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Biomedical subjects

G Henze

Publications and source records attributed to G Henze.

At least 109 records · Page 6Linked to original sources
PubMed1994

Low-grade non-Hodgkin's lymphoma after high-grade non-Hodgkin's lymphoma in a child with ataxia telangiectasia.

BACKGROUND: Non-Hodgkin lymphomas (NHL) account for approximately 50% of neoplasms in patients with ataxia telangiectasia (AT). Prognosis is poor. Published data regarding the treatment of NHL in patients with AT suggested that these children respond poorly to therapy. The authors report on an infant with AT with mediastinal high-grade T-NHL who remained in continuous complete remission after chemotherapy. Diagnosis of AT was established after tumor diagnosis. METHODS AND RESULTS: The 7-month-old boy was treated according to the acute lymphoblastic leukemia-Berlin, Frankfurt, Münster 86 protocol. The therapeutic response was prompt, but therapy had to be stopped because of severe side effects. Surprisingly, the boy remained in a stable complete remission for 3 1/2 years. Then tumors in both kidneys occurred and the child died a few months later. Postmortem examination demonstrated large tumors in both kidneys caused by a low-grade malignant lymphoma of B-cell lineage. CONCLUSION: Congenital immune deficiency should be ruled out at diagnosis of rare malignancies in respect to age. NHL in patients with AT can be cured, but poor tolerance to chemotherapy has to be considered. Patients whose disease has been cured may be at high risk for development of a second independent malignancy.

Ataxia Telangiectasia↗
PubMed1994

Detection of allelic loss within the beta 1-interferon gene in childhood acute lymphoblastic leukemia using differential PCR.

Deletion of the short arm of chromosome 9p involving the beta 1-interferon (IFN) gene has been implicated in the process of malignant transformation in lymphomas and acute lymphoblastic leukemias. Since cytogenetic analysis is frequently unsuccessful in clinical samples, we used a recently described differential PCR technique to detect losses within the beta 1-IFN gene in 86 acute leukemias. Using differential PCR, no beta 1-IFN deletion was detected in 44 acute myeloid leukemia (AML) and eight control samples. However, five of 42 acute lymphoblastic leukemia (ALL) probes (12%) exhibited loss of the beta 1-IFN gene (three common ALL, two T-ALL). Cytogenetic analysis was performed independently in three of these five cases and revealed abnormalities of chromosome 9p in two samples. Two of five T-ALL cases exhibited a loss within the beta 1-IFN gene, compared with 3/29 c-ALLs, suggesting a predominance of IFN gene loss in T-ALLs. These data indicate that PCR can be used for rapid detection of gene dosage phenomena in clinical leukemia samples.

Acute Disease↗
PubMed1994

Life-threatening infectious mononucleosis: is it correlated with virus-induced T cell proliferation?

Infectious mononucleosis is a well-established clinical entity characterized by the proliferation of B lymphocytes that are infected with Epstein-Barr virus (EBV). These lymphocytes give rise to an increase in specifically reacting cytotoxic T cells, which leads to self-limitation of the lympho-proliferative process. We describe the case of a 1-year-old boy who developed life-threatening EBV infection in association with liver failure, depletion of bone marrow, and severe encephalitis. The fact that clinical cure was achieved when acyclovir (50 mg/[kg.d]) and prednisolone (1 mg/[kg.d]) were administered indicates a correlation between antiviral therapy and clinical improvement. Hypogammaglobulinemia--which had not been present at the onset of disease--persisted after clinical recovery. During the acute phase of the illness, the patient's blood lymphocytes were predominantly T cells, most of which contained the EBV genome, as shown by in situ hybridization; some of these cells stained positive for EBV-specific latent membrane protein. Examination of peripheral blood mononuclear cells in vitro revealed an exceedingly high histocompatibility antigen-unrestricted cytotoxicity against the K562 cell line, which is normally not an immunogenic target of cytotoxic cells in patients infected with EBV. This anomalous natural killer cell-like T cell function suggests that EBV infection of T cells might cause auto-aggressive activity, which was probably responsible for the severity of the infection in our patient.

Cell Division↗
PubMed1994

Low-dose natural interleukin-2 and recombinant interferon-gamma following autologous bone marrow grafts in pediatric patients with high-risk acute leukemia.

Twenty-two patients with high risk hematologic malignancies (13 c-ALL, two B-ALL/NHL, four T-ALL, two AML M2, one pre-pre B-ALL) entered a phase I/II trial with cyclic administration of low dose natural interleukin-2/recombinant interferon-gamma (nIL-2/rIFN-gamma) following autologous bone marrow transplantation (ABMT), in order to induce a cytotoxic antileukemic effect. Eighteen patients subsequently relapsed, corresponding to a Kaplan-Meier estimate of disease-free survival (DFS) of 18%. Compared with a historical group of autologous bone marrow recipients who have not received immunotherapy, there is no significant difference according to DFS. Immunophenotyping of peripheral lymphocytes at the onset and end of therapy cycles revealed the most significant mean increase among the NK cell population (262/microliters +/- 51 vs. 354/microliters +/- 36, p = 0.004). However, even CD3 positive T cells rose significantly (591/microliters vs. 689/microliters, p = 0.04). In vitro NK cell activity tested against the NK sensitive myeloid leukemic cell line K562, and LAK cell activity tested against the LAK sensitive Burkitt lymphoma cell line Raji, was only low. An additional in vitro stimulus with nIL2, however, led to a therapy-dependent increase of cytotoxicity which was significant against Raji cells (25% +/- 4 vs. 41% +/- 5, p = 0.0124) indicating that low dose nIL2/rIFN-gamma enhances precursors of potentially cytotoxic cells in vivo.

Acute Disease↗
PubMed1993

Positional stability of sources during low-dose-rate brachytherapy for cervical carcinoma.

PURPOSE: A presumed advantage of high dose rate gynecologic applicators is the fixed relationship maintained between applicator and anatomic structures during the brief exposure. However, it has never been demonstrated that movement of applicators during low dose rate procedures is significant. Therefore, we assessed the magnitude of changes in positioning and attendant alterations in dosimetry which occur during LDR applications. METHODS AND MATERIALS: Fifteen consecutive cervix cancer patients who were treated with combined external beam and brachytherapy (Fletcher-Suit-Delclos applicator), agreed to have orthogonal pelvic radiographs prior to after-loading and following removal of Cesium-137 sources. RESULTS: The median duration of the insertion was 56.5 hours. The average shift was 3.0 mm. Detailed analysis of source movement showed the following changes in median dose (external plus implant): point A, 1.4%; point B, 1.7%; point P, 0.9%; bladder point, 1.9%; rectal point, 2.6%. CONCLUSION: The geometric relationships between the intracavitary gynecologic applicator and the target tissue as well as the critical structures can be adequately maintained throughout the course of a low dose rate implant. Source movement does not result in significant dose changes in terms of decreased cure rates or added complications. Thus, while rationale for high dose rate applicators continues to be proposed, maintenance of a fixed geometric relationship should not be an impetus for the selection of high dose rate intracavitary applicators when treating cervical tumors.

Adult↗
PubMed1993

Superior prognosis in combined compared to isolated bone marrow relapses in salvage therapy of childhood acute lymphoblastic leukemia.

Three hundred twenty-six children with bone marrow (BM) relapse of non-B acute lymphoblastic leukemia (ALL) were stratified according to the time of relapse in three consecutive multicenter trials--ALL-REZ BFM 83, 85, and 87. Employing an intensive polychemotherapy regimen, extramedullary involvement appeared to be predictive of superior outcome in both strata as well as in the whole group (probability of 7-year event-free survival (EFS) 42% in combined vs. 15% in isolated BM relapse, P = 0.015). Children with combined BM relapse occurring later than 6 months after completion of front-line therapy reached EFS estimates of 60%. We conclude that results of conventional polychemotherapy with BFM relapse protocols are equivalent to those achieved by bone marrow transplantation in children with late combined BM relapse.

Adolescent↗
PubMed1993

Diminished cord blood lymphocyte L-selectin expression in neonatal bacterial infection.

L-Selectin, a leukocyte surface glycoprotein involved in white blood cell extravasation, is rapidly down-regulated after leukocyte activation. We prospectively determined lymphocyte L-selectin expression in freshly obtained cord blood samples of 98 neonates (gestational age 25-42 weeks). In eight infants with bacterial infection, the mean percentage of L-selectin(high) lymphocytes was 32.5% (SD 20.1%), compared to 60.1% (SD 18.7%) in the control group (P < 0.01). A percentage of L-selectin(high) lymphocytes of less than 42% had a sensitivity of 75% and a specificity of 82% in identifying infected newborns. Cord blood lymphocyte L-selectin expression was independent of gestational age, birth weight, umbilical artery pH, hematocrit, white blood cell count, absolute neutrophil count, C-reactive protein level, or maternal fever before delivery while there was a weak correlation with the newborn's immature/total ratio and platelet count. To our knowledge, this is the first report demonstrating downregulation of human lymphocyte L-selectin expression following activation of the immune system in vivo.

Cell Adhesion Molecules↗
PubMed1993

Randomized comparison of 36-hour intermediate-dose versus 4-hour high-dose methotrexate infusions for remission induction in relapsed childhood acute lymphoblastic leukemia.

PURPOSE: Pharmacokinetics, toxicity, and therapeutic efficacy of two different methotrexate (MTX) infusions for remission induction of relapsed childhood acute lymphoblastic leukemia (ALL) were investigated in a randomized multicenter trial. PATIENTS AND METHODS: Sixty patients with early bone marrow relapse received a polychemotherapy induction protocol starting with either 12 g/m2 MTX as a 4-hour infusion (high-dose [HDM]) or 1 g/m2 as a 36-hour infusion (intermediate-dose [IDM]). In HDM, leucovorin (LCV) was administered orally (12 times, 15 mg/m2 every 6 hours), beginning at hour 24. In IDM, only two doses were administered at hours 48 and 54. RESULTS: Median serum MTX concentrations during infusion were 716 mumol/L in HDM and 7.2 mumol/L in IDM. In HDM, MTX serum levels at hour 24 (median, 2.8 mumol/L) were significantly less than steady-state levels of IDM. Concentrations greater than 1 mumol/L were maintained for 36 hours with HDM and 45 hours with IDM. General tolerance to treatment was better in the HDM group. Mucosal lesions occurred significantly more often and were more severe after IDM treatment. A median treatment delay of 3 days was required in the IDM group but not in the HDM group. At day 15, complete remission (CR) was documented in 45% of IDM- and 48% of HDM-treated patients. Persistent blasts (> 5%) appeared more frequently in HDM than in IDM (35% v 19% of patients; P = NS). After completion of induction therapy, 28 of 30 patients in each group achieved CR. CONCLUSION: Both regimens produced the same remission rates. The tendency to better antileukemic activity of IDM was accompanied by more severe side effects as a consequence of long-lasting cytotoxic MTX levels. Hence, long-term infusion of IDM followed by low-dose LCV is an effective treatment for recurrent ALL.

Adolescent↗
PubMed1993

Partial trisomy 1q, an uncommon chromosomal aberration in erythroleukemia.

A 2 years 4 months old boy with erythroleukemia (FAB-M6) and Down's syndrome is described. Chromosome analysis of bone marrow leukemic blasts revealed apart from the trisomy 21 a partial trisomy of the long arm of chromosome 1:1q23-->1qter in all cells and trisomy 8 mosaicism. To the best of our knowledge this is the first time that a partial trisomy of chromosome 1 in association with erythroleukemia has been described. Previous reports of other hematologic malignancies with aberrations of chromosome 1 indicate that the breakpoint 1q23 is nonrandom and that trisomies of chromosome 1 plays a crucial role in the course of development of hematologic malignancies. This could probably also be true for erythroleukemias.

Child, Preschool↗
PubMed1993

Fractionated total body irradiation and high-dose VP-16 with purged autologous bone marrow rescue for children with high risk relapsed acute lymphoblastic leukemia.

Twenty-two children with ALL in high risk second (n = 13), third or subsequent complete remission (n = 9) were treated with high-dose VP-16 60 mg/kg and fractionated total body irradiation (fTBI) 12 Gy, 2 x 2 Gy daily followed by autologous BM rescue. Prior to transplantation all patients had been treated according to intensive German BFM front-line or BFM relapse protocols. In all cases the marrow was purged using monoclonal antibodies attached to magnetic microspheres. All patients engrafted. There was no severe toxicity related to the pre-transplant high-dose chemoradiotherapy. Two patients died in the early course of transplantation from infections (Legionella and Aspergillus). Sixteen patients relapsed within 259 days (median 109 days); 13 died from leukemia. Four patients are alive in CR at a median of 1328 days with a Karnofsky score of 100%. The Kaplan-Meier estimation shows a probability of event-free survival (EFS) of 18% and a probability of relapse of 80%. Considering the otherwise poor prognosis of these children the results are acceptable although the high relapse rate is still disappointing. We conclude that high-dose VP-16 and fTBI combined with ABMT is a curative treatment for some children and should therefore be considered for those who lack an HLA-identical sibling donor. In future better therapy concepts are needed either in pre-transplant conditioning regimens or in post-transplant treatment schedules.

Adolescent↗
PubMed1992

Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group.

In 1981 the BFM group introduced a new treatment strategy for B-cell acute lymphoblastic leukemia (B-ALL). A cytoreductive prephase (prednisone/cyclophosphamide) was followed by eight 5-day courses of chemotherapy. Fractionated cyclophosphamide, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), and MTX intrathecally were administered at each course and cytosine arabinoside (ARA-C)/teniposide (VM-26) was given alternately with doxorubicin. In study ALL-BFM-83, central nervous system (CNS) chemotherapy was intensified by adding dexamethasone, while MTX/ARA-C was administered intraventricularly. Therapy duration was reduced to six courses. In study ALL-BFM-86, MTX 0.5 g/m2 was replaced by high-dose (HD) MTX, 5 g/m2 (24-hour infusion), and MTX/ARA-C/prednisolone intrathecal therapy was introduced. Doses of ARA-C and VM-26 were increased and fractionated, cyclophosphamide was partially replaced by ifosfamide, and vincristine was added. CNS irradiation was 24 Gy for prevention and 30 Gy for overt disease in studies ALL-BFM-81 and -83, but was omitted in ALL-BFM-86. In all, 87 patients were enrolled, 22 (8 CNS-positive) in study All-BFM-81, 24 (7 CNS-positive) in study ALL-BFM-83, and 41 (0 CNS-positive) in study ALL-BFM-86. The estimated 5-year duration of event-free survival (EFS) was 43% in study ALL-BFM 81, 50% in study ALL-BFM-83, and 78% in study ALL-BFM-86 (minimal follow-up, 25 months). Nineteen of 24 relapses occurred while on therapy or shortly thereafter. In study ALL-BFM 81, the CNS was the most frequent site of failure. In ALL-BFM-83, there were no isolated CNS relapses, but more bone marrow (BM) relapses occurred. In ALL-BFM-86, localized manifestations were the predominant site of failure, no isolated BM relapses occurred, and only one CNS relapse was diagnosed. No single parameter exerted a consistent influence on outcome with one exception. The presence of residual disease after the first two courses was correlated with an increased risk of therapy failure. We conclude that an intensive, short-pulse therapy delivered within a 4-month period is highly effective in the treatment of B-ALL. In addition to fractionated cyclophosphamide/ifosfamide, a 24-hour infusion of HD MTX 5 g/m2 in conjunction with an i.th. therapy is an important component for prevention of both systemic and CNS relapses. CNS irradiation is not needed for CNS-negative patients.

Adolescent↗
PubMed1992

Contouring structures for 3-dimensional treatment planning.

Three-dimensional (3-D) treatment planning is a labor-intensive process with contouring of the target volume and critical normal tissues being a significant time-consuming component. The use of 3-D treatment planning on a routine basis may be limited by the time required to complete treatment plans. Despite the need to increase the efficiency of the process, there is little literature addressing the speed and accuracy of contouring systems. In an attempt to initiate systematic analysis of the contouring process, data sets consisting of 10 CT images each were developed on two patients with esophageal carcinoma. Nine different operators manually contoured structures (target volume, spinal canal, lungs) on the data sets using four different contouring systems present in our department. These included both commercially available systems and those developed by the authors. There was a wide variation in the hardware and software characteristics of these systems. The time required to contour the CT data sets was recorded and analyzed. The contouring accuracy was assessed by comparison with a standard template derived from the CT data set for each image. The contouring time was found to be dependent on the system design, previous contouring experience, and the type of drawing instrument (lightpen vs mouse). The mean contouring time ranged from 26 minutes per patient for the fastest system to 41 minutes for the slowest. Potential clinically significant errors in contouring were rare for the spinal canal and lungs but present at a greater rate for the target volume (30.3%). The implications of this finding are discussed.

Adenocarcinoma↗
PubMed1992

[Renal cell cancer in childhood].

Renal cell carcinoma is a rare disease in children and difficult to distinguish from Wilms-tumor before surgery. We present case histories of two children with renal cell carcinoma and discuss the problems of differential diagnosis versus nephroblastoma, therapy and prognosis. In contrast to Wilms-tumors, the most common kidney-tumor in children occurring mostly in young infants, renal cell carcinoma is rare in childhood and predominantly manifests in school-age. Only a few cases of renal cell carcinoma in younger children are described in the literature. Diagnostic imaging cannot reliably distinguish renal cell carcinoma from other neoplasm of the kidney. However, hematuria in patients with small tumors or no response to preoperative chemotherapy may indicate the presence of renal cell carcinoma rather than nephroblastoma. The determination of "tumor-associated trypsin inhibitor" (TATI) might give further contribution of differential diagnosis. It was measured only in one of our patients and was markedly elevated. Complete surgical resection (nephrectomy with lymphadenectomy) is a curative therapy in patients with tumors limited to the kidney. Chemotherapy and irradiation show no convincing effect. In metastatic tumors therapy with interleukin 2 may be successful.

Carcinoma, Renal Cell↗
PubMed1991

Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission after intensive primary and relapse therapy according to the BFM- and CoALL-protocols: results of the German Cooperative Study.

Fifty-one children between 26 and 214 months of age (median, 100 months) with acute lymphoblastic leukemia (ALL) were grafted in second remission from HLA-identical sibling donors (except for two patients who were grafted with a marrow with 1 antigen-mismatch). Initial treatment and relapse therapy were similar in all patients according to the BFM- and CoALL-protocols (front line: 38 patients according to BFM-protocols and 13 patients according to CoALL-protocols; relapse: 12 patients in study ALL-REZ-BFM 83, 17 in ALL-REZ-BFM 85, 20 in ALL-REZ-BFM 87, and two in ALL-REZ-BFM 90). The conditioning regimens were different, consisting of cyclophosphamide (CY) total body irradiation (TBI) plus (n = 27), VP-16-TBI (n = 23), and CY-TBI and ARA-C (n = 1). Three patients had a second graft after conditioning with CY-TBI for the first transplantation. The second ablative regimen consisted of CY plus VP-16 in the first patient and CY plus busulfan in the two other patients, one of whom relapsed again. All patients but three had bone marrow (BM), either isolated or combined, relapses. Twenty-nine of the patients are in continuous complete remission (CCR), ranging from 1 to 67 months after transplantation with a median time of 30 months. One patient was lost to follow-up in continuous remission. Nine patients died from treatment-related complications (infections and graft-versus-host disease) and 12 patients suffered a leukemic relapse; three of them received a second graft and two are in CCR. Kaplan-Meier analysis yields an event-free survival (EFS) of 0.52 +/- 0.08. The probability of a 7-year relapse-free interval (RFI) is 0.68 +/- 0.08. EFS for patients with late relapses is 0.47 +/- 0.12 and for patients with early relapses 0.56 +/- 0.1. The RFI for patients with late relapses is 0.65 +/- 0.12 and for patients with early relapses 0.69 +/- 0.11. There is a nonsignificant trend towards superior results for patients grafted after conditioning with VP-16 plus TBI. When all patients who are not in CCR at day +125 (which is the median interval between relapse diagnosis and BM transplantation [BMT]) are excluded from the chemotherapy results, there is no significant difference between the results of BMT and chemotherapy for late relapses. On the other hand, there is a significant advantage between chemotherapy and BMT for early relapses over chemotherapy (P less than or equal to .01).

Adolescent↗
PubMed1991

Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group.

Between April 1985 and March 1987 130 children and adolescents up to 18 years of age with first relapse of acute lymphoblastic leukemia (ALL) were registered on the stratified and randomized multicentric trial ALL-REZ BFM 85 designed for patients pretreated with intensive front-line therapies. Stratification criteria were time and site of relapse: bone marrow (BM) relapse on or up to 6 months after stopping front-line therapy (group A), BM relapse beyond 6 months after therapy (group B), and isolated extramedullary relapse at any time (group C). Treatment consisted of alternating courses of polychemotherapy including randomly administered high- or intermediate-dose methotrexate (HDMTX:12 g/m2 as 4-hour infusion; IDMTX: 1 g/m2 as 36-hour infusion). During maintenance therapy the patients received daily oral thioguanine and biweekly intravenous (IV) MTX. The overall second complete remission (CR) rate was 92% (groups A, B, and C: 88%, 92%, and 100%), and the probability of event-free survival (EFS) at 6 years is 0.31 +/- 0.04 (groups A, B, and C: 0.18 +/- 0.05, 0.30 +/- 0.07, and 0.72 +/- 0.11). HDMTX did not prove to be superior to IDMTX, which led to premature stopping of randomization. Risk factor analyses showed early relapse, particularly BM relapse within 18 months, and T-cell phenotype to be independent predictors of poor outcome. The incidence of central nervous system (CNS) relapses following BM relapse was 19%, indicating that reprophylaxis to the CNS with IV/intrathecal (IT) MTX was insufficient. For 17 children who received bone marrow transplantation in second CR from HLA-compatible siblings the EFS was 0.53 +/- 0.12 at 5 years. Their outcome was not influenced by the above-mentioned risk factors. With the proposed treatment regimen long-lasting second remissions can be achieved in about one third of patients even after intensive front-line treatment.

Adolescent↗
PubMed1991

Erythroblastopenia in two patients after splenectomy and polychemotherapy.

Acquired erythroblastopenia is a rare disorder of the hematopoietic system associated with viral infections, autoimmune diseases, and drugs. We report on two patients who became anemic due to maturation-arrest at the proerythroblast level, without alterations of white blood cell or platelet counts. Both patients had been splenectomized and had undergone chemotherapy for nephroblastoma or Hodgkin's disease, respectively, at the same pediatric oncology unit. Erythropoietin levels were elevated in both patients. Antibodies against specific viruses, particularly parvovirus B 19, could not be detected in patient sera. Both patients responded to infusions of 7 S immunoglobulin with a rapid increase of the reticulocyte counts. In both cases, complete clinical remission was observed after a duration of 5 months. Heat-inactivated serum obtained during the acute phase and after remission as well was found to be inhibitory for normal bone marrow granulocyte and erythrocyte progenitor growth in vitro. The simultaneous appearance of this rare disorder in two otherwise unrelated patients treated at the same unit prompts speculations about a viral etiology.

Antineoplastic Combined Chemotherapy Protocols↗