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B Heinze

Publications and source records attributed to B Heinze.

At least 37 records · Page 2Linked to original sources
PubMed1994

Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group.

As curative bone marrow transplantation is available only to a minority of patients with chronic myelogenous leukemia (CML), drug therapy remains of central interest. Several nonrandomized studies have suggested that interferon-alpha (IFN) may prolong survival in CML. In a randomized multicenter study the influence of IFN versus busulfan or hydroxyurea (HU) on survival of Philadelphia-positive (Ph+) CML was examined. A total of 513 Ph+ patients were randomized for treatment as follows: 133 for IFN, 186 for busulfan, and 194 for HU. IFN-treated CML patients have a significant survival advantage over busulfan-treated (P = .008), but not over HU-treated patients (P = .44). The longer survival is due to slower progression to blast crisis. Median survival of IFN-treated patients is 5.5 years [5-year survival, 59%; 95% confidence interval (CI), 48%-70%], of busulfan-treated patients, 3.8 years (5-year survival, 32%; CI, 24%-40%), and of HU-treated patients, 4.7 years (5-year survival, 44%; CI, 36%-53%). Patients who continue on IFN survive longer than those in whom IFN is discontinued before blast crisis (P = .007). Complete hematologic IFN-responders have a survival advantage over partial responders or nonresponders (P = .02). Cytogenetic IFN-responders have no significant survival advantage over nonresponders (P = .2). Patients who attain white blood cell (WBC) counts of 10 x 10(9)/L or less have a survival advantage in the IFN (P = .007) and HU (P = .05) groups. Whereas toxicity in the IFN group was considerably higher than in the busulfan or HU groups, long-lasting cytopenias necessitating discontinuation of therapy as observed with busulfan have not been seen with IFN or HU. The problems of conventional prognostic scores (Sokal's score, Score 1) that we observed in IFN-treated patients support the idea that IFN changes the natural course of CML. We conclude that, with regard to survival of CML in the chronic phase, IFN is superior to busulfan and as effective as HU. Whether and to what extent IFN is superior to HU appears to depend, at least in part, on the degree of WBC suppression by HU-therapy and on the risk profile of the patients.

Adolescent↗
PubMed1994

RAPD reactions from crude plant DNA. Adding RNase A as a "helper enzyme".

As opposed to standard polymerase chain reaction (PCR) using specific primers, genome analysis involving short random primers, for example RAPD, may yield inconsistent results if crude plant DNA preparations are used as the template. When RNase A, a thermostable enzyme, was added to such reactions, highly repeatable banding patterns were obtained from crude plant DNA, thus speeding up analyses substantially.

Biotechnology↗
PubMed1994

Detection of HRX-FEL fusion transcripts in pre-pre-B-ALL with and without cytogenetic demonstration of t(4;11).

The t(4;11)(q21;q23) characterizes a distinct clinical entity of childhood and adult acute lymphoblastic leukemia (ALL) with a pre-pre-B-phenotype, monocytoid features, coexpression of CD15 and/or CDw65 and a dismal prognosis. The molecular correlate of the t(4;11) has been identified as a fusion transcript of HRX, a gene on 11q23 with homology to drosophila trithorax gene, and FEL, a serine-proline-rich gene on 4q21 of unknown function. The aim of the current study was to establish a reverse transcription-polymerase chain reaction (RT-PCR) approach for the rapid and sensitive detection of the HRX-FEL fusion transcript associated with the t(4;11). For this purpose, two groups of patients were studied: group A comprised cases with cytogenetically proven t(4;11) including three infant and four adult pre-pre-B-ALL, as well as the two cell lines RS4;11 and MV4;11. Group B consisted of ten adult pre-pre-B-ALL with the identical phenotype, but without cytogenetic confirmation of t(4;11). Using primers complementary to HRX and FEL cDNA sequences 300 to 500 bp 5' and 3' of published breakpoints, respectively, specific amplification products were obtained in all nine cases of group A and in nine of the ten cases of group B. Three different types of fusion transcripts were identified by sequence analysis with HRX breakpoints at nucleotides 4086 and 4218 and FEL breakpoints at nucleotides 1413, 1416, and 1458. These data indicate that RT-PCR allows the detection of HRX-FEL fusion transcripts in the vast majority of cytogenetically proven and immunophenotypically suspected t(4;11) ALL. Hence, this technique may allow identification of a further subset of high risk ALL and may also be useful for the monitoring of minimal residual disease in t(4;11) ALL.

Adult↗
PubMed1994

[Leukocyte transfusion as therapy of recurrent CML after allogenic bone marrow transplantation].

Eight patients with relapsed chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation (BMT) were treated with alpha-interferon and leukocyte transfusions of the bone marrow donor. Six patients responded with disappearance of leukemic cells (Ph1, BCR-ABL) and reestablished donor hemopoiesis. All six patients developed bone marrow hypoplasia and graft-versus-host disease (GvHD). Three of the six patients died of cerebral bleeding, infection and GvHD, respectively. The remaining three patients are alive and well at day 418, 677, 818 after leukocyte transfusions. Two patients relapsed with more advanced disease of CML after BMT and failed treatment. Donor leukocyte transfusions provide an effective therapy for patients with relapsed CML after BMT, but are associated with a high mortality due to bone marrow hypoplasia and GvHD.

Antigens, CD↗
PubMed1993

Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. The German CML Study Group.

In a randomized multicenter study the influence of hydroxyurea versus busulfan on the duration of the chronic phase and on survival of chronic myelogenous leukemia (CML) was determined. In addition cross resistance and adverse reactions of the drugs were analyzed. From July 1983 to January 1991, 441 CML patients were randomized to receive hydroxyurea or busulfan. Of these, 90.7% were Philadelphia positive; 25.7% were low, 38.2% intermediate, and 36.2% high risk patients according to Sokal's score. The median survival of the busulfan treated Philadelphia-positive patients is 45.4 months and of the hydroxyurea group 58.2 months (P = .008). The survival advantage for the hydroxyurea treated patients is recognized in all risk groups. Sixty four patients reached therapy resistance before blast crisis and were crossed over to the alternative drug. The 23 patients with primary hydroxyurea had a median survival of 5.6 years, the 41 patients with primary busulfan therapy a median survival of 2.7 years (P = .02). Adverse reactions were less frequent with hydroxyurea with no severe adverse effects (lung fibrosis, long lasting bone marrow aplasia). The analysis of white blood cell counts in the course of treatment showed lower counts in the hydroxyurea patients. We conclude that hydroxyurea is superior to busulfan in therapy of CML in chronic phase and should be used as first line therapy. Busulfan may have a role as secondary therapy after hydroxyurea resistance or intolerance.

Blast Crisis↗
PubMed1993

Interferon-alpha and donor buffy coat transfusions for treatment of relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation.

Eight patients with chronic myeloid leukemia relapse after allogeneic BMT were treated with IFN-alpha and buffy coat transfusions (BC) of the bone marrow donor. The antileukemic effect of this treatment was directly demonstrated in 4 patients by the disappearance of Philadelphia chromosome-positive metaphases or the loss of detectable BCR-ABL transcripts by polymerase chain reaction. In 2 patients in whom cytogenetic or polymerase chain reaction analysis was not performed, a change in hemopoietic chimerism with recurrence of donor-type hemopoiesis was demonstrated. Two patients, both treated in advanced stages of hematological relapse after BMT, did not respond. However, severe side effects of the treatment were observed: graft-versus-host disease (GVHD) occurred in 5 patients. Two of these patients progressed to severe chronic GVHD and 1 patient ultimately died of this complication. GVHD occurred in 5 of the 6 responding patients; one patient responded without developing clinical symptoms of GVHD. Six patients developed bone marrow hypoplasia after IFN/BC treatment, and pancytopenia occurred in 4 patients. None of these 4 patients recovered spontaneously and 2 patients died of complications of pancytopenia (cerebral bleeding, infection). Our results demonstrate that treatment of chronic myeloid leukemia relapse with IFN and BC transfusions is highly effective in patients with relapse in chronic phase. The occurrence of GVHD and pancytopenia, however, resulted in a high treatment-associated morbidity and mortality. Whereas a response to treatment was observed in 1 patient without GVHD, indicating that GVHD and a graft-versus-leukemia effect may be clinically separable, bone marrow hypoplasia occurred in all responding patients.

Adult↗
PubMed1993

The German CML study, comparison of busulfan vs. hydroxyurea vs. interferon alpha and establishment of prognostic score 1.

From July 1983 to January 1991 a total of 622 patients were randomized (585 eligible) to compare the effects of hydroxyurea, interferon alpha (IFN), and busulfan on the duration of chronic phase, and survival. Further goals included the determination of prognostic parameters. 598 CML patients were documented and 575 evaluable. The Ph-status was known for 547 patients. 89.4% of the patients were Ph-positive (+). 11% had additional chromosome aberrations. The median survival of Ph+ patients by now is 4.2 years, that of Ph-patients 1.4 years. Ph-negative patients are older, tend to have lower cell counts and, as a group are more ill at diagnosis. A survival difference of about one year is expected between busulfan and hydroxyurea treated patients. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, number of erythroblasts and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined which was superior to Sokal's score in the study population. 164 patients were randomized to receive IFN. In 54 patients (33%) IFN had to be terminated because of adverse effects, therapy resistance or other reasons. Clinically relevant neutralizing antibodies were detected in 9 cases. Most frequent adverse events were flu-like symptoms in 74%, gastrointestinal symptoms in 52%, and neurologic-psychiatric symptoms in 30% of patients. Reduction of the Ph-chromosome was observed in 13% of evaluable patients (10 of 75). In 4 patients complete cytogenetic remissions were observed, in three of these ongoing. Cytogenetic responders have a survival advantage. Interferon treated Philadelphia-negative CML patients have no survival disadvantage. The study is expected to allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.

Adult↗
PubMed1993

Influence of graft-versus-host disease on the eradication of minimal residual leukemia detected by polymerase chain reaction in chronic myeloid leukemia patients after bone marrow transplantation.

To evaluate the remission quality of Philadelphia chromosome (Ph)-positive, BCR/ABL-positive CML patients after allogeneic bone marrow transplantation (BMT) we used the polymerase chain reaction (PCR) to detect BCR-ABL specific RNA in addition to Southern blotting, cytogenetic, and hematological investigation. Fifty-five bone marrow samples of 27 patients in clinical remission were studied by PCR, 0.5 to 99 months (median 8 months) after BMT. The median clinical follow-up of this cohort of patients is 24 months (1-109) after BMT. BCR-ABL transcripts could be detected in 16 out of 27 patients (59%). Risk factors for minimal residual leukemia (MRD) as defined by PCR were the kind of graft-versus-host disease (GvHD) prophylaxis (patients with T-cell-depleted grafts had a higher rate of MRD in comparison to patients treated with methotrexate/cyclosporin A) and the presence or absence of GvHD after BMT (patients without GvHD had a higher incidence of MRD than patients with GvHD). Moreover, the detection of minimal residual leukemia had prognostic significance. Out of 16 patients with minimal residual leukemia as detected by PCR, four patients relapsed clinically and two further cases relapsed cytogenetically. In contrast none of the patients lacking evidence of minimal residual leukemia relapsed. Serial PCR analysis may prove helpful in deciding about further therapeutic interventions (e.g. interferon therapy or adoptive immunotherapy) before leukaemic relapse becomes manifest after BMT.

Adult↗
PubMed1992

The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features.

Translocation (6;9)(p23;q34) is a cytogenetic aberration that can be found in specific subtypes of both acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This translocation is associated with an unfavourable prognosis. Recently, the genes involved in the t(6;9) were isolated and characterized. Breakpoints in both the dek gene on chromosome 6 and the can gene on chromosome 9 appear to occur in defined regions, which allows us to diagnose this type of leukemia at the molecular level. Moreover, because of the translocation a chimeric dek-can mRNA is formed which, as we show here, is an additional target for diagnosis via cDNA-preparation and the polymerase chain reaction (PCR). We studied 17 patients whose blood cells and/or bone marrow cells showed a t(6;9) with karyotypic analysis. Fourteen patients suffered from AML, one patient had a refractory anemia with excess of blasts in transformation (RAEBt), one patient had an acute myelofibrosis (AMF), and one patient a chronic myeloid leukemia (CML). In nine cases studies at the DNA and RNA levels were possible while in seven cases only the DNA could be analyzed. In one case only RNA was available. Conventional Southern blot analysis showed the presence of rearrangements of both the dek gene and the can gene. In both genes, breakpoints cluster in one intron in the patients investigated. The presence of a consistent chimeric dek-can product after cDNA preparation followed by the PCR was demonstrated. We conclude from our data that the t(6;9) is found in myeloproliferative disorders with typical clinical characteristics. This translocation results in highly consistent abnormalities at the molecular level.

Adolescent↗
PubMed1992

Chronic myelogenous leukemia: recent developments in prognostic evaluation and chemotherapy. The German CML Study Group.

Recent developments in CML research are illustrated by the results of one large randomized multicenter study carried out by the German CML Study Group. From July 1983 to January 1991, a total of 703 CML patients were recruited; 624 patients were randomized to compare hydroxyurea and interferon alpha (IFN) with busulfan. The median survival of Ph+ patients by now is 3.95 years, that of Ph- patients 1.1 years. Some difference in survival is recognizable between the treatment arms, but this is not yet significant. Fewer adverse effects are being observed in the hydroxyurea group. Ph-negative patients tend to have lower white blood cell and platelet counts. Patients (164) were randomized to receive IFN. In 50 patients (30%) IFN had to be terminated because of adverse effects, therapy resistance, or other reasons. Reduction of the Ph-chromosome was observed in 20% of evaluable patients. In 3 patients complete cytogenetic remissions were observed. Clinically relevant neutralizing antibodies were detected in 9 cases. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, erythroblasts, and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined and compared to Sokal's score. It is expected that the study results will allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.

Bone Marrow Transplantation↗
PubMed1991

Detection of chimeric BCR-ABL genes in acute lymphoblastic leukaemia by the polymerase chain reaction.

Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL) is most common in adults and is associated with poor prognosis. Since karyotypic identification of the Philadelphia translocation has been hampered by technical difficulties, we used the polymerase chain reaction (PCR) to look for the BCR-ABL rearrangement in stored samples from a selected group of 314 German ALL patients. BCR-ABL transcripts were found in 77 of 179 adults and were restricted to those with B-precursor leukaemias. 55% of adult common ALL patients had BCR-ABL and its presence correlated with poor overall survival and remission duration. Of 135 children with common ALL, 5 (6%) primary cases and 8 (17%) with recurrent neoplasias were PCR-positive. We recommend prospective evaluation of BCR-ABL analysis with PCR in patients with a B-precursor leukaemia.

Adult↗
PubMed1991

[Multicenter prospective controlled study of therapy of chronic myeloid leukemia. Comparison of busulfan, hydroxyurea and interferon alpha (April 1990 status)].

In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon alpha instead of busulfan prolongs the chronic phase of Philadelphia-positive CML. Additional goals are the examination, whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By September 5, 1990, 593 CML-patients had been randomized, 221 for busulfan, 228 for hydroxyurea and 144 for interferon alpha. The average age is about 51 years. By April 30, 1990, 106 patients had reached the end of the chronic phase, 126 had died. The median survival of Philadelphia-positive patients was 3.95 years, that of all patients 3.75 years. The median observation time of all patients was 1.34 years (mean 1.60 years). At present, no significant difference in survival is recognizable between the three treatment arms, although fewer adverse effects have been observed in the hydroxyurea arm.

Busulfan↗
PubMed1990

Establishment and characterization of a new Epstein-Barr virus transformed cell line from a human B cell lymphoma.

We have established a new cell line from a patient with centrocytic B cell lymphoma. Highly purified peripheral blood B cells from patient DUL (WBC counts 158,000/microliters) were infected in vitro with Epstein-Barr virus (EBV), and CD20+ B cells were cloned into 96 well culture plates with the aid of a cell sorter autoclone device. As shown by GTG-banding and Southern blot analysis, out-growing EBV-positive clones had the same chromosomal abnormalities and identical monoclonal IgH gene rearrangement as the original EBV-genome-negative leukemic B cell clone. Surface marker analysis with a panel of monoclonal antibodies revealed identical patterns on EBV-negative and -positive clones, with the exception of PCA1 (reactive with plasma cells) which was negative on freshly explanted leukemic B cells but positive on EBV-converted clones.

Antigens, Surface↗
PubMed1989

A phase I/II study of recombinant interferon alpha 2a and hydroxyurea for chronic myelocytic leukemia.

Nine previously untreated patients with Philadelphia chromosome-positive chronic myelocytic leukemia (CML) were treated with recombinant interferon alpha 2a (rIFN-alpha 2a) and hydroxyurea. Patients received 6 X 10(6) U rIFN-alpha 2a daily for the first week and 3 X 10(6) U rIFN-alpha 2a daily for the second week. As maintenance treatment starting on day 15, patients received 3 X 10(6) U rIFN-alpha 2a 3 times a week. Simultaneously, hydroxyurea was given, starting at a dose of 40 mg/kg on day one. The maintenance dosage was adjusted to the white blood cell count. Two patients responded with complete hematological remissions but without cytogenetic and molecular-genetic improvements. Seven patients responded with partial hematological remissions. Response to therapy was rapid; normal white blood cell counts were reached after a median of 12 days. The doses of rIFN-alpha 2a and hydroxyurea needed to keep the leucocyte count in the normal range were low (3 X 10(6) U rIFN-alpha 2a 3 times per week, 0.5-1.5 g hydroxyurea/day). Acute toxicity of the combination therapy consisted of fever (9 of 9 patients), flulike symptoms (7 of 9 patients), pruritus and/or rash (3 of 9 patients) and evidence of a tumor cell lysis syndrome (1 of 9 patients). The side effects were not dose-limiting. Combination therapy with rIFN-alpha 2a and hydroxyurea for CML is well tolerated and allows quick and effective hematological control of the disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Evaluation of remission state in chronic myeloid leukemia patients after bone marrow transplantation using cytogenetic and molecular genetic approaches.

The remission state of 13 Philadelphia positive chronic myeloid leukemia patients was studied after bone marrow transplantation (BMT) by cytogenetic and Southern blot analysis of the breakpoint cluster region (BCR) gene. Eight of 13 patients showed neither clinical nor genetic evidence of residual disease. In two patients hematological relapse was confirmed by cytogenetic and molecular analysis. Evidence for residual leukemic cells in otherwise complete remission was obtained genetically in three patients. One of the latter cases revealed BCR rearrangement despite negative cytogenetic findings, while in another patient cytogenetic relapse was observed without demonstrable rearrangement within the major BCR. Our results may indicate that cytogenetic and molecular genetic methods complement rather than replace each other for the detection of residual CML cells after BMT.

Adolescent↗
PubMed1988

Blast crisis of Philadelphia chromosome-positive chronic myelocytic leukemia (CML). Treatment results of 69 patients.

We have studied the clinical courses of 69 patients with blastic crises of Philadelphia chromosome positive CML to identify parameters that were associated with an increased response rate or survival. Cytogenetic analysis at the time of blastic transformation revealed additional chromosome changes in 70% of the patients tested. Bone marrow fibrosis was detected in 58% of evaluable patients. Lymphoblastic transformation was seen in 28% of the patients tested with cell surface marker analysis. The value of 5'-nucleotidase as a marker for distinguishing lymphoid from non-lymphoid blast crisis was confirmed. Of 57 evaluable patients, 23 (40%) responded to therapy (CR/PR longer than 14 days). Median survival was 75 days. Longer survival was related to the following factors: Ph1-chromosome as the only detectable cytogenetic abnormality; lymphoblastic transformation; no bone marrow fibrosis; high percentage of blasts and promyelocytes in the bone marrow, and response to therapy. No prognostic significance was associated with age, sex, Tdt, LDH, spleen size, duration of the chronic phase of the disease, white blood cell count, Hb, platelet count and percentages of basophils, eosinophils, erythroblasts and blasts and promyelocytes in the peripheral blood. These data confirm the poor prognosis of patients with blastic crisis of CML treated by conventional chemotherapy.

Adult↗