Acute pancreatitis due to severe hypertriglyceridemia in the COVID-19 era: The role of therapeutic plasma exchange.

The psychosocial consequences of the COVID-19 pandemic caused multifaceted challenges in clinical and therapeutic practices. This was the case at the Therapeutic Apheresis Unit of the Padua University Hospital too. Several published reports describe the increase in alcohol and food addiction diseases. In this context, during the last months, the Padua Therapeutic Apheresis Unit treated many more patients with acute pancreatitis due to severe hypertriglyceridemia with therapeutic plasma exchange than in the previous ten years. Furthermore, retrospective cohort studies have been recently published describing the onset of acute pancreatitis during the COVID-19 infection even if, to date, there is still insufficient evidence to estabilish a direct causality. Anyway, the COVID-19 pandemic translated into changes of the overall disease prevalence scenario and therefore the Padua Therapeutic Apheresis Unit will need to reorganise its Therapeutic Apheresis activity.

To Transplant or Not to Transplant During the SARS-CoV-2 Pandemic? That Is the Question.

The novel coronavirus disease 2019 has grown to be a global public health emergency. The rapid spread of the infection has raised many questions in the oncohematological scientific community regarding the appropriateness of high-dose chemotherapy with autologous stem cell transplantation (ASCT). We here report two cases of patients who received ASCT at our Institute during the epidemic in Italy, affected with Hodgkin lymphoma and germ cell tumor, respectively. The two patients underwent a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on hospital admittance and during the period of bone marrow aplasia. They were attended to exclusively by dedicated health care staff who followed specifically implemented protocols for bedside nursing and care. They completed the procedure without unexpected side effect. Our experience demonstrates how ASCT can be performed safely if procedures are reorganized ad hoc to reduce the risk of SARS-CoV-2 infection.

The Italian Register of therapeutic apheresis: How it has grown, how it has changed.

In Italy therapeutic apheresis procedures were carried out for the first time in the '70s. in the '80s the Italian Society of Hemapheresis was founded, formerly named SIDE, now SIdEM (Italian Society of Hemapheresis and Cellular Manipulation). From the beginning, the collection and the analysis of activity data have been seen as a way to improve the knowledge on mechanisms of action, to identify the correct rationale in order to intervene in the most appropriate clinical indications. Over the years the data collection has been refreshed and today we can rely on information representing the evolution of TA in Italy, from an organizational/technological viewpoint and according to clinical indications. Over the years the aspects that have mainly changed are the technologies, the organizational and managerial aspects and, above all, the clinical indications. The primary indication for therapeutic apheresis is still today the thrombotic thrombocytopenic purpura, but corrently, whenever a disease recognizes an autoimmune pathogenesis, the use of apheresis may be a valid therapeutic tool in the event of failure or partial efficacy of conventional drug therapy. The continuous monitoring of apheresis activity through Registries is a useful tool to follow the evolution of the apheresis practice.

Therapeutic apheresis during pregnancy: A single center experience.

INTRODUCTION: Therapeutic apheresis (TA) represents a treatment option for pre-existing conditions or diseases occurring during gestation. Although pregnancy is not a contraindication per se, due to the lack of evidence-based guidelines and presumed risk of maternal/fetal adverse events there is a general resistance to its application. MATERIAL AND METHODS: Between January 2005 and August 2017, at the Apheresis Unit of the University Hospital of Padua 936 TA procedures were performed during 57 pregnancies in 48 patients: 813 Plasma Exchange sessions, 119 Immunoadsorptions, 4 Red Blood Cell exchanges. The treated disease were as follows: antiphospholipid syndrome (18 patients), autoimmune congenital heart block (18), myasthenia gravis (3), Rh alloimmunization (2), systemic sclerosis (1), suspected autoimmune encephalitis (1), severe hypertriglyceridaemia (1), post partum hemolytic-uremic syndrome (1), sickle cell disease (1), lupus nephritis (1) and thrombotic thrombocytopenic purpura (1). RESULTS: In the time period considered the apheresis sessions applied to pregnant women were 7.1% of the total (n = 13.251). The median age at the first treatment was 33 years. The median week of gestation (WG) at the beginning of treatments was 21. Twenty (2.1%) sessions were complicated by adverse events, none requiring or prolonging hospitalization. There were 50 live births, 5 spontaneous abortions and 2 voluntary terminations of pregnancy. Median WG at delivery was 35 and caesarean section was performed in 46 cases. CONCLUSIONS: Our data showed that TA in pregnancy is well tolerated. Close collaboration between clinician, obstetrician and TA specialist is crucial to ensure a good outcome of high-risk pregnancies.

Italian Registry of Therapeutic Apheresis.

Since the 80s the Italian Society of Apheresis and Cell Manipulation (SIdEM) started to monitor the adverse events of therapeutic apheresis (TA) procedures. In subsequent years other variables were added and a national TA registry was created, with a fluctuating adhesion over the years. From 2010 to 2013 the Registry was shared with the Italian Society of Nephrology (SIN): the collection method required data of each patient and a lack of adhesion was observed, mainly because of a heavy workload needed to fill out all the fields. SIdEM was then forced to simplify the form by collecting aggregated data. At the same time, the Italian Privacy Authority (IPA) gave a negative opinion on the use of the SIdEM-SIN registry because it did not prevent the possibility to identify the patients and raised the question whether a national registry could be managed by a scientific society or if it should be under the control of the Regulatory Authority (CNS - National Blood Centre). Since 2015 SIdEM has continued to collect aggregated data, with a simple form sent to each Italian TA unit. Today the main limitation of our Registry is the absence of informatic and financial support and the main limit of all TA Registries is represented by the voluntary adhesion, which can be limited by lack of time and interest or reluctance to show and share own data. In the last year SIdEM has started to work with the CNS in order to implement and integrate the Registry into the Information System of the Transfusion Units (SISTRA), a system that monitors the activities of the whole Italian blood system.The hypothesis of a Global Registry is fascinating. In order to have the greatest adhesion it should be easy and fast to fill in and, possibly, based on aggregated data.

Personalized treatment with immunoadsorption and intravenous immunoglobulin in a case of severe Rh alloimmunization during pregnancy unresponsive to plasma - exchange.

INTRODUCTION: Despite prophylaxis, a small proportion of RhD-negative women may develop anti-D antibodies after a sensitizing event occurring during pregnancy or delivery of a D-positive baby. Intrauterine transfusion (IUT) is the treatment of choice in case of fetal anemia, but it cannot be performed early during pregnancy. Combined treatment with therapeutic plasma-exchange (TPE) and intravenous immunoglobulin (IVIG) can avoid or delay IUT. Immunoadsorption (IA) could represent a more effective treatment in selected cases. CASE REPORT: We report a D-negative female with a history of induced abortion and hydrops fetalis, referred at 8 weeks of gestation with a high anti-D titer. Despite implementing a TPE-IVIG protocol, the patient experienced a spontaneous abortion. At the beginning of her fourth pregnancy, only after a partially effective intensive TPE course, cycles of IA-IVIG were performed. Despite a suboptimal response on the anti-D titer, Doppler ultrasonographic measurements of the fetal middle cerebral artery peak systolic velocity first showed evidence of anemia at 30 weeks of gestation and a IUT was required. After the IUT, anemia persisted with a subsequent dramatic rise in titer, requiring an emergent cesarean section. The infant subsequently underwent successful treatment with IVIG, phototherapy and exchange transfusion and was discharged 7 weeks later without neurological deficits. DISCUSSION: The treatment of high titer anti-D antibodies during pregnancy may require a multidisciplinary approach with utilization of different apheresis strategies in order to have a successful pregnancy outcome.

Successful treatment of pyoderma gangrenosum with granulocyte and monocyte adsorption apheresis.

Pyoderma gangrenosum is a neutrophilic dermatosis clinically characterised by the presence of painful skin ulcerations with erythematous and undetermined borders and histologically by the presence of neutrophilic infiltrates in the dermis. Granulocyte and monocyte adsorption apheresis, also called granulocytapheresis, is a therapeutic strategy for extracorporeal immunomodulation that selectively removes activated granulocytes and monocytes/macrophages from the peripheral blood. Here, we report a case of a 73-year-old patient affected by a severe form of pyoderma gangrenosum presenting with multiple painful ulcers and pustules on his trunk and extremities. The disease was resistant to high doses of methylprednisolone and methotrexate and successfully treated by granulocyte and monocyte adsorption apheresis. To the best of our knowledge, this is the first report on the efficacy of granulocyte and monocyte adsorption apheresis in pyoderma gangrenosum in Europe.

Spontaneous splenic rupture following stem cell mobilization with G-CSF and plerixafor in AL amyloidosis.

BACKGROUND: AL amyloidosis is a rare plasma cell dyscrasia with multiorgan involvement. Good risk patients are candidate to high dose chemotherapy and autologous stem cell transplantation. However both transplantation and stem cell collection entail significant risk in such patients. Plerixafor is a novel mobilizing agent approved for use in "poor mobilizer" patients with lymphoma and multiple myeloma; experience in systemic amyloidosis patients is limited. CASE REPORT: We describe a case of spontaneous splenic rupture following administration of G-CSF and plerixafor in a patient with AL amyloidosis who previously underwent heart transplantation due to amyloid heart involvement. RESULTS AND CONCLUSION: This is the first report of spontaneous splenic rupture following stem cell mobilization with G-CSF and plerixafor in AL amyloidosis. The role of plerixafor has to be established. AL amyloidosis patients undergoing stem cell mobilization need careful monitoring of signs and symptoms of spontaneous splenic rupture.

Treatment of Acute Graft-versus-Host Disease in Childhood with Extracorporeal Photochemotherapy/Photopheresis: The Padova Experience.

Acute graft-versus-host disease (aGVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Systemic steroid treatment represents the first-line therapy for aGVHD and is associated with a response rate of 30% to 60%. Steroid-resistant patients have a poor prognosis with high transplantation-related mortality (TRM). Several second-line therapies have been proposed for the management of unresponsive aGVHD, without proven beneficial effects on patients' outcome or overall long-term survival. For these reasons, extracorporeal photochemotherapy/photopheresis (ECP), a cell-based approach to control GVHD that spares generalized immunosuppression, seems to be promising. In this study, we report the outcome of 72 consecutive pediatric patients treated with ECP between 1997 and 2013 for aGVHD. Among them, 21 patients had steroid-resistant aGVHD, 42 had steroid-dependent aGVHD, and 9 did not receive steroid as first-line therapy because of clinical contraindications. A complete response was obtained in 72% of patients, a partial response was observed in 11%, and there was no response in 17% of patients. At day +180, TRM was 4% in the whole cohort; TRM was 3% and 20% among responders and nonresponders to ECP, respectively (P < .0001). The 5-year overall survival was 71%, showing a difference between responders and nonresponders of 78% and 30%, respectively (P = .0004). The 5-year time to progression of primary disease was 81%, without any significant difference between the 2 groups. Moreover, the 5-year progression-free survival of primary disease was 72%, with a significant difference (P = .0007) between responders (79%) and nonresponders (30%) to ECP. In conclusion, this study demonstrates that ECP is highly effective in aGVHD without a negative impact on primary disease.

Plasma exchange effectively removes 52- and 60-kDa anti-Ro/SSA and anti-La/SSB antibodies in pregnant women with congenital heart block.

BACKGROUND: Pregnant women positive for 52- and 60-kDa anti-Ro/SSA and anti-La/SSB antibodies can suffer from congenital heart block (CHB), a passively acquired autoimmune disease. STUDY DESIGN AND METHODS: We evaluated the efficacy of plasma exchange (PE) in removing 52- and 60-kDa anti-Ro/SSA and anti-La/SSB antibodies in pregnant women with CHB treated with a combined therapy including PE, intravenous immunoglobulins, and steroids. Antibody levels were monitored in 10 consecutive pregnant women diagnosed with CHB and prospectively followed between 2009 and 2013. Assaying was performed using a homemade enzyme-linked immunosorbent assay test on blood samples collected immediately before and after PE sessions. RESULTS: A significant decrease in mean post-PE antibody levels was noted in all the cases examined. An analysis of antibody level trends in the samples collected before PE sessions showed that there was a steady, significant decrease in 90% of the patients with 52-kDa anti-Ro/SSA, in 80% of those with 60-kDa anti-Ro/SSA antibodies, and in 100% of those with anti-La/SSB antibodies. CONCLUSION: This study demonstrates that PE is effective in removing antibodies linked to the pathogenesis of CHB. PE treatment was found to have a long-term efficacy in all the women positive for anti-La/SSB antibodies and in most of the women positive for 52- and 60-kDa anti-Ro/SSA antibodies. It is interesting that the significant, immediate, and long-term fall in antibody levels that was observed in these patients took place in all the women whose CHB was reversed. This finding could give PE an important role in the treatment of CHB.

Therapeutic apheresis in pregnancy: General considerations and current practice.

It is widely known that pregnancy does not represent a contraindication to therapeutic apheresis (TA) techniques. In fact, since the first experiences of TA in pregnancy for the prevention of hemolytic disease of the newborn, several diseases are at present treated with TA, mainly within 6 clinical categories: (a) TA is a priority and has no alternative equally effective treatment (e.g., thrombotic thrombocytopenic purpura); (b) TA is a priority but there are alternative therapies not contraindicated in pregnancy (e.g., myasthenia gravis); (c) TA is an effective tool of saving/avoiding drugs contraindicated in pregnancy (e.g., systemic lupus erythematosus); (d) TA is a treatment of specific conditions/complications of pregnancy with maternal and/or fetal risk (e.g., antiphospholipid syndrome); (e) TA is a treatment of specific conditions of pregnancy with exclusive fetal risk (e.g., hemolytic disease of the newborn); (f) TA is a treatment of disease which is strongly indicated and can exceptionally occur during pregnancy (e.g., Goodpasture's syndrome). When dealing with TA pregnant patients, some technical aspects due to the physiological changes of gestation have to be carefully considered, in particular the increase of the circulating blood volume. Moreover a multidisciplinary medical team, including an obstetrician, a clinical consultant, specialist in TA and in transfusion medicine, and a neonatologist stand as a basic requirement for the proper management of some clinical conditions that may be characterized by high maternal and fetal risk.

Plasma-exchange as a "rescue therapy" for dermato/polymyositis in acute phase. Experience in three young patients.

There are few data in the literature supporting the efficacy of plasma-exchange in dermato/polymyositis. The authors report three cases of patients with acute disease phase showing severe pharyngo-esophageal muscle weakness unresponsive to conventional therapy (corticosteroids and immunosuppressant agents) who were treated with plasma-exchange. As the patients were at high risk of "aspiration pneumonia", tracheostomy and PEG tubes were placed. The patients underwent a series of plasma-exchange for a mean of 15 weeks, during which time they progressively recovered muscle strength, their serum muscle enzyme values returned to normal levels, and MRI showed resolution of muscle edema. The tracheostomy and PEG tubes could be removed. Our findings suggest that plasma-exchange in association with immunosuppressant agents could play a relevant role in the management of dermato/polymyositis in acute phase.

Stress, burnout, and job satisfaction in 470 health professionals in 98 apheresis units in Italy: A SIdEM collaborative study.

AIMS: In Italian and international background, there are no studies focusing on stress, burnout indicators, and job satisfaction in health professionals working in the apheresis units. This study aims to fill this void both for scientific and clinical reasons. METHODS: The participants were 470 health professionals (220 physicians, 250 nurses), mostly female (73.4%), with an average age of 48.09 (with the 5° percentile under 32 years and the 95° percentile over 60), working in the Apheresis Units in the North (228), in the Center (131) and in the Southern-islands of Italy (111). The health professionals' years on the job were principally between one and 10 years (40.2%) or from 11 to 20 years (33.2%). The prevalent activity was therapeutic apheresis (48.5%). The self-report questionnaires were proposed electronically by a protected online site. RESULTS: Important stress levels were identified in the health professionals. Physicians principally showed medium (47.5%) and high (35.8%) stress levels. Stress levels of nurses were mostly low (57.7%) or medium (25.7%). Female gender in nurses [t(268) = -3.29; P = 0.001] and in physician professions [t(217) = -3.01; P = 0.03] was a risk factor for stress. Both job categories were placed at a high risk level for burnout syndrome comparing with normative scales, especially the health professionals working in the center of Italy for the scales "Emotional exhaustion" [F(2) = 4.39; P = 0.013] and "Professional inefficacy" [F(2) = 4.38; P = 0.013]. CONCLUSIONS: Health professionals working in the apheresis unit show high stress levels and burnout risk. New preventive programs and specific clinical interventions should be constructed.

Prognosis of scleroderma renal crisis: a long-term observational study.

BACKGROUND: Despite the efficacy of angiotensin-converting enzyme (ACE) inhibitors, the prognosis of patients with Scleroderma renal crisis (SRC) is characterized by a high rate of mortality and progression into end-stage renal disease (ESRD). Our aim was to evaluate the prognosis of SRC in our cohort of scleroderma patients. METHODS: We reviewed clinical charts of all our patients who developed SRC from 1980 to 2005. Outcome measures were ESRD, patients' survival and SRC-related mortality. ESRD was defined as the need for chronic dialysis; survival was calculated from the time of SRC occurrence by Kaplan-Meier method. All patients were treated with ACE inhibitors and 10 patients were also treated with plasma exchange (PEx). Indications to PEx were concomitant micro-angiopathic haemolytic anaemia or intolerance to high doses of ACE inhibitors. SPSS package was used for calculation. RESULTS: Of 606 patients, affected with systemic sclerosis, who came at our observation during the aforementioned interval, 20 (3.3%) developed SRC. One year after SRC onset, 55% of patients developed ESRD. The survival rate was 70% at 1 year and 50% at 5 years; the mortality rate related to SRC was 35%. Notably, in the subgroup of patients treated with PEx, 20% developed ESRD; the survival rate was 90% at 1 year and 70% at 5 years; the mortality rate related to SRC was 10%. CONCLUSIONS: Short-term prognosis of SRC has improved, but long-term prognosis remains disappointing. PEx in addition to ACE inhibitors seems to be a therapeutic option in patients with SRC who develop micro-angiopathy or are intolerant to high doses of ACE inhibitors.

Plasma exchange and immunoadsorption effectively remove antiphospholipid antibodies in pregnant patients with antiphospholipid syndrome.

Conventional therapy with aspirin and/or heparin is at times incapable of preventing complications in high risk pregnancies of patients with antiphospholipid syndrome (APS). In those cases, a so-called second-line treatment protocol is used in addition to conventional therapy strategies. This manuscript is a report on three APS pregnant patients who were successfully treated with plasma exchange (PE) (two cases) or with immunoadsorption (IA) (one case) as a second-line treatment strategy. The efficacy of these procedures in removing anticardiolipin (aCL) and anti-ß(2)glycoprotein I (aß(2)GPI) antibodies from blood was evaluated. Serum samples were collected before and after 87 apheretic treatment sessions. Serum IgG/M aCL and IgG/M aß(2)GPI antibodies were determined using an "in-house" enzyme-linked immunosorbent assay and showed that all three patients had medium/high IgG aCL and aß(2)GPI titers. All three women had a successful pregnancy. A significant decrease in IgG aCL (P = 0.0001) and aß(2)GPI (P = 0.0001) antibody titers was observed after PE and IA sessions. There was moreover a significant, steady fall in serum IgG aCL pretreatment levels during the course of all three pregnancies (P = 0.0001, P = 0.0001, P = 0.001). The fall in IgG aß(2)GPI was significant in two of the patients (P = 0.0001, P = 0.0001) both with high antibody titers, but not in one with medium antibody titers, who was treated with PE (P = 0.17).

[Apheresis in antiphospholipid syndrome (APS)]. / L'aferesi nella sindrome da Anticorpi Antifosfolipidi (APS).

Antiphospholipid syndrome (APS) is a rare clinical disorder characterized by thromboembolic manifestations and/or obstetric complications. Along with the clinical symptoms and signs, serum antiphospholipid antibodies have to be detected. APS can be primary, i.e., without any concomitant disorders, or secondary to other autoimmune diseases, particularly systemic lupus erythematosus. Criteria for the diagnosis of APS have been clearly established. Hyperacute APS (or catastrophic antiphospholipid syndrome), often with a poor prognosis, must meet four criteria: involvement of three or more organs, rapid evolution of clinical manifestations, microangiopathic occlusion of small blood vessels at biopsy, and presence of antiphospholipid antibodies. The rationale for apheresis treatment is the removal of pathogenetic antibodies involved in the development of tissue damage. Our experience includes 23 patients, in particular 15 women treated for 19 pregnancies. According to the National Guidelines Program, the effectiveness of apheresis in catastrophic syndrome has a level of evidence of V/VI, with a strength of recommendation A; in highrisk pregnancy it has a level of evidence of V with a strength of recommendation B. It will be necessary to better define the prognosis of various categories of pregnant patients with APS, as well as useful laboratory parameters to monitor its clinical course and anticipate any complications of pregnancy.

[Role of antibodies in kidney transplant]. / Ruolo degli anticorpi nel trapianto di rene.

Rejection is one of the most frequent causes of graft loss after a kidney transplant. In this context, in the last few years the essential role of antibodies in the anti-graft immune response has become more evident. Antibody-mediated damage has been classified into four histological patterns: hyperacute rejection, caused by the presence of pre-existing donor-specific antibodies directed against HLA or non-HLA antigens; acute antibody-mediated rejection, usually due to antibodies elicited following transplantation; chronic antibody-mediated rejection, which can develop months or years after the first appearance of circulating antibodies; and Cd4 deposition without morphologic evidence of active rejection, previously described as ''accommodation''. In recent years, thanks to the development of specific desensitization protocols, it has become possible to transplant patients sensitized to donor HLA antigens. Recently, besides consolidated protocols which include immunoglobulin administration associated or not with plasmapheresis, novel approaches of therapeutic apheresis with specific removal of antibodies and bortezomib, an agent that can efficiently decrease donor-specific antibody levels, have been developed. As far as the treatment of antibody-mediated rejection is concerned, different immunosuppressive strategies have been used. These include the combination of immunoglobulin administration and plasmapheresis with or without the use of an anti-CD20 monoclonal antibody. More recently, an innovative therapy with eculizumab has proved to be very effective against acute antibody-mediated rejection. The debate regarding the cause-effect relationship between the development of an early post-transplant humoral immune response in patients with stable graft function and premature graft loss remains open to discussion. Clinical studies are underway to provide an adequate answer to this question. In conclusion, comprehension of the fundamental role of antibodies and the consolidation of desensitization techniques together with early treatment of antibody-mediated rejection remain important objectives to improve long-term allograft survival.

The Italian Registry of Pediatric Therapeutic Apheresis: a report on activity during 2005.

The results of the 2005 Survey of the Italian Society for Apheresis and Cell Manipulation (SIdEM) reporting on the pediatric procedures carried out in 18 Italian Apheresis Units are presented here. Utilizing a standardized questionnaire, the survey collected data on techniques, types of blood separators, clinical indications, and adverse events. A total of 1,693 apheresis procedures were carried out in 355 pediatric patients: 219 plasma-exchange, 291 peripheral blood stem cell collections, 791 extracorporeal photochemotherapy (ECP), 265 LDL-apheresis, 71 erythro-exchange, 9 cytoreductive apheresis, 47 immunoadsorption sessions. Adverse events were registered in 94 procedures (5.6%), most of which of mild entity, e.g., insufficient flow rate (50.0%) and symptomatic hypocalcemia (24.4%). Our data indicate that all types of apheresis procedures can be safely carried out in children. ECP, utilized primarily for the treatment of graft versus host disease (GvHD) and rejection of solid organ transplantation, are burgeoning procedures in pediatric patients, whereas plasma exchange, which is a common treatment in adults, is infrequently utilized in pediatric medicine.

Treosulfan-Based Conditioning Regimen in Sibling and Alternative Donor Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease.

BACKGROUND AND OBJECTIVES: Lack of suitable donors and regimen related toxicity are major barriers for hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD). The aim of the study is the assessment of efficacy and toxicity of Treosulfan-based conditioning regimen for SCD also when alternative donors such as mismatched unrelated donor and haploidentical donor are employed. METHODS: We report our single-center experience: 11 patients with SCD received HSCT with a Treosulfan/Thiotepa/Fludarabine/Anti-thymoglobulin conditioning regimen between 2010 and 2015. The donor was a matched sibling donor (n= 7), a haploidentical parent (n= 2), a matched unrelated donor (n= 1) or a mismatched unrelated donor (n=1). The haploidentical and mismatched unrelated donor grafts were manipulated by removing TCRαß and CD19 positive cells. RESULTS: All patients survived the procedure and achieved stable engraftment. Stable mixed chimerism was observed in 5/11 patients. Grade III-IV regimen related toxicity was limited to mucositis and no grade III-IV graft-versus-host disease (GvHD) occurred. No SCD manifestation was observed post transplant and cerebral vasculopathy improved in 3/5 evaluable patients. Organ function evaluation showed no pulmonary, cardiac or renal toxicity but gonadal failure occurred in 1/4 evaluable patients. CONCLUSION: Our data suggest that Treosulfan is associated with low toxicity and may be employed also for unrelated and haploidentical donor HSCT.