P. Marson

Extracorporeal photochemotherapy may improve outcome in children with acute GVHD

Acute GVHD (aGVHD) is a major cause of morbidity and mortality after unrelated BMT (UBMT). Our purpose was to analyze the role of extracorporeal photochemotherapy (ECP) in controlling grade II–IV aGVHD in children given UBMT. Of 41 consecutive children, 31 developed grade II–IV aGVHD after UBMT: 16 had a good response to steroids (GR group), whereas 15 underwent ECP (ECP group) within 100 days of UBMT. Eligibility criteria for starting ECP were steroid resistance, dependence or viral reactivations. Criteria for judging response to aGVHD treatment were that the resolution of all signs were considered a complete response (CR), at least a 50% improvement was classified as a partial response (PR) and stable or progressive disease was judged as no response (NR). On completing ECP, the CR rate was 73%, whereas the GR group had a CR rate of 56% by day 100. The 2-year overall survival and progression-free survival rates were 57 and 67% in the GR group vs 85 and 87% in the ECP group. Our data seem to suggest that ECP may improve outcome in patients after UBMT. These findings need to be confirmed in a larger population.

Autoantibodies of systemic rheumatic diseases in the healthy elderly

Antinuclear antibodies, anticardiolipin antibodies and IgM rheumatoid factor were determined in 300 healthy aged subjects, comparing their prevalence to that in 100 healthy subjects aged between 19 and 44 years and 352 patients under 65 years of age, affected by various systemic rheumatic diseases. Increased production of IgM rheumatoid factor and antinuclear and anticardiolipin antibodies was found as characteristic of aged humans, and suggested that a correction for age should be considered in evaluating the clinical significance of autoantibody profiles in elderly patients.

Plasma exchange for the management of the catastrophic antiphospholipid syndrome : importance of the type of fluid replacement

Dear Sir, Therapeutic plasma exchange (TPE) is actually a reliable treatment option for catastrophic antiphospholipid syndrome (CAPS), as beneficial effects have been clearly demonstrated, with improved patient survival. In fact, TPE can remove pathological antiphospholipid antibodies and cytokines, TNF-alpha and complement activation products. Adverse effects, mostly reversible, have been shown in about 5% of patients [1]. In 2003, a treatment algorithm for CAPS was proposed, where TPE (and ⁄or IVIG) was indicated in the presence of a life-threatening condition and as an adjunctive therapy after effective anticoagulation with intravenous heparin and high-dose steroids [2]. Application of this protocol could be the main reason to account for the significant reduction in mortality in CAPS from 2001 [3]. The note, which had been added to the treatment algorithm [2], points out that TPE should be performed with fresh frozen plasma (FFP) and it is specially indicated if schistocytes are present, so very likely emphasizing the possibility of an overlapping syndrome with thrombotic microangiopathy. This new subset, recently named ‘microangiopathic antiphospholipid syndrome’ [4], consists of CAPS plus some clinical features of thrombotic thrombocytopenic purpura (TTP), where TPE using FFP or cryo-depleted plasma is actually the gold standard treatment [5]. FFP contains natural anticoagulants, such as AT-III, but also a quantity of clotting factors which could worsen the thrombotic storm of CAPS. In a recent review, Erkan [6] highlighted a series of therapeutic controversies in the management of CAPS without evidence-based answers, in particular on the exact role of FFP during TPE. Thus, it has been concluded that ‘it is unknown if TPE with FFP or with a different replacement fluid such as human albumin solution would result in different outcomes in CAPS’. Indeed, a literature review on the replacement fluid of TPE in CAPS shows very discordant options, including FFP [7, 8], solvent ⁄detergent plasma [9] and albumin solution [10, 11]. In this regard, Koenig et al. [12] described a 19-year old female affected with primary antiphospholipid syndrome, who developed HELLP (haemolytic anaemia, elevated liver enzymes and low platelets) syndrome during pregnancy, complicated by CAPS with hepatic and intestinal infarctions, bone marrow necrosis and severe thrombocytopenia in the puerperium. In this patient no response to TPE with FFP was recorded and she recovered by means of IVIG together with anticoagulant therapy. Moreover, Espinosa et al. [13] described a 32-year-old man showing a well-defined microangiopathic disease with cerebral, renal and cardiac involvement and markedly raised antiphospholipid antibody levels, who fully recovered after TPE using 5% albumin as a replacement fluid. The FFP use in TPE for CAPS has been suggested also in the clinical applications of therapeutic aphaeresis proposed by the American Society for Apheresis in 2007 [14], where CAPS was first included in category III indication, along with diseases with insufficient evidence, conflicting results or unclear risk-to-benefit of aphaeresis treatment. Subsequently, CAPS has been considered as a paradigmatic example of such a category indication, besides discussing whether ‘we do more harm than good by exposing the patient to blood donors through the administration of plasma products’ [15].

A single institution's experience (1982-1999) with plasma-exchange therapy in patients with fulminant hepatic failure.

Fulminant hepatic failure is a rare, but often fatal complication of acute viral hepatitis. This condition, in absence of orthotopic liver transplantation (OLTx) surgery, is associated with a high mortality rate, despite the improvement of general intensive care. Plasma-exchange (PEx) therapy has been long used to treat FHF, in particular by removing toxic substances and correcting the severe coagulopathy. In this study we describe our experience with PEx treatment of FHF, beginning in 1982. Seventy patients affected with FHF due to various causes (HBV=40; cryptogenic/non-A, non-E=15; Amanita phalloides=8; other=7) were treated with PEx (altogether 348 sessions). Overall survival rate, comprising patients undergoing OLTx, was 51%, a little higher than what we observed in patients (N=49) treated solely by PEx, i.e., 41%. The best outcome predictor was FHF aetiology, owing to the good survival rate in patients with Amanita phalloides intoxication and the very poor prognosis of patients suffering from cryptogenic/non-A, non-E FHF. Moreover, the marked increase in prothrombin time and alpha-fetoprotein levels after 48 hours from admission was associated with a good prognosis, whereas the patients age and coma grade were not clearly predictive of survival. Additionally, lymphocyte subpopulation, resulting in a CD4/CD8 ratio lower than 1.0 along with CD8 activation with HLA-DR strong expression, were associated with a high rate of mortality and morbidity. Our data indicate that PEx therapy can improve survival in patients with sufficient residual capacity of liver regeneration. Moreover, the identification of certain prognostic factors may be useful for the rational planning of therapeutic strategy in FHF.

Intrathecal synthesis of oligoclonal bands in rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome: new evidence supporting immunological pathogenesis.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome (ROHHADS) is a rare, but potentially lethal, pediatric disorder. To date, nearly 80 patients have been reported in the literature; however, the etiopathogenesis is still unclear and debated. Both genetic and paraneoplastic or immune-mediated causes have been supposed to be involved in this syndrome. Nonetheless, at this time, a diagnostic biomarker is not available and diagnosis is based exclusively on clinical criteria. Aiming to establish the immune-mediated pathogenesis, we report 2 children with a clinical picture consistent with ROHHADS and whose cerebrospinal fluid analysis disclosed an intrathecal synthesis of oligoclonal bands. Even if many aspects remain to be explained, this finding suggests that ROHHADS could share similar pathogenetic mechanisms with other immune-mediated central nervous system disorders, and even more important, it might pave the way to a therapeutic chance for these patients by means of immunotherapy.

A preliminary survey of the apheresis activity in Italy: a perspective for the Italian Registry of apheresis.

Data collection on the apheresis activity in Italy throughout 1997 was performed by means of a standardized questionnaire. These data, provided by 96 Apheresis Units from 13 Italian regions, albeit rough, are sufficiently informative. In 1997, a total number of 170,373 apheresis sessions was carried out, with a clear-cut prevalence of productive apheresis (92%) that was performed by all Apheresis Units. Lombardy, Venetia and Latium were the most active regions for therapeutic apheresis (56% of total activity). (Int J Artif Organs 2000; 23: 114–8)

Treatment of symptomatic HyperLp(a)lipoproteinemia with LDL-apheresis: a multicentre study

LDL-apheresis (LDLa) efficacy in the treatment of symptomatic HyperLp(a)lipoproteinemia -HyperLp(a)- has been studied in a multicentre trial. After 3.1+/-2.7 years of weekly and biweekly treatment, the data from 19 patients (males:12; females:7; aged 53.8+/-9.3 years; mean body mass index: 24.6+/-2.3 Kg/m²) were evaluated. Data were collected using the same questionnaire shared by 5 participating centres. A total of 2331 procedures were performed. A mean of 3593.7+/-800.3 ml of plasma or 8115.3+/-2150.1 ml of blood, depending upon the technique used (H.E.L.P., D.A.LI., Dextransulphate, Lipocollect 200), was regularly treated on average every 10.1+/-2.6 days. Baseline mean Lp(a) levels were 172.3+/-153.8 mg/dL. The mean pre-/post-apheresis Lp(a) levels decreased from 124.5+/-107.2 mg/dL (p<0.001 vs baseline) to 34.2+/-40.6 mg/dL (p<0.001 vs pre-). Baseline mean LDL-cholesterol (LDLC) levels were 152.3+/-74.6 mg/dL. The mean pre-/post-apheresis LDLC levels decreased from 130.4+/-61.1 mg/dL (p<0.004 vs baseline) to 41.2+/-25.1 mg/dL (p<0.001 vs pre-). The hypolipidemic drugs given to the patients during LDLa were: ezetimibe+simvastatin, atorvastatin, rosuvastatin, pravastatin, acipimox, and omega-3 fatty acids. 58% of the patients had arterial hypertension. Cigarette smokers were 5.3%. Alcohol intake was present in 21%. 52.6% were physically active. Patients with coronary artery disease (CAD) submitted to coronary catheterization before LDLa were 95%. In 5.5% (#1) CAD recurred despite treatment with LDLa. 79% were submitted to coronary revascularization before LDLa. CAD was: monovasal in 8 patients (42.1%), bivasal in 5 (26.4%), trivasal in 4 (21%), plurivasal in 2 (10.5%). In 94.5% of the sample the lesions were stable (< 0% deviation) over 3.1+/-2.7 years. 37% had both CAD and extra-coronary artery disease. This multicentre study confirmed that long-term treatment with LDLa was at least able to stabilize CAD in the majority of the individuals with symptomatic HyperLp(a).

A case of vinblastine overdose managed with plasma exchange.

Severe, life‐threatening toxicity may be caused by errors in chemotherapy administration. To contribute with some useful information on drug‐induced toxic effects and salvage therapy, we report a case of vinblastine (VBL) overdose (25 mg/m2) in a 12‐year‐old child affected by an end‐stage metastatic primitive neuroectodermal tumor. Early signs of toxicity were acute, severe musculoskeletal pain and fever. This was followed by intestinal hypotonia, severe esophagitis, and peripheral neuropathy. Two consecutive plasma exchange procedures were performed at 4 and 18 hr after the administration of the overdose of VBL. The overall toxicity this child experienced was much less severe than expected; this finding, in combination with the known pharmacokinectis data of VBL in children, made us hypothesize that plasma exchange might have had a role in lowering the side effects of drug over dosage.

Changes in HCV viremia following LDL apheresis in a HCV positive patient with familial hypercholesterolemia.

It has been suggested that hepatitis C virus (HCV) can be associated with beta-lipoprotein in human serum. According to this, the LDL receptor could promote endocytosis of such a virus. In the present study, we evaluated the changes in HCV viremia in a HCV positive patient with familial hypercholesterolemia, undergoing both selective (DALI System, Fresenius) and non-selective (plasma exchange) LDL apheresis. HCV-RNA levels did not decrease following selective LDL apheresis, on the contrary showed a random, odd variation pattern (from –35% to +72%). Conversely, plasma exchange steadily induced a drop in HCV viremia (–35/43%), to a lower extent than that of a totally intravascular plasmaprotein, i.e., alpha 2-macroglobulin (–53/54%). These data indicate that beta-lipoprotein may not function as a plasma carrier of HCV, at least in the present case. Moreover, a continuous, quantitatively unforeseeable circulation of HCV virions from the intravascular plasma compartment to other extravascular and intracellular sites, seems to occurr during an apheresis session.

Immunosuppressive treatment in a heart transplantation candidate with antiphospholipid syndrome

SummaryDilated cardiomyopathy secondary to a devastating anterior myocardial infarction developed in a young patient with the antiphospholipid antibody syndrome. Due to severe left ventricular failure, heart transplantation was considered. To reduce antiphospholipid antibody titer, plasmapheresis followed by immunosuppressive treatment with cyclosporin and azathioprine were attempted in the pretransplant period. The antibody titer normalized after plasmapheresis, but then rose sharply despite immunosuppressive drugs. This case report underscores the failure of cyclosporin, a treatment not previously reported, to control autoimmunity in antiphospholipid syndrome. Moreover, progressive renal insufficiency can develop as a result of the long-term use of this drug.