Miroslav Tomíška

Pulse cyclophosphamide for corticosteroid-refractory graft-versus-host disease.

Summary:Corticosteroid-resistant GVHD is difficult to manage and is associated with high morbidity and mortality. Cyclophosphamide (Cy) is an established immunosuppressive and cytotoxic drug widely used as part of pretransplant conditioning regimens. In a retrospective study of 15 patients who had not responded to corticosteroids (nine with acute GVHD, three with GVHD after donor leukocyte infusion, and three progressive chronic GVHD), pulse Cy at a median dose of 1 g/m2 was very effective in the treatment of skin (100% response), liver (70% response), and the oral cavity (100% response). Severe intestinal GVHD responded poorly. The toxicity profile was acceptable, with manageable, short-term myelosuppression in some patients. The risk of opportunistic infections, mixed chimerism, relapses, or post-transplant lymphoproliferative disease was not increased. Overall survival was 57%, with median and maximum follow-up of 9 and 37 months, respectively. The cost of the drug was negligible, especially when compared to monoclonal antibodies. Pulse Cy requires further investigation in corticosteroid-resistant GVHD.

I/D ACE gene polymorphism in survival of leukemia patients -- hypothesis and pilot study.

Angiotensin-I converting enzyme (ACE) is involved not only in intracellular volume regulation but also in proliferation control. Since both ACE gene polymorphism (I/D ACE) and ABO blood group determine ACE level in peripheral blood and probably also in bone marrow, the hypothesis to the interindividual differences in survival of leukemic patients was suggested. The data of 25 patients of both sexes with acute myelogenous (AML), acute lymphatic (ALL), chronic myelogenous (CML) and chronic lymphatic (CLL) leukemia treated by conventional were used for the study. The overall survival (SUR) was estimated as the time from the date of diagnosis to the date of death. The difference between patients individual SUR (iSUR) and median SUR according to the type of leukemia (mSUR) was calculated. This difference (iSUR-mSUR) varied with I/D ACE genotype (p<0.02) but neither with diagnosis nor with ABO blood group. The regression model for iSUR calculation, from mSUR and I/D ACE genotype, has been suggested.

Sepsis and septic shock

Mortality from septic shock is considerable despite the advantages of cardiovascular support and antibiotic therapy. Understanding the pathophysiology of sepsis enables clinicians to institute rational intervention directed towards the pathophysiological mechanisms. This article reviews definitions of sepsis and offers a brief overview of ist pathophysiology. Current knowledge on the pathophysiological mechanism of cytokines and modulation of systemic cytokine levels during sepsis and septic shock is discussed. The important role of cytokines in sepsis and septic shock may require more detailed investigations of the cytokine pathophysiological network.

Bone Marrow as Multidimensional Orbit Oscillator after Autologous Bone Marrow Transplantation

The local renin‐angiotensin system (RAS) in bone marrow is probably involved in the control of hematopoiesis. Earlier observations suggest the relationship between the frequency of sodium and potassium concentration changes in urine and bone marrow recovery after chemotherapy. The purpose of this study was to prove the relationship between sodium and potassium excretion changes in urine and granulocyte counts in peripheral blood after autologous bone marrow and peripheral blood stem cell transplantation.