Jaroslav Malý

Beneficial effect of plasma exchange in the treatment of toxic epidermal necrolysis: A series of four cases

Introduction: Toxic epidermal necrolysis (TEN) is a rare, life‐threatening disease with a high mortality rate that is linked to drug toxicity. There is a lack of data about the underlying pathophysiologic mechanisms and treatment options. The only widely accepted treatment of TEN is withdrawal of the offending drug followed by supportive care. The potential roles of corticosteroids, intravenous immunoglobulin (IVIG) and plasmapheresis (TPE) remain controversial. Aims: We present four patients with severe TEN (all with >80% involvement of body surface) who were treated with TPE following unsuccessful treatment with corticosteroids/IVIG. Methods: TPE was performed using a COBE Spectra blood cell separator. ACD‐A was used as anticoagulant fluid and the target‐washed plasma volume was one body volume. Plasma was replaced by a 5% solution of human albumin + Ringers lactate. Results: The mean number of TPE sessions was 5.25 ± 2.22 (range 3–8). Drugs were implicated as an etiologic agent in each case. TPE led to prompt improvement of acute condition and general health as well as halting of disease progression. Additionally, the restoration of the epithelium began in all four patients. Conclusion: Plasmapheresis should be considered as an alternative treatment modality for patients with the most severe form of TEN if initial treatment with other agents, including corticosteroids and/or IVIG, fails. Drugs were suspected to be the cause of TEN in all four cases. J. Clin. Apheresis, 2012.

Biological prognostic markers in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most frequent leukemic disease of adults in the Western world. It is remarkable by an extraordinary heterogeneity of clinical course with overall survival ranging from several months to more than 15 years. Classical staging sytems by Rai and Binet, while readily available and useful for initial assessment of prognosis, are not able to determine individual patients ongoing clinical course of CLL at the time of diagnosis, especially in early stages. Therefore, newer biological prognostic parameters are currently being clinically evaluated. Mutational status of variable region of immunoglobulin heavy chain genes (IgVH), cytogenetic aberrations, and both intracellular ZAP- 70 and surface CD38 expression are recognized as parameters with established prognostic value. Molecules regulating the process of angiogenesis are also considered as promising markers. The purpose of this review is to summarize in detail the specific role of these prognostic factors in chronic lymphocytic leukemia.

High-dose chemotherapy followed by autologous stem cell transplantation changes prognosis of IgD multiple myeloma

Immunoglobulin D (IgD) multiple myeloma (MM) is a rare plasma cell disorder constituting less than 2% of all MM cases. Survival of patients with IgD MM is generally shorter than that of patients with other types of monoclonal (M-) protein. We have retrospectively analyzed patients with IgD MM participating in clinical trials of the Czech Myeloma Group. Twenty-six IgD MM patients treated between 1996 and 2006 were identified, 14 (54%) men and 12 (46%) women. The median age was 61 years (range: 37–79 years). Ten of 26 patients (39%) were treated with first-line high-dose chemotherapy (HDCT) using melphalan 200 mg/m2 followed by autologous stem cell transplantation (ASCT). Thirteen of 26 patients (50%) received conventional chemotherapy (CHT), mostly melphalan and prednisone or a vincristine/doxorubicin/dexamethasone (VAD) regimen. Treatment responses were evaluable for 23 of 26 (89%) patients. All HDCT patients had treatment responses, including seven patients (70%) with complete responses and three patients (30%) with partial responses. The median progression-free survival was 18 months for HDCT patients and 20 months for CHT patients. The median overall survival (OS) for all patients was 34 months. The median OS for the HDCT group has not yet been reached (70% of the patients are still alive). In contrast, the median OS for CHT patients was only 16 months. The difference in OS between the two groups was statistically significant (P=0.005). In conclusion, the overall response rate for patients with IgD MM aged 65 years or less treated with HDCT and ASCT is similar to that seen in other MM types.

Safety and Tolerability of Long Lasting LDL-apheresis in Familial Hyperlipoproteinemia

Abstract:  The aim of this work is to arbitrate the incidence of side effects and tolerability of long lasting LDL‐apheresis in familial hyperlipoproteinemia. 1200 procedures were performed and the last 463 of them were evaluated. An immunoadsorption method of LDL‐apheresis was used (continuous blood cell separator Cobe Spectra; secondary device: automated adsorption‐desorption ADA, Medicap; absorption columns: Lipopak). As a whole, 6.26% adverse events were found and subsequently resolved by standard symptomatic therapy. Vaso‐vagal reactions (symptoms of neurovegetative lability) were the most common adverse effects, presented as malaise, weakness, slight and short‐term drop in blood pressure or other general signs. They were all well controlled by symptomatic therapy. We conclude that LDL‐apheresis in the hands of experienced personnel is a safe procedure. An acceptable procedure duration limit, balancing the possibility to achieve a targeted cholesterol level while still maintaining an acceptable patient tolerance, was confirmed to be 4 hours.

Haemorheopheresis could block the progression of the dry form of age‐related macular degeneration with soft drusen to the neovascular form

Purpose:  To evaluate the influence of haemorheopheresis on anatomical and functional findings in patients with soft‐drusen maculopathy.

Venous Thromboembolism in Young Female While on Oral Contraceptives: High Frequency of Inherited Thrombophilia and Analysis of Thrombotic Events in 400 Czech Women:

Oral contraceptive use is a common risk factor for venous thromboembolism in women of reproductive age. The presence of inherited thrombophilia further increases this risk. Methods: We analyzed a large group of 400 Czech women with venous thromboembolism in association with oral contraceptive with regard to duration of use at the time of manifestation of venous thromboembolism, the frequency of inherited and acquired thrombophilia, the frequency of eliciting risk factor for thrombosis including immobilization, surgery, administration of plaster cast, long travel, and so on, and the type of thrombosis. The mean age of the women was 26 years, and the average duration of use was 45 months at the onset of thrombosis. Results: Venous thrombosis solely due to the pill occurred in 57% of the women, and in the other 43%, an additional transient eliciting factor was recognized. Among the clinical manifestation, distal thrombosis prevailed (N = 231, 58%) followed by proximal deep vein thrombosis (N = 65, 16%), pulmonary embolism (N = 21, 5%), and thrombosis in unusual sites (N = 20, 5%). Inherited or acquired thrombophilia was diagnosed in 195 (49%) women: factor V Leiden mutation in 35%, congenital deficiency of antithrombin in 1.8%, protein C in 0.8%, protein S in 1%, F IIG20210A in 5%, and antiphospholipid syndrome (APS) in 5.3%. Among the most common risk factors were immobilization of lower limb, minor and major surgery, and trauma. Conclusion: The results confirm that venous thromboembolism is a multifactorial disease in which thrombophilia screening is needed in young symptomatic women on the pill with thrombosis. The results also emphasize the value of proper thromboprophylaxis in women while on oral contraceptive in situations of increased risk for venous thromboembolism.

The importance of rheological parameters in the therapy of the dry form of age-related macular degeneration with rheohaemapheresis

To date, rheological treatment is the only chance to control the advanced dry form of age-related macular degeneration and arrest its progression to legal blindness. Rheohaemapheresis can change the main rheological parameters, blood and plasma viscosity, as well as change erythrocyte aggregability, improve erythrocyte flexibility and lead to substantial improvement when other methods of therapy fail. In this study, we describe changes in the levels of rheological efficacy indicators after rheohaemapheresis and their clinical significance in the dry form of age-related macular degeneration (AMD). Seventy-two patients with AMD were randomised; 34 controls, and 38 patients were treated with rheohaemapheresis (separator Cobe Spectra + Evaflux filter). After the procedures, α2-macroglobulin levels decreased by approximately 58%, fibrinogen by approximately 65%, IgM by approximately 67%, LDL cholesterol by approximately 71%, apolipoprotein B by approximately 65%, and lipoprotein (a) by approximately 42%. These decreases correspond with a decrease in blood and plasma viscosity (14/12%), clinical improvement (arrest of disease progression, even visual improvement in some cases), and heretofore-unreported improvement (even reattachment) of drusen retinal pigment epithelium detachment. Our modification of rheohaemapheresis is safe (5.4% of patients experienced clinically insignificant side effects).

Monotherapy with low-dose thalidomide for relapsed or refractory multiple myeloma: better response rate with earlier treatment

Background:  Thalidomide is an immunomodulatory drug used in the treatment of relapsed or refractory multiple myeloma (MM). The optimal dosing regimen of thalidomide is not known.

Prevention of Infection Transmission during Stem Cell Transplantation

Group of 152 patients (investigated before autologous transplantation) and 35 healthy donors for allogeneic transplantation was examined for the risk of infection transmission that can be associated with the infusion of cryopreserved peripheral blood progenitor cells to the patient and/or cross-contamination of stored grafts. No laboratory signs of active infection were found in 22 donors (63 %) and in 91 patients (60%). The most common was active infection by herpes viruses — 50 cases in patients, 21 cases in donors; hepatitis B was found in only two cases. The rate of clinically unsuspected (but dangerous) infections in donors and patients thus remains relatively high in spite of the fact that the system of donor search and the whole transplantation procedure have improved in the last years. The system of safety assurance is extremely important and the whole palette of preventive tests according to EBMT (European Blood and Marrow Transplantation Group) and ISHAGE (International Society for Hemotherapy and Graft Engineering) is fully justified.

Is radioiodine administration in patients with papillary thyroid multifocal microcarcinoma unnecessary

Summary Radioiodine (RAI) has played a crucial role in differentiated thyroid cancer treatment for more than 60years. However, the use of RAI administration in patients with papillary thyroid microcarcinoma (even multifocal) is now being widely discussed and often not recommended. In accordance with European consensus, and contrary to the American Thyroid Association (ATA) guidelines, we recently performed RAI thyroid remnant ablation in a patient with differentiated papillary multifocal microcarcinoma. The post-therapeutic whole-body scan and SPECT/CT revealed the real and unexpected extent of disease, with metastases to upper mediastinal lymph nodes. This finding led to the patient’s upstaging from stage I to stage IVa according to the American Joint Committee on Cancer/International Union Against Cancer criteria. Learning points 131I is a combined beta–gamma emitter, thus allowing not only residual thyroid tissue ablation but also metastatic tissue imaging. RAI remnant ablation omission also means post-treatment whole-body scan omission, which may lead to disease underestimation, due to incorrect nodal and metastatic staging. RAI should be considered also in “low-risk” patients, especially when the lymph node involvement is not reliably documented. Lower administered RAI activity (30mCi, 1.1GBq) may be a workable compromise in low-risk patients, not indicated for RAI remnant ablation according to ATA guidelines.