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Background and objectivesLack 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.MethodsWe 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 TCRαβ and CD19 positive cells.ResultsAll 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.ConclusionOur data suggest that Treosulfan is associated with low toxicity and may be employed also for unrelated and haploidentical donor HSCT.

We designed intermediate dose etoposide + G-CSF 16 microg/kg as a Peripheral Blood Stem Cell (PBSC) mobilization schedule suitable for outpatient administration. Forty-one Lymphoma patients received intermediate dose etoposide (200 mg/m(2) i.v. day +1, +2, +3) +G-CSF 16 microg/kg/day. Results of PBSC mobilization in these patients were compared with those of a group of 37 lymphoma patients mobilized using cyclophosphamide (CTX) at dosage of 4 g/m(2) + G-CSF 10 microg/kg/die. Mean peak of CD34+ cells achieved in P.B. and total CD34+ cells harvested were higher in patients mobilized with intermediate dose etoposide (p = 0.003 and p = 0.004, respectively). After transplantation recovery of polymorphonucleate neutrophils (PMN) > 0.5 x 10(9)/L did not differ significantly between groups: 11.7 days in intermediate dose etoposide group and 11.5 days in CTX group (p = 0.7). Intermediate dose etoposide + G-CSF 16 microg/kg resulted in a maximum length of neutropenia (PMN < 0.5 x 10(9)/L) of 2 days and neutropenic fever was registered during only 3/41 courses (7.3%). Intermediate dose etoposide + G-CSF 16 microg/kg is a highly effective mobilizing therapy, further, it has the advantage of low hematologic toxicity and can be easily administered as outpatient treatment.

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We have prospectively collected data on Adverse Events (AE) that occurred in 179 Hemopoietic Progenitor Cell (HPC) infusions performed in patients affected with haematological neoplasm, after high dose chemotherapy. Stem cell source was Hemopoietic Progenitor Cells Aphaeresis (HPC-A) in 157 cases and Hemopoietic Progenitor Cells Bone Marrow (HPC-BM) in 22 cases. In all cases, an endotoxin-free DMSO was used. One or more AE were registered in 51/179 infusions (28.6%). Frequency of AE was higher after HPC-A than after HPC-BM (31.3% versus 4.5%, (chi square test: p=0.008). In univariate logistic regression other factors found important for AE were: Age (p=0.028), Number of Total Nucleated Cells infused/kg (P=0.002), Volume/kg infused (p=0.057), Volume of Packed Red Blood Cells (p=0.019), a content of Non-Mononuclear Cells >0.500 × 108/Kg (<p=0.0001) and Actual Time of infusion (p=0.058). When all aforementioned factors were evaluated in multivariate logistic regression only Age of patient (P=0.024) and a content of Non-Mononuclear Cells > 0.5×108/kg (P=0.0003) remained significant. No cardiovascular events were recorded during infusions. A significant correlation existed between reduction of cardiac frequency both with Volume/Kg infused (r 0.221; p=0.02) and with Actual Time of infusion (r 0.269; p=0.005). In conclusion, while Cardiovascular Changes are influenced by Volume/Kg infused and by Actual Time of infusion, Non-Cardiovascular AE are dependent on patient Age and on contamination by Non-Mononuclear Cells in apheretic harvests.

Haploidentical transplantation in children can extend the opportunity for transplantation to almost every patient lacking a human leukocyte antigen (HLA)?matched donor and offer this treatment to every child with an otherwise incurable disease. Although initial attempts were associated with a high transplant-related mortality, recent insights into the biology of haploidentical transplantation, the availability of effective ex vivo large-scale graft-manipulation technology, and improved supportive care strategies have led to significantly better outcomes. Concurrently, the indication for haploidentical transplantation has been extended, including different malignant and nonmalignant conditions. Worldwide donor registries include mainly donors of Caucasian origin. Patients of non-Caucasian origin have a lower chance of finding a suitable unrelated donor. Haploidentical transplantation allows the treatment of children independently of their ethnic background in a timely fashion. One of the major advantages of using a related donor is the possibility of collecting or generating additional cellular products from the same donor to open the possibility of enhancing both the antitumor effects of the graft and the immunologic reconstitution after transplantation.

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