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U Germing

Publications and source records attributed to U Germing.

70 records · Page 4Linked to original sources
PubMed1998

Dyshematopoiesis in de novo acute myeloid leukemia: cell biological features and prognostic significance.

Dyshematopoiesis was found in 44 (42.3%) of 104 cases of de novo acute myeloid leukemia (AML). Dyshematopoietic AML (dys-AML) and AML without hematopoietic dysplasia (non-dys-AML) were compared with regard to biological, hematological, immunophenotypic, and cytogenetic parameters as well as prognostic criteria. Median age of patients was 55 years in both groups. In dys-AML, the median leukocyte count (p = 0.04), peripheral blast (p = 0.02) and medullary blast cell count (p < 0.001) were significantly decreased, whereas the median platelet count (p - 0.04) was increased. Immunophenotyping demonstrated that leukemic blast cells in dys-AML more frequently expressed the adhesion molcules CD54 (p = 0.05) and CD58 (p = 0.08) than leukemic cells in non-dys-AML. Cytogenetically, we distinguished two karyotypic patterns, one group with a normal karyotype or prognostically favorable single chromosome aberrations ("P(0)-karyotype"), and another one with unfavorable single aberrations or complex aberrations ("P(1)-karyotype"). The incidence of these groups was not significantly different between dys-AML and non-dys-AML. Complete remission rate (CRR) after induction chemotherapy (p = 0.03) and overall survival time (OS; p = 0.03) were significantly lower in dys-AML. In addition, median disease free survival (DFS; p = n.s.) was inferior compared to non-dys-AML. In the dys-AML as well as in the non-dys-AML patient group, CRR, DFS, and OS were decreased in the P(1)-compared to the P(0)-subgroup. We conclude that dyshematopoietic AML is characterized by specific cell biological features and that hematopoietic and cytogenetic status represent complementary prognostic factors in de novo AML.

Acute Disease↗
PubMed1997

Fatal hyperleukocytic syndrome in a patient with chronic myelomonocytic leukemia.

A 53-year-old male patient was admitted to our hospital with painful splenomegaly. He was diagnosed as having chronic myelomonocytic leukemia (CMML) with leukocytosis, monocytosis, increased lysozyme concentrations in serum und urine, and lack of the Philadelphia chromosome. The clinical course of the disease was characterized by rapidly rising leukocyte counts, cutaneous infiltrates, respiratory insufficiency and neurological symptoms. Excessive hyperleukocytosis with a significant increase in monocytic cells led to microcirculatory obstruction, vascular endothelial damage and organ malfunction. This complication could not be prevented by low-dose chemotherapy with cytosine arabinoside. The patient finally died from pulmonary and cerebral hyperleukocytic syndrome.

Fatal Outcome↗
PubMed1996

[The prognostic significance of serum thymidine kinase in the myelodysplastic syndrome].

OBJECTIVE: To assess the prognostic value of serum thymidine kinase (sTK) activity in patients with the myelodysplastic syndrome (MDS). PATIENTS AND METHODS: The study included 255 patients (144 men, 111 women, median age 67 [14-97] years) in whom primary MDS had been diagnosed between 1986 and 1995 (refractory anaemia [RA]: n = 40; RA with ring sideroblasts: n = 38; RA with increased blasts: n = 76; RA with increased blasts in transformation: n = 45; chronic myelomonocytic leukaemia: n = 56). 69 healthy persons (28 men, 41 women, median age 33 [24-62] years) served as controls. The normal laboratory range for sTK was between 0.9 and 4.9 U/microliter. RESULTS: At time of diagnosis 83% of patients had sTK levels higher than 5 U/microliter. There was no relationship between sTK levels and the proportion of medullary blasts. But serum sTK levels correlated with LDH activity (P < 0.0005) and with peripheral leukocyte count (P = 0.003). At all times patients with sTK levels < 10 U/microliter had a higher survival rate than those > or = 10 U/microliter. Cumulative survival rates in both groups was 69 +/- 10% (< 10 U/microliter) and 43 +/- 11% (> or = 10 U/microliter), respectively, after 2 years and 37 +/- 9% (< 10 U/microliter) and 20 +/- 7% (> or = 10 U/microliter) after 5 years (P = 0.0002). Multivariate analysis showed that sTK, haemoglobin concentration and proportion of medullary blasts were independent prognostic survival factors. CONCLUSIONS: Most patients with MDS have an increased sTK level when the diagnosis is made. This reflects the impaired proliferation and differentiation of haematopoiesis. sTK is a simply and rapidly measured prognostic indicator for estimating survival probability of patients with MDS.

Adolescent↗
PubMed1994

Serum deoxythymidine kinase in myelodysplastic syndromes.

BACKGROUND: Previous studies have shown that serum levels of deoxythymidine kinase (sTK) provide useful prognostic information in various malignancies, such as Hodgkin's disease, non-Hodgkin's lymphomas, multiple myeloma, and acute myeloid leukemia (AML). METHODS: Using a radioenzyme assay, the authors determined sTK in 146 patients with primary myelodysplastic syndromes (MDS). Morphologic subtypes were refractory anemia (RA) in 18 patients, RA with ring sideroblasts (RARS) in 24, RA with excess of blasts (RAEB) in 41, RAEB in transformation (RAEB/T) in 29, and chronic myelomonocytic leukemia (CMML) in 34. RESULTS: Enzyme levels ranged from 1.1 to 829 U/microliters. One hundred fifteen (79%) patients had elevated sTK levels (more than 5 U/microliters) at the time of diagnosis. In advanced stages of MDS (RAEB, CMML, and RAEB/T) enzyme activities were higher than in early stages (RA and RARS) (P < 0.05). However, sTK levels were not correlated with the percentage of medullary blast cells. Among other parameters tested, the best correlation with sTK was found for serum lactate dehydrogenase (LDH) activity (r = 0.29; P < 0.0005). As shown by life table analysis, sTK activity at diagnosis provided useful information regarding the prognosis of patients. For patients with sTK levels of less than 10 U/microliters, actuarial survival after 2 years was 65%, compared with 33% for those with enzyme values of 10 U/microliters or greater. The 5-year cumulative survival rates were 34% and 14%, respectively (P < 0.0005). However, sTK levels at diagnosis were not useful for predicting transformation to AML. Nine of 61 (15%) patients with sTK of less than 10 U/microliters had AML develop, whereas 15 of 57 (26%) patients with sTK of 10 U/microliters or greater had disease progress to acute leukemia (chi-square, 1.64; P = 0.2). CONCLUSIONS: Considering the lack of correlation with bone marrow blasts, the authors conclude that increased sTK levels in MDS are primarily attributable to intramedullary destruction of hematopoietic precursors and do not reflect the leukemic blast cell burden. This appears similar to the ineffective hematopoiesis of vitamin B12 deficiency, which is associated with elevated levels of sTK and LDH. The data suggest that sTK is a prognostic parameter that can be used to predict the survival of patients with MDS. However, multivariate analysis shows that the predictive value of sTK is not superior to that of LDH.

Adolescent↗
PubMed1994

Risk assessment in primary myelodysplastic syndromes: validation of the Düsseldorf score.

We have recently proposed a scoring system for risk assessment in primary myelodysplastic syndromes (MDS). In this score, one point is allocated to each of the following four parameters: bone marrow blasts > or = 5%, LDH > 200 U/l, hemoglobulin concentration < or = 9 g/dl, and platelet count < or = 100 x 10(9)/l. In a published series of 235 untreated patients with primary MDS, three prognostic groups (group A, score 0; group B, score 1 or 2; group C, score 3 or 4) were identified which differed significantly in both survival and rates of leukemic transformation. The present study was undertaken to reexamine the usefulness of our scoring system by applying it to an independent population of 263 newly diagnosed MDS patients. Morphological subtypes were RA in 53 (20%), RARS in 32 (12%), pure sideroblastic anemia (PSA) in 41 (16%), RAEB in 60 (23%), RAEB/T in 34 (13%), and CMML in 43 cases (16%). The predictive value of the Düsseldorf score could be assessed in 244 of 263 patients (initial LDH levels or platelet counts lacking in 19 cases). Forty-two patients were assigned to group A (low risk), 132 to group B (intermediate risk), and 70 to group C (high risk). Two-year cumulative survival was 86% in group A, 57% in group B and 14% in group C. Five-year cumulative survival was 53, 26 and 0%, respectively (p < 0.00005). Cumulative risk of AML 2 years after diagnosis was 3% in group A, 12% in group B, and 41% in group C (p < 0.05). Additional validation of the score was provided by extended follow-up of the initial patient population on which the scoring system was based. Survival curves in this patient population developed as predicted by the score. An important advantage of the Düsseldorf score is its ability to identify high-risk patients among the RA and RARS subgroups, even though by definition medullary blasts are less than 5%. The inclusion of LDH levels as a prognostic parameter also qualifies the Düsseldorf score for a correct assessment of CMML patients. In the new study population, LDH was confirmed as an important prognostic factor. After 2 years, actuarial survival for patients with LDH levels < or = 200 U/l was 61%, compared with 34% for patients with LDH > 200 U/l. Five-year cumulative survival was 32 and 14%, respectively (p < 0.00005).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

[Myelodysplastic syndromes. The epidemiological and etiological aspects].

From a total of 18,416 bone-marrow biopsy reports entered into the Düsseldorf Bone Marrow Registry between 1975 and 1990 those of patients diagnosed as having preleukaemia, myeloid dysplasia, panmyelopathy with hypercellular bone marrow, refractory anaemia, sideroblastic anaemia or smoldering leukaemia were reanalyzed together with patient-data. If the diagnosis of myelodysplastic syndrome (MDS) was confirmed, the original blood and bone-marrow smear was re-examined and classified, 584 cases in all (3.2%). During the same period acute myeloid leukaemia had been diagnosed in 506 patients (2.8%). The average annual incidence of MDS in the Düsseldorf area was 3.65 per 100,000 inhabitants. Over 80% of cases occurred from the age of 60 years, while 7% were younger than 50 years. The sex ratio was the same in all subgroups of MDS, except chronic myelomonocytic leukaemia (male:female ratio 1:1.57). 31 patients (5.3%) had received ionizing radiation and/or cytostatic or immunosuppressive treatment for various underlying diseases before MDS had been diagnosed (secondary MDS). Preceding occupational contact with organic solvents could not be excluded with certainty in 12 patients. These data suggest that MDS is a relatively frequent disease of hematopoiesis among the older age groups. The proportion of secondary (treatment-induced) forms is small and does not explain the recently observed increased incidence.

Age Factors↗
PubMed1992

[Secondary hemochromatosis in polytransfused patients with myelodysplastic syndromes].

In a retrospective analysis we assessed the data of 46 patients with myelodysplastic syndromes (MDS), who had received more than 50 blood transfusions during the course of disease. The number of units given ranged from 50 to 155 (mean 79). 20 patients (RA n = 4, RARS n = 12, RAEB n = 1, RAEB/T n = 2, CMML n = 1), followed up between 8 and 108 months (mean survival time 39.4 months), developed a secondary hemochromatosis. More than 40% of the patients showed signs of heart failure, in some cases accompanied by cardiac arrhythmias. 11 patients also suffered from hepatopathy and 5 developed diabetes mellitus. Secondary hemochromatosis was particularly common in patients with RARS. Refractory congestive heart failure secondary to hemochromatosis was the cause of death in 14 patients, whereas none died from hepatic insufficiency. We conclude that the risk of secondary hemochromatosis should not be neglected in polytransfused patients with MDS. In some cases, particularly those with favorable prognostic features of MDS, it may shorten life expectancy. The availability of a new oral iron chelator (1,2-dimethyl-3-hydroxypyrid-4-one or L1) offers a promising and practicable approach to prevent this complication.

Adult↗
PubMed1992

Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system.

In an attempt to identify prognostic factors for survival and leukemic transformation, 235 untreated patients with primary myelodysplastic syndromes (MDS) were analyzed in a single center retrospective study. To the well known FAB classification of MDS a supplementary group of patients with pure sideroblastic anemia (PSA) was added, characterized by the absence of dysplastic features of non-erythroid cells. Accordingly, the morphological subtypes were refractory anemia (RA), n = 55; PSA, n = 40; RA with ring sideroblasts (RARS), n = 33; RA with excess of blasts (RAEB), n = 53; RAEB in transformation (RAEB/T) n = 29; and chronic myelomonocytic leukemia (CMML), n = 25. Having screened 28 clinical, cytological, and laboratory parameters by univariate analysis, multiple regression analysis identified six variables with independent prognostic value: percentage of bone marrow blasts, serum LDH activity, PSA, hemoglobin concentration, age, and platelet count. If patients with PSA were excluded, the FAB classification no longer contributed independent prognostic information. Based on the results of this multivariate analysis, a simple scoring system was devised for predicting the survival of patients with MDS. A score of unity was allocated to each of the following parameters: bone marrow blasts greater than or equal to 5%, LDH greater than 200 U/I, hemoglobin less than or equal to 9 g/dl, and platelets less than or equal to 100 x 10(9)/I. As a function of their total score, patients were divided into three risk groups (group A, score 0; group B, score 1-2; group C, score 3-4), which differed significantly in both survival and rates of leukemic transformation. The cumulative survival 2 years after diagnosis was 91% in group A, 52% in group B, and 9% in group C (p less than 0.00005). The actuarial risk of transformation to acute myeloid leukemia at 2 years was 0, 19, and 54%, respectively (p less than 0.05). The inclusion of LDH enzyme levels qualified this scoring system for an accurate assessment of patients with CMML whose prognosis is viewed too favorably when rated by other scores. Furthermore, this score was able to identify those patients with RA and RARS who, without showing an excess of marrow blasts, have an unfavorable prognosis.

Adolescent↗
PubMedDate not supplied

Early occurrence of an adenocarcinoma after allogeneic bone marrow transplantation in a patient with AML.

Several reports have showed an increased risk of secondary malignancies after bone marrow transplantation (BMT), especially after total body irradiation (TBI). We report on a 39-year-old female who underwent BMT with a matched unrelated donor because of acute myeloid leukemia in second complete remission. Previously, the patient received chemotherapy for induction, consolidation, maintenance and reinduction after diagnosis of relapse. Conditioning regimen consisted of cyclophosphamide and TBI. MTX and CSA was administered for GvHD prophylaxis. Engraftment was confirmed on day 28. Within 6 months following BMT, no complication occurred. Continuous complete remission was demonstrated by repeated bone marrow smears. On day 300 the patient complained of chest pain and dyspnea. X-ray and CT-scan showed thickening of the pleura and pleural effusion. A pleuracarcinosis was diagnosed by cytologic examination of a pleural aspirate. By an open thoracotomy a disseminated inoperable disease became apparent. Diagnosis of an adenocarcinoma was confirmed by histologic examination. The patient died 2 months later due to disseminated tumour in complete remission of AML. Solid tumours are rare as secondary malignancies after BMT. Usually the neoplasmas are late events occurring more than 10 years after BMT. In this case predisposing factors such as genetic disposition, long-term smoking, intensive pretransplant chemotherapy, TBI and immunosuppression may have lead to the early secondary malignancy.

Adenocarcinoma↗
PubMedDate not supplied

Massive extramedullary disease progression in a patient with stable multiple myeloma during G-CSF priming for peripheral blood progenitor mobilization.

High dose therapy followed by autologous peripheral blood progenitor cell (PBPC) transplantation has recently become an encouraging treatment option for younger patients with multiple myeloma (MM). The influence of the growth factors used for progenitor mobilization on myeloma cells is not known. We report on a patient suffering from IgG kappa myeloma who had been in stable, very good partial remission for seven months after standard therapy until PBPC mobilization with granulocyte-colony stimulating factor (G-CSF, Filgrastim) was initiated. Massive extramedullary disease progression occured coincidentally with the administration of G-CSF. The case suggest the possibility of myeloma stimulation by G-CSF during PBPC mobilization.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Transdermal fentanyl during high-dose chemotherapy and autologous stem cell support.

We report on our experience in the use of transdermal fentanyl in management of acute pain due to mucositis WHO-grade IV during high-dose chemotherapy (HDC) and autologous stem cell support (APBSCT). Between 8/96 and 12/98 74 patients received HDC and PBSCT for progressive disease or relapse of non-Hodgkin's lymphoma (n=32), multiple myeloma (n=37), Hodgkin's lymphoma (n=5). All patients suffered from mucositis WHO-grade IV with a need for continuous pain management. Instead of pethidine i.v. fentanyl TTS was used. Sufficient analgesia was achieved mostly with a dose of 50 microg/h. There was no need of supplementary analgesia. Relevant fentanyl-associated side effects were not seen. Patient compliance and acceptance were excellent. The results suggest that transdermal fentanyl is reliable in pain management of chemotherapy-associated mucositis grade IV.

Administration, Cutaneous↗