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Biomedical subjects

W Helbig

Publications and source records attributed to W Helbig.

At least 19 recordsLinked to original sources

Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy.

About 30% of adults with acute lymphoblastic leukemia (ALL) and 20% to 40% of children and adults with acute myelogenous leukemia (AML) never achieve remission, even with intensive chemotherapy. Most die of resistant leukemia, often within 6 months or less. In this study of 126 patients with resistant ALL or AML, allogeneic bone marrow transplants from HLA-identical siblings produced remissions in 113 of 115 (98%) evaluable patients. The 3-year probability of leukemia-free survival was 21% (95% confidence interval, 15% to 29%). Leukemia-free survival was similar in ALL (23%, 12% to 40%) and AML (21%, 14% to 31%). Only 3 of 27 patients at risk relapsed more than 2 years posttransplant.

Adolescent

[Therapy of bacterial infections in neutropenic and immunocompromised patients].

Neutropenias, especially extended an long-lasting stages, lead to life-threatening endogenous infection. Therefore, after taking off materials for bacteriological investigations an empirical schedule of a combined high dose, treatment with broad-band antibiotics and/or antimycotics has immediately to be introduced and to continue until the body temperature and the peripheral blood granulocytes are normalized. In case of treatment failure one should complete the therapy by other additional antibiotics or correct the combination of its in respect to the results of the microbiological investigations. Supplements of this antimicrobial treatments are immunoglobulins and growth factors (G-CSF, GM-CSF). In case of an expected neutropenica the use of the selective gut decontamination or the reverse isolation of the patient can be of essential advantage.

Anti-Bacterial Agents

[Immunohistologic investigations of paraffin-embedded lymph nodes after bone marrow transplantation in autopsy samples].

A histological and immunohistochemical analysis of paraffin-embedded lymph nodes from 31 autopsies after bone marrow transplantation (BMT) was performed (20 allogeneic, 10 autologous, 1 syngeneic). Monoclonal antibodies against CD 45RB, CD 20, CD 21, CD 35. CD 43, CD 45RO, CD 76 and Ki-B3, and antisera for detection of S 100-protein and immunoglobulin isotypes were used. None of the lymph nodes showed a regular reconstitution. The lymphoid cells, scattered in a diffuse pattern, were mainly CD 43-positive. Most of them also expressed the CD 45RO antigen. CD 20- and Ki-B3 positive lymphoid cells were nearly absent within the first 100 days after BMT. After that time B cell follicles were detectable in a few cases. Surprisingly, in nearly all cases with infectious complications, numerous plasma cells could be found. The origin of this plasma cells is discussed.

Antibodies, Monoclonal

Dose-reduced induction therapy for acute leukaemias decreases both the complete remission (CR) rate and the probability of leukaemia-free survival (LFS).

Especially in AML but also in ALL a dose reduction during the induction therapy effected distinctly both a diminution of the CR rate and a shortening of the LFS. For these reason reduced treated patients are to exclude from final analysis of study in order to obtain a objective comparison of the four postremission treatment modalities. There was no difference concerning treatment related mortality between "correct" and "reduced" induction therapy.

Acute Disease

T-cell depletion and haematological side effects of two cytotoxic monoclonal antibodies.

We investigated two cytotoxic monoclonal antibodies of BL-series (BL-IIIB4 and BL-IIG2) according to T-lymphocyte depletion from bone marrow. Both antibodies work together with human complement similar Campath-1, which was tested parallelly. The extent of T-cell depletion is about 95% for all three antibodies. On the other hand the haemopoietic side effects tested by CFU-GM recovery and LTBMC are for the BL-antibodies not as strong as for Campath-1, especially in view of LTBMC. T-cell regeneration could be shown in long term cultures. Our results indicate a possible suitability of the two investigated antibodies for T-cell depletion of bone marrow.

Antibodies, Monoclonal

[Results of therapy of 100 patients with acute leukemia--a retrospective unicenter 5-year analysis].

The results of therapy in 100 patients who newly fell ill (68 AML, 32 ALL) with acute leukaemia were evaluated (1981 to 1985). The 5-year-survival chance of all patients is 15% for AML, 18% for ALL, first of all it is depending on the degree of remission obtained. The CR rate is nearly 43% (AML) and 66% (ALL), respectively, shows a dependence upon age and is impaired above all by a high early death rate (supportive therapy). With increasing aggressiveness the results of the remission induction therapy improve, as it becomes clear in a comparison with an evaluation of patients 1965-1980 (CR: 15-32%). Also in the postremission therapy the results of intensive forms of therapy are more favourable: 4 years recurrence-free survival after CR in autologous bone marrow transplantation 50%, in allogenic bone marrow transplantation 40%, in cyclic chemotherapy 17%, in oral permanent therapy 0%. Starting from these findings the present conception of the therapy of acute leukaemias is discussed in connection with the literature.

Adolescent

The use of long-term bone marrow cultures (LTBMC) to detect hematotoxic side effects of purging methods.

With a view to the establishment of purging methods it is necessary to investigate complete-remission bone marrow as the real target of purging, rather than bone marrow from healthy donors. The results of LTBMC are superior to those of GM-CFC where the hematopoietic recovery of bone marrow is concerned. One-stage LTBMC after bone marrow manipulations may reflect mixed hematopoietic/stromal effects. The use of two-stage LTBMC allows the evaluation of the stem cell recovery without the possible influence of a damaged microenvironment.

Bone Marrow

Allogeneic bone marrow transplantation for leukaemia and aplastic anaemia. Results of the Leipzig BMT Group.

In acute leukaemias there was a stable plateau in the survival curve at 45% after two years if grafted in first complete remission (n = 20) but only 13% of the patients are disease-free alive if grafted in a more advanced stage of the disease (n = 8). In 16 patients transplanted for chronic myeloid leukaemia the overall survival is 40%, in cases with graft-versus-host disease (GVHD) prevention by cyclosporine survival rate could be improved. Only 8 patients with severe aplastic anaemia, partially in low performance status were able to be transplanted; three died of infections, another by acute GVHD. The fatal complications in our study characterize the international well-known major problems in BMT: GVHD, interstitial pneumonitis, infections, graft failure in aplastic anaemia and recurrence of leukaemia, especially in more advanced leukaemia stage.

Anemia, Aplastic

Acute and late effects in the course of and after total body irradiation with following bone marrow transplantation in patients with different forms of leukaemia.

The acute reaction in the course of a total body irradiation (TBI) appears in an organ-specific damage of the stem cells. Moreover, there are unspecified central-nervous stress reactions. Clinical reactions are obtained by the study and symptomatic therapy is proposed. 90 patients with different forms of leukaemia were observed. We documented the course in a specific "protocol system". Reactions like an increase of body temperature, changes of pulse and blood pressure were registered. The occurrence of gastro-intestinal reactions is a typical symptom of the acute radiation syndrome e.g. vomiting and diarrhoea are demonstrated in dependence of the applicated dose of irradiation. Further symptoms of TBI appeared in the later period. Mucositis, parotitis, a decreased function of the salivary glands and diarrhoea as well as vomiting are characterized by different intensity and temporary termination. A difference between allogeneic and autologous transplantation is caused by a medicamental additional treatment. During the late period these symptoms will disappear completely. Moreover, after TBI and BMT late effects are a cataract and some changes in the hormonal system demanding a specific correction or substitution respectively.

Adolescent

Autologous bone marrow transplantation (ABMT) using unpurged marrow as intensification for first complete remission in acute leukaemia (AL).

In order to assess the clinical advantage of autologous bone marrow transplantation (ABMT) without ex vivo purging, the results in 26 patients (10 AML, 16 ALL) in 1. CR were analyzed retrospectively. All patients received 3 consolidation cycles "in-vivo purging" before marrow harvesting. Beside relapses infections and cardiac failure were the most frequent complications. After 1 to 12.5 months 11 cases relapsed with a higher probability in patients who had a longer period of induction and between CR and ABMT. 12 patients became relapse-free survivors 6 to 53 months after ABMT with a stable plateau after 12.5 months for 8 patients. In conclusion, ABMT following "in-vivo purging" as the strongest one-step postremission therapy in patients with acute leukaemias may be a way for better long-term results in these patients.

Adolescent

Immune recovery following bone marrow transplantation.

83 patients undergoing allogeneic or autologous BMT because of haematologic malignancies have been studied before and after transplantation at different intervals. The determinations consisted of lymphocyte counts, E-rosetting, lymphoblastic response, evaluation of serum immunoglobulin levels, skin testing, and in a smaller part of the patients surface marker studies using monoclonal antibodies of the BL-series. At first after BMT the lymphocyte and T cell counts went to normal between 4-18 weeks post transplant, about 4 weeks earlier in autologous than in allogeneic BMT. T suppressor cells showed an early increase compared to T helper cells which normalized much slower about 6 months after BMT. Lymphoblastic responses, however, tended to normal not before the second half of the first year both in autologous and allogeneic transplantation. Skin test reactivity became normal during the 2nd and 3rd year posttransplant, which was more complete in autologous than in allogeneic BMT. The IgG and IgM levels were depressed for half a year and IgA levels for 2 years. The most striking aspect was the multiphase course of lymphoblastic response in every individual patient. We suggest this to be the expression of sequential differentiation of donor lymphocytes.

Anemia, Aplastic

Endocrine dysfunction after total body irradiation and bone marrow transplantation.

The present report describes our data regarding changes of endocrine parameters after total body irradiation (TBI) and bone marrow transplantation (BMT). Endocrine glands are usually resistant to irradiation under morphological aspects. But new methods of determination and sensitive tests were developed in the last few years. Now it is possible to detect already small functional changes. Endocrine studies in the course of the disease were followed serially at 16 patients with TBI and BMT. Pretransplant conditioning consisted of single-dose irradiation combined with a high-dose, short-term chemotherapy. Reactions of the endocrine system showed a defined temporary order. Changes of ACTH and cortisol were in the beginning. The pituitary-adrenal cortex system responds in a different way. The pituitary-thyroid system develop a short-term "low-T3-syndrome" reflecting the extreme stress of the organism. At the same time we obtained an increase of thyroxine. Testosterone and luteotropic hormone, the sexual steroids showed levels representing a primary gonadal insufficiency. The studies in the posttransplant period yielded a return to the normal range at most of the hormonal levels with the exception of the sexual steroids. Sterility is one of the late effects of TBI. A tendency towards hypothyroidism could be noticed in some cases being only subclinical forms. Reasons and possible therapy are discussed.

Adrenocorticotropic Hormone

Germ monitoring of patients, staff and environment in reverse isolation.

To estimate the efficiency of germ-poor for patients who underwent BMT or ABMT in reverse isolation we investigated the staff, patients and the environment of the BMT unit bacteriologically and mycologically between 1/85 to 3/87. On patient's body surface gram-negative germs were not estimated but coagulase negative staphylococci persisted. Only in few cases aerobic spores were detectable, seldom enterococci, corynebacterium and fungi. Staff members had a distinct higher grade of contamination inside the BMT-unit but outside of isolation rooms. We found sporadically staphylococcus aureus and germs of the mouth cavity on hands and fore head. Although gram negative rods were seldom detected in environmental studies, humid regions of the ward remain to be problematic zones.

Bacteria

Lethal complications in 30 patients after allogeneic BMT (BMT) and autografted (ABMT) patients (1980-1986) examined by autopsy.

Lethal and accompanying complications from 29 allogeneic, 8 autologous, and 1 syngeneic transplanted pts., died between 1980 and 1986 at the BMT-Center Leipzig were revisited. An important problem was that of systemic and local infections. We observed a predominance of bacterial and fungal infections within the first 3 weeks p.t., and later on a period of predominantly virus-associated infections. The most common early death (up to 3 months p.t.) was related to ICP, as a rule caused by CMV. GvHD was a common finding at autopsy, and GvHD of the bowel seems to facilitate infectious inflammations of the bowel. There was a positive correlation between severe GvHD and the occurrence of ICP. Neither of the died BMT pts. showed signs of relapse. After ABMT ICP did not occur. The lethal complications were septicaemia, local infections, relapse and haemorrhagic diathesis. A toxic effect of DMSO in 3 pts. must be taken into account. In conclusion, a rather small number of lethal factors indicates the steps in improving results of transplantation in the future.

Adolescent

Growth of hemopoietic cells after incubation with VP 16-213.

We examined the effect of various concentrations of VP 16-213 (25-125 microM/l, 2-h incubation on normal and complete remission bone marrow from patients with acute leukaemia and on leukaemic blasts. The maximal tolerated dose of the drug for normal bone marrow GM-CFC was between 75 and 100 microM/l whereas that for complete remission bone marrow was distinctly lower. More early stem cells measured by aid of LTBMC were more resistant in normal, but not in every remission bone marrow. We have to examine if these LTBMC results are influenced by a damaged microenvironment by using 2 stage LTBMC. Spontaneous leukaemic cells showed a different, sometimes lower sensitivity to VP 16-213 doses maximally tolerated by normal hemopoietic cells so that the VP 16-213 incubation must not be effective for every leukaemia.

Bone Marrow