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Biomedical subjects

D Hoelzer

Publications and source records attributed to D Hoelzer.

At least 307 records · Page 17Linked to original sources
PubMed1988

Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults.

In a prospective multicenter study, 368 acute lymphoblastic leukemia (ALL) patients aged 15 to 65 years were treated with an intensified induction and reinduction regimen; 272 (73.9%) achieved complete remission (CR). The median remission duration (MRD) is 24.3 months, and the probability of being in continuous CR (CCR) at greater than 5 years is .37. The median survival for all 368 patients is 27.5 months, and the probability of being alive at 5 years is .39. For the 272 patients in remission the median survival is 58.4 months, and the probability of being alive at 5 years is .49. A lower CR rate was seen for patients with bleeding at diagnosis or with splenomegaly/hepatosplenomegaly. The prognostic factors unfavorable for remission duration were time to CR greater than 4 weeks v less than 4 weeks (P = .0002), age greater than 35 years v less than 35 years (P = .0008), leukocyte count greater than 30,000/microL v less than 30,000/microL (P = .0112), and null ALL v common ALL (c-ALL)/T cell ALL (T-ALL) (P = .05). The remission duration correlated strongly (P = .0001) with the number of these independent prognostic factors. In patients with none of these adverse factors the MRD has not yet been reached, with one adverse factor the MRD is 21.9 months, and with two or three adverse factors the MRD is only 9.6 months. For the immunologic subtype T-ALL, the probability of being in CCR at greater than 5 years is .55; for c-ALL, .34; and for null ALL, .24. According to these results, patients were stratified into a low-risk group with a CCR rate of .62 and a high-risk group with a CCR rate of .28, with the latter now allocated to either further chemotherapy or bone marrow transplantation in first remission.

Adolescent↗
PubMed1987

In vitro differentiation of a null-acute leukemia: T-lymphoid surface antigen expression associated with rearrangement in T-cell receptor beta chain variable genes.

We describe a human acute unclassified leukemia with a unique t(4;17) translocation that coexpresses T-lymphoid and myeloid surface antigens after in vitro culture in the presence of the tumor promoter, TPA. Under these conditions, the joining regions of the immunoglobulin heavy chain and T-cell receptor gamma and beta chain complexes remained in germ line configuration. A T-cell receptor beta chain variable gene probe, however, revealed the presence of rearrangements in the V beta M3-2 gene region after bilineage differentiation. These results may be pertinent to the interrelationship of T-cell receptor gene rearrangements and the control of T-cell antigen surface expression.

Acute Disease↗
PubMed1987

Defective in vitro growth of the hemopoietic progenitor cells in the acquired immunodeficiency syndrome.

In addition to immunologic derangement, hematological abnormalities have been reported in the majority of patients with acquired immunodeficiency syndrome (AIDS). In this study 15 patients with AIDS or AIDS-related complex (ARC) were evaluated for the in vitro growth of hemopoietic progenitor cells. In all patients a significant reduction of growth (mean +/- SEM) of colony-forming unit-granulocyte, erythrocyte, macrophage, (megakaryocyte) (CFU-GEM) (1.2 +/- 0.3), burst-forming unit-erythroid (BFU-E) (17 +/- 10), CFU-megakaryocyte (CFU-Mk) (1.7 +/- 0.6), and CFU-granulocyte-macrophage (CFU-GM) (35 +/- 10) was observed in comparison with normal controls. Depletion of T cells from the bone marrow before culture led to a significant increase in colony growth, which indicated an imbalance of the normally modulating T cell subsets. This increase was reversed by readdition of autologous T cells causing a decrease in colony growth to a degree, dependent on the T4 to T8 ratio. A decreased number of hemopoietic progenitor cells and/or a defective modulation of progenitor cell growth, normally carried out by T lymphocyte subsets, might be the cause of the hematological abnormalities in AIDS patients.

AIDS-Related Complex↗
PubMed1987

Human acute unclassified leukemia with a unique t(4;17) chromosomal translocation expresses T lymphoid and myeloid surface antigens after in vitro culture.

Bilineage differentiation along both the T lymphoid and the myeloid lineage while in in vivo diffusion chamber (DC) and in vitro suspension culture was observed in a case of acute unclassified leukemia (null-AL) and t(4;17). Prior to culture, the blast cells were TdT and la positive but did not express any lineage-specific antigenic markers. Furthermore, the immunoglobulin heavy chain and T cell receptor beta-chain genes were in germline configuration. Cytogenetically, all metaphases had the unique translocation t(4;17) (q25;q23) prior to and after culture, supporting the leukemic origin of the cells. During both DC culture and suspension culture with and without tetradecanoyl-phorbol-acetate (TPA), a substantial increase in the absolute and relative number of cells expressing both myeloid and T lymphoid antigenic markers occurred. Double-fluorescence analysis demonstrated the expression of antigenic markers of both lineages on the same population of cells, and electron microscopy revealed the induction of myeloperoxidase after both DC and suspension culture. Immunoglobulin heavy chain and T cell receptor beta-chain genes remained in germline configuration after treatment with TPA, when analyzed with JH and CT beta probes, respectively. These findings indicate that this case represents a null-AL with dual-lineage capabilities, which has probably arisen from the malignant transformation of a bipotential stem cell of lymphoid and myeloid progeny.

Antigens, Neoplasm↗
PubMed1987

Effects of recombinant alpha and gamma interferons on the in vitro growth of circulating hematopoietic progenitor cells (CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM) from patients with myelofibrosis with myeloid metaplasia.

Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder due to clonal expansion of a pluripotent hematopoietic progenitor cell with secondary marrow fibrosis. No definitive treatment has as yet been devised for this condition, which shows a marked variability in clinical course. To evaluate whether excessive hematopoietic progenitor cell proliferation could be controlled by recombinant human interferon alpha (rIFN-alpha) and gamma (rIFN-gamma), we studied the effects of these agents on the in vitro growth of pluripotent and lineage-restricted circulating hematopoietic progenitor cells in 18 patients with MMM. A significant increase in the growth (mean +/- 1 SEM) per milliliter of peripheral blood of CFU-GEMM (594 +/- 253), CFU-Mk (1,033 +/- 410), BFU-E (4,799 +/- 2,020) and CFU-GM (5,438 +/- 2,505) was found in patients as compared with normal controls. Both rIFN-alpha and rIFN-gamma (10 to 10(4) U/mL) produced a significant dose-dependent suppression of CFU-GEMM, CFU-Mk, BFU-E, and CFU-GM growth. Concentrations of rIFN-alpha and rIFN-gamma causing 50% inhibition of colony formation were 37 and 163 U/mL for CFU-GEMM, 16 and 69 U/mL for CFU-Mk, 53 and 146 U/mL for BFU-E, and 36 and 187 U/mL for CFU-GM, respectively. A marked synergistic effect was found between rIFN-alpha and rIFN-gamma: combination of the two agents produced inhibitory effects greater than or equivalent to those of 10- to 100-fold higher concentrations of single agents. These studies (a) confirm that circulating hematopoietic progenitors are markedly increased in MMM, (b) indicate that these presumably abnormal progenitors are normally responsive to rIFNs in vitro, and (c) show that IFNs act in a synergistic manner when used in combination. Because rIFN-gamma can downregulate collagen synthesis in vivo, this lymphokine could be particularly useful in the treatment of patients with MMM.

Antibodies, Monoclonal↗
PubMed1987

Effect of recombinant interferons alpha and gamma on human bone marrow-derived megakaryocytic progenitor cells.

Interferons (IFNs) have been shown to suppress the proliferation of human pluripotent hematopoietic progenitor cells, CFU-GEMM, and committed erythroid (BFU-E, CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. However, no information is yet available concerning the effect of IFNs on human megakaryocytic progenitor cells CFU-Mk. Furthermore the mechanisms underlying the inhibitory activity of IFNs are still controversial. Therefore highly purified recombinant IFN preparations, rIFN-alpha and rIFN-gamma, were assessed for their influence on in vitro growth of human bone marrow-derived CFU-Mk as well as CFU-GEMM. In addition, the role of hematopoietic accessory cells, that is, adherent cells and T lymphocytes, in the mediation of the suppressive effect of rIFNs was examined. When added to unseparated bone marrow cells, both rIFN preparations significantly inhibited colony formation with 50% inhibition of CFU-Mk occurring at 22 U/mL for rIFN-alpha and 59 U/mL for rIFN-gamma, while 50% inhibition of CFU-GEMM occurred at 59 U/mL for rIFN-alpha and 101 U/mL for rIFN-gamma. The suppressive effect of rIFN-alpha and rIFN-gamma was selectively abolished by monoclonal antibodies (MoAbs) against rIFN-alpha and rIFN-gamma, thus confirming that the inhibitory activity was due to the rIFN preparations used. The antiproliferative effect of rIFN-alpha and rIFN-gamma on CFU-GEMM growth was not associated with a decrease in the percentage of mixed colonies containing megakaryocytic cells as assessed by use of the MoAb C17.28 against platelet glycoprotein IIIa. Removal of adherent cells and T lymphocytes from the target bone marrow cells had no influence on the suppressive effect of rIFN-alpha, whereas it significantly reduced the inhibitory effect of rIFN-gamma on the growth of megakaryocytic colonies and the other hematopoietic progenitors. The data indicate that (1) human megakaryocytopoiesis is markedly inhibited by rIFN-alpha and rIFN-gamma, and (2) the inhibitory effect of rIFN-alpha is due to a direct action on hematopoietic progenitor cells, whereas the effect of rIFN-gamma is mediated to a significant degree through accessory cell populations.

Bone Marrow Cells↗
PubMed1987

Acute lymphoblastic leukemia in adults: recent progress, future directions.

The data reviewed indicate substantial recent progress in the treatment of ALL in adults. Most patients, greater than 70% to 80%, will achieve a remission following induction chemotherapy with vincristine, prednisone, and an anthracycline. Additional drugs do not convincingly increase the remission rate; their effect on remission duration is unknown. Although continuation therapy has not been critically evaluated in randomized trials, the longest remissions have been reported in individuals receiving consolidation/intensification, particularly in the immediate postremission period. Presently, a disease-free survival is 35% to 45% at greater than 5 years when this type of consolidation/intensification therapy is used. The precise value of conventional maintenance chemotherapy in adult ALL is unknown. CNS prophylaxis is necessary; the standard of treatment remains cranial radiation and intrathecal methotrexate. Alternative approaches are currently being studied such as systemic treatment with high doses of methotrexate or cytarabine. Recently, prognostic factors have been better defined. In recent studies with intensive treatment, time to response, age, WBC, immunologic subtype and cytogenetic data can be used to divide patients into a low-risk group with a projected disease-free survival of 60% or more and a high-risk group with a disease-free survival of 20% to 25%. The definition of risk groups in adult ALL may be useful in determining future further optimal therapeutic approaches.

Adolescent↗
PubMed1986

Effect of intensified chemotherapy on the pluripotent haematopoietic progenitor cells CFU-GEMM in adult acute lymphoblastic leukaemia.

In order to analyse the short-term and long-term effects of intensified induction chemotherapy, the frequency, cellular composition and proliferative state of the pluripotent haemopoietic progenitor cells CFU-GEMM was investigated in a total of 35 patients with acute lymphoblastic or acute undifferentiated leukaemia at diagnosis, as well as during and after therapy. At diagnosis, the number of CFU-GEMM/ml bone marrow aspirate was significantly reduced to 12.1 (95% confidence interval 2.1-70) as compared to healthy controls (50.4/ml; 95% confidence interval 66-3846/ml). While immediately after the end of induction therapy, the respective values for CFU-GEMM were still decreased (30.4/ml; 95% confidence interval 8.4-108); values not significantly different from normal were reached within the following 4 weeks. During and after cessation of maintenance therapy again no significant deviation from normal values was observed. Immunological analysis of single colonies revealed that during the early phase after remission induction only 60 +/- 7% of mixed colonies contained megakaryocytic cells (normal 86 +/- 3%; P less than 0.01) while normal values were found during and after maintenance therapy. Cell cycle analysis disclosed highly increased proliferative activity of pluripotent progenitor cells during marrow regeneration after induction therapy as well as during maintenance therapy, but a return to the resting state after cessation of maintenance therapy. It is concluded that this intensive chemotherapy regimen does not result in any apparent long-term damage to the pluripotent haemopoietic progenitor cells.

Acute Disease↗
PubMed1986

TAD-induction therapy for 175 adults with acute myeloid leukemia, followed by consolidation and maintenance therapy. The joint study of Ulm and Tübingen.

175 patients with acute myeloid leukemia were treated between February 1980 and March 1985 with a TAD-induction therapy, three intensified consolidation cycles (COAP, COAP, AD), and a two-year mild maintenance therapy. The median age of the patients was 44 years, range 15-68 years. 62.3% of all patients attained complete remission and 13.7% partial remission. The median duration of remission was 10 months and the median survival time of patients in complete remission was 20 months. Patients older than 50 years had a higher early death rate (17.6) than younger patients (8.9%), but no difference was found in remission rates or in the median duration of remission and of survival. These results are in line with those of comparable studies.

Adolescent↗