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Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapeutic approach in the treatment of multiple myeloma, and the recent approval of the first two CAR T-cell products could result in improved outcomes. However, it remains a complex and expensive technology, which poses challenges to health-care systems and society in general, especially in times of crises. This potentially accelerates pre-existing inequalities as access to CAR T-cell therapy varies, both between countries, depending on the level of economic development, and within countries, due to structural disparities in access to quality health care-a parameter strongly correlated with socioeconomic status, ethnicity, and lifestyle. Here, we identify two important issues: affordability and access to CAR T-cell treatment. This consensus statement from clinical investigators, clinicians, nurses, and patients from the European Society for Blood and Marrow Transplantation (EBMT) proposes solutions as part of an innovative collaborative strategy to make CAR T-cell therapy accessible to all patients with multiple myeloma.

Contains fulltext : 293550.pdf (Publisher’s version ) (Open Access) For hematopoietic cell transplantation (HCT) and cellular therapy (CT), clinical patient care is localized, and practices may differ between countries and from center to center even within the same country. Historically, international guidelines were not always adapted to the changing daily clinical practice and practical topics there were not always addressed. In the absence of well-established guidelines, centers tended to develop local procedures/policies, frequently with limited communication with other centers. To try to harmonize localized clinical practices for malignant and non-malignant hematological disorders within EBMT scope, the practice harmonization and guidelines (PH&G) committee of the EBMT will co-ordinate workshops with topic-specific experts from interested centers. Each workshop will discuss a specific issue and write guidelines/recommendations that practically addresses the topic under review. To provide clear, practical and user-friendly guidelines when international consensus is lacking, the EBMT PH&G committee plans to develop European guidelines by HCT and CT physicians for peers' use. Here, we define how workshops will be conducted and guidelines/recommendations produced, approved and published. Ultimately, there is an aspiration for some topics, where there is sufficient evidence base to be considered for systematic reviews, which are a more robust and future-proofed basis for guidelines/recommendations than consensus opinion. 01 juni 2023

Contains fulltext : 293484.pdf (Publisher’s version ) (Open Access) From 2016 EBMT and JACIE developed an international risk-adapted benchmarking program of haematopoietic stem cell transplant (HSCT) outcome to provide individual EBMT Centers with a means of quality-assuring the HSCT process and meeting FACT-JACIE accreditation requirements relating to 1-year survival outcomes. Informed by previous experience from Europe, North America and Australasia, the Clinical Outcomes Group (COG) established criteria for patient and Center selection, and a set of key clinical variables within a dedicated statistical model adapted to the capabilities of the EBMT Registry. The first phase of the project was launched in 2019 to test the acceptability of the benchmarking model through assessment of Centers' performance for 1-year data completeness and survival outcomes of autologous and allogeneic HSCT covering 2013-2016. A second phase was delivered in July 2021 covering 2015-2019 and including survival outcomes. Reports of individual Center performance were shared directly with local principal investigators and their responses were assimilated. The experience thus far has supported the feasibility, acceptability and reliability of the system as well as identifying its limitations. We provide a summary of experience and learning so far in this 'work in progress', as well as highlighting future challenges of delivering a modern, robust, data-complete, risk-adapted benchmarking program across new EBMT Registry systems. 01 juni 2023

Whilst the basic principles of HSCT remain the same, regardless of the age of the patient, there are a number of important additional considerations relating to transplantation of our younger and older patients and those of adolescent age. The principles outlined in this chapter serve as a valuable reminder supporting age-appropriate patient-centred care delivery. This chapter initially focuses on transplanting the child and its physiological and psycho-social aspects. Subsequently, the nursing challenges in the AYA population will be addressed. This chapter ends with considerations for treatment and care for the older adult.

Haematopoietic stem cell transplantation (HSCT) generally includes preparative or conditioning regimens containing combinations of chemotherapy and/or radiotherapy and sometimes immunotherapy. These regimens, as well as other treatments before and after HSCT such as immunosuppressive drugs to prevent graft-versus-host disease (GvHD) (see Chap. 11), may affect the patient’s organs and tissues and cause both early and long-term complications. In the evolving field of stem cell therapies, some complications that traditionally have been regarded as early complications are now, due to changes in preparative regimens and choice of stem cell source, sometimes seen later in the post-transplant outpatient setting. The complications covered in this chapter generally occur within 100 days post-HSCT and are thus classified as early complications. Two of the most common early complications are oral complications/mucositis and sepsis. Some other relatively rare complications are also covered here: haemorrhagic cystitis (HC), endothelial damage syndromes including engraftment syndrome (ES), idiopathic pneumonia syndrome (IPS), diffuse alveolar haemorrhage (DAH), thrombotic microangiopathy (TMA) and sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD). For all complications, recommendations for prevention and principles for nursing care are presented since careful nursing monitoring and prompt intervention and care may have an impact on patients’ morbidity and mortality.

Over recent years cellular therapy has seen substantial progress across Europe, particularly cell-based immunotherapy/ immune effector cells (IECs), with the approval of autologous CD19 CAR-T products for patients with relapsed/refractory B-cell malignancies-diffuse large B cell lymphoma, acute lymphoblastic leukaemia (paediatric, teenage and young adult) and mantle cell lymphoma). Whilst this development has delivered benefit to patients with poor risk disease, there is potential for associated toxicities which require careful patient selection, assessment, monitoring, treatment and follow-up care. Nurses play a crucial role in supporting patients throughout this pathway. This chapter focuses on autologous cell-based immunotherapies (CAR-T) process, infusion, toxicities, management and the patient pathway, whilst also exploring non-cell-based immunotherapies, cell therapy in solid tumours and the role of clinical trials.

Sinusoidal obstructive syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a potentially life-threatening complication following haemopoietic stem cell transplantation (HSCT). The availability of new drugs for malignant hematological conditions has allowed more patients to be eligible for allogeneic haematopoietic stem cell transplants, which has translated into a significant proportion of transplant patients having multiple risk factors for VOD/SOS. Based on these considerations, we undertook a dedicated weekly VOD/SOS ward round, aiming to facilitate early diagnosis of VOD/SOS and pre-emptively identify patients at risk, where a careful evaluation of differential diagnosis is essential. Herein, we present the results of our VOD/SOS ward round; between September 2020 and April 2022, 110 consecutive patients were evaluated in a focused VOD/SOS ward round. From the 110 patients, 108 had undergone HSCT and had at least one known risk factor for developing VOD/SOS. The median number of risk factors present in the VOD/SOS group and non-VOD/SOS group was five (range: three to six) and three (range: zero to seven), respectively. Late-onset VOD/SOS was diagnosed in 45% of our patients. The early identification of patients with multiple risk factors for VOD/SOS allowed an earlier diagnosis and the administration of defibrotide on the same day of diagnosis, which was two days earlier than our previous experience prior to the implementation of this protocol.

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.

Sexual dysfunction after allogeneic hematopoietic cell transplantation (allo-HCT) is a common long-term complication. We conducted a European multicenter cross-sectional study of adult allo-HCT recipients who had survived >2 years and their partners to investigate sexual functioning after HCT and to evaluate whether discussion about sexual functioning between the transplant team and the survivor and partner was perceived to have taken place. In total, 136 survivors (77 males, 59 females) and 81 partners (34 males, 47 females) participated. Median age was 56 and 54 years in male and female survivors, respectively. Forty-seven percent of male and 65% of female survivors and 57% of male and 59% of female partners reported clinically relevant sexual problems. Sixty-two percent of survivors and 79% of partners reported that sexual functioning had not been discussed with them during transplant. Standardized sexual functioning scores were correlated with self-reported health status in survivors (rho = 0.24, p = 0.009). The high prevalence of sexual dysfunction warrants additional studies focusing on the impact of changes in sexuality for patients as well as their partners. Future studies should also investigate which methods that are effective in preventing or treating sexual problems after allo-HCT.

Complex nursing care for patients on the CAR-T cell therapy pathway involves many different nursing roles that have important functions at different stages in the pathway. Within the multiprofessional team, nurse education is critical to safe and competent care and to the patient’s treatment experience. As we consider the education needs of the nursing workforce throughout the entire patient pathway, including the supply chain, chain of custody, and clinical care delivery, we recognize the important roles of expert nurses, practice educators, and the wider multiprofessional team in sharing their knowledge and experience. Nurse education strategies should include referring nursing teams to facilitate seamless patient care throughout referral, treatment, and follow-up to optimize communication and appropriately meet patient and caregiver information needs.

Sufficient communication between hematopoietic stem cell transplantation (HSCT) and pediatric intensive care unit (PICU) teams is pivotal for a successful advanced support in the PICU for HSCT-related complications. We evaluated perceived communication and barriers between both teams with the aim of providing recommendations for improvement. In this cross-sectional survey, a self-designed online questionnaire was distributed among ESPNIC and EBMT members. Data were analyzed using descriptive statistics. Over half of HSCT respondents employed a transfer indication protocol and patient assessment tool, but less structured checklist prior to patient transfer. Nearly all PICU respondents perceived this checklist as improvement for communication. Most HSCT and PICU physicians have daily rounds upon patient transfer while this is mostly missing between nursing teams. Half of both HSCT and PICU nurses indicated that HSCT training for PICU nurses could improve communication and patient transfer. Most respondents indicated that structured meetings between HSCT and PICU nurses could improve communication. Overall there is good communication between HSCT and PICU units, although barriers were noted between members of both teams. Based on our findings, we recommend use of a structured and specific checklist by HSCT teams, HSCT training for PICU personnel, and structured meetings between HSCT and PICU nurses.

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.

Although it is considered a relatively rare disorder, veno-occlusive disease (VOD) is one of the main causes of overall, non-relapse mortality associated with haematopoietic stem cell transplantation (HSCT). This article, based on the consensus opinion of haemato-oncology nurses, haemato-oncologists and pharmacists from both adult and paediatric services at the VOD International Multi-Disciplinary Advisory Board at the European Society for Blood and Marrow Transplantation (EBMT) meeting, Istanbul, 2015, aims to explore the multidisciplinary approach to care for the management of VOD, with an emphasis on current challenges in this area. The careful monitoring of HSCT patients allows early detection of the symptoms associated with VOD and timely treatment, ultimately improving patient outcomes. As part of a multidisciplinary team, nurses have an essential role to play, from pretransplant assessment to medical management and overall care of the patient. Physicians and pharmacists have a responsibility to facilitate education and training so that nurses can work effectively within that team.

Dosing regimens for antithymocyte globulin (ATG) and anti-CD52 antibody (alemtuzumab) for graft vs. host disease prophylaxis (GVHD) are empiric or weight-based, and do not account for individual patient factors. Recently, it has been shown that recipient peripheral blood absolute lymphocyte count (ALC) on the day of ATG administration interacts with the dose of ATG administered to predict transplantation outcome. Similarly, we wanted to analyze if the recipient ALC interacts with alemtuzumab dosing to predict outcomes. We retrospectively compared 364 patients, 124 patients receiving ATG (anti-thymocyte globulin) for GVHD prophylaxis, and undergoing unrelated first allogeneic transplant for myeloid and lymphoid malignancies (group 1) to 240 patients receiving alemtuzumab (group 2), in similar time period. There was no difference in survival or acute and chronic GVHD between 60 and 100 mg of alemtuzumab dosing. Unlike ATG (where the pre-transplant recipient ALC interacted with ATG dose on day of its administration (day 1) to predict OS and DFS (p = 0.05), within alemtuzumab group, the recipient ALC on second day of alemtuzumab administration (day 2) and its interaction with alemtuzumab dose strongly predicted OS, DFS and relapse (p = 0.05, HR-1.81, 1.1-3.3; p = 0.002, HR-2.41, CI, 1.3-4.2; and p = 0.003, HR-2.78, CI, 1.4-5.2), respectively. ALC (day 2) of 0.08 × 109/lit or higher, had a specificity of 96% in predicting inferior DFS. Like ATG, there is definite but differential interaction between the recipient peripheral blood ALC and alemtuzumab dose to predict OS, DFS, and relapses.

Compared to standard-conditioned regimens, reduced-intensity conditioning and T-cell depletion deliver lower transplant-related mortality and decreased graft-vs-host disease after allogeneic hematopoietic stem-cell transplantation. These advantages may however be mitigated by increased relapse rates and delays in achievement of full donor chimerism (FDC). Pre-emptive donor lymphocyte infusions (pDLI) facilitate the conversion of mixed (MDC) to FDC. However, there is a lack of published data on the risk/benefit analysis of this intervention. We performed a retrospective analysis of 119 patients who received 276 pDLI doses for falling CD3 chimerism, CD3

This open access textbook, endorsed by the European Society for Blood and Marrow Transplantation (EBMT), provides adult and paediatric nurses with a full and informative guide covering all aspects of transplant nursing, from basic principles to advanced concepts. It takes the reader on a journey through the history of transplant nursing, including essential and progressive elements to help nurses improve their knowledge and benefit the patient experience, as well as a comprehensive introduction to research and auditing methods. This new volume specifically intended for nurses, complements the ESH-EBMT reference title, a popular educational resource originally developed in 2003 for physicians to accompany an annual training course also serving as an educational tool in its own right.This title is designed to develop the knowledge of nurses in transplantation. It is the first book of its kind specifically targeted at nurses in this specialist field and acknowledges the valuable contribution that nursing makes in this area. This volume presents information that is essential for the education of nurses new to transplantation, while also offering a valuable resource for more experienced nurses who wish to update their knowledge.

Haematopoietic stem cell transplantation (HSCT) cures many haematological cancers. Recovery post-HSCT is physically and psychologically challenging, lasting several months. Beyond the first post-transplant year, a fifth report difficulties encompassing practical, social and emotional domains, including finance and employment. We investigated the feasibility, acceptability and impact of a life coaching intervention designed to address psychosocial ‘survivor’ concerns of HSCT recipients and facilitate transition to life post-treatment. A concurrent embedded experimental mixed-method design was employed. Pre- and post-intervention data collection comprised qualitative semi-structured telephone interviews and quantitative postal questionnaires. Seven purposively sampled HSCT recipients (

Allogeneic stem cell transplantation was successfully performed in 1968, and its use has grown significantly over the past five decades with the total number now exceeding 1.5 million patients (Niederwieser et al. Haematologica. 107:1045–1053, 2022). HSCT is a curative treatment for many haematological cancers and other disorders. Almost 40,000 HSCT procedures are performed Europe-wide per annum (Passweg et al. Bone Marrow Transplant. 51(6):786–92, 2016), and the number of transplant recipients achieving ‘long-term survival’ and with late effects directly related to their treatment (Majhail et al. Hematol Oncol Stem Cell Ther 5(1):1–30, 2012) is increasing (Penack et al. Blood Adv 4:6283–6290, 2020). This growth in survivors is the result of improvements in transplant knowledge and expertise, refinements to conditioning regimes, developments in supportive care and increased numbers of procedures due to broadening transplant indications.The most common cause of death after transplant is relapsed disease. Yet, even without disease relapse, long-term survival is complex for many as other causes of mortality such as graft versus host disease (GvHD), infection, second malignancy, respiratory disease and cardiovascular disease (CVD) (Savani et al. Blood. 117:3002–9, 2011) prove difficult to address.Recovery post-HSCT is challenging, lasting several months to years. These individuals are susceptible to the development of post-treatment physical and psychological sequelae years to decades after completion of treatment leading to a reduced life expectancy with greater morbidity when compared to an age-adjusted population (Socié et al. N Engl J Med 341:14–21, 1999). Survivors with late effects experience significantly poorer physical and mental health, report more unmet needs for care and have significantly greater use of health services compared with survivors without late effects (Treanor et al. Psychooncology 22(11):2428–2435, 2013).Furthermore, as the number of survivors continues to grow, their long-term health problems and subsequent needs demand increasing resource and attention from late effects services. These services must remain agile and responsive, develop capacity to provide continuing expertise and oversight and collaborate with the other specialist services for input when needed.The unpredictable, complex and multifactorial nature of these long-term and late effects in HSCT survivors means that patients require regular life-long assessment guided by rigorous protocols. However, it is important to remember that even using standardised protocols, these should be different for adults and children and the resulting care must be tailored to the needs of the individual. And finally, further consideration is needed for the growing number of young people and adult survivors in long-term follow-up who have been treated in childhood and transitioned into adult long-term follow-up care.

Prior to haematopoietic stem cell transplant (HSCT), conditioning therapy is used for disease eradication, creation of space for engraftment and immunosuppression. Conditioning therapy includes combinations of chemotherapy, radiotherapy and/or immunotherapy and can be administered in the immediate days leading up to, and sometimes the days immediately following, the cell infusion. Total body irradiation (TBI) is generally used as part of conditioning regimens preceding allogeneic HSCT and is able to target sanctuary sites where some drugs cannot reach. Cancer immunotherapy treatment harnesses the body’s natural defences to fight the cancer, by involving components of the immune system. Conditioning therapy can have acute and chronic side effects which vary depending on the intensity of the treatement. Nursing implications include patient education and information, toxicity assessments, close monitoring and protocolised, evidence-based action plans. Stem cell infusion is usually a safe procedure but can cause adverse reactions ranging from flushing and nausea to life-threatening anaphylaxis. There should be written policies for the administration of cellular therapy products, and nurses must have comleted training and achieved competency in order to safely administer haematopoietic stem cells.

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.

This is an analysis in 171 patients comparing BEAM-Auto and BEAM-Allo (alemtuzumab)-hematopoietic stem cell transplantation in relapsed follicular lymphoma. BEAM-Allo group had a lower 10 years cumulative incidence of relapse(31.4% vs 55.1%, p = 0.042), a trend to a plateau in survival but no statistical differences in OS or DFS, and a TRM of 24%. When transplanted in CR BEAM-Allo patients had better OS and DFS. Incidence of acute and chronic GVHD was 16.6% and 22%. 29% of BEAM-Allo patients received DLI (all but two remain in CR and alive). Our data supports Allo-HSCT as a potential curative treatment for selected patients with FL.

Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning (RIC) offers a potential cure for patients with myelodysplastic syndrome (MDS) who are ineligible for standard-intensity regimens. Previously published data from our institution suggest excellent outcomes at 1 yr using a uniform fludarabine, busulfan, and alemtuzumab-based regimen. Here we report long-term follow-up of 192 patients with MDS and acute myelogenous leukemia (AML) secondary to MDS (MDS-AML) transplanted with this protocol, using sibling (n = 45) or matched unrelated (n = 147) donors. The median age of the cohort was 57 yr (range, 21 to 72 yr), and median follow-up was 4.5 yr (range, 0.1 to 10.6 yr). The 5-yr overall survival (OS), event-free survival, and nonrelapse mortality were 44%, 33%, and 26% respectively. The incidence of de novo chronic graft-versus-host disease (GVHD) was low at 19%, illustrating the efficacy of alemtuzumab for GVHD prophylaxis. Conversely, the 5-yr relapse rate was 51%. For younger patients (age 60 yr having a 5-yr OS of 15% and relapse rate of 66%. Patients receiving preemptive donor lymphocyte infusions had an impressive 5-yr OS of 67%, suggesting that this protocol may lend itself to the incorporation of immunotherapeutic strategies. Overall, these data demonstrate good 5-yr OS for patients with MDS and MDS-AML undergoing alemtuzumab-based RIC-HSCT. The low rate of chronic GVHD is encouraging, and comparative studies with other RIC protocols are warranted.

Reduced-intensity conditioned (RIC) hematopoietic stem cell transplantation (HSCT) has improved the accessibility of transplantation in patients previously ineligible. We report the results of allografting following conditioning with fludarabine, busulphan, and alemtuzumab in 62 patients with myelodysplastic syndromes (MDSs) (matched sibling donors [24] or volunteer unrelated donors [VUDs, 38]). The median age for sibling recipients was 56 years (range, 41-70 years) and for VUD recipients, 52 years (range, 22-65 years), with a median follow-up (survivors) of 524 days (range, 93-1392 days) and 420 days (range, 53-1495 days), respectively. The nonrelapse mortality (NRM) at days 100, 200, and 360 was 0%, 5%, and 5%, respectively, for siblings and 11%, 17%, and 21%, respectively, for VUD. The overall survival at one year was 73% for siblings and 71% for VUDs, with a disease-free survival (DFS) of 61% and 59%, respectively. The prognostic significance of the International Prognostic Scoring System (IPSS) was preserved. Of recipients, 86% achieved full-donor chimerism. The cumulative incidence at day 100 of grades III to IV graft-versus-host disease (GVHD) for VUD recipients was 9% and for sibling recipients, 0%. There were 26 patients (16 sibling and 10 VUD) who received donor lymphocyte infusion (DLI) at a median of 273 days (range, 126-1323 days). RIC allogeneic HSCT using this protocol appears to be safe and permits durable donor engraftment. Longer follow-up is required to confirm any potential survival advantage. (Blood. 2004;104:1616-1623)

New transplant approaches are urgently needed for patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor (UD) or who have failed UD or cord blood transplant. Patients with refractory SAA are at risk of later clonal evolution to myelodysplastic syndrome and acute leukemia. We report our pilot findings with haploidentical hematopoietic stem cell transplantation (haploHSCT) using uniform reduced-intensity conditioning with postgraft high-dose cyclophosphamide in 8 patients with refractory SAA or patients who rejected a prior UD or cord blood transplant. Six of 8 patients engrafted. Graft failure was associated with donor-directed HLA antibodies, despite intensive pre-HSCT desensitization with plasma exchange and rituximab. There was only 1 case of grade II skin graft-versus-host disease. We show that haploHSCT can successfully rescue refractory SAA patients who lack donor-directed HLA antibodies but not in the presence of donor-directed HLA antibodies. This novel protocol for haploHSCT for SAA has been adopted by the European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party for a future noninterventional, observational study to further evaluate its efficacy.

Relapse occurs in 30%-50% of recipients of T cell–depleted (TCD) reduced-intensity conditioned (RIC) hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Despite limited published supportive data, donor lymphocyte infusion (DLI) is used preemptively (pDLI) to improve donor chimerism and prevent relapse, and therapeutically (tDLI) after disease recurrence. We evaluated the efficacy and toxicity of pDLI and tDLI in 113 patients after TCD (alemtuzumab, n = 99; antithymocyte globulin, n = 14) RIC HSCT for AML or MDS. Recipients of pDLI (n = 62) had an estimated 5-year overall survival (OS) of 80% and an event-free survival of 65%. More than one-half (52%; n = 32) of the patients received pDLI within 6 months post-HSCT; despite this, the 5-year incidence of graft-versus-host disease was only 31% (95% confidence interval [CI], 19%-43%). Recipients of tDLI (n = 51) had an estimated 5-year OS of 40% and a 5-year relapse/progression rate of 69% (95% CI, 54%-81%). Recipients of tDLI at >6 months post-HSCT had a significantly superior 5-year OS after tDLI compared with those treated earlier (P = .008). The cumulative incidence of graft-versus-host disease at 5 years after tDLI was 45% (95% CI, 23%-65%). We demonstrate that pDLI safely promotes durable remission after TCD RIC HSCT for AML or MDS, and that tDLI salvages patients after late relapse with greater efficacy.

Haematopoietic SCT (HSCT) offers the only potentially curative option in chronic myelomonocytic leukaemia (CMML). In this study, we report on single-centre results of 18 patients with CMML who have undergone allogeneic HSCT. The median age of patients was 54 years. Seven patients had AML, which had transformed from CMML. Overall, 11 patients received stem cells from an unrelated donor. A total of 15 patients received a T-cell-depleted fludarabine/BU-based reduced-intensity conditioning HSCT. The actuarial 3-year OS, non-relapse mortality (NRM) and relapse incidence for the cohort was 31±11%, 31±14% and 47±13%, respectively. Patients with favourable cytogenetics had a 3-year disease-free survival of 65±17%, whereas none of the seven patients with intermediate or poor risk cytogenetics survived beyond 2 years (P0.01). No patients with favourable risk cytogenetics died from NRM causes, while the 2-year NRM for the intermediate/poor risk cytogenetics subgroup was 71±22% (P0.02). In terms of disease status at transplantation, patients who had5% BM blasts had a 3-year disease-free survival of 46.9±19% compared with those with5% blasts at the time of transplantation (that is, 20.0±13%). Recipient age, type of conditioning regimen or stem cell dose did not have a significant impact on overall outcomes. Our data support existing evidence that allogeneic HSCT is a feasible therapeutic option for CMML, with the ability to attain long-term remission among patient subgroups.

Chronic cutaneous graft-vs-host disease (GVHD) is generally classified by whether lesions have a lichenoid or sclerodermatous morphology. Other unusual clinical forms have been reported that exhibit the features of dermatomyositis and lupus erythematosus. Within a large population of individuals who underwent allogeneic stem cell transplantation because of hematologic malignancy, a group of patients was identified in whom severe and persistent eczema developed.We prospectively evaluated 10 adult patients with unexplained eczematous dermatosis after allogeneic hematopoietic stem cell transplantation. The dermatosis developed between 2 and 18 months (mean, 7.5 months) after receipt of the transplant, exhibited the typical clinical features of dermatitis, and became erythrodermic in each case. The patient group had strong risk factors for chronic cutaneous GVHD: 8 had received a transplant from an unrelated donor, 7 had evidence of extracutaneous GVHD, and 7 had a history of acute cutaneous GVHD. Sampling of lesional skin revealed the histologic features of GVHD coexisting with the changes of dermatitis. The patients were treated with topical corticosteroid and systemic immunosuppressive agents. Six patients also received psoralen-UV-A. Four patients achieved prolonged remission. Six patients died, 5 of infective complications and 1 of relapsed leukemia.The eczematous dermatosis observed represents a novel form of chronic cutaneous GVHD that we named eczematoid GVHD. Eczematoid GVHD is an aggressive, chronic dermatosis that requires substantial immunosuppression therapy to achieve control. It is associated with a poor prognosis. Although atopy can be transmitted to an individual from a hematopoietic stem cell transplant, none of the donors in this series gave a history of an atopic disorder. Therefore, other factors must be implicated in provoking the expression of an eczematous phenotype in individuals with underlying chronic graft-vs-host activity.

This prospective study evaluated the outcomes of 75 successive patients receiving a FBC (fludarabine, busulphan, alemtuzumab) reduced-intensity conditioning (RIC) regimen for myelodysplastic syndromes (MDS) using volunteer unrelated donors(VUD). The prognostic significance of a variety of clinical variables including the recently described haematopoietic cell transplantation co-morbidity index (HCT-CI) was assessed. The median age of the cohort was 52.0 years (range: 19-68 years) with a median follow-up of 1038.5 d. Forty-nine patients (65%) had an International Prognostic Scoring System stage of > or = Intermediate-2, 35 (46%) had intermediate or poor risk cytogenetics, and 23 patients(31%) were human leucocyte antigen-mismatched. The actuarial 3-year overall survival (OS) and disease-free survival (DFS) was 43% [95% confidence interval (CI): 37-49] and 41% (95%CI: 35-47) respectively, and the cumulative incidence of extensive chronic graft-versus-host disease was 22%. On multivariate analysis, presence of either one class II mismatch or a two-antigen mismatch adversely influenced transplant-related mortality, DFS and OS. In addition, disease status at transplantation and the haematopoietic cell transplantation-specific comorbidity index were independent variables for overall survival. In contrast, both advanced age and pre-transplant cytogenetic status did not significantly affect overall outcomes. RIC regimens using VUD was associated with durable long-term survival even in older patients with MDS, and the use of a pre-transplant comorbidity index may help to improve patient selection for transplantation.

Reduced-intensity conditioning has in the last few years revolutionized allogeneic hematopoietic stem cell transplantation (allo-HSCT).[1-6][1] The reduced toxicity has extended its availability to groups of patients hitherto ineligible because of advanced age or comorbidity. Alemtuzumab (CAMPATH-1H

Abstract 2022 Introduction: Follicular Lymphoma is the most common indolent lymphoma, characterized by an indolent course, multiple recurrence, responses to chemotherapy, risk of transformation into a high grade lymphoma and with a median overall survival of 10–12 years. Transplantation (autologous and allogeneic) has improved the overall outcome of this disease, however a continuous pattern of relapse is observed essentially in the autologous setting. Allogeneic transplant has shown encouraging results in terms of long term overall survival (OS) and disease free survival (DFS), with acceptable transplant related mortality (TRM) and with significantly lower relapse rate. Objective: To analyse retrospectively the outcome of relapsed follicular lymphoma patients who received BCNU (carmustine), cytarabine, etoposide, melphalan-alemtuzumab allogeneic HSCT (BEAM-C allo) or BEAM-autologous HSCT (BEAM-auto). Results: The study includes 74 consecutive patients with relapsed advanced stage follicular lymphoma who received BEAM-C allo (n=38) and BEAM-auto (n=36) between 1992 and 2010. Patients characteristics are summarized in Table 1. Median follow-up of surviving patients was 6.1 years. Patients undergoing allo transplants were younger than those who unbderwent and autologous procedure (50 vs 54 years, p=0.018). 1y and 5y TRM was higher in the allo transplant group (27% and 27% vs 6% and 6%; p=0,011). The Cumulative incidence of relapse (CIR) was lower in the allo at 1, 2 and 5 years (11%, 14% and 18% vs 28%, 49% and 60%, p=0,000). Significant differences were not observed in 1, 2 and 5 years OS between allo and auto transplant groups (74%, 74% and 69% vs 85%, 69% and 51%; p=0,217), but we found a strong trend in DFS difference between both groups at 1, 2 and 5 years (65%, 61% and 58% vs 69%, 43% and 33%; p=0.089) observing a plateau around 60% after 2 years in the allograft group. The rate of graft versus host disease (GvHD) was low with 14% acute GvHD (2.6% grade 3–4 GvHD) and 28% chronic GvHD (10% of extensive chronic GvHD). Analysis of the whole cohort (n=74) showed that patients in CR before transplant (n=28) had better 1, 2 and 5 years DFS following a allotransplant (69%, 69% and 69% vs 79%, 36% and 18%; p=0.012). These differences did not affect the 1, 2 and 5 years OS (76%, 76% and 76% vs 93%, 76% and 56%; p=0,214). TRM for the allo transplant group was 24% and 0% R in the auto (p=0,064) in patients when achieved CR before transplant. There were no difference in OS (p=0,785) and DFS (p=0,954) between allo or auto patients in partial response (PR) before transplant. A subgroup analysis of patients with high grade transformation before transplant did not show any differences in OS (p=0,823) or EFS (p=0,526).between allo and auto groups. Conclusions: Long term follow-up of Follicular Lymphoma patients has shown a continuous pattern of relapse when patients receive an autologous transplant, after 5 years. whereas patients undergoing allo transplant, despite a higher mortality, have a 5 year OS and DFS of 60% with a plateau been achieved in both curves after 2 years suggesting that these patients may be cured. Prospective randomised studies are still required to answer the the role of these two approaches in follicular Lymphoma. Disclosures: No relevant conflicts of interest to declare.

Abstract 4216 Patients who relapse after allogeneic bone marrow transplant (BMT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) have a poor prognosis. Salvage treatments rely on further chemotherapy, donor lymphocyte infusions (DLI) and experimental therapies. However, the treatments are often toxic and the prognosis grim particularly in patients over the age of 60 years. More recently, DNMT3A inhibition such as 5-Azacytidine (5-Aza) and Decitabine have been shown not only to have an antileukemic activity, but are also capable of inducing an antileukemic cytotoxic T lymphocyte response as well as reversal in the ratio of Tregs to Th17 CD4 cellular reactions. We therefore evaluated the role of these agents in 17 patients who have relapsed post-transplant. The indications for transplant were AML (n=13), of whom 9 had transformed from either MDS (n=5), aplastic anaemia (n=1), MDS/MPD (n=1), myelofibrosis (n=1) or CML (n=1); Of the remainder: Refractory anaemia with excess blasts II (n=2); plasmacytoid dendritic cell leukemia (n=1); MPD/MDS with trisomy 21 (n=1). 13 were treated with 5-Aza; 6 Decitabine and 2 had both 5-Aza and Decitabine as separate courses. In total, there were 20 courses of treatment, each comprising of a variable number of cycles of 5-Aza or Decitabine. 5-Aza was administered at a standard dosage of 75mg/m2 for 7 days every 28 days and Decitabine 20mg/m2 for 5 days every 28 days. There was no toxicity from the treatment such that patients required a dose reduction. charcteristics mean (RANGE) Age (yrs) 52 (35–67) Days from transplant before starting demethylating agent for overt relapse 559 (38–1956) Blast % before starting 5-Aza or Decitabine 25.7 (1–91) Number of cycles of 5-Azacytidine per course completed (n=14) 4 (1–15) Number of cycles of Decitabine (n=6) 2.5 (2–3) Duration of response from stopping 5-Aza or Decitabine treatment before relapse 186 (177–195) Pre-treatment blast % in responders (n=11) 22 (1–89) Pre-treatment blast % in non-responders (n=9) 31 (4–91) Responses were categorized as stable disease (SD), partial response (PR), morphological (MR) or complete cytogenetic remission (CCR) and were seen in 11 of 20 courses of treatment (55%) of which SD = 2, PR = 2, MR = 7, CCR = 0. Specifically 2 patients had SD whilst they remained on 5-Azacytidine. Of the 2 with PR, 1 had a drop in blast percentage but did not enter into remission. The other with plasmacytoid dendritic cell leukemia relapsed with recurrence of biopsy proven skin lesions had a transient response on 5-Azacytidine but progressed during the 5th cycle. 7 achieved a MR ( In the majority of patients, donor chimersm remained unchanged pre and post 5-Aza and Dec. 2 patients received DLI immediately post 5-Azacyditine as consolidation. Out of the 17 patients, 5 had graft-versus-host-disease (GVHD) temporally associated with commencing 5-Aza or Decitabine. 2 in this group had GVHD (grade 1–3) and 3 chronic GVHD (grade 1–3). These results suggest that demethylating agents are effective following allogeneic BMT. It is encouraging that of the patients who responded, over half had a pre-transplant diagnosis of AML however more numbers are required to support this. The effect of these agents are thought to be both antileukemic for example by increasing expression of tumour associated antigens, and immunomodulatory by delaying the effect on the methylation pattern of genes that result in a significant decrease in Tregs. Disclosures: Mufti: Celgene Corporation: Consultancy, Research Funding, Speakers Bureau.

Abstract 1304 Disease relapse following allogeneic haematopoietic stem cell transplant (HSCT) for MDS/AML remains one of the primary causes of treatment failure, particularly in the setting of T-cell depleted reduced-intensity conditioning (RIC). Pre-emptive immunotherapy such as the use of donor lymphocyte infusions (DLI) is one strategy utilized to prevent relapse, although this approach may be associated with an increased risk of GvHD. We present our experience, evaluating toxicity and efficacy of pre-emptive DLI for the treatment of mixed donor chimerism (MDC) in a cohort of high risk MDS/AML patients who received a uniform alemtuzumab-based RIC HSCT protocol. 37 patients received a RIC protocol using fludarabine, busulphan and alemtuzumab. The stem cell source was BM (n=8) and PBSC (n=29) with a median cell dose of 2.40 and 5.34×106̂ CD34/kg respectively. The donor source was from HLA-matched sibling (n=20), HLA-matched unrelated (n=14) with 3 1-allele mismatched unrelated donors. Peripheral blood CD3 chimerism was monitored at day 30, 60, 100, 180 and 1 year post-HSCT. Patients with MDC (defined as CD3 The median age of the cohort at transplant was 59 yrs (25-71). At the time of initial diagnosis 70% of the patients had an advanced stage disease (RAEBI/II (24%) or AML(46%)). Mean donor CD3 chimerism at the time of DLI was 44% (range: 0–76%) and median time to DLI was 195 days (range: 22 to 732 days). The median number of DLI doses was 3 (range:1-5) with a median total CD3 dose of 4.9×106̂ CD3/kg (range: 5×105̂ to 4.15×108̂). The majority of patients (83%) achieved full donor chimerism (FDC, >95%) at a median time of 193 days following the start of DLI (range: 47–732 days). The incidence of GVHD was 54%, however the incidence of severe (acute grade III,IV or chronic extensive) GvHD was limited at 21%. Skin was the commonest site of involvement with GvHD. The number of DLI doses, the total DLI dose infused, recipient age, donor source and disease stage all had no association with the development of GvHD or attainment of FDC post DLI. At last follow-up, 10 patients had died due to disease relapse(4), PTLD(1), GvHD/CMV(1), multi-organ failure(1), cerebral haemorrhage(1), infection(1) and encephalopathy(1). Evidence of relapsed disease was seen in 7 patients, and 3 patients proceeded to a second RIC HSCT. The 2-yr actuarial OS, TRM and DFS was 81%+/−6%, 14%+/−6%, and 68%+/−8% respectively. Encouragingly, the median OS for survivors post-DLI was 2537 days (range: 805–3287 days). Neither donor source, disease stage nor the presence of GvHD post-DLI had any impact on TRM, relapse or OS. Patients who achieved FDC post DLI had a 2-yr OS of 84%+/−7% when compared with those who failed to achieve FDC: 60%+/−21%, p=0.23. In conclusion, the use of pre-emptive DLI HSCT is associated with a low incidence of severe GvHD and a low TRM and relapse. In combination with an alemtuzumab-based RIC HSCT, this approach facilitates the attainment of durable long-term remission in patients whilst reducing the procedure related toxicity. Disclosures: No relevant conflicts of interest to declare.

Abstract 2265 Poster Board II-242 While reduced intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT) regimens have expanded the scope of transplantation, use of these regimens are associated with a higher relapse rate. Disease relapse following following allo-HSCT in acute myeloid leukemia(AML) and high-risk myelodysplastic syndromes(MDS) is associated with a particularly poor prognosis. We performed a retrospective analysis on 157 consecutive patients with high risk (AML/MDS) who received a uniform fludarabine-busulphan based RIC HSCT at our centre between Jul 2002 and Oct 2006 and identified 45(28%) patients who had subsequent cytogenetic or morphological relapse. We proceeded to analyse the patient/disease characteristics of the 45 patients to predict response to salvage therapy. The patient diagnoses were: 19 MDS RAEB I/II, 17 AML, 6 CMML, 3 CML-blast crisis. All patients had received intensive chemotherapy prior to transplantation (median 2 courses, range 1-6). 7 patients were receiving a second allo-HSCT. At time of transplantation, 34 patients had 5% blasts. 81% of patients had intermediate/poor risk cytogenetics. The median patient age at time of relapse was 52yrs (range:24-72). The median time to relapse was 246 days(range:34-1034). The median survival following relapse was 203 days, with a 2-year OS from time of relapse of 24%+/-6%. On univariate analysis, the time to relapse post-HSCT was the most significant predictive factor of OS post-relapse. All patients who had relapsed 180 post-HSCT was 43%+/-10% (p5% blasts at time of allograft had an inferior post-relapse 2-yrs OS when compared with those in remission (9% vs 29%, p=0.1). Patients were further analysed based on the salvage treatment received; no therapy: 5, donor lymphocyte infusions(DLI) only:6, chemotherapy only:12, intensive chemotherapy (defined as a regimen containing high dose arabinose cytarabine) followed by DLI:17, second allograft:5. There was a significant difference in therapy given dependant on the time-post relapse, with 18/22 patients who had early relapse receiving either no therapy, or DLI/chemotherapy alone, while 18/23 late relapsing patients received intensive chemotherapy+DLI or a 2nd allograft. At one year post-relapse, only 1 patient who received DLI only (out of those who received no therapy/DLI only/chemotherapy only) was alive. In contrast, 10/22 patients who received either intensive chemotherapy+DLI or a 2nd allograft were alive and in durable remission with a median survival post-relapse of 1767 days (range:1123-2581), with no significant difference in outcomes between either form of therapy (2 year post-relapse OS: chemo/DLI 47% vs 2nd allograft 40%). In conclusion, the disease kinetics and time to relapse following RIC HSCT play a significant role in determining subsequent outcomes. The prognosis of patients who relapse within 6 months remains extremely poor. In contrast, we demonstrate that of patients who relapse after 6 months, treatment with chemotherapy followed by cellular therapy (either in the form of intensive chemotherapy followed by DLI, or a 2nd RIC followed by HSCT), can effectively salvage a significant proportion of patients with attainment of durable long-term remissions. Disclosures: Off Label Use: fludarabine, alemtuzumab- used off-label for transplant conditioning. Marsh:Genzyme: Consultancy, Honoraria.

Abstract 2266 Poster Board II-243 Reduced-intensity conditioning haematopoietic stem cell transplantation has dramatically improved the accessibility and safety of transplantation in groups of patients previously ineligible because of age or comorbidity. We report the long term results of allografting following reduced intensity conditioning with Fludarabine® 30 mg/m2 i.v. ( Day –9 to Day –5); busulphan 4mg/kg/day oral or 3.2mg/kg/day i.v. (Day –3 to Day –2) & alemtuzumab 20mg i.v. ( Day –8 to Day –4) in patients with myelodysplastic syndromes. Immunosuppression comprised cyclosporine 1.5 mg/kg iv 12 hourly from Day –1 titrated to plasma trough levels of 150-200 ng/l. Peripheral blood stem cells (PBSC) or bone marrow was infused on Day 0. Filgrastim 300 mcg iv/sc was administered from Day +7 to neutrophil engraftment (neutrophils ≥ 0.5×109/l). 213 patients with Myelodysplastic Syndrome (RCMD-RS=5, RCMD=44, RAEB-1=19, RAEB-2=36, CMML=18, TLD-AML=91)(IPSS Low=7, Int-1=46, Int-2=39, High=12) received transplants from matched sibling donors (57) or volunteer unrelated donors (VUD)(156 ). The median age for sibling recipients was 56 years (38-72) and for VUD recipients 55 years (19-71). All had relative or absolute contraindications to receiving standard myeloablative conditioning allografts. 52 of 57 sibling HSCTs utilised PBSCs compared with 106 of 156 VUD HSCTs, with a median CD34 cell dose of 5.11×106 (0.7-17.5) and 5.2×106 (0.44-19.90) respectively. On high resolution typing 46 VUD grafts were mismatched. There was no difference in engraftment latency between sibling and VUDs, with the median time to neutrophil engraftment (>0.5×109/l) of 14 days (9-57) and 13 days (8-31) and platelets(>20×109/l), 14 days (7-120) and 15 days (3-120) respectively. With a median follow-up of 2202 days (718-3709)(siblings) and 1693 days (29-3659)(VUD), the treatment related mortality (TRM) at Day100, 200 and 360 and 5 years was 4%, 9% 13% and 27% respectively for siblings; 8%, 17% and 25% and 28% for VUD (p=0.48). 12% of TRM deaths were due to CMV and 8% to PTLD. The Kaplan-Meier overall survival at 5 years was 46% for siblings and 41% for VUD(p=0.28), with a disease free survival (DFS) of 30% and 35% (p=0.94) respectively. The prognostic significance of some of the IPSS and diagnostic groups was preserved with a DFS of 46% in the “Low & Int-1” group at 5 years; 23% in “Int-2”; 0 % in “High”, 21% in CMML and 37% in TLD-AML. (p=ns, except Low-Int-1 vs. CMML(0.005), H (0.002) and Int-2(0.014)). The DFS was 80% in RCMD-RS, 49% in RCMD, 19% in RAEB-1 and 13% in RAEB-2.(p=ns except RCMD vs. CMML(0.015), RAEB-2(0.023)). Patients with TLD-AML had received more pre-transplant chemotherapy (median 3 courses (1-6)) compared with IPSS-High (median 1(1-3)). Patients who did not require cytotoxic chemotherapy had a 5 year DFS of 60%(p=0.003). There was no statistical difference in 5 year DFS between patients requiring induction chemotherapy in CR1(29%), CR2 (25%), PR (20%), or with progressive/relapsed disease (22%). The median DFS for these groups were 410, 362, 158 and 271 days. Lineage specific (CD3 & CD15) chimerism results were available on 133 patients. 40% achieved full donor T-cell chimerism (>95%) with 72% achieving full donor engraftment in unfractionated bone marrow by Day100, with a 24% cumulative incidence of Grade II to IV denovo aGvHD and 9% extensive cutaneous cGvHD. 83 patients (41(74%) sibling & 42(26%)VUD) received the first dose of incremental DLI at a median of 195 days (60-1323) post transplant. 53 received DLI for persistent mixed or declining donor chimerism, 11 for cytogenetic relapses and 19 morphological relapses. The desired effect was achieved in 67%, 45% and 42% respectively. A graft versus leukaemia effect was demonstrable. RIC allogeneic HSCT with fludarabine, busulphan and alemtuzumab appears to be potentially curative with a plateaux in DFS after 5 years. Further follow-up in patients with Low-Int-1 and Int-2 MDS and CMML is required to determine if there is a survival advantage for transplanted patients. Disclosures: Off Label Use: fludarabine, alemtuzumab- used off-label for transplant conditioning.

Abstract 3362 Poster Board III-250 Several groups have used in-vivo T-cell depletion in conjunction with RIC HSCT protocols in an attempt to improve engraftment and reduce the incidence of graft-versus-host disease. However, the potential benefits of this approach are potentially offset by an attenuation of the graft-versus-leukaemia effect. While, anti-thymocyte globulin(ATG) and alemtuzumab are commonly used in RIC HSCT protocols, there is limited data available on the comparative effects of either form of T-cell depletion on clinical outcomes. We performed a retrospective analysis on 65 patients with high risk AML/MDS who underwent a HLA-matched sibling donor RIC HSCT receiving either ATG or alemtuzumab. All patients received fludarabine (30mg/m2 x 5 days intravenously), and either oral busulphan (4mg/kg x 2 days) or IV busulphan (3.2mg/kg x 2 days). From Jan 2002-Jun 2005, 41 patients received GvHD prophylaxis with alemtuzumab (20mg x 5 days intravenously) followed by cyclosporin A post-transplant. From Jun 2005 onwards, 21 patients received GvHD prophylaxis with ATG (Thymoglobulin, Genzyme) (total 6mg/kg over 3 days intravenously) followed by methotrexate and cyclosporine A post-transplant. All patients had either MDS RAEB I/II (n=26), or de novo/secondary AML (n=39). The median recipient age was 57 years (range:39–65) for ATG and 56.0yrs (39-72) for alemtuzumab. All ATG patients received PBSC with a median CD34 cell dose of 5.15×106/kg (2.04 – 9.23). 37/41 alemtuzumab patients received PSBC with median CD34 cell dose of 5.10×106/kg (1.86 – 13.9). Both groups were matched for donor/recipient age, disease type, cytogenetic risk, disease stage at transplantation, cell dose. Median follow-up (for survivors) was 721 days (range: 187–1138) for ATG group and 2082 days (1094-3233) for the alemtuzumab group. Median time to neutrophil (>0.5×10 9/kg) and platelet (>20×10 9/kg) regeneration was 13 days and 14 days respectively, with no significant difference between both arms. There was 1 case of primary graft failure with ATG but none in patients receiving alemtuzumab. Lymphoid (CD3) engraftment was significantly slower in the alemtuzumab arm, with only 41% vs 75% patients attaining full donor chimerism(>95% donor) at day 100. There was no significant difference in the incidence of grade II-IV acute GvHD (ATG: 15%, Alemtuzumab 9%). However, patients who received ATG had a significantly higher incidence of chronic extensive GvHD (34% vs 6%, p=0.03). In addition, a significantly larger proportion of patients receiving alemtuzumab required subsequent DLI therapy (68% vs 19%). On univariate analysis, there was no significant difference in 2-year OS, and TRM between the alemtuzumab vs ATG group (56.1%+/-8% vs 73.7%+/-10%, p=0.25), and (19.5%+/-7% vs 10.6% +/- 7%, p=0.43). However, the use of ATG was associated with a significantly lower 2-year relapse incidence (28.4%+/-15% vs 51.5%+/-8%, p=0.04), and superior DFS (63.6%+/-14% vs 39.0%+/-8%, p=0.03). In summary, our experience indicates that in patients with high risk MDS or AML undergoing a sibling donor RIC HSCT, use of ATG confers a higher incidence of extensive chronic GvHD with a consequently lower relapse incidence and more favourable DFS when compared with alemtuzumab. In the setting of sibling RIC HSCT, the use of ATG for T-cell depletion may thus be more suitable for patients with more aggressive disease. In contrast the use of alemtuzumab at the dose reported may be more suitable for treatment of patients with stable/lower-risk disease, or for the treatment of non-haematological malignancies. Further studies with regards to dose titration of both ATG and alemtuzumab in specific disease settings are warranted. Disclosures: Off Label Use: fludarabine, alemtuzumab- used off-label for transplant conditioning. Marsh:Genzyme: Consultancy, Honoraria.

The use of reduced intensity conditioning regimens (RIC) has facilitated the allografting of older patients while concurrently reducing the transplant-related mortality associated with allogeneic haematopoietic stem cell transplantation. At present, there is limited data available on the longer-term efficacy and safety of RIC HSCT. We performed a retrospective study on the long term outcomes of patients with haematological malignancies who received RIC HSCT at our center over an 8 year period from Jan 1997 to Dec 2005. A total of 263 adult patients received RIC HSCT, of which 135 patients (51%) survived for 2 or more years and were analysed for long-term outcomes and complications. The median recipient age among our long term survivors at HSCT was 49 years (range: 24–66), with an M: F ratio of 1.6:1 and median follow-up of 51.8 months (range 23.9–100.3). All patients received alemtuzumab (CAMPATH 1H) based RIC regimens with cyclosporin A as post-transplant GvHD prophylaxis. 61 were sibling donor and 74 were volunteer unrelated donor (VUD) transplants. 90 patients (66%) had a myeloid malignancy (mainly AML and MDS), 35 (26%) had lymphoid malignancy and 9 (7%) had myeloma. The stem cell source was PBSC in 98(73%) and bone marrow in 37(27%) cases. Using a 2-year landmark analysis, the actuarial survival at 3 and 5 years was 96% (95% CI: 94.3–97.7) and 91.6% (95% CI: 88.6- 94.6) respectively. There were 8 deaths in the cohort. Four deaths (50%) were due to late relapses, with 4 others due to respiratory failure(1), HBV reactivation with fulminant hepatic failure(1), adenovirus infection(1), chronic GvHD with invasive pulmonary aspergillosis(1). 44 patients had prior acute GvHD (33%). 20(15%) developed chronic GvHD (13 cutaneous involvement, 1 hepatic, 2 hepatic and cutaneous, 5 bronchiolitis obliterans). 18 other patients developed GvHD post donor lymphocytes infusion (DLI). The cumulative incidence of active cGvHD at 3 years and 5 years was 8% and 4% respectively. Significant infectious complications occurred in 38 patients (28%) of which 20 had VZV reactivation most commonly involving the trigeminal nerve. A further 14 had pulmonary problems (9-recurrent chest infections, 2-pneumocystis carinii pneumonia, 2-IPA, 1-TB). Endocrine complications included hyperthyroidism (2 cases) and hypothyroidism (14 cases). In addition, there were 4 cases (8% incidence) of premature menopause and 4 cases (5% incidence) of erectile dysfunction. Secondary malignancy occurred only in 1 patient who developed squamous cell carcinoma of the skin. In addition there were 4 cases of moderate renal impairment, 2 cases of cerebral ischaemic attacks, 8 reports of immune thrombocytopenia/ autoimmune haemolytic anemia. Patients who survive beyond 2 years following alemtuzumab-based RIC HSCT have an excellent overall survival, with a low incidence of chronic GvHD. Nevertheless, late complications of HSCT are still frequent in this cohort. Our data suggests that late effect in patients following RIC HSCT is different from those seen in patients following myeloablative HSCT. Prospective studies are warranted in long-term survivors of RIC HSCT in order to guide appropriate longer-term follow-up.