCT is curative, and MAC is associated with increased transplant-related morbidity and mortality, especially in the unrelated setting. We used a RIC regimen with alemtuzumab, fludarabine, and melphalan in a seven-month-old patient with CAMT who underwent a MUD HSCT. The transplant was well tolerated with few complications. Neutrophil and platelet engraftment occurred on day +12 and +29, respectively, and she had 100% donor chimerisms on days +19.

Relapse after allogeneic hematopoietic SCT (HSCT) carries a poor prognosis and is a common cause of death. Outcomes of children who relapse post HSCT are not well known. In this retrospective multicenter study we included 532 patients who underwent allogeneic HSCT and examined the outcomes of 160 patients (30%) who relapsed. Treatment options after relapse included (i) palliative therapy with non-curative intent (n=43), (ii) salvage chemotherapy (without a second HSCT, n=55) or (iii) salvage chemotherapy followed by a second HSCT (n=62). Sixty two patients underwent a second HSCT. The 1-year disease-free survival (DFS) for those given palliative therapy, chemotherapy alone and who underwent a second transplant was

Autoimmune lymphoproliferative syndrome (ALPS), a disorder of programmed cell death, could be due to a congenital defect in the Fas signaling pathway or other pathways for apoptosis. Most cases present with lymphoproliferation and certain autoimmune features such as thrombocytopenia, neutropenia, and anemia are due to excessive production of antibodies by B lymphocytes. Majority of cases present within the first few years of life. We report a case of ALPS presenting at birth which was refractory to splenectomy and immunosuppressive therapy, but responded to pentostatin followed by hematopoietic stem cell transplantation (HSCT). Pediatr Blood Cancer 2011; 57: 336–337. © 2011 Wiley-Liss, Inc.

Severe congenital neutropenia is an autosomal recessive disorder characterized by maturation arrest at the promyelocyte/myelocyte phase in the bone marrow, absolute neutrophil count

Abstract 4472 Introduction: Children undergoing hematopoietic stem cell transplantation (HSCT) are at risk of developing vitamin D deficiency (VDD). However, data on vitamin D status and its correlation with bone mineral density (BMD) in the long term survivors after childhood HSCT is limited. The aim of this study was to determine the prevalence of VDD among long term survivors after HSCT in childhood, and to evaluate the correlations between vitamin D and BMD. Methods: A retrospective study was carried out in patients seen in Long Term follow-up Clinic (LTFC) at our institution from January 2011 to July 2012. Vitamin D deficiency (VDD) and insufficiency (VDI) were defined as serum 25-hydroxyvitamin D (25-OHD) Results: Ninety eight patients underwent 103 HSCTs between 1990 and 2010. Fifty two (53%) patients were > 5 years out of transplant. A total of 114 vitamin D levels were recorded for the 98 patients, the median 25-OHD level was 26 (range 7 – 68 ng/mL). In 68/114 (60%) observations the 25-OHD levels were less than < 30ng/mL. Of these, 10 (9%) patients had VDD (levels < 15ng/mL, while 58 (51%) had VDI. There were no significant correlations between 25-OHD levels and age at HSCT, gender, underlying diagnosis, type of transplant, or development of acute or chronic GVHD (Table 2). There was a trend towards lower 25-OHD levels after non-TBI based conditioning regimen (p = 0.047). BMD was performed in 83 patients (85%). Low BMD was found in nearly one-third to half of patients tested: 29%, 54%, and 33% of the patients had BMDlumbar, BMDhip and BMDWB Z scores of < −1.0, respectively, while 5%, 9% and 5% of the patients had BMDlumbar, BMDhip and BMDWB Z scores < −2.5, respectively. The median Z scores of the BMDlumbar, BMDhip, and the BMDWB were −0.3 (range −4.2 to 2.4), −1.1 (range −3.3 to 1.9), and −0.4 (range −5.4 to 2.7) respectively. In patients with BMD < −2.5 and < −1.0, the corresponding median 25-OHD was 26 (range 7 – 62 ng/mL) and there was no significant association. Spearman correlation between 25-OHD D level, BMDWB and BMDlumbar showed a correlation coefficient of −0.24 (p value: 0.0409) and −0.22 (p value: 0.0546) respectively. There was no correlation between normal vitamin D levels, VDI and VDD with BMD of the hip, lumbar spine and whole body. Discussion: Low 25-OHD ( Disclosures: No relevant conflicts of interest to declare.

Abstract 838 Background: Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in persons with Fanconi anemia (FA). However, results in those with pretransplant cytogenetic abnormalities (CA), myelodysplastic syndrome (MDS) or acute leukemia (AL) are less favorable, although only limited data are available. Thus, the current study was designed to use data from the Center for International Blood and Marrow Transplant Research (CIBMTR) to evaluate the outcomes of these patients after HCT. Patients and Methods: This is a retrospective analysis of 113 FA patients with CA (n=54), MDS (n=45), or AL (n=14) before allogeneic HCT, and who were reported to CIBMTR from 1985 to 2007 by 46 centers worldwide. Overall survival (OS) probability was estimated using the Kaplan-Meier method. Engraftment and acute and chronic graft-vs-host-disease (GvHD) were determined using cumulative incidence estimates to accommodate competing risks. Univariate analyses were conducted to evaluate the prognostic impact of key variables. The small sample size precluded multivariate analysis. Fifty four patients had CA including complex abnormalities (n=18), chromosome (Chr) 1 abnormalities (n=8), chr 3 abnormalities (n=1), chr 5 abnormalities (n=3), chr 7 abnormalities (n=4) and other non-complex abnormalities (n=20). Pretransplant conditioning regimens were radiation-based in 67 patients and chemotherapy-based in 46 patients. The donor source was bone marrow/peripheral blood (matched related, n=82; unrelated, n=16), or cord blood (related, n=2; unrelated, n=13). Results: Absolute neutrophil count (ANC) recovery occurred in 78% and 85% of patients, at day 28 and day 100, respectively. At day 100, the cumulative incidences of acute GvHD grade II–IV and III–IV were 26% (95% confidence intervals [CI] 19–35), and 12% (95% CI 7–19), respectively. Chronic GvHD cumulative incidences were 20%, 23%, and 23% at 1, 3, and 5 years, respectively. Primary graft-failure occurred in 18 patients. Cumulative incidence of secondary graft-failure at 2 years was 9% (95% CI 4–15). Survival probabilities were 64%, 58%, and 55% at 1, 3, and 5 years, respectively. Exclusion of subjects with chr 1 abnormalities did not alter the results (log-rank P value=.81). In univariate analysis, among the entire cohort, none of the following variables affected survival: use of fludarabine or radiation in the conditioning regimen, the presence of AL/MDS as compared to only CA, or year of transplant. Age at transplant was the only variable significantly correlated with 5-year OS (≤ 14 years vs. > 14 years, 69% vs. 39%, respectively; P =0.001). When analysis was restricted to recipients of related donor HCT (n=82), age again correlated with 5-year survival (≤ 14 years vs. > 14 years, 78% vs. 34%, respectively; P Conclusion: Our analysis indicates that persons with FA and pretransplant CA, MDS, or AL have a reasonable survival with HCT. The analysis also suggests that survival may be better in younger persons and in those with only CA pretransplant. No firm conclusions can be drawn from this study regarding the impact of the conditioning regimens; the current data, however, suggest that radiation-based conditioning regimens are not associated with a survival advantage as has been suggested by previously published data. Disclosures: No relevant conflicts of interest to declare.

Abstract 2280 Poster Board II-257 The HLA Class II antigen DR15 (common alleles 1501, 1502) is of interest in the pathobiology of T-lymphocyte mediated marrow failure (myelodysplastic syndrome (MDS), severe aplastic anemia (SAA) and paroxysmal nocturnal hemoglobinuria (PNH). Available data suggest that the presence of DR15 in patients with MDS is associated with an increased response rate to immunosuppressive therapy (IST) with ATG. While DR15 is overrepresented in patients with SAA and PNH, its presence has not been clearly shown to correlate with outcome after hematopoietic stem cell transplant in these diseases. We studied 1422 patients with SAA (30% were DR15+) who received HLA-identical sibling bone marrow (85%) or peripheral blood progenitor cells (15%) and were transplanted in 1990 – 2006 to determine whether the presence of HLA DR15 affected hematopoietic recovery, graft-versus-host disease or overall survival. The study was confined to matched sibling transplants to eliminate HLA-disparity as a driving force for any observed differences. High resolution HLA typing to discriminate between DR15 and DR16, the serological splits of DR2 was available for all subjects. Most patients (80%) had idiopathic SAA and 50% of patients were Caucasian. Patient, disease and transplant characteristics of patients with and without DR15 were similar. Proportions of patients who had received prior IST were similar among those with and without DR15. In multivariate analysis, after adjustment for significant factors, neutrophil recovery at day 28 (odds ratio [OR] 1.02, p=0.905), platelet recovery at day 100 (OR 0.95, p=0.776), secondary graft failure at 2 years (OR 0.66, p=0.123), acute (hazard ratio [HR] 0.88, p=0.345) and chronic (HR 1.09, p=0.519) graft-versus-host disease and overall mortality (HR 1.22, p=0.102) risks were similar in patients with and without DR15. Factors associated with higher mortality after transplantation included aracteristics as reported previously, including age older than 40 years (HR 2.74, p Disclosures: No relevant conflicts of interest to declare.