AIMS AND BACKGROUND: Both flow cytometric DNA ploidy and proliferative activity have been indicated as potential prognostic indicators in colorectal cancer. Due to tumor biological heterogeneity, these parameters are best assessed with multiple sampling. METHODS: We undertook a prospective study on 52 patients with Duke's D colorectal tumors looking at multiple samples of the primary tumors and liver metastases. DNA ploidy and tumor proliferative activity (derived from proliferating cell nuclear antigen, PCNA FCM expression) were evaluated. RESULTS: Of primary tumors, 36/52 (69.2%) were aneuploid in at least 1 sample, with a median value of the DNA index of the aneuploid peak of 1.58. On liver metastases, 42/52 (80.7%) patients were aneuploid in at least 1 sample with a median DNA index of the aneuploid peak of 1.64. Identical or nearly identical histograms from different tumor samples were observed in only 18/52 (34.6%) of the primary tumors and in 15/52 (28.8%) of the liver metastases. The PCNA values for primary tumors ranged from 5 to 28% (median value = 16.5%). In the liver metastases, PCNA values ranged from 12 to 38% (median value = 19.8%). Proliferative activity was lower for diploid than for aneuploid tumors. DNA ploidy and PCNA expression of the deep specimen of primary tumors were similar to those of the liver metastasis of the same patient while this concordance was not complete in the case of superficial biopsy specimens. CONCLUSIONS: If correctly performed, FCM techniques allow an accurate analysis of DNA ploidy and proliferative activity and both these measurements can offer considerable potential for a more comprehensive approach to colorectal cancer.

Adenocarcinoma↗

PubMedDate not supplied

MOPP/ABV/CAD chemotherapy with and without recombinant human granulocyte-macrophage colony stimulating factor in untreated, unfavorable prognosis Hodgkin's disease.

Seventeen consecutive patients with previously untreated poor prognosis Hodgkin's disease (clinical stage II and III with systemic symptoms, and stage IV) received 6 courses of aggressive chemotherapy, with (9 patients) and without (8 patients) the addition of recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF). Chemotherapy (MOPP/ABV/CAD regimen) included full doses of nitrogen mustard, lomustine (CCNU), vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine and bleomycin, and was administered between days 1 and 15 of each course. Course were planned for 28-day intervals. rhGM-CSF was given at a dose of 5 micrograms/kg/day subcutaneously from day 16 to 26 of each course. With cytopenia (i.e. white blood cell, WBC, count < 3.0 x 10(9)/L and/or platelet count < 100 x 10(9)/L) delaying courses was preferred to administering reduced drug dosages. Substantial delays (ranging from 7 to 28 days) in delivering cytostatics were necessary between 70% of courses. The cumulative mean number of days for which the courses had to be delayed before completing the 6 MOPP/ABV/CAD courses was 57. The percentage of planned doses of cytotoxic drugs (nitrogen mustard, melphalan, epidoxorubicin, procarbazine) actually administered was 92%. Causes of treatment delay were presented by leucopenia in 82% and by leuco-thrombocytopenia in 23% of the courses. The WBC nadir was constantly encountered at day 20-21 following completion of courses, and slightly worsened with subsequent courses. The decrease in platelet values was milder than that in WBC counts. There were no differences in any of the above parameters between patients treated with MOPP/ABV/CAD alone or followed by rhGM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Flow cytometry: its applications in hematology.

The techniques of flow cytometry are becoming more and more important for the clinical hematology laboratory. No longer a novelty confined to a few specialized institutions as it was 10 years ago, flow cytometry has blossomed into a mature discipline. The methodology is well-known, the mechanical apparatus is readily available, and the role it plays in clinical hematology is increasingly appreciated. The burgeoning number of scientific articles devoted to this topic attests to the interest it has aroused as a tool for both medical research and patient care. In fact, more than a thousand such papers are now published each year and it would be impossible to deal with all the methodologies and applications of FCM currently utilized or under development. Throughout this paper four relevant hematologic fields are briefly discussed, in which FCM appears to be of great help at present: the immunophenotyping of leukemias and lymphomas, the measurement of proliferative activity and DNA ploidy in hematological malignancies, the detection of drug resistant leukemic cells and the use of FCM in the study of platelets.

Flow Cytometry↗

PubMedDate not supplied

Circulating progenitor cell collection: experience from 275 leukaphereses in various malignancies and in healthy donors.

BACKGROUND: Blood cell transplantation has become a new type of support in high-dose chemotherapy (HDC) for several oncologic and hematologic diseases. Over the last few years the demand for circulating progenitor cell (CPC) collection by blood cell separators has grown dramatically, and transfusion services must manage new CPC programs. MATERIALS AND METHODS: A protocol for optimizing the collection and clinical use of CPC is described. The results of 275 harvestings were studied: 128 patients were divided into 5 groups according to tumor type (A: breast cancer; B: Hodgkin's disease; C: non-Hodgkin lymphoma; D: multiple myeloma; E: various solid tumors). An additional group (F) consisted of 11 healthy donors. Factors affecting collection (mobilizing regimen or previous radiation therapy) and side effects were investigated. RESULTS: The mean values of mononuclear cells (MNC x 10(7)/kg) and CD34+ cells (x 10(6)/kg) collected per leukapheresis in the 6 respective groups were: 31.4 and 4.6 in group A; 26.4 and 3.4 in group B; 21.8 and 5.8 in group C; 24.6 and 2.4 in group D; 26.8 and 2.9 in group E; 60 and 6 in group F. Previous chemotherapy and/or radiation therapy were the main factors influencing CPC harvesting. The different chemotherapy regimens employed demonstrated no significant differences in their mobilizing efficacy. Side effects related to leukapheresis were few (2.3% of the procedures) and manageable. CONCLUSIONS: CPC collection is feasible in a wide range of clinical situations. Careful clinical evaluation of patients, accurate monitoring of progenitor cell release and collection timing are important for obtaining a sufficient number of CPC for hemopoietic recovery. Previous chemotherapy and radiotherapy are the main factors influencing CPC harvests. The mobilizing regimens employed showed no substantial differences in their efficacy.

Adult↗

PubMedDate not supplied

The expression of proliferation and quiescence associated antigens in acute myeloid leukemia correlates with survival duration: analysis of 15 refractory cases.

In this study, blast cells from 15 patients with acute myeloid leukemia resistant to induction therapy were examined with two monoclonal antibodies that identify, respectively, the nuclear protein specifically expressed in non proliferating cells (statin) and the proliferating cell nuclear antigen (PCNA). We found that statin values varied widely, ranging from 0.6% to 14.7% (mean value 6.4%). When the patients were subdivided according to the mean value, those presenting with higher statin values survived for a shorter period of time than the ones characterized by lower levels (p = 0.003). We observed a wide variation in the range of PCNA values; however, if an agreement between survival duration and at least one of the proposed markers was considered, all but one case displayed concordance between survival duration and PCNA and/or statin values (in addition, 4/15 cases showed agreement for both markers). These preliminary data could indicate a possible discriminating prognostic factor between categories of patients characterized by different aspects of resistance, perhaps susceptible to different salvage therapy approaches.

Acute Disease↗

PubMedDate not supplied

Cytokine receptors, growth factors and cell cycle in human bone marrow and peripheral blood hematopoietic progenitors.

BACKGROUND AND OBJECTIVE: An increasing number of growth factors have been shown to be responsible for the proliferation, survival and enhanced function of many cell types within the hemopoietic system. The action of these hemopoietic growth factors in stimulating cell growth and survival applies both to cells within the progenitor compartment and mature cells. Whether a specific cytokine influences in vivo hematopoietic progenitor cell proliferation or survival depends on cytokine-mediated modulation or target cell cytokine receptors, cell proliferation, and cell death regulator genes and other pathways. To address these issues, particularly in view of the current and future clinical use of hemopoietic growth factors, the Italian Society of Experimental Hematology organized a Meeting in Florence on July 4th, 1996. INFORMATION SOURCES: The material examined in the present review includes full papers and abstracts published in journals covered by the Science Citation Index and Medline. All the participants to the Meeting in Florence have been actively working in the field of biology and clinical application of hemopoietic growth factors. Summaries of their oral presentations at the Florence Meeting are reported in the Appendix to this article. STATE OF ART AND PERSPECTIVES: Myelopoietic growth factors particularly granulocyte (G-) colony-stimulating factor (CSF) and granulocyte-macrophage (GM)-CSF, have been available for clinical use for only a few years but they have already markedly changed the management of chemotherapy-induced neutropenia, the use of dose-intensive chemotherapy regimens and the practice and safety of autologous stem cell transplantation. While these growth factors have been rapidly introduced as routine agents in the management of cancer patients, they have continued to generate a considerable amount of fundamental research into the biology of hematopoiesis as well as the growth regulation of normal and cancer cells. For instance, one goal of cancer treatment is to protect hematopoietic stem and progenitor cells from the damaging effects of chemotherapy, while maintaining their anticancer action. Any means of preferentially and reversibly suppressing the proliferation of normal hematopoietic stem and progenitor cells while leaving the proliferation of tumor cells and their susceptibility to chemotherapy unmodified, could potentially optimize treatment efficacy. In this field, the possibility of using colony-stimulating factors as myeloprotective agents in dose-intensive chemotherapy to enhance anticancer activity could be an attractive goal of current anti-cancer treatment modalities.

Bone Marrow Cells↗

PubMedDate not supplied

[Novel ways of using hemopoietic growth factors].

The myelopoietic growth factors, in particular G-CSF and GM-CSF have been available for clinical use for only a few years but they have already profoundly affected the management of chemotherapy-induced neutropenia, the use of dose-intensive chemotherapy regimens, and the practice and safety of autologous stem cell transplantation. While these growth factors have rapidly been introduced as routine agents in the management of cancer patients, they have continued to generate a considerable amount of basic research on the biology of hematopoiesis as well as on the growth regulation of normal and tumor cells. One attractive possibility offered by growth factors is to protect hemopoietic stem and progenitor cells from the toxic effects of chemotherapy, while not diminishing its anti-tumor action. Any means of preferentially and reversibly suppressing the proliferation of normal hemopoietic stem and progenitor cell while leaving unmodified the proliferation of tumor cells and their susceptibility to chemotherapy, could potentially optimize treatment efficacy. In the present paper, we have briefly discussed the possibility to use the myeloid growth factors as myeloprotective agents in the context of drug-intensified chemotherapy on the basis of the results obtained during some clinical trials recently conducted in patients with advanced cancer.

Antineoplastic Agents↗