Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Société Française de Greffe de Moelle.

PURPOSE: To compare hematologic recovery in patients receiving allogeneic blood cell transplantation (BCT) with those receiving allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: One hundred eleven patients with leukemia in the early stages and with HLA-matched sibling donors were randomized in this study. One hundred one underwent transplantation. Standard procedures for collection and transplantation were used. Patients did not receive prophylactic granulocyte colony-stimulating factor after undergoing transplantation. In addition to clinical end points being established, a prospective and comparative economic evaluation of the first 6 months after transplantation was performed. RESULTS: Groups were balanced for patient, donor, and transplant characteristics. Blood cell collection led to the collection of a higher number of CD34(+) and CD3(+) cells than did bone marrow collection (P < 10(-6)) without reported side effects for the donor. Patients in the BCT group reached platelet counts of 25 and 50 x 10(9) platelets/L 8 and 11 days earlier than did the BMT group (P < 10(-4) and P < 10(-5)), respectively. This resulted in fewer platelet transfusions during the first 180 days after transplantation (P =.002) for the former group. The time to reach neutrophil counts of 0.5 and 1 x 10(9) neutrophils/L was 6 and 7 days shorter, respectively, in the BCT group than in the BMT group (P < 10(-5)). This quicker hematologic recovery was associated with a shorter length of hospitalization and a decrease in total cost of procedure during the first 6 months. CONCLUSION: This study establishes that allogeneic BCT results in quicker hematologic recovery but is associated with a higher occurrence of chronic graft-versus-host disease.

[Prescription of a hematopoietic growth factor, lenograstim, in current practice. Results and commentaries of a national survey from April 1995 to March 1996]. / Prescription d'un facteur de croissance hématopoïétique, le lénograstime, en pratique courante. Résultats et commentaires, à partir d'une enquête nationale réalisée d'avril 1995 à mars 1996.

OBJECTIVES: The French drug authorities audited first-time prescription of hematopoietic growth factors using a prescription follow-up survey. Data collected between April 1995 and March 1996 were analyzed then criticized by three clinical experts working in three different areas where lenograstime is most widely used. METHODS: First-time prescription data and follow-up information were recorded on separate inclusion and follow-up diaries by the prescribing physicians. The delivering pharmacies complete the diaries and addressed them to the INSERM unit 330 for analysis. RESULTS: There were 7,102 inclusion diaries and 1376 follow-up diaries from 234 different hospital facilities. Lenograstime was most frequently prescribed in patients with lymphoma (19%), breast cancer (16.4%), and lung cancer (13.8%). Prescriptions involved 377 different chemotherapy protocols, including 196 which concerned a single patient. At the first prescription, lenograstime was given as a preventive measure in 61% of the cases and for curative therapy in 25.3%. The planned duration of preventive treatment was longer than the true period of treatment. DISCUSSION: Pr Rossi, hematologist, Pr Misset, cancerologist and Pr Lebeau, pneumologist criticized the findings.

Mobilisation of healthy donors with lenograstim and transplantation of HLA-genoidentical blood progenitors in 54 patients with hematological malignancies: a pilot study.

Blood cell transplantation (BCT) is now common practice in the autologous setting. We performed a pilot study of allogeneic BCT, collected after the priming of an HLA-identical sibling with a glycosylated rhu-G-CSF (lenograstim) (10 microg/kg). Fifty-four patients were included (38 +/- 11; M/F = 33/21; CML (n = 17), AML (n = 14), ALL (n = 15); MDS (n = 8)). Transplant procedures were standard (TBI regimen = 47 (87%); MTX-CsA: n = 37; CsA-PDN: n = 17). No serious adverse events were reported in donors. A median of 11 (3.5-29.1) x 10(6)/kg CD34+ cells, 332 (33-820) x 10(6)/kg CD3+ cells were collected. Four patients did not engraft (early death: n = 2; graft failure: n = 2). Fifty-one patients initially recovered 0.5 x 10(9)/l ANC and 25 x 10(9)/l platelets at 15 (10-30) and 13 (9-188) days. 29/51 and 29/38 experienced grade > or =2 acute and chronic GVHD. With a median follow-up of 25 months (18-36), relapse rate is 16% +/- 8, survival and DFS probabilities are similar (50% +/- 13). A better outcome is documented for patients under 45 years and in the early phase of the disease (n = 28), with an identical survival and DFS of 71% +/- 13. In conclusion, lenograstim is a potent rhu-G-CSF for mobilisation of allogeneic hematopoietic progenitors. Two-year follow-up indicates good haematological recovery but some concerns about graft failure and chronic GVHD have arisen deserving prospective evaluation.

Extensive apoptosis of lung T-lymphocytes maintained in vitro.

The phenotypic and functional properties of T cells recovered from the lung indicate that many of these cells have been recently activated. Because such recently activated cells are often more susceptible to death through apoptotic mechanisms, the viability of lung T cells recovered from bronchoalveolar lavage and those isolated from peripheral blood was compared. The progressive loss of viable cells following in vitro culture was considerably greater for lavage T cells than blood T cells, and was observed for cells from both patients with sarcoidosis and control subjects. Following 4 days of culture, 76 +/- 14% of blood cells, but only 31 +/- 13% of lavage cells from sarcoid patients were viable. The evaluation of morphologic features and flow cytometric profiles, as well as the demonstration of typical oligonucleosomal fragmentation of DNA extracted from these cells indicated that lavage T cells were dying by apoptotic mechanisms. CD4+ T cells appeared to be particularly sensitive to apoptosis. Most lavage T cells from controls and sarcoid patients expressed Fas (CD95) antigen. Although some lavage T Cells were sensitive to Fas-induced apoptosis, the viability of lavage T cells was not improved by incubation in the presence of a monoclonal antibody that inhibits Fas-induced apoptosis. Culture in the presence of interleukin 2 did prevent, at least in part, the progressive death of lavage T cells, suggesting that the viability of T cells in the lung may depend on the presence of locally delivered trophic signals. These studies emphasize that T cells on the alveolar surface are in a different state of activation and differentiation compared with that of circulating T cells, and offer a possible explanation for the impaired functional capacities observed for lavage T cells in some in vitro studies.

Colony-stimulating factors as an adjunct to chemotherapy in small cell lung cancer.

Myelosuppression is the major dose-limiting toxicity of chemotherapy in small cell lung cancer (SCLC). The capacity of colony stimulating factors (CSFs) to stimulate granular neutrophil recovery may be of great value to prevent or cure febrile neutropenia and to increase dose-intensity. The aim of this review was to assess the current use of CSFs in SCLC on the basis of experimental and clinical data. Primary CSF administration has been shown to reduce the incidence of febrile neutropenia, hospital admission rate, and antibiotic use subsequent to cyclophosphamidedoxorubicin-high dose etoposide (CDE) chemotherapy, without improvement of survival or disease control. Primary CSF administration may be recommended when the expected incidence of febrile neutropenia is at least 40%. This benefit has not been established with less myelosuppressive regimens, such as cisplatin-etoposide (PE), which remains an alternative combination of SCLC when standard doses are used. A trial comparing high-dose CDE + CSF with PE would be of considerable interest. There is currently little clinical basis for the use of CSFs to increase chemotherapy dose-intensity, outside clinical trials. Peripheral blood progenitor cells mobilized with CSFs offer interesting prospects. Further studies, with later initiation, shorter duration or lower doses of CSFs, are warranted to improve the cost-effectiveness of CSFs. CSF therapy in addition to antibiotics is normally not justified in febrile neutropenia, except perhaps in selected patients with sepsis syndromes, hypotension or pneumonia.

[Chemotherapy of small cell bronchial cancers. Prognostic importance of complete response (1,280 patients). Groupe Petites Cellules]. / Chimiothérapie des cancers bronchiques à petites cellules. Importance pronostique d'une réponse complète (1,280 patients). Groupe Petites Cellules.

OBJECTIVE: Pretherapeutic prognostic factors for patients given chemotherapy for small cell lung carcinoma have been widely studied. We evaluated response to chemotherapy in patients included in 4 multicentric trials with less restrictive entry criteria in order to determine the contribution of clinical outcome as a predictive factor. METHODS: Pretherapeutic and therapeutic prognostic factors were assessed in 1280 patients included in 4 successive multicentric therapeutic trials on chemotherapy for small cell lung carcinoma conducted from January 1, 1983 to April 1, 1992. Logrank test for univariate analysis and Cox's stepwise method for multivariate analysis were used to evaluate the results. RESULTS: Univariate analysis identified pretherapeutic factors as significant for prognosis: Karnofsky index (p < 0.0001), alkaline phosphatase level (p < 0.0002), white cell count (p < 0.0005), age (p = 0.0007), presence of brain metastasis (p = 0.0004), presence of liver metastasis (p = 0.03), initial extension (p = 0.04). Multivariate analysis taking into account pretherapeutic and therapeutic factors demonstrated that complete response after the second and after the sixth treatment session were predictive of longer survival (p = 0.0001). This factor was more powerful than all the pretherapeutic factors including the Karnofsky index, initial extension and brain metastasis. CONCLUSION: For patients with small cell lung carcinoma, the prognostic value of early response to chemotherapy suggests that high-doses should be used starting at the first session.

[Treatment of small cell bronchopulmonary cancers]. / Traitement des cancers bronchopulmonaires à petites cellules.

nn small cell lung cancer, the main treatment modality is chemotherapy, combinated with early thoracic radiation therapy for patients with complete response. The treatment of relapse with chemotherapy is efficient. The precocity of the response after initiating multimodality treatment is the main prognosis factor. The prophylactic cranial irradiation reduce the frequency of brain metastases, but has no significant effect on survival. Patients with very limited small cell lung cancer (TNM stage I and II) can be managed by surgery. Association with colony stimulating factors can lessen the severity of neutropenic and infectious episodes. The role of maintenance therapy by interferon alpha in clinically disease free patients is suggested.

[Consequences of specific prevention on the diagnosis of Pneumocystis carinii pneumonia in patients with HIV infection. Comité SIDA de l'Hôpital Saint-Antoine]. / Conséquences de la prophylaxie spécifique sur le diagnostic de pneumocystose pulmonaire chez les sujets infectés par le VIH. Comité SIDA de l'Hôpital Saint-Antoine.

In a prospective study the authors compared the clinical, radiological, biochemical and diagnostic features of Pneumocystis carinii pneumonia (PCP) in HIV-infected patients who were or were not receiving a specific prophylactic treatment. The study included 386 patients with suspected PCP, 201 of whom were under specific prophylactic therapy. Induced expectoration and/or bronchoalveolar lavage provided a diagnosis of PCP in 89 patients, 21 of whom were under specific prophylaxis. Apart from a number of circulating CD4 lymphocytes that was significantly lower in the patients under prophylaxis, there was no significant difference between the two groups. Thus, being under specific prophylaxis should have no effect on the diagnosis of PCP in HIV-infected patients.