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Twenty-six bone marrow transplantations were performed at the West Germany Tumour Centre at Essen between December 1975 and December 1981. Three patients had aplastic anaemia, 23 acute leukaemia. Of the leukaemia patients 13 had a recurrence and ten were in full remission at the time of the transplantation. Two of the patients with a recurrence received deep-frozen autologous marrow from the remission phase. One patient with aplastic anaemia had an identical twin as donour, while all other patients received allogeneic marrow from histocompatible family members. Eleven patients are still alive, all three of those with aplastic anaemia, one of those with leukaemia in a recurrence, and seven of those with acute leukaemia in full remission. Two of the survivors have a chronic graft-host reaction, but the others are symptom-free, after an observation period of up to four years. Main causes of death were leukemic recurrence (6), infection (5), and graft-host reaction (2). It would seem that at present bone marrow transplantation offers the best chance of a cure for severe aplastic anaemic and acute leukaemia in adults, but only if transplantation is undertaken early and not in the end-stage of the disease.

Eighteen patients with advanced squamous cell carcinoma of the esophagus without prior chemotherapy were treated with carboplatin. Based on experimental data a split dose of carboplatin of 130 mg/m2 g

In four cases of severe neutropenia of unknown origin we found a strong inhibition of the growth of granulocyte-macrophage (GM) progenitor cells. The development of GM colonies in culture (GM-CFU-c) was more than 80% reduced in comparison to the control group. In particular, the interleukin 3-(IL-3) and granulocyte macrophage colony-stimulating factor-(GM-CSF) dependent growth was affected; a combination of growth factors (IL-3, GM-CSF, and G-CSF, the granulocyte colony-stimulating factor) resulted in a less reduced growth. The findings were primarily compatible with drug-induced bone marrow failure. Among the medications given to the patients, famotidine, an H2-receptor blocker, was discussed as an agent which possibly triggers off this process. After the withdrawal of famotidine, in three cases a continual increase of the growth of GM precursors was detected, reaching the normal level 7-17 days later. In one case, further investigations of the progenitor cells could not be carried out due to the death of the patient, but the rapid increase of neutrophils in the peripheral blood after withdrawal of famotidine pointed to the recovery of hematopoiesis. In vitro studies showed that famotidine, depending on the dose, inhibits the single growth factor-dependent colony growth (IL-3, GM-CSF, or G-CSF) of bone marrow progenitors from a concentration as low as 10 micrograms/ml. With the combination of all three growth factors only slight inhibitory effects were detectable (up to 150 micrograms/ml famotidine). These results indicate that famotidine, in common with other H2-receptor antagonists, can affect hematopoietic progenitor cells. However, the plasma concentration of famotidine normally used in ulcer therapy does not seem to influence the hematopoiesis. Apparently, the progenitor cells of only a few patients possess a higher sensitivity to the blockade of H2-receptors at this concentration of famotidine. This was demonstrated in one case (patient 3) 2 years after the patient had recovered from famotidine-induced neutropenia. The growth of peripheral myeloid, erythroid, and multilineage progenitor cells of this patient was remarkably reduced even at famotidine concentrations of 0.1-5.0 micron/ml whereas in the control group no inhibition was detected at these famotidine concentrations. Again, the IL-3-dependent colony formation was more affected than in the case of the combination of IL-3, GM-CSF, and G-CSF. After the removal of accessory cells the inhibitory effect of famotidine persisted, demonstrating that accessory cells do not play a major role in this process.

Eighteen patients with advanced squamous cell carcinoma of the esophagus without prior chemotherapy were treated with carboplatin. Based on experimental data a split dose of carboplatin of 130 mg/m2 given on days 1, 3 and 5 was administered. In cases showing no WBC and platelet suppression, an escalated dose of 160 mg/m2 was proposed. Out of 18 evaluable patients no complete and partial responses were observed and there were only 5 patients with stable disease (27.8%) lasting 2-7 months. Therefore, carboplatin in the regimen used shows no meaningful antitumor activity in patients with advanced esophageal carcinoma. The escalated dose (mean 107-123% of the starting dose) was well tolerated and was followed by only minor gastrointestinal and hematological toxicity. Therefore, this regimen can be recommended for future trials.

The interpretation of cytological and histological preparations is sometimes difficult in hematological practice and does not allow a diagnosis characteristic of the differentiation capacity or the functional state of hematopoietic cells. Since the introduction of specific antibodies into clinical diagnostics, a more distinctive analysis is possible [1, 2]. However, neither of these investigations gives details about the growth factor susceptibility or growth behavior of hematopoietic precursors. On the other hand, modern methods in therapy offer biological alternatives in using substances regulating the proliferation and differentiation of blood progenitors [3]. Recent clinical trials with cytokines such as interferon and tumor necrosis factor (TNF) indicate that the individual elaboration of a biological treatment strategy is a crucial prerequisite of the successful therapeutic effect [4]. It seems that not only the optimal concentration but also the ideal combination of growth factors should be worked out individually from patient to patient [5–7]. Consequently, for the critical use of growth regulating factors in vivo the screening of the functional state of the organism is essential.

In einer randomisierten Studie wurden 79 Patienten entweder mit cis-DDP 3 mg/kg i.v. Tag 1 und Bleomycin 15 mg/m2 i.v. kontinuierlich Tag 2–5 (Arm A) oder weniger aggressiv mit Methotrexat

32 patients (10 females and 22 males) with chemotherapy-resistant tumors were again treated with the previously ineffective chemotherapy after plasmapheresis. 19 of 32 patients showed a minor response or no change lasting more than 3 1/2 weeks; in 10 of the 32 patients it lasted for more than 8 weeks.

A two-dimensional numerical model study and comparison of the polar dipole-dipole and Schlumberger resistivity arrays are presented. A catalog of dipole-dipole and Schlumberger apparent resistivity pseudo-sections is presented. It is concluded that: for the Schlumberger array, data can be accurately interpreted only if the resistivity structure is horizontally layered, and conductive bodies having a depth of burial greater than their width are not observed; for the dipole-dipole array, complex anomaly patterns unrelated in appearance to the causative structure result from simple models; hence, a familiarity with model results is essential to interpretation of these data.

Twenty-six bone marrow transplantations were performed at the West Germany Tumour Centre at Essen between December 1975 and December 1981. Three patients had aplastic anaemia, 23 acute leukaemia. Of the leukaemia patients 13 had a recurrence and ten were in full remission at the time of the transplantation. Two of the patients with a recurrence received deep-frozen autologous marrow from the remission phase. One patient with aplastic anaemia had an identical twin as donour, while all other patients received allogeneic marrow from histocompatible family members. Eleven patients are still alive, all three of those with aplastic anaemia, one of those with leukaemia in a recurrence, and seven of those with acute leukaemia in full remission. Two of the survivors have a chronic graft-host reaction, but the others are symptom-free, after an observation period of up to four years. Main causes of death were leukemic recurrence (6), infection (5), and graft-host reaction (2). It would seem that at present bone marrow transplantation offers the best chance of a cure for severe aplastic anaemic and acute leukaemia in adults, but only if transplantation is undertaken early and not in the end-stage of the disease.

In 53 patients with metastatic breast cancer and increased CEA serum levels (greater than 10 micrograms/l) the CEA titer within the first 8 weeks after commencement of chemotherapy was compared with results of therapy. Among 30 patients in whom CEA values had decreased by at least 30% of pretreatment values 12 showed remission, 15 no change and 3 progression of the malignancy. Among 23 patients with unchanged or increasing CEA values during therapy 19 had progression, 3 an arrest and one a remission of the disease. In the one patient with remission the course of the disease was unusual inasmuch as the CEA value increased to 240 micrograms/l serum and liver metastases regressed excessively at the same time. This lead to the assumption of CEA release by tumour necrosis during therapy. The results suggest that in metastatic breast cancer and increased CEA values remission generally cannot be expected should the CEA value remain unchanged or rise within the first 8 weeks after initiation of treatment. In contrast, a decrease of CEA within that time may be considered a prognostically favourable sign which, however, does not mean clinically relevant reduction of tumour size in every case. For evaluation of treatment sufficient precision of CEA determinations must be guaranteed.

Bei einigen Autoimmunerkrankungen gelingt es durch Plasmapherese eine klinische Besserung zu erreichen; zugleich wird in der Regel eine Verminderung von Autoantikorpern bzw. Immunkomplexen beobachtet. Bei der multiplen Sklerose (MS) ist das krankheitsverursachende bzw. krankheitsunterhaltende Agens bislang nicht bestimmt worden. Jedoch spielen wahrscheinlich verschiedentlich nachgewiesene Antikorper gegen Oligodendrozyten und basisches Myelinprotein, sowie Serumfaktoren, die die Lymphozytentransformation und die neuromuskulare Aktivitat hemmen, im Krankheitsprozes der MS eine wichtige Rolle. Der Versuch, diese Faktoren durch Plasmapherese zu eliminieren, kann bei der Foudroyanz einiger klinischer Verlaufe als geboten angesehen werden.

The cryoprotective effect of hydroxyethylstarch has been tested in mice and in man using the spleen colony technique (CFU-S test) or the agar colony technique (CFU-C test) as viability assays for the haemopoietic stem cell. In mice we found a mean CFU-S recovery of 88.7%+/-3.9% when a rapid, and 77.8%+/-3.2% when a slow, stepwise dilution method was applied to remove the protective medium (17.5-20% hydroxyethylstarch+20% calf serum) after thawing. In man the rapid dilution after thawing gave a mean CFU-C recovery of 80% but a wide scatter.

The preliminary results of a controlled study for treatment of 33 patients with squamous cell carcinoma of the head and neck region with regimen A: cis-DDP (3 mg/M2 dl) plus Bleomycin (15 mg/m2 i.v. continuously d2-6) against regimen B: Methotrexate (30 mg/m2 i.v. dl + 6) and vindesine (3 mg/m2 i.v. dl + 7) were as follows: complete remission (cr): 1 X A, 0 X B; partial remission (pr): 6 X A, 4 X B; minor response (mr): 3 X A, 7 X B; no change (nc): 2 X A, 0 X B; progression (pg): 5 X A, 5 X B. Due to progressive disease 8 patients were further treated with the alternative regimen with following results: cr: 1 X A; mr: 1 X A, 2 X B; nc: 1 X B; pg: 3 X A. Considering prognostic factors it could be demonstrated that primary chemotherapy (pc) was more effective that applied after operation and/or radiotherapy (secondary chemotherapy = sc): cr + pr: (= 53%), 4 X sc (= 22%); nc + pg: 1 X pc (= 7%), 7 X sc (= 39%).

The nature of the inhibitory activity of sera of patients with metastatic cancer on in vitro immunoassays remains unclear. Serum glycoprotein levels in cancer patients show a reasonable correlation with the clinical status, especially with progressive metastatic disease. Glycoproteins like acute phase reactants have been connected with immunosuppressive activity in cancer patients' sera. In this study, we examined the influence of glycoprotein fractions of normal and cancer sera, separated by Con A immunoadsorption, on the mixed lymphocyte culture as a reference system for suppressive activity. Glycoprotein rich fractions with the utmost recovery of the acute phase reactants inhibited the mixed lymphocyte culture in a dose-dependent manner. This effect was more pronounced in patients sera as compared to control sera. But there is evidence of additional blocking activity in the glycoprotein poor serum fraction, indicating blocking factors still to be identified.

Auch heute noch sterben Patienten mit akuten Myeloblastenleukamien bei intensiver Chemotherapie zu 60 bis 70% an todlichen Infekten, wenn keine entsprechenden Vorsichtsmasnahmen getroffen werden. Diese bestehen heute in einer umgekehrten Isolation (reverse isolation), um die Patienten vor den Keimen der Umwelt zu schutzen. Wir verwenden zur Isolation 2 laminar down flow-Zelte. Zusatzlich unterteilten wir die in den sterilen Zelten behandelten Patienten in solche, die nur isoliert waren, d. h. sterile Bettwasche, steriles Essen, sterile Medikamente, Hautdesinfektion usw. bekamen, und solche, die zusatzlich dekontaminiert wurden, d.h. zu den oben erwahnten Masnahmen orale, nicht absorbierbare Antibiotika und ein auf seine Sensibilitat getestetes Antimykotikum bekamen.

52 patients with epidermoid cancer of the head and neck region were either treated with cis-DDP and bleomycin (arm A) or with methotrexate and vindesine (arm B). In case of resistance patients were further treated with the alternative regimen (A leads to B or B leads to A). Treatment results are superior in arm A. Complete and partial remission were in A: 54%, in B: 31%, after crossover 46% and 0%, respectively. Status of pretreatment (operation and/or radiotherapy) is of minor importance for arm A than for the "soft" treatment of arm B. Preliminary analysis of survival and remission duration shows no significant difference in regard to A or B and status of pretreatment. However, those patients resistant to B and further treated with A have an increase of median survival from 3 to 9 months (p = 0.02). With primary chemotherapy inoperable tumors can be made operable with curative intention.

An attempt has been made to standardize the method of large volume plasma exchange in tumor patients on the basis of an albumin-electrolyte exchange solution. Problems relating to the alteration of tumor patients' serum proteins are discussed. Three patients with malignancies successfully underwent therapeutic plasmaphereses.

Patienten mit rezidivierendem oder metastasierendem Rektum- oder Kolonkarzinom haben sehr oft, wenn der Tumor im kleinen Becken wachst, unertragliche Schmerzen, die mit keiner konservativen Analgetikatherapie beherrscht werden konnen. Die Lebensqualitat dieser Patienten mit diesem sogenannten Post-Proktektomiesyndrom ist erheblich vermindert, sie sind an das Bett gefesselt und haufig von Morphinderivaten abhangig. Bevor eine chirurgische Schmerzausschaltung durchgefuhrt werden sollte, z. B. durch eine Rhizotomie oder Chordotomie, kann eine intraarterielle Beckenperfusionstherapie mit 5-Fluorouracil eine Schmerzlinderung oder Schmerzfreiheit mit Anheben der Lebensqualitat erreichen (Hafstrom et al. [2]).

Treatment of patients with advanced squamous head and neck tumors demonstrates even with best surgical and x-ray techniques only five year survival rats between 10 and 30%. Chemotherapy in addition seems to improve these results. From July 79 to January 80 21 patients with advanced squamous-cell carcinoma at the head and neck region were treated in a controlled pilot study with Cisplatinum/Bleomycin or Methotrexate/vindesine. 6 patients were primarily treated with chemotherapy, all other secondary progressive disease after surgical and x-ray procedure. Without respect to the generally cell tolerated therapy modality on overall remission induction rate of 50 and 70% was observed. In a subsequent randomized controlled multicentric study both regimes will be compared concerning remission, survival and toxicity.

Normal wound closure and optimal cicatrisation which is equally satisfactory from the medical and from the cosmetic standpoint is contingent on the early formation of fibrin, which has to be sufficiently stabilised by factor XIII and is subjected to gradual, generalised or local fibrinolysis. Thus, the fibrin sealant — at one time just wishful thinking among the medical profession — has become an indispensible treatment modality for patients with congenital or acquired bleeding disorders, and has helped to improve certain operative procedures. The indications for which fibrin sealant is used at the Gottingen University Medical Hospital are listed in Table 1 ; nearly all of them have been described in the spate of literature on fibrin sealant published over the past few years.

79 patients were randomized and treated either with cis-DDP 33 mg/kg i.v. day 1 and BLM 15 mg/m2 i.v. continuously day 2-6 (arm A) or less aggressively with MTX 30 mg/m2 i.v. day 1 + 6 and VDS 3 mg/m2 day 2 + 7 (arm B). Patients with inadequate response were further treated with the alternative regimen ("cross over"). Regarding response rates therapy A was superior to B (p = 0.01) respectively p = 0.05 for the cross over patients. Not pretreated in comparison to pretreated patients demonstrated not significantly better results. Pretreated patients had statistically superior response rates with arm A than with arm B (p = 0.05). All other prognostic factors were without any influence on treatment results. CR induced by chemotherapy (2 X) in not pretreated patients could be increased by additional surgery and X-ray therapy (CR = 26X). Survival times demonstrated no difference between both regimes. Chemotherapy was of less influence on median survival times after 39 months than in comparison to post-chemotherapeutically performed surgery +/- radiotherapy in 44 not pretreated patients. Chemotherapy: CR + PR to MR + NC + PD 16 respectively 13 months with 38 respectively 48% survivors (p = 0.25). Surgery +/- radiotherapy: CR + PR median not reached yet, MR + NC + PD 13 months with 60 respectively 18% survivors (p = 0.001).

Chemotherapy resistance in cancer patients may be due to serum blocking factors, which can be diminished or eliminated by large volume plasma exchange (PE). This procedure was performed with the IBM blood cell separator in 69 patients resistant to chemotherapy. Immediately after PE the chemotherapy was given but it was reinstituted, if clinical evaluation revealed partial remission, minor response or no change. 37 out of 69 patients (53.6%) responded again, 32 (46.4%) did not. Response duration ranged from 2 to 45 weeks. Best clinical results were obtained in patients with colorectal cancer, 15 out of 23 showed improvement between 4 to 45 weeks. Serum blocking activity was measured using a modified mixed lymphocyte culture assay (MLC). There was a 80% positive correlation between clinical course of patients and MLC levels, if basic activity before the first PE was compared to MLC inhibition before the following PE's.

44 patients with advanced squamous cell carcinoma of the head and neck were randomized and treated preoperatively either with arm "A": cis-DDP (3 mg/kg iv day 1) and BLM (15-20 mg iv continuously day 2-6) or arm "B": MTX (30 mg/m2 iv day 1 + 6) and VDS (3 mg/m2 iv day 2 + 7). Treatment with arm "A" was superior producing 73% complete and partial remissions (CR + PR) compared to 40% for arm "B" (p = 0,05). The number of patients with CR could be increased from 2 to 26 by surgery and/or radiotherapy. The median survival for patients with chemotherapeutically induced CR and PR was 16 months but this did not differ significantly from the median survival (13 months) of non responders (p = 0.25). For patients with CR and PR achieved by surgery and/or x-ray therapy the median survival point has not yet been reached, and this is significant compared to the non responders (p = 0.001). Five of 26 patients with CR died after 39 months of observation and 6 are living with recurrence. In addition to clinical trials, chemotherapy is indicated for patients with inoperable tumours. The value of chemotherapy can only be answered by randomized trials comparing chemotherapy combined with standard procedures against surgery and radiotherapy alone.

Im folgenden berichten wir uber die zytostatische Wirksamkeit von CDDP bei 20 Patienten, die nach Behandlung mit konventionellen zytostatischen Schemata als ausbehandelt anzusehen waren.

In a phase-II trial, 18 patients with intractable pelvic and perineal pain caused by local recurrent and/or metastatic colorectal carcinoma resistant to combinations of analgesics, systemic cytostatic chemotherapy and/or radiation were treated with intra-arterial perfusion therapy using 15-30 mg 5-FU/kg body wt./day for 1-5 days. Of 18 patients, ten achieved complete pain relief for 3-32 weeks (mean, 15.7 weeks); after the perfusion therapy eight used less than 50% of the amount of analgesics required before treatment; one patient had only a minor response; two patients were treated unsuccessfully. Side effects were mild and controllable. One patient died subsequent to arterial embolism in the leg where the catheter was placed; pelvic perfusion therefore appears risky in patients with severe arteriosclerosis.

Veranderungen innerhalb der Kompartimente thymusabhangiger (T) und bursa- bzw. bursa-aquivalent-abhangiger (B)-Lymphozyten des peripheren Blutes unter pathologischen und auch therapeutischen Bedingungen beanspruchen in zunehmendem Mase das Interesse des Klinikers. Einer der Grunde hierfur ist die Frage nach der Herkunft der bei hamatologischen Systemerkrankungen proliferierenden oder akkumulierenden Zellpopulation. Dieses Problem war es auch, das uns zu systematischen Untersuchungen der Verteilung T- und B-Zellen-typischer Marker bei Patienten mit Leukamien, Morbus Waldenstrom und immunologischen Defektzustanden veranlaste. Wir haben das Vorhandensein membranstandiger Immunglobuline (Ig) als B-Zell-Eigenschaft und die Eigenschaft der spontanen Rosettenbildung mit Hammelblutkorperchen als T-Zellen-Spezifitat sowie die Stimulierbarkeit durch Phytohamagglutinin (PHA) und PokeweedMitogen (PWM) fur unsere Untersuchungen herangezogen. Die methodischen Voraussetzungen des Rosettentestes wurden an Thymuszellen eines 16 Wochen alten menschlichen Feten und an fetalen Milzzellen gepruft. Dabei fanden sich im Thymus 45% rosettenbildender Lymphozyten oder auch E-Rosetten, wahrend in der Milz keine Rosettenbildung festzustellen war.

The intravenous administration of the inhibitor of platelet adhesiveness RA 233 to blood donors before and during cell separation did not increase the yield of platelets in the final concentrate.