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Acute lymphoblastic leukemia ( ALL) in the elderly is characterized by its ominous prognosis. On the other hand, imatinib has demonstrated remarkable, although transient, activity in relapsed and refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL), which prompted us to assess the use of imatinib in previously untreated elderly patients. ALL patients aged 55 years or older were given steroids during 1 week. Ph+ve cases were then offered a chemotherapy-based induction followed by a consolidation phase with imatinib and steroids during 2 months. Patients in complete response (CR) after consolidation were given 10 maintenance blocks of alternating chemotherapy, including two additional 2-month blocks of imatinib. Thirty patients were included in this study and are compared with 21 historical controls. Out of 29 assessable patients, 21 (72%, confidence interval (CI): 53 - 87%) were in CR after induction chemotherapy vs 6/21 (29%, CI: 11 - 52%) in controls (P = 0.003). Five additional CRs were obtained after salvage with imatinib and four after salvage with additional chemotherapy in the control group. Overall survival ( OS) is 66% at 1 year vs 43% in the control group ( P = 0.005). The 1-year relapse-free survival is 58 vs 11% ( P = 0.0003). The use of imatinib in elderly patients with Ph+ ALL is very likely to improve outcome, including OS.

We report on the population of point sources discovered during an 18.5 ksec Chandra ACIS-S observation of the Sombrero Galaxy. We present the luminosity function, the spectra of the 6 brightest sources, consider correlations with globular clusters (GCs) and with planetary nebulae (PNe), and study the galaxy's population of SSSs. We detected 122 sources, 22 of them are identified as luminous supersoft X-ray sources (SSSs). There is an over density of SSSs within 1.5 kpc of the nucleus, which is itself the brightest X-ray source. SSSs are also found in the disk and halo, with 1 SSS in a globular cluster (GC). Several sources in Sombrero's halo are good candidates for SSS models in which the accretor is a nuclear-burning white dwarf. In total, 32 X-ray sources are associated with GCs. The majority of sources with luminosity > 1e38 erg/s are in GCs. These results for M104, an Sa galaxy, are similar to what has been found for elliptical galaxies and for the late-type spiral M31. We find that those optically bright GCs with X-ray sources house only the brightest X-ray sources. We find that, in common with other galaxies, there appears to be a positive connection between young (metal-rich) GCs and X-ray sources, but that the brightest X-ray sources are equally likely to be in metal-poor GCs. We propose a model which can explain the trends seen in the data sets from the Sombrero and other galaxies. Thermal-time scale mass transfer can occur in some of the the younger clusters in which the turn-off mass is slightly greater than $0.8 M_\odot$; multiplicity may play a role in some of the most massive clusters; accretion from giant stars may be the dominant mechanism in some older, less massive and less centrally concentrated clusters.

Objective The present study was designed to compare directly the frequency of circulating LTC-IC and E-LTC-IC mobilized in peripheral blood (PB) after chemotherapy supported by either G-CSF (PB-G) or GM-CSF (PB-GM) in comparison to steady-state bone marrow (BM) and PB (PB-ST) values in the same patients. Materials and Methods Long-term cultures (LTC) were performed from 20 patients with malignant lymphoma at saturating cell concentrations to assess bulk progenitor cell production and by limiting dilution assay (LDA) to measure both frequency of LTC-IC and their proliferative and differentiation capacities. Results While CFC production in bulk LTC was higher at weeks 3–5 with PB-G than with PB-GM samples, week-5 LTC-IC and week-10 LTC-IC (E-LTC-IC) frequencies were not different using a LDA. However, the number of CFC derived from a single LTC-IC was higher in PB-G patients than in PB-GM patients ( p = 0.01). Interestingly, the frequency of LTC-IC per 1 × 10 5 MNC in mobilized PB positively correlated with one-year marrow progenitor cell recovery, in contrast to the number of autografted CD34 + cells and CFU-GM per kg. Conclusion Both G-CSF and GM-CSF resulted in similar increases in LTC-IC and E-LTC-IC in PB at comparable levels to those present in BM. However, the differentiation capacity of LTC-IC was higher after mobilization with G-CSF than with GM-CSF, suggesting qualitative differences in LTC-IC mobilized with these growth factors.

Summary Background: Serum CA125 (sCA125) was recently reported to be of clinical value in the staging and follow-up of patients with non-Hodgkin's lymphoma (NHL). This report aims to investigate the prognostic value of a new serologic index combining sCA125 and LDH serum levels. Patients and methods: One hundred thirty-seven patients were studied, sixty-three with histologically proven low-grade NHL, and seventy-four with a high-grade subtype. Results: sCA125 and LDH levels were elevated in more than one third of patients. sCA125 was more frequently increased than LDH in low-grade NHL. In this group, complete remission (CR) was achieved in 87, 45, and 0% (P - < 2 x 10~ 6 ) of patients with normal sCA125 and LDH serum levels (Low-risk group), one parameter increased (Intermediate-risk group), and increased sCA125 and LDH serum levels (high-risk group), respectively. The estimated five-year overall survival was 97%, 67% and 22% for low, intermediate, and high-risk groups, respectively. This combination was the only parameter predictive of RFS and OS in multivariate analysis (P < 0.0001). Conclusions: In this study the combination of s-LDH and sCA125 levels (normal vs. abnormal) was found to be an important prognostic factor in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.

Summary Background: The topoisomerase II-targeted drugs, epipodophyllotoxins and anthracyclines, have been shown to induce therapy-related AML (t-AML) characterized by a short latency period after chemotherapy, the absence of prior myelodysplastic syndrome and stereotyped chromosome aberrations. Few reports have been published on patients treated with the anthracenedione mitoxantrone which also targets topoisomerase II. We observed 10 cases of such t-AML over a 7-year-period in breast cancer patients treated with mitoxantrone combined with fluorouracil, cyclophosphamide and regional radiotherapy, and in three cases with vindesine. Patients and methods: We retrospectively analyzed patients referred to our hospital for AML with a past history of polychemotherapy for breast cancer, including mitoxantrone, either as adjuvant (8 patients)/neoadjuvant (1 patient) therapy or for metastatic disease (1 patient). We studied the probability of developing t-AML in a prospective series of 350 patients treated with an adjuvant FNC regimen (mitoxantrone, fluorouracil, cyclophosphamide) and radiation therapy. Results: The median age was 45 years (range 35-67). t-AML developed 13-36 months (median 16) after beginning chemotherapy for breast cancer, and 4-28 months (median 10.5) after ending treatment. As described in t-AML following treatment with epipodophyllotoxins or anthracyclines, we found a majority of FAB M4, M5 and M3 phenotypes (7 of 10), and characteristic karyotype abnormalities that also can be found in de novo AML: breakpoint on chromosome Ilq23 (3 patients), inv(16)(pl3q22) (2 patients), t(15;17)(q22;qll) (1 patient), t(8;21)(q22;q22) (1 patient) and del(20q)(ql 1) (1 patient). The prognosis was poor. All patients died of AML shortly after diagnosis. Since two patients had been enrolled in a prospective trial for the treatment of breast cancer which included 350 patients, the probability of developing t-AML was calculated to be 0.7% from 25-40 months, using the Kaplan-Meier method (95% confidence interval (95% CI): 0.1-4.5). Conclusions: The combination of mitoxantrone with cyclophosphamide, fluorouracil, and radiation therapy can induce t-AML, as with other topoisomerase II-targeted drugs. Despite a low incidence, the prognosis appears to be poor.

Hematopoietic reconstitution has been studied in 180 patients after autologous bone marrow transplantation based on peripheral blood cell (PBC) recovery time and marrow progenitor counts sequentially tested for up to 4 years. Several factors that could influence hematopoietic reconstitution have been analyzed including sex, age, diagnosis, disease status, conditioning regimen, graft progenitor content, graft in vitro purging, and postgrafting administration of growth factors. Before transplantation, marrow progenitor values were normal only for colony-forming unit granulocyte macrophage (CFU-GM) in contrast to colony-forming unit-erythroid (CFU-E), burst-forming unit-erythroid (BFU-E), and colony-forming unit-megakaryocyte (CFU-Meg). After transplantation, as described with allogenic grafts, these values remained low for several years, although PBC counts were nearly normalized within a few weeks. Pregraft values were reached after 2 years for CFU-GM and BFU-E, and after 4 years for CFU-E, while CFU-Meg failed to reach pregraft values after this time. Normal levels were reached after 4 years only by CFU-GM. On univariate and multivariate analysis, the following factors appeared to delay both PBC and marrow progenitor reconstitution: underlying disease (particularly acute myeloid leukemias), graft characteristics such as low stem cell content and in vitro purging, conditioning regimens with total body irradiation or busulfan, and lack of postgraft administration of growth factors. In conclusion, high-dose therapy followed by bone marrow transplantation induces a deep and prolonged impairment of hematopoiesis irrespective of any alloimmune reaction or postgraft immunosuppressive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

We have discovered new diffuse radio sources likely associated with groups of galaxies at low redshift (0.01-0.04) and without apparent AGN by using the WENSS and WISH catalogs to perform an unbiased survey. These sources resemble the radio halos, mini-halos, and 'relics' of rich clusters, which are thought to be powered by shocks and turbulence from infall into their deep potential wells. Our detection of similar sources within the shallow potential wells of groups of galaxies challenges this model. Their radio luminosities are approximately two orders of magnitude higher than expected from the extrapolation of the apparent rich cluster radio/X-ray luminosity relation. Even if these sources are misidentified distant clusters, they would lie above the apparent rich cluster radio/X-ray luminosity relation in the literature, suggesting that detections of radio halos and relics thus far may be more biased than previously thought., Conference proceedings, "Origins and Evolution of Cosmic Magnetism". 2 pages, 2 figures

We present an overview of unbiased studies of diffuse extragalactic radio sources. We use a previously developed filtering technique to remove compact sources from large surveys such as WENSS, WISH, and NVSS and examine the residual diffuse emission. A search of these residuals, unbiased by optical or X-ray selection, has uncovered a wide variety of diffuse sources, including those associated with groups of galaxies, ``blank'' fields, and previously unrecognized diffuse radio galaxy emission, as well as halos and relics of rich clusters. A second, targeted survey of the brightest X-ray clusters results in a number of new sources, and illuminates some important selection effects. When the well-established relationship between X-ray and radio halo luminosities is extrapolated to lower levels, the apparent correlation holds quite well for any type of diffuse source, even background noise. The observed correlations must therefore be scrutinized for possible selection effects before physical interpretations are made. We briefly mention a wide-field mapping project to search for large-scale structures, and goals for the next generation of studies in magnetic field - angular size parameter space., Comment: Conference proceedings, "Origins and Evolution of Cosmic Magnetic Fields". 4 pages, 5 figures. Minor changes due to referee reports; accepted for publication

Objective The aim of this study was designed to compare the in vivo long-term hematopoietic potential of bone marrow and peripheral blood grafts. Materials and Methods Marrow progenitor cell recovery was assessed for up to 4 years in 227 patients. One hundred patients were treated for malignant lymphomas by autologous bone marrow transplantation (BMT) and 127 by peripheral blood progenitor cell transplantation (PBPCT). Results Marrow progenitor cell counts were decreased for several years with both bone marrow and peripheral blood grafts. They were not different according to the origin of the graft, despite the reduced duration of peripheral blood cell recovery observed after PBPCT. Granulocyte colony-stimulating factor (G-CSF) used for PB graft mobilization and after transplantation resulted in faster neutrophil recovery compared to granulocyte-macrophage colony-stimulating factor (GM-CSF) with no evidence of decreased marrow progenitor cell recoveries. On the other hand, postgraft administration of GM-CSF enhanced long-term colony-forming unit granulocyte-macrophage reconstitution only after BMT. Factors that influenced marrow progenitor cell reconstitution have been identified by univariate and multivariate analysis: age, gender, type of lymphoma, and postgraft administration of hematopoietic growth factors (HGF) for the whole patient group; gender, graft progenitor cell yields, and type of HGF (G-CSF vs GM-CSF) for the PBPCT group; and only type of HGF for the BMT group. Conclusion Despite faster peripheral blood cell recovery, persistent deficiency of marrow progenitor cells was found several years after PBPCT, as observed after BMT. G-CSF–mobilized PBPCT resulted in faster neutrophil recovery compared to GM-CSF mobilization, with no difference in long-term hematopoietic reconstitution.

Background Chronic plantar fasciitis is not very known and the diagnosis is frequently missed. Trends for the diagnosis have been performed with the new methods of imaging. Objectives Determine the abnormal features of the chronic plantar fasciitis and find an efficient and accurate method of treatment. Methods 12 patients with chronic plantar fasciitis have been referred to us: men 7, women 5; mean age 55 years; mean duration of the disease 10 months. Ultrasound has been performed in 5 cases and MRI in 7 cases. Results Imaging showed increased thickness, reduced echogenicity of the plantar fasciitis and/or inflammatory changes. Ultrasound guided injection of steroids of the enlarged, hypoechoic plantar fascia, has been performed in 7 patients who had failed to conservative treatment. Conclusion The procedure resulted in complete relief of symptoms in 6 of 7 patients.

Mediastinal large-cell lymphoma with sclerosis (MLCLS) is a distinctive subtype of non-Hodgkin's lymphoma (NHL) with unique clinicopathology aspects and aggressive behavior. Prompt diagnosis and aggressive chemotherapy followed by consolidation radiotherapy may result in long-term survival in the majority of cases. However, a subset of patients do not respond to first-line or salvage treatment and have a poor prognosis. We report here a 27-year-old man with MLCLS resistant to several conventional chemotherapies and to radiotherapy who achieved a very good partial remission after one year's treatment with daily oral cyclophosphamide (100 mg/day). This is the first report of refractory MLCLS with good response to daily oral cyclophosphamide. This case suggests that daily oral monochemotherapy might be beneficial for some patients with mediastinal large-cell lymphoma with sclerosis refractory to conventional intravenous chemotherapies and radiotherapy.

The complete remission (CR) rate after intensive chemotherapy for acute myelogenous leukemia (AML) remains low in elderly patients, mainly because of a higher infectious mortality rate related to neutropenia and an increased incidence of adverse prognostic factors. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to potentially recruit leukemic blasts into cell cycle and improve cytotoxic effects when given during chemotherapy, and to shorten the duration of neutropenia when administered after chemotherapy. Two hundred forty patients aged 55 to 75 years who had newly diagnosed AML were randomly assigned to receive placebo or Escherichia coli-derived GM-CSF (5 micrograms/kg/d by 6-hour intravenous infusion) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of neutrophils, or evidence of regrowth of leukemia, or up to day 28. Induction chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine (100 mg/m2/d on days 1 to 7). The study drug was not administered subsequent to the induction course. Patients who achieved a CR received continuous maintenance therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year age subgroup, patients were randomly assigned to receive or not a consolidation course before maintenance therapy. The CR rate was similar in the GM-CSF and placebo groups (63% and 60.5%, respectively; P = .79). The mortality, rate of resistant disease, and rate of regrowth of leukemia were also similar in both groups. The time to neutrophil recovery was shorter in patients who received GM-CSF (24 v 29 days; P = .0001), but the incidence and characteristics of infectious events were not different. The 2-year disease-free survival (DFS) rate was significantly improved in the GM-CSF group (48% v 21% in the placebo group; P = .003). This effect was highly significant in the cohort of patients aged 55 to 64, but only marginal in patients/=65 years of age. There was a trend toward a longer overall survival (OS) in the GM-CSF group (P = .082). In summary, the administration of GM-CSF, concomitantly with chemotherapy and thereafter during induction course in AML, shortened the time to neutrophil recovery, but did not improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS were significantly prolonged in patients aged 55 to 64 treated with GM-CSF. These results are promising and further evaluation of myeloid growth factors in AML is warranted.

Three intensive consolidation strategies are currently proposed to younger adults with acute myeloid leukemia (AML) in first complete remission (CR): allogeneic or autologous bone marrow transplantation (BMT) and intensive consolidation chemotherapy (ICC). Patients aged 15 to 50 years with de novo AML received an induction treatment with 7 days of cytarabine and either idarubicin or rubidazone. After achievement of a CR, patients up to the age of 40 and having an HLA-identical sibling were assigned to undergo an allogeneic BMT. All the other patients received a first course of ICC with high-dose cytarabine and the same anthracycline as for induction. They were then randomly assigned to either receive a second course of ICC with amsacrine and etoposide or a combination of busulfan and cyclosphosphamide followed by an unpurged autologous BMT. Of 517 eligible patients, 367 had a CR, but only 219 (59.5%) actually received the planned intensive postremission treatment (73 allogeneic BMT, 75 autologous BMT, and 71 ICC). With a median follow-up of 62 months, the 4-year disease-free survival (DFS) of the 367 patients in CR was 39.5%. The 4-year overall survival (OS) of the 517 eligible patients was 40.5%. In multivariate analysis, DFS and OS were influenced only by the initial white blood cell count and by the French-American-British classification. The type of postremission therapy had no significant impact on the outcome. There was no difference in the 4-year DFS and OS between 88 patients for whom an allogeneic BMT was scheduled (respectively, 44% and 53%) and 134 patients of the same age category and without an HLA-identical sibling (respectively, 38% and 53%). Similarly, there was no difference in the outcome between autologous BMT and ICC. The 4-year DFS was 44% for the 86 patients randomly assigned to autologous BMT and 40% for the 78 patients assigned to ICC (P = .41). The 4-year OS was similar in the two groups (50% v 54.5%, P = .72). The median duration of hospitalization and thrombocytopenia were longer after autologous BMT (39 v 32 days, P = .006, and 109.5 v 18.5 days, P = .0001, respectively). After a first course of ICC, a second course of chemotherapy is less myelotoxic than an unpurged autologous BMT but yields comparable DFS and OS rates.

Recombinant tissue plasminogen activator (rt-PA) is an effective treatment for veno-occlusive disease (VOD) after bone marrow transplantation (BMT). However rt-PA therapy is limited by the risk of hemorrhagic complications. There is little guidance about the use of rt-PA for patients with severe VOD and severe hemorrhage. We report the case of a 16-year-old woman who developed severe VOD associated with life-threatening hemorrhagic cystitis (HC). A dramatic improvement in VOD was obtained after administration of recombinant tissue plasminogen activator (rt-PA). HC was managed with continuous bladder irrigation and blood transfusions. Administration of rt-PA was followed by a moderate increase in blood transfusion requirement but rt-PA did not cause dramatic aggravation of the HC. We conclude that severe HC might not be a contraindication to rt-PA therapy and such patients can be included in randomized trials conducted to determine the efficacy and risk benefit of rt-PA therapy for VOD.

We conducted a randomized multicenter study to compare the efficacy and safety of two antibiotic regimens (cefepime [2 g b.i.d.] plus amikacin or ceftazidime [2 g t.i.d.] plus amikacin) as first-line therapy for fever in patients with hematologic malignancies and neutropenia. A total of 353 patients were randomized according to a 2:1 (cefepime:ceftazidime) ratio. Two hundred-twelve patients in the cefepime group and 107 in the ceftazidime group (90% of all patients) were evaluable for efficacy. The polymorphonuclear neutrophil count was100/mm3 on enrollment for 70% of the patients. The mean duration of neutropenia was 26 days. The efficacy in both study arms was comparable, although a trend in favor of cefepime was seen in terms of therapeutic success (response rate, 27% vs. 21% for the ceftazidime group). The overall response rate after glycopeptides were added to the regimens was 60% for the cefepime group and 51% for the ceftazidime group; the bacterial eradication rates were 81% vs. 76%, respectively, and the rates of new bacterial infections were 14% vs. 18%, respectively. We conclude that the combination cefepime/amikacin is at least as effective as the reference regimen of ceftazidime/amikacin in this setting.

Dose-intensive treatment followed by ABMT is currently used in different approaches to treat breast cancer patients. An active non cross-resistant regimen combining cyclophosphamide (C), mitoxantrone (M) and melphalan (A) (CMA), was developed as the conditioning regimen before ABMT. The purpose of this phase II study was to evaluate this protocol and the duration of its effect in metastatic patients, who responded to chemotherapy. Criteria for inclusion included histologically documented breast cancer, age55 years and the first detection of measurable metastatic lesions. Following first-line chemotherapy in responding patients, histologically negative bone marrow was collected and cryopreserved. Then, intensification with cyclophosphamide (120 mg/kg), mitoxantrone (60 mg/m2), and melphalan (140 mg/m2) was followed by ABMT. Sixty-one metastatic breast cancer patients with a mean age of 40 years were included. Sites of measurable metastases included: liver 24, lung 14, central nervous system four, pleura three, skin six, and chest wall six, nodes eight and bone marrow one. Nineteen patients had lesions in two or more sites, and 22 had bone involvement. The response of 60 patients could be evaluated: before ABMT 31 were in clinical complete response (CR), 22 in partial response50% (PR), and seven had new progression. After ABMT, 36 patients were in CR, 16 in PR, one progressed and one was stable. Seven (11.5%) toxic deaths occurred. Mean time for hematological recovery was 32.5 days, without hematopoietic growth factors. Median survival was 33 +/- 9.4 months from the start of therapy, and 25.7 +/- 4.6 months from the date of ABMT. Median event-free survival was 20 months from the start of therapy, and 13 +/- 2 months from ABMT. With a median follow-up of 51 months, probability of actuarial survival, measured from the beginning of initial chemotherapy, was 36%, and event-free survival was 18%. In metastatic breast cancer responding to chemotherapy, high-dose consolidation with CMA and ABMT resulted in a median survival of 33 months. These results lay the ground work for evaluation in a randomized trial in metastatic breast cancer.

The use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) as an adjunct to autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cell (PBPC) transplantation was evaluated in 59 lymphoma patients. Patients were divided into three groups. In group I (n = 21) patients received rhGM-CSF (5 micrograms/kg daily) at the time of PBPC collection and during the recovery phase post-infusion. In group II (n = 12) patients received rhGM-CSF as an adjunct to ABMT. In group III (n = 26) they were grafted with bone marrow without rhGM-CSF. Administration of rhGM-CSF (groups I and II) significantly reduced the time to myeloid engraftment, the number of febrile days and the median duration of antibiotics administration and of hospital stay when compared with the group in which patients did not receive rhGM-CSF. The only difference between ABMT and PBPC, given with rhGM-CSF support, was observed in the duration of hospitalization (group Igroup II, P0.05). These data show that rhGM-CSF is highly effective in reducing the duration of aplasia following BMT and PBPC transfusion, and there appears to be little difference in efficacy between these techniques, provided that patients also receive rhGM-CSF.

Hematopoietic reconstitution has been studied in 180 patients after autologous bone marrow transplantation based on peripheral blood cell (PBC) recovery time and marrow progenitor counts sequentially tested for up to 4 years. Several factors that could influence hematopoietic reconstitution have been analyzed including sex, age, diagnosis, disease status, conditioning regimen, graft progenitor content, graft in vitro purging, and postgrafting administration of growth factors. Before transplantation, marrow progenitor values were normal only for colony-forming unit granulocyte macrophage (CFU-GM) in contrast to colony-forming unit-erythroid (CFU-E), burst-forming unit-erythroid (BFU-E), and colony-forming unit-megakaryocyte (CFU-Meg). After transplantation, as described with allogenic grafts, these values remained low for several years, although PBC counts were nearly normalized within a few weeks. Pregraft values were reached after 2 years for CFU-GM and BFU-E, and after 4 years for CFU-E, while CFU-Meg failed to reach pregraft values after this time. Normal levels were reached after 4 years only by CFU-GM. On univariate and multivariate analysis, the following factors appeared to delay both PBC and marrow progenitor reconstitution: underlying disease (particularly acute myeloid leukemias), graft characteristics such as low stem cell content and in vitro purging, conditioning regimens with total body irradiation or busulfan, and lack of postgraft administration of growth factors. In conclusion, high-dose therapy followed by bone marrow transplantation induces a deep and prolonged impairment of hematopoiesis irrespective of any alloimmune reaction or postgraft immunosuppressive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

A 56-year-old man with refractory B-cell lymphocytic non-Hodgkin's lymphoma was treated in a Phase II study with interleukin-2 (IL-2) (Roussel-Uclaf, Romainville, France). The patient had involvement of multiple lymph nodes and medullary and peripheral blood (3.6 x 10(9) monoclonal CD19-positive [CD19+] B-lymphocytes/l). After a 5-day cycle of IL-2 treatment, an eightfold increase of the monoclonal CD19+ population was observed (27 x 10(9) monoclonal CD19+ cells). The lymphocytosis decreased dramatically during the second cycle (days 15 to 19) of IL-2 treatment, resulting in 6 x 10(9)/l peripheral lymphocytes, with 5.5 x 10(9) B-lymphocytes. As soon as day 20, peripheral B-cells again increased considerably, with 32 x 10(9) CD19+ cells/l at day 27. The CD19+ population remained monoclonal as assessed by kappa/lambda cell-surface phenotyping and kappa gene rearrangement evaluation. Kinetics of the monoclonal B-lymphocyte response to IL-2 paralleled the natural killer/lymphokine-activated killer and T-cell response, with a 4-day latency period, suggesting an indirect enhancing effect of IL-2. Before and during IL-2 treatment, peripheral B-lymphocytes never expressed detectable levels of the p55 IL-2 receptor. However, the p75 IL-2 receptor was expressed significantly in the IL-2-responsive monoclonal B-cell population. Tumor necrosis factor alpha, a known (in vitro) B-cell tumor growth factor, reached high serum levels during IL-2 treatment. Response evaluation at day 45 showed stability of the lymph node involvement and the marrow lymphocyte infiltrate. At day 45, peripheral B-cell lymphocytosis was 7.5 x 10(9)/l. To the knowledge of the authors, this is the first report of an in vivo IL-2-induced reversible increase of peripheral monoclonal B-cell lymphocytosis.

We report a case of acute hepatitis B after autologous stem cell transplantation (ASCT) in a patient with low-grade non-Hodgkin's lymphoma. At diagnosis of the hematological disease, the patient had the characteristic serology of a previous hepatitis B infection, being Ag HBs negative, hepatitis B virus core antibody positive (anti-HBC) and hepatitis B virus surface antibody weakly positive. He developed fatal hepatitis B after autologous stem cell transplantation, suggesting reactivation consequent to immunosuppression.

Sir: Immunocompromised patients develop severe fungal infections. Infections caused by opportunistic fungi such as Candida spp and Aspergillus spp have been reported with increasing frequency. The fungi of the genus Chaetomium, commonly found in soil and products of cellulose degradation, which are among the emerging fungal pathogens, are difficult to diagnose and to treat. We report a case of pleural effusion due to Chaetomium globosum after autologous bone marrow transplantation (BMT). A 19-year-old woman was admitted to the intensive care unit because of severe sepsis 2 days after autologous BMT. She had a 3-month history of pulmonary large B-cell type centroblastic lymphoma. She received total corporeal irradiation, chemotherapy (carmustine, etoposide and cyclophosphamide) and autologous BMT. Severe sepsis began on day 2. Chest X-ray revealed pneumonia and pleural effusion in the left lung. Hematological laboratory findings were: white cell count 0.2 109/l, hemoglobin 81 g/l, platelet count 30 109/l. Blood creatinine level was 59 mmol/l and blood lactate level 1.68 mmol/l. The patient was treated with broad spectrum antimicrobial agents (tienamycin, vancomycin, amikacin and amphotericin B) associated with growth factor (granulocyte colonystimulating factor). Bacterial blood and urine cultures were sterile, as was culture of the removed central venous catheter. Fungal blood cultures were also sterile. Routine bacterial culture of the exudate from thoracentesis was sterile. Direct microscopy was negative. Culture on Sabouraud dextrose agar medium at 37 C remained sterile after 20 days. One culture on the same medium at 30 C showed a fast-growing, single, filamentous, dingy white colony, turning dark gray in 4 days. Numerous dark subglobose perithecia (250±300 mm) covered by long lateral and terminal septate straight or wavy granulous hairs were produced. The perithecia contained clubshaped asci with pedicels (35±45/ 12±15 mm), each ascus contained eight dark lemon-shaped ascospores (9±13/8±9 mm) with a single germinative pore. The fungus was identified as Chaetomium globosum (Fig.1). No improvement occurred in spite of treatment and recovery of neutropenia on day 9. The patient developed the acute respiratory distress syndrome and was mechanically ventilated after tracheal intubation on day 9. Septic shock and acute renal failure then occurred, necessitating dialysis on day 35. The patient eventually developed multiple organ failure and died on day 40. Postmortem right lung biopsy showed aspecific fibrosis and macrophage alveolitis. Chaetomium species belonging to saprobic homothallic ascomycetes have rarely been isolated as etiological agents of opportunistic infections in immunocompromised patients. In this case of severe sepsis after autologous BMT, Chaetomium globosum was suspected as the initial pathogen because no other microorganism was cultured and Chaetomium was isolated from an usually sterile fluid, (i. e., pleural effusion). Nevertheless, it grew quickly but only when incubated at 30 C and not at 37 C. Postmortem biopsy did not reveal the fungus but the biopsy was performed 40 days after the onset of the sepsis and treatment. No conclusion was possible regarding the role of the fungus in the death of the patient.Chaetomium globosum is the most prevalent species isolated in clinical infections, which are mostly cutaneous or nail infections. Chaetomium globosum has a lower growing temperature than other Chaetomium spp [1], which suggests that infections might occur in cooler sites. However, invasive infections have been reported in severely immunocompromised patients with leukemia [2±5], renal transplants [6], brain abcesses in drug addicts [1], and peritonitis in a patient on peritoneal dialysis [7]. Most of these patients died. Our patient was treated with amphotericin B, but the clinical efficacy of antifungal treatment on Chaetomium sp has not been fully established. Mortality is high for invasive infections due to Chaetomium sp, which is emerging as a pathogen and is difficult to prove and to treat in these severely immunocompromised and infected patients.

Hematopoietic growth factors (GF) have greatly facilitated the mobilization and collection of peripheral blood (PB) stem cells. However, some patients fail to mobilize sufficient numbers of hematopoietic progenitor cells (HPC) to ensure rapid and durable engraftment. Interactions between the chemokine SDF-1 and its receptor CXCR4 have been shown to play a central role in the homing of HPC. To investigate a possible additional role of SDF-1 in the mobilization of CD34+ progenitor cells into PB, we examined the association of SDF1 gene polymorphism with circulating CD34+ cell counts after GF-priming. 63 patients (pts) were studied (48 malignant lymphoma, 8 myeloma and 7 solid tumors), after mobilization with G-CSF alone (n=11), chemotherapy (CT) and G-CSF (n=36) or GM-CSF (n=16). PB CD34+ cell counts were assessed when leukocytes reached 1,000/μl and graft collection performed when CD34+ counts reached 20/μl. The SDF1 3′G/A genotyping was performed on PB mononuclear cell DNA by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) which can detect the G to A mutation. Out of the 63 pts, 21 were able to mobilize 50 CD34+ cells/μl or more in PB. Their characteristics were not statistically different from others in terms of diagnosis, age, sex, number of previous CT courses, previous radiotherapy, marrow involvement or mobilizing regimens. Distribution of SDF1 genotypes in normal controls and in patients according to their mobilizing capacity was as follows: These results provide evidence for an association of the SDF1 3′A allele with more efficient mobilization of CD34+ progenitor cells into PB and suggest an involvement of SDF-1 in mobilization mechanisms.

The value of high-dose therapy with autologous stem cell transplantation as first-line therapy in poor prognosis Hodgkin's disease is controversial and we report the results of evaluation of twenty-six patients who were selected for this procedure from February 1989 to July 1994. They were all patients with stage IV at diagnosis with at least two other unfavourable characteristics, i.e. B symptoms, mediastinal mass greater than 0.45 of the thoracic diameter, two or more extranodal sites, bone marrow involvement, inguinal node involvement, serum lactic dehydrogenase greater than 400 IU/L, or low hematocrit. At the time of transplantation, 19 patients were in complete remission and 10 were in partial remission > or = 50%. Procedure-related mortality in the first 90 days post-graft was 7% overall. Of the 24 evaluable patients, 22 (92%) were assessed as complete responders, and 2 (8%) had progression of disease at 6 months. The actuarial overall survival (OS), disease-free survival (DFS) and event-free survival (EFS) at 5 years were 69%, 79% and 58%, respectively. The Cox proportional hazards model was used to assess prognostic factors. In univariate analysis only one prognostic factor was found to be significantly associated with improved DFS, i.e. low serum lactic dehydrogenase (LDH) (DFS at 5 years: 92% if LDH < 400 IU/L vs 44% if LDH 400 IU/L, P = 0.007). DFS rates between first complete remission and first partial remission groups were not significantly different (DFS at 5 years: 87% vs 66%, p = 0.15). These first results are encouraging but randomized studies are needed.