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Biomedical subjects

H Löffler

Publications and source records attributed to H Löffler.

At least 19 recordsLinked to original sources
PubMed1992

Combined effect of very early intensification and prolonged post-remission chemotherapy in patients with AML.

The study combines the effects of prolonged postremission chemotherapy with that of very early intensification. 900 adult patients at all ages with newly diagnosed AML uniformly received TAD for induction and consolidation followed by monthly myelosuppressive maintenance for 3 years. In patients of 60+ years with persistent bone marrow blasts a second TAD course was given. In all patients of less than 60 years a second induction course started on day 21 even in aplasia with no blasts. Second induction was randomly either TAD or HAM. In the younger age group 69% attained CR and similar in the two arms the CR rate after 5 years is 35%. Including the 50% patients attaining CR in the higher age group the CR rate after 5 years is 32%. In 40 patients receiving allogeneic BMT and 21 patients receiving autologous BMT in first CR relapse free survival is similar to that from chemotherapy alone in a matched pair analysis. We conclude that age adapted very early intensification followed by prolonged postremission chemotherapy represents a therapeutic progress.

Adolescent↗
PubMed1992

Acute myelogenous leukaemia in children under 2 years--experiences of the West German AML studies BFM-78, -83 and -87. AML-BFM Study Group.

Clinical, morphological, immunological, cytogenetical and prognostic features of 84 children under 2 years of age with AML in studies AML-BFM-78, -83 and -87 were retrospectively analysed. There was a high incidence of acute monoblastic leukaemia (FAB M5) (41 patients--49%) and acute megakaryoblastic leukaemia (FAB M7) (study AML-BFM-87: five patients--13%) in this age group. Acute monoblastic leukaemia was associated with hepatosplenomegaly, extramedullary organ manifestations and chromosomal abnormalities involving 11q23. The probability of an 11-year event-free survival of all patients under 2 years of the three studies combined was 39% (SD 6%). While the event-free survival rates of patients aged 2 years and older could be improved in studies AML-BFM-83 and -87 compared with study AML-BFM-78, overall prognosis in children under 2 years in the three consecutive studies remained unchanged. The event-free survival rate of children with acute monoblastic leukaemia in both age groups was comparable (7 yr-EFS (AML-BFM-83 and -87): much less than 2 years--43% (SD 9%), =/much greater than 2 years--33% (SD 9%); P much greater than 0.5). This also applied to other risk groups. In conclusion, taking the high incidence of acute monoblastic and megakaryoblastic leukaemia in children under 2 years into account, no significant differences between children under 2 years or older children concerning response to therapy and overall prognosis could be evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Longterm effects of prolonged maintenance and of very early intensification chemotherapy in AML: data from AMLCG.

In order to further improve the cure rate in AML we investigated the effect of more chemotherapy--in terms of its intensity and its duration--in 2 studies. In our 1981 study patients received TAD 1-2 courses for induction, 1 course for consolidation and randomly no further treatment or monthly myelosuppressive maintenance for 3 years. Evaluating 213 responders remission duration was clearly longer in the maintenance group with 24% CCR after 5 and 10 years. In our 1985 study the same successful strategy was further intensified by a second induction course given regardless of response to the first course to all patients up to 60 years of age while older patients received standard induction as before. This age-adapted concept resulted in a further increase of 5 years CCR in the 461 responders to as much as 34% not achieved for unselected patients in other multicenter trials. 20 patients receiving auto-BMT in first CR show the same relapse free survival as their counterparts receiving chemotherapy according to the 1985 protocol in a matched-pair analysis. We conclude that both very early intensification and prolonged maintenance contribute to a higher cure rate that is not further improved even by a maximum intensity short-term treatment. The limits of chemotherapy in AML may be overcome by modulating its myelotoxicity and antileukemic potency using GM-CSF as shown in 2 studies of our group.

Acute Disease↗
PubMed1992

Intensive chemotherapy and bone marrow transplantation for myelodysplastic syndromes.

In myelodysplastic syndromes (MDS), complete remission rates of acute myelogenous leukemia (AML)-type chemotherapeutic regimens vary widely, ranging from 15% in patients with myelodysplasia after previous cytotoxic therapy to 61% in patients with refractory anemia with an excess of blasts in transformation without previous exposure to leukemogenic chemicals. The duration of remission is usually short, and those that exceed 24 months are unusual. Results of treatment are identical in the different types of MDS. No sufficient data on aggressive therapy are available for refractory anemia and refractory anemia with ringed sideroblasts. Prognostically favorable subgroups of patients are defined by age (below 45 or 50 years), no prior history of cytotoxic drug exposure, and absence of cytogenetic aberrations, especially of chromosomes 5 and/or 7. In contrast to AML-type chemotherapy, allogeneic bone marrow transplantation following high-dose (radio) chemotherapy offers a significantly greater chance of cure with a long-term relapse-free survival rate of 30% to 60%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[Intensified therapy of severe lupus erythematosus].

14 female patients (mean age 28 [18-56] years) with severe systemic lupus erythematosus (SLE) were treated after discontinuing previous immunosuppressive therapy, according to an intensified protocol, with three plasmaphereses (days 1-3), followed by pulse cyclophosphamide (12 mg/kg i.v. each on days 3-5) and then oral immunosuppression (cyclophosphamide 1-5 mg/kg daily, depending on white blood cell count; prednisone equivalent 2.0 decreasing to 0.1 mg/kg, according to response, for 6 months). The aim of "synchronization" of plasmaphereses with subsequent cyclophosphamide pulse-therapy is to damage pathogenic lymphocyte clones during maximal compensatory activation induced by plasmapheresis. In all patients there was rapid improvement from the nephritis, pneumonitis, cytopenia, CNS abnormalities and polyserositis. The lupus activity index (SLAM) fell clearly, from initially 28.4 (13-37) points to 8.9 (2-13) after 6 months. Treatment was discontinued after this fall in 12 patients. A recurrence was observed in two patients, at 12 and 39 months respectively. Another patient died from liver cirrhosis of unknown aetiology. Nine patients are under observation but without treatment at present, in essential remission after 2 years (5-51 months), with a SLAM of 2.8 (0-7) points. "Synchronization" of plasmaphereses with subsequent pulse cyclophosphamide achieved rapid improvement and it resulted, for the first time, repeatedly in long-term treatment-free clinical remissions.

Adolescent↗
PubMed1991

Ultrastructural demonstration of peroxidase expression in acute unclassified leukemias: correlation to immunophenotype and treatment outcome.

The lineage affinity of 57 cases of acute unclassified leukemias (AUL) was reevaluated by ultrastructural analysis of peroxidase expression (POEM) in combination with immunophenotyping and analysis of immunoglobulin gene configuration. Twenty-three cases of myeloid and three cases of megakaryocytic differentiation were identified by detection of ultrastructural myeloperoxidase (UMPO) and platelet peroxidase (UPPO). No significant correlation was noted between myeloid marker expression and POEM positivity, whereas presence of CD 19 or CD 24 antigen significantly correlated with POEM negativity (P = .001 and .023, respectively). Ig gene rearrangements including oligoclonal patterns were also recorded in 8 of 14 UMPO+ patients tested. Fourteen UMPO+ patients responded poorly to an ALL/AUL chemotherapy regimen with a low complete remission (CR) rate of 29% and a short median remission duration (MRD) of 5 months. The POEM- patients proved very heterogenous with respect to immunophenotype and Ig gene rearrangement. Seventeen of 21 patients tested had Ig gene rearrangements, including oligoclonal patterns. Combined data suggest that a proportion of these cases probably derive from a very immature lymphoid progenitor cell, particularly because 15 POEM- AUL patients showed a response to ALL/AUL chemotherapy comparable to that observed in patients with definitive acute lymphoblastic leukemia (ALL) (CR rate 80%, MRD 20 months). Thus, ultrastructural analysis of peroxidase expression can provide decisive prognostic information in AUL patients.

Acute Disease↗
PubMed1991

Ifosfamide and ACNU in experimental allogeneic bone marrow transplantation.

We have tested ifosfamide and ACNU for their effectiveness in preventing graft rejection following allogeneic bone marrow transplantation. The engraftment-promoting potency of both was compared to that of the standard agent cyclophosphamide. LEW rats received a lethal dose (35 mg/kg) of busulfan followed by injection of 1 x 10(8) (CAP x LEW) F1 marrow cells, which are unable to induce a graft vs host reaction in LEW recipients. Rejection of the marrow graft was assessed by monitoring haematocrit and granulocyte count either until death of the animal or until day 80. Surviving animals received a donor-type skin graft to confirm the persistence of allogeneic haematopoiesis. Because of its weak immunosuppressive properties, busulfan by itself is unable to allow engraftment of allogeneic marrow. Therefore, ifosfamide and ACNU and cyclophosphamide as the standard agent could be tested for their capacity to prevent marrow graft rejection. The following rejection rates were observed: cyclophosphamide: 30 mg/kg 100%, 60 mg/kg 60%, 90 mg/kg 20%, 120 mg/kg and 180 mg/kg 0%; ACNU: 3, 5, 7, and 10 mg/kg 100%, 15 mg/kg 45%, 20 and 30 mg/kg 0%; ifosfamide: 60-120 mg/kg 100%, 180 mg/kg 68%, 240 and 360 mg/kg 0%. Thus, 240 mg/kg ifosfamide or 20 mg/kg ACNU is nearly equivalent to the standard dose of 120 mg/kg cyclophosphamide in engraftment-promoting potency in allogeneic bone marrow transplantation.

Animals↗
PubMed1991

High-dose cytostatic agents in allogeneic bone marrow transplantation: comparison of the engraftment promoting potential.

We investigated the potential of various cytostatic agents for preventing graft rejection following allogeneic bone marrow transplantation. LEW rats received a lethal dose (35 mg/kg) of busulfan followed by injection of 1 x 10(8) F1(CAP x LEW) marrow cells, which are unable to induce a graft-versus-host reaction in LEW recipients. Rejection of the marrow graft was assessed by monitoring haematocrit and granulocyte counts. Due to its weak immunosuppressive activity, busulfan by itself is unable to allow engraftment of allogeneic marrow. Therefore, agents administered in addition to busulfan can be tested for their capacity to prevent marrow graft rejection. 120 mg/kg of cyclophosphamide, 20 mg/kg of ACNU and 240 mg/kg of ifosfamide completely prevented rejection of the allogeneic marrow. Maximum doses of BCNU applicable in conjunction with busulfan reduced the rejection rate to 12% (30 mg/kg) and 17% (40 mg/kg), whereas the antitumour agents thiotepa, melphalan, and carboplatin exhibited a very limited engraftment-promoting potential in this experimental setting. Thus, BCNU (carmustine), ACNU (nimustine), and ifosfamide might be suitable candidates for conditioning of allogeneic bone marrow graft recipients.

Animals↗
PubMed1991

Lymphohaematopoietic chimaerism after bone marrow transplantation for chronic myeloid leukaemia: results of simultaneous cytogenetic analyses on T-cell colonies, myeloid, and erythroid progenitor cells.

Various lymphohaematopoietic compartments represented by cells from T-cell colonies, myeloid progenitor cells (CFU-GM), erythroid progenitor cells (BFU-E), and bone marrow after short-term culture (BM) have simultaneously been analysed in 15 patients receiving 17 bone marrow transplants for Philadelphia chromosome (Ph) positive chronic myeloid leukaemia (CML) or acute lymphoblastic leukaemia (ALL). The marrow grafts were not T-cell depleted. Ten patients without relapse did not show any myeloid cells of host origin until their last follow-up or until death. However, in four of these patients single lymphoid host cells not carrying the Ph chromosome were found after BMT without clinical consequences. In patients with cytogenetic or haematological relapse Ph positive metaphases were first detected in any of the progenitor cell compartments along with residual donor cells in two of three patients. BM became Ph positive after various time intervals. Another patient with CML became Ph positive in all compartments investigated at the same time. The only patient with Ph positive ALL remained completely Ph negative also when haematological and clinical relapse was evident. All patients with relapse exhibited complex clonal and non-clonal chromosomal aberrations at the time of recurrence of the Ph chromosome. Such abnormalities not identical to those usually found with evolution of the disease and preferentially occurring in progenitor cells preceded the reappearance of Ph positive metaphases in one of our patients.

Adolescent↗
PubMed1991

Influence of cytostatic treatment on the coagulation system and fibrinolysis in patients with non-Hodgkin's lymphomas and acute leukemias.

Cytostatic therapy is known to aggravate tumor-induced coagulopathy. Therefore, we have studied the effect of different chemotherapeutic regimens on the activation of coagulation and fibrinolysis in patients with non-Hodgkin's lymphomas or acute leukemias. In non-Hodgkin's lymphoma patients treated with an aggressive protocol (COL-BLAM) and in leukemia patients (TAD-9) fibrinopeptide A, prothrombin fragment (F1 + 2) and thrombin antithrombin III complexes (TAT) increased (Tables 4 and 6), while D-dimer did not deviate significantly. The ratio D-dimer/TAT consequently showed a significant decrease, indicating increased formation of thrombin after release of procoagulant factors, which is not paralleled by an activation of fibrinolysis. Both these groups were also characterized by an increase in uric acid and in C-reactive protein and plasminogen-activator inhibitor, two acute-phase reactants. In contrast, patients with non-Hodgkin's lymphomas treated with a less aggressive protocol (COP) showed no significant changes in hemostatic variables, uric acid, or acute-phase reactants. The release of procoagulant factors relates to the cytostatic sensitivity of the tumor and to a high tumor-cell destruction. Our results further emphasize the need for large-scale studies on antithrombotic prophylaxis in patients undergoing cytostatic treatment.

Acute Disease↗
PubMed1991

High-dose chemotherapy and autologous bone marrow transplantation in relapsing angioimmunoblastic lymphadenopathy with dysproteinemia (AILD).

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) or lymphogranulomatosis X is a lymphoproliferative disorder with a histological picture resembling that of reactive lesions but with frequent cytogenetic and molecular abnormalities characteristic of malignant T cell lymphoma. Clinically, the disease runs a fatal course in the majority of patients although occasional spontaneous remissions have been observed. Median survival approaches only 1 year even with the most effective treatment protocols implemented so far. Fewer than 20% of patients survive 5 years after diagnosis and cure seems exceedingly rare. High-dose chemotherapy (HDCT) followed by autologous bone marrow transplantation (ABMT) represents a promising new treatment modality for patients with advanced lymphoma conceivably including AILD. We report the first patient with relapsed AILD successfully treated by HDCT and ABMT. This 21-year-old male is alive and free of disease 27 months after ABMT with a Karnofsky score of 100%.

Adult↗
PubMed1991

Successful stimulation of autologous bone marrow recovery by GM-CSF and IL-3 after an unrelated donor BMT for juvenile CML complicated by graft failure.

We report the case of a boy with juvenile chronic myeloid leukemia (jCML), who after initial treatment with interferon alpha-2 (IFN) and hydroxyurea underwent bone marrow transplantation (BMT) from a matched unrelated donor complicated by graft failure. Subsequent stimulation of hematopoiesis by GM-CSF and IL-3 promoted autologous recovery. In contrast to the course of disease pre-BMT, the boy is now off any therapy remaining in complete remission more than 500 days after BMT.

Bone Marrow↗
PubMed1991

Remission of juvenile chronic myeloid leukemia following graft failure of an unrelated marrow transplant and autologous recovery of marrow function promoted by GM-CSF and IL-3.

The unusual course of a boy with juvenile chronic myeloid leukaemia is presented. After bone marrow transplantation (BMT) from an unrelated donor followed by graft failure and subsequent stimulation by rhu GM-CFC and II-3, this patient experienced complete recovery of autologous haematopoiesis. At 17 months post-BMT the patient was off any therapy with completely normal blood counts and no signs of disease.

Bone Marrow Transplantation↗
PubMed1990

[Sweet's syndrome after T-lymphoblastic lymphoma and before the manifestation of a secondary acute myeloid leukemia].

Thirty-two months after the diagnosis and treatment of a T-lymphoblastic lymphoma with bone marrow involvement had been made in a 30-year-old patient, he developed fever up to 40 degrees C during maintenance treatment with methotrexate and 6-mercaptopurine. Later there were tender, blue-red skin eruptions, leukocytopenia (1.4 x 10(9)/l) and thrombocytopenia (29 x 10(9)/l). Histological examination of a skin biopsy revealed acute febrile neutrophilic dermatosis (Sweet's syndrome). Bone marrow biopsy revealed hyperplastic myelopoiesis. There was no evidence for acute myeloid leukaemia or lymphoma recurrence. After the maintenance treatment had been discontinued, treatment with methylprednisolone, 60 mg, was begun. The signs of Sweet's syndrome regressed, but thrombocytopenia and mild leukocytopenia remained. Six months later it was found by morphological and immunological tests that he had acute myeloid leukaemia without any chromosomal abnormalities. There was still no evidence for a recurrent T-lymphoblastic lymphoma.

Adult↗