Treatment-induced changes in 31P-MRS (magnetic resonance spectroscopy) spectra of sera from patients with acute leukemia.

31P-nuclear magnetic resonance (NMR) spectra were obtained in vitro from sera of 40 healthy volunteers and 30 patients with acute leukemia (AL) at the time of diagnosis and repeated up to 2-13 times during therapy. All spectra consisted of inorganic phosphate (Pi) peak (used as a reference peak) and two peaks from phospholipids (PL): one peak due to phosphatidylethanolamine and sphingomyelin (PE + SM) and second peak due to phosphatidylcholine (PC). Prior to initiation of therapy 31P spectra of sera of patients with acute leukemia differed from spectra of sera of normal individuals. Peak intensities of the PL were low in relation to Pi. During therapy leading to remission, resonance from PL progressively increased approximately to the spectral pattern in normal sera. Contrary to that, in non-responders the intensities of the phospholipids peaks remained unchanged. Long-term follow-up 31P-MRS studies showed not only a good correlation between this 31P-MRS evolution of sera and the response to the therapy but also showed changes in phospholipids' levels in the following days during and after therapy. Moreover, correlations were found between high-density lipoprotein (HDL), cholesterol (CHOL) and low-density lipoprotein (LDL) concentrations measured by conventional techniques and peak intensities of PC and of PE + SM acquired by 31P-MRS.

The significance of carboxy-terminal telopeptide of type I collagen (ICTP) and osteocalcin (OC) in assessment of bone disease in patients with multiple myeloma.

Bone disease occurring in multiple myeloma is usually evaluated using radiological methods. These methods, however, provide not much information about the dynamic process of bone resorption and formation. This study analysed levels of serum markers of bone turnover (ICTP and OC), reflecting function of osteoclasts and osteoblasts. It demonstrates increased level of ICTP in 75 patients with MM compared to control group (8 persons) and patients with Waldenström's macroglobulinemia (10 persons). The level of ICTP was also higher in patients with more advanced bone disease and probably in higher stage of disease according to Salmon and Durie classification. This tendency was not observed in relation to OC. Result of the research confirms that ICTP may incur sensitive and specific markers of bone lesions in multiple myeloma.

Application of 31P NMR spectroscopy in clinical analysis of changes of serum phospholipids in leukemia, lymphoma and some other non-haematological cancers.

The sodium salt of cholic acid added to serum caused separation of three phospholipid peaks located upfield from inorganic phosphate (Pi) due to phosphatidylethanolamine with sphingomyelin (PE + SM), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC). 31P NMR spectra were obtained from the sera of 15 healthy volunteers, 10 individuals suffering from acute leukemia, 4 persons with malignant lymphomas, 13 patients with digestive tract tumors and 5 with renal cell carcinoma. The present studies confirmed our previous observation that the 31P spectra of sera of patients with acute leukemia and malignant lymphomas revealed a significant decrease in the phospholipid level at the time of diagnosis and displayed a good correlation between spectral parameters and stage of disease in patients responding and non-responding to therapy. Contrary to the preliminary studies, peaks from PE + SM and PC, and also a peak from LPC were observed. Changes in phospholipids in the 31P NMR spectra observed in patients suffering from digestive tract tumors and renal cell carcinoma were primarily dependent on the advance of the disease. Most of our patients with these cancers were in the early stage of the disease, and the spectra showed statistically significant decrease only in the LPC peak area, and no statistically significant changes of peak areas of PC and PE+SM in comparison to the control group. In conclusion, we can state that the LPC peak area is the most sensitive indicator in the monitoring of treatment in acute leukemia and malignant lymphomas. Our results also showed that LPC peak areas were decreased in the early stages of digestive tract tumors and a renal cell carcinoma.

Natural killer (NK) activity in patients with Hodgkin's disease before, during and after multiple-agent therapy.

Natural killer (NK) cell activity was investigated in 108 patients with Hodgkin's disease (HD) during the course of the disease and in 50 healthy volunteers. NK activity of peripheral blood lymphocytes was evaluated against 51Cr labeled K562 cell line in 4 hr Cr release assay. The mean NK activity was highly significantly lower in patients before treatment and in patients in the active phase of the disease during treatment compared with controls, whereas in patients in complete clinical remission was significantly higher. However, in patients responding to treatment NK activity was increasing, reaching normal rate in remission and was exceeding further during remission duration. Nonresponders to treatment showed considerable decrease of NK activity to undetectable values. The pretreatment level of NK activity was not related to subsequent prognosis of the individual patient.

Differences in the blast cells sensitivity to cytostatic drugs in various acute leukemia types and their clinical implications.

In 80 patients with AML, ALL, BC-CML and other proliferative blood diseases, the sensitivity of blast cells to cytostatics (vincristine, cytosine arabinoside, daunorubicin, l-asparaginase, hydrocortisone) was determined. The studies were made with the use of liquid scintillation measuring the inhibition of 3HTdR incorporation induced by the cytostatics tested. It has been shown that the method makes it possible to demonstrate individual reactivity of acute leukemia blasts to cytostatics. Variations in the individual sensitivity to cytostatics were mostly seen in acute myeloblastic leukemia, blastic crisis of chronic myelocytic leukemia, less often in acute lymphocytic leukemia.

[Hematological disorder caused by a giant myoma of the uterus]. / Zaburzenia hematologiczne wywolane miesniakiem macicy.

OBJECTIVES: Polycythaemia means an increase in the number of red blood cells and usually a corresponding increase in the haematocrit and in the quantity of haemoglobin. Regarding etiology, primary and secondary forms of polycythaemia can be distinguished. The primary form--polycythaemia vera--is caused by autonomous erythroblastic hyperplasia. Secondary polycythaemia--erythrocythosis--may arise as a consequence of erythropoietin (EP) overproduction due to tissue hypoxia. These changes may stimulate the EP synthesis in the kidneys. EP may also be produced in metaplastic cells. STUDY DESIGN: A 59-year-old woman was admitted to the Clinic of Haematology of the Wroclaw Medical University with a 10-years' history of significant increase in HB, VPRC and RBC. Physical examination showed an obvious plethora and a large intra-abdominal painless tumour. Laboratory data revealed increases in Hb, VPRC, RBC and EP. A bone marrow aspiration was normal. During surgery, a large leiomyoma of the uterus was found and a total hysterectomy was performed. Pathological examination showed the tumour to be fibroleiomyoma. 4 weeks after surgery Hb, VPRC, RBC and EP, all returned to normal levels. RESULTS: Excluding the effect of the renal compression, it can be concluded that erythropoietin secreted by the the tumour caused the secondary haematological changes.

[Effect of brown enriched Livex on the general condition of patients with proliferative diseases of the bone marrow and lymphatic system]. / Wplyw Livexu brazowego wzbogaconego na stan ogólny chorych z chorobami rozrostowymi szpiku i ukladu chlonnego.

Brown Livex, a preparation of animal blood in doses of 5.0 g twice daily was given to 33 patients with proliferative diseases of bone marrow and lymphatic system during and after treatment with cytostatic agents. The course of treatment was 3 months. The effect of the preparation was studied on the wellbeing of the patients, body weight, general fitness (Karnofsky scale) and the levels of haemoglobin, haematocrit and beta-lipoproteins. The control groups comprised 20 patients with similar diseases and similar cytostatic treatment. In the studied group a positive effect was observed of the preparation on weight gain (26 out of 33 patients), well-being (24 of 33) and general fitness (17 of 33). In the control group during the same-time of observation weight loss was noted in 11 of 20 cases, well-being deterioration in 7 of 20, and decreased general fitness in 7 of 20. Livex treatment had no effect on haemoglobin level, haematocrit value, total serum protein, albumins and beta-lipoproteins.

[Results of the treatment of non-Hodgkin's lymphoma with 6 cytostatic drug combination]. / Wyniki leczenia chloniaka nieziarniczego 6-lekowym zestawem cytostatyków.

In 20 patients with non-Hodgkin lymphoma as the first treatment and in 10 patients with the same diagnosis as the second treatment (group II) has been applied the therapeutical protocol proposed by I. Koza et al., composed of 4 monthly cycles of cyclophosphamide, vincristine, bleomycin, methotrexate and prednisone and in the other 4 cycles of doxorubicin, vincristine bleomycin, prednisone. The diagnosis in the I group was: immunoblastic lymphoma in 13 cases, other high grade lymphomas in 5 and low grade lymphoma in 2 cases. In the group II half of the patients showed low or intermediate grade lymphoma but with maximal clinical advancement and resistance to previous therapy. Complete remission (CR) has been obtained in 12 patients of the I group, partial remission (PR) in 7, 1 patient did not respond to therapy. In 3 cases relapse of the disease has been noted, including 2 patients in whom relapse occurred before finishing therapy: the patients remained resistant to alternative one. In the group II the PR and CR has been obtained in 5 and 3 cases respectively: 2 patients with immunoblastic lymphoma resistant to previous therapy did not respond either. Among undesirable effects myelosuppression, mainly granulocytopenia has been mostly noted: infection and septic shock was a cause of death in 1 patient. In 2 patients severe polyneuropathy and in 2 other mucositis of the digestive tract was noted. The treatment used gives beneficial results as induction therapy in cases of immunoblastic lymphoma and enables obtaining remission in therapy resistant cases of low grade lymphoma.

[Lymph node involvement as a primary localization of extramedullary blast crisis of chronic granulocytic leukemia (PBS)]. / Zajecie wezlów chlonnych jako pierwotna, pozaszpikowa lokalizacja przelomu blastycznego przewleklej bialaczki szpikowej (PBS).

Among 28 patients with blastic crisis of chronic granulocytic leukemia (CGL) its primary symptom in four persons was lymph nodes enlargement. In two of them histopathologic examination confirmed myeloblastic infiltration. Lymph nodes involvement appeared 1-7 months before the onset of blastic transformation in peripheral blood and bone marrow: myeloblastic in two patients, promyelocytic in one and lymphoblastic myeloblastic (bi-phenotypic) in one. Survival time from nodal infiltration was 8-16 months and from the diagnosis of CGL 16-105 months. Remission of the disease after first blastic crisis was achieved in three patients. Cytogenetic examinations disclosed double Ph chromosome in three and single Ph chromosome in one patient.

Haemolytic crises caused by Hoya carnosa in a patient with G6PD deficiency.

Haemolytic crises caused by contact with Hoya carnosa were observed in a 45-years old woman. The investigation of erythrocyte enzymes displayed both G6PD deficiency and its diminished affinity to G-6-P. Some properties of dehydrogenases isolated from erythrocytes of the patient's brother and son were also changed although clinical signs of haemolysis were absent.

[Treatment of acute leukemia in adults with cytosine arabinoside and thioguanine]. / Leczenie ostrej bialaczki doroslych arabinozydem cytozyny i tioguanina.

After treatment of acute leukaemia in adults with cytosine arabinoside and thioguanine complete and partial remission was achieved in 50% of cases. In view of short-lasting remissions achieved maintenance treatment with other cytostatic agents was necessary. The authors called attention to the fact that in the cases with remission the counts of granulocytes and platelets increased early during cytostatic treatment and the number of blast cells fell rapidly. In cases without response to this treatment these early signs of normalization of peripheral blood morphotic elements were not observed.

Tracheo- and bronchoesophageal fistulas in Hodgkin's disease.

Among 330 patients with Hodgkin's disease, in five development of fistula between the respiratory and alimentary tract was observed; tracheoesophageal in three and bronchoesophageal in two patients. Generalization of the disease was the cause of fistula in three patients; it appeared as a result of necrosis of the neoplastic infiltration during cytostatic treatment or radiotherapy. In the fourth patient the fistula was of iatrogenic origin (radiation induced damage), and in the fifth it was the result of secondary neoplasm (bronchial anaplastic cancer).

[Long-term (over 10-years) survival in Hodgkin's disease]. / Dlugotrwale (ponad 10-letnie) przezycie w chorobie Hodgkina.

61 patients with Hodgkin's disease, i.e., 40.9% of all HD pts hospitalized in the years 1970-1981 are more than 10 years survivors: 46 are alive and 15 died of underlying disease or its complications. The most important prognostic factor at diagnosis was clinical advancement and the form A or B of HD. Age and sex also influenced survival but to a lesser degree. Patients living in CCR were more likely to have MC histology than those with relapsing disease, who more often showed LD and LP type. Among 5 persons with second neoplasms four disclosed NS type of HD. No statistical differences in clinical prognostic factors were encountered between further alive and those who died after more than 10-yrs. Almost all patients were able to normally continue their familial and professional lives.

Application of 31P NMR spectroscopy to monitor chemotherapy-associated changes of serum phospholipids in patients with malignant lymphomas.

31P spectra were obtained from 22 healthy volunteers and 35 patients with malignant lymphomas. Sera from patients were collected at the time of diagnosis and at several time-points during therapy. Long-term follow-up studies showed a good correlation between the 31P NMR spectra of sera and the clinically evident response of the disease to the chemotherapy. During therapy leading to remission resonance from phospholipids increased progressively resulting in spectra similar to those seen in normal sera. By contrast, in patients who did not respond to therapy the intensities of the phospholipid peaks remained relatively low or became progressively reduced as the disease progressed. To understand the source of the spectral differences, we also examined the concentrations of high-density lipoprotein, low-density lipoprotein, cholesterol, and triglycerides. In individuals responding to the treatment, both high-density lipoprotein and cholesterol increased to the point where they were statistically equivalent to those from healthy volunteers.

Chemotherapy-associated changes in 31P MRS spectra of sera from patients with multiple myeloma.

31P NMR spectra were obtained from sera of 22 healthy volunteers and 20 patients with multiple myeloma at the time of diagnosis and repeated up to five times during therapy. All spectra consisted of a Pi peak (used as a reference peak) and two peaks from phospholipids (PL): one peak due to phosphatidylethanolamine and sphingomyelin (PE + SM) and a second peak due to phosphatidylcholine (PC). Prior to therapy, peak intensities of the phospholipids were low relative to Pi. During therapy leading to remission, the resonance from PL progressively increased to approximate the spectral pattern seen in normal sera. By contrast, in non-responders an opposite trend was noted: the intensities of the phospholipid peaks became progressively reduced or remained unchanged. Long-term follow-up studies showed a good correlation between this 31P MRS evaluation of sera and the response of the disease to the therapy. In addition to the correlation with tumor response, our studies also show significant correlations between area, intensities of peaks of PE + SM, PC, and the concentrations of high-density lipoprotein (HDL) (correlation coefficients 0.46, 0.43, 0.59, respectively; p < 0.001). We found that the concentration of HDL in serum of patients with multiple myeloma was significantly reduced. In individuals responding to therapy HDL levels increased to the point where there were no statistically significant differences between them and healthy volunteers. In patients not responding to therapy, HDL concentration did not increase.(ABSTRACT TRUNCATED AT 250 WORDS)

[Disorders in the menstrual cycle and fertility of women with Hodgkin's disease]. / Zaburzenia miesiaczkowania i rozrodczosc kobiet chorych na chorobe hodgkina.

Sixty two women with Hodgkin's disease were questioned about disorders in their menstrual cycle and fertility. Menstrual cycle disorders were noted by 38 respondents, i.e. over 60%. Amenorrhoea persisted in 24 of these women. These disorders were significantly more frequent in patient over 30 year of age. There were 52 labours in the group of 38 women with menstrual cycle disorders prior to them, and 21 labours in a group of 24 women without any abnormalities. Hodgkin's disease was diagnosed in 6 patients during pregnancy: 2 of them were treated with irradiations on the upper part of the body while 4 remained untreated. After radiotherapy, there were 2 deliveries in women of the group with menstrual cycle disorders, and 9 deliveries in women without such disturbances. Answers to the supplied questionnaire did not provide any information on the congenital abnormalities in neonates.

[Diagnostic difficulties in Gaucher disease: report of two cases]. / Trudnosci w rozpoznawaniu choroby Gauchera: opis dwóch przypadków.

Diagnostic difficulties of Gaucher disease, a disorder resulted from a deficient activity of glucocerebrosidase is reported. Gaucher disease was described in the 16 year old male, 5 years after manifestation of the very first symptoms (fracture and osteomyelitis). At the age of 14, the cirrhosis due to viral hepatitis accompanied with splenomegaly was diagnosed. This findings was not associated with the earlier osseous disorders. Histopathologic examination of the removed spleen facilitate the diagnosis. The second case refers to 20 year old female. Clinical symptoms and additional test pointed to malignant neoplasm of thyroid, the reproductive organs or cancer of indistinguishable primary focus with metastases in the liver. Trepanobiopsy of bone marrow had made an accurate diagnosis possible, while determination of beta-glucosidase activity in peripheral white blood cells, chitotriosidase activity, and molecular investigations of gene specific to beta-glucocerebrosidase proved it.

[Effect of livex on hypochromic anemia]. / Wplyw livexu na niedokrwistosc z niedoboru zelaza.

Livex is a lyophilised preparation of the bovine blood which contains 70% of proteins and 0.3% of iron. Livex was given to 25 patients with iron deficiency anemia (group I), and 25 patients with lymphoreticular malignancies accompanied by iron deficiency with or without anemia. The dose was 5 g t.i.d. for 3 months. The majority of patients of group I were women. Excessive menstrual bleeding and chronic gastritis were most common causes of iron deficiency in this group. Livex statistically significantly increased hemoglobin, hematocrit, corrected reticulocyte count, mean erythrocyte hemoglobin, serum iron, percent transferrin saturation, and leukocyte count. Therapy produced significant increase in serum iron, total iron binding capacity, and percent transferrin saturation in patients with lymphoreticular malignancies.