Hemoperfusion with CytoSorb as Adjuvant Therapy in Critically Ill Patients with SARS-CoV2 Pneumonia.

We report a preliminary experience of adjuvant therapy with Hemoperfusion (HP) in patients with Severe Acute Respiratory Syndrome-CoronaVirus 2 (SARS-CoV2) pneumonia. Currently, there are no approved treatments for CoronaVirus Disease 19 (COVID-19); however, therapeutic strategies based on the preclinical evidence include supportive measures, such as oxygen supplementation, antiviral, and anticoagulant agents. Despite these treatments, 10% of patients worsen and develop severe acute respiratory distress syndrome (ARDS). Since the pathogenic mechanism of ARDS is an uncontrolled inflammatory state, we speculate that removing inflammation effectors from blood may contrast tissue injury and improve clinical outcome. In a scenario of dramatic medical emergency, we conducted an observational study on 9 consecutive patients hospitalized in COVID Intensive Care Unit, where 5 of 9 consecutive patients were treated with HP, due to the emergency overload made it impossible to deliver blood purification in the other 4 patients. COVID-19 was diagnosed through the identification of virus sequences by reverse transcription-PCR on respiratory specimens. All patients had severe pneumonia requiring continuous positive airway pressure. HP was started in all patients 6-7 days after hospital admission. The treated patients (T) received 2 consecutive sessions of HP using CytoSorb cartridge. Our results show a better clinical course of T compared to control patients (C), in fact all T except 1 survived, and only 2 of them were intubated, while all C required intubation and died. Lymphocytopenia worsened in C but not in T. C-reactive protein decreased in both patients, but to a greater extent in T. IL-6, IL-8, and TNF-α decreased after HP, IL-10 did not change. Respiratory function remained stable and did not worsen in T compared to C. The limited sample size and observational study design preclude a sound statement about the potential effectiveness of HP in COVID-19 patients, but our experience suggests a potential therapeutic role of adjuvant CytoSorb HP in the early course of CO-VID-19 pneumonia. A randomized clinical trial is ongoing.

A phase II trial of autologous transplantation of bone marrow stem cells for critical limb ischemia: results of the Naples and Pietra Ligure Evaluation of Stem Cells study.

Critical limb ischemia (CLI) is a vascular disease affecting lower limbs, which is going to become a demanding challenge because of the aging of the population. Despite advances in endovascular therapies, CLI is associated with high morbidity and mortality. Patients without direct revascularization options have the worst outcomes. To date, 25%-40% of CLI patients are not candidates for surgical or endovascular approaches, ultimately facing the possibility of a major amputation. This study aimed to assess the safety and efficacy of autologous bone marrow (BM) transplantation performed in "no-option" patients, in terms of restoring blood perfusion by collateral flow and limb salvage. A multicenter, prospective, not-controlled phase II study for no-option CLI patients was performed. Patients were subjected to intra-arterial infusion of autologous bone marrow and followed for 12 months after the treatment. Variation of blood perfusion parameters, evaluated by laser Doppler flowmetry or transcutaneous oximetry, was set as the primary endpoint at 12 months after treatment and amputation-free survival as the secondary endpoint. Sixty patients were enrolled and treated with BM transplantation, showing improvement in objective and subjective measures of perfusion. Furthermore, survival analysis demonstrated improved amputation-free survival rates (75.2%) at 12 months after the treatment. This study provides further evidence that autologous bone marrow transplantation is well tolerated by CLI patients without adverse effects, demonstrating trends toward improvement in perfusion and reduced amputation rate, confirming the feasibility and safety of the procedure.

Ifosfamide, epirubicin, etoposide (IEV) and autologous peripheral blood progenitor cell transplant: a feasible and effective salvage treatment for lymphoid malignancies.

The IEV schedule consisted of epirubicin 100 mg/m2 on day 1, etoposide 150 mg/m2 on days 1-3, and ifosfamide 2.5 g/m2 on days 1-3. Patients who proceeded to haematopoietic stem cell transplants (HDTs) received conditioning therapy with BEAM [for the Hodgkin's Lymphoma (HL) and non-Hodgkin's Lymphoma (NHL) groups], or melphalan 100 mg/m2 and mitoxantrone [for the multiple myeloma (MM) patients]. The study consisted of 65 patients with a median age of 53 years: 27 had aggressive NHL, 20 had HL, 7 had indolent NHL, and 11 had MM. Fifty-five patients received IEV for a disease that was refractory to conventional induction regimens, or that was in first or second relapse; 4 patients were treated with IEV while in complete response (CR) after chemotherapy in order to mobilise peripheral blood stem cells (PBSCs). Ninety percent of patients with HL responded to IEV, and 85% achieved CR. Both aggressive and indolent NHLs were less responsive (ORR 50 and 33%, respectively; CRR 41 and 16.5%, respectively). MM patients displayed an intermediate responsiveness (ORR 50% and CRR 30%). IEV was well tolerated in most patients. No life- threatening infections were recorded. PBSC mobilisation was successful in 37 out of 39 patients (95%) and led to the collection of a median of 16, 12, and 13.7 x 10(6) CD34+ cells/kg in patients with HL, NHL, and MM, respectively. All 37 patients underwent an autologous stem cell transplant following a 1 to 2 month interval after the end of IEV. Two patients were submitted to an allogeneic transplant. The median overall survival rate in HL, aggressive NHL, and indolent NHL is 32 (5-60), 16 (2-46), and 14 (4-42) months, respectively. Median EFS is 31 (5-60), 7 (2-46), and 7.5 (4-42) months, respectively. In conclusion, our study confirms that IEV +/- HDT is a well-tolerated and effective salvage treatment for lymphoid malignancies, and that IEV acts as an excellent stem cell mobiliser.

Combination of liposomal daunorubicin (DaunoXome), fludarabine, and cytarabine (FLAD) in patients with poor-risk acute leukemia.

Sixty-two patients with high-risk acute leukemia were treated with the FLAD regimen [3 days of treatment with fludarabine 30 mg/m(2), cytarabine (AraC) 2 g/m(2), and liposomal daunorubicin 80 mg/m(2)]. The acute myeloid leukemia (AML) patients were either refractory to standard induction regimens (8), were in first or second relapse (13), or received therapy as first-line treatment [21 patients, 16 were above 60 years of age and 5 had post-myelodysplastic syndrome (MDS) AML]. The acute lymphoblastic leukemia (ALL) patients were treated for relapsed (7) or refractory disease (10). Three patients had chronic myeloid leukemia (CML) in the blastic phase. FLAD was well tolerated by most patients. Ten major infectious complications were recorded while no signs of cardiac toxicity were observed. Five patients (8%) died before day 28 with hypocellular marrow, mainly of infection or hemorrhage, and response could not be evaluated. Complete response rate was 62% and 69% among AML patients treated at diagnosis or for relapsed disease, respectively, and 59% among the ALL patients. Furthermore, FLAD managed to overcome the negative impact of poor prognosis karyotype in ALL patients, since five of the seven patients with t(9;22) or complex karyotype achieved complete remission (CR). Nine patients underwent bone marrow transplantation (BMT). Among the AML patients who were treated at diagnosis or for relapse, the median duration of CR was 7 months (range: 2-18) and 8 months (range: 2-26), respectively. Median survival among these patients was 8 (range: 1-40) and 12 (range: 1-30) months, respectively. Similar values were found in ALL patients. In conclusion, FLAD may be an effective alternative treatment for patients with relapsed AML and for patients with ALL who failed first-line therapy.

AMIL survey (anemia in Internal Medicine in Liguria).

The aim of the present study was to evaluate the epidemiology of anemias in Internal Medicine Departments. The study involved all patients discharged between May 1 and June 15, 2001 who, at the time of admission, had presented with hemoglobin levels < 12 g%. One thousand and nineteen data collection forms were deemed suitable for analysis and were divided according to the etiology and severity of the anemia. We discovered that simple diagnostic tests (reticulocyte count) were underused, that the majority of anemias were not corrected during hospitalization and that most inpatients of Internal Medicine wards in our Region are elderly (mean age 75 years) and suffer from polypathologies. We believe that further observational studies should be carried out in order to evaluate the progress of patients with anemia and to establish guidelines for the diagnosis and treatment.