[Preliminary assessment of immune reconstitution after autologous peripheral hematopoietic stem cell transplantation (AHSCT)].

BACKGROUND & OBJECTIVES: Though high dose chemo-therapy combined with autologous hematopoietic stem cell transplantation (AHSCT) has made great progress on the treatment of chemo-sensitive malignant tumors, the relapse rate remains high. Successful immune reconstitution after AHSCT may reduce recurrence; therefore this study was to explore the characteristics of immune reconstitution after AHSCT and assess its feasibility in clinical use. METHODS: Twenty four cases after AHSCT were enrolled in our study. There were 19 Non-hodgkin Lymphoma (NHL), 3 Hodgkin Lymphoma (HD) and 2 rhabdomyosarcoma. Nineteen cases had achieved complete remission (CR) while 5 partial remission (PR) before AHSCT. All cases were administered Interleukin (IL)-2 and Interferon (IFN)-alpha after AHSCT. Some patients were given thymus factor and/or CIK infusion. Phenotypes of peripheral blood T, B, NK subsets and immunological profile of TH1/TH2 by intracellular staining of cytokines after PMA/ionomycin stimulation were evaluated. RESULTS: 75% of the cases achieved CR while 4.17% were progression of disease (PD) and 16.67% were relapsed during the median follow-up time of 12 (2-60) months. The changes of immune parameters after AHSCT were as followed: (1) CD4+T cells (normal control 33.5+/-6.9%) started to decrease dramatically one month after AHSCT, which was 2.5-13% (median rate 5.6%)in the 2nd month; and then slowly increased to 10-20% in the 7th month, but did not return back to normal even after one year in all patients. In addition, reversed ratio of CD4/CD8 lasted for a long period of time. B cells also began to decrease 1 month after AHSCT, and recovered to normal in the 4th month. But B cells remained 0% in the 6th month and 1% in 12th month in patients treated by rituximab before receiving AHSCT. The ratio of NK cells was 10-20% (higher than normal controls) in the 2nd month, then returned to normal thereafter. (2) The cytokine secretion by T cell: there were 48.79% patients whose TH1 was lower than normal controls or at the lower limit of normal range. All the patients with normal TH1 were treated by IFN-alpha or CIK cell infusion. TH2 was much higher than normal level among 68.29% cases and this abnormality lasted at least for 1 year in some cases. TH2 at normal range was only observed in cases receiving IFN-alpha treatment. Furthermore, IFN-alpha could significantly decrease TH2 level. (3) Increasing tendency of CD4+CD25+/CD4+, CD4+CD69+/CD4+ ratio was observed in patients received additional thymus factor treatment compared to those did not. CONCLUSIONS: Administration of CIK cells, thymus factor, IL-2 and IFN-alpha after AHSCT could improve the immunologic function of patients, and TH1/TH2 ratio may virtually reflect the immune status of patients. However more information is required to make prognostic assessments of immune reconstruction and the long-term survival rate.

[A clinico-immunological assessment of the efficacy of combined methods of treating patients with different immunopathological forms of focal scleroderma]. / Kliniko-immunologicheskaia otsenka éffektivnosti kompleksnykh metodov lecheniia bol'nykh s razlichnymi immunopatologicheskimi formami ochagovoi sklerodermii.

To help the physicians choose a rational scheme of combined therapy of patients with various immunopathologic forms of focal scleroderma, the authors present a clinical and immunologic assessment of the efficacies of 2 combined therapeutic courses, enzyme immunotherapy and penicillin immunotherapy, as well as of the individual course of tactivin immunotherapy. Inclusion of tactivin in any complex therapeutic scheme appears to be necessary. In patients suffering from the condition for a long time, with multiple foci of involvement, tactivin should be combined with enzymic drugs, like hyaluronidase (lydase). Enzyme immunotherapy promoted a more active resolution of the skin process. Penicillin immunotherapy alone is disputable, and further studies of such treatment are necessary. Enzyme immunotherapy should be considered as the optimal scheme of rational combined treatment for focal scleroderma.

Thymomodulin: biological properties and clinical applications.

Thymomodulin (Ellem Industria Farmaceutica s.p.a., Milan, Italy) is a calf thymus acid lysate derivative, composed of several peptides with a molecular weight range of 1-10 kD. Thymomodulin did not exhibit any mutagenic effect. Furthermore, thymomodulin used in animal studies showed no toxicity even when used at high concentrations. Of major significance are the observations in murine and human systems that thymomodulin remains active when administered orally. In vitro and in vivo administered thymomodulin was able to induce the maturation of T-lymphocytes. Additionally, studies in vitro showed that this thymic derivative can enhance the functions of mature T-lymphocytes with cascading effects on B-cell and macrophage functions. Extensive human clinical trials with thymomodulin showed that this agent can improve the clinical symptoms observed with various disease processes, including infections, allergies and malignancies, and can improve immunological functions during ageing.

Update and future perspectives of a thymic biological response modifier (Thymomodulin).

Thymomodulin (Ellem Industria Farmaceutica spa, Milan, Italy) is a calf thymus acid lysate with immunomodulating activities. It is composed of several peptides with a molecular weight range of 1-10kD. Extensive studies in animal systems showed that Thymomodulin exhibited no, or very little toxicity even when used at high doses. Studies done in vitro and in vivo demonstrated that Thymomodulin is a biologically active compound which regulates the maturation of human and murine pre T lymphocytes, as well as modulate the functions of apparently mature human and animal B and T lymphocytes. It was observed that Thymomodulin can promote myelopoiesis as demonstrated by an increase of granulocyte-macrophage colonies in agar. Although additional studies to examine its target cell lineage are required, it appears that Thymomodulin exhibits specificity toward T cells. Therefore, enhancement of other cell lineage functions by Thymomodulin may be indirect, and mainly due to its effect on T cells. Of major importance is to note that Thymomodulin is prepared in a manner which allows it to maintain its biological activity when administered orally.

Steroid economising effects of a calf thymus extract in three patients with juvenile chronic arthritis.

Recent therapeutic trials in rheumatology using different immunomodulating agents have given encouraging results. In this study an aqueous calf thymus extract (CTE) was administered to three patients, two with systemic juvenile chronic arthritis (JCA), Still's disease, who could not be weaned from steroids during 2 years of conventional therapy, and one girl with a chronic juvenile monarthritis who had responded unsatisfactorily to nonsteroidal antirheumatics for 19 months. A striking clinical improvement was observed in all three patients. Prednisone (PRED) was discontinued in one case with systemic (JCA) and 0.25 mg/kg body weight/day is presently being given to the other patient. The girl is doing well on 4 mg chloroquin kg body weight/day; indomethacin (IND) was discontinued. Laboratory data including cellular immunoreactivity normalized in all three patients.