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Annals of Hematology | 1989

Polycythemia vera. A clinical study of 141 patients

B. Anger; U. Haug; R. Seidler; H. Heimpel

SummaryThe clinical course of 141 unselected patients (64 m, 77 f, median age 59) with polycythemia vera (PV), treated during the period 1967 to 1986 was analyzed to study prognostic factors and the correlation between treatment strategies and complication rates. Therapy was performed according to a prospectively defined treatment protocol. Primary control of the disease was achieved by phlebotomy. Marrow suppression by radioactive phosphorus or low dose busulphan was used only as a second-line therapy or to lower high platelet counts. The clinical course of the patients was characterized by a low rate of acute leukemia (4%) and a high rate of thromboembolic complications (40%). Myelofibrosis developed in 17 patients (12%). Median survival of the patients was 9.4 years. The prognostic influence of several parameters at the time of diagnosis was tested: age, sex, spleen size, percentage of blood blasts + promyelocytes, leucocyte count, platelet count, hemoglobin, hematocrit, reticulocyte count and the values of the lactatdehydrogenase (LDH) and the alkaline neutrophil phosphatase (ANP) all had no significant influence on the length of survival. The prognosis of PV patients with atypical disease presentation at diagnosis was not different from patients with typical disease.


Annals of Hematology | 1989

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

B. Anger; Franz Porzsolt; R. Leichtle; Barbara Heinze; Claus R. Bartram; H. Heimpel

SummaryNine 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 6×106 U rIFN-alpha 2a daily for the first week and 3×106 U rIFN-alpha 2a daily for the second week. As maintenance treatment starting on day 15, patients received 3×106 U rIFN-alpha 2 a 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 (3×106 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.


Annals of Hematology | 1986

Deficient IFNα production in hairy cell leukemia

F. Porzsolt; R. Janik; G. Heil; O. Brudler; Ar. Raghavachar; S. Scholz; U. Papendick; H. Heimpel

SummarySince the application of low doses of IFN-alpha is necessary to maintain remissions in Hairy Cell Leukemia (HCL) it is of interest whether peripheral blood mononuclear cells (MNC) of HCL patients can be induced in vitro to produce IFN-alpha. 9 patients suffering from advanced HCL were included in the study. The diagnoses were confirmed by characteristic findings in peripheral blood and bone marrow biopsies. For IFN treatment we initially used natural IFN-alpha (Bioferon) and switched later to recombinant IFN-alpha2 (Boehringer). MNC of 5 patients before IFN therapy and of 6 patients during IFN therapy (2–47 weeks) were induced by phythemagglutinin (PHA), Corynebacterium parvum (C.p.), and sendai virus (SV). PHA is known to induce IFN-gamma. Both, C.p. and SV induced IFN-alpha but no IFN-gamma in MNC of healthy controls and of IFN treated breast cancer patients. In HCL patients normal antiviral activities could be induced by PHA. Zero or only low antiviral activities could be induced in MNC from 9 patients tested on 22 occasions. It is concluded that MNC from patients with advanced HCL can be induced to produce IFN-gamma but no IFN-alpha. Since IFN-alpha but not IFN-gamma is produced by monocytes it is likely that reduced numbers of monocytes which were found in our HCL patients before and during IFN treatment account for the described deficiency of IFN-alpha production.


Annals of Hematology | 1991

Spontaneous interferon-α antibodies in a patient with pure red cell aplasia and recurrent cutaneous carcinomas

Otto Prümmer; Norbert Frickhofen; W. Digel; H. Heimpel; Franz Porzsolt

SummaryHigh-titered spontaneous interferon (IFN) antibodies were detected in a patient with pure red cell aplasia (PRCA), a benign mediastinal tumor, and recurrent cutaneous carcinomas. The circulating IFN antibodies reacted broadly with various human IFN-α subtypes (20–140×103 neutralizing units/ml serum) but not with IFN-β or IFN-γ, and they neutralized the antiviral activity of the patients endogenous IFN-α. The IFN-αbinding activity was restricted to the IgG1 subclass in a nonmonoclonal manner. Whereas the PRCA repeatedly responded to immunosuppression with high-dose cyclosporin A (CSA) and CSA plus plasmapheresis, IFN antibody production continued during treatment with cyclophosphamide and CSA. Serological analysis revealed past infection with parvovirus B19 and persistent B19 IgM titers. Antibody-mediated impairment of the IFN-α system might have favored the development of both PRCA and the various cutaneous carcinomas in this patient.


Annals of Hematology | 1989

Daunomycin, cytosin-arabinoside and VP-16 (DAV) for myeloid blast crisis of CML

B. Anger; H. Heimpel

SummaryNine patients with myeloid blast crisis of Philadelphia chromosome-positive chronic myelocytic leukemia received 1–3 courses of intensive induction chemotherapy with DAT (daunomycin, cytosin-arabinoside and 6-thioguanin) or DAV (daunomycin, cytosin-arabinoside and VP-16). Eight patients responded with clearing of blasts from peripheral blood giving a response rate of 89%. However, bone marrow aplasia with less than 5% blasts was seen in only 2 patients. These 2 patients subsequently received an allogeneic bone marrow transplant and achieved complete remissions of 3 and 6 month duration. All patients died due to progression of blast crisis. Median survival of the group was 164 days. These results were compared to a historical control group of 31 patients with myeloid blast crisis treated with vincristine and prednisone. Despite a significantly better response rate with DAV or DAT (8 of 9 versus 9 of 31, p=0.01) survival was not significantly different than that of the control group.


Annals of Hematology | 1989

Cryocrystalglobulinemia: pH-dependent precipitation of a monoclonal IgG-kappa-immunoglobulin

A. Schoengen; T. Schreiner; V. Anselstetter; Thomas Binder; J. Galle; L. Weber; H. Heimpel

SummaryCryoglobulinemia is seen in a minority of patients with plasma cell dyscrasias and can be of clinical relevance if intravascular gelling or precipitate formation occurs at low temperatures. We observed a patient suffering from IgG-kappa multiple myeloma which was complicated by instability of the immunoglobulin forming crystalline precipitates at low pH and low temperature. Short exposure to extreme cooling initiated an unusual course terminating in disseminated vascular occlusion and fatal outcome which was connected with an adverse effect of blood exchange. Crystal formation was noticed in anticoagulated blood samples even at 37°C. In vitro studies showed a critical pH dependency of solubility of the immunoglobulin close to the physiological pH of the blood. These observations suggest that the fatal outcome was due to a vicious circle of ischemia, metabolic acidosis and intravascular precipitations, initiated not only by low acral temperatures but by cold-induced ischemic tissue acidosis as well. Serum of patients with monoclonal gammopathy and cryoglobulinemia should be tested for pH dependent immunoglobulin insolubility.


Annals of Hematology | 1986

Biallelic heavy chain immunoglobulin gene rearrangement in acute nonlymphocytic leukemia

Claus R. Bartram; Aruna Raghavachar; H. Heimpel

SummaryAcute nonlymphocytic leukemia (ANLL) was diagnosed in 18 patients based on morphological, cytochemical and immunological criteria. Leukemic cells of these cases were subjected to Southern blot analysis and subsequent hybridization to heavy chain immunoglobulin and T-cell-receptor gene probes. A rearrangement within the immunoglobulin joining region was detected in 2 cases, while the T-cell-receptor β-chain gene was in germline configuration in all samples investigated. These data confirm recent reports indicating that immunoglobulin heavy chain gene rearrangements are not restricted to B-lineage neoplasms.


Annals of Hematology | 1986

Treatment results of nine patients with Burkitt's lymphoma.

B. Anger; Donald Bunjes; Felix Carbonell; E. Kurrle; H. Heimpel

SummaryFrom 6/79 until 2/86, 9 patients (median age 39) with Burkitts lymphoma were treated. Stage D disease was seen in 7 cases, stage C in two and stage A in one. The main symptom was abdominal pain or a rapidly progressing abdominal tumor. Three patients had bone marrow involvement and two had a Burkitts leukemia. Three had typical chromosomal aberrations. Therapy consisted of a variety of chemotherapy regimens plus additional radiotherapy and/or bulk surgery. Two patients achieved complete remissions (of 6 and 20+ months duration), and 4 partial remissions were obtained. The remaining patients had either progressive, drug resistant disease or died early. One patient is currently alive and in complete remission at 20+ months. A second patient is alive at 20+ months in partial remission with traces of IgM-paraprotein still detectable. The main causes of death were tumor-lysis syndrom (4 patients) and therapy related sepsis with progressive tumor (3 patients). This poor outcome is probably due to a high proportion of high-risk patients and suboptimal therapy for this rapidly proliferating tumor.


Annals of Hematology | 1987

Blood group change in a patient with blastic transformation of a myelodysplastic syndrome

N. Xiros; H. Northoff; B. Anger; W. Heit; H. Heimpel

SummaryLoss of certain red blood cell antigens has been described in patients with acute myelocytic leukemia (AML). This paper describes the loss of blood group A antigen in a patient with AML. The acute leukemia in this patient was preceded by a myelodysplastic syndrome for several months. At the time of diagnosis the patients red cells showed the 0 Rh(D)+ phenotype. After induction of complete remission with two courses of Daunorubicin, Cytosin-arabinosid, and Etoposid his blood group reverted to A2. Serological studies including saliva analysis revealed that the original blood group was very likely A.


Infection | 1982

Verträglichkeit eines neuen, intravenös applizierbaren Immunglobulin-präparats und sein Effekt auf die Serumglobulinkonzentration

W. Hansi; H. Heimpel; S. Barandun; O. Lutz

In a controlled prospective study, 212 patients were evaluated in 13 different hospitals with regard to the clinical tolerance of a new gammaglobulin preparation which can be administered intravenously. The age of the patients ranged from one day to 83 years. Patients with a primary or secondary immunoglobulin deficiency and patients with normal serum immunoglobulin concentrations were included in the study. In 811 infusions a total of 7128 g gammaglobulin were applied; the maximum dosage was 30 g/day. We saw a transient, recurrent and spontaneously reversible fever reaction in one patient with long-term substitution because of a primary immunodeficiency syndrome. Otherwise, no serious side-effects were seen in clinical or laboratory controls. Patients controlled for their serum gammaglobulin concentrations before and after the infusions showed a significant rise of 112.5 mg/100 ml for each infusion of 3 g gammaglobulin. The new preparation also showed an estimated half-life of 23 days, thus making it a good possibility for long-term substitution in immunodeficient patients.ZusammenfassungIm Rahmen einer kontrollierten prospektiven multizentrischen Studie wurde an 13 verschiedenen Kliniken bei 212 Patienten im Alter von einem Tag bis 83 Jahre ein neues intravenös applizierbares Immunglobulinpräparat auf seine Verträglichkeit untersucht. Der Einsatz erfolgte bei Patienten mit primärem und sekundärem Antikörpermangelsyndrom, wie auch bei solchen mit normalen Immunglobulinkonzentrationen im Serum. Insgesamt wurden bei 811 Behandlungen 7128 g Immunglobulin mit einer maximalen Dosierung von 30 g pro Tag infundiert. Außer einer spontan reversiblen flüchtigen Temperaturerhöhung, die bei einer Patientin mit Antikörpermangelsyndrom im Rahmen einer Dauersubstitution wiederholt auftrat, wurden weder klinisch noch laborchemisch wesentliche Nebenwirkungen registriert. Bei einem Teil der Patienten wurden Immunglobulinkonzentrationsmessungen vor und nach Infusion durchgeführt. Dadurch konnte ein signifikanter Anstieg der Konzentration um 112,5 mg/100 ml und übertragene Einheit Immunglobulin von je 3 g beobachtet werden. Bei einer geschätzten Halbwertszeit von 23 Tagen ergibt sich mit dem vorliegenden Präparat eine gute Möglichkeit zur Dauersubstitution immundefizienter Patienten.SummaryIn a controlled prospective study, 212 patients were evaluated in 13 different hospitals with regard to the clinical tolerance of a new gammaglobulin preparation which can be administered intravenously. The age of the patients ranged from one day to 83 years. Patients with a primary or secondary immunoglobulin deficiency and patients with normal serum immunoglobulin concentrations were included in the study. In 811 infusions a total of 7128 g gammaglobulin were applied; the maximum dosage was 30 g/day. We saw a transient, recurrent and spontaneously reversible fever reaction in one patient with long-term substitution because of a primary immunodeficiency syndrome. Otherwise, no serious side-effects were seen in clinical or laboratory controls. Patients controlled for their serum gammaglobulin concentrations before and after the infusions showed a significant rise of 112.5 mg/100 ml for each infusion of 3 g gammaglobulin. The new preparation also showed an estimated half-life of 23 days, thus making it a good possibility for long-term substitution in immunodeficient patients.

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A. Ganser

Goethe University Frankfurt

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