PubMed Health⌕ Search

Biomedical subjects

H Löffler

Publications and source records attributed to H Löffler.

At least 91 records · Page 5Linked to original sources
PubMed1996

Secondary acute leukaemias with 11q23 rearrangement: clinical, cytogenetic, FISH and FICTION studies.

Three patients with secondary acute leukaemia after treatment with topoisomerase II inhibitor agents are described. Two patients had acute myeloid leukaemia (AML). FAB M5a, one had pro-B-acute lymphoblastic leukaemia (ALL). The interval between initiation of chemotherapy and the onset of secondary acute leukaemia was 19-20 months. 11q23 rearrangements were detected in all cases. They were due to translocations t(11;19) (q23;p13.3), t(11;16)(q23;p13) and t(4;11)(q21;q23), respectively. Fluorescence in situ hybridization (FISH) with Yeast Artificial Chromosome (YAC) probe 13HH4 spanning the ALL-1 gene on 11q23 confirmed that in each case the ALL-1 gene had been disrupted by the translocations. The study underlined the relationship between the development of secondary acute leukaemias with 11q23 rearrangement and previous chemotherapy with topisomerase II inhibitor agents. So far, however, only six adult patients with secondary ALL with t(4;11) after treatment with topoisomerase II inhibitor agents have been reported. All with t(4;11) mostly occurs in infants or young children. Our patient received epirubicin continuously for >19 months. This indicates that both myeloid and lymphoid leukaemias with involvement of the ALL-1 gene can be induced by exogenous agents, especially topoisomerase II inhibitors. Thus they may have a common biological background. This hypothesis was substantiated by means of combined immunophenotyping and FISH (FICTION). In the case of AML M5a with t(11;19), the tumour cells with ALL-1 rearrangement expressed CD34. Moreover, the pro-B-ALL with t(4;11) was CD34 positive. These findings suggest that the cell of origin of secondary AML and ALL with 11q23 rearrangement is an immature haemopoietic progenitor cell.

Acute Disease↗
PubMed1996

Glass slide smears are a suitable source for RT-PCR-based analysis of chromosomal aberrations in leukaemias.

The polymerase chain reaction (PCR) is a well-established method to detect cytogenetic abnormalities. The handling of fresh specimens is difficult, therefore a method to use smears of blood or bone marrow as a source would be advantageous. Furthermore, such a technique would give the opportunity to investigate retrospectively bone marrow smears in leukaemias without cytogenetic results. The aim of the present study was to investigate the influence of staining procedures and laboratory handling of smears. We chose CML cases as a model. We demonstrated that smears are a suitable source for PCR without loss of information caused by previous routine laboratory handling.

Base Sequence↗
PubMed1996

Incidence and implication of additional chromosome aberrations in acute promyelocytic leukaemia with translocation t(15;17)(q22;q21): a report on 50 patients.

Acute promyelocytic leukaemia (APL) is characterized by the translocation t(15;17)(q22;q21). Usually t(15;17) is the sole cytogenetic abnormality, but some patients show other chromosome aberrations in addition to t(15;17). The influence of additional chromosome aberrations on the clinical outcome of patients with t(15;17) is unclear. We have analysed 50 cases of APL carrying the translocation t(15;17). Additional chromosome aberrations were observed in 17/47 patients (36%) studied at initial diagnosis and in all three patients studied at relapse. In nine cases (18%) an additional chromosome 8 and in six cases (12%) an isochromosome of the long arm of the derivative chromosome 17 was observed. Various structural rearrangements in addition to t(15;17) were detected in nine patients (18%). Clinical follow-up data were available for 44 patients studied at diagnosis. A complete remission (CR) was achieved in 34 patients (77%). 10 patients (23%) died within 1 month after diagnosis due to infection or bleeding, eight (24%) relapsed within 10-18 months after initial diagnosis. 28 patients are alive 2-93 months after diagnosis (25 in first CR, two in second and one in third CR) (median follow-up 18.5 months). Bone marrow transplantation was performed in six patients (three in first CR, two in second CR, one in third CR), all are alive and in CR. An influence of secondary chromosome anomalies on prognosis was not observed. However, if a higher rate of long-term remission can be reached, specific secondary chromosome aberrations might turn out to be of prognostic value.

Adolescent↗
PubMed1996

Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia.

The clinical and biological significance of additional chromosome aberrations was investigated in a large series of 66 adult patients with Philadelphia (Ph) chromosome positive acute lymphoblastic leukaemia (ALL). Additional chromosome changes were observed in 71% of the cases. 9p abnormalities were identified in 26%, and monosomy 7 as well as hyperdiploid karyotypes 50 were both found in 17% of cases. 9p anomalies were characterized by a low complete remission (CR) rate (58%) and an extremely short median remission duration (MRD: 100 d). In patients with monosomy 7, the poor treatment outcome was confirmed (CR rate 55%: MRD 113 d). In contrast, all patients with hyperdiploid karyotypes 50 achieved CR, and the overall survival was superior to all other Ph-positive ALL patients except those without additional chromosome aberrations. Exclusive rearrangement of the minor breakpoint cluster region of the BCR gene and lack of coexpression of myeloid-associated antigens in cases with 9p anomalies as well as a high frequency of rearrangements of the major breakpoint cluster region of the BCR gene in patients with monosomy 7 (89%) further substantiated that additional chromosome aberrations may characterize distinct subgroups of Ph-positive ALL. Moreover, the necessity of the complementing use of chromosome banding analyses, polymerase chain reaction (PCR) assays, and fluorescence in situ hybridizations in the accurate identification of Ph-positive patients has become evident due to variant Ph translocations in 3%, and negative PCR assays in 4% of the cases.

Adolescent↗
PubMed1996

Acute myeloid leukemia with translocation (8;21). Cytomorphology, dysplasia and prognostic factors in 41 cases. AML Cooperative Group and ECOG.

The translocation t(8;21) is one of the most common structural aberrations in acute myeloid leukemia (AML). Excellent response rates and a better relapse-free survival have been described. We analyzed specific morphologic and cytochemical features including dysplasia and other prognostic factors in 41 patients with AML and t(8;21) who underwent aggressive chemotherapy in two national cooperative group studies. Five patients were classified as AML M1 and 36 as AML M2 according to the FAB criteria. Auer rods were detected in 28 patients (68%), however in only 16 patients were they "thin and elongated" as has been described as typical for t(8;21). The presence or absence of Auer rods did not appear to be associated with disease-free survival in this sample. Dysgranulopoiesis was detected in 31/41 patients (90%); five of these patients additionally had dyserythropoiesis (12%). In six cases (15%), dysmegakaryopoiesis was seen in combination with dysgranulopoiesis. Only one patient had trilineage dysplasia. Dysplastic features had no influence on prognosis. Additional cytogenetic abnormalities were detected in 24/41 patients. Twelve male (48%) and four female (25%) had a loss of a sex chromosome. This was correlated with a better disease-free survival (p = 0.039). The complete remission rate (CR) to chemotherapy was 90%. The early death rate was 10%. Disease-free survival of the complete responders was 60% at two years with no relapses observed in ten patients with 2-6 years of follow up. This favorable disease-free survival was observed with a variety of post-induction regimens and t(8;21) had been detected as an independent factor for good prognosis. The need for very intensive therapy, such as bone marrow transplantation, is unanswered at this time.

Adult↗
PubMed1996

Fifty-one patients with acute myeloid leukemia and translocation t(8;21)(q22;q22): an additional deletion in 9q is an adverse prognostic factor.

The translocation t(8;21)(q22;q22) occurs in 6 to 12 percent of patients with AML, and usually predicts a good response to chemotherapy with a high remission rate and a relatively long median survival. The influence of additional chromosome aberrations on the clinical outcome of patients with t(8;21) is unclear. We analyzed 51 cases of acute myeloid leukemia carrying a translocation t(8;21)(q22;q22); 23 female and 28 male patients. The complete remission rate was 92 percent and median overall survival was 52.4 months. The median overall survival of female patients was significantly worse than of male patients (37.2 months vs not reached, P = 0.025). Additional chromosome aberrations were detected in 41 patients at diagnosis (80 percent), 31 (61 percent) had lost a sex chromosome, seven (14 percent) showed a partial deletion of the long arm of chromosome 9 and in three patients (6 percent) a gain of chromosome 8 was observed. Whereas the loss of a sex chromosome had no influence on prognosis, a partial deletion of the long arm of chromosome 9 was an unfavorable prognostic factor. The median overall survival of the seven patients with del(9q) was only 12.5 months and thus significantly shorter than in patients with only t(8;21) or with t(8;21) and additional sex chromosome loss (median survival not reached: P = 0.0010).

Acute Disease↗
PubMed1996

The underlying cellular mechanism of fibrosis.

Fibrosis is a common sequela of various exogenous insults to a variety of parenchymal tissues. The underlying mechanisms of the induction and progression of fibrosis both at the molecular and cellular level have not been clarified so far. In the present study the cellular processes that ultimately may lead to interstitial fibrosis are described using the model of radiation-induced terminal differentiation in the fibroblast/fibrocyte cell system. The data reported herein will provide evidence that exogenously induced changes in the proliferation and differentiation pattern of the fibroblast/fibrocyte cell system based on either autocrine and/or paracrine mediators represent the underlying cellular mechanism of fibrosis. Using co-culture systems of parenchymal cells (fibroblasts and type II pneumocytes), the intercellular communication via cytokines, which may lead to fibrosis have been studied. TGF beta 1 could be described as one key modulator of these cellular processes.

Animals↗
PubMed1996

Randomized study of the combination of hydroxyurea and interferon alpha versus hydroxyurea monotherapy during the chronic phase of chronic myelogenous leukemia (CML Study II). The German CML Study Group.

It is the long-term goal of the German CML Study Group and of the Süddeutsche Hämoblastosegruppe (SHG) to improve survival of patients with chronic myelogenous leukemia (CML). In a first randomized study (CML Study I) monotherapies with hydroxyurea or interferon alpha (IFN-alpha) were compared with a standard busulfan regimen with regard to duration of the chronic phase and survival. The main results of this study were published, 1-3 and a long-term follow up is planned. In a second randomized study the effect of the combination of IFN-alpha and hydroxyurea versus hydroxyurea monotherapy on survival is being investigated. This paper provides a first preliminary report on the study concept, patient recruitment, state of documentation and initial patients' characteristics 9 months after closure of the study.

Adult↗
PubMed1996

High dose intravenous immunoglobulins in systemic lupus erythematosus: clinical and serological results of a pilot study.

OBJECTIVE: To investigate the effect of high dose intravenous immunoglobulins (IVIG) in systemic lupus erythematosus (SLE). METHODS: Twelve patients with mildly to moderately active disease were given 30 g of sulfonated IVIG preparation on each of Days 1-4 and 21-24. RESULTS: Within 6 weeks the mean disease activity score, the Systemic Lupus Activity Measure (SLAM), declined from 7.33 (range 3-15) to 5.25 (range 0-10) (p < 0.01). In 9/12 patients the SLAM dropped by at least 2 points. In 3/12 patients the improvement lasted 5 to 12 months. Within 1 week after initiation of therapy most patients showed a decline in ds-DNA antibodies, whereas titers of antinuclear antibodies and complement proteins were not affected. The treatment was well tolerated, with the exception of transient hypotension in one patient. CONCLUSION: In this uncontrolled study, IVIG had temporary beneficial effects in mildly to moderately active SLE.

Adolescent↗
PubMed1995

Autologous progenitor cell transplantation: prior exposure to stem cell-toxic drugs determines yield and engraftment of peripheral blood progenitor cell but not of bone marrow grafts.

Agents with stem cell-toxic potential are frequently used for salvage therapy of Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (NHL). Because many patients with relapsed or refractory lymphoma are candidates for autologous progenitor cell transplantation, possible toxic effects of salvage chemotherapy on progenitor cells must be taken into account. In a retrospective study, we have analyzed the influence of a salvage regimen containing the stem cell-toxic drugs BCNU and melphalan (Dexa-BEAM) on subsequently harvested bone marrow (BM)- and peripheral blood-derived progenitor cell grafts (PBPC) and compared it with other factors. Progenitor cells were collected from 96 patients with HD or high-grade NHL. Seventy-nine grafts were reinfused (35 PBPC and 44 BM) after high-dose chemotherapy. Compared with patients autografted with BM, hematopoietic recovery was significantly accelerated in recipients of PBPC. For PBPC, the number of Dexa-BEAM cycles ( > or = v > 1) was the predominate prognostic factor affecting colony-forming unit-granulocyte-macrophage (CFU-GM) yield (66 v 6.8 x 10(4)/kg, P = .0001), CD34+ cell yield (6.6 v 1.6 x 10(6)/kg, P = .0001), neutrophil recovery to > 0.5 x 10(9)/L (9 v. 11 days, P = .0086), platelet recovery to > 20 x 10(9)/L (10 v 15.5 days, P = .0002), and platelet count on day +100 after transplantation (190 v 107 x 10(9)/L, P = .031) using univariate analysis. Previous radiotherapy was associated with significantly lower CFU-GM and CD34+ cell yields but had no influence on engraftment. Patient age, patient sex, disease activity, or chemotherapy other than Dexa-BEAM did not have any prognostic impact. Multivariate analysis confirmed that Dexa-BEAM chemotherapy was the overriding factor adversely influencing CFU-GM yield (P < .0001), CD34+ cell yield (P < .0001), and platelet engraftment (P < .0001). BM grafts were not significantly affected by previous Dexa-BEAM chemotherapy or any other variable tested. However, prognostic factors favoring the use of BM instead of PBPC were not identified using joint regression models involving interaction terms between the graft type (PBPC or BM) and the explanatory variables investigated. We conclude that, in contrast to previous radiotherapy or other chemotherapy, exposure to salvage regimens containing stem cell-toxic drugs, such as BCNU and melphalan, is a critical factor adversely affecting yields and performance of PBPC grafts. Marrow progenitor cells appear to be less sensitive to stem cell-toxic chemotherapy. PBPC should be harvested before repeated courses of salvage chemotherapy involving stem cell-toxic drugs to preserve the favorable repopulation kinetics of PBPC in comparison with BM.

Adolescent↗
PubMed1995

Clinical significance of surface antigen expression in children with acute myeloid leukemia: results of study AML-BFM-87.

Immunophenotyping using a panel of 15 antibodies was performed in 267 (87%) and cytogenetic analysis in 196 (64%) of 307 children under 17 years of age enrolled in the AML-BFM-87 study. Treatment consisted of cytosine arabinoside, daunorubicin, etoposide induction and a 6-week seven-drug consolidation chemotherapy, followed by two blocks of high-dose cytosine arabinoside with or without cranial irradiation and maintenance therapy for 1 year. Five-year event-free survival for patients with immunophenotypic data was .43 +/- .03 SE. The diagnostic value of the pan-myeloid reagents CD13, CD33, and CDw65 for the recognition of childhood acute myeloid leukemia (AML) was high with a sensitivity of 98% (positivity of at least one of these antigens), whereas, with the exception of CD41 for French American British (FAB) subtype M7, the expression of single cell-surface antigens showed no correlation with morphologic or cytogenetic subgroups. On the other hand, characteristic subgroups of AML defined by morphologic features and karyotypes could be described by low or high rates of surface antigen expression compared with those of other patients. These immunophenotypic features most probably associated with specific entities include expression of CD34 or CD13 and absence of CD14 or CD4 in M2 with Auer rods/t(8;21); absence of HLA-DR, CD34, and CD14, but expression of CD33 in M3/t(15;17); positivity of either CD34 or CD13 and either CD14 or CD2 for M4Eo/inv(16); and absence of either CD34 or CD13 and expression of either CD33 or CDw65 and either CD15 or CD4 for M5/t(9;11). In FAB M0, negativity of one or two of the three panmyeloid-associated markers (CD13/33/w65) was common; and cytogenetic results frequently showed random abnormalities. Expression of lymphoid-, progenitor- and most myeloid-associated antigens had no influence on the prognosis, whereas the outcome was significantly better for children with M2 with Auer rods, M3, or M4Eo or for those with the associated karyotypes t(8;21);t(15;17) and inv(16) than for other patients.

Acute Disease↗
PubMed1995

Long-term follow-up of adults with acute lymphoblastic leukemia in first remission treated with chemotherapy or bone marrow transplantation. The Acute Lymphoblastic Leukemia Working Committee.

OBJECTIVE: To determine whether the conclusions of a 1991 study, which showed that adults with acute lymphoblastic leukemia in first remission had similar leukemia-free survival rates when treated with chemotherapy or HLA-identical sibling bone marrow transplantation, remain valid after more than 4 years of additional follow-up. DESIGN: Retrospective comparison of two cohorts of patients using left-truncated Cox regression to adjust for differences in baseline characteristics and time to treatment. SETTING AND PATIENTS: Chemotherapy recipients were 484 consecutive patients with acute lymphoblastic leukemia in first remission treated in 44 hospitals in Germany that were participating in two consecutive trials of the German Acute Lymphoblastic Leukemia Therapy Trials Group. Transplant recipients were 234 consecutive recipients of HLA-identical sibling bone marrow transplants for acute lymphoblastic leukemia in first remission in 98 centers, worldwide, reporting data to the International Bone Marrow Transplant Registry. INTERVENTIONS: Intensive combination chemotherapy or HLA-identical sibling bone marrow transplantation preceded by high-dose chemotherapy with or without total body irradiation. MEASUREMENTS: Relapse, treatment-related mortality, and leukemia-free survival rate 9 years after first complete remission. RESULTS: The conclusions of our previous analyses were confirmed. Actuarial relapse probabilities at 9 years were 66% (95% CI, 61% to 70%) for chemotherapy and 30% (CI, 22% to 37%) for transplantation (P < 0.0001). The leukemia-free survival rates at 9 years were 32% (CI, 27% to 37%) for chemotherapy and 34% (CI, 28% to 40%) for transplantation (P > 0.02). CONCLUSIONS: Fewer relapses but more treatment-related deaths were seen with transplantation than with chemotherapy. Thus, leukemia-free survival rates were similar in adults receiving transplantation and adults receiving chemotherapy for acute lymphoblastic leukemia in first remission.

Antineoplastic Agents↗
PubMed1995

Primary transplantation of allogeneic peripheral blood progenitor cells mobilized by filgrastim (granulocyte colony-stimulating factor)

Transplantation of allogeneic peripheral blood progenitor cells (PBPCs) may have advantages over bone marrow transplantation (BMT) with regards to the speed of hematopoietic and immunologic recovery, which may then shorten the time spent in hospital and decrease costs. The recipient might also profit by an enhanced graft-versus-leukemia reaction exerted by the high number of natural killer cells contained in such grafts. The donor could be spared the discomfort and risks of general anesthesia and marrow harvesting. Primary transplantation of unmanipulated allogeneic PBPCs has not been reported so far because the vast amount of T cells contained in the collection product was thought to cause severe graft-versus-host disease. We present preliminary data on primary transplantation of allogeneic PBPCs in patients who either suffered from advanced leukemia or had a donor unable to undergo general anesthesia. Eight patients with a median age of 42 years suffering from acute myelogenous leukemia (AML) in first remission (n = 3), AML in third remission, AML in relapse (n = 2), acute lymphoblastic leukemia in second remission, or chronic myelogenous leukemia in accelerated phase received myeloablative therapy followed by transplantation of unmanipulated allogeneic PBPCs mobilized with granulocyte colony-stimulating factor (5 to 10 micrograms/kg of body weight of filgrastim administered for 5 to 6 days) in their HLA-identical donors. Hematopoietic reconstitution was achieved in all patients with a median of 15.5 (16.5) days after transplant needed to surpass an absolute neutrophil count of 0.5 (1.0) x 10(9)/L. The median time to an unsupported platelet count greater than 20 (> 50) x 10(9)/L was 19.5 (41) days after grafting. Three patients did not exhibit signs of acute graft-versus-host disease (GVHD), grade I disease was seen in one patient, and three patients experienced grade II disease limited to the skin. The only patient with severe acute GVHD (grade III) refused to take his oral cyclosporin regularly and had ineffective serum levels for most of the time until relapse. Six of eight patients are currently alive without evidence of disease between 61 and 533 days after grafting; two patients grafted for AML in relapse achieved a complete remission after transplantation but relapsed again and died of leukemia on days +48 and +70, respectively. Primary transplantation of unmanipulated allogeneic PBPCs is feasible and results in long-term engraftment without causing detrimental GVHD.

Adolescent↗
PubMed1995

Bowman-Birk proteinase inhibitor (BBI) modulates radiosensitivity and radiation-induced differentiation of human fibroblasts in culture.

The radiosensitivity and differentiation pattern of cultured normal human fibroblasts was analysed as a function of treatment of the cells with the Bowman-Birk proteinase inhibitor (BBI). Upon irradiation with doses from 0 to 8 Gy normal human fibroblasts are induced to a premature terminal differentiation within 14-21 days of postirradiation incubation. Treatment of the cells with 10 microM BBI for 2 h prior to the irradiation procedure resulted in a significant shift of the radiation survival curve, increased SF2 values 0.63 vs. 0.84 and the cell type composition of the test fibroblast cultures. Upon pretreatment with BBI the radiation-induced premature terminal differentiation of progenitor fibroblasts to postmitotic fibrocytes could significantly be inhibited. Based on this data, it can be postulated that BBI may serve as a radioprotector of normal fibroblasts which are involved in radiation-induced tissue injuries like radiation fibrosis.

Cell Differentiation↗