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Biomedical subjects

R Dopfer

Publications and source records attributed to R Dopfer.

At least 55 records · Page 3Linked to original sources

[Transplantation of bone marrow from unrelated donors in chronic myeloid leukemia].

Bone marrow transplantations in four patients (aged 8-28 years, median 27 years) with chronic myeloid leukaemia (CML) were performed from unrelated donors who were HLA-identical and MLC-negative. One patient was in the stage of refractory blast crisis, one in a chronic phase, and two in the second chronic phase. Conditioning treatment consisted of fractionated radiation and administration of cyclophosphamide; in the patients with their second chronic phase additionally etoposide. Cyclosporin A and methotrexate were administered to prevent graft versus host reaction. The patient in the blast crisis died on day 12 after transplantation of Candida pneumonia. The other three patients are still alive 128, 306 and 530 days, respectively, after transplantation, only a mild form of graft versus host disease having occurred. It is suggested that for patients younger then 50 years with CML in the chronic phase an unrelated donor should be searched for in the absence of a familial donor.

Bone Marrow Transplantation↗

Chemotherapy for bone marrow relapse of childhood acute lymphoblastic leukemia.

Results of the BMF study group trials ALL-REZ 83 and 85 for relapsed acute lymphoblastic leukemia (ALL) are presented. For children with late marrow relapse, remission rates of about 90% were seen in both studies. In children treated for early marrow relapse, the remission rate in study ALL-REZ 85 was superior (86% vs 62%). The probability of event-free survival for all patients and for those with early marrow relapse was also statistically significant (P less than 0.05). Children with T-cell ALL had an extremely unfavourable prognosis in both studies.

Adolescent↗

Unusual course of a Chlamydia pneumonia in an infant with IgG2/IgG4-deficiency.

An unusual case of Chlamydia trachomatis (C. trachomatis) pneumonia, complicated by the development of a pneumothorax, is reported in an IgG2/IgG4 deficient infant delivered by caesarean section. C. trachomatis was isolated initially from a throat smear and subsequently from pleural effusions. Serological examinations using the complement fixation test were negative in sera of both mother and child. However, using immunofluorescence the presence of an acute or recent infection was confirmed by IgM-antibodies in the serum of the infant and IgA-antibodies in the serum of the mother. At the age of 7 months the girl suffered from impetigo contagiosa which was partially resistant to antibiotic treatment. IgG-subclass deficiency was diagnosed after the onset of this disease and the girl was then treated by immunoglobulin transfusion.

Antibodies, Bacterial↗

[131I]-metaiodobenzylguanidine in the treatment of metastatic neuroblastoma. Clinical, pharmacological and dosimetric aspects.

Ten children with stage III or IV neuroblastoma that had either relapsed or was refractory were treated with [131I]-metaiodobenzylguanidine (MIBG) from 1984 to 1986. The total dose ranged from 4,365 to 21,900 MBq and was given in one to five courses. Two patients achieved a complete remission (CR), two, a partial remission (PR), and three, an arrest of the disease. Pharmacological studies showed that 93% of detectable radioactivity was attributable to MIBG at the beginning of the infusion. However, by the end of the infusion this had decreased to 88%. The terminal half-life of MIBG was 37.0 h, whereas that of non-MIBG-bound iodine was 71.6 h. Therefore, the radioactivity-time product of non-MIBG-bound 131I was much higher than that of MIBG. Dosimetric studies showed a mean level of absorbed radiation for the total body of 160 microGy/MBq, a liver irradiation of 540 microGy/MBq and a mean tumour radiation of 10,500 microGy/MBq.

3-Iodobenzylguanidine↗

Lysis of neuroblastoma cells by the ADCC-reaction: granulocytes of patients with chronic granulomatous disease are more effective than those of healthy donors.

Granulocytes from healthy donors lyse human neuroblastoma cells in the ADCC-reaction using antibody MAb 14.18 directed to ganglioside GD2 present on the surface of most neuroblastoma cells. Addition of catalase, superoxide dismutase and azide do not impair this process. Granulocytes from patients with chronic granulomatous disease (CGD) kill neuroblastoma cells even better than those collected from healthy donors. These results indicate that reactive oxygen intermediates (ROI) are not involved in killing of neuroblastoma cells using MAb 14.18, and that granulocytes from patients with CGD may compensate for defects in generation of reactive oxygen intermediates by more effective oxygen-independent killing mechanisms. One patient with CGD was treated with interferon-gamma. During and after treatment, generation of ROI could not be detected and neuroblastoma cell killing was not significantly altered.

Antibody-Dependent Cell Cytotoxicity↗

In vitro induction of lymphokine-activated killer (LAK) activity in patients with neuroblastoma.

Therapy of disseminated neuroblastoma remains an unsolved problem in pediatric oncology. Therefore, new therapeutic approaches have to be developed for this malignancy. In this paper, we investigated the possibility of the in vitro generation and expansion of lymphokine-activated killer (LAK) cells in patients with disseminated neuroblastoma. Although the patients had very low Natural Killer (NK) activity, it was possible to induce LAK activity in peripheral mononuclear lymphocytes (PMNC) by incubation with Interleukin-2 (IL-2). Moreover, the PMNCs could be expanded up to 50-fold in the presence of Interleukin-2 while maintaining or even increasing their LAK activity. The target cells were neuroblastoma cell lines and, in one case, autologous neuroblastoma cells. Additionally, it was possible to induce LAK cell activity against autologous neuroblastoma cells in bone marrow-derived mononuclear cells.

Bone Marrow↗

Bone marrow transplantation in childhood leukaemia--experience and strategies in the Federal Republic of Germany.

BMT has gained its place in the treatment of childhood leukaemia. Nevertheless, there are still many questions open. In acute lymphoblastic leukaemia children should normally be grafted in 2nd remission (CR). Some high risk cases, however, should probably be grafted in 1st CR. It is not clear whether children with late relapses benefit more from BMT than from renewed chemotherapy. Children with a relapse during maintenance therapy, however, have a better survival rate with BMT. In acute nonlymphoblastic leukaemia certain high risk patients should be grafted in 1st CR but it has still to be shown that BMT is superior to chemotherapy in such cases. It is not clear whether children with a relapse following intensive chemotherapy (such as the BFM-protocols) will benefit from BMT at all. In chronic myelocytic leukaemia, BMT in chronic phase should be performed. Thus, for the first time cure has become possible for this disease. Waiting for acceleration or even the occurrence of a blast crisis decreases the chance of survival after BMT dramatically. Since complications of BMT such as graft-versus-host reaction or severe infections are less frequent in children, relapses remain the main problem after BMT in childhood leukaemia.

Bone Marrow Transplantation↗

Bone marrow transplantation in children with neuroblastoma.

Neuroblastoma is the third most frequent malignant tumor in childhood. One-third of the patients over one year of age at the time of diagnosis suffer from the disseminated form (stage IV). Despite highly aggressive chemotherapy survival rates are poor. One hundred and eighty-seven patients with neuroblastoma stage IV have been treated according to the German protocol NB 85. The probability of disease free survival is only 15% after 70 months. Treatment strategy in our protocol includes autologous and allogeneic bone marrow transplantation (BMT) for patients with stage IV (and greater than 1 year old). Twenty-two patients were grafted (7 allogeneic and 15 autologous). The conditioning regimen consisted mainly of high-dose melphalan (180 mg/m2) and total body irradiation (TBI) (3.4 Gy). Survival rates are discussed in the context of the chemotherapy protocol. Our own experience with autologous BMT is poor, despite of different purging methods. For this reason we decided to focus on allogeneic BMT. We have grafted five patients within the last 3 years. Three of them are alive and well, on died from veno-occlusive disease 70 days after BMT, and the remaining patient, grafted from a syngeneic donor, died from relapsing tumor. The main problem in neuroblastoma stage IV is resistance to chemotherapy. Intensification of the conditioning regimen or double autografting leads to a rate of toxic deaths close to 20% (Zucker, EBMT 1987) which is not tolerable. New improvements in the conditioning regimen have to be found to increase the effect of BMT.

Bone Marrow Transplantation↗

Influence of allogeneic bone marrow transplantation on the endocrine system in children.

With increasing survival rates of children grafted for different malignancies concerns about the longterm side effects of this treatment are growing. Therefore, investigations on the function of endocrine systems were conducted in a total 28 patients grafted for various reasons: ALL (N = 18), AML (N = 1), SAA (N = 3), CML(N = 4), neuroblastoma (N = 2). The results can be summarized as follows: 1. The extent of hormonal derangements is primarily dependent on the extent of irradiation prior to BMT. Integrity of hormonal systems was found in cases without irradiation (SAA) or if TBI did not exceed 3 Gy. 2. Primary hypogonadism was present in 18 patients. 3. Primary hypothyroidism was present in 2 patients. 4. Growth impairment was observed in 8 patients. In four of these cases growth hormone deficiency was the cause. In four other cases with graft-versus-host-disease and hepatic involvement SmC/IGF I levels were severely diminished. The data suggest that in most cases BMT itself has relatively few negative effects on the endocrine regulatory system. However, more detailed investigations before and after BMT will be needed to further validate these observations.

Anemia, Aplastic↗

[Systemic salmonella infections in chemotherapy in 2 children with acute lymphoblastic leukemia].

A 15 year old patient with acute lymphoblastic leukemia, previously diagnosed as being a salmonella carrier, developed S. typhimurium sepsis after allogeneic bone marrow transplantation, in spite of pretreatment with chloramphenicol. Clinical improvement and termination of salmonella excretion were achieved by treatment with multiple antibiotics. Another patient with acute lymphoblastic leukemia, a 3 year old boy not previously identified as a salmonella carrier, also developed sepsis and osteomyelitis, together with pathological fractures during chemotherapy. Chloramphenicol, administered after isolation of S. typhimurium from blood cultures, led to resolution of the bony defects, complete recovery, and cessation of salmonella excretion. Selective cultures for salmonellae seem indicated in patients with malignant diseases, prior to chemotherapy.

Adolescent↗

Significant association of acute lymphoblastic leukemia with HLA-Cw7.

Frequencies of all defined HLA-A, -B, -C (-DR) antigens were determined in 142 (59) Germans suffering from acute lymphoblastic leukemia (ALL) with differentiation of immunologically defined or age-related subgroups of the disease. A highly significant rise of the HLA-C locus antigen Cw7 was found in ALL patients, particularly those over the age of 11 in comparison with local German and Caucasian controls of the Ninth Int. Histocompatibility Workshop (WS). Only slight differences of HLA-Cw7 frequencies were observed within the four immunologically defined ALL subtypes of all or age-related patient groups. HLA-A, -B, or -DR antigens, as well as HLA-ABC three-locus haplotypes were similarly distributed in patients and their local or Caucasian controls. The results indicate HLA-linked genetic factors conferring susceptibility to ALL in adults, particularly those presenting with B-, T-, and Null-ALL.

Adolescent↗

Correlation between low CSA plasma concentration and severity of acute GvHD in bone marrow transplantation.

Between 1982 and 1986 51 patients were treated with ciclosporin a (CSA) to prevent graft versus host disease (GvHD) after bone marrow transplantation (BMT). Major side effects of the drug were tremor, hypertension, hepatotoxicity and nephrotoxicity. Acute GvHD 0 degree to II degree occurred in 80% of our patients, and GvHD III degree and IV degree in 20% despite the use of CSA. Two to four days before the onset of GvHD, CSA serum levels were significantly lower on the average in patients who developed GvHD III degree and IV degree compared to the others. Our data indicate that plasma CSA concentrations higher than 250 ng/ml should be achieved to reduce the severity of GvHD after BMT.

Acute Disease↗

High frequency of graft-versus-host-like syndromes following syngeneic bone marrow transplantation.

Occurrence of acute graft-versus-host reactivity-like (GvHR) syndromes has been shown in at least 3 and possibly in 4 further cases of 9 patients with bone marrow transplants from identical twin donors. The diagnosis of GvHR-like syndromes is based on clinical, immunologic, and histologic features indistinguishable from those observed in graft-versus-host disease (GvHD) grades I-III of patients receiving allogeneic major histocompatibility complex (MHC) matched bone marrow transplants. Induction of GvHR-like symptoms appeared to be correlated with reactivated viral infections after bone marrow transplantation (BMT) or, like in animal models, was due to specific conditioning therapy with cyclophosphamide. The high incidence of acute GvHR-like syndromes in the first months after syngeneic BMT suggests inability of the immune system to discriminate appropriately self from nonself antigens during a normal tolerance induction period after grafting.

Adolescent↗