HSCT Survivors Research Articles

The late effects of haematopoietic stem cell transplants in paediatric patients: a 25 year review.

A rare, large single centre study covering all long-term health outcomes of paediatric allogeneic HSCT survivors, to provide comprehensive local data, and identify gaps and future directions for improved care. To document endocrine sequelae and other late effects of all HSCT recipients. Retrospective review. Royal Children's Hospital Melbourne. 384 children and adolescents received HSCT. 228 formed the study cohort; 212 were alive at commencement of data accrual. None. Incidence of endocrinopathies; fertility, growth, bone and metabolic status; subsequent malignant neoplasms (SMNs). Gonadotoxicity was more common in females (p<0.001). Total body irradiation (TBI) conditioning was more toxic than chemotherapy alone. All females receiving TBI or higher cyclophosphamide equivalent doses (CED) developed premature ovarian insufficiency (POI) . In males, impaired spermatogenesis +/- testicular endocrine dysfunction was associated with increasing testicular radiation exposure. Preservation of gonadal function was associated with younger age at HSCT. Of sexually active females, 22% reported spontaneous pregnancies. Short stature was common, with growth hormone axis disruption in 30% of these. Of patients exposed to thyroid radiation 51% developed nodules, 30% malignant. Metabolic disturbances included hypertension, dyslipidemias, with both excess and underweight reported. Fragility fractures occurred in 6%; avascular necrosis in 6%. 13% developed SMNs, risk continuing to rise throughout follow-up. We confirm gonadal dysfunction, multiple endocrine and metabolic abnormalities, thyroid cancer and SMNs, as common sequelae of HSCT, and identify gaps in management - particularly the need for informed fertility counselling and pretreatment fertility preservation, evaluation and management of bone health, and underline need for early lifestyle modification, long-term surveillance, and prospective planned studies aimed at reducing complication risk.

Taste alterations in patients following hematopoietic stem cell transplantation: A qualitative study

ObjectiveThis study aims to explore the experiences and consequences of taste alterations in patients undergoing HSCT, how they respond to these changes, and the factors that influence their responses. MethodsIn this descriptive qualitative study, face-to-face semi-structured individual interviews were conducted with 31 patients undergoing HSCT in a comprehensive hospital in Hubei, China. The interview data were transcribed and analyzed using Colaizzi's seven-step analysis. The Symptom Management Theory was applied to design the study and identify key themes. ResultsThree key themes were identified from the theory: (1) the complexity and diversity of taste experiences; (2) coping strategies; and (3) the multifaceted challenges of coping. Taste alterations in HSCT patients were characterized by diversity and dynamism. Patients employed three distinct coping styles in response to taste alterations: active coping, reluctant submission, and passive coping. These coping styles were influenced by various factors, including the specific treatment modalities of HSCT, individual patient characteristics, and the healthcare environment. ConclusionsThe experience of taste alterations among HSCT patients is intricate and varied, and the importance of addressing this symptom can easily be underestimated. Management of taste alterations is influenced by multiple factors. Nursing staff should give careful attention to taste alterations in HSCT survivors, enhance their expertise in managing taste alterations, provide robust health education, conduct regular screening and assessments, and formulate individualized intervention plans to assist patients in actively and effectively managing taste alterations.

Long-term survivors demonstrate superior quality of life after haploidentical stem cell transplantation to matched sibling donor transplantation

BackgroundIt has been well-documented that haplo-identical hematopoietic stem cell transplantation (HID-HSCT) can provide outcomes comparable to conventional matched sibling donor (MSD) HSCT, however, little is known about the effects on quality of life (QoL) in long-term survivors. This study is to investigate the differences in longitudinal performance of QoL between HID and MSD HSCT using a comprehensive assessment system.MethodsThis prospective study enrolled consecutive patients who had received allogenic-HSCT (allo-HSCT) between January 2018 and December 2019 in our center. All patients were informed to complete QoL questionnaires including the Mos 36-Item Short-Form Health Survey (SF-36) and the Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT, version 4), using an online applet, before transplantation and at scheduled time points after transplantation. The linear mixed-effects model was used to analyze the variation trend of different dimensions of both SF-36 and FACT-BMT with different follow-up times.ResultsOf the 425 participants, recipients of HID and MSD who survived more than 1 year (n = 230) were included in the final analysis of QoL (median age [range]: 36, [15, 66]). The 3 year overall survival (OS) of HID and MSD was 82.42% and 86.46%, respectively. QoL was assessed using both SF-36 and FACT-BMT and there was longitudinal recovery with clinical significance in the cohort. Compared to MSD-HSCT patients, HID-HSCT recipients demonstrated superior QoL performance in some subscales describing physical and mental wellness. Specifically, the difference in physical performance is more remarkable using FACT-BMT whereas that in mental wellness is more significant using SF36. In the subsequent stratified analysis, patients with a history of aGVHD or CMV reactivation demonstrated inferior QoL.ConclusionsLong-term survivors of HID HSCT achieved better QoL in some sub-scales compared to MSD HSCT. In addition, SF-36 and FACT-BMT demonstrated different performance thus combination of both improved capacity of the evaluation system.

Kidney Dysfunction Post-Allogeneic Transplant: High Incidence of TMA and Kidney GvHD

Introduction:Kidney dysfunction is an important problem in adult recipients of allogeneic stem cell transplantation (HSCT) and independently predicts overall survival and non-relapse mortality. Kidney dysfunction occurs in ~50% of transplant recipients. More than 20% of all survivors of HSCT in long-term follow up develop chronic kidney disease. However, there is currently limited data on the cause and consequences of kidney dysfunction in adult recipients after allogeneic HSCT.Common causes of kidney dysfunction after HSCT include chemotherapy or radiation toxicity, infections, sepsis, hepatic sinusoidal obstruction, drug toxicities due to immunosuppressive medications, thrombotic microangiopathy, as well as acute or graft versus host disease (GvHD). Kidney biopsies are seldom obtained and hence the tissue diagnosis in these patients often remains speculative. Early identification of the causes of kidney dysfunction may help define preventive and therapeutic strategies and improve outcome.Hence, in August 2016, we designed a prospective study at our center to systematically evaluate kidney dysfunction in adult recipients of allogeneic HSCT. Herein we present our initial report of 8 kidney biopsies.Methods:All adult HSCT recipients with kidney dysfunction were evaluated by Nephrologists to determine the need for kidney biopsy. Kidney dysfunction was defined as either (i) acute kidney failure or (ii) proteinuria. Acute kidney failure was defined by the ‘ Kidney Disease: Improving Global Outcomes (KDIGO)‘ criteria. Proteinuria was defined as (i) spot urine albumin to creatinine ratio of ≥1 (equivalent to ≥1 g in 24 hours). Kidney biopsies were done under ultrasound guidance and the tissue specimens were interrogated by light, immunofluorescence and electron microscopy.Results:A total of 8 HSCT recipients (including one patient who had a biopsy prior to Aug 2016) underwent kidney biopsies. The patient and transplant characteristics are summarized in Table 1.Seven of the 8 pts had AML. One patient had NHL in CR2. Four patients received a MUD transplant. Two received MRD transplants. Two received combined haploidentical and single unit cord blood transplant (haplo-cord). Six of the 8 patients received conditioning with fludarabine and melphalan. One patient received additional 400 Gy TBI. One patient received additional azacytidine.Median time to neutrophil engraftment was 13.5 days (range 9-20). Median time to platelet engraftment was 19 days (range 14-76). There were no cases of graft failure. All patients also demonstrated either acute or chronic GvHD of other organs - most commonly skin.All kidney biopsies were performed without complications. Kidney biopsies were done at median 254 days after transplantation (range 126-680). Baseline serum creatinine (mg/dL) prior to transplant was 0.95 (median, range 0.65-1.1, reference range: 0.64-1.27 mg/dL). Creatinine at time of biopsy: 3.0 (median, range 1.53-5.07). Urine albumin/creatinine ratio: 832 (median, range 55-2864, reference range: <30).The kidney biopsy findings are summarized in Table 2. All patients had evidence of endothelial cell injury, either acute or chronic. Three patients had features suggestive of GvHD of the kidney while one patient had BK virus nephropathy.Four of the 8 recipients died; 80 days (median, range 39-124) from the biopsy, 346 days (median, range 178-804) from transplantation. The clinical outcome is summarized in Table 3.Conclusions:Kidney biopsies post-transplant are an important diagnostic tool that should be considered for prolonged kidney dysfunction or proteinuria, particularly in the setting of other post-transplant complications. Our single-center biopsy results highlight the under-recognition of kidney dysfunction complications and complexities observed post-transplant. All kidney biopsies performed were instrumental in treatment planning. Further investigation is needed to define criteria for diagnosis and to understand the pathophysiology. This requires multi-disciplinary engagement as well as a proactive approach for obtaining kidney biopsies. With appropriate transfusion support, percutaneous kidney biopsies were performed safely without complication. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Psychometric properties of the Arabic version of the medical outcomes study social support survey in cancer survivors post-HSCT

ABSTRACT The purpose of this study was to evaluate the reliability and validity of the Arabic version of the Medical Outcomes Study Social Support Survey (MOS-SSS) in Arabic cancer survivors post-Hematopoietic Stem Cell Transplantation (HSCT). This study of existing cross-sectional data was conducted using data from 63 Arabic patients who were at least three months post-HSCT. The data demonstrated that the Cronbach’s alphas for the Arabic version of the MOS-SSS subscales were strong, indicating good internal consistency. Factorial validity of the Arabic version was supported using confirmatory factor analysis; the MOS-SSS had a four-factor, multidimensional structure as hypothesised. Convergent validity with the EORTC QLQ-C30 also was supported. In conclusion, this study showed that the Arabic version of the MOS-SSS demonstrated excellent evidence of convergent and factorial validity as well as strong internal consistency reliability in this sample of Arabic HSCT survivors.

Survivorship care for allogeneic transplant patients in the UK NHS: changes centre practice, impact of health service policy and JACIE accreditation over 5 years.

Care of long-term survivors of allogeneic transplant is known to be variable despite international guidelines and accreditation standards. In 2014 a survey of UK NHS-based adult transplant centres identified significant barriers to delivery of long-term follow-up services. In 2019, we repeated the survey to assess changes over a 5-year period when health service policies had mandated JACIE accreditation incorporating standards for long-term care. Improvements were seen in the number of centres having a dedicated long-term follow-up clinic for allogeneic transplant recipients (52% versus 33%) and a standard operating procedure (88% versus 69%). Inclusion of psychological support in standard operating procedures remained low at both time points (32% versus 28%). There was ongoing variation in practice regarding vaccination programmes, access to cancer screening, and audit processes between centres. Perceived barriers to implementation of comprehensive long-term follow-up clinics were similar in 2019; mainly resourcing clinical staff and psychological support. Whilst the survey reflects the changing practice of transplant centres, best explained by increasing recognition of late effects and survivorship by clinicians, health service policy and JACIE accreditation standards, further developments are warranted to address unmet healthcare needs of long-term HSCT survivors, especially access to psychological support, cancer screening and vaccinations.

A mixed-methods study of the disease experience in hematopoietic stem cell transplantation survivors: the contribution of text analysis

Objectives Few studies have detected qualitative and quantitative aspects of patients who underwent HSCT during childhood. The aims of this study are to explore the most recurrent narrative themes of HSCT experience in families five years after the procedure, and to observe statistical correlations between meaning attributed to the experience and defined variables. Methods Thirty-five families of pediatric HSCT survivors participated in the research. Both survivors and their families were asked to write a brief composition about their disease experiences. Qualitative analysis of the texts was performed using the T-LAB software. Information about medical aspects and psychological problems in HSCT survivors were collected with interviews and administering the Child Behavior Checklist 6–18. Results HSCT survivor families that reported the presence of externalizing and internalizing symptoms focused on thematic areas concerning broken families with separation between parents and the affected child versus healthy children. Conclusions Long term psychological problems seem to be connected to the perception of family disruption. Specifically, family relationships seem to be the factor that protects from or enhances the risk of psychopathology in HSCT survivors. Moreover, the use of metaphoric terms to refer to HSCT presents higher associations with psychopathology. On the contrary, the possibility of referring directly to the transplantation is associated with psychological well-being. It is important to consider the family as a group in order to improve care.

The challenge of long-term follow-up of survivors of childhood acute leukemia after hematopoietic stem cell transplantation in resource-limited countries: A single-center report from Brazil.

With the number of long-term HSCT survivors steadily increasing, attention needs to be focused on the late complications and quality of life. We therefore analyzed the outcome of 101 pediatric patients (<18years old at the time of HSCT) transplanted for acute leukemia between 1981 and 2015 at Complexo Hospital de Clínicas, Federal University of Paraná, Brazil, and who survived at least two years after HSCT. The median follow-up was 5.9years (2.0-29.0); median age at follow-up was 17.5years (2.98-39.0). The 5-year cumulative incidence of relapse was 27.5% (95% CI 18.6%-36.4%). Two-year cumulative incidence of chronic GVHD was 21.8% (95% CI 13.7%-29.8%). Of the 101 patients, 72 patients (71.3%) presented with late effects. Those surviving longer after HSCT experienced more complications. Patients who received TBI-based regimen developed more late effects (P=.013) and more endocrinological complications (P=.024). Endocrinological complications were the most common late sequelae found in this study. For childhood survivors, quality of life was not influenced by age (at HSCT or at last visit), time from HSCT, gender, donor, or GVHD. For survivors that no longer were children, only age at last visit impacted financial domain measures, irrespective of gender, donor, or GVHD. The current study confirms the high burden late complications after pediatric HSCT have on the survivors and underlines the importance of extended follow-up.

Cognitive and psychological outcomes of pediatric allogeneic hematopoietic stem cell transplantation survivors in a single center in China.

To investigate the cognitive and psychological outcomes of pediatric allogeneic HSCT survivors in China.A total of 135 3 to 18 years old children and adolescents who underwent allo-HSCT and survived at least 3 months post-HSCT were recruited and completed the assessments. Cognitive and psychological functions were assessed via age-appropriate standardized measures. Clinical information was extracted from the medical records.Forty one 3 to 6 years old children completed Psychological Questionnaires for 3 to 6 years Children. The scores of 21(51.2%) children in cognitive development dimension, 18(43.9%) in motor development dimension, 16(39.0%) in language development and social development dimension, 15(36.6%) in emotion and will dimension and 14(34.1%) in living habits dimension were less than the standard. Fifty six 8 to 16 years old children and adolescents completed the Depression Self-rating Scale for Children and 9 (16.1%) of these met the criteria of depression. Sixty nine 7 to 16 years old children and adolescents completed the screening for Child Anxiety Related Disorders and 7 (10.1%) of these met the criteria of anxiety, especially social phobia and school phobia. Eighty nine 6 to 18 years old children and adolescents completed the Symptom Checklist-90 and 43.8% to 77.5% of these experienced mild symptoms like obsession-compulsion (77.5%), hostility (64%), and interpersonal sensitivity (60.7%). Children treated with total body irradiation (TBI) showed more cognitive impairments like motor deficits than those without TBI. Also older children and adolescents had more symptoms like psychoticism.These findings demonstrated cognitive and psychological late effects of pediatric allo-HSCT survivors in a single center in China and highlighted that the survivors conditioned with TBI had more cognitive impairments and older children and adolescents had more symptoms. Early intervention in these children and adolescents might minimize the cognitive losses and psychological effects.

PB2373 LIVER DISEASE DURING AND AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN EGYPT (SINGLE CENTER EXPERIENCE)

Please indicate where the abstract has been published before: egyptian socitey of hepatology and gastroenterology journalBackground:Hematopoietic stem cell transplantation has a rapid increase over the last decade. It is an established therapy for many hematological disorders. HSCT had many possible serious complications. One of those complications is hepatic dysfunction.Hepatic complication in autologous HSCT survivors could be early complications include drug toxicity, infections and long‐term liver complications from chronic viral hepatitis, iron overload or original disease relapse.Aims:is to determine the prevalence, etiology of liver disease in Egyptian population who had HSCTMethods:this study is cross‐sectional study in December 2016 including 88 patients who had autologus transplantation in Ain Shams University HospitalsResults:In autologus patients the first cause of hepatotoxicity is conditioning regimen involving 27% of the patients. Second cause is flare of viral hepatitis affecting 8% of the patients. In third place is sepsis that leads to elevated liver function which occurred in 6% of our patients, these figures were also dramatically changed after D + 100 and lower hepatotoxicity percentage occurs as 11% of the patients had liver injury caused by drugs and only 1% patients had viral hepatitis reactivation.imageSummary/Conclusion:Drug hepatotoxicity is main cause of liver injury in BMT unit in Ain Shams University in Egyptian population.

LONG-TERM EFFECTS OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION AMONG SURVIVORS AT UNIVERSITY HOSPITAL CENTRE ZAGREB

The number of long-term survivors after allogeneic hematopoietic stem cell transplantation is increasing daily, and late effects of such treatment cause significant quality of life impairment. We analysed the data of 111 long-term survivors that were transplanted at the University Hospital Centre Zagreb in the period between 1986 and 2009. For the investigated population survival median time was 15 years (range 2–33). Our results were similar to those reported by other researchers, and have shown a rising trend over a longer follow-up period. The cumulative incidence of cardiovascular and endocrine complications, solid tumors, chronic graft versus host disease (GvHD), liver, renal and pulmonary diseases is 64%, 42%, 33%, 32%, 28%, 17% and 14%, respectively. Further analysis confirmed that the spontaneous recovery of menstrual cycle was more likely among patiens transplanted in childhood than in adulthood (45% vs 18%). Premature ovarian insufficiency (POI) was detected in 71% of female patients transplanted in adult age. However, five women gave birth to six healthy children in this study population, where two pregnancies occurred after spontaneous recovery of ovarian function, one after the use of hormone replacement therapy (HRT) for POI, and other three occurred after assisted reproductive treatment. The results obtained can be used as a guideline for prevention and early detection of late effects with the purpose of enabling better life for long-term survivors of HSCT in the Republic of Croatia.

Pregnancy Rates and Pregnancy Outcomes after Hematopoietic Stem Cell Transplantation in Childhood: a Cross-Sectional Survey of the EBMT Pediatric WP

Introduction: In the last decade transplant activity increased constantly and consequently the number of long-term survivors. Most applied conditioning regimes are known to impair normal puberty development and can lead to infertility. Pregnancies in women who had undergone a HSCT as well as in partners of transplanted men have been documented. However, the true incidence of pregnancies and its related complications in patients transplanted during their childhood remains unknown. The Pediatric WP of the EBMT conducted a study aiming to analyze pregnancy rates and to evaluate pregnancy outcomes in survivors of childhood HSCT. Material and Methods: In this study, we first evaluate the available data on the EBMT registry. To collect additional data a survey was conducted between July 2017- June 2018. 203 centers with pediatric activity reported to the EBMT patients were asked to fill-out the survey with 36 items related to treatment plan, pregnancies and pregnancies outcome. Adoptions were not considered in the study. Results: Data obtained from the EBMT database “Promise” reported that 62'988 pediatric patients were transplanted in the EBMT centers from 1995 to end of 2016. In 484 (0.76%) patients a conception after HSCT has been reported. 341/484 patients (70%) had an allograft, 134 of them (40%) were males. 143/484 had an autologous, 53 of them (37%) were male. The median age of patients was 15.02 years (range 0.6 - 17.9 years), was similar for male and females regardless of whether they were auto or allogeneic transplanted. 283 patients (58%) had conditioning regimes containing alkylating agents, irradiation or both.Data obtained from the conducted survey provide precise information of 27 (13 %) EBMT centers from 16 countries about 114 pregnancies of 99 patients and their partners. Pregnancies were in 30/99 (30%) from partners of post HSCT male patients and 60/99 (70%) were of post HSCT females. Underlying diseases for HSCT were reported in 82 of all 99 patients. 47/82 (57%) had a malignant disease and35/82 (43%) had a non-malignant disease. 29/99 (29%) had a reduced conditioning regime, 70/99 (71%) a myeloablative conditioning regime. 25/82 (30%) received TBI as part of the conditioning regimes. Regarding conception in patients post TBI, 12/23 (52%) became naturally pregnant (2/12 had 2 Gy only), 9/23(39%) required assisted fertilization and 2 used cryopreserved sperms. In patients conditioned without TBI, 54/59 (92%) had a natural conception, 4/59 (7%) required assisted fertilization and 1 used cryopreserved sperms. In 90/99 (90%) patients pregnancy resulted in a livebirth. 13 of the 90 livebirths (14%) were preterm, with a higher proportion than in normal the population (5.5-11%) and 6 of the 90 livebirths (6%) presented a low birthweight which is comparable to the normal population (6.5%).Conclusion: This study confirms a low pregnancy rate in survivors of childhood HSCT. Natural conception was possible when patients are conditioned without TBI. After TBI, pregnancy assisted fertilization techniques may increase pregnancy rate. The number of live births and complications indicate the need to advise survivors of childhood HSCT about the potential risks and outcome of pregnancy and advise them appropiately. DisclosuresBader:Cellgene: Consultancy; Neovii: Research Funding; Medac: Patents & Royalties, Research Funding; Riemser: Research Funding; Novartis: Consultancy, Speakers Bureau.

A mixed methods analysis of perceived cognitive impairment in hematopoietic stem cell transplant survivors.

Hematopoietic stem cell transplant (HSCT) survivors may show evidence of objective cognitive impairment; however, perceived cognitive problems and their impact on quality of life are less well-understood. The purpose of this study was to explore HSCT survivors' perceptions of cognitive impairment and its effect on daily life functioning. Sixty-nine autologous and allogeneic HSCT survivors nine months to three years posttransplant experiencing mild survivorship problems completed a brief structured interview regarding perceived cognitive impairment since transplant. Data were coded and content analyzed. The frequency of participants reporting cognitive problems by domain and associations between reports of cognitive problems and age, depressed mood, anxiety, and health-related quality of life were examined. Overall, 49 of the 69 participants (71%) reported cognitive impairments after transplant: 38 in memory (55%), 29 in attention and concentration (42%), and smaller numbers in other domains. There were no significant differences in problems reported by transplant type. Of the 50 participants who worked before transplant, 19 (38%) did not return to work following transplant, with 12 citing cognitive and health problems as being the reason. There were significant associations between reports of cognitive impairment and younger age (p = 0.02), depressed mood (p = 0.02), anxiety (p = 0.002), and health-related quality of life (p = 0.008). A large proportion of survivors reported cognitive impairment following HSCT that impaired daily life functioning. Perceived cognitive impairment was associated with younger age, greater distress and reduced health-related quality of life.

282 - Kidney Dysfunction Post-Allogeneic Transplant: High Incidence of TMA and Kidney GvHD

Abstract Introduction: Kidney dysfunction is an important problem in adult recipients of allogeneic stem cell transplantation (HSCT) and independently predicts overall survival and non-relapse mortality. Kidney dysfunction occurs in ~50% of transplant recipients. More than 20% of all survivors of HSCT in long-term follow up develop chronic kidney disease. However, there is currently limited data on the cause and consequences of kidney dysfunction in adult recipients after allogeneic HSCT. Common causes of kidney dysfunction after HSCT include chemotherapy or radiation toxicity, infections, sepsis, hepatic sinusoidal obstruction, drug toxicities due to immunosuppressive medications, thrombotic microangiopathy, as well as acute or graft versus host disease (GvHD). Kidney biopsies are seldom obtained and hence the tissue diagnosis in these patients often remains speculative. Early identification of the causes of kidney dysfunction may help define preventive and therapeutic strategies and improve outcome. Hence, in August 2016, we designed a prospective study at our center to systematically evaluate kidney dysfunction in adult recipients of allogeneic HSCT. Herein we present our initial report of 8 kidney biopsies. Methods: All adult HSCT recipients with kidney dysfunction were evaluated by Nephrologists to determine the need for kidney biopsy. Kidney dysfunction was defined as either (i) acute kidney failure or (ii) proteinuria. Acute kidney failure was defined by the ‘ Kidney Disease: Improving Global Outcomes (KDIGO)‘ criteria. Proteinuria was defined as (i) spot urine albumin to creatinine ratio of ≥1 (equivalent to ≥1 g in 24 hours). Kidney biopsies were done under ultrasound guidance and the tissue specimens were interrogated by light, immunofluorescence and electron microscopy. Results: A total of 8 HSCT recipients (including one patient who had a biopsy prior to Aug 2016) underwent kidney biopsies. The patient and transplant characteristics are summarized in Table 1. Seven of the 8 pts had AML. One patient had NHL in CR2. Four patients received a MUD transplant. Two received MRD transplants. Two received combined haploidentical and single unit cord blood transplant (haplo-cord). Six of the 8 patients received conditioning with fludarabine and melphalan. One patient received additional 400 Gy TBI. One patient received additional azacytidine. Median time to neutrophil engraftment was 13.5 days (range 9-20). Median time to platelet engraftment was 19 days (range 14-76). There were no cases of graft failure. All patients also demonstrated either acute or chronic GvHD of other organs - most commonly skin. All kidney biopsies were performed without complications. Kidney biopsies were done at median 254 days after transplantation (range 126-680). Baseline serum creatinine (mg/dL) prior to transplant was 0.95 (median, range 0.65-1.1, reference range: 0.64-1.27 mg/dL). Creatinine at time of biopsy: 3.0 (median, range 1.53-5.07). Urine albumin/creatinine ratio: 832 (median, range 55-2864, reference range: The kidney biopsy findings are summarized in Table 2. All patients had evidence of endothelial cell injury, either acute or chronic. Three patients had features suggestive of GvHD of the kidney while one patient had BK virus nephropathy. Four of the 8 recipients died; 80 days (median, range 39-124) from the biopsy, 346 days (median, range 178-804) from transplantation. The clinical outcome is summarized in Table 3. Conclusions: Kidney biopsies post-transplant are an important diagnostic tool that should be considered for prolonged kidney dysfunction or proteinuria, particularly in the setting of other post-transplant complications. Our single-center biopsy results highlight the under-recognition of kidney dysfunction complications and complexities observed post-transplant. All kidney biopsies performed were instrumental in treatment planning. Further investigation is needed to define criteria for diagnosis and to understand the pathophysiology. This requires multi-disciplinary engagement as well as a proactive approach for obtaining kidney biopsies. With appropriate transfusion support, percutaneous kidney biopsies were performed safely without complication. Download : Download high-res image (217KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.

Post-transplant adaptive function in childhood cerebral adrenoleukodystrophy.

ObjectiveHematopoietic stem cell transplantation (HSCT) is the only treatment known to slow or halt inflammatory demyelination among boys with the cerebral form of X‐linked adrenoleukodystrophy (cALD), a devastating childhood condition affecting the central nervous system. HSCT can lead to a range of adverse outcomes including fatality. Previous studies have examined the potential predictors of post‐HSCT survival and neurologic functioning. However, little is known about patients' daily‐life adaptive functional outcomes (i.e., ability to communicate, maintain social relationships, and independently execute tasks of daily living). The purpose of this retrospective cohort study was to identify which patient characteristics and treatment‐related variables predict long‐term adaptive function among the survivors of HSCT for cALD.MethodsWe obtained caregiver ratings of adaptive functioning of 65 transplant survivors at an average of 4.6 years (range: 1.0–24.1 years) post‐HSCT. Using linear regression with penalized maximum likelihood estimation, we modeled the relative contribution of pre‐transplant neurocognitive test performance, MRI severity, transplant regimen, and length of time since transplant on patient adaptive functioning outcomes.ResultsHigher radiographic disease severity and poorer performance on baseline neurocognitive tests requiring fine motor skills and visual perception were associated with inferior adaptive functioning after HSCT. Use of radiation during the transplant preparative regimen also predicted poorer adaptive outcomes.InterpretationIn addition to radiological disease severity, baseline neurocognitive test performance is associated with post‐transplant adaptive functional outcomes. Neurocognitive measures may play an important role in prognostic counseling and post‐transplant treatment planning for patients considering HSCT for cALD.

A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax 301-309 -Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients

We previously reported that the T-cell receptor (TCR) repertoire of human T-cell lymphotropic virus type 1 (HTLV-1) Tax301-309-specific CD8+ cytotoxic T cells (Tax301-309-CTLs) was highly restricted and a particular amino acid sequence motif, the PDR motif, was conserved among HLA-A*24:02-positive (HLA-A*24:02+) adult T-cell leukemia/lymphoma (ATL) patients who had undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR+ CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-1. On the other hand, the TCR repertoires in Tax301-309-CTLs of asymptomatic HTLV-1 carriers (ACs) remain unclear. In this study, we directly identified the DNA sequence of complementarity-determining region 3 (CDR3) of the TCR-β chain of Tax301-309-CTLs at the single-cell level and compared not only the TCR repertoires but also the frequencies and phenotypes of Tax301-309-CTLs between ACs and ATL patients. We did not observe any essential difference in the frequencies of Tax301-309-CTLs between ACs and ATL patients. In the single-cell TCR repertoire analysis of Tax301-309-CTLs, 1,458 Tax301-309-CTLs and 140 clones were identified in this cohort. Tax301-309-CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was exclusively observed in all ACs and ATL patients. However, there was no correlation between PDR+ CTL frequencies and HTLV-1 proviral load (PVL). In conclusion, we have identified, for the first time, a unique amino acid sequence, PDR, as a public TCR-CDR3 motif against Tax in HLA-A*24:02+ HTLV-1-infected individuals. Further investigations are warranted to elucidate the role of the PDR+ CTL response in the progression from carrier state to ATL.IMPORTANCE ATL is an aggressive T-cell malignancy caused by HTLV-1 infection. The HTLV-1 regulatory protein Tax aggressively promotes the proliferation of HTLV-1-infected lymphocytes and is also a major target antigen for CD8+ CTLs. In our previous evaluation of Tax301-309-CTLs, we found that a unique amino acid sequence motif, PDR, in CDR3 of the TCR-β chain of Tax301-309-CTLs was conserved among ATL patients after allo-HSCT. Furthermore, the PDR+ Tax301-309-CTL clones selectively expanded and showed strong cytotoxic activities against HTLV-1. On the other hand, it remains unclear how Tax301-309-CTL repertoire exists in ACs. In this study, we comprehensively compared Tax-specific TCR repertoires at the single-cell level between ACs and ATL patients. Tax301-309-CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was conserved in all ACs and ATL patients, regardless of clinical subtype in HTLV-1 infection.

Provision of long-term monitoring and late effects services following adult allogeneic haematopoietic stem cell transplant: a survey of UK NHS-based programmes.

Despite international guidelines, optimal delivery models of late effects (LE) services for HSCT patients are unclear from the clinical, organizational and economic viewpoints. To scope current LE service delivery models within the UK NHS (National Health Service), in 2014, we surveyed the 27 adult allogeneic HSCT centres using a 30-question online tool, achieving a 100% response rate. Most LE services were led and delivered by senior physicians (>80% centres). Follow-up was usually provided in a dedicated allograft or LE clinic for the first year (>90% centres), but thereafter attrition meant that only ~50% of patients were followed after 5 years. Most centres (69%) had a standard operating procedure for long-term monitoring but access to a LE Multi-Disciplinary Team was rare (19% centres). Access to medical specialities necessary for LE management was good, but specialist interest in long-term HSCT complications was uncommon. Some screening (endocrinopathy, cardiovascular) was near universal, but other areas were more limited (mammography, cervical smears). Funding of extra staff and investigations were the most commonly perceived barriers to implementation of LE services. This survey shows variation in the long-term follow-up of allogeneic HSCT survivors within the UK NHS and further work is warranted to optimize effective, sustainable and affordable models of LE service delivery among this group.

330 - Echocardiographic Abnormalities in Long-Term Survivors of Pediatric HSCT

330 - Echocardiographic Abnormalities in Long-Term Survivors of Pediatric HSCT

Identifying Cardiovascular Risk in Survivors of Childhood Leukaemia Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation

Background: Survivors of childhood with haematopoietic stem cell transplantation and total body irradiation (HSCT/TBI) have an increased cardiometabolic risk without overt obesity. Aim: To describe cardiometabolic risk in HSCT/TBI survivors and identify anthropometric measurements of adiposity representative of cardiometabolic risks in HSCT/TBI survivors. Method: Childhood leukaemia survivors treated with HSCT/TBI (n = 21, 11 males) were compared with chemotherapy-only (n = 31) and obese non-leukaemic controls (n = 30). All subjects (16–26 years) had blood pressure and auxological measurements (body mass index, waist and hip circumferences) and blood tests (triglycerides, high-density lipoprotein [HDL], and oral glucose tolerance tests). Central adiposity was defined as either increased waist circumference (WC), waist-to-height ratio (WHtR) (>0.5), or waist-to-hip ratio (WHR) (males >0.9, females >0.85). Results: HSCT/TBI survivors showed higher prevalence of hypertriglyceridaemia than both comparison groups and higher prevalence of reduced HDL compared to the chemotherapy-only group. The WHR reported a higher prevalence of increased adiposity in HSCT/TBI survivors compared with WC and WHtR, but such differences were not observed in the other groups. In the HSCT survivors, WHR had the highest number of significant associations with metabolic risk factors, and metabolic risks worsen with time elapsed since primary treatment. Conclusions: HSCT/TBI survivors have high cardiometabolic risk that is not sufficiently reflected by WC alone. WHR is a useful surrogate marker for increased cardiometabolic risk in HSCT/TBI survivors.

Outcome of Patients with Second Cancer after Hematopoietic Stem Cell Transplantation: On Behalf of the Complications and Quality of Life Working Party of the EBMT

BackgroundHematopoietic stem cell transplantation (HSCT) is potentially a curative treatment for a number of life-threatening malignant and non-malignant disorders. Despite significant improvements in outcome over time, long-term survivors are at risk for late complications and their mortality remains higher than expected. Second cancers are well-known late complications, associated with substantial mortality. Although we know the incidence and risk factors for many second cancers there is a paucity of data on their outcome after HSCT. We aimed to estimate the outcome of second cancers after HSCT using a large cohort of patients from the EBMT registry, and to compare their survival to similar cancers from a general population.MethodThis retrospective observational study was based on the mandatory minimum data set centers report to the EBMT. We identified all patients with second cancers (excluding malignant hematopoietic and lymphoid neoplasms; non-melanoma skin cancers) treated with HSCT in Europe (including Turkey and Israel), between 1977-2015. Primary diagnoses were acute leukemia (23%), chronic leukemia (9%), lymphoma (34%), plasma cell disorders (23%), solid tumors (4%), myelodysplastic syndromes and myeloproliferative neoplasms (6%) and acquired marrow failure syndromes (1%). For the different types of solid tumors, median and overallsurvival werecalculated (from time of diagnosis of the second cancer). Results were analyzed separately for patients treated with autologous and allogeneic HSCT (table 1). For six prevalent second cancers (breast, lung, melanoma, oropharyngeal, colorectal, prostate; table 2), the age-standardized 5-year overall survival (according to the International Cancer Survival Standard; ICSS) of HSCT patients with second cancer diagnosed since the year 2000 was compared to cancer patients from a general population (EUROCARE, European Cancer Registry, period 2000-2007).ResultsFrom the EBMT registry 4152 second cancers out of 220617 (1.88%) HSCT patients were extracted: 1450 (1.79%) out of 80784 patients after allogeneic, and 2702 (1.93%) out of 139833 patients after autologous HSCT. The median age of the patients at HSCT and at diagnosis of second cancer was 53 years (range 1.2-86) and 59 years (3.2-88), respectively. For allogeneic HSCT is was 46 years (1.2-73) and 54 years (3.2-77), for autologous HSCT, 56 years (1.7-86) and 62 years (4.5-88), respectively. The median follow-up time since transplantation of all patients was 121 months (range 5-409); it was 146 months (12-409) for allogeneic, and 114 months (5-354) for autologous HSCT. The median follow-up time since diagnosis of second cancer was 35 months (range 0-240); it was 38 months (0-240) for allogeneic, and 33 months (0-228) for autologous HSCT.The distribution and survival outcomes of second cancers are shown on table 1. Overall survival following diagnosis of second cancers depends mostly on the type of cancer. No relevant differences in median survival and 5-year overall survival were seen between patients treated with autologous or allogeneic HSCT (table 1). For second breast, lung and prostate cancers no difference in 5-year overall survival wasobserved,compared to cancer patients from a general population (table 2). Melanoma and colorectal cancers had worse, and oropharyngeal cancer better overall survival, compared to the EUROCARE control group.ConclusionThis large population-based analysis on second cancers among HSCT survivors showed that the outcome for patients developing a second cancer after HSCT is mainly dependent on the type of cancer. It seems that for a number of second cancer overall survival is comparable to cancer patients from a general population. A systematic comparison is now required for all post HSCT second cancers. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.