[Marginal zone B-cell lymphoma affecting the skin: histological and phenotypic study of 49 cases]. / Lymphome cutané de la zone marginale : étude histologique et immunophénotypique de 49 cas.

BACKGROUND: No histological or clinical criteria allow distinction between primary cutaneous marginal zone B-cell lymphoma (MZL) and secondary cutaneous forms of systemic marginal zone B-cell lymphoma. Consequently, staging alone can indicate the origin of lymphoma. Lymphoma is considered as primary cutaneous only if no other extracutaneous sites are found. We studied the histological appearance of 49 cutaneous lymphomas in order to find distinctive criteria indicative of an extracutaneous origin. MATERIALS AND METHODS: This was a retrospective descriptive study of histological appearance for 49 patients with cutaneous marginal lymphoma: 29 cases of the primary form and 20 cases with extracutaneous involvement. RESULTS: Comparison of histological criteria did not reveal any differences between the primary cutaneous form and others forms. No prognostic criteria for relapse were found. DISCUSSION: A cutaneous tropism of primary MZL suggested the hypothesis of specific cutaneous receptors on B-cells that could have led to different histological appearances depending on the origin of the lymphoma. However, our study did not confirm this hypothesis.

Inhibition of normal lymphocyte proliferation by Indirubin-3'-monoxime: a multifactorial process.

Indirubin-3'-monoxime (IO) is a derivative of Indirubin, compound of a Chinese medicinal recipe used to treat various diseases including leukemia. In this study, we investigated to what extent IO inhibits the growth of normal human lymphocytes. We defined various experimental conditions of peripheral blood lymphocyte treatment: IO introduced (i) on unstimulated lymphocytes, (ii) or on stimulated lymphocytes at the time of phytohemagglutinin stimulation (L1 protocol), (iii) 48 h after the beginning of stimulation (L2 protocol), and (iv) after nocodazole synchronization of stimulated lymphocytes. IO induces a concentration dependent cytotoxic effect yielding a characteristic sub-G1 peak in normal stimulated lymphocytes. Cell death was partly due to necrosis and apoptosis. Normal unstimulated lymphocytes remained insensitive to the cytotoxic effect of 10 microM IO treatment. A cell cycle inhibition was observed after IO treatment, stronger for the L1 than for the L2 protocol, without induction of polyploidy after Nocodazole synchronization. These cellular consequences were associated with a decrease in CDK activity, and with CDK and cyclin gene expression modifications. The inhibition of lymphocyte proliferation by IO indicates that indirubin derivatives may be potent immunosuppressive agents.

Bone marrow involvement in systemic lupus erythematosus.

BACKGROUND: Besides peripheral cytopenias, bone marrow abnormalities, such as fibrosis, pure red cell aplasia and aplastic anemia have been reported in patients with systemic lupus erythematosus (SLE), suggesting that bone marrow may be a 25 target organ in SLE. AIM: Our objective was to describe this bone marrow involvement. METHODS: This registry is a nationwide retrospective study. Centers provided data concerning medical history, SLE manifestations, type of hematologic disorder, treatments and outcome. Bone marrow aspirations and/or biopsies were transferred for centralized review. RESULTS: Thirty patients from 19 centers were included. Central hematologic manifestations comprised bone marrow fibrosis (n = 17; 57%), pure red cell aplasia (n = 8; 27%), myelodysplastic syndrome (n = 3; 10%), aplastic anemia and agranulocytosis (n = 1; 3% each). Bone marrow involvement was diagnosed concomitantly with SLE in 12 patients. Bone marrow biopsies showed fibrosis in 19 cases, including one case of pure red cell aplasia and one case of agranulocytosis and variable global marrow cellularity. Treatments included corticosteroids (90%), hydroxychloroquine (87%), rituximab (33%), intravenous immunoglobulins (30%), mycophenolate mofetil (20%) and ciclosporine (20%). After a median follow-up of 27 months (range: 1-142), 24 patients manifested complete improvement. No patient died. CONCLUSIONS: This registry comprises the largest series of SLE patients with bone marrow involvement. It demonstrates the strong link between SLE and bone marrow fibrosis. Patients with atypical or refractory cytopenia associated with SLE should undergo bone marrow examination to enable appropriate, and often effective, treatment. Long-term prognosis is good.

v-erbA oncogene abrogates growth inhibition of chicken embryo fibroblasts induced by retinoic acid.

Retinoic acid inhibits chicken embryo fibroblast (CEF) proliferation by altering the G1 phase of the cell cycle with induction of a strong increase in the generation time. This growth-inhibitory response to retinoic acid is abrogated by expression of the v-erbA oncogene, suggesting an interference between retinoic acid receptors and the v-ErbA oncoprotein. Moreover, CEF expressing either the v-src, v-jun or v-fos oncogenes are also insensitive to retinoic acid treatment. In contrast, CEF expressing either the v-myc, v-myb-ets, v-mil, v-sea or v-erbB oncogenes are still sensitive to retinoic acid. These data strongly suggest functional interferences between the retinoic acid receptors and the AP-1 transcription factor complex in the control of expression of genes involved in CEF proliferation.

Intensive and sequential combination chemotherapy for aggressive malignant lymphomas (protocol LNH-80).

Ninety-seven patients with aggressive malignant lymphoma (ML) were treated with an intensive and sequential chemotherapy (protocol LNH-80). There were 42 patients with intermediate grade ML, 53 patients with high-grade ML, and two patients with true histiocytic ML. Most of the patients were in advanced stage: 21 stage III and 61 stage IV. The LNH-80 protocol schedule comprised three phases: (1) induction with three courses of an intensified CHOP-Bleo (cyclophosphamide, doxorubicin, vindesine, methylprednisolone, and bleomycin); (2) consolidation with cytarabine, followed by high-dose methotrexate and folinic acid rescue, then asparaginase; and (3) final intensification with two courses of CVAP-Bleo (cyclophosphamide, teniposide, cytarabine, methylprednisolone, and bleomycin). CNS prophylaxis included one injection of methotrexate during each induction course and the drugs of the consolidation phase. In cases of initial CNS localization, cranial radiotherapy was added. Eighty-four patients (87%) went into complete remission (CR), 18 (21%) of whom relapsed, usually during the phase of treatment or within 6 months of completing chemotherapy. Sixty-three patients are alive with an overall median follow-up of 24 months. The median survival time and the median disease-free survival have not been reached, and the survival curve seems to have plateaued at above 60%. There was no statistical difference between intermediate-grade ML (CR 90%, relapse 18%) and high-grade ML (CR 84%, relapse 24%). The toxicity of this treatment is mainly encountered during the induction phase: almost all patients had short-term neutropenia, less than 0.500 g/L in 57, with a documented infection in 25. Overall treatment-related mortality was 6%, with four patients dying during the induction phase.

Myeloid differentiation antigens identify leukemic cell subpopulations with different cell cycle characteristics.

In order to assess the proliferative capacity of leukemic subpopulations and to know whether it can be related to the stage of maturation, the expression of two surface antigens identifying distinct steps of leukocyte differentiation (CD15 and CD34) was studied by flow cytometry in correlation with DNA content in 16 cases of acute myeloid leukemia (AML). The surface markers were studied by indirect immunofluorescence, using the monoclonal antibodies VIMD5 (anti-CD15) and MY10 (anti-CD34). The percentage of cells stained by each antibody and the intensity of staining were heterogeneous. Double-staining showed that a small percentage of cells coexpressed both antigens. A correlation was found between the percentage of cells stained by MY10 and the percentage of cells in S + G2 + M in the whole population (p less than 0.05). The percentage of cells in S + G2 + M was significantly higher in MY10-positive than in MY10-negative cells (p less than 0.005), and also higher in VIMD5-positive than in VIMD5-negative cells (p less than 0.005). In the 14 cases expressing both antigens, the percentage of cells in S + G2 + M was higher in VIMD5-positive than in MY10-positive cells (p less than 0.05), whereas there was no difference between VIMD5-negative and MY10-negative cells. It is concluded that the phenotype heterogeneity observed in leukemic cell populations is associated with differences in proliferative capacities. The subset of leukemic cells with the more mature phenotype (CD15-positive) has the highest proliferative activity.

DNA, RNA, and protein content in adult acute myeloid leukemia: effects of cytostatic drugs in vivo.

DNA, RNA, and/or protein cellular content were studied by flow cytometry in 52 cases of acute myeloid leukemia before and on day 4 of remission induction treatment. Bone marrow (BM) samples were stained after fixation by acridine orange for DNA and RNA content (37 cases) and by propidium iodide and fluorescein isothiocyanate for DNA and protein content (52 cases). A positive correlation was found between pretreatment protein content and BM blast involvement: the higher the percentage of blasts in BM smears the higher the mean protein content (p less than 0.05). Protein content was higher in monoblastic leukemia (M4 and M5) than in the granulocytic types (M1, M2, M3) (p less than 0.05). S + G2 + M was higher in patients with protein content below 80 arbitrary units than in the subgroup with protein content above this threshold (p less than 0.05). Pretreatment RNA content, estimated by the RNase-sensitive fraction of G1 cells, was significantly higher in undifferentiated and M1 leukemias than in the other cytological groups (p less than 0.0001). This fraction was higher in patients who subsequently achieved complete remission, but it was not related to BM blast involvement or proliferative fraction of cells. During cytostatic treatment the changes in RNA and protein content did not follow a typical pattern. The connections between variations of DNA, RNA, and protein content and prognosis are examined and their possible relation to drug-induced blast cell maturation is discussed.

Continuous-infusion daunorubicin and carboplatin for high-risk acute myeloid leukemia in the elderly.

Since continuous infusion of daunorubicin and of carboplatin have shown efficacy and reduced toxicity in early phase studies in acute myeloid leukemia (AML), 34 elderly patients with high-risk AML were treated with continuous infusion daunorubicin, 30 mg/m2 per day, from day 1 to day 4, and carboplatin, 200 mg/m2 per day from day 3 to day 7. Seven patients had therapy-related AML and/or AML following a myelodysplastic syndrome at diagnosis, 15 were in first and two in second relapse, and 10 were resistant to previous anthracycline and cytarabine therapy. Nine patients or 26%, with a 95% confidence interval (CI) ranging from 18-67%, achieved complete remission, including one patient at diagnosis (14%, CI: 0-58%), seven with relapsed AML (41%, CI: 18-67%), and one with resistant AML (10%, CI: 0-45%). Median durations of neutropenia below 0.5 x 10(9)/l and of thrombocytopenia below 20 x 10(9)/l were 24 and 20 days respectively. Severe toxicity included infections in 20 patients (59%), bleeding in two (6%), cardiac anomalies in two (6%), and vomiting in one (3%). Overall four patients (12%) died from chemotherapy related toxicity and 21 (62%) had resistant disease. Median overall survival was 4 months and median disease-free survival 8 months. We conclude that this regimen had efficacy with reduced toxicity in relapsed patients. Higher dosages for the same drugs could be tolerated by better risk patients for precise evaluation of cross reactivity with cytarabine-based regimens.

Expression of cell cycle regulatory proteins in chronic lymphocytic leukemias. Comparison with non-Hodgkin's lymphomas and non-neoplastic lymphoid tissue.

The expression of certain cell cycle regulatory proteins: cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin E, Bcl2 and PCNA was examined in peripheral blood lymphocytes (PBL) from 25 cases of chronic lymphocytic leukemias (CLL) in order to analyze a possible cell cycle involvement of CLL lymphocytes. For comparison, we also studied the expression of these proteins in: 23 samples of non-Hodgkin's lymphoma (NHL) tissue of different histological types, 10 samples of non-neoplastic lymphoid tissue (NLT), non-stimulated PBL (NS-PBL) and PHA-stimulated PBL (PHA-PBL) from three healthy donors. Samples were lysed and proteins were resolved on polyacrylamide gel followed by Western blot. The expression of cdk4 and cyclin E, both known to act in early cell cycle stage, was approximately on the same level in all groups of lymphoid pathology examined. In particular, we found that that 19 out of 24 CLL cases were cyclin E positive and all but one were cdk4 positive, ie they expressed these markers over twice the level of non-stimulated healthy PBL. The cdk1 expression was above the level seen in NS-PBL in 14 (56%) cases, but the average expression was significantly lower than in the other tissues examined, including low-grade lymphomas. Cdk2 expression was comparable in CLL and in low malignancy grade NHL, but weaker than in other NHL and in NLT. Cyclins A and B, normally observed in advanced cell cycle phases, were not seen in any CLL case. The presence of cdk4 and cyclin E in the blood cells of the majority of CLL cases studied, as well as cdk1 and cdk2 in some cases, indicate that the CLL cells are not quiescent, but are blocked in an early stage of the G1 cell cycle phase, and/or that the expression of these proteins is pathologically deregulated.

Enhanced expression of p16ink4a is associated with a poor prognosis in childhood acute lymphoblastic leukemia.

The tumor suppressor gene p16ink4a is homozygously deleted in numerous T as well as in some B lineage acute lymphoblastic leukemia (ALL). We therefore analyzed the clinical and biological implications of this feature by studying p16ink4a expression in 58 cases of childhood ALL. mRNA and protein were significantly correlated and both appeared more highly expressed in B than in T lineage ALLs: 13 out of the 15 T cell ALLs did not show any p16ink4a expression. The main result of this study is the strong prognostic value of p16ink4a expression. When stratifying the patients in three groups according to p16ink4a expression, we observed in univariate analysis: (1) the shortest disease-free survival for patients presenting a high p16ink4a level; (2) contrasting with the good prognosis in the group of patients expressing p16ink4a at low level; (3) while cases without any expression of the inhibitor were associated with a medium course of the disease (P=0.0165). This prognostic value was confirmed by the multivariate analysis showing therapeutic regimen and p16ink4a protein expression as the only variables retained in the model. A specific metabolic profile related to cellular survival and proliferation was observed in each of the three p16ink4a expression groups. Among the cell cycle-related proteins we analyzed, only p21waf1 bcl-2 and CDK4 were significantly and positively correlated to p16ink4a. Furthermore, CDK6 was also strongly expressed in the group of cases with high p16ink4a level. An enhancement of p16ink4a, p21waf1 and bcl-2 was previously described in prolonged cellular survival, while aging cells showed a decrease in CDK4 expression. The concomitant high expression of the oncogenic protein CDK4 (and of CDK6), we observed, may amplify the leukemic advantage of prolonged lifespan blast cells by favoring cell progression through G1 phase. These data suggest that at least two mechanisms may be associated in the oncogenesis of very aggressive ALLs, ie deregulation of cell multiplication and prolonged blast lifespan.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) to increase efficacy of intensive sequential chemotherapy with etoposide, mitoxantrone and cytarabine (EMA) in previously treated acute myeloid leukemia: a multicenter randomized placebo-controlled trial (EMA91 Trial).

The EMA86 study showed efficacy of intensive sequential chemotherapy with mitoxantrone, 12 mg/m2 day on days 1-3, etoposide, 200 mg/m2/day as a continuous infusion on days 8-10 and cytarabine (araC), 500 mg/m2/day as continuous infusion on days 1-3 and 8-10 (EMA regimen) in previously treated patients with AML. The goal of the EMA91 study was to determine whether administration of GM-CSF between the two sequences of EMA chemotherapy and during the second sequence could increase therapeutic efficacy by potentially increasing leukemic cell recruitment into the S phase of cell cycle before the second sequence. One hundred and ninety-two patients aged less than 65 years with previously treated AML received GM-CSF, 5 microg/kg/day or placebo from day 4 to day 8 of EMA chemotherapy. One hundred and twenty were refractory and 72 were in first relapse after a complete remission (CR) of more than 6 months duration. CR rates after one course of chemotherapy were 65% in the GM-CSF group (refractory: 51%; first relapse: 89%), not significantly different from the 59% CR rate (refractory: 46%; first relapse: 81%) in the placebo group. Median time to recovery of neutrophils was 38 and 37 days and median time to last platelet transfusion 32 and 32 days respectively in the GM-CSF and placebo groups. WHO grade > or = 3 non-hematologic toxicities were mainly sepsis (45% and 51%, respectively) and mucositis (34% and 31%) and did not differ between the two groups. Toxic death rate was 5% and 8%, respectively, in the GM-CSF and placebo groups. Patients achieving CR were scheduled to receive six courses of maintenance with reduced-dose EMA. Time to progression tended to be longer in the GM-CSF group (median 154 vs 115 days, progression-free rate at 18 months 33% vs 19%, P = 0.08), particularly in refractory patients (P = 0.06). However, at the current follow-up, this did not translate into a significantly longer disease-free survival and survival. Cell cycle studies showed increased recruitment of cells in the S phase between day 4 and day 8 in the GM-CSF group compared to placebo (P = 0.006). However, this did not significantly relate to prognosis in this cohort of patients. GM-CSF might marginally increase efficacy of sequential chemotherapy without increasing its toxicity in the absence of any detected relationship between this effect and observed leukemic cell recruitment into the cell cycle.

[Thrombocytosis and essential thrombocythemia in childhood]. / Thrombocytoses et thrombocytémies essentielles de l'enfant.

Thrombocytosis is frequently observed in pediatric patients. Among them the secondary thrombocytosis are the most frequent and result from several causes. The rarely primary thrombocytosis can be either constitutive (and often familial) or acquired (essential thrombocythemia). The purpose of this article is to give diagnostic orientation and to suggest which biological tests should be performed.

CD40 ligation alters the cell cycle of differentiating keratinocytes.

CD40 is expressed in normal human keratinocytes, especially in the basal cell layer. We have recently reported that CD40 ligation strongly inhibits keratinocyte proliferation and induces their differentiation. In this study, the CD40 pathway that prevents keratinocyte growth was investigated. We first reported that interferon-gamma treatment potentiated the CD40-mediated inhibition of keratinocyte proliferation. CD40-CD40 ligand interactions, in the presence or absence of interferon-gamma, neither enhanced spontaneous keratinocyte apoptosis, nor did it enhance apoptosis induced by various agents. More importantly, we showed that CD40 signaling altered the keratinocyte cell cycle, as demonstrated by a decreasing number of cells in the G1 and S phases and an accumulation in G2/M phase of the cell cycle. Furthermore, western blot analysis of cell cycle regulatory proteins, showed a decrease in cyclin A and E expression in CD40-activated keratinocytes. Collectively, these results indicate that CD40 ligation inhibits keratinocyte renewal by a mechanism independent of cell apoptosis and that modulation of the keratinocyte cell cycle is an additional outcome of CD40 signaling.

Phase I study of interleukin-6 in children with solid tumours in relapse.

The aim of this study was to evaluate the feasibility, toxicity and efficacy of escalating doses of subcutaneous recombinant interleukin-6 (IL-6) in children with solid tumours in relapse. Recombinant IL-6 was administered subcutaneously once daily for 14 consecutive days, with a 14 day follow-up period. The starting dose for IL-6 was 1 microgram/kg/day and was escalated in subsequent patients groups until 10 micrograms/kg. Doses were escalated every 3 patients, provided that grade III or IV organ toxicity did not occur at the preceding dose level. Twelve patients were treated, three at each dose level. No grade 3-4 major organ toxicity was observed. Flu-like symptoms and fatigue were the most common side effects. All these symptoms resolved after the end of IL-6 administration. Significant increases in acute-phase proteins (CRP [C reactive protein], fibrinogen) and ESR (Erthrocyte sedimentation rate) were observed in all patients. Stimulatory effects on thrombocytopoiesis were observed at every dose level, and were maximal at 5 micrograms/kg and 10 microgram/kg. There was no tumour response observed during IL-6 administration. Pharmacokinetic profiles performed in 3 patients are consistent with previous reports in adults. IL-6 is a promising new cytokine for paediatric oncology, in particular to increase thrombocyte counts. We recommend that further studies in children proceed at a dose of 5-10 micrograms/kg/day in a once or, better, twice daily administration.

Plasma cell proliferation in monoclonal gammopathy: relations with other biologic variables--diagnostic and prognostic significance.

PURPOSE: We investigated the place of direct plasma cell proliferation analysis beside other biologic data in monoclonal gammopathy, particularly the serum level of C-reactive protein (C-RP) PATIENTS: Eighty patients were studied at the time of their diagnosis. Patients with a serum creatinine level greater than 200 mumol/L were excluded. METHODS: Plasma cell proliferation analysis was performed after bromodeoxyuridine incorporation and double immunoenzymatic labeling on cytological smears, making determination of the plasma cell labeling index (LI) possible. The other biologic variables studied were related to tumor burden (plasmacytosis, hemoglobin, serum levels of monoclonal immunoglobulin, albumin) or to kidney function (creatinine). beta 2-microglobulin (beta 2-M), C-RP, lactic dehydrogenase (LDH), and calcemia were also assessed. RESULTS: No correlation was found between LI and serum C-RP. LDH was the sole variable significantly correlated to C-RP (P < 0.01). Besides the biologic parameters used for the staging according to the Durie and Salmon classification, beta 2-M, albumin and LI were significantly different between stages (P < 0.0002, < 0.0004, < 0.00001). LDH and C-RP showed no significant difference. Results were similar when patients with and without bone lesions were analyzed separately. Multivariate analysis ranked these variables as follows with respect to prognostic value: beta 2-M, LI, and age. CONCLUSION: Among the variables analyzed, LI is the sole true reflector of cell proliferation. We confirm its diagnostic and prognostic value.

Comparison of anti-fading agents used in fluorescence microscopy: image analysis and laser confocal microscopy study.

To ascertain the ability of commercial and home-made anti-fading media to reduce the decrease of fluorescein isothiocyanate (FITC) fluorescence, we studied the bleaching characteristics of FITC-stained Reh 6 cells mounted in buffered glycerol and in anti-fading media. We measured the intensity of fluorescence over time with a confocal laser scanning microscope and a standard epifluorescence microscope coupled to an image analysis system. Most of the anti-fading media effectively retard fading but each has drawbacks. Better results were obtained with media containing p-phenylenediamine (solutions in buffered glycerol, Vectashield, Fluorstop). However, Mowiol, Slowfade, n-propyl gallate (20 g/liter) were also effective in retarding fading. Most of them, except Mowiol, reduced fluorescence intensity. We concluded that the choice of anti-fading medium would depend on the desired results: a slower decay of fluorescence despite an initial quenching of fluorescence or a lower retardant effect with no decrease in initial fluorescence intensity. Moreover, the combination of Mowiol with another anti-fading medium may be a useful compromise when a strong retardant effect is required without marked quenching of the initial fluorescence.

Double immunocytochemical labeling of cell and tissue samples with monoclonal anti-bromodeoxyuridine.

We describe a new monoclonal antibody (designated Bu20a) against bromodeoxyuridine (BrdU). This antibody was selected by screening against human tissues using the APAAP technique, and shows no crossreactivity with normal nuclei. It stains BrdU incorporated into the nuclei of a wide range of cell types, including human tonsil lymphoid cells, normal mouse tissues, and human tumors growing in nude mice. A double-labeling technique is described using this antibody in which cell smears or tissue sections are first labeled by an immunoperoxidase procedure for a cellular antigen (e.g., mouse or human histocompatibility class II antigen, T-lymphocyte antigen, keratin) and BrdU is then detected by indirect immunofluorescence. This procedure, which was applied to a variety of human and animal cells and tissues, is of wide potential value in analyzing the phenotype of S-phase cells and in co-localizing antigen expression and BrdU incorporation in tissue sections.

Significant reduction in the binding of a monoclonal antibody (LYP 18) directed against the IIb/IIIa glycoprotein complex to platelets of patients having undergone extracorporeal circulation.

Extracorporeal circulation (ECC) used in open heart surgery gives rise to several hemostatic defects. This work investigates the effect of ECC on patient platelets membrane glycoproteins IIb/IIIa. A monoclonal antibody (LYP 18) directed against the IIb/IIIa complex was used on patient platelets in binding and flow cytometry studies, before and at the end of ECC. An antithrombospondin (LYP 8) monoclonal antibody and a monoclonal antibody (LYP 7) directed against an alpha-granule glycoprotein of 136 kdaltons, present on the platelet surface after secretion, were used in binding studies together with electron microscopy to assess the release of alpha-granules. Results obtained in 7 patients show a significant reduction (p less than 0.02) in the number of LYP 18 monoclonal antibody binding to platelets having undergone ECC (n = 49,725 +/- 16,275) compared to platelets drawn before ECC (n = 72,671 +/- 13,302). Flow cytometry studies indicate a decrease (p less than 0.02) in the percentage of platelets bearing the LYP 18 determinant following ECC (75 +/- 12% vs 66 +/- 14%). Binding of monoclonal antibodies LYP 8 and LYP 7 and electron microscopy studies of patient platelets having undergone ECC do not show degranulation. These results suggest possible cleavage of the IIb/IIIa complex following ECC but no release of alpha-granules.

Cell-cycle prognostic value in adult acute myeloid leukemia. The choice of the best variables.

Flow cytometry with simultaneous analysis of DNA and protein content allows a most exhaustive study of cell-cycle for the prognostic evaluation of acute myeloid leukemia (AML). Sixty-seven cases of AML were studied before any form of chemotherapy had been undertaken. We determined the following cell-cycle variables: S, S + G2 + M, low protein content fraction (LPC-fraction) and high protein content fraction of G1 (HPC-G1). Patients were stratified according to age: S and S + G2 + M phases were higher for patients over 50 who did not achieve a complete remission. LPC-fraction was significantly lower for patients older than 50 who did not achieve a complete remission not only compared to the complete remission group of patients over 50, but also compared to the younger non responder group. The duration of survival was significantly longer when LPC-fraction was higher than 26% and HPC-G1 lower than 70%. Length of survival was also better when S + G2 + M was longer than 5.75%. Analysis of the therapy failure showed that S + G2 + M and LPC-fraction were significantly different between the complete remission group and the group of patients dying in aplasia. Overall, patients older than 50 with a proliferative leukemia had a worse prognosis.

The Australian Vietnam Veterans Health Study: I. study design and response bias.

BACKGROUND: The Australian Vietnam Veterans Health Study was set up to examine the post-war health of former soldiers 20 or more years after service and to examine the relation of combat exposure to physical and mental health. METHOD: A prospective cohort study of a simple random sample of 1000 male Australian Army Vietnam veterans used information gathered from Army records, from personnel interview and questionnaires. Military records were used to examine response bias by determining the differences between 641 interviewed veterans, 50 known deceased veterans and 309 non-respondents (including 48 refusers and 213 non-traceable). RESULTS: Differences were evident between respondents and non-respondents, with logistic regression modelling pointing to pre-enlistment employment, antisocial behaviour, intelligence and post-Vietnam AWOL (absent without leave) as the most important discriminants with non-respondents performing worse. Compared to respondents, deceased left school earlier, had higher rank in Vietnam and at discharge, had a higher overall number of charges but not a higher rate overall, and were less likely to have gone AWOL. Deceased also received more casualty reports than respondents and non-respondents, were better behaved during service, and were better emotionally adjusted than non-respondents. Respondents compared with the Australian population had equivalent or better current socioeconomic status. CONCLUSION: There seems little bias due to non-response, but deceased tend to come from and older cohort than in the other two groups.