Immune status of children with and without severe infection during remission of malignant disease.

The immune status of children with malignant disease in remission was assessed usingvarious immune function tests. Children with infections had significantlymore neutropenia, hypogammaglobulinaemia, and impaired cell-mediated immune responses than those without. These two groups combined had much more absolute lymphopenia and impairment of both cell-mediated immunity and antibody-producing capacity thancontrol children with non-malignant conditions. Regular immunological evaluation isrecommended for children with malignant disease when new intensive treatment schedules are under trial and for individual patients particularly prone to develop infections during treatment.     

Myeloid stem cell kinetics in children hypertransfused during remission induction of acute lymphoblastic leukemia

Experimental studies in animals and recent preliminary clinical evidence raised the possibility that hypertransfusion might be capable of producing a beneficial effect on granulopoiesis recovery following irradiation or chemotherapy. This prompted us to design a study to determine the effect of hypertransfusion on the blood and marrow CFU-c of leukemic children during remission induction. Nineteen children with acute lymphoblastic leukemia have been randomized in pairs to normotransfused (Hb: 12-14 g/dl) and hypertransfused (Hb: 16-18 g/dl) groups. Anti-leukemic chemotherapy (vincristine and adriamycin weekly during 4 weeks and prednisone daily) was identical in all children. As expected, suppression of erythropoiesis was observed in the hypertransfused group. During the first three courses of chemotherapy, the number of marrow CFU-c remained very low in both groups. One week after the third course of chemotherapy the number of bone marrow CFU-c began to increase in both groups. One week after course four the CFU-c value was significantly larger in the hypertransfused group. We also observed that circulating CFU-c were almost absent before induction chemotherapy, whereas their number increased after course three and was higher in the hypertransfused group and remained higher after course four. These results show the kinetics of bone marrow recovery after chemotherapy and suggest that hypertransfusion increases the rate of recovery of granulopoiesis.     

Symptomatic epilepsy associated with intracranial calcifications in children with acute lymphoblastic leukemia (ALL)

Acute and long-term sequels of central nervous system (CNS) prophylaxis with irradiation and intrathecal chemotherapy in children suffering from acute lymphoblastic leukemia (ALL) include vasculopathies, leucoencephalopathies, intracranial calcifications, intellectual and neurological impairment. We report two children at the age 5 and 8 years who manifested partial motor or complex seizures and intracranial calcifications 2-4 years after the diagnosis of ALL had been established. The occurrence of these disorders was much earlier than reported in the literature. Both children received prophylactic CNS treatment with irradiation and intrathecal methotrexate (MTX). Their brain CT scans and EEG had been normal before the first epileptic seizure was registered. Children are now seizure free on carbamazepine, and a boy with complex partial and myoclonic seizures is also on valproate and vigabatrine. Symptomatic epilepsy associated with intracranial calcifications and persisting EEG changes might occur as side effects of ALL treatment.     

Effects of immunotherapy and chemotherapy on immunocompetence. A study of patients with acute myeloblastic leukemia in remission

Summary The immunocompetence of 33 patients with acute myeloblastic leukemia in remission and treated with cytostatics (CT) was studied. In addition to cytostatics some of the patients were given immunotherapy (CT+IT).In an attempt to demonstrate immunization against allogeneic leukemic blast cells (or their extracts) or immunostimulation after immunotherapy or, alternatively, immunodepression after maintenance chemotherapy without immunotherapy, delayed hypersensitivity tests and lymphocyte stimulation tests were performed. In most cases PHA seemed to be a stronger stimulator than allogeneic lymphocytes and these seemed to be stronger than allogeneic blasts, although no difference was statisically significant.No significant differences were found in vitro or in vivo between the reactions of CT and CT+IT patients or their lymphocytes to allogeneic myeloblasts or to allogeneic lymphocytes. However, numerically, in vitro and in vivo CT+IT patients reacted more to myeloblasts, CT patients more to lymphocytes. This could suggest antigens on leukemic myeloblasts that are not found on lymphocytes. With present methods we could demonstrate neither immunodepression in patients given only chemotherapy nor nonspecific immunostimulation after immunotherapy. There was no significant difference between the two treatment groups in lymphocyte reactivity against PHA and allogeneic lymphocytes. Nor was the lymphocyte reactivity different from that in a group of healthy persons.Decreasing lymphocyte reactivity to PHA and allogeneic lymphocytes seemed to herald relapse.     

Decreased hormone content of immune cells in children during acute lymphocytic leukemia (ALL) - effect of treatment

Histamine, serotonin and triiodothyronine (T3) content of different circulating lymphocyte subsets of leukemic (acute lymphocytic leukemia, ALL) and non-leukemic (control) children were investigated by multicolor flow cytometry. The hormone contents of the cells were followed from the time of diagnosis till the end of treatment. Each hormone could be detected in every time in the investigated cell types, although the amounts of them changed during the treatment.T lymphocytes: Significantly lower amount of serotonin was found in each T cell subsets (Th, Tc and activated T lymphocytes) of leukemic children compared to the healthy control group at the time of diagnosis and it was permanently low during the maintenance therapy. The decreased amount of serotonin could be demonstrated in Tc and Th cells even at one year after the end of treatment. However, there was no alteration in the histamine and T3 content of T cell subsets in the time of diagnosis, but significant decrease was detected during the maintenance therapy and after treatment.NK cells: The serotonin and T3 contents of NK cells (both NK and NKT subsets) were significantly lower at the time of diagnosis and during the maintenance therapy. Similar decrease was detected in the case of serotonin in B cells. Although there was no difference in the T3 content of B cells at the time of diagnosis, significantly lower amounts could be detected during the therapy compared to the healthy control group. The serotonin concentration remained low for years after the end of treatment, both in B and NK cells. These observations might have diagnostic and prognostic importance.     

Mitotic index in the bone marrow of children during the clinical course of acute lymphoblastic leukemia (ALL)]

From 31 children with acute lymphoblastic leukaemia the mitosis index in the bone-marrow was determined before the onset of therapy and during the clinical progress. Initially, the mean white mitosis index lay with 3.4% below that of the normal test persons, it rose significantly in the hematologic full remission and showed a decreasing tendency with a great range of dispersion in the recidive. The most lowered mitosis index was found in the final stage. Strong shifts in the kariologic distributions make a remaining in the prophase of the mitosis evident. The influence of polychemotherapy on the mitosis index and the phases of mitosis is discussed. Correlations between the mitosis index and clinical as well as paraclinical parameters were only to be found with respect to granulocytes and lymphoblasts. The considerable ranges of fluctuations of the mitosis index and the lack of congruity with the clinical progress of ALL allow no ensured assertions to be made for the single patient. It seems to be important in eosinophilia and in leukaemoid reactions.     

Enhancement of defective monocyte function during immunotherapy with recombinant interferon

Summary The influence of immunotherapy with high dose (50×10⁶ units/m²) recombinant leukocyte A interferon on blood monocyte functions was studied in eight patients with bronchogenic carcinoma. Monocyte chemotactic responsiveness (MCR) was initially depressed (9.8±1.6 cells/field) compared to healthy controls (17.6±5.1 cells/field), P<0.01. Recombinant interferon was administered three times weekly, and after 7 days a significant improvement in chemotaxis was observed (16.6±3.0 cells/field), P<0.05. The MCR remained normal until cessation of interferon therapy (>1 month). Phagocytic and candidacidal activities were normal in the patients and were not influenced by treatment with interferon. In conclusion, high dose recombinant interferon given to cancer patients caused a normalization of defective blood monocyte chemotaxis, which persisted for >1 month.     

Studies on delayed hypersensitivity of patients with Hodgkin's disease during remission.

The studies of skin sensitivity, the reactivity to intradermally transferred lymphocytes and lymphocytic transformation in vitro showed that delayed hypersensitivity had been slightly impaired in patients with Hodgkin's disease during long time remission. The regression of the disease favoured the recovery of the lymphocytic functions and the delayed type immune reactions associated with them. These data suggest that the enhancement of the delayed hypersensitivity of the tumour defence respectively could promote the treatment or prevention of the disease.     

Immune response to sublingual immunotherapy in children allergic to mites

Allergic rhinitis (AR) is characterized by Th2 polarized immune response. Specific immunotherapy modifies this arrangement restoring a physiologic Th1 profile. Sublingual immunotherapy (SLIT) is widely prescribed, but there is no early marker of response. The aim of this study is to investigate possible marker of SLIT effectiveness. Thirty children with mite allergy were studied: 15 were treated with drugs alone, 15 with SLIT and drugs on demand. The study lasted 2 years. Visual analogue scale (VAS) for symptoms and medication score were evaluated. Serum cytokines (IL-2, IL-4, IL-6, IL-8, IL-10, IFN-gamma, MCP-1, and TNF-alpha) were assessed by ELISA before and after 1 and 2 year SLIT. SLIT-treated children obtained a significant improvement of symptoms and a reduction of drug use, whereas children treated with a drug alone did not obtained any change. IL-10 significantly increased, whereas Th2-dependent and pro-inflammatory cytokines significantly decreased. In conclusion, the present study demonstrates that 2-year SLIT is capable of inducing immunologic hyporeactivity to mites.     

Monitoring antioxidant enzymes in red cells during allergen immunotherapy

The aim of this report was to answer the question how specific immunotherapy influences the antioxidant enzyme system in patients with respiratory allergy and in longer perspective to find markers suitable to assess the efficacy of treatment. In open prospective randomised study 28 patients (18 females and 10 males, age 14–48 years) with seasonal respiratory allergy were treated with allergen immunotherapy. Subjects received subcutaneous therapy with allergens absorbed on calcium phosphate or aluminium hydroxide and were analyzed by the established protocol at the beginning, after three and 12 month of the treatment. In all treatment group red cell superoxide dismutase and glutathione peroxidase activities were in the normal range in allergic patients both before and during the treatment. Catalase activity in the allergic patients was lower as compared with controls and a significant increase of the enzyme activity occurred during and at the end of the treatment. In patients treated with calcium phosphate adsorbed allergen there was a continous increase of catalase activity from beginning up to the end of observation. In the case of the aluminium hydroxide treatment there was an increase from the baseline values up in the third month of the treatment and a decrease on the 12^th month. In summary, the present results open the question that allergen immunotherapy may cause imbalance of oxidants and antioxidants. To support our findings larger controlled field studies are needed.