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Post-remission options were compared in a population of 262 relapsing and refractory acute myeloid leukemia patients achieving complete remission (CR) after the same re-induction according to etoposide?–?mitoxantrone?–?cytarabine (EMA) trials. The selection of post-remission therapy depended on trial recommendations, age, performance status, and availability of an HLA-identical sibling. One hundred and thirty patients received chemotherapy consolidation courses, 50 received autologous stem cell transplantation (SCT), and 43 underwent allogeneic bone marrow transplantation (BMT), while 39 did not receive any additional therapy. The preliminary analysis identified 3 favorable prognostic factors correlated with event-free survival (EFS): M3 subtype, previous CR duration >?1 year, and transplantation. Three year EFS was 68 vs. 23% with autologous SCT and allogeneic BMT in M3 patients and, respectively, 41 vs. 20% in non-M3 patients. Three year probabilities of treatment-related mortality were 11 and 47%, respectively. A statistical model was conceived with adjustment on prognostic factors and post-remission option. In the multivariate analysis, autologous SCT appeared significantly better than allogeneic BMT ( P <0.01) or chemotherapy ( P ?=?0.001), while allogeneic BMT was not statistically different than chemotherapy. This indicates a high treatment-related toxicity with allogeneic BMT in patients re-induced by highly intensive chemotherapy, and therefore a tendency for a better outcome with autologous SCT as post-remission treatment in those patients. [ABSTRACT FROM AUTHOR]

Background: Although controlled-rate freezing and storage in liquid nitrogen are the standard procedure for peripheral blood progenitor cell (PBPC) cryopreservation, uncontrolled-rate freezing and storage at -80 degrees C have been reported.Study Design and Methods: The prospective evaluation of 109 autologous PBPC transplantations after uncontrolled-rate freezing and storage at -80 degrees C of apheresis products is reported. The cryoprotectant solution contained final concentrations of 1-percent human serum albumin, 2.5-percent hydroxyethyl starch, and 3.5-percent DMSO.Results: With in vitro assays, the median recoveries of nucleated cells (NCs), CD34+ cells, CFU-GM, and BFU-E were 60.8 percent (range, 11.2-107.1%), 79.6 percent (6.3-158.1%), 35.6 percent (0.3-149.5%), and 32.6 percent (1.7-151.1%), respectively. The median length of storage was 7 weeks (range, 1-98). The median cell dose, per kg of body weight, given to patients after the preparative regimen was 6.34 x 10(8) NCs (range, 0.02-38.3), 3.77 x 10(6) CD34+ cells (0.23-58.5), and 66.04 x 10(4) CFU-GM (1.38-405.7). The median time to reach 0.5 x 10(9) granulocytes per L, 20 x 10(9) platelets per L, and 50 x 10(9) reticulocytes per L was 11 (range, 0-37), 11 (0-129), and 17 (0-200) days, respectively. Hematopoietic reconstitution did not differ in patients undergoing myeloablative or nonmyeloablative conditioning regimens before transplantation.Conclusion: This simple and less expensive cryopreservation procedure can produce successful engraftment, comparable to that obtained with the standard storage procedure. [ABSTRACT FROM AUTHOR]

To evaluate the feasibility and efficacy of CD34+ cell immunoselection from routine peripheral blood stem cell (PBSC) harvests in very small children a prospective study was performed in 15 children with advanced neuroblastoma weighing 20 kg or less. Products of two consecutive leukaphereses carried out on a COBE Spectra separator after G-CSF alone mobilization were pooled for immunoselection on Ceprate column. The median number of CD34+ cells and total CFU-GM collected were respectively 5.9 × 106/kg (range 2.3–23.4) and 126.9 × 104/kg (range 52.9–559.9). After separation the median number of CD34+ cells in the adsorbed fraction was 2.6 × 106/kg (range 1–9.8) with a median purity of 54% (range 21–82) and a median of 95.7-fold (range 35–250) enrichment. Thirteen patients underwent autografts with CD34+ PBSCs after a busulfan 600 mg/m2 + melphalan 180 mg/m2 preparative regimen. The median number of days to achieve an absolute granulocyte count of 0.5 × 109/l and a platelet count of 20 × 109/l were respectively, 12 (range 10–24) and 35 (range 25–43). The median number of platelet transfusions was nine (range 2–15). We conclude that safe and effective immunoselection and transplantation of CD34+ PBSC can be accomplished in children with low body mass. [ABSTRACT FROM AUTHOR]

Fibrin stabilising factor (FSF) was studied in the circulating blood of 196 children. These 196 children comprised three groups: 131 controls (group A), 20 children with diseases of potential repercussion on FSF determination (group B), and 45 children with Schönlein-Henoch syndrome (group C). Determinations from groups A and B produced normal values, but results from group C were significantly lower at the onset of the vasculitis. Seventeen children with Schönlein-Henoch syndrome have had complications, in 7 of whom these were severe. The decrease in FSF levels was correlated with the severity of such complications, and an increase in FSF was associated with recovery. Determination of FSF activity appears to help in the diagnosis of Schönlein-Henoch vasculitis, as well as helping to monitor the course of the disease and assessing the risks of complications. [ABSTRACT FROM AUTHOR]

INTRODUCTION:: Among patients with indolent form of B-cell chronic lymphocytic leukemia, some of them will progress into more advanced stages. To better define this subpopulation of patients, we attempted to define some parameters capable of predicting a pejorative clinical outcome. MATERIALS AND METHODS:: Eighty-eight previously untreated patients with B-cell chronic lymphocytic leukemia in Binet stage A were analysed to study the prognostic value of simple serological variables: soluble CD23 (sCD23), β2 microglobulin (β2m), lactate-dehydrogenase activities and albumin level. Results were compared to other conventional clinical and biological parameters by univariate and multivariate statistical analysis. RESULTS:: Our data show that: (1) among those studied, sCD23 >50 u/ml was the only serological significant parameter clearly correlated with disease progression and (2) stage A′′ patients (hemoglobin level between 100 and 120 g/l and/or lymphocytosis >30.109/l), axillary lymph nodes and hypogammaglobulinemia were found to be other variables associated with a pejorative outcome. These four variables enabled the establishment of a scoring system, capable of predicting disease progression since 66% of the patients with a score 2 are going to evolve into advanced stages vs 12% with a score <2. Furthermore, the time to progression is shortened when the score is increasing. CONCLUSION:: Our findings show the prognostic relevance of a scoring system including sCD23 level. This score could be taken into account in the treatment strategy of B-cell chronic lymphocytic leukemia.The Hematology Journal (2000) 1, 301–306 [ABSTRACT FROM AUTHOR]

A multicentre single-arm study testing the efficacy and toxicity of the oral combination of fludarabine and cyclophosphamide (FC) over 5 d in 75 patients with untreated B cell-chronic lymphocytic leukaemia. Oral FC demonstrated high efficacy with overall (OR) and complete response (CR) rates of 80% and 53%, respectively. Out of the 30 CR patients studied for Minimal Residual Disease (MRD) using 4-colour flow-cytometry and the 22 using Clonospecific polymerase chain reaction, 22 (66%) and 16 (68%), respectively, were MRD negative. Median survival and median treatment-free interval had not been reached at 7 years of follow-up. Median progression-free survival (PFS) was 5 years. Toxicity was acceptable, with 52% and 16% of National Cancer Institute grade 3/4 neutropenia and infections, respectively. Gastrointestinal toxicity was mild. Oral FC demonstrated a high efficacy and an acceptable safety profile and may be considered as the standard first line treatment in chronic lymphocytic leukaemia.

Severe autoimmune hemolytic anemia (AIHA) can cause life-threatening hemolysis requiring red blood cell transfusions (RBT). The efficiency of RBT could be improved with the use of plasma exchanges (PEx) before RBT. The objective of this study was to assess the effectiveness of PEx in severe AIHA of adults. All adult patients with severe AIHA requiring RBT were included in this single center retrospective case-control study. The end point was change in hemoglobin (Hb) level after RBT, depending on whether PEx was done (experimental group) or not (control group). Thirty-one sessions of RBT following PEx were performed on the 5 patients of the experimental group and were compared with the 7 sessions of BT without PEx performed on the 4 patients of the control group. Despite a lower mean Hb value before the session of RBT (5.7 g/dl vs. 7.2 g/dl, P = 0.04) in the control group, the mean Hb value 5 (4-7) days following RBT (8.7 g/dl vs. 8.6 g/dl, P = 0.85) was not different in the experimental and in the control group, respectively. In a second analysis in which each patient was his own control (31 sessions of RBT following PEx vs. 51 sessions of RBT alone), the gain in Hb was not different (1.4 g/dl vs. 1.9 g/dl, P = 0.67). When RBT are required in severe AIHA of adults, the use of a single PEx before BT does not increase the efficiency of RBT based on day 5 evaluation.

Doxorubicin-based immunochemotherapy, with interferon, has been shown to improve survival in patients with advanced follicular lymphoma. High-dose chemotherapy with stem-cell support is effective in follicular lymphoma in relapse but remains controversial as a first-line therapy. In a randomized study using a purged autologous stem-cell support, we compared these 2 approaches in patients with advanced follicular lymphoma. Newly diagnosed advanced follicular lymphoma patients (172 patients) were randomly assigned either to an immunochemotherapy regimen (cyclophosphamide, doxorubicin, teniposide, prednisone, and interferon) or to a high-dose therapy followed by purged autologous stem-cell transplantation. Compared with the patients who received chemotherapy and interferon, patients treated with high-dose therapy had a higher response rate (69% vs 81%, P = .045) and a longer median event-free survival (not reached vs 45 months). This did not translate into a better survival rate due to an excess of secondary malignancies after transplantation. The Follicular Lymphoma Prognostic Index identified a subgroup of patients with a significantly higher event-free survival rate after high-dose therapy. Autologous stem-cell transplantation cannot be considered as the standard first-line treatment of follicular lymphoma for patients younger than 60 years old with a high tumor burden.

Hairy cell leukemia (HCL) is a rare hematological disorder of unknown origin. Thirteen familial cases of HCL have been reported, with 28 relatives affected. Here we report 2 cases of HCL in a family associated with HLA haplotypes A2, B7 and Bw4/6.

Ongoing studies in B-cell chronic lymphocytic leukemia are evaluating autologous peripheral blood stem cell (PBSC) transplantation in first remission following fludarabine therapy. However, fludarabine could impair PBSC harvest. In 38 patients after frontline oral fludarabine and cyclophosphamide (FDR-CY) therapy, we prospectively evaluated steady state filgrastim- or lenograstim-primed PBSC mobilization to collect 2.0 x 106/kg or more CD34 cells. The first mobilization, performed a median of 178 days (range, 69-377 days) from the last FDR-CY course, was unsuccessful in 32 patients. This result was significantly associated with a low platelet count before mobilization but not with age, interval from last FDR-CY course, initial stage, remission status, or other blood parameters. Finally, after 1, 2, and 3 mobilizations in 27, 10, and 1 patients, 2.0 x 106/kg or more CD34 cells were collected in only 12. Explorations of the mechanism of poor mobilization and adaptation of PBSC harvest policies after fludarabine treatment are therefore warranted.

Enteroviral meningoencephalitis was diagnosed in a patient with an immunodeficiency syndrome acquired after treatment with rituximab for a relapsed primary B-cell lymphoma. A second meningoencephalitic episode was diagnosed 6 months later and was successfully treated with a combination of immunoglobulins and pleconaril. The infection was persistent since the enterovirus genome was detected in five sequential specimens of cerebrospinal fluid collected over 9 months. An echovirus 13 isolate was isolated in the first three samples. The viral sequence encoding the VP1 capsid protein of the three isolates was determined and was compared with that of four control viruses. The virus isolates recovered from the patient shared >99% nucleotide sequence similarity with one another. In a phylogenetic tree, they were directly related to a control virus obtained from a patient hospitalized in 2000 during an outbreak of enterovirus meningitis. The epidemiological origin of a chronic echovirus infection in a patient with immune deficiency suggests that the echovirus had been continuously circulating in the general population after the outbreak that had revealed its emergence.

Treatment with the chimeric anti-CD20 monoclonal antibody rituximab induces rapid and long-lasting depletion of circulating B cells. We report the occurrence of enteroviral meningoencephalitis following rituximab therapy in 1 child with immune thrombocytopenia and in 1 adult patient with relapsed B cell lymphoma.

To comparatively assess first-line treatment with fludarabine and 2 anthracycline-containing regimens, namely CAP (cyclophosphamide, doxorubicin plus prednisone) and ChOP (cyclophosphamide, vincristine, prednisone plus doxorubicin), in advanced stages of chronic lymphocytic leukemia (CLL), previously untreated patients with stage B or C CLL were randomly allocated to receive 6 monthly courses of either ChOP, CAP, or fludarabine (FAMP), stratified based on the Binet stages. End points were overall survival, treatment response, and tolerance. From June 1, 1990 to April 15, 1998, 938 patients (651 stage B and 287 stage C) were randomized in 73 centers. Compared to ChOP and FAMP, CAP induced lower overall remission rates (58.2%; ChOP, 71.5%; FAMP; 71.1%; P <.0001 for each), including lower clinical remission rates (CAP, 15.2%; ChOP, 29.6%; FAMP, 40.1%; P =.003). By contrast, median survival time did not differ significantly according to randomization (67, 70, and 69 months in the ChOP, CAP, and FAMP groups, respectively). Incidences of infections (< 5%) and autoimmune hemolytic anemia (< 2%) during the 6 courses were similar in the randomized groups, whereas fludarabine induced, compared to ChOP and CAP, more frequent protracted thrombocytopenia (P =.003) and less frequent nausea-vomiting (P =.003) and hair loss (P <.0001). For patients with stage B and C CLL first-line fludarabine and ChOP regimens both provided similar overall survival and close response rates, and better results than CAP. However, there was an increase in clinical remission rate and a trend toward a better tolerance of fludarabine over ChOP that may influence the choice between these regimens as front-line treatments in patients with CLL.

Autologous peripheral blood progenitor cell (PBPC) transplantation is now commonly used in children. The ontogenic differences in haematopoiesis published in recent years suggest differences in the categories of mobilized PBPCs between children and adults. We investigated the frequency and distribution of mature progenitor cells (colony-forming cells, CFCs) and primitive progenitor cells [CD34+ CD38- and CD34+ Thy-1+ cells, long-term culture-initiating cells (LTC-ICs)] in children and adults mobilized using granulocyte colony-stimulating factor alone. We found similar proportions of granulocyte colony-forming units (CFU-G) and/or macrophage CFUs (CFU-M), mixed lineage CFUs (CFU-Mix) and megakarocyte CFUs (CFU-Mk), CD34+ CD38- and CD34+ Thy-1+ cells, and LTC-ICs (16.5 +/- 3.5 vs. 10.65 +/- 5 per 104 CD34+ cells), which produced the same number of CFCs (5 +/- 1 vs. 6 +/- 1 CFCs/LTC-ICs) in PB CD34+ cells from children and adults. However, we noted a higher proportion of erythroid blast-forming units (BFU-E) in PB CD34+ cells from adults (x 1.5, P = 0.003). Using cord blood as a third ageing point, we observed an inverse age-related propensity for commitment to the monocyte/macrophage lineage that was still found after normalizing the data per body weight and processed blood mass. This ontogeny-related programming was detected from the LTC-IC level, which produced 1.7 times more CFU-M in children than in adults (P = 0.048). These subtle differences in commitment between children and adults, shown here for the first time, are of interest for the in vitro manipulation of PBPCs and, in particular, for application in adoptive immunotherapy in children.

In spite of the recent improvement in the outcome of acute promyelocytic leukaemia (APL) with treatment combining all trans retinoic acid (ATRA) and chemotherapy (CT), some patients with this disease still have a poor outcome. The prognostic significance of chromosomal abnormalities in addition to t(15;17) in APL is uncertain. We examined the prognostic significance of secondary chromosomal changes in 292 patients included in a European trial who were treated with ATRA and CT. The incidence of chromosomal abnormalities in addition to t(15;17) was 26% and trisomy 8 was the most frequent secondary change (46% of the cases with secondary changes). No significant differences were seen with regard to age, sex, initial white blood cell count, % of circulating blasts, platelet count, fibrinogen level and incidence of microgranular variants between patients with or without additional rearrangements. Outcome was also similar between patients with t(15;17) alone and patients with t(15;17) and other clonal abnormalities for complete remission (92% vs. 93% respectively), event-free survival at 2 years (76.1% vs. 78.1% respectively), relapse at 2 years (16.7% vs. 11.6% respectively) and overall survival at 2 years (79.9% vs. 79.5% respectively). Analysis according to the type of induction treatment (ATRA followed by CT or ATRA plus CT) or the type of maintenance treatment (with ATRA, low-dose CT or both) also failed to show any difference between the two groups. Thus, in a large cohort of APL patients treated with ATRA and CT, additional chromosomal abnormalities had no impact on prognosis.

Thrombocytosis is a common feature of myeloproliferative disorders but may also result from various conditions including chronic iron deficiency, hemorrhage, chronic inflammation and splenectomy. We report two cases of secondary thrombocytosis caused by isolated and congenital asplenia, mimicking essential thrombocythemia. These two adult cases of spleen agenesis were unexpected. We conclude that in thrombocytosis without clinical evidence of splenomegaly, attentive screening of blood in search of Howell-Jolly bodies and abdominal ultrasonography should always be performed not only to detect mild spleen enlargement but also to make sure of the presence of this organ.

Immunoselected CD34+ peripheral blood progenitor cell (PBPC) transplantation is now frequently used to support autologous hematopoiesis after myeloablative therapy, its feasability having been proved by several groups. However, we and others observed delayed platelet recovery. We hypothesized that immunoselection processing might induce selective loss of megakaryocyte progenitors, or a decrease in their proliferation. We used a colony-forming units megakaryocyte (CFU-Mk) assay to evaluate these consequences and predict platelet recovery in patients. In CD34+ PBPCs from 10 children with solid tumors, we observed no selective loss in CFU-Mk numbers during immunoselection processing and no impairment of clonogenicity. The CFU-Mk yield (59.2 +/- 11.3%) was at least similar to the CD34+ yield (44.2 +/- 3.8%). We assessed the predictive value of CFU-Mk numbers infused for recovery of platelet lineage. We found an inverse correlation between the time taken to reach a platelet count greater than 50 x 10(9)/L and only the CFU-Mk dose (r = -0.71; p = 0.022) among the different type of progenitors, including colony-forming units granulocyte-macrophage (CFU-GM), burst-forming units erythrocyte (BFU-E) and colony-forming units-mixed (CFU-Mix). These findings suggest that CFU-Mk number could be used as sole predictive functional parameter for platelet reconstitution in children after immunoselection of CD34+ cells, in particular for low CD34+ cell dose, and thus as an indicator for initial quality of hematopoietic cells before in vitro expansion.

No treatment has proved its efficiency in CLL. Autologous transplantation is now under consideration for the youngest patients. We assayed progenitor cells (CFU-GM, BFU-E, CD34) in the peripheral blood of 28 untreated CLL patients and found an increase of all these progenitors in CLL compared to controls. There was no statistical difference between stage A versus stages B and C for CFU-GM and BFU-E. In contrast, CD34 cells were higher in stages B and C as compared to stage A. This finding could be explained by a high number of circulating clonal cells in advanced stages of the disease.

We report a case of IgA-kappa multiple myeloma in a 68-year-old woman that was revealed by concomitant pleural and pericardial effusion. These effusions were found to be caused by myeloma and were verified by cytological examination of the pleural fluid and pericardial biopsy. The patient had neither osteolytic lesions nor Bence-Jones proteinuria. After a pericardiocentesis, her condition improved with a melphalan and prednisolone treatment. As far as we know, such a phenomenon is rare and has never been reported yet as a way of diagnosing multiple myeloma.

All transretinoic acid (ATRA) followed by daunorubicin (DNR)-AraC chemotherapy (CT) has improved the outcome of acute promyelocytic leukemia (APL) by comparison to CT alone. In a randomized trial, (1) we compared 2 induction schedules (ATRA followed by CT [ATRA-->CT] and ATRA plus CT [ATRA+CT, with CT added on day 3 of ATRA treatment]) and (2) we assessed the role of maintenance treatment. Four hundred thirteen patients CT and ATRA+CT (initially randomized patients); patients with a WBC count greater than (high WBC count group, n = 163) and patients 66 to 75 years of age with a WBC count greater than 5,000/microL (elderly group, n = 42) were not initially randomized and received ATRA+CT from day 1 and ATRA -->CT, respectively. All patients achieving CR received 2 additional DNR-AraC courses (only 1 in patients 66 to 75 years of age) and were then randomized for maintenance between no treatment, intermittent ATRA (15 days every 3 months) for 2 years, continuous low-dose CT (6 mercaptopurine + methotrexate) for 2 years, or both, using a 2-by-2 factorial design. Overall, 381 (92%) of the patients achieved complete remission (CR), 31 (7%) suffered an early death, and only 1 patient had leukemic resistance. ATRA syndrome occurred in 64 patients (15%) and was fatal in 5 cases. The CR rate was similar in all induction treatment groups. Event-free survival (EFS) was significantly lower in the high WBC group (P =.0002) and close to significance in the elderly group (P =.086) as compared with initially randomized patients. Relapse at 2 years was estimated at 6% in the ATRA+CT group, versus 16% in the ATRA-->CT group (P =.04, relative risk [RR] =.41). EFS at 2 years was estimated at 84% in the ATRA+CT group, versus 77% in the ATRA-->CT group (P =.1, RR =.62). Two hundred eighty-nine patients were randomized for maintenance. The 2-year relapse rate was 11% in patients randomized to continuous maintenance CT and 27% in patients randomized to no CT (P =.0002) and 13% in patients randomized to intermittent ATRA and 25% in patients randomized to no ATRA (P =.02). An additive effect of continuous maintenance CT and intermittent ATRA was seen, and only 6 of the 74 patients who received both maintenance treatments had relapsed. Overall survival was improved in patients who received maintenance CT (P =.01), and there was a trend for better survival in patients who received maintenance ATRA (P =.22). Our findings strongly suggest that early addition of chemotherapy to ATRA and maintenance therapy combining continuous CT and intermittent ATRA can reduce the incidence of relapse in APL. This effect already translates into significantly better survival for maintenance treatment with continuous CT.

There is a need for fast and sensitive methods to evaluate the response of patients with chronic myeloid leukaemia (CML) to interferon-alpha (IFN-alpha) therapy to complement cytogenetic analysis of Philadelphia (Ph) chromosome-positive metaphases. We have used interphase FISH (fluorescence in situ hybridization) and competitive RT-PCR (reverse transcriptase-polymerase chain reaction) techniques for detection of BCR-ABL-positive cells to measure suppression of leukaemic clone in a series of 51 follow-up samples from 24 CML patients undergoing IFN-alpha treatment. Interphase FISH analysis of the malignant clone in bone marrow using BCR and ABL probes was found to be highly correlated to conventional G-banding metaphase examination (r = 0.98). RT-PCR quantification of BCR-ABL mRNA transcripts in blood also showed a high degree of concordance with the proportion of Ph-positive metaphases (r = 0.93). In addition, the degree of cytogenetic response did not influence the equivalence between karyotype analysis and molecular methods. We concluded that interphase FISH and competitive RT-PCR provide reliable information on residual tumour burden and response to IFN-alpha in CML patients. These molecular methods may significantly improve the efficiency of residual disease monitoring during IFN-alpha therapy of CML.

Background: To determine whether chlorambucil treatment benefits patients with indolent chronic lymphocytic leukemia (CLL), we conducted two randomized trials in 1535 patients with previously untreated stage A CLL., Methods: In the first trial, 609 patients were randomly assigned to receive either daily chlorambucil or no treatment; in the second trial, 926 patients were randomly assigned to receive either intermittent chlorambucil plus prednisone or no treatment. Median follow-up for the first and second trials exceeded 11 and 6 years, respectively. The end points were overall survival, response to treatment, and disease progression., Results: Treatment of indolent CLL did not increase survival in either trial. In the treated group, as compared with the untreated group, the relative risk of death was 1.14 (95 percent confidence interval, 0.92 to 1.41; P=0.23) in the first trial and 0.96 (95 percent confidence interval, 0.75 to 1.23; P=0.74) in the second trial, with 76 percent and 69 percent of patients, respectively, having a response to therapy. Although chlorambucil slowed disease progression, there was no effect on overall survival. In the untreated group in the first trial, 49 percent of patients did not have progression to more advanced disease and did not need therapy after follow-up of more than 11 years; however, 27 percent of patients with stage A CLL died of causes related to the disease., Conclusions: Chlorambucil does not prolong survival in patients with stage A CLL. Since deferring therapy until the disease progresses to stage B or C does not compromise survival, treatment of indolent CLL is unnecessary.

Eyelid localisation of non-Hodgkin's lymphoma is rare, and even more so when it is bilateral. We report a 58 year-old man who presented with an eyelid localisation of lymphoplasmacytoid lymphoma. The initial treatment was chemotherapy with good improvement but the relapse lead us to give radiotherapy with no further relapse 20 months later. Radiotherapy is the current treatment of localised eyelid lymphomas with excellent results. The prognosis is related to the initial staging and the 10-year survival rate is close to 80%.

We report the experience of three French centres which evaluated high-dose therapy (HDT) as consolidation therapy for poor prognosis Hodgkin's disease (HD). From March 1986 to April 1990, 23 consecutive patients with poor prognosis stage IV HD underwent HDT followed by autologous bone marrow transplantation (ABMT) after achieving either complete remission (CR1) or good partial response (GPR1) (reduction mass> 75%). The median age was 31 years (range 18 to 55 years), 14 were male. All patients except one initially had at least 2 poor prognosis factors such as: systemic symptoms (n = 19), bulky tumor (n = 16), more than one extranodal site (n = 9), bone marrow involvement (n = 5), lymphocyte count < or = 1.10(9)/1 (n = 8) and biological stage B (n = 21). All patients had previously been treated with alternating MOPP/ABVD. Ten patients were in GPR1 and 13 in CR1 before transplant. The conditioning regimens were: CBV (n = 17), BEAM (n = 5), BEAC (n = 1) followed by bone marrow rescue. Radiotherapy was introduced just before the conditioning regimen for 6 patients or after ABMT for 5 patients. Nine of 10 patients in GPR1 achieved CR after ABMT but one died early of treatment-related toxicity. Five of 22 patients who were in CR posttransplant, relapsed (3, 4, 4, 18, 36 months). Seventeen patients remain alive in continuous CR with a median follow-up of 60 months (range: 30-100 months). The overall survival (OS) and disease-free survival (DFS) projected at 5 years are 92% and 77% respectively. Consolidation by HDT and ABMT proved to be well tolerated. An international trial is currently underway to attempt to demonstrate a clear benefit on survival for this subset of poor prognosis HD patients.

Purpose: To confirm and extend encouraging preliminary results of timed sequential chemotherapy (TSC) in patients with previously treated acute myelogenous leukemia (AML)., Patients and Methods: We report the results of the regimen of mitoxantrone on days 1 to 3, etoposide on days 8 to 10, and cytarabine on days 1 to 3 and 8 to 10 (EMA) in 133 patients, with a median follow-up of 40 months., Results: Sixty percent of patients, with a 95% confidence interval (CI) ranging from 51% to 68%, achieved complete remission (CR), including 44% (CI, 32% to 57%) of refractory patients and 76% (CI, 64% to 86%) of late first-relapse patients (P = .0002). Twenty-nine percent of patients did not respond to therapy, and 11% died from toxicity. Median duration of neutropenia and thrombocytopenia was 31 days and 29 days, respectively. Severe nonhematologic toxicity included sepsis in 54% of patients and mucositis in 23%. Postinduction therapy included a second course of EMA in 27 patients, maintenance in 10, autologous bone marrow transplantation (BMT) in 12, and allogeneic BMT in 13. Median survival of patients who did not have transplantation performed is 7 months, with 11% (CI, 4% to 18%) survival at 5 years. Median disease-free survival (DFS) is 8 months with 20% (CI, 8% to 32%) DFS at 5 years. Twenty-eight percent (CI, 15% to 44%) of nontransplanted patients who achieved CR had an inversion of CR duration. Previous refractoriness was the main factor associated with poor prognosis for CR achievement, DFS, and survival., Conclusion: These results confirm initial reports on TSC and show that approximately 20% of patients with first relapse after therapy can enjoy prolonged DFS using chemotherapy only.

Most patients with Hodgkin's disease (HD) are cured with chemotherapy and/or radiotherapy. However, half of those with advanced stage disease (IIIB, IV) do not respond adequately to treatment or relapse. Salvage therapy used in such cases gives from 10% to 50% complete remission but only 10% long term survival. The results of bone marrow transplantation reported in acute leukemia and non-Hodgkin's lymphoma encouraged some authors to develop this new therapeutic strategy in Hodgkin's disease. In the early 1980's promising results were achieved when refractory and relapsed patients were selected to receive myeloablative therapy followed by bone marrow transplantation. Today, high dose chemotherapy with hematopoietic stem cell transplantation (HSCT) is used more and more often in poor prognosis Hodgkin's disease. After a review of the literature concerning the results of transplantation in Hodgkin's disease, we develop the numerous problems associated with this procedure which remain to be solved such as: the optimal indication, the timing of HSCT, the type of graft, the conditioning regimen, the place of radiotherapy and the optimal use of hematopoietic growth factors. We conclude with future prospects.

The level of blast cells in peripheral blood in acute myeloid leukemia (AML) varies in individual patients. The bone marrow egress of hematopoietic cells is an unclear phenomenon in which cell deformability and cytoadhesion to the extracellular matrix are involved. One component of deformability is the membrane fluidity. Using fluorescence polarization, we have studied the fluidity of blast cell membranes from 22 AML patients. This membrane was found to be highly fluid and a statistically significant correlation was found between the increase in membrane fluidity and the number of blast cells in the blood. Studying interaction between blast cells and several components of bone marrow stroma, we found adhesion to fibronectin and fibroblastic extracellular matrix. Adhesion to the extracellular matrix was inversally correlated to the level of blast cells in the blood. The observed increase in membrane fluidity and reduction of adhesion to bone marrow stroma may result in an increase of blast cells egress in AML.