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D Hoelzer

Publications and source records attributed to D Hoelzer.

At least 55 records · Page 3Linked to original sources
PubMed2001

Murine M2-10B4 and SL/SL cell lines differentially affect the balance between CD34+ cell expansion and maturation.

The ability of bone marrow stroma to modulate hematopoietic progenitor cell expansion is of considerable interest for gene transfer strategies and transplantation of limited stem cell numbers. We compared the capacity of 2 murine stromal cell lines to affect the balance between maturation and proliferation of human CD34+ cells in short-term expansion cultures. In 7-day serum-free cultures, cytokine-induced amplification of granulocyte-macrophage colony-forming cells (CFC-GM), erythroid burst-forming units (BFU-E), and total cells was significantly increased by the presence of genetically engineered Sl/Sl and M2-10B4 stromal cells in a 1:1 ratio (Sl/M2 cells) compared with stroma-free cultures (P < .05). Sl/M2 cultures generated 21-fold more mature CD15+ cells than stroma-free cultures, without further amplifying the number of CD34+ cells. The addition of serum led to a further increase of CFC-GM, total cells, and CD15+ cells, whereas BFU-E were no longer maintained. Pure Sl/Sl stromal layers were likewise superior to stroma-free cultures in expansion of CD34+ cells and total cells when serum was present. However, the differentiation of CD34+ cells was less pronounced in Sl/Sl cultures compared with Sl/M2 layers, as demonstrated by a lower content of CD15+ cells. Neutralization experiments revealed differential contributions of Flt3 ligand and thrombopoietin to the support of total cell and CFC expansion by Sl/M2 and Sl/Sl stromal feeders.

Adjuvants, Immunologic↗
PubMed2001

Effective treatment with rituximab in a patient with refractory prolymphocytoid transformed B-chronic lymphocytic leukemia and Evans syndrome.

A 65-year-old male who had been diagnosed as having chronic lymphocytic leukemia (CLL) stage Rai 0 three years previously presented in October 1998 with progressive disease (splenomegaly, increasing lymphocytosis: 30/nl) and 50% prolymphocytes in his peripheral blood. The patient was refractory to initial treatment with fludarabine and epirubicin, and 2-chlorodeoxyadenosine. Additionally, the patient developed Evans syndrome. Therapy with cyclophosphamide, vincristine, and prednisone lead to an improvement of hemolysis, but the patient remained thrombocytopenic. Subsequently, lymphocytes further increased to 135/nl, and cyclophosphamide 3 g/m2 was again given but without effect on the peripheral lymphocyte count. At this stage, therapy with rituximab 375 mg/m2 four times weekly was initiated. The platelet count normalized within 1 week after the first dose of rituximab, and the lymphocyte count dropped within 2 months to 1.1/nl. This case demonstrates that patients with prolymphocytoid transformed B-CLL refractory to purine analogs and alkylating agents and autoimmune-hemolytic disease can effectively and safely be treated with rituximab and indicates that an investigation of antibody therapy is warranted in this patient group.

Aged↗
PubMed2001

AC133 expression on acute myeloid leukemia blasts: correlation to FAB and to CD34 expression and possible implications for peripheral blood progenitor cell purging in AML.

AC133 is an antigen expressed on CD34+ hematopoietic progenitor cells. In acute myeloid leukemia (AML) it is expressed on leukemic blasts of most FAB subtypes. However, few data are available regarding coexpression of other surface antigens. We measured AC133 expression on AML blasts from 28 consecutive patients at initial diagnosis (n=26) or at diagnosis of first relapse (n=2) and on 26 leukapheresis products from 14 patients. In AML AC133 correlated with CD34 expression (Spearman r=0.4711, P=0.0114) and even stronger with combined CD34/CD33 expression (Spearman r=0.5083, P=0.0068). In leukapheresis products AC133 expression correlated with CD34 expression (Spearman r=0.7495, P=0.002) and the yield of the obtained amount of CD34+ cells (Spearman r=0.6484, P=0.0121). In conclusion AC133 expression is closely related to CD34 expression in AML. In leukapheresis products AC133 provides an additional marker for selection of PBPC autografts in AC133- AML.

AC133 Antigen↗
PubMed2001

Mutation analysis of the DNA-damage checkpoint gene CHK2 in myelodysplastic syndromes and acute myeloid leukemias.

Checkpoint genes code for a family of proteins which sense DNA damage in eukaryotic cells. They play an important role in the control of the cell cycle. The human CHK2 is a homolog of the yeast G(2) checkpoint kinases known as CDS1 and RAD53. The CHK2 may be a tumor suppressor gene because it was found to be mutated in some individuals with the Li-Fraumeni syndrome. These cases had a normal, non-mutated p53 gene. We performed a mutational analysis of the CHK2 gene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) in 41 bone marrow samples from individuals with myelodysplastic syndrome (MDS) and 41 samples of acute myeloid leukemias (AML). We found a novel G to C transversion resulting in a change from Ala to Gly at codon 507 of CHK2 in one MDS sample, but normal cells from this individual did not have the abnormality. In addition, we demonstrated a previously described polymorphism at codon 84 (A to G at nucleotide 252) of exon 1 of CHK2 in three of 41 MDS and three of 41 AML patients. The presence of a CHK2 mutation in MDS highlights the importance of alterations of cell cycle checkpoint genes in this disease.

Acute Disease↗
PubMed2001

Frequent loss of heterozygosity in the region of D1S450 at 1p36.2 in myelodysplastic syndromes.

To understand the underlying mechanisms in myelodysplastic syndromes (MDS) by identifying target tumor suppressor genes, we performed a detailed deletional mapping of the short arm of chromosome 1 in 38 paired samples of bone marrow and peripheral blood obtained from individuals with MDS by PCR amplification of a total of 23 highly informative microsatellite sequences. We identified the commonly deleted region between D1S508 and D1S244. LOH of this region was found in five patients (13%). In addition, LOH at 1p was associated with a poor clinical outcome, suggesting that the deletion of a gene in this region may be involved in the course of this disease. By analyzing the chromosomal map of this region, we found TNFRSF12 as a candidate tumor suppressor gene. However, our search for mutations in this gene did not identify somatic mutations in MDS. Our findings are consistent with the possible existence of an as-yet unknown tumor suppressor gene in this region that is altered in MDS.

Adult↗
PubMed2001

Protection against severe disease is conferred by DERAA-bearing HLA-DRB1 alleles among HLA-DQ3 and HLA-DQ5 positive rheumatoid arthritis patients.

Experimental studies in transgenic mice have suggested that HLA-DQ predisposes to rheumatoid arthritis (RA), but could also modulate disease severity by presenting peptides derived from self-DR molecules. In particular, a short amino acid sequence, (70)DERAA(74), in the third hypervariable region of HLA-DRB1 confers protection for the disease, while particular HLA-DQ [DQB1*0501/DQA1*01 (DQ5) and DQB1*03/DQA1*03 (DQ3)] molecules predispose to the disease. We have therefore analyzed the allelic distribution of HLA-DRB1, DQA1, and DQB1 and the presence of rheumatoid factor and nodules among 199 German RA patients and 196 healthy controls. Our results show that HLA-DQB1*03/DQA1*03 (or DRB1*04) predisposes to RA more than HLA-DQB1*0501/DQA1*01 (i.e., DRB1*01 and DRB1*10). Homozygosity for DQ3 confers the strongest genetic risk for RA (OR = 19.79 compared to OR = 10.05 for two doses of shared epitope (SE) positive HLA-DRB1 alleles). Furthermore, patients carrying both predisposing DQ and (70)DERAA(74)-positive HLA-DRB1 alleles are more often rheumatoid factor (RF) negative than patients carrying predisposing DQ alleles alone. Only one out of 14 patients (7%) with a protective combination (DQ3/(70)DERAA(74) and DQ5/(70)DERAA(74)) had rheumatoid nodules compared to 67 out of 144 patients (46.5%) with predisposing DQ alleles alone (OR = 0.12, 95% CI: 0.02-0.72, p = 0.004). These results demonstrate a protective role of (70)DERAA(74)-positive DRB1 alleles against disease severity among RA patients.

Alleles↗
PubMed2001

Transforming growth factor-beta1 interferes with thrombopoietin-induced signal transduction in megakaryoblastic and erythroleukemic cells.

OBJECTIVE: Thrombopoietin (TPO) and transforming growth factor-beta(1) (TGF-beta(1)) have been shown to exert opposite effects on proliferation and megakaryocytic differentiation of hematopoietic cells. To determine whether TGF-beta(1) interferes directly with TPO-induced signal transduction in hematopoietic cells, we compared the regulatory effects in the TPO-responsive cell lines Mo-7e and HEL. MATERIALS AND METHODS: The cells were stimulated by 100 ng/mL TPO and/or 100 ng/mL TGF-beta1 and analyzed for proliferation (3H thymidine incorporation), viability (trypan blue exclusion), and protein expression and phosphorylation (Western blot). RESULTS: TPO enhanced the proliferation of Mo-7e cells as determined by 3H-thymidine incorporation, whereas TGF-beta1 suppressed baseline cell growth and antagonized the proliferative effect of TPO. TPO-induced proliferation also was reduced by a specific inhibitor of the mitogen-activated protein kinase (MAPK) pathway (PD098059), which inhibits activation of the MAPK extracellular signal-regulated kinases (ERK) ERK1 and ERK2, and AG490, an inhibitor of Janus kinase-2, which completely blocked TPO-induced proliferation. As demonstrated by Western blotting, TGF-beta1 reduced the TPO-stimulated ERK1/ERK2 and STAT5 phosphorylation in Mo-7e and HEL cells. This effect was completely reversed by preincubation with a tyrosine phosphatase inhibitor (Na3VO4), which suggests that TGF-beta1 activated a phosphatase. Although STAT3 also was activated by TPO, STAT3 activation remained unaltered by TGF-beta1. CONCLUSION: Taken together, these data suggest that TGF-beta1 modulates TPO-mediated effects on megakaryocytic proliferation by interfering with TPO-induced signal transduction, particularly by reducing the activities of MAPK ERK1/ERK2 and STAT5.

Cell Differentiation↗
PubMed2001

Hematologic and cytogenetic remission by STI571 (Glivec) in a patient relapsing with accelerated phase CML after second allogeneic stem cell transplantation.

We describe the clinical activity of the ABL kinase inhibitor STI571 in a patient with accelerated phase of chronic myeloid leukemia (CML) relapsing after a second allogeneic BMT and with minimal levels of donor chimerism. STI571 resulted in rapid elimination of leukemic cells with ensuing prolonged severe leukopenia and neutropenia complicated by neutropenic fever and colitis. Subsequent hematopoietic recovery was driven by donor derived cells and was associated with grade 3 graft-versus-host disease (GVHD). STI571 induced sustained hematological and cytogenetic remission combined with controllable GvHD, therapeutic goals not achieved by two preceding allogeneic transplants and repeated donor lymphocyte transfusions (DLT).

Antineoplastic Agents↗
PubMed2001

TGF beta-induced SMAD2 phosphorylation predicts inhibition of thymidine incorporation in CD34+ cells from healthy donors, but not from patients with AML after MDS.

Cells from patients with MDS-derived AML display heterogeneous proliferative responses to transforming growth factor beta (TGF beta). We analyzed growth inhibition and SMAD2 phosphorylation by TGF beta in CD34+ cells from nine patients, as compared to normal controls. While TGF beta consistently inhibited thymidine incorporation of normal cells (41% of control, P < 0.05), cells from patients with AML were growth-inhibited in only four of seven cases (40%), whereas TGF beta stimulated thymidine incorporation in the three other samples (166%). Remarkably, TPO reverted the stimulatory effect of TGF beta to profound growth inhibition. Upon exposure to TGF beta, SMAD2 protein was phosphorylated in normal CD34+ cells (n = 3), CD34+ leukemic blasts from all examined patients with AML (n = 4), and in the myeloid leukemic cell lines M-07e and HEL. TGF beta inhibited TPO-mediated thymidine incorporation, cell proliferation and survival in all samples analyzed. In M-07e cells and CD34+ cells from healthy donors, this inhibition was enhanced by an antagonist of JAK2 (AG490), but not a MEK-1 antagonist (PD098059). Conversely, in CD34+ cells from a patient with AML, both AG490 and PD098059 significantly enhanced TGF beta-mediated suppression of TPO-induced thymidine incorporation. Thus, in MDS-derived AML, altered responses to TGF beta may be due to defects downstream of SMAD2 and may involve MAPK activation.

Acute Disease↗
PubMed2001

Prospective BCR-ABL analysis by polymerase chain reaction (RT-PCR) in adult acute B-lineage lymphoblastic leukemia: reliability of RT-nested-PCR and comparison to cytogenetic data.

The reliability of routine BCR-ABL RT-nested-PCR was evaluated in 1453 B-lineage ALL or hybrid leukemia at initial diagnosis by RT-nested-PCR. All BCR-ABL-positive (n = 642) and 176 BCR-ABL-negative samples underwent a second RT-PCR. In 518 patients, karyotyping and/or FISH was compared to the BCR-ABL status. The second RT-PCR revealed in 155/642 initially positive samples a divergent result (153 BCR-ABL-negative, two other transcripts) that in most cases turned out to be caused by contaminations in the first RT-nested-PCR. Confirmatory RT-PCR detected 2/176 false negative first RT-nested-PCR results. Thirty-nine specimens remained ambiguous despite different RT-PCR approaches. As far as cytogenetic evaluation and FISH is available (n = 23), the majority but not all patients with an ambiguous RT-PCR result were Ph-negative (n = 18). RT-nested-PCR and cytogenetics yielded in 346 of 383 evaluable samples a concordant result. Differing results are given and account in part to the lower sensitivity of karyotyping. Taken together, confirmed RT-PCR detected BCR-ABL fusion transcripts consistently in 487 out of 1453 ALL samples (c-ALL: 43%, pre-B ALL: 34%, pro-B ALL: 5%, B-ALL: 0%, hybrid leukemia: 5/11). Since false positive initial RT-nested-PCR data were frequent, either confirmatory second RT-PCR or FISH analysis is warranted to guarantee sensitive and reliable results of utmost clinical relevance.

Adult↗
PubMed2001

Down-stream regions of the POZ-domain influence the interaction of the t(11;17)-associated PLZF/RARalpha fusion protein with the histone-deacetylase recruiting co-repressor complex.

INTRODUCTION: Acute promyelocytic leukemia (APL) patients with t(15;17)(PML/RARalpha positive) achieve remission upon t-RA treatment, whereas patients with t(11;17)(PLZF/RARalpha positive) do not. Both APL translocation products bind to the histone deacetylase (HD)-recruiting nuclear co-repressor complex (HD-NCR) in a ligand-dependent manner through their RARalpha portion. Differently to PML/RARalpha, PLZF/RARalpha also binds the HD-NCR in a ligand-independent manner through the PLZF portion of the fusion protein (PLZF#), which seems to be crucial for the t-RA resistance of t(11;17) APL patients. MATERIALS AND METHODS: The t-RA sensitivity of U937 cells was tested by the nitro-blue tetrazolium reduction (NBT) assay and by analysis of t-RA-induced type II transglutaminase activity. The interaction between HD-NCR and PLZF/RARalpha was investigated by in vitro binding assays. RESULTS: (i) Deletions in PLZF# convert PLZF/RARalpha from a repressor to an activator of t-RA response in U937 cells; (ii) the effect of PLZF/RARalpha on t-RA-signaling is regulated by the POZ-domain and its down-stream regions of PLZF#; (iii) there are additional binding sites for HD-NCR in PLZF# and (iv) PLZF# not only directly binds but also regulates the binding of PLZF/RARalpha to the HD-NCR. CONCLUSIONS: At least two different mechanisms responsible for the aberrant recruitment of HD-NCR complexes by PLZF# are regulating the different t-RA-sensitivity of the PLZF/RARalpha and PML/RARalpha positive APL blasts: one is related to the direct binding of the different members of the HD-NCR complex to PLZF#; the other is an enforcing effect of PLZF# on the affinity of the PLZF/RARalpha fusion protein to the HD-NCR complex.

Chromosomes, Human, Pair 11↗
PubMed2001

Deregulated expression of prostate apoptosis response gene-4 in less differentiated lymphocytes and inverse expressional patterns of par-4 and bcl-2 in acute lymphocytic leukemia.

INTRODUCTION: Prostate apoptosis response gene-4, known as par-4, is a new proapoptotic factor functionally required but not sufficient for apoptosis. Since there is evidence from prostate cancer cells that par-4 is involved in regulation of bcl-2 we assessed expression of par-4 and bcl-2 in different populations of normal and neoplastic lymphocytes. MATERIALS AND METHODS: Expression of par-4 mRNA and protein in different subpopulations of normal and neoplastic lymphocytes was assessed by reverse transcription polymerase chain reaction and Western blot. RESULTS: Par-4 mRNA was not detectable in lymphocytes of healthy volunteers (n = 10), but was present in the majority of samples of chronic lymphocytic leukemia (n = 30), chronic lymphocytic leukemia/prolymphocytic leukemia (n = 6) and acute lymphocytic leukemia (n = 10). Par-4 protein was expressed unanimously in samples of mononuclear cells from healthy volunteers and patients with CLL, but less frequently in immature lymphocytes, including neoplastic cells of CLL/PLL and ALL. The decreased frequency of par-4 expression in immature subpopulations was confirmed by results on lymphocytic cell lines at various stages of maturation. Comparing the expressional patterns of par-4 and bcl-2 there was an inverse relationship of both proteins in ALL and different lymphocytic cell lines, indicating a functional relationship of par-4 and bcl-2. CONCLUSIONS: This study establishes par-4 as a factor expressed in the majority of normal and neoplastic lymphocytic cells, demonstrating a decreased frequency of protein expression in less differentiated lymphocytes and an inverse expressional pattern of par-4 and bcl-2 in lymphocytic cell lines and ALL.

Apoptosis Regulatory Proteins↗
PubMed2001

T-large granular lymphocyte leukaemia with natural killer cell-like cytotoxicity and expression of two different alpha- and beta-T-cell receptor chains.

We describe a case of cytotoxic T-large granular lymphocyte leukaemia showing typical morphological features, expressing antigens characteristic for cytotoxic T cells and exhibiting marked natural killer-like cytotoxicity towards different target cells. Moreover, characterization of the T-cell receptors revealed simultaneous expression of two different types of beta-chains as well as alpha-chains by the malignant cell clone. The patient had an 8 year history of indolent disease, before progressing to an aggressive clinical course hardly responsive to chemotherapeutic treatment. This is the first description of a peripheral T-cell neoplasm expressing four distinct types of T-cell receptor molecules.

Disease Progression↗
PubMed2001

Older patients with high-risk fungal infections can be successfully allografted using non-myeloablative conditioning in combination with intensified supportive care regimens.

Leukaemic patients with advanced disease and severe fungal infections as well as older patients with substantial co-morbidity are usually excluded from conventional allotransplantation because of increased morbidity and mortality. We approached allogeneic transplantation in four patients with a median age of 62 years (one chronic myeloid leukaemia in blast crisis, one high-risk acute myeloid leukaemia (AML) in first complete remission (CR1), one AML in 2nd relapse, one AML in CR2 with pre-existing fungal lung infections (two aspergillus, two mucor) and additional co-morbidity (diabetes n = 2, aortic aneurysm n = 1, arterial sclerosis n = 2) by combining non-myeloablative conditioning with an intensified supportive care regimen, including amphotericin B and 4-12 (median 9) prophylactic granulocyte transfusions from granulocyte colony-stimulating factor (G-CSF)-stimulated volunteer donors. G-CSF was also given to patients until neutrophil recovery. All four patients recovered to a neutrophil count of 0.5 x 109/l after a median of 11.5 d (range 11-13 d). Prophylactic granulocyte transfusions also reduced the need for platelet transfusions and minimized mucositis. All patients were discharged at a median of 25 d (range 18-59 d) and are alive and well after a median follow-up of > 390 d (range 336-417 d) without evidence of leukaemia. Regression of the fungal lesions was documented in three patients, with a slight progression detected by computerized tomography scan of the chest in one patient. We conclude that pulmonary fungal infections are not a contraindication for allogeneic stem cell transplantation, if non-myeloablative conditioning regimens are used in combination with granulocyte transfusions, intravenous amphotericin B and G-CSF.

Acute Disease↗
PubMed2001

A new approach to evaluating intestinal acute graft-versus-host disease by transabdominal sonography and colour Doppler imaging.

An objective and non-invasive method to assess the extent, severity, course and prognosis of acute graft-versus-host disease (aGvHD) of the gastrointestinal tract would be of great importance. As high-resolution ultrasonography (HRU) and colour Doppler imaging (CDI) are used in inflammatory and ischaemic bowel diseases, we introduced these techniques to evaluate acute intestinal GvHD. In this study, 12 patients with suspected intestinal and/or severe cutaneous aGvHD were investigated by HRU and CDI. The structure and thickness of the bowel wall and the blood flow pattern in the superior mesenteric artery (SMA) as well as in the bowel wall were evaluated. All patients showed thickened bowel wall segments, especially in the ileocaecal region. Even in patients without any clinical signs of intestinal involvement (3/12), sonographic changes were observed. In six patients with severe diarrhoea, sonographic signs of secretory diarrhoea were observed. In 4/12 patients, an increased arterial blood flow in the bowel wall was demonstrated as a typical characteristic of an inflammatory bowel process. In contrast, in 4/12 patients, ischaemic bowel wall lesions with high-resistance flow pattern in the SMA were found. These patients did not respond to immunosuppressive therapy and died. In conclusion, HRU is a useful tool for detecting acute bowel GvHD even before clinical symptoms. Moreover, HRU and CDI can be applied to define the severity of aGvHD and to identify patients with a poor prognosis.

Acute Disease↗
PubMed2001

Expression of interleukin-18 and its monokine-directed function in rheumatoid arthritis.

OBJECTIVES: To investigate the expression of and monokine induction by interleukin 18 (IL-18; also called interferon-gamma inducing factor, IGIF), in peripheral blood mononuclear cells (PBMC) and cultured synoviocytes from rheumatoid arthritis (RA) patients. METHODS: We carried out IL-18 Western blotting and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) of cytokines in PBMC [IL-18, IL-1beta and tumour necrosis factor alpha (TNF-alpha)] and long-term cultured fibroblast-like synoviocytes (FLS) [IL-18, IL-1beta, TNF-alpha, IL-6, interferon gamma (INF-gamma) and [granulocyte-macrophage colony stimulating factor (GM-CSF)] from RA patients and controls. FLS were isolated from RA synovial membranes (FLS(SM)) and RA synovial fluids (FLS(SF)), osteoarthritis (OA) FLS(SM) and FLS(SF) from spondyloarthropathy patients. FLS were characterized by fluorescence-activated cell sorting of the FLS. PBMC and FLS from RA patients and control subjects were stimulated with recombinant human IL-18 and IL-1beta (rHuIL-18/rHuIL-1beta), and TNF-alpha, IL-1beta and MMP-1 were measured by ELISA in supernatants. RESULTS: Constitutive expression of IL-18 mRNA was significantly reduced whereas that of TNF-alpha was enhanced in RA PBMC. Persistent low expression of IL-18, TNF-alpha, GM-CSF and IL-1beta was observed in RA and OA FLS(SM) as well as spondyloarthropathy FLS(SF). In contrast, high constitutive expression of IL-18 in FLS (CD90/Thy-1- and CD54-positive, CD14- and CD86-negative), accompanied by persistent high levels of TNF-alpha, GM-CSF and IL-1beta expression, was restricted to synovial fluid-derived FLS obtained from RA patients. IFN-gamma was not detectable in any culture, but IL-6 mRNA was equally expressed in all FLS cultures. rHuIL-18 was effective in stimulating TNF-alpha and IL-1beta secretion in PBMC from healthy controls, but failed to stimulate TNF-alpha and IL-1beta secretion from PBMC in 11 of 12 RA patients, and all FLS cultures. rHu-IL-1beta, but not rHu-IL-18, induced interstitial collagenase (MMP-1) in FLS. CONCLUSIONS: Persistent high production of proinflammatory cytokines in RA-FLS(SF) may be relevant for chronic progression in RA synovitis. Levels of TNF-alpha and IL-1beta expression are increased in RA-FLS(SF), but are independent of IL-18. The pathological function of enhanced IL-18 expression in RA-FLS(SF) remains to be further elucidated.

Adult↗
PubMed2001

Treatment of aggressive, or progressing indolent peripheral T- and NK-cell neoplasias by combination of fludarabine, cyclophosphamide and doxorubicine.

BACKGROUND: Regarding standardization of treatment, classification, and pathophysiology of peripheral T- and NK-cell neoplasias the current knowledge is markedly behind that of B-cell lymphomas, which are approximately 10 times more frequent. In May 2000, the study group 'Peripheral T- and NK-cell Neoplasias' was founded in Frankfurt/M. This group decided on a clinical protocol and a scientific program for research on the pathophysiology of these entities. Rationales for the therapeutic regimen are the efficacy of cyclophosphamide and doxorubicine as shown in protocols for treatment of high grade lymphoma, the synergism of cyclophosphamide and fludarabine, and reports demonstrating the efficacy of fludarabine in T-cell neoplasias. PATIENTS AND METHODS: Patients will be treated with a combination of fludarabine (30 mg/m(2) days 1-3), cyclophosphamide (1000 mg/m(2) day 1) doxorubicine (25 mg/m(2) day 2+3) (FCD). For patients > or =65 years a dose-reduced FCD regimen will be administered. In patients included in the treatment study and additionally in patients with indolent disease not requiring therapy, scientific projects on the biology of peripheral T- and NK-cell neoplasias will be performed. CONCLUSIONS: Expected conclusions of the projected study are the establishment of treatment and diagnostic standards, and improvement of classification of these entities by clinical, morphologic and biologic parameters.

Aged↗