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T Klingebiel

Publications and source records attributed to T Klingebiel.

At least 109 records · Page 6Linked to original sources
PubMed1997

Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood.

PURPOSE: To evaluate the role of allogeneic bone marrow transplantation (BMT) in children with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: Forty-three children with CMML given BMT and reported to the European Working Group on Myelodysplastic Syndrome in Childhood (EWOG-MDS) data base were evaluated. In 25 cases, the donor was a human leukocyte antigen (HLA)-identical or a one-antigen-disparate relative, in four cases a mismatched family donor, and in 14 a matched unrelated donor (MUD). Conditioning regimens consisted of total-body irradiation (TBI) and chemotherapy in 22 patients, whereas busulfan (Bu) with other cytotoxic drugs was used in the remaining patients. RESULTS: Six of 43 patients (14%), five of whom received transplants from alternative donors, failed to engraft. There was a significant difference in the incidences of chronic graft-versus-host disease (GVHD) between children transplanted from compatible/one-antigen-mismatched relatives and from alternative donors (23% and 87%, respectively; P < .005). Probabilities of transplant-related mortality for children given BMT from HLA-identical/one-antigen-disparate relatives or from MUD/ mismatched relatives were 9% and 46%, respectively. The probability of relapse for the entire group was 58%, whereas the 5-year event-free survival (EFS) rate was 31%. The EFS rate for children given BMT from an HLA-identical sibling or one-antigen-disparate relative was 38%. In this latter group, patients who received Bu had a better EFS compared with those given TBI (62% v 11%, P < .01). CONCLUSION: Children with CMML and an HLA-compatible relative should be transplanted as early as possible. Improvement of donor selection, GVHD prophylaxis, and supportive care are needed to ameliorate results of BMT from alternative donors.

Bone Marrow Transplantation↗
PubMed1996

The recurrence patterns of stages I, II and III neuroblastoma: experience with 77 relapsing patients.

BACKGROUND: Recurrences of neuroblastoma Evans' stage I-III are infrequent events and the types of its progression have rarely been reported. Therefore, we investigated the patterns of progression in a large series of patients with long follow-up. PATIENTS AND METHODS: The sites of relapse and time to progression and death of 381 consecutive patients in three cooperative trials (NB 79, 82, 85) with follow-up of 5-16 years were analysed. The Southern blot technique was used for N-myc investigation of tumor tissue. RESULTS: Of the 77 relapsing patients, 41 (53%) had local and 36 (47%) systemic recurrences. The relapses occurred in 9 of 76 stage I patients (6 local/3 systemic), in 4 of 82 stage II (1 local/3 systemic) and 64 of 223 stage III neuroblastoma (34 local/30 systemic) patients. The main sites of distant metastasis were bone marrow (41%), lymph nodes (39%) and bone (37%). The median transition time from localised to metastatic neuroblastoma was 13 months and the outcome as poor (overall survival 9 +/- 5%) as that of the primary metastatic disease (14 +/- 3%). Fifty-three children died of tumor progression and 15 patients of treatment-related complications or other non-tumor conditions. The median age at diagnosis was 43 months for the group with systemic relapse compared to 19 months with only local and 10 months without recurrences (p < 0.001). Elevated serum LDH levels at first diagnosis were seen in 81% with metastatic, in 55% with local and in 33% with no tumor progression (p < 0.001). N-myc amplification was found in 4/14 with local and in 6/12 with metastatic recurrences. CONCLUSION: The high incidence of systemic relapse and the long transition time suggest that transition from localised to metastatic neuroblastoma is not an uncommon pathway.

Adolescent↗
PubMed1996

Expression of PKC isozyme and MDR-associated genes in primary and relapsed state AML.

For investigation of relative differences in mRNA expression levels and of correlations in the expression of genes possibly involved in multidrug resistance (MDR) of acute myelogenous leukemias (AML), a complementary DNA polymerase chain reaction (cDNA-PCR) analysis was established for the genes encoding MDR1/P-glycoprotein, the multidrug resistance-associated protein (MRP), topoisomerase II alpha, topoisomerase II beta, topoisomerase I, glutathione S-transferase pi, protein kinase C (PKC) isozymes alpha, beta 1, beta 2, epsilon, eta, theta and cyclin A. In a first descriptive study comprising samples of childhood or adult AML we calculated the mean values from primary (n=14) or relapsed (n=23) states of the diseases, respectively. We found in the latter significant increases of MDR1, MRP, gst pi, and PKC theta gene expression. MDR1 and MRP gene expression levels were generally correlated (rs= +0.4128, P<0.02, n=37), as well as topoisomerase II alpha and cyclin A gene expression levels (rs= +0.8727, P<0.0001, n=35). Within the group of relapsed state AML a significant negative correlation between the gene expression levels of MDR1 and topoisomerase II alpha (rs= -0.5500, P<0.01, n=22) was observed. Remarkably, highly significant positive correlations were found for MDR1/PKC eta (rs= +0.5560, P<0.001, n=32), MRP/PKC theta (rs= +0.6573, P<0.0001, n=34) and MRP/PKC eta (rs= +0.5241, P<0.005, n=32).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

[Differential diagnosis of childhood osteomyelitis--classification according to scintigraphic, radiologic and magnetic resonance tomographic characteristics].

We present a retrospective study on children with the final diagnosis osteomyelitis, who have been examined in Tübingen from 1985 to 1991. The different types of infantile osteomyelitis were classified due to the causative organism and findings in 3-phase scintigraphy and X-ray films. For the chronic type of osteomyelitis the study was extended to the years from 1979 to 1991 and the results of an earlier report were included. We worked up 17 cases of acute/peracute osteomyelitis, including 5 cases of early infancy, 2 cases of tuberculosis, 2 Brodie's abscesses, 5 plasmacellular types, 2 cases of primary chronic multifocal osteomyelitis (PCMO), and 5 cases of unspecific chronic osteomyelitis. All cases were examined with scintigraphy, X-ray films and in part with magnetic resonance tomographic imaging. In 23 cases scintigrams and X-ray films were performed in the follow-up. We show the importance of scintigraphy for the early detection and localisation of osteomyelitis, the importance of findings on X-ray films for the specific diagnosis of osteomyelitis, and the importance of magnetic resonance tomography for high-resolution detection of the expansion of osteomyelitis.

Acute Disease↗
PubMed1996

Which children do benefit from bone marrow transplant? The EBMT Paediatric Diseases Working Party.

The development of chemotherapy in childhood ALL has been the leader of the success story of paediatric oncology. At least 2/3 of the children can be cured nowadays at the first attempt of treatment. From the remaining again 1/3 can be treated successfully for the relapse of their disease with conventional therapeutic strategies. This means, however, that there is no chance for cure with chemotherapy alone for 20 to 25% of the children. BMT has been shown for a long time to be an alternative therapy especially in those cases in which conventional chemotherapy fails. In spite of the fact that many children with ALL have been transplanted during recent years there is still no general agreement on the question which children need BMT. However a few statements can be made: The value of ABMT in ALL is probably not better than that of chemotherapy alone. In 1st CR a group of children can be defined, which might benefit from BMT. In 2nd CR the value of chemotherapy depends very much from the duration of 1st remission. Allogeneic BMT is the only chance for cure in very early relapses, superior to chemotherapy in early and late relapses and possibly equal to chemotherapy in very late relapses. The paper tries to summarise our current knowledge about the situation.

Bone Marrow Transplantation↗
PubMed1996

Autologous versus allogeneic BMT in AML: the European experience. Report of the EBMT--Pediatric Diseases Working Party.

The Austrian-German-Italian (AGI) Pediatric Bone Marrow Transplantation Registry includes now data of 520 patients grafted for acute myeloid leukemia (AML) by autologous and allogeneic stem cells. In first complete remission (CR1) 145 patients with allografts had a possibility of event free survival (pEFS) of 0.57 and 140 patients with autografts a pEFS of 0.46. In second complete remission (CR2) autografted patients (n = 70) had a pEFS of 0.36 and allogeneic patients (n = 41) of 0.34. Patients with no CR went worse (allogeneic pEFS 0.15 n = 37; autologous pEFS 0.17 n = 6). Therefore, from the European data the following conclusions can be drawn: neither in CR1 nor in CR2 any statistical advantage for a particular transplantation type can be found. To assess the value of transplantation with family mismatch donors or matched unrelated donors (MUD) basing on these data pool is not possible. The following decisions should be reached: 1) BMT for AML with mismatched or unrelated donors should be done only within cooperative European trials. 2) Generally accepted definitions of indications for BMT in AML are needed. 3) Study protocols concerning conditioning are necessary.

Bone Marrow Transplantation↗
PubMed1996

Unrelated-donor bone marrow transplantation for Philadelphia chromosome-positive chronic myelogenous leukemia in children: experience of eight European Countries. The EBMT Paediatric Diseases Working Party.

From September 1988 to December 1995 forty-four children (age < 17 years) with Ph1 Chronic Myelogenous Leukemia (CML) received unrelated donor marrow transplantation in 8 European Countries. Thirty-three evaluable children were typed by serological testing on HLA-A, B, and DR loci. Thirty of them were further DR subtyped by DNA techniques. Twenty-four pairs were 6 antigen matched. Seven were mismatched at 1 locus (2 pairs at A and B loci respectively and 3 at DR locus). Two out of 30 pairs evaluated by molecular biology had one antigen mismatched at DRB1 locus. Thirty-two (96%) out of 33 evaluable children reached a sustained granulocyte count higher than 0.5 x 10(9)/l at a median of 21 (range 14-88) days after transplantation. The remaining child failed to engraft. Two children developed secondary graft failure. A platelet count greater than 50 x 10(9)/l sustained for at least seven consecutive days without transfusion support was reached at a median of 25 (range: 20-144) days by 24 out of 33 evaluable children and 9 children never recovered to above 50 x 10(9)/l. Twenty-one out of 33 evaluable children developed grade I (n = 7), grade II (n = 8), grade III (n = 2) or grade IV (n = 4) acute GvHD (63%). Seven of the 30 evaluable children surviving more than 100 days developed chronic GvHD (20%) which was limited in 4 cases and extensive in 3. Relapse occurred in 3 of the 44 (7%) children at 2 to 24 months (median 14). Twenty-four month relapse rate was 14%. Seventeen out of 44 children (38%) died of transplant related mortality (TRM), 4 (9%) of secondary tumor, 4 (9%) of infections, 3 (7%) of organ failure, 1 (2%) of interstitial pneumonia, 5 (11%) of unknown causes. Actuarial TRM was 61% for children grafted before December 1991 and 33% for children grafted after January 1992 (p = .01). EFS was 49.7%; it was 65% for children receiving more than 3.5 x 10(9)/Kg MNC.

Adolescent↗
PubMed1995

Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side effects of antiviral therapy after bone marrow transplantation.

Culture-based preemptive therapy with ganciclovir was shown to reduce the incidence of cytomegalovirus (CMV) disease after bone marrow transplantation (BMT). Culture techniques did not detect CMV in 12% to 13% of patients before the onset of CMV disease. In a prospective study, 71 patients either received preemptive therapy based on polymerase chain reaction (PCR) technique (37 patients) or on culture assays (34 patients). In both groups, therapy was continued until clinical signs disappeared and PCR negativity was documented. Twenty-two patients in the PCR group and 15 patients in the culture group received antiviral therapy. PCR allowed detection of the virus (median day, +32 v day +49; P = .006) and introduction of antiviral therapy (median day, +44 v day +54; P = .02) earlier than did culture assays. The incidences of CMV disease (2 of 37 v 8 of 34 in PCR group v culture group, respectively; P = .02) and CMV-associated mortality (0 of 37 v 5 of 34 in PCR group v culture group, respectively; P = .02) were decreased, and the duration of ganciclovir therapy (P < .001) was shorter in the PCR-monitored group. Incidence and median duration of severe neutropenia (less than 500/microL) were lower in the PCR group (two v eight episodes, P = .02; median duration, 1.5 v 5 days, P = .04), as was the incidence of nonviral infections during/after antiviral therapy (2 of 37 v 9 of 34; P = .012). Thus, preemptive therapy based on more sensitive detection methods such as the PCR assay reduces the incidence of CMV disease and CMV-related mortality. Additionally, stopping and withholding antiviral therapy in a PCR-negative patient is safe and allows reduction of the duration and side effects of antiviral therapy.

Adolescent↗
PubMed1995

Autologous bone-marrow transplants compared with chemotherapy for children with acute lymphoblastic leukaemia in a second remission: a matched-pair analysis. The Berlin-Frankfurt-Münster Study Group.

It is unclear how best to treat children with acute lymphoblastic leukaemia (ALL) who are in a second remission. Treatment with bone-marrow transplants from HLA-identical siblings results in a statistically greater likelihood of leukaemia-free survival than does chemotherapy. Less than 25% of relapsed patients are able to benefit from this therapy due to a lack of matching donors; chemoradiotherapy or autologous BMT are considered for the rest. We compared treatment results for children who underwent autologous BMT with those who had chemotherapy. All patients were registered between 1983-94 in the multicentre trials. We selected groups of patients by matching variables associated with treatment outcome and duration of second remission. 52 matched-pairs were studied. The probability of event-free survival at 9 years was 0.32 (SD 0.07) for patients receiving chemotherapy versus 0.26 (SD 0.07) for patients who underwent autologous BMT. For two groups--children with prognostic factors indicating high risk of relapse and those with factors indicating lower risk--the outcome from transplantation did not differ significantly from that of chemotherapy: no advantage of autologous BMT over chemotherapy as post-induction treatment for children with ALL in a second remission could be detected with regard to event-free survival. Because autologous BMT has been used as the final step of treatment it is possible that its relative ineffectiveness has been due to the lack of continuation therapy after transplant. Attempts should be made to complement autologous BMT by subsequent immunotherapy, molecular biotherapy, chemotherapy, or a combination of these.

Adolescent↗
PubMed1995

A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma.

9 patients with stage IV neuroblastoma were treated with 19 courses of human/mouse chimeric monoclonal antiganglioside GD2 antibody ch14.18 at dose levels of 30, 40 and 50 mg/m2/day for 5 days per course. The maximum tolerated dose (MTD) per injection was 50 mg/m2/day. 7 patients received more than one course of treatment, and none revealed any human anti-mouse antibody (HAMA) response. Clinical side-effects of patients treated with ch14.18 were abdominal and joint pains, pruritus and urticaria. One patient presented with a transient pupillatonia, while 2 others showed a unilateral atrophy of the optical nerve that was probably attributable to prior therapies. A complete remission was seen in 2 patients, partial remission in 2 patients, a minor response in 1 patient and stable disease in 1 patient. 3 patients showed tumour progression. Thus, our results indicate that treatment with chimeric MAb ch14.18 can elicit some complete and partial tumour responses in neuroblastoma patients.

3-Iodobenzylguanidine↗
PubMed1995

Autologous transplantation with peripheral blood stem cells in children and young adults after myeloablative treatment: nonrandomized comparison between GM-CSF and G-CSF for mobilization.

Recombinant human granulocyte-monocyte colony-stimulating factor (rhGM-CSF) was compared with recombinant granulocyte colony-stimulating factor (rhG-CSF) in 34 patients for mobilization of peripheral blood stem cells (PBSC) and for posttransplantation use. Peripheral blood stem cell mobilization was initiated by a single 1 h infusion of cyclophosphamide (4 g/m2) in all patients, followed by either a continuous infusion of rhGM-CSF (250 micrograms/m2/day) in 17 patients (group A) or a daily subcutaneous injection of rhG-CSF (10 micrograms/kg/day) in 17 patients (group B). PBSC were collected using a Fenwal CS 3000 continuous flow blood cell separator in one to three sessions. All patients suffered from various childhood malignancies. No difference in the number of collected cells among both groups was found. A mean of 2.7 x 10(8)/kg mononuclear cells (MNC) and of 7.9 x 10(4)/kg CFU-GM (colony-forming unit-granulocyte-macrophage) were collected in group A. In group B, 2.3 x 10(8)/kg MNC and 11.8 x 10(4)/kg CFU-GM were collected. In 33 patients, PBSC were reinfused after myeloablative therapy. Patients of group A (n = 17) were treated with rhGM-CSF (250 micrograms/m2/day) starting day +1, and patients in group B (n = 16) were treated with rhG-CSF (10 micrograms/kg/day) i.v. All patients showed a rapid and complete hematopoietic recovery without significant differences in both groups. Time to achieve 0.5 x 10(9)/L granulocytes was 10.9 days in group A and 11 days in group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Expression of mdr1, mrp, topoisomerase II alpha/beta, and cyclin A in primary or relapsed states of acute lymphoblastic leukaemias.

In a series of 60 ALL samples drawn during different stages of the disease we used a cDNA-PCR approach to analyse the relative mRNA levels of the MDR-associated genes encoding mdr1/P-glycoprotein, mrp, and the topoisomerase II isozymes alpha and beta. Expression analysis of the cyclin A gene was included to examine cellular proliferation activity. The expression of gapdh served as an internal standard. Calculating the mean values we found: (i) a distinctly lower mdr1 gene expression in primary ALL and first relapses compared to bone marrow from healthy donors, (ii) no change in mdr1 and mrp, but a decreased topoisomerase II alpha gene expression in first relapses of ALL compared to the primary leukaemia, and (iii) increased mdr1 and mrp levels combined to decreased topoisomerase II alpha levels in recurrent relapses of ALL showing significant correlations (mdr1/mrp: rs = +0.6833, P < 0.05; mdr1/topoII alpha: rs = -0.6727, P < 0.05). The expression of the topoisomerase II alpha gene was correlated to that of cyclin A, indicating a link of its expression to cellular proliferation. Our findings suggest that a multifactorial MDR including mrp appears particularly in recurrent relapses of ALL, which often do not respond to chemotherapy. Nonetheless, some individual samples showed gene expression levels very different from the mean values calculated for a particular state of the leukaemia, indicating the need of an individual expression analysis of MDR-associated genes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Isolated extramedullary relapse in children with acute lymphoblastic leukemia: a comparison between treatment results of chemotherapy and bone marrow transplantation. BFM Relapse Study Group.

The purpose of this study was to determine the therapeutic efficacy of different treatment strategies, namely chemotherapy, allogeneic and autologous bone marrow transplantation (BMT), for extramedullary relapse of acute lymphoblastic leukemia (ALL) in children in second or subsequent remission. Between 1983 and 1993, 165 patients up to 19 years of age with extramedullary relapse of ALL were registered in the multicenter ALL-REZ BFM trials. One hundred and thirty four children received chemotherapy only; 17 children were grafted from HLA-identical sibling donors 152 days (46-392 days) after diagnosis of relapse, and 14 children underwent autologous BMT after a median time of 137 (range 23-300) days. Event-free survival (EFS) at 5 years was 0.47 +/- 0.05 for patients receiving chemotherapy: 0.76 +/- 0.07 for late, 0.33 +/- 0.08 for early and 0.33 +/- 0.07 for very early relapsed patients. Sixty five patients are in complete remission (CR), 61 patients relapsed, 5 died from therapy related complications, 2 patients in CR were lost to follow-up and one patient developed a second malignancy. For patients who had undergone BMT, EFS at 5 years was 0.36 +/- 0.10 without significant difference between autologous BMT (8 of 14 in CR, 6 relapsed) and allogeneic BMT (6 of 17 in CR, 4 died of acute toxicity, and 7 relapsed).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Remission of a lymphoproliferative disorder occurring after second BMT from an unrelated donor in a 5-year-old boy with severe aplastic anemia.

A 5-year-old boy with severe aplastic anemia failed to respond to cyclosporine (CYA), prednisolone and antilymphocyte globulin (ALG). No suitable sibling marrow donor was available, but an HLA-matched unrelated donor was identified. The patient was conditioned with cyclophosphamide (CY), 50 mg/kg/day for 4 days, total nodal irradiation (8 Gy), and ALG 30 mg/kg/day for 3 days. GVHD prophylaxis consisted of daily CYA, methotrexate (MTX) and ALG. The patient failed to achieve sustained engraftment. He was reconditioned with high-dose prednisolone and anti-T lymphocyte monoclonal antibody OKT3. The boy was reinfused with the same donor marrow on day 0 (+49/first BMT). No GVHD prophylaxis was given the second time. He received G-CSF on days 0 to +20 after the second transplant. Full engraftment was achieved on day +16 (+65). However, on day +31 (80) he developed a biopsy-proven B cell lymphoproliferative disorder (BLPD). After the OKT3 administration was stopped and treatment with ganciclovir and high-dose immunoglobulin was initiated, the BLPD resolved and the patient was discharged on day +50 (99). He is currently well with a functioning graft 266 (305) days posttransplant, with no sign of GVHD.

Anemia, Aplastic↗
PubMed1994

High-dose consolidation with local radiation and bone marrow rescue in patients with advanced neuroblastoma.

Twenty-six children with advanced neuroblastoma were consolidated with cisplatin, BCNU, etoposide, melphalan, 21 Gy of local radiotherapy, and bone marrow rescue in a multicenter study. All patients were over 1 year of age at diagnosis. Twenty-two patients were treated in first complete or partial remission and four in second complete or partial remission. Hematologic rescue was autologous (n = 23), allogeneic (n = 2), or syngeneic (n = 1). Extrahematological toxicity involved primarily the gastrointestinal mucosa. Among five fatal toxicities, three included intestinal hemorrhage. Fourteen patients relapsed after BMT, four of them at the primary site. Seven children survive progression-free after 16-56 months. These results are essentially not different from a single-center study with the same protocol or from other published studies. The value of megatherapy for patients with advanced neuroblastoma or for a subgroup of them can only be established on a larger number of patients than most national trials accrue.

Antineoplastic Combined Chemotherapy Protocols↗