Only limited data are available regarding myocardial iron overload in adult patients with transfusion dependent acquired anemias. To address this topic using MRI T2* we studied 27 consecutive chronic transfusion dependent patients with acquired anemias: (22 myelodysplastic syndrome, 5 primary myelofibrosis). Cardiac MRI T2* values obtained ranged from 5.6 to 58.7 (median value 39.8) milliseconds. Of the 24 analyzable patients, cardiac T2* correlated with transfusion burden (p=0.0002). No patient who had received less than 290 mL/kg of packed red blood cells (101 units=20 grams of iron) had a pathological cardiac T2* value (< 20 ms). All patients who had received at least 24 PRBC units showed MRI T2* detectable hepatic iron (liver T2* value ≤6.3 ms). Only patients with severe hepatic iron overload (T2* <1.4 ms) showed cardiac T2* value indicative of dangerous myocardial iron deposition. Serum ferritin was not significantly correlated with cardiac T2* (p=0.24). Gradient echo T2* magnetic resonance imaging provides a rapid and reproducible method for detecting myocardial iron overload which developed after a heavy transfusion burden equal to or greater than 290 mL/kg of packed red blood cell units.

In recent years, new conditioning regimens have been explored in patients not eligible for conventional transplant with the aim to reduce transplant-related mortality. In a phase II multicentric prospective trial, we investigated the safety and feasibility of the treosulfan-fludarabine combination prior to allogeneic hematopoietic stem cell transplant in patients with various hematological malignancies not eligible for conventional regimens because of previous intensive treatment, older age, and comorbidities. Forty-six consecutive patients, median age 48 years (range 17-69), were enrolled. Sixteen of them were in complete remission, and 20 had a HSCT comorbidity index 1. Forty-four patients had regular and sustained engraftment, and 39 out of 40 evaluable patients developed complete chimerism. Nonhematological toxicity was limited. Risk of transplant-related mortality was 9% (95% CI, 2-17%) at day 1100 and plotted at 15% (95% CI, 7-22%) after 7 months. The estimated overall survival and progression-free survival with a median follow-up of 20 months were 51% and 38%, respectively. The estimated 30 months progression-free survival for patients transplanted in remission was 56%. The treosulfan-fludarabine combination is a reduced-toxicity but myeloablative regimen that can be proposed to patients not fitting criteria for conventional transplant regimens. Longer follow-up and further prospective studies are necessary to evaluate this regimen. Am. J. Hematol. 83:717-720, 2008. V

In recent years, with the aim of reducing transplant-related mortality, new conditioning regimens have been explored in patients not eligible for conventional haemopoietic stem cell transplantation. In this setting, we investigated safety and feasibility of the treosulfan-fludarabine-thiotepa combination prior to allogeneic haemopoietic stem cell transplantation in patients with advanced lympho-proliferative diseases and at high transplant risk. Twenty-seven consecutive patients, median age 43 years (range 19-60), entered this study. All of them were affected by lympho-proliferative disease in advanced phase and have been heavily pre-treated. The median haemopoietic stem cell transplant co-morbidity index was 1 (range 0-3). Twenty-five patients had regular engraftment, while the remaining two patients were not evaluable for early deaths. Non-haematological toxicity was limited. No patient developed veno-occlusive disease. The estimated probability of overall survival and progression-free survival with a median follow-up of 40 months was 52% (95% confidence interval 33-73) and 50% (95% confidence interval 30-70) respectively. Six patients have relapsed; all of them were not in remission before transplantation. The treosulfan-fludarabine-thiotepa combination is a reduced toxicity but myeloablative regimen that can be proposed to patients not fitting criteria for conventional myeloablative transplant regimens. Longer follow-up and prospective randomized studies are necessary to evaluate this regimen.

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The basis of allogeneic hemopoietic stem cell (HSC) transplantation in thalassemia consists in substituting the ineffective thalassemic erythropoiesis with and allogeneic effective one. This cellular replacement therapy is an efficient way to obtain a long lasting, probably permanent, clinical effective correction of the anaemia avoiding transfusion requirement and subsequent complications like iron overload. The first HSC transplant for thalassemia was performed in Seattle on Dec 2, 1981. In the early eighties transplantation procedure was limited to very few centres worldwide. Between 17 December 1981 and 31 January 2003, over 1000 consecutive patients, aged from 1 to 35 years, underwent transplantation in Pesaro. After the pioneering work by the Seattle and Pesaro groups, this therapeutic approach is now widely applied worldwide. Medical therapy of thalassemia is one of the most spectacular successes of the medical practice in the last decades. In recent years advances in knowledge of iron overload patho-physiopathology, improvement and diffusion of diagnostic capability together with the development of new effective and safe oral chelators promise to further increase success of medical therapy. Nevertheless situation is dramatically different in non-industrialized countries were the very large majority of patients live today. Transplantation technologies have improved substantially during the last years and transplantation outcome is likely to be much better today than in the ‘80s. Recent data indicated a probability of overall survival and thalassemia free survival of 97% and 89% for patients with no advanced disease and of 87% and 80% for patients with advanced disease. Thus the central role of HSC in thalassemia has now been fully established. HSC remains the only definitive curative therapy for thalassemia and other hemoblobinopathies. The development of oral chelators has not changed this position. However this has not settled the controversy on how this curative but potentially lethal treatment stands in front of medical therapy for adults and advanced disease patients. In sickle cell disease HSC transplantation currently is reserved almost exclusively for patients with clinical features that indicate a poor outcome or significant sickle-related morbidity.

Background The management of high dose chemotherapy followed by autologous or allogeneic hemopoietic stem cell transplantation requires an intravenous line for administrations of high-dose chemotherapy, blood and platelet transfusions, antibiotics and parenteral nutrition. In this context a safe central venous access is a basic tool for patients management. The aim of our phase II prospective study is to evaluate feasibility, safety and cost of the use of peripherally inserted central catheters (PICC) for the management of hemopoietic stem cell transplantation. Methods Inclusion criteria included inpatient who needed program of autologous and allogenic hematopoietic stem cell transplantation regardless the underlined hematological disease or white cells and platelets counts. All patients were submitted to a preliminary evaluation of arms vascular anatomy by ultrasonography. All implantation procedures has been done under ultrasound guide with radiographic control after insertion. The PICC cost analysis was performed on the cost of devices, insertion and daily management and compared with a historical cohort of patients with short term central venous catheter (CVC). The study was approved by institutional review board. All patients provided a written informed consent. Results From March 2007 to July 2013 76 consecutive PICC have been implanted in 74 patients for autologous or allogenic stem cell transplantations. There were 37 male and 37 females. Median age was 55 years, range 22-70. With regard to disease, 11 patients (15%) had Hodgkin Lymphoma, 13 (17.5%) non Hodgkin lymphoma, 9 (12%) acute lymphoblastic leukemia, 35 (47%) multiple myeloma, 4 (5.5%) acute myelogenous leukemia, and 2 (3%) other hematological disease. Fifty-five PICC (72%) have been used for single autologous stem cell transplantation, 10 (13%) for double autologous stem cell transplantation and 11 (15%) for allogenic transplantation. Catheter insertion was successful in all instances. PICC median life was 119 days (1-457) for a total of 10877 days of implanted PICC. At the time of this analysis 4 out of 76 PICC (5%) are still “in situ” and in use and 72 (95%) have been removed. Reason for removal was end of therapy in 58 instances (80.5%), accidental withdrawal in 8 (11%), patient death in 1 (1.5%) and catheter related complication in 5 (7%). Catheter related complications were the following: 2 occlusions, 3 suspected PICC-related sepsis. Only 1 episode of confirmed PICC-related septicemia (0.1/1000 days/PICC) was recorded and S.Aureus was isolated. There were only 2 cases (2.6%) of symptomatic PICC-related thrombotic complications which has requested conservative management. Twenty-five of 76 PICC (33%) were power PICC. No patients presented the need for a additional central venous access. Regarding the economic aspect, the actual daily cost of PICC was 1.98 €/day versus 3.40 €/day of the short term CVC (45% lower). Conclusions These data encourage the use of PICC in the autologous and allogenic stem cell transplantation because of insertion easiness, duration of life, cost and low rate complication. Disclosures: Off Label Use: Bendamustine.

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Background. Allogeneic hemopoietic stem cell transplantation is the treatment of choice for high and intermediate risk acute myeloid leukemia (AML) and for higher risk myelodysplastic syndrome (MDS). Standards preparative regimens TBI-CY and BU-CY have been widely used and extra hematologic toxicity remains a concern. Even if the combination of intravenous formulation Busulphan-CY has shown lower toxicity and suggested favorable safety and efficacy profile new drugs associations are continuously explored. Recently the association Busulphan-Fludarabine has replaced the Bu-Cy regimen with the aim to further reduce toxicity. In our Institution we started to use this regimen as preparation for allogeneic transplantation in patients with AML and MDS in October 2008 using Busulphan in a single daily infusion with the primary objective of evaluating safety and efficacy. Methods. Since October 2008 to May 2014, 23 consecutive patients (19 males, 4 females) entered this study. Median age was 56 years (range 35-63). Thirteen patients presented with first remission AML, five with first or more advanced relapse or resistant disease and five with intermediate II or high risk MDS. Conditioning consisted of intravenous Busulphan (Busilvex® 9,6 -12,8 mg/kg) given once daily in a 4 hours infusion in association with Fludarabine 160 mg /m2 for 4 consecutive days. Fifteen patients received HSCs from HLA identical siblings, 1 from a family mismatched donor, 7 from matched unrelated donors. Source of stem cells was bone marrow in 13 patients, peripheral blood stem cells in 9 patients, and both in 1 patient. CSA + short MTX was used as GVHD prophylaxis and anti-Lymphocyte globulins (Thymoglobulin® or ATG Fresenius®) was added in case of unrelated donor transplants Toxicity was evaluated by WHO toxicity scale Common Terminology Criteria for Adverse Events (CTCAE) version 3. Acute Graft versus Host Disease was evaluated in patients with engraftment and graded according to the revised Glucksberg scale. Internal review board approved study. All patients gave written informed consent to procedure. Results. All patients regularly engrafted (mean time to neutrophils >500/microliter was 13 days (range 11-15). Seven patients experienced gastro-intestinal toxicity (1 grade III mucositis, 2 grade II mucositis, 4 grade I mucositis); 3 patients had grade II cystitis. Overall grade >II toxicity occurred in a single patient (4%). Acute grade IV gastro-intestinal- GvHD occurred in 1 patient, while 12 patients presented grade I skin GvHD. Cr. GVHD occurred in 4/18 evaluable patients (moderate in 1). CMV reactivation occurred in 15/23 patients (65%), no patient developed life-threatening bacterial or fungal infection. Eight out of 23 patients have died (35%) all but one by recurrent disease and 1 by grade IV acute GvHD. Fifteen patients are alive (65%), 14 in complete remission, with a median follow-up of 8 months (range 2-37 months). Conclusion. This single Centre report, even if with limited number of patients, underlines that the association of intravenous single dose infusion Busulphan plus Fludarabine is a safe and effective conditioning regimen in AML/MDS patients. Intravenous Busulphan administered once daily is convenient, well tolerated and effective. Further prospective studies are warranted. Disclosures No relevant conflicts of interest to declare.