ABSTRACT
Between 1996 and 2004, a total of 708 patients were enrolled in the acute myeloid leukaemia (AML) '96 and '02 studies of the East German Study Group (OSHO). Of these, 138 patients (19.5%) had unfavourable cytogenetics defined as complex karyotype, del (5q)/-5, del (7q)/-7, abn (3q26) and abn (11q23). In all, 77 (56%) achieved complete remission 1 (CR1) after induction chemotherapy and were eligible for haematopoietic cell transplantation (HCT). HCT was performed after a median of two cycles of consolidation chemotherapy (CT) in the AML '96 and one cycle in the AML '02 study (P=0.03). After a median follow-up of 19 months, overall survival (OS) at two years was significantly better in the donor group (52+/-9%) versus the no-donor group (24+/-8%; P=0.005). Differences in outcomes were mainly because of a lower relapse incidence in patients after HCT (39+/-11%) compared with a higher relapse incidence in patients undergoing CT (77+/-10%; P=0.0005). Treatment-related mortality was low and not statistically significantly different between the two treatment groups (15+/-7 and 5+/-5% for HCT and chemotherapy, respectively; P=0.49).We conclude that early HCT from related or unrelated donors led to significantly better OS and leukaemia-free survival compared with chemotherapy in patients with unfavourable karyotype.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation/mortality , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Adolescent , Adult , Disease-Free Survival , Female , Hematopoietic Stem Cell Transplantation/methods , Humans , Karyotyping , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Recurrence , Remission Induction , Survival Rate , Transplantation, Homologous , Young AdultABSTRACT
A 42-year-old female patient with acute myeloid leukemia presented with fever and heavy chest pain after her first cycle of specific chemotherapy. Acute myocardial infarction was excluded, but surprisingly, parasitic inclusions in erythrocytes became obvious in Pappenheim and Giemsa-stained peripheral blood smears. The patient did not remember a tick bite but acknowledged having received several blood transfusions in her recent medical history. Suspicion of malaria was ruled out by use of a dip-stick test. The diagnosis of Babesia microti infection was finally established by specific polymerase chain reaction (PCR). Six weeks after initiation of specific treatment, PCR turned negative and a positive immunoflourescence assay (IFA) with an IgG titer of 1:128 indicated seroconversion. Subsequent screening of donors involved in the transfusion of blood products to the patient demonstrated borderline reactivity for Babesia microti (IgG-titer 1:32) in 1 out of 44 individuals. Neither the patient nor the positively tested blood donor had travelled to North America or Asia. Therefore, this is the first confirmed autochthonous human infection in Europe.
Subject(s)
Babesia microti/pathogenicity , Babesiosis/diagnosis , Transfusion Reaction , Zoonoses/transmission , Acute Disease , Adult , Animals , Babesiosis/epidemiology , Babesiosis/genetics , Blood Donors , Female , Furans , Germany , Humans , Leukemia, Myeloid , ThiophenesABSTRACT
PURPOSE: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma. METHODS: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles. RESULTS: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. CONCLUSIONS: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Lymphoma, Follicular/drug therapy , Lymphoma, Mantle-Cell/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bendamustine Hydrochloride , Cyclophosphamide/administration & dosage , Disease-Free Survival , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Lymphoma, Follicular/mortality , Lymphoma, Mantle-Cell/mortality , Lymphoma, Non-Hodgkin/drug therapy , Male , Middle Aged , Nitrogen Mustard Compounds/administration & dosage , Prednisone/administration & dosage , Survival Analysis , Treatment Outcome , Vincristine/administration & dosageABSTRACT
BACKGROUND AND OBJECTIVE: Low grade non-Hodgkin lymphomas (l-NHL) are rarely showing complete or sustained remissions to conventional chemotherapy. Thus, many therapeutic strategies try to improve the remission rates and outcome in relapsed and refractory l-NHL. Bendamustine (B) is a non-cross resistant alkylating agent shown to be highly effective in lymphoproliferative and other malignant diseases. In an open phase-II study we evaluated the efficacy and toxicity of B in combination with vincristine (O) and prednisolone (P) in heavily pretreated relapsed or refractory l-NHL. PATIENTS AND METHODS: 22 patients (median age 61.5 years, range 39-77 years) with relapsed or refractory low grade NHL: immunocytoma (IC) n = 11, centroblastic-centrocytic (CB-CC) n = 6, centrocytic (CC) n = 2, others n = 3, were treated with BOP as follows: patients up to 75 years: 60 mg/m2 B for 5 days; patients over 75 years: 50 mg/m2 B for 5 days. All patients received 2 mg vincristine (O) on day 1, 100 mg/m2 prednisolone (P) on day 1-5; repetition day 29. Prior to BOP patients were pretreated with 1-4 chemotherapy protocols. An average of 5 courses of BOP were administered (range 2-8). In most patients BOP was followed by a maintenance therapy (IFN-alpha n = 11, chlorambucil n = 4, etoposide n = 2). RESULTS: Objective remission was achieved in 19/22 (86%) patients, complete remission (CR) in 10/22 (45%), partial remission (PR) in 9/22 (41%) and no change (NC) in 3/22 (14%) patients. The mean duration of remission was 16.1 months. Predominant features of side effects of the BOP protocol were myelotoxicity of WHO grade III/IV in 8 of 109 cycles leukopenia (8%), thrombocytopenia 3 cyles (3%) and anaemia in 4 cycles (4%). We observed one WHO grade IV infectious episode. Other side effects were mild and rare. There was a decline of the CD4/8 in more than 50% of patients. However, these changes were not accompanied by a higher rate of infectious episodes. CONCLUSION: Salvage therapy of refractory and relapsed l-NHL with BOP results in a high objective remission rate. Together with a maintenance therapy most patients achieved a long-term disease-free survival. Myelotoxicity and the inversion of the CD4/CD8 ratio were frequently observed side effects.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/administration & dosage , Cisplatin/administration & dosage , Lymphoma, Non-Hodgkin/drug therapy , Vincristine/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/adverse effects , Cisplatin/adverse effects , Female , Humans , Male , Middle Aged , Salvage Therapy , Treatment Outcome , Vincristine/adverse effectsABSTRACT
Bendamustine, an alkylating agent without cross-resistance to cyclophosphamide is active in a variety of lymphoproliferative and other malignancies. In an open phase-II study we treated 23 patients with a median age of 62 years at study entry (43-86 years) with advanced, refractory or relapsed (Rai stage III n = 9, Rai stage IV n = 14) chronic lymphocytic leukemia (CLL) with bendamustine. At study entry, only 13 patients were chemotherapy-naive. The treatment schedule with bendamustine was as follows: for patients up to 70 years 60 mg/m2 for 5 days, for patients over 70 years 50 mg/m2 for 5 days, repetition at day 29. Remission criteria were used according to Cheson et al. (1996). All patients were evaluable for toxicity and 20 for response. An objective remission was achieved in 15/20 patients (75%), including six patients with complete remission (CR). Three of the complete responders had no chemotherapy prior to bendamustine. No change (NC) occurred in 5/20 patients (25%). Median overall survival after bendamustine treatment is 13.6 months (1-46 months) and 16.6 months (1-46 months) in patients responding to bendamustine. In total, 74 courses of bendamustine were applied. Therapy-related anemia and thrombocytopenia were rare. However, WHO grade III/IV leukocytopenia occurred in 38/74 cycles (51%), resulting in treatment-related mortality in 3/23 patients (13%). These patients were severely immunocompromised due to pretreatment or the underlying disease. As a corollary of the study, a general prophylactic antibiotic treatment (trimethoprim/ sulfamerazine) was instituted. A general feature was the decline of the CD4/CD8 ratio: mean before therapy: 1.36; after two courses: 0.98; after four courses: 0.6, as documented in all patients who received at least two courses of bendamustine (n = 12). All evaluable patients showed a decline in the CD4/8 ratio. However, this decline was not clearly related to an increased risk of infectious episodes. We observed mainly cutaneous allergic reactions (three WHO grade I; one WHO grade II) leading to a cessation of bendamustine treatment in 4/23 patients (18%). Bendamustine is highly effective in advanced or refractory CLL. In multiple pretreated or otherwise severely immunocompromised patients bendamustine might lead to additional immunosuppression with subsequent infectious complications.
Subject(s)
Alkylating Agents/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Nitrogen Mustard Compounds/therapeutic use , Adult , Aged , Aged, 80 and over , Alkylating Agents/adverse effects , Antineoplastic Agents, Alkylating/therapeutic use , Bendamustine Hydrochloride , CD4-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/drug effects , Cyclophosphamide/therapeutic use , Female , Humans , Immunophenotyping , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Male , Middle Aged , Nitrogen Mustard Compounds/adverse effects , Random Allocation , Time FactorsABSTRACT
We examined the efficiency of disease-specific "standard" chemotherapies epirubicin, cyclophosphamide (EC); cyclophosphamide, vincristine, doxorubicin, etoposide, prednisolone (CHOEP); epirubicin, ifosfamide (EPI/IFOS) for peripheral blood progenitor cell (PBPC) mobilization in comparison to well-characterized mobilization protocols, i.e. etoposide, ifosfamide, cisplatin, epirubicin (VIPE) and dexamethasone, carmustine, etoposide, cytarabine, melphalan (DexaBEAM). Twenty-seven patients with various malignancies underwent 75 apheresis procedures for PBPC collection. Median cell yields from all 75 aphereses were 1.18 x 10(5) mononuclear cells/kg [range (0.28-3.7) x 10)8)], 1.4 x 10(5) granulocyte/macrophage-colony-forming units (CFU-GM)/kg [range (0.2-11) x 10(5)] and 3.3 x 10(6) CD34+cells/kg [range (0.35-17.7) x 10(6). CD34+/ CD90+ cells could be mobilized by all mobilization regimens used. The difference observed in the mobilization of CD34+ cells was only of low significance when the mobilization regimens were compared, whereas the mobilizations of MNC and CFU-GM were significantly different between the groups. Breast cancer patients treated with the VIPE regimen (including pretreated women) had a significantly higher CFU-GM rate than patients treated with EC (P=0.0005). Mobilized CD34+ PBPC were correlated with CFU-GM in all apheresis products. The linear correlation coefficients differed for the various mobilization groups: DexaBEAM (r=0.9, P < 0.0001), VIPE (r=0.68, P=0.0024), CHOEP (r=0.52, P=0.022), EPI/ IFOS (r=0.34, P=0.11) and EC (r=0.23, P=0.2). We conclude that clonogenic assays can provide additional information about the autotransplant quality, particularly when alternative or new mobilization regimens are being investigated.
Subject(s)
Antigens, CD34/analysis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blood Component Removal , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cells/drug effects , Neoplasms/blood , Neoplasms/drug therapy , Carmustine/administration & dosage , Cell Separation/methods , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Epirubicin/administration & dosage , Etoposide/administration & dosage , Female , Flow Cytometry , Granulocytes/cytology , Hematopoietic Stem Cells/cytology , Humans , Ifosfamide/administration & dosage , Macrophages/cytology , Male , Melphalan/administration & dosage , Prednisolone/administration & dosage , Vincristine/administration & dosageABSTRACT
BACKGROUND: The availability of hemopoetic growth factors and the retransfusion of autologous peripheral blood stem cells (PBSC) have enabled high-dose chemotherapy (HDT) options for the treatment of advanced solid tumours, during recent years. Though the transfusion of PBSC can manage the myelosuppression, dose-escalation ist still limited by non-haematological toxicity. METHOD: Usually, HDT has been given after a proceeding dose-intense chemotherapy that allowed the evaluation of chemosensitivity of the disease and resulted in a stem cell mobilization into the peripheral blood. The autologous bone marrow transplantation has almost completely been replaced by retransfusion of PBSC together with hemopoietic growth factors as specific supportive treatment. The PBSC are harvested by apheresis using a blood cell separator. RESULTS: Results on the efficacy of HDT are available for breast, testicular, ovarian, small cell lung cancer as well as melanoma, glioblastoma and soft-tissue sarcoma. The studies showed the feasibility and efficacy of HDT with tolerable toxicity. CONCLUSION: High-dose chemotherapy will be of increasing importance in the treatment strategies of primary solid tumors, in the near future.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Cell Growth Factors/administration & dosage , Hematopoietic Stem Cell Transplantation , Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Combined Modality Therapy , Dose-Response Relationship, Drug , Female , Hematopoiesis/drug effects , Humans , MaleABSTRACT
Experimental allergic uveitis (EAU) is an induced autoimmune disease by administering soluble retinal S antigen and complete Freund's adjuvant (CFA). In rabbits, the result is the occurrence of chorioretinitis in 90% of the cases. The first inflammation is followed by spontaneous relapses. The EAU of the rabbit was utilized to study the effects of the dialyzable leucocyte extract (DLE) on the course and the intensity of the disease in this autoimmune model. The DLE preparations examined differed with regard to their origin or the immunological stimulation of the initial material (DLE from humans (DLE Hu) and DLE from the normal rabbit (DLE RaO) or rabbits which had EAU (DLE RaEAU) and rabbits which had received CFA (DLE Ra (CFA). One unit of DLE corresponds to the extract from 10(9) cells. The administration of DLE starts with the onset of inflammation. 4 x 0.5 units were administered during the first week, 1 x 0.5 units per week from the 2nd to the 12th week. All preparations decrease the cumulative frequency of the days of illness significantly. The duration of the initial inflammation is reduced in all animals treated, but only in part significantly. There appears a graduation of efficacy: DLE RaEAU greater than DLE Ra CFA greater than DLE Hu greater than DLE RaO. Overall, it can be seen that, on the one hand, there is no specificity or restriction of the species for the efficacy and, on the other hand, the extent of the effects depends on the degree of the immunological stimulation. The maximum efficacy of DLE RaEAU is not exclusively due to the transmission of an antigen-specific sensitization.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Autoimmune Diseases/therapy , Immunologic Factors/therapeutic use , Leukocytes/chemistry , Uveitis/therapy , Animals , Antigens/immunology , Arrestin , Cell Extracts , Dialysis , Disease Models, Animal , Eye Proteins/immunology , Immunologic Factors/isolation & purification , RabbitsABSTRACT
In a search for alternative therapeutic methods other than corticosteroids and cytostatics, the effect of a dialyzable leukocyte extract (DLE), the antimetabolite 5-fluorouracil and the immunosuppressive agent cyclosporin A in corticosteroid-resistant idiopathic uveitis was studied. When DLE was administered to 26 patients who had uveitis forms with exogenous triggering (e.g., infection), as well as forms with an autoimmune background, there was a reduction in the number and duration of recurrences and a statistically proven prolongation of the inflammation-free intervals. This was particularly true in anterior and posterior uveitis and to a lesser extent in the intermediate form. No side effects were observed. 5-Fluorouracil, injected subconjunctivally, is indicated in intermediate uveitis with marked vitreous infiltration and beginning proliferation. Corneal erosion occurs relatively often. During treatment with cyclosporin A (low dose, 5 mg/kg of body weight per day), 14 of 17 patients (9 with intermediate uveitis, 6 with retinal vasculitis, 1 with sympathetic ophthalmia, 1 with panuveitis) showed improved results; in 2 cases the findings remained stationary and only 1 case had low-grade deterioration. If one takes into consideration the fact that in this patient any therapy would have failed, the results are convincing. This is particularly true of retinal vasculitis. There is no effect in cases of central hemorrhagic chorioretinopathy. So far, there have been no serious side effects.
Subject(s)
Cell Extracts/therapeutic use , Cyclosporins/therapeutic use , Fluorouracil/therapeutic use , Leukocytes , Uveitis/drug therapy , Adrenal Cortex Hormones/therapeutic use , Adult , Child , Chronic Disease , Humans , Uveitis/therapyABSTRACT
26 patients with idiopathic uveitis (anterior uveitis 11, intermediate uveitis 8, posterior uveitis 7) were treated with Dialysable Leukocyte Extract (DLE) for a long period. In comparison with the period before DLE in anterior and posterior uveitis the numbers of relapses decrease, the inflammation-free intervals become longer. These prolongations are significant. In cases with intermediate uveitis such a significance is not available. But in all types of uveitis DLE therapy shortens the duration of inflammatory episodes. These effects lead to a highly significant decrease of the portion of the period during and after DLE therapy in which inflammatory signs occur in comparison with the period before DLE therapy. The latter result becomes evident for all types of uveitis.
Subject(s)
Cell Extracts/therapeutic use , Leukocytes/immunology , Lymphokines/therapeutic use , Tissue Extracts/therapeutic use , Uveitis/therapy , Adolescent , Adult , Child , Chronic Disease , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Recurrence , Uveitis/immunologyABSTRACT
Twelve patients with extremely severe uveitis and two patients with necrotizing (chorio-)retinitis were treated with a combination of antibiotics consisting of penicillin G, gentamicin and metronidazole. The antibiotics were administered in 5 cases (all uveitis patients) after unsuccessful long-term treatment with other drugs, in nine cases after short-term treatment with other drugs or immediately. The treatment was effective in 10 of the uveitis patients, including all 5 cases in which the previous treatment had been unsuccessful. In 2 cases it was ineffective. It was effective, however, in both of the cases of necrotizing (chorio-)retinitis. The duration of the required treatment with antibiotics was not significantly prolonged in cases which had previously undergone long-term treatment with other drugs. However, the clinically detectable onset of improvement of vision and of the findings was significantly delayed. Despite some cogent connections between the antibiotics therapy and the improvement in the clinical picture, no well-founded conclusions as to etiology can be derived for the uveitis or necrotizing (chorio-)retinitis patients in question. The successful treatment of problematic cases identifies therapy with antibiotics as a therapeutic alternative.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Chorioretinitis/drug therapy , Uveitis/drug therapy , Adolescent , Adult , Chorioretinitis/pathology , Drug Therapy, Combination , Female , Gentamicins/therapeutic use , Humans , Male , Metronidazole/therapeutic use , Middle Aged , Necrosis , Penicillin G/therapeutic useABSTRACT
21 patients with diseases due to immunological causes were treated 6 times at an interval of four weeks by administering 5 E TF or 1 E TF each per 10 kg of body weight. TF consisted of 5 different large pool TF charges of 420 to 822 buffy-coats of fresh stored whole blood. Clinical and immunological investigations as well as biochemical ones in the laboratory were made before and after treatment. Large pool TF is clinically effective in 9 from 18 patients and immunologically in 16 from 18 patients. There is a greater effect in immunodeficiencies than in autoimmune diseases. TF is not able to remove the defect for a long time. Repeated administrations are required. TF therapy may be regarded as a substitution therapy. At first, the intervals have to be chosen according to clinical parameters (recidive of the disease or crisis respectively). There is a good compatibility of TF. Side-effects could not be observed. The frequent immunological conversions after score evaluation indicate, however, that in comparison to the clinical appearance the course of the disease must be seen to be much more complex than it can be expressed by in vitro correlates of immunological responses. Statistically ensured correlations of single tests concerning the clinical course could also not be found. Large pool TF provides favourable conditions for controlled therapy trials in order to elucidate those findings of therapy which hitherto had been a subject of controversy (e.g. autoimmune diseases, tumours).
Subject(s)
Immune System Diseases/drug therapy , Transfer Factor/therapeutic use , Adolescent , Adult , Aged , Antibody Formation , Child , Child, Preschool , Humans , Infant , Injections, Intramuscular , Middle Aged , Rosette Formation , Skin Tests , Transfer Factor/administration & dosage , Transfer Factor/immunologyABSTRACT
1. In non-Hodgkin-lymphomas with leucaemic form of the course a significant percental decrease of the number of T-lymphocytes and an also significant increase of the number of B-lymphocytes was to be proved. The increase of the B-lymphocytes concerned among others cells which carry the ME-receptor. 2. In non-Hodgkin-lymphomas with aleucaemic form of the course in decrease of the absolute number of lymphocytes a relative and absolute increase of the subpopulation of lymphocytes carrying the ME-receptor was provable. 3. In the course control of 7 patients with non-Hodgkin-lymphoma under polychemotherapy in 5 cases a discrepancy between the number of rosette-forming cells and the total number of lymphocytes appeared. 4. In the monotherapy of patients with CLL in favourable clinical development a percental increase of the T-cells is objectifiable after one year. A similar development was to be found in 3 patients after the first cycle with CVP.
Subject(s)
Antineoplastic Agents/administration & dosage , B-Lymphocytes/drug effects , Leukemia/drug therapy , Lymphoma/drug therapy , T-Lymphocytes/drug effects , Adult , Aged , Cyclophosphamide/administration & dosage , Drug Therapy, Combination , Female , Humans , Leukocyte Count , Male , Middle Aged , Prednisolone/administration & dosage , Receptors, Fc/immunology , Rosette Formation , Vincristine/administration & dosageABSTRACT
In 29 patients suffering from adenocarcinom of the corpus uteri, who had been treated with high doses of norethisterone acetate (NEA) alone or in combination with irradiation, we performed a study in order to find out whether NEA will produce a clinically measurable and noteworthy modification of glucose tolerance. -- For this purpose, the glucose assimilation coefficient (k value), apart from its first determination, will be determined 6 weeks later under current therapy. The comparison of both values shows a statistically significant decrease of the k value after 6 weeks in all patients whose first value was k less than or equal to 1. For the patients with a first value of k greater than 1 a significant development was not detectable. The alteration of the k value under NEA therapy in patients with a primarily decreased value (n = 11; in 5 of them diabetes known) was accompanied merely by 2 diabetics with changes in the day profile of such an extent that a correction of therapy was necessary.