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Biomedical subjects

P Carde

Publications and source records attributed to P Carde.

At least 37 records · Page 2Linked to original sources
PubMed1998

Goralatide (AcSDKP), a negative growth regulator, protects the stem cell compartment during chemotherapy, enhancing the myelopoietic response to GM-CSF.

The aim of our study was to investigate the protection afforded to the bone marrow by Goralatide (AcSDKP), an inhibitor of hemopoietic stem cell proliferation, when administered alone or in combination with a growth factor (granulocyte/macrophage colony-stimulating factor [GM-CSF]) during iterative cycles of Ara-C (cytarabine) treatment. In control mice receiving the inhibitor alone without Ara-C, the number of granulocytes was reduced during treatment, and a surge in number of peripheral blood cells was observed after its completion. Peripheral hematological responses were monitored during 3 consecutive cycles of Ara-C chemotherapy and the resultant nadir and recoveries. Analysis of variance of the treatment effects pooled over the 3 cycles showed that a treatment regimen in which the inhibitor was administered during the myelotoxic periods of chemotherapy confirmed the existence of a surge after completion of administration of the inhibitor and showed a significant protective effect. When the cycles of chemotherapy plus Goralatide were followed by GM-CSF, the recovery from leukopenic nadirs was accelerated and the white blood cells and granulocyte levels were markedly increased over those observed in control mice and in mice treated either with Goralatide alone or with GM-CSF alone. The differences were highly significant. A consistent and significant increase (p < 0.001) in platelet count was also noted in animals given Goralatide in conjunction with Ara-C or Ara-C + GM-CSF. After three treatment cycles, this response to the CSF was far better in mice treated by the inhibitor than when CSF was given alone, suggesting a protection of the stem cell pool.

Animals↗
PubMed1998

The tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (Goralatide) protects from doxorubicin-induced toxicity: improvement in mice survival and protection of bone marrow stem cells and progenitors.

The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP or Goralatide), a physiological regulator of hematopoiesis, inhibits the entry into the S-phase of murine and human hematopoietic stem cells. It has been shown to reduce the damage to specific compartments in the bone marrow resulting from treatment with chemotherapeutic agents, ionizing radiations, hyperthermy, or phototherapy. The present study was performed to assess the therapeutic potential of AcSDKP in vivo in reducing both the toxicity and the hematopoietic damage induced by fractionated administration of doxorubicin (DOX), a widely used anticancer drug. Here we showed that AcSDKP could reduce DOX-induced mortality in mice and could protect particularly the long-term reconstituting cells (LTRCs) in addition to colony forming units-spleen, high proliferative potential colony-forming cells, and colony-forming units-granulocyte-macrophage (CFU-GM) from DOX toxicity. The protection against DOX-induced mortality in mice was improved when AcSDKP was administered for 3 days, at a dose of 2.4 micrograms/d, by continuous subcutaneous (SC) infusion or fractionated s.c. injections starting 48 hours before DOX treatment. Moreover, the recovery of the CFU-GM population in the AcSDKP-DOX-treated mice was optimized by the subsequent administration of granulocyte colony-stimulating factor (G-CSF). The coadministration of AcSDKP with DOX may improve its therapeutic index by reducing both acute hematotoxicity on late stem cells and progenitors and long-term toxicity on LTRCs. Optimization of these treatments combined with G-CSF may provide an additional approach to facilitate hematopoietic recovery after cancer chemotherapy.

Animals↗
PubMed1998

VIP (etoposide, ifosfamide and cisplatinum) as a salvage intensification program in relapsed or refractory Hodgkin's disease.

Forty-two patients with refractory (15 patients) or relapsed (27 patients) Hodgkin's disease (HD) were included in a prospective single center study evaluating the efficacy of a regimen VIP combining etoposide 75 mg/m2/day days 1-5, ifosfamide 1.2 g/m2/day days 1-5 and cisplatinum 20 mg/m2/day days 1-5, one course every 4 weeks as salvage therapy in patients with refractory or relapsed Hodgkin's disease, potentially eligible for high-dose chemotherapy with reinjection of hematopoietic stem cells (HSC). If patients were considered chemosensitive after two courses of VIP, high-dose chemotherapy followed by the reinjection of HSC was planned. After two courses of VIP, 67% achieved an objective response including 38% complete responses. Overall, 28 patients went on to high-dose therapy with reinjection of HSC, and 46% of grafted patients are in a sustained complete remission. When the overall patient population is considered, 33% are in complete remission (CR) with a median follow-up of 37 months. A CR of less than 12 months and refractory disease were associated with a poor survival. These results showed that the VIP regimen is effective in relapsed or refractory HD and allows high-dose therapy to be given in the case of most responding patients. However, results in patients with refractory disease or a first complete remission of less than 12 months need to be further improved.

Adolescent↗
PubMed1998

T-cell clonal expansion in patients with B-cell lymphoproliferative disorders.

We investigated whether T-cell clonal expansion could be found in the blood of 14 untreated patients with B-cell lymphoproliferative disorders [5 B-chronic lymphocytic leukemia (CLL), 4 myelomas, 5 non-Hodgkin lymphoma (NHL)]. The putative presence of T-cell clonotypes was analyzed with a polymerase chain reaction-based method determining V-D-J junction size patterns in 24 T-cell receptor (TCR) V beta subfamilies. This high-resolution method, analyzing CDR3 sizes of TCR transcripts, was used in conjunction with cytometric analysis of the corresponding T-cell subpopulations with 18 TCR V beta-specific monoclonal antibody. We found multiple dominant T-cell clonotypes in the blood of most patients with B-CLL or myeloma as well of a patient with stage IV NHL. In some cases, T-cell clonal expansion was so dominant that the percentage of these clonal T-cell subpopulations in blood represented more than the mean +2 SD value determined in a series of healthy controls. We conclude that a systemic antigen-specific (i.e., leading to clonotypic expansion) immune reaction involving few TCR clonotypes is a hallmark of disseminated B-cell malignancies. The nature of the putative antigens recognized is not known presently. Nonetheless, such insights into the T-cell repertoire of these patients may help to reassess the potential of immunotherapeutic strategies in B-cell malignancies.

Adult↗
PubMed1998

Maintenance of remission with human recombinant interferon alfa-2a in patients with stages III and IV low-grade malignant non-Hodgkin's lymphoma. European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group.

PURPOSE: Interferon alfa has shown significant activity in patients with low-grade malignant non-Hodgkin's lymphoma (NHL). In 1985, we initiated a prospective randomized study in which the potential benefit of interferon alfa given as maintenance treatment was investigated after tumor load reduction was achieved with chemoradiotherapy in patients with advanced low-grade malignant non-Hodgkin's lymphoma. PATIENTS AND METHODS: The study involved 347 patients with stage III or IV disease, 315 satisfying the eligibility criteria. All were treated with a regimen of cyclophosphamide, vincristine, and prednisone (CVP) given every 3 weeks for eight cycles. Thereafter, patients were eligible for iceberg irradiation. Finally, all patients were completely restaged, and responding and stable-disease patients were then randomized, 122 to interferon alfa-2a maintenance, 3 million U three times weekly for 1 year; and 120 to no further treatment. RESULTS: Seventy-nine percent of the patients response to CVP, ie, 45% complete remissions (CR) and 34% partial remissions (PR). In the group of randomized patients, the response rate after CVP plus or minus radiotherapy was 90%. As compared with control patients, patients in the interferon (IFN) maintenance group had a tendency toward a prolonged time to progression (TTP) (median, 132 v 87 weeks; P = .054, adjusted for response to CVP). However, overall survival was similar in both groups. Interferon was well tolerated. The median dose of IFN actually received corresponded to 90% of the planned cumulative dose. The treatment had to be stopped because of toxicity in 16 patients (15% of the patients in whom IFN was started). CONCLUSION: Interferon maintenance treatment in the phase of minimal residual disease of patients with advanced low-grade malignant NHL increased TTP at the borderline of statistical significance, without remarkable toxicity. However, overall survival was not influenced.

Adult↗
PubMed1998

Phase II trial of fludarabine monophosphate in patients with mantle-cell lymphomas.

PURPOSE: The aim of this phase II trial was to assess the efficacy of fludarabine monophosphate in untreated and pretreated mantle-cell lymphomas (MCL). PATIENTS AND METHODS: Fifteen patients with MCL were included in the study. In two cases, fludarabine was the first-line therapy, the second in four cases, the third in five cases, and the fourth in four cases. The diagnosis of MCL was based on the criteria of the European Lymphoma Task Force (ELTF), with morphologic, immunologic, and cytogenetic data. Patients were treated with intravenous fludarabine 25 mg/m2/d for 5 days every 4 weeks. RESULTS: Toxicity of fludarabine was mild: World Health Organization (WHO) grade 3 and 4 granulocytopenia occurred in 15 of 56 assessable cycles (cy) (27%), there was no grade 3 or 4 thrombocytopenia, one grade 3 bacterial lung infection, and no treatment-related death. There were five partial responses (33%) but no complete response. The duration of these responses was short and ranged from 4 to 8 months. CONCLUSION: These results suggest that fludarabine can be moderately effective in the treatment of MCL. Fludarabine appears to be far less effective than in chronic lymphocytic leukemia (CLL) and follicular non-Hodgkin's lymphoma (NHL). Therefore, fludarabine should be evaluated in association with other chemotherapeutic agents in MCL.

Adult↗
PubMed1997

Mantle cell lymphomas: characteristics, natural history and prognostic factors of 45 cases.

We reviewed 77 cases considered as lymphocytic lymphomas of intermediate differentiation or diffuse centrocytic lymphomas. Forty-five cases were diagnosed as mantle cell lymphoma (MCL). The architectural pattern was diffuse in 95%, 8 cases presented large blastoid cells and CD5 positivity was observed in 28/34 cases. Of 20 cases studied, 8 presented a t(11;14)(q13;q32). Patient characteristics were: median age 59 years, B symptoms in 38%, 87% stages III-IV, bone marrow involvement in 67% with peripheral leukemic cells in 24%. Forty-four patients were treated with chemotherapy and 7 received radiotherapy. The complete response (CR) rate was 58%. Of the 26 CR, 19 relapsed at a median of 15 months. Disease-free survival was 42% and overall survival was 73% at 3 years. In a univariate analysis, overall survival was related to liver and bone marrow involvement, the presence of peripheral lymphomatous cells and achieving a complete response.

Adult↗
PubMed1997

Translocation t(4;11)(q21;q23) and MLL gene rearrangement in acute lymphoblastic leukemia secondary to anti topoisomerase II anticancer agents.

Secondary therapy-related, acute lymphoblastic leukemia (S-ALL) is less common than its myeloblastic counterpart. S-ALL with MLL gene rearrangements have only been reported on six previous occasions. Only three of these had t(4;11)(q21;23) S-ALL with MLL-AF4 fusion transcript has only been reported in one earlier case. In this report a rare case of S-ALL with MLL-AF4 transcript is described in a 36 year old woman treated for breast carcinoma with chemotherapy which included the topoisomerase II inhibitor, VP-16. The precise incidence of MLL gene rearrangement in S-ALL still remains to be clarified.

Adult↗
PubMed1997

[Hodgkin's disease trials conducted by the European Organization of Research and Treatment of Cancer (EORTC): their impact on the progress of cancerology].

Hodgkin's disease is a rare event that allowed key progress in the field of Oncology. Starting 1964 the EORTC has conducted a series of comprehensive controlled trials of outmost importance from the time of the first cures achieved with extended field radiotherapy until the observation that dose-response relationships could occur both for tumor control and for the incidence of second leukemia, cardiac, and pulmonary toxicities. Each of these steps is depicted in some detail. The contributions of the EORTC include in particular the first demonstration ever of the positive impact of an adjuvant chemotherapy on the freedom from progression and overall survival of a cancer (1964-1972), the identification of prognostic factors usable to adapt the aggressivity of treatment to patient's risks and the role of excess mortality from iatrogenic origin. Directions are indicated to insure a continuous progress to the Oncology field through additional Hodgkin's disease studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Persistent improved results after adding vincristine and bleomycin to a cyclophosphamide/hydroxorubicin/Vm-26/prednisone combination (CHVmP) in stage III-IV intermediate- and high-grade non-Hodgkin's lymphoma. The EORTC Lymphoma Cooperative Group.

CHOP has been and still is regarded by many as the 'standard' treatment of advanced non-Hodgkin's lymphoma. In 1980 the EORTC Lymphoma Cooperative Group started a study to evaluate the addition of vincristine and bleomycin to its standard four-drug combination chemotherapy, CHVmP (cyclophosphamide, hydroxorubicin, Vm-26, prednisone). Eligible patients were stage III or IV, intermediate- to high-grade non-Hodgkin's lymphoma (Working Formulation E-I). One-hundred-eighty-nine patients were entered, of whom 140 were eligible and evaluable. A previous report showed an improved response rate and failure-free survival (FFS) and overall survival for the combination CHVmP-VB. At ten years, the outcome still favors the addition of vincristine and bleomycin. The FFS was 34% vs. 23% and the overall survival 34% vs 22%. This difference was mainly due to a difference in CR rate (74% vs. 49%), Relapse-free survival for patients reaching a CR was the same in both arms. When the patients were grouped according to the International Prognostic Factor Index, no statistically significant difference could be observed in favor of one treatment within either group. This trial clearly demonstrates the benefit gained by the addition of vincristine and bleomycin to 'standard' chemotherapy for intermediate and high-grade non-Hodgkin's lymphoma.

Adolescent↗
PubMed1997

Patients with stage III/IV Hodgkin's disease in partial remission after MOPP/ABV chemotherapy have excellent prognosis after additional involved-field radiotherapy: interim results from the ongoing EORTC-LCG and GPMC phase III trial. The EORTC Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie.

BACKGROUND: Failure to reach complete remission (CR) with chemotherapy in advanced stages of Hodgkin's disease is considered a poor prognostic factor for progression-free and overall survival. The role of radiotherapy after chemotherapy-induced remission is controversial. PATIENTS AND METHODS: In 1989, the EORTC/GPMC started a randomized phase III trial on involved-field RT (IF-RT) after MOPP/ABV hybrid-induced remission in patients with stage III/IV Hodgkin's disease. In this ongoing trial, patients in CR after chemotherapy are randomized between IF-RT and no further treatment. Patients in partial remission (PR) all receive IF-RT. Patients, age 15-70 years, with previously untreated stage III/IV Hodgkin's disease are eligible. The randomized treatment arms are still blinded. The interim analysis of May 1996 focuses on the outcome of patients in chemotherapy-induced PR. RESULTS: A total of 405 of 493 registered patients were evaluable for response to chemotherapy. Fifty-nine percent of patients attained a CR, 37% a PR, and only 4% failed to respond. The IF-RT was actually given to 90% of the PR patients. After a median follow-up of 43 months, the five year progression-free and overall survival for patients in PR was 75% and 87%, respectively. CONCLUSION: IF-RT after MOPP/ABV-induced partial remission in stage III/IV Hodgkin's disease produces excellent failure-free and overall survival. Early intensification of treatment of this group of patients is not indicated.

Adult↗
PubMed1996

Sjögren's syndrome with acute renal failure caused by renal pseudolymphoma.

A 56-year-old man with Sjögren's syndrome was found to have acute renal failure. Immunopathologic analysis of renal biopsy specimens showed polyclonal lymphocytic interstitial infiltration. DNA analysis of the T-cell receptor and the heavy chain immunoglobulin genes showed a polyclonal pattern of gene rearrangements. Renal failure caused by this pseudolymphoma regressed dramatically with steroid therapy. This is the first reported case of proven renal pseudolymphoma that regressed with steroid therapy.

Acute Kidney Injury↗
PubMed1996

Hodgkin's disease. Diagnostic procedures.

The current movement towards "minimal' staging may induce an unexpected movement, calling for "more intensive' treatments. Indeed, some of the changes, such as the renunciation of the staging laparotomy and the lymphangiogram, make the final stage less secure and require reassuring treatments, i.e. more extensive radiotherapy or chemotherapy. This is not surprising when one considers the importance of the information that was brought by the laparotomy and the fact that laparotomy could not be replaced by any other procedure with comparable yield. The use of powerful initial prognostic factors, together with objective biological parameters, either non-specific ones coupled with long-term and adequate testing such as the ESR, albumin, blood counts, or new and promising tests such as for the soluble CD30 antigen, should make up for the loss. In addition, a dynamic approach to the disease, i.e. the repetition at reasonable intervals of initially abnormal biological, functional or imaging tests may provide the most reliable information to ensure the patient's safety.

Diagnosis, Differential↗
PubMed1996

Alternating chemotherapy and radiotherapy for limited-stage intermediate and high-grade non-Hodgkin's lymphomas: long-term results for 96 patients with tumors > 5 cm.

BACKGROUND: The role and timing of radiotherapy for optimal treatment of localized aggressive non-Hodgkin's lymphoma (NHL) is controversial. We report the long-term results of a single-institution pilot study of alternating chemotherapy (CT) and radiotherapy (RT) in patients with clinical stages I or II tumors exceeding 5 cm. PATIENTS AND METHODS: From 1981 to 1992, 96 patients with stages I-II aggressive NHL received an alternating regimen of CT and RT consisting of 8 cycles of CT with 3 courses of RT interjected after the 2nd, 3rd and 4th cycles of CT. The CT combined cyclophosphamide, doxorubicin, teniposide and prednisone every 28 days. Each RT course was started 8 to 10 days after CT (15 Gy in 6 fractions to initially involved and contiguous areas). RESULTS: The median age was 54 years. The disease predominantly located in the head and neck area was stage II in 63% of patients. Bulky tumors (10 cm or larger) were found in 24% of patients. Six patients discontinued CT because of acute toxicity (mucositis). The mean relative dose intensity achieved for doxorubicin, cyclophosphamide and teniposide were 72%, 82%, and 78%, respectively. Late toxicity consisted mostly of severe xerostomia lasting more than 2 years in 7 patients irradiated in Waldeyer's ring. The complete response (CR) rate was 91%; 20 of the 86 patients in CR relapsed (3 locally only). The median follow-up was 61 months, and at 5 years, overall survival (OS) was 77%. Classification according to the International Prognostic Factor Index was possible for 54 patients, all but three of whom were in the 'low risk' group (0-1 factor). Bulky disease was the only unfavorable prognostic factor (P < 0.001) for CR, freedom from progression (FFP) and OS rates; the low relative dose intensity of CT achieved in this study did not affect outcome. CONCLUSION: Alternating chemo-radiotherapy for localized aggressive NHL was feasible and yielded long-term results comparable to those obtained with standard treatments, despite a reduction in dose intensity considerably below that of CHOP which suggested synergistic effects of CT and RT in this scheme.

Adolescent↗
PubMed1996

Who are the high-risk patients with Hodgkin's disease?

The opinions concerning the prognosis of relapsing Hodgkin's disease (HD) are conflicting, although a number of clinical and biological parameters have been Identified. One reason is the rarity of large scale studies, another is the variability of populations and pretreatments In this particular disease, all factors that influence the relative weight of these parameters. Conversely, a large number of prognostic studies have been published in newly diagnosed HD, whether they concerned advanced or localized patients. Surprisingly, not so many parameters are common to these studies. Therefore, prognostic indexes are hardly usable, except if taken with great prudence. These uncertainties hamper the possibilities of conducting ample controlled studies designed to assess the best treatment modalities for high-risk HD, for both advanced or localized patients.

Age Factors↗
PubMed1995

Should poor risk patients with Hodgkin's disease be sorted out for intensive treatments?

Death remains a common event in patients with advanced stage Hodgkin's disease (HD) and also occurs in early stages. Identification of the population of HD patients who would best benefit from an intensification of the treatment is therefore necessary in both cases. A comparative review of prognostic criteria must be attempted through recent randomized trials using conventional treatment, independently of criteria used by the autologous bone-marrow transplant (ABMT) teams which rather aim to select relapsing patients. When freedom from progression (FFP) is considered in recent large series, the factors which most often predict for a high risk of failure are bulky mediastinum, B symptoms, stage in advanced HD and the number of nodal areas in early HD. However, prognostic data available to date cannot sort out any group of patients that would clearly require a high dose/potentially risky therapy. Because of the failure to identify consensual prognostic factors, the population considered till now for upfront intensification is restricted to a very small subgroup of patients with advanced disease (< to 5% of them), which makes the conduct of randomized trials very difficult within reasonable delays. The potential to identify and to clear part of the difficulties encountered with the prognostic analysis depends on the population studied: size of the data base, follow-up, disease stages, treatments given, outcome criteria selected. Finally, "sorted out" new patients with advanced and perhaps early stage HD may benefit from treatment intensification. As the initial selection characteristics are still poorly defined, a proposition is made to collect, eventually through the International Data Base for Hodgkin's Disease (IDHD) pertinent recent trials and to launch a survey. The results of the survey will be discussed at the Third International Symposium on Hodgkin's lymphoma in Köln (21-23 September 1995). Hazards of intensified regimens may be better quantified by then, so that newer more efficient strategies may be designed.

Antineoplastic Combined Chemotherapy Protocols↗