Extracorporeal photochemotherapy in heart transplant rejection: A single-center experience.

BACKGROUND: The addition of extracorporeal photochemotherapy (ECP) to standard immunosuppressive therapy has been suggested to be beneficial in the treatment of recurrent/persistent heart rejection. METHODS: We reviewed medical data of heart transplant recipients who received ECP between 2010 and 2016 at our institution. RESULTS: During the study period, eight patients underwent nine ECP courses. The median time from transplant to ECP was 18 months (range 9-54). Indications for ECP were recurrent rejection in 6 patients, persistent rejection in 1 patient and mixed rejection with hemodynamic compromise in 1 patient. Additional criteria for patients' selection were represented by relevant comorbidities limiting the increase of immunosuppressive therapies. ECP was performed on an outpatient basis in 6 out of 8 patients. The median ECP duration was 12 months (range 1-18). Three out of 8 patients responded to ECP showing negative endomyocardial biopsies at the end of treatment. No additional rejection episodes were observed at their follow up (at 44, 72 and 31 months). Four of 8 patients failed to respond to ECP treatment, one patient has been judged not evaluable. Reduction of immunosuppressive therapies was obtained in all 3 responsive patients but also in 3 patients with a stable grade of rejection. The median duration of the follow up was 26 months (range 6-80). Two patients died at 6 and 21 months after beginning ECP. Survival after ECP was 78.2% at 26 months. No adverse effect or infectious complications associated with ECP were reported. CONCLUSIONS: The low response rate (37.5%) in our case series could be partially explained by patient selection, the treated patients representing a high-risk sub-set group. Further studies to provide evidence of a role for ECP in heart rejection treatment or prophylaxis are needed.

Pregnancy associated thrombotic thrombocytopenic purpura: Practical issues for patient management.

Thrombotic thrombocytopenic purpura (TTP) is a severe, life-threatening disease that needs urgent diagnosis and prompt therapeutic intervention. In pregnant women TTP may complicate the course of gestation putting mother and child at vital risk. Differential diagnosis with other obstetric and medical disorders may be difficult due to the overlap of several clinical and laboratory findings. Our understanding of the pathophysiology of TTP has allowed ADAMTS13 testing to have a central role in confirming the clinical diagnosis but the main limitation is that an ADAMTS13 assay is not available in "real time". Here we report the clinical course and treatment outcome of two young women with clinical manifestations of pregnancy associated TTP and briefly discuss the main topics of disease diagnosis and management.

Efficacy and safety of peripheral blood stem cell mobilization and collection: a single-center experience in 190 allogeneic donors.

BACKGROUND: In the past two decades peripheral blood stem cells (PBSCs) have increasingly replaced marrow as stem cells source for allogeneic transplantation. The PBSC donation initially applied only to related donors; later, due to the safety of the procedure, it was extended to unrelated donors. STUDY DESIGN AND METHODS: We have retrospectively collected data regarding mobilization, collection, and short- and long-term follow-up of 190 consecutive donors, 174 related and 16 unrelated. All donors followed a standard protocol for mobilization and underwent at least one PBSC collection. Follow-up in related donors was performed every 4 months in the first year and then annually, with no time limits, while unrelated donors were monitored for 10 years. RESULTS: All 190 donors completed the established mobilization protocol. The mobilizing capacity was significantly greater in males and in donors less than 60 years old. No case of major toxicity by granulocyte-colony-stimulating factor was found, nor thromboembolic events. The total dose of CD34+/recipient (median 5.8×10(6)/kg recipient/body weight) was statistically correlated with age, CD34+ before and after mobilization, and collection efficiency. Compliance to follow-up was 66%, with a significant difference between related and unrelated (63% vs. 100%, p=0.03). During follow-up no significant abnormalities in hematologic variables or hematologic malignancies were reported. CONCLUSION: Our study allowed us to define the PBSC donation as "a safe procedure for the donors," with short- and long-term effects limited to a small percentage of donors and "effective for the recipient," due to the dose of collected CD34+, adequate for transplantation in almost all recipients.

Graves' Disease Thyrotoxicosis and Propylthiouracil Related Agranulocytosis Successfully Treated with Therapeutic Plasma Exchange and G-CSF Followed by Total Thyroidectomy.

Antithyroid drugs can be a rare cause of agranulocytosis (0.5% of treated patients). Suspension of these drugs is mandatory in these patients and may result in worsening hyperthyroidism. We report the case of a 27-year-old woman who is 3 months post-partum, breastfeeding, and suffering with Graves' disease hyperthyroidism treated first with methimazole and then with propylthiouracil due to a methimazole allergy. She was admitted for urosepsis and agranulocytosis. The patient was diagnosed with propylthiouracil related agranulocytosis, diffuse toxic goiter and thyro-gastric syndrome. Antithyroid drug therapy was stopped resulting in a worsening of thyrotoxicosis. Agranulocytosis was treated with 8 doses of G-CSF with full recovery. To rapidly restore euthyroidism and to perform a thyroidectomy, the patient received 6 therapeutic plasma exchange (TPE) procedures, to clear thyroid hormones and anti-TSH receptor antibodies from blood, resulting in a pre-surgical euthyroid state without antithyroid drug therapy. Two years after thyroidectomy, the patient is well under thyroid hormone replacement therapy with a normal granulocyte count.

Between language and space: a cross-domain interaction.

We document for the first time the effect of a spatial deficit on an spoken language task. Right brain-damaged patients with and without neglect were administered a task of emphatic stress. Patients listened to 60 subject-verb-object sentence pairs. The emphatic stress could be placed on the subject, on the verb or on the object word. Patients had to judge whether the two sentences were same or different for the position of the emphatic stress. The judgements were more impaired in patients with neglect and when the stress was placed at the beginning of the sentence (on the subject word), that is to say, at the leftmost location of a hypothetical spatial representation of the heard sentence. We hypothesize that auditory language undergoes a spatial transcoding, and that this transcoding is affected by the presence of a spatial bias like that observed in patients with neglect.

The use of G-CSF during first line chemotherapy adversely affects the yield of PBSC mobilization in non-Hodgkin's lymphoma patients.

Regardless the mobilization procedure used there is a great variability from patient to patient in the yield of CD34 collections for autologous transplantation. We analyzed retrospectively our non-Hodgkin's lymphoma survey of 60 patients harvested with G-CSF alone after a unique first line chemotherapy; 67% of patients harvested a sufficient number of CD34+ cells during the first attempt of mobilization. The charachteristics of leukaphereses procedures were the same for all the patients. Sex, age, months from the end of chemo- or radio-therapy did not have a significance in influencing mobilization capability, while requirement of G-CSF during chemotherapy was statistically different from failures to successes: 16/20 (80%) of patients failing to reach the target of 2x10(6)/kg CD34+ cells had required G-CSF support during previous chemotherapy versus 18/40 (45%) in the successful group (p 0,005). Our observation supports the hypotesis that individual biological charachteristics of each patient are the most important factors in affecting mobilization capability, deserving further investigation: mobilization schedules tailored on a given patient would minimize the rate of failures, avoiding a second attempt of collection that implies additional economic expenses and negative consequences on the maintenance of dose intensity.

Autologous stem cell transplantation for Hodgkin's lymphoma: results and prognostic factors in 51 high-risk patients.

Autologous stem cell transplantation (ASCT) is largely employed in primary resistant or recurrent Hodgkin's Lymphoma (HL), while its role early in the course of the disease is still controversial. Our purpose was to analyse the results of 51 high-risk HL patients autografted at our Institution and the role of possible prognostic risk factors for the outcome. Twelve (23.5%) patients were in complete remission at transplant and were transplanted as having an high risk disease; 20 (39.5%) patients were in partial response and 19 (37.0%) were transplanted as primary induction failure. At a median time of 38 (6-111) months from ASCT, 36 (70.5%) patients are alive in complete remission, 8 (15.5%) patients are alive with disease and 7 (14.0%) died for progression. Thirty out of 32 (94.0%) patients transplanted with responsive disease (either complete or partial response) are alive without disease. Six out of 19 (32.0%) patients transplanted with resistant disease are alive in complete remission. The overall survival of the entire population is 77.0% at 60 (14-151) months from diagnosis. Disease free survival of the 22 patients that achieved a complete remission after ASCT (16 in partial response and 6 with resistant disease) is 100%. In our experience, more than 90% of patients transplanted with responsive but high risk disease, seem achieving and maintaining a durable complete remission, and more than 30.0% of patients submitted to ASCT with refractory disease can be potentially rescued by transplant.