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Biomedical subjects

M Kubel

Publications and source records attributed to M Kubel.

At least 19 recordsLinked to original sources

Second unrelated bone marrow transplantation without additional conditioning therapy after engraftment failure.

A 37-year-old female highly alloimmunized by multiple transfusions received a sex matched HLA-identical unrelated bone marrow transplant for hypoplastic MDS-RA with moderate myelofibrosis. Conditioning consisted of total body irradiation, cyclophosphamide and ATG, GVHD prophylaxis consisted of CsA, MTX and prednisolone. The CD34+ stem cell content of the first graft was relatively low due to an inadequate harvest. The patient appeared not to have engrafted by day 23 post-BMT. She therefore received a second sex mismatched HLA-identical unrelated bone marrow graft on day 25 after two days of 3.5 mg/kg methylprednisolone from a different donor. Over the ensuing days, the first marrow showed slow engraftment followed by engraftment of the second graft. The first graft was then rejected, as monitored by peripheral blood studies of chimerism. No signs of acute GVHD were observed. Despite successful trilineage engraftment and complete second donor chimerism, the patient died from disseminated toxoplasmosis encephalitis and pneumonia on day +104.

Adult↗

Rhinocerebral zygomycosis following bone marrow transplantation in chronic myelogenous leukaemia. Report of a case and review of the literature.

We report on a man suffering from chronic myelogenous leukaemia treated by allogeneic bone marrow transplantation who, in the late post-transplantation phase, developed a hyperacute fatal invasive rhinocerebral zygomycosis. The origin of the ascending infection was the sinus sphenoidalis from which fungal hyphae spread to the central nervous system via the skull and the dura mater. The first symptoms of this severe infection were cerebral convulsions and a bilateral total amaurosis. The isolation of the pathogen from post mortem tissue was not successful. The present case is compared with previous reports of zygomycoses after bone marrow transplantation.

Adult↗

[Detection of mixed lymphoid chimerism after allogeneic bone marrow transplantation: demonstration by interphase cytogenetics in paraffin-embedded tissue].

In bone marrow transplantation (BMT) the detection of residual host lymphoid or haematopoietic cells surviving conditioning therapy is because of its association to graft-versus-host disease, graft-versus-leukemia reaction, and relapse of leukemia a matter of great interest. We studied the occurrence of this mixed lymphoid chimerism (MC) in the formol-fixed lymphatic tissue of lymph nodes and spleen from 21 autopsies after allogeneic sex-mismatched BMT (5 females, 16 males, survival 5 to 1140 days after BMT). In situ hybridisation with biotinylated centromer-specific anti-X- and anti-Y-chromosome probes was performed on pepsin-digested paraffin sections. The number of double X-, single X-, and Y-chromosome bearing cells was analysed microscopically. Because of artefacts only 14 cases remained for valid investigation. MC was detected in 6 cases (5 out of 11 males 5 days to 840 days and 1 out of 3 females 76 days after BMT). MC occurred after whole body irradiation with 10 Gy (n = 5) and 7 Gy (n = 1). In 1 autopsy relapse of leukemia caused host cell infiltration. Cases with MC did not express histological signs of acute or chronic graft-versus-host disease, but 5 out of 8 with complete lymphoid chimerism did. The sensitivity of interphase cytogenetics on paraffin embedded tissue is low.

Autopsy↗

[Serological diagnosis of cytomegalovirus-induced interstitial pneumonia in patients following bone marrow transplantation].

For diagnosis of the interstitial pneumonia conditioned by cytomegalovirus (CMV) an indirect immunofluorescence test was used to measure IgM and IgG antibodies to CMV in 369 serum specimens from 41 patients after bone marrow transplantation (BMT). An interstitial pneumonia conditioned by CMV was diagnosed in 5 patients either serological (4 patients) or by detection of cytomegaloviral infection typical inclusion bodies in lung cells (1 patient). The detection of antibodies to CMV for diagnosis of interstitial pneumonia conditioned by CMV is problematical in the phase immediately after BMT because bone marrow recipients are severely immunosuppressed by radiation and cytotoxic drugs received before transplantation. New method for detection of CMV-specific antigens are necessary.

Adolescent↗

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↗

[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↗

[HLA and leukemia].

HLA-A, -B, -C characteristics were determined in 85 AML patients and in 47 ALL patients as well as in 95 pairs of parents of leukemic patients. The detected antigen frequencies of patients were compared with those of 2,947 donors from Leipzig. A significant increase of frequency was found for Cw4 and in the group of ALL patients (p = 0.05), an increase of frequency could be observed for B22 and in the group of PR/NR patients for pcor = 0.05. A correlation between A9 and longer survival time in leukemic patients could not be found. Parents of leukemic patients (but not the patients themselves) showed a limited genetic heterogeneity with respect to the HLA system.

Acute Disease↗

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↗

Plasma exchange for removal of anti-A and anti-B group antibodies in AB0 major-incompatible bone marrow transplantation.

Between 1980-1986 seven patients underwent AB0-major incompatible bone marrow transplantation. Incompatible anti-A and anti-B antibodies could be decreased by the plasma exchange from titers 8-256 down to 0-8. Our practice combined with additional depletion of erythrocytes from marrow allowed to transplant all patients successfully, however, one patient demonstrated an acute haemolytic reaction during infusion of marrow. Plasma exchange was fairly well tolerated, however, 4 patients developed slight urticarial reactions. Both thrombocytopenic patients overcompensated the platelet loss caused by the exchange.

ABO Blood-Group System↗

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↗

[Blood cell substitution within the scope of hematologic intensive therapy for supportive hemotherapy with erythrocyte, thrombocyte and granulocyte concentrates].

Nowadays the application of blood cell concentrates corresponding to indication is in nearly all cases superior to the whole-blood transfusion. For the substitution of erythrocytes are to be recommended buffy coat-free concentrates, for special indications also cryopreserved ones in order to avoid complications (sensitization, transmission of viruses). Concentrates of thrombocytes are to be administered nearly exclusively in disturbances of formation and may be used for the short-term application as pooled randomized preparations, in a medium period better may be used as individual donor preparation. In order to avoid sensitizations, but always when HLA-antibodies occur, HLA-compatible individual donor concentrates must be used. Particularly in the patient with immune deficiency the possible transmission and the growth of stem cells with subsequent graft-versus-host disease (therefore the concentrates should be irradiated with 15-30 Gy) and the transmission of cytomegaly viruses (CMV), respectively, which can be minimized using CMV-negative donors, is to be taken into consideration. Prophylactically applied concentrates of thrombocytes evidently co-determine the therapeutic success of the highly aggressive chemotherapy; transplantation of bone marrow could not be performed without them. On account of the danger of the transmission of CMV concentrates of granulocytes are administered only strongly therapeutically in life-threatening infections, when the patient shows a decrease of the number of granulocytes below 0.5 Gpt/l. However, the substitution must be performed consequently over at least 3 days and up to the proof of clinical effectiveness, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Grouping and Crossmatching↗