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Biomedical subjects

O Hartmann

Publications and source records attributed to O Hartmann.

At least 199 records · Page 11Linked to original sources
PubMed1987

Incubation of autologous bone marrow graft with ASTA Z 7557: comparative studies of hematological reconstitution after purged or nonpurged bone marrow transplantation.

Thirty-three patients with advanced solid tumors were treated by high-dose chemotherapy (combined high-dose melphalan), followed by cryopreserved autologous bone marrow transplantation (ABMT). Thirteen of them had bone marrow (BM) tumor involvement at diagnosis, and BM harvest was purged with 50 micrograms/ml ASTA Z 7557 before cryopreservation. Following incubation, in vitro growth of granulomonocytic colony-forming cells (GM-CFC) was regularly inhibited (greater than 99%). Hemopoietic reconstitution after purged and nonpurged ABMT was studied. All patients experienced engraftment. However, peripheral leukocyte and granulocyte recoveries were delayed significantly in patients receiving purged BM (mean 27 and 26 days) compared with those observed in patients receiving nonpurged BM (mean 18 and 18 days). These results confirm that purged BM, despite GM-CFC depletion after in vitro treatment, ensures engraftment after high-dose chemotherapy, but prolonged pancytopenia is observed and postgraft hemopoietic recovery is delayed. A clinical trial is necessary to evaluate the efficiency of the purging technique in eradicating residual tumor cells.

Adult↗
PubMed1987

Hyponatremia and renal sodium wasting in patients receiving cisplatinum.

Three children with malignant solid tumors developed hyponatremia with renal sodium wasting associated with other signs of tubular dysfunction, such as hypokalemia or hypomagnesemia, a few days after cis-diammine dichloroplatinum (CDDP) administration. The normalization of serum electrolyte disturbances was obtained with increased parenteral intakes in fluids and electrolytes, and renal sodium wasting stopped by itself a few days later.

Adolescent↗
PubMed1986

Treatment of advanced neuroblastoma with high-dose melphalan and autologous bone marrow transplantation.

Fifteen children with advanced neuroblastoma according to Evans' classification (1 with stage III and 14 with stage IV) were treated with high-dose melphalan (HDM) followed by autologous bone marrow transplantation. Before HDM, all patients had been extensively treated with multimodality therapy for a median duration of 9 months. At the time of HDM, seven children were in partial remission (PR) with measurable residual tumor and 8 were in complete remission (CR) or good partial remission (GPR). No reduction in measurable tumor size was observed in any of the PR patients. However, when HDM was used as consolidation therapy (CR and GPR patients) survival appeared encouraging, since five of eight patients are alive with no evidence of disease at (NED) 29+ to 54+ months after HDM. Tolerance of this high-dose chemotherapy was satisfactory; gastrointestinal toxicity appeared to be the most important limiting factor. These results suggest that chemotherapy including high-dose melphalan is promising when used as consolidation therapy in patients who have already attained CR with conventional therapies.

Adolescent↗
PubMed1986

Pharmacokinetics of high-dose melphalan in children and adults.

Melphalan pharmacokinetics were studied in 20 children with stage IV neuroblastomas or Ewing's sarcomas and in 10 adults with AML, ALL, or small cell lung carcinomas, after IV administration of high doses (140 mg/m2 with furosemide-induced diuresis and 180 mg/m2 without induced diuresis) and high fluid intake (3000 ml/m2/day). Unchanged melphalan was assayed in plasma and cerebrospinal fluid by means of a high-performance liquid chromatographic procedure. The elimination half-life (t1/2 less than 80 min) allows autologous bone marrow transplantation 24 h after the drug administration. In some children we were able to detect melphalan in cerebrospinal fluid samples.

Adolescent↗
PubMed1986

The role of massive therapy with autologous bone marrow transplantation in Burkitt's lymphoma.

Burkitt's lymphoma has proved to be a very useful model for the evaluation of both massive therapy regimens and purging techniques. Results from several centres now confirm a number of general principles in relation to the use of ABMT procedures in this tumour. Patients in whom conventional chemotherapy has failed can be cured by massive therapy but this should be limited to those who have responded to salvage regimens or have only achieved first PR. Chemoresistant relapse is unlikely to be cured and the high probability of a transient response does not justify the procedure in such cases. Important ongoing clinical studies include the use of ABMT in first CR for CNS disease or B-cell ALL. Results in allogeneic grafts suggest that current massive therapy regimens are curative in only 20-50% of patients (Appelbaum and Thomas, 1983) and new combinations are, therefore, still required. Phase I and II studies in patients with 'resistant relapse' are investigating the use of sequential high-dose alkylating agents and role of TBI. It is of particular importance to develop effective conventional 'salvage' regimens. Recent experience indicates that the combination of high-dose cisplatin and VP 16 is useful; other possibilities include high-dose interferon and high-dose cytarabine. Purging techniques in BL are now at an advanced stage and the combination of immunological and chemical treatments, once of proven efficacy in individual patients at a laboratory level, should be the subject of randomized studies.

Antibodies, Monoclonal↗
PubMed1986

Severe gram-negative infections in neutropenic children cured by imipenem/cilastatin in combination with an aminoglycoside.

Nine severe Gram-negative septicaemias in neutropenic (less than 500 neutrophils/mm3) children with neoplastic diseases were treated with imipenem/cilastatin (75 mg/kg/day) in combination with an aminoglycoside. The bacterial strains (Pseudomonas aeruginosa 7, P. putida 1, Enterobacter cloacae 1) were resistant to penicillins and cephalosporins, or were isolated during treatment with a broad-spectrum penicillin to which the bacterial strain was sensitive in vitro. The mean duration of neutropenia was 18.5 (3-51) days and duration of treatment 20 (8-51) days. Pyrexia was controlled in 2.8 (1-10) days and eradication of the pathogen from blood in one day. No clinical and biological adverse reaction was observed. These results show imipenem/cilastatin to be an effective treatment of infections in severely immunocompromised patients.

Adolescent↗
PubMed1986

High-dose busulfan and cyclophosphamide with autologous bone marrow transplantation support in advanced malignancies in children: a phase II study.

Twenty children with advanced, nonleukemic malignancies entered a phase II study of high-dose busulfan-cyclophosphamide followed by bone marrow transplantation (BMT). All had disease refractory to conventional and/or high-dose chemotherapy (HDC). There were ten neuroblastoma patients, six non-Hodgkin's lymphoma, three Ewing's sarcoma, and one rhabdomyosarcoma. Eight had primarily resistant disease, ten were in second progressive relapse, and two in third progressive relapse. One patient was not evaluable for response. Among the 19 evaluable patients the responses observed were complete response (CR), seven; partial response (PR), three; objective effect, five; and failure, four. However, survival was poor: 15 patients died, two are alive with disease, and three are alive with no evidence of disease (NED) at 8+, 11+, 14+ months post-BMT. Toxicity was high but considered as acceptable, taking into account the terminal state of these patients. Seven treatment-related deaths were observed. This combination therapy proved to be highly effective, with a response rate of 50%, and its value for eradication of residual disease in less advanced patients should be investigated.

Adolescent↗
PubMed1986

High-dose methotrexate and continuous infusion Ara-C in children's non-Hodgkin's lymphoma: phase II studies and their use in further protocols.

Twenty-three children with refractory or relapsed non-Hodgkin's lymphoma (NHL) received high-dose methotrexate (HD-MTX), and 9 received Ara-C by continuous intravenous infusion, as phase II studies. They all had previously received a protocol including vincristine, adriamycin, cyclophosphamide, IV push Ara-C, asparaginase, intrathecal MTX, and cranial irradiation, and had failed to respond or had relapsed. HD-MTX was given at the dose of 6 g/m2 or more with leucovorin rescue, Ara-C at the dose of 100 mg/m2/day by continuous infusion over 10 days. Among the 22 evaluable patients receiving HD-MTX, 10 responses (7 CR; 3 PR) were observed. Among the 9 patients receiving Ara-C, 4 responded (1 CR; 3 PR). Toxicity in those previously heavily treated patients was acceptable. These two drugs are now successfully included in childhood NHL treatment protocols.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

High-dose melphalan with or without marrow transplantation: a study of dose-effect in patients with refractory and/or relapsed acute leukemias.

Dose-effect relationships of high-dose melphalan were evaluated in 37 patients with measurable relapsed or refractory acute leukemias. Thirteen patients (Group 1) received 70-100 mg/m2 of melphalan without marrow rescue and 24 patients (Group 2) received 140-180 mg/m2 of melphalan followed by marrow transplantation. Patients in both groups were comparable with respect to age, sex, diagnosis, and status of the leukemia. The complete remission rate was 23% in Group 1 versus 75% in Group 2 (P less than 0.01). Hematological recovery of remission patients was not statistically different in either group. Nonhematological toxicity was comparable in the two dose ranges examined. These results demonstrate the existence of a dose-response effect of high-dose melphalan regimens in relapsed acute leukemias, without marked increases in nonhematological toxicity with these doses.

Acute Disease↗
PubMed1986

Modified chemotherapy with carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) and autologous bone marrow transplantation in 24 poor-risk patients with acute lymphoblastic leukemia.

Twenty-four poor-risk patients with acute lymphoblastic leukemia received a modified regimen of carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) followed by autologous bone marrow transplantation (ABMT). Nineteen patients were in second or subsequent complete remission (CR) when treated with this regimen; 3 died early, 2 died of pneumonia in CR, 11 relapsed within 3 months (median), and 3 remain in CR with no maintenance therapy 14-24 months after ABMT. Of the 5 patients with measurable disease who were treated, 3 had CR and 1 remains in CR without maintenance therapy more than 28 months after ABMT. The toxicity of this regimen was acceptable, but late pulmonary toxic effects remain a major concern. These results are poor in terms of efficacy, and new effective methods of eradicating acute lymphoblastic leukemia in patients with poor prognosis should be investigated.

Adolescent↗
PubMed1985

Hematopoietic recovery following autologous bone marrow transplantation: role of cryopreservation, number of cells infused and nature of high-dose chemotherapy.

Twenty-nine patients were treated with single or combined high-dose melphalan therapy followed by autologous bone marrow transplantation. Hematopoietic recovery from these treatments was studied. No correlation was found between the number of GM-CFC infused and the time required for hematopoietic recovery. It is suggested that this correlation is only demonstrable for low 'doses' of infused bone marrow cell and/or GM-CFCs. The role of bone marrow cell preservation techniques was examined and results were similar for fresh and cryopreserved bone marrow. The erythrocyte, lymphocyte and granulocyte levels of the patients reported here reached a normal or subnormal hematological steady state 3 months after autograft. Our results confirm the value of cryopreservation techniques. Hematopoietic recovery was short and of the same duration whether the patients were given single or combined high-dose melphalan before autologous bone marrow transplantation. These results also demonstrate the value of such transplantation in shortening the myelosuppression caused by high-dose chemotherapy.

Adolescent↗
PubMed1985

[Olfactory neuroblastoma disclosed by blindness in a 9-month-old girl].

A case of olfactory neuroblastoma in a 9 month-old girl is reported. Blindness and purulent meningitis were the first symptoms. Radiological examinations including CT scan revealed a sphenoidal tumor with penetration of the meninges. Surgery revealed an ethmoido-sphenoidal tumor mass extending into the pituitary fossea which consisted of malignant cells with the histological aspect of esthesioneuroblastoma. The rarity of this tumor in early childhood and its clinical polymorphism are emphasized.

Blindness↗
PubMed1984

Hypercalcemia preferentially occurs in unusual forms of childhood non-Hodgkin's lymphoma, rhabdomyosarcoma, and Wilms' tumor. A study of 11 cases.

Unusual clinical, radiologic, or histologic findings were found in 11 of 17 cases of hypercalcemia associated with childhood tumors. Four children had undifferentiated lymphoblastic lymphoma with extensive bone involvement, but no visceral or neurologic involvement. At diagnosis, four adolescents with rhabdomyosarcoma had numerous metastases, particularly in the breasts and bone marrow. Three infants had renal tumor without bone metastases. Histologically, their tumors differed from classical nephroblastoma and resembled the malignant rhabdoid tumors of the kidney. These findings allow individualization of three distinct groups of tumors with unusual features which may suggest the presence of hypercalcemia. These tumors appear to have a poor prognosis since all patients but one died of their malignancy.

Adolescent↗
PubMed1984

Nonseminomatous malignant germ cell tumors in children. Multidrug therapy in Stages III and IV.

Thirty-five children with Stage III and IV nonseminomatous malignant germ cell tumors were treated, between June 1, 1977 and December 31, 1982, at Institut Gustave-Roussy, Villejuif, France, and Hospital General de Ninos, Buenos-Aires, Argentina: 11 sacrococcygeal, 12 ovarian, 6 testicular, 5 intrathoracic, and 1 intrabdominal site. All of them had yolk sac component with high level of AFP, seven had also elevated level of HCG. Thirteen patients had primary chemotherapy, 18 received chemotherapy after incomplete surgical excision, and 4 patients with testicular Stage III tumors had chemotherapy immediately following retroperitoneal lymphadenectomy after orchiectomy, because of persistently elevated AFP levels. The chemotherapy regimen for 1 year's duration, repeated every 21 days, and consisted of 6 courses of dactinomycin-Cytoxan (cyclophosphamide) D1 to D5 and vincristine, Adriamycin (doxorubicin) D21, bleomycin D23, and cisplatin D24. Only three patients received complementary radiotherapy. The toxicity of the chemotherapy regimen was severe, but only one death was due to the therapy (pulmonary fibrosis with bleomycin). The number of surviving patients without evidence of disease was 12 of 16 for Stage III and 12 of 19 for Stage IV. The 25-month survival rate was 63% with a follow-up of 11 months to 5.5 years (median, 22 months). This constitutes a dramatic improvement when compared with the survival rate of 21% of 48 similar patients treated at Institut Gustave-Roussy between 1968 and 1977 with surgery, radiotherapy, and chemotherapy (methotrexate, dactinomycin, and Cytoxan).

Abdominal Neoplasms↗