Long-term results of a prospective randomized trial evaluating G-CSF priming in intensive induction chemotherapy followed by autologous stem cell transplantation in elderly patients with acute myeloid leukemia.

Few studies have evaluated granulocyte colony-stimulating factor (G-CSF) priming in elderly patients with intensively treated acute myeloid leukemia (AML), and no data are available for genetically defined AML subgroups. We provide long-term results (median follow-up 7.6 years) of a randomized trial in which 183 patients (median age 67 years) received G-CSF prior to (G-CSF priming) or after two cycles of induction chemotherapy.

Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909.

T cells with specificity for antigens derived from Wilms Tumor gene (WT1), Proteinase3 (Pr3), and mucin1 (MUC1) have been demonstrated to lyse acute myeloid leukemia (AML) blasts and multiple-myeloma (MM) cells, and strategies to enhance or induce such tumor-specific T cells by vaccination are currently being explored in multiple clinical trials. To test safety and immunogenicity of a vaccine composed of WT1-, Pr3-, and MUC1-derived Class I-restricted peptides and the pan HLA-DR T helper cell epitope (PADRE) or MUC1-helper epitopes in combination with CpG7909 and MontanideISA51, four patients with AML and five with MM were repetitively vaccinated. No clinical responses were observed.

Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia.

Mutations in the nicotinamide adenine dinucleotide phosphate(+)-dependent isocitrate dehydrogenase gene 2 (IDH2) have recently been found in patients with acute myeloid leukemia (AML) as well as in patients with leukemic transformation of myeloproliferative neoplasms. We analyzed 272 adult patients with cytogenetically normal AML (CN-AML) for the presence of IDH2 mutations in codons R140 and R172. IDH2 mutations of amino acid 140 or 172 could be identified in 12.

Impact of IDH1 R132 mutations and an IDH1 single nucleotide polymorphism in cytogenetically normal acute myeloid leukemia: SNP rs11554137 is an adverse prognostic factor.

Purpose: We assessed the prognostic impact of IDH1 R132 mutations and a known single nucleotide polymorphism (SNP) located in the same exon of the IDH1 gene in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers.

Patients And Methods: IDH1 exon four was directly sequenced in 275 CN-AML patients from two subsequent AML multicenter treatment trials and 120 healthy volunteers. Moreover, mutations in NPM1, FLT3, CEBPA, and WT1 were analyzed, and mRNA expression of IDH1 was quantified.

Single nucleotide polymorphism in the mutational hotspot of WT1 predicts a favorable outcome in patients with cytogenetically normal acute myeloid leukemia.

Purpose: We assessed the prognostic impact of a known single nucleotide polymorphism (SNP) located in the mutational hotspot of WT1 in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers.

Patients And Methods: WT1 exons 7 and 9 from 249 CN-AML patients from multicenter treatment trials AML-SHG Hannover 0199 (Clinical Trials Identifier NCT00209833) and 0295, and 50 healthy volunteers were analyzed by direct sequencing. NPM1, FLT3, CEBPA, and MLL were assessed for mutations and WT1 expression was quantified.

HLA-identical sibling allogeneic peripheral blood stem cell transplantation with reduced intensity conditioning compared to autologous peripheral blood stem cell transplantation for elderly patients with de novo acute myeloid leukemia.

We conducted a retrospective registry-based analysis to compare the outcome of 361 allogeneic human leukocyte antigen (HLA)-identical peripheral blood stem cell transplants (PBSCT) with reduced intensity conditioning (RIC) to that of 1369 autologous (auto) PBSCT in patients aged 50 years or older with de novo acute myeloid leukemia (AML), performed from 1997 until 2003 and reported to the European Group for Blood and Marrow Transplantation. Median age was 58 and 57 years in the RIC and auto groups, respectively. RIC patients had more advanced disease at the time of transplant.

Prognostic value of minimal residual disease quantification by real-time reverse transcriptase polymerase chain reaction in patients with core binding factor leukemias.

Purpose: In patients with acute myeloblastic leukemia with t(8;21) or inv(16) aberrations (core binding factor [CBF] leukemias), minimal residual disease (MRD) can be sensitively detected during and after chemotherapy by use of molecular methods. However, the prognostic impact of qualitative MRD detection is still under debate. In this study, the prognostic value of MRD quantification in patients with CBF leukemias was assessed.

Indications for and results of splenectomy in different hematological disorders.

The objective of this retrospective study was to determine the indications for splenectomy in hematological disorders and to analyze the results depending on the indication leading to surgery. Fifty-six patients with various hematological disorders were splenectomized between 1990 and 1994. The main indication was noted.

[Splenectomy in osteomyelofibrosis. Indications and outcome].

Osteomyelofibrosis is a myeloproliferative disorder in which fibrosis and sclerosis finally lead to bone marrow obliteration. Liver and spleen compensate for bone marrow loss with extramedullary hematopoiesis. In some patients the resulting splenomegaly causes severe symptoms such as local compression, thrombocytopenia and hemolytic anemia.

Simultaneous presence of t(11;14) and a variant Burkitt's translocation in the terminal phase of a mantle cell lymphoma.

Little is known about the clinical significance of secondary chromosome aberrations in lymphomas with t(11;14)(q13;q32), the characteristic change of mantle cell lymphomas. Here we present a patient with mantle cell lymphoma, who showed a variant Burkitt's translocation t(2;8)(p12;q24) in addition to t(11;14) during the progression of the disease. An involvement of chromosome 8q24, the localization of the c-myc gene, has so far been described in only four patients, who seemed to have a fatal clinical course.

In vivo/ex vivo T cell depletion reduces the morbidity of allogeneic bone marrow transplantation in patients with acute leukaemias in first remission without increasing the risk of treatment failure: comparison with cyclosporin/methotrexate.

We have performed a non-randomised GVHD prophylaxis trial comparing cyclosporin/methotrexate with in vivo/ex vivo T cell depletion with the monoclonal antibodies Campath 1G/1M in patients with acute leukaemias in first complete remission. We observed significantly less acute and chronic GVHD, neutropenic fever and severe mucositis in the T cell depletion group. The incidence of graft rejection and relapses was no higher than in the cyclosporin/methotrexate group.

Structural analysis of the deoxycytidine kinase gene in patients with acute myeloid leukemia and resistance to cytosine arabinoside.

Deficiency of deoxycytidine kinase (dCK) activity represents one possible cause of resistance to cytosine arabinoside (ara-C). Mutations of the dCK gene have recently been shown to be responsible for dCK deficiency and increased resistance in vitro. In order to define the relevance of this mechanism in vivo, we analyzed the dCK gene in 16 adult patients with relapsed/refractory acute myeloid leukemia (AML) and clinical resistance to standard-dose and/or high-dose ara-C.

Simultaneous administration of granulocyte colony-stimulating factor (Filgrastim) and induction chemotherapy in acute lymphoblastic leukemia. A pilot study.

The present study was designed to determine whether Filgrastim, a neutrophil-specific hematopoietic growth factor, could be administered simultaneously with intensive induction chemotherapy for adult acute lymphoblastic leukemia (ALL). The effect of Filgrastim on the severity of chemotherapy-induced neutropenia, fever, and infections was assessed in 15 patients treated according to the protocol of the German multicenter ALL (GMALL) trial 04/89. Filgrastim (5 micrograms/kg/day) was given concurrently with successive cycles of cyclophosphamide, cytosine-arabinoside (ara-C), 6-mercaptopurine (6MP), prednisone (PRD), intrathecal methotrexate, and prophylactic cranial irradiation.

Frequency of bone marrow T cells responding to HLA-identical non-leukemic and leukemic stimulator cells.

Grafted immunocompetent cells are considered responsible for GVHD as well as for the elimination of residual leukemic cells ('graft-versus-leukemia reactivity', GVLR) in leukemic patients after allogeneic BMT. Clinical and experimental investigations have given contradictory answers to the question whether GVHD and GVLR are two manifestations of the same process or separate immunologic processes. We have addressed this question by analysing the primary in vitro response of BM-derived proliferating and cytotoxic T lymphocyte precursors (PTLp and CTLp) in HLA identical relative pairs (n = 17).

Aggressive chemotherapy combined with G-CSF and maintenance therapy with interleukin-2 for patients with advanced myelodysplastic syndrome, subacute or secondary acute myeloid leukemia--initial results.

Aggressive chemotherapy of advanced myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) evolving from MDS, subacute AML and secondary AML has usually been associated with low complete remission (CR) rates, a high incidence of early death, and low disease-free survival. We therefore have initiated a phase-III trial of aggressive chemotherapy consisting of idarubicin, cytosine arabinoside, and VP-16 to improve the CR rate. Each chemotherapy cycle is followed by G-CSF to accelerate neutrophil recovery and to reduce the incidence of infections.

AMSA combination chemotherapy in patients with acute myelogenous leukemia unsuitable for standard antileukemic treatment.

Forty-eight patients with acute myelogenous leukemia (AML) not eligible for anthracycline or mitoxantrone treatment, mostly due to cardiac contraindications, were given aggressive therapy using m-amsacrine (AMSA) in combination with conventional or high-dose cytarabine for remission induction. Twenty-nine patients (60.4%) responded to treatment, and complete remission was attained in 19 (39.

ABO-incompatible bone marrow transplantation.

In the past 10 years 201 HLA-identical bone marrow transplantations (BMT) were performed with major ABO incompatibility in 41 (20%) and minor ABO incompatibility in 35 (18%) patients. ABO compatibility between donor and recipient showed no influence on granulocyte and platelet recovery after BMT. Erythrocyte reconstitution was significantly (p < 0.

Frequency, specificity, and phenotype of clonally growing human alloreactive interleukin-2-secreting helper T lymphocyte precursors.

Limiting dilution cultures were performed to detect allospecific IL-2-secreting helper T lymphocyte precursors (HTL-p) among human peripheral blood mononuclear cells, E-rosette-purified (E+) and cell-sorter-separated CD4+/8- as well as CD4-/8+ T cell subsets. Split-well cultures were set up prior to restimulation to assess the antigen specificity of the response. Frequencies of alloreactive IL-2-secreting HTL-p in fully HLA-mismatched responder/stimulator cell combinations ranged from 1/200 to 1/900 (among PBMNC), from 1/50 to 1/301 (among E+ T cells), from 1/36 to 1/220 (among CD4+ T cells), and from 1/38 to 1/450 (among CD8+ T cells).

Graft failure after T cell-depleted bone marrow transplantation: clinical and immunological characteristics and response to immunosuppressive therapy.

We have investigated the clinical and immunological features of 10 cases of graft failure after T cell-depleted marrow transplantation. In addition, the hypothesis that the process of graft failure can be reversed by immunosuppressive therapy with cyclosporin + steroids +/- monoclonal antibodies was tested in seven patients. Early graft failures (before day 50) presented a uniform clinical syndrome with a host T lymphocytosis preceding the loss of the graft.

Transient pancytopenia. A report from the International Agranulocytosis and Aplastic Study.

From a population-based study on the incidence of potentially drug-associated blood dyscrasias 28 cases were identified with pancytopenia. Who recovered within 90 days after diagnosis. Early recovery occurred more frequently in patients showing normal or increased cellularity of the bone marrow than in patients with bone marrow hypoplasia.

Comparative analysis of in vivo T cell depletion with radiotherapy, combination chemotherapy, and the monoclonal antibody Campath-1G, using limiting dilution methodology.

We have investigated the efficacy of standard conditioning regimens for bone marrow transplantation in depleting functional T lymphocytes in vivo and have compared it with the efficacy of the monoclonal antibody Campath-1G. Using limiting dilution techniques the frequencies of proliferating T cell precursors (PTL), cytotoxic T cell precursors (CTL-p), helper T cell precursors (HTL-p), and mature helper T cells (HTL) were determined before and after treatment. Both total body irradiation and combination chemotherapy with busulfan/cyclophosphamide were highly efficient at depleting PTL, CTL-p, and HTL-p (0-4 days) but spared HTL to a variable extent (0-99.