The impact of total body irradiation on the outcome of patients with follicular lymphoma treated with autologous stem-cell transplantation in the modern era: a retrospective study of the EBMT Lymphoma Working Party.

BACKGROUND: The aim of this study was to investigate the impact of the high-dose regimen on the outcome of patients with follicular lymphoma (FL) having had autologous stem-cell transplantation (ASCT) in a recent time period. PATIENTS: Between 1995 and 2007, 2233 patients with FL had their first ASCT with either a total body irradiation (TBI)-containing regimen or carmustin, etoposide, cytarabine and melphalan (BEAM), of which 47% were autografted in first remission. RESULTS: After a median observation time of 73 months (interquartile range 30-107), 5- and 10-year non-relapse mortality (NRM) was similar (6% and 10% in both groups). No significant NRM differences became evident after multivariate adjustment for confounders. Secondary malignancies were observed in 9.7% and 7.9% of the patients after TBI and BEAM (P = 0.19), which were treatment-related myelodysplastic syndromes/acute myelogenous leukaemia (t-MDS/AML) in 3.4% and 2.8% (P = 0.57). The median time to t-MDS/AML was around 50 months in both groups. Because of a lower relapse incidence, TBI was associated with better event-free survival reaching statistical significance in the patients transplanted in first remission but not in those transplanted beyond first remission. CONCLUSIONS: In patients with FL who received TBI-based ASCT after 1995 increased NRM and t-MDS/AML risks did not emerge compared with BEAM while disease control was at least equivalent.

Rituximab induction immunotherapy for first-line low-tumor-burden follicular lymphoma: survival analyses with 7-year follow-up.

BACKGROUND: The purpose of this study was to report long-term results of rituximab induction monotherapy in patients with low-tumor-burden follicular lymphoma (LTBFL). PATIENTS AND METHODS: Of 49 first-line LTBFL patients who received weekly doses of rituximab (375 mg/m(2)), 46 have been followed with a long-term analysis of clinical and molecular responses. RESULTS: Best clinical response (at any staging within a year following treatment) was 80%, 24 (52%) patients had complete or unconfirmed complete response, 13 (28%) had partial response and 9 (20%) had stable or progressive disease. Of 31 patients having a positive bcl2-JH rearrangement, 15 (48%) became negative following treatment. After 83.9 months of follow-up (95% confidence interval 6.4-92.8 months), the median progression-free survival is 23.5 months and overall survival (OS) is 91.7%. Five patients died (one progression, one myelodysplasia, one diffuse large B-cell lymphoma and two solid tumors). Seven patients (15%) are progression-free including five who are bcl2 informative. No unexpected long-term adverse event has been observed. CONCLUSION: A significant proportion of patients remain progression-free 7 years after a single 4-dose rituximab treatment in first-line LTBFL. The 7-year overall survivalOS is very high in this selected population of patients.

A 4-weekly course of rituximab is safe and improves tumor control for patients with minimal residual disease persisting 3 months after autologous hematopoietic stem-cell transplantation: results of a prospective multicenter phase II study in patients with follicular lymphoma.

BACKGROUND: This study explored the efficacy and safety of rituximab as treatment of clinical or molecular residual disease after autologous stem-cell transplantation (ASCT) in follicular lymphoma (FL). PATIENTS AND METHODS: Forty patients with CD20+ FL and clinically (group A, n = 14) or clono-specific PCR-detectable (group B, n = 25) residual disease persisting 3 months after ASCT received rituximab 375 mg/m² once weekly for 4 weeks. RESULTS: Response rate at day 50 was 36% [90% confidence interval (CI) 15-61] in group A (World Health Organization criteria) and 52% (90% CI 34-70) in group B (conversion PCR-undetectable status to undetectable status). The best response rate was 71% [nine complete responses (CRs) and one partial response] in group A and 76% in group B. At 36 months, all 10 responses persisted in group A, whereas 46% of patients in group B still had PCR-undetectable disease. Furthermore, 68% of patients in group B were still in clinical CR. Rituximab after ASCT was safe with few grade 3-4 toxic effects (15% patients), mainly acute reactions and infections. CONCLUSION: Rituximab induced a high rate of durable CRs in patients with clinically detectable disease, as well as durable eradication of PCR-detectable disease in patients with FL after ASCT. Continued molecular responses assessed with a highly sensitive and clono-specific PCR technique were correlated with an excellent disease control.

Recognition of radiographers in the workplace: Why it matters.

INTRODUCTION: Recognition of radiographers' work has received limited research attention to date, notably its link with wellbeing at work (i.e., job and career satisfaction) and emotional exhaustion. This research focuses on these links and examines more precisely the mediational psychological mechanism (i.e., professional identification) that could explain these relationships. METHODS: This was a cross-sectional, quantitative study with data obtained through an online survey. The sample comprised 713 radiographers working in France. Structural equation modeling was used to test the mediational model. RESULTS: Results of structural equation analysis suggest that radiographers who perceive more professional recognition from their supervisors, colleagues and patients are those who identify most with their profession and who are most satisfied by their job and their career; they also show lower levels of emotional exhaustion. These results underline the crucial role of recognition in the workplace for these professionals. CONCLUSION: Recognition is one of the basic needs of an individual, and satisfying this need is a crucial issue for organizations. This paper focuses on the importance of recognition for radiographers, notably to protect their psychological health and increase their well-being at work and in their professional career. PRACTICAL IMPLICATIONS: Health organizations and supervisors should be aware of the importance of recognizing radiographers' work in order to improve their psychological health, enhance their perceived quality of life at work, and have a positive perception of their career and their work.

Neutrophil role in in vivo anti-lymphoma activity of rituximab: FCGR3B-NA1/NA2 polymorphism does not influence response and survival after rituximab treatment.

BACKGROUND: Neutrophils could play an important role in in vivo rituximab anti-lymphoma activity. FcgammaRIIIb is expressed only by neutrophils and FcgammaRIIIb-neutrophil antigen (NA)1/NA2 polymorphism influenced phagocytosis of immunoglobulin G1-opsonized particles. We formulated the hypothesis that if neutrophils are critical cells for in vivo rituximab activity, FcgammaRIIIb-NA1/NA2 polymorphism could influence the response to rituximab. PATIENTS AND METHODS: FCGR3B-NA1/NA2 genotypes were determined in 46 patients having received rituximab for a previously untreated, follicular, non-Hodgkin's lymphoma. The clinical response and the disappearance of the BCL2-JH gene rearrangement in both peripheral blood and bone marrow were evaluated at 2 months (M2) and each year during 7 years. RESULTS: They were 13% homozygous for FCGR3B-NA1, 61% homozygous for FCGR3B-NA1/NA2 and 26% heterozygous. The objective response rates at M2 were 67% in homozygous FCGR3B-NA1 patients compared with 75% in homozygous FCGR3B-NA2 and 75% in heterozygous patients (not significant). We found no difference for progression-free and overall survival by FCGR3B-NA1/NA2 genotypes. CONCLUSION: These results indicate no association between FCGR3B-NA1/NA2 polymorphism and response to rituximab indicating no significant role of phagocytosis mediated by neutrophils in in vivo mechanism of rituximab activity.

[Health care units in the French blood banks, why?]. / Les structures de soins dans les établissements de transfusion sanguine, pourquoi faire ?

In France for several years, many patients have been treated in Blood Transfusion Centers belonging to the EFS. This partnership between public hospitals and EFS is appreciated by the patients who find a competent staff in transfusion and apheresis process, in a more pleasant environment than in hospital. There is a total of 93 Health Care Units in Blood Transfusion Centers. Sixty-three of these Health Care Units perform only transfusions and bleeding. In the remaining 30 Health Care Units apheresis, peripheral blood hematopoietic stem, cell harvesting, plasmatic exchanges and extracorporeal photopheresis are also performed. Despite the perfect fit between hospital needs, comfort and easiness for patients, an economical problem remains. At the present time, the reimbursement rate by national health insurance is below the real cost. If unsolved, this discrepancy could force an end to this beneficial partnership.

VAD-PECC regimen in the treatment of advanced-stage multiple myeloma.

PURPOSE: This prospective study was undertaken to evaluate the efficacy of combination chemotherapy with alternating cycles of vincristine, doxorubicin, and dexamethasone (VAD) and prednisone, vindesine, carmustine, and cyclophosphamide (PECC) in poor-risk multiple myeloma (MM). PATIENTS AND METHODS: Forty-four patients were previously untreated; 36 had been pretreated with an alkylating agent-containing regimen and had refractory or relapsed MM. All previously untreated patients had a high tumor burden at inclusion (stage III according to the Durie and Salmon classification). Logistic regression and the Cox proportional hazards models were used to assess the association between patient characteristics and response rate and survival, respectively. RESULTS: The overall response rate was 68% for previously untreated patients, compared with 54% for previously treated patients (P = .16). The median survival time for all patients was 28 months: 53 months in previously untreated patients, and 18 months in previously treated patients. Univariate analysis showed that the predictive factors that had a significant affect on survival in the newly diagnosed patients were age, therapeutic response to VAD-PECC, low pretreatment Karnofsky score, high baseline serum beta 2-microglobulin (beta 2M) level, bone marrow impairment, and renal insufficiency at the start of treatment. When these parameters were used as continuous variables in multivariate analysis, three were found to correlate with survival: serum beta 2M, followed by therapeutic response and Karnofsky score. In the previously treated group, only Karnofsky score entered the Cox model. CONCLUSION: These results indicate that combination VAD-PECC chemotherapy is an effective treatment that results in high response rates and long-term survival in advanced MM.

A randomized trial of amsacrine and rubidazone in 39 patients with acute promyelocytic leukemia.

Thirty-nine patients with untreated acute promyelocytic leukemia (APL) were randomly allocated to receive rubidazone (zorubicin) 200 mg/m2/d, days 1 to 4 plus cytarabine (Ara C) 200 mg/m2/d, days 1 to 7 (arm A, 21 patients), or amsacrine (Amsa) 150 mg/m2/d, days 1 to 4 plus Ara C 200 mg/m2/d, days 1 to 7 (arm B, 18 patients). Prophylaxis of disseminated intravascular coagulation was made by platelet transfusions and heparin. In case of leukemic resistance, patients received a second course with 2 days of rubidazone (arm A) or Amsa (arm B) and 3 days of Ara C. Patients who achieved complete remission (CR) received three consolidation courses with the two drugs used for induction and maintenance therapy for 3 years. Two patients in arm A and one in arm B were allografted in first CR. Initial characteristics were similar in both arms. In arm A, 18 patients (86%) reached CR, two had hypoplastic death, and one had leukemic resistance after two courses. In arm B, 12 patients (66%) achieved CR, two had early death (CNS bleeding, one case; ventricular fibrillation, one case), and four had resistant leukemia after two courses. The difference in CR rate between the two arms was not significant. In arm A, disease-free survival (DFS) showed a plateau at 54.3% after 34 months (95% confidence interval [CI], 32.1% to 74.9%), with eight CRs longer than 34 months. In arm B, DFS was significantly shorter (P less than .03), showing a plateau at 16.7% after 38 months (95% confidence interval, 4.7% to 44.6%), and only two prolonged CRs were seen. The difference in DFS remained significant after censoring allografted patients and patients who died in CR (one in arm A, two in arm B). Our results suggest that Amsa-Ara C combinations may be inferior to anthracycline-Ara C combinations in the treatment of APL, because they seem to provide shorter DFS and, possibly, a higher incidence of initial leukemic resistance. However, studies with larger numbers of patients are required.

Purging of bone marrow in autologous bone marrow transplantation for non-Hodgkin's lymphoma: a case-matched comparison with unpurged cases by the European Blood and Marrow Transplant Lymphoma Registry.

PURPOSE: The use of in vitro purging of bone marrow in autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma (NHL) has been a controversial issue; its benefit is as yet unproven. Its effect on the clinical outcome of ABMT in these patients is still unclear. We look at this issue using data from the European Blood and Marrow Transplant (EBMT) Lymphoma Registry. PATIENTS AND METHODS: Seventeen hundred twenty-six patients with NHL have been reported to the EBMT registry, of whom 270 had bone marrow purged at transplant. Two hundred twenty-four of these patients were compared with a case-matched group of 224 unpurged patients who had undergone the same procedure. The case matching was made following selection of the main prognostic factors for progression-free survival (PFS) by multivariate analysis. Response, complications, and outcome in ABMT were analyzed. RESULTS: Time to hematologic engraftment, response to ABMT, and number of procedure-related deaths were similar in purged and unpurged patients. The overall survival (OS) rate was 54% at 5 years in purged patients and 48.3% in unpurged patients (P = .1813). The PFS rate was 44.3% and 44.6%, respectively (P = .1961). Patterns of relapse, including bone marrow relapse, were similar in both groups. Patients with low-grade lymphoma did not have a significantly improved PFS if the bone marrow was purged (P = .1757); however, they did have a significantly improved OS (P = .00184). This increased OS was found to be associated with non-totalbody irradiation (TBI) conditioning and also with the purged patients undergoing transplantation at large transplant centers (P = .0016). CONCLUSION: Purging of bone marrow in ABMT for NHL does not affect the rate of hematologic engraftment or risk of procedure-related death (PRD). There is no significant difference in PFS for patients whose bone marrow is purged as compared with unpurged.

The role of autologous bone marrow transplantation in 46 adult patients with non-Hodgkin's lymphomas.

Forty-six patients with non-Hodgkin's lymphoma (NHL) were treated with autologous bone marrow transplantation (ABMT) in two different institutions. All patients were pretreated with conventional chemotherapy. Three different conditioning regimens were used, and 20 patients underwent bone marrow purging. Twelve patients were treated in first complete remission (CR); eight are in unmaintained CR 8 to 104 months after ABMT. Five patients were grafted in first partial remission (PR) after conventional therapy; all achieved CR, and all remain in prolonged CR (first CR for four patients, second CR for one patient). Of 21 patients with chemosensitive relapses, 13 patients are in prolonged unmaintained CR 8 to 94 months after ABMT. Eight patients with resistant disease remained uncured by ABMT; all eight died, six from progressive illness and two from toxicity. The current 3-year disease-free probability is 60% for all patients, 0% for refractory disease; 82% for first PR or CR, and 60% for sensitive relapses (SRs). These results confirm the efficacy of ABMT in the treatment of chemosensitive NHL with bad prognosis.

Prospective randomized placebo-controlled study of granulocyte-macrophage colony-stimulating factor without stem-cell transplantation after high-dose melphalan in patients with multiple myeloma.

PURPOSE: To evaluate the impact of granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo on the durations of intravenous (IV) antibiotic use, hospitalization, neutropenia, and fever, as well as remission rates, after high-dose melphalan (HDM) without stem-cell transplantation (SCT) in patients with multiple myeloma (MM). PATIENTS AND METHODS: One hundred two patients with high-risk MM were randomized 2:1 in a prospective multicenter trial to receive 5 microg/kg/d GM-CSF (69 patients) or placebo (33 patients) starting the day after 140 mg/m2 IV melphalan for up to 21 days. RESULTS: GM-CSF significantly reduced neutropenia after HDM (median, 23.5 v 29 days; P = .0468), with a trend to reduce the duration of hospitalization (median, 32 v 38 days; P = .0841). Nevertheless, GM-CSF did not significantly reduce infectious toxicity as regards the number of days with fever (median, 5 v 3; P = .359), the number of days with IV antibiotics (median, 22 v 27; P = .14), or early deaths, with an 11.5% treatment-related mortality rate in the GM-CSF group (eight of 69 v two of 32 patients in the placebo group; P = .686). There was no difference in response rates between the two groups of patients. CONCLUSION: GM-CSF after HDM without SCT is feasible and significantly shortens neutropenia with a trend toward reduction of hospitalization duration, but does not significantly reduce the morbidity and mortality of such therapy. Thus, when intensive therapy is indicated, given that the mortality of HDM followed by SCT reported in the literature is less than 5% and patients are discharged at approximately day 15, despite the risk of contamination by clonogenic malignant cells, SCT appears to be preferable to GM-CSF after HDM.

Comparison of high-dose therapy and autologous stem-cell transplantation with conventional therapy for Hodgkin's disease induction failure: a case-control study. Société Francaise de Greffe de Moelle.

PURPOSE: To determine the prognostic factors and outcome of first-line induction failure Hodgkin's disease patients who were treated with a salvage regimen of high-dose chemotherapy and autologous stem-cell transplantation, and to compare them with matched, conventionally treated patients. PATIENTS AND METHODS: We retrospectively analyzed data relating to 86 Hodgkin's disease patients who underwent autologous stem-cell transplantation after failure of the first chemotherapy regimen, either because they did not enter a complete remission and experienced progression of disease less than 3 months after the end of their first-line treatment or because they showed evidence of disease progression during first-line therapy. Graft patients were matched with 258 conventionally treated patients (three controls per case) for age, sex, clinical stage, B symptoms, and time at risk; patient data were obtained from international databases. RESULTS: Among the 86 graft patients, the median age at diagnosis was 29 years (range, 14 to 57 years). Thirty-nine percent of patients had stage II disease, 23% had stage III disease, and 38% had stage IV disease. Seventy percent of the patients received chemotherapy and 30% received combined modality therapy; 60% of the patients received a seven- or eight-drug regimen. After this first-line treatment, 91% had disease progression and 9% had a brief partial response. Eighty patients received a second-line treatment; pretransplantation status was as follows: 24% of patients had a complete remission, 38% had a partial remission (PR), 14% had stable disease, and disease progression occurred in 24%. With a median follow-up of 22 months (range, 4 to 105 months) from diagnosis, the 5-year event-free survival and overall survival rates from transplantation were 25% and 35% (95% confidence intervals, 15 to 36 and 23 to 49), respectively. In multivariate analysis, the pretransplantation disease status after salvage therapy was the only significant prognostic factor for survival (PR: relative risk = 2.8, P = .017; progressive disease: relative risk (RR) = 5.26, P < .001). From diagnosis, the 6-year overall survival rates of the graft patients and 258 matched conventionally treated patients were 38% and 29%, respectively (P = .058). CONCLUSION: Autologous stem-cell transplantation represents the best therapeutic option currently available for patients with primary induction failure and is associated with acceptable toxicity. Response to second-line treatment before high-dose chemotherapy is the only prognostic factor that can be correlated with survival.

Long-term cultures to evaluate engraftment potential of CD34+ cells from peripheral blood after mobilization by chemotherapy with and without GM-CSF.

In this study we used a long-term culture system to evaluate engraftment potential of human peripheral blood (PB) cells mobilized by chemotherapy (CT) associated or not with granulocyte-macrophage colony-stimulating factor (GM-CSF). In six patients who underwent blood cell transplantation, PB CD34+ cells were cultured after mobilization and were compared to CD34+ cells in steady state from PB and bone marrow (BM). Qualitative differences were shown between PBC samples obtained after CT with and without GM-CSF. Despite similar CFU-GM counts at culture initiation, GM-CSF-mobilized CD34+ cells might contain a lower proportion of primitive stem cells, as suggested by the significant decrease in CFU-GM numbers produced beyond week 5 compared to CT-mobilized CD34+ cells (p = 0.033). Likewise, the percentage of CFU-GM produced beyond week 5 in relation to initial input was significantly lower than steady-state PB (p = 0.039) and than CT-mobilized CD34+ cells (p = 0.033). However, this CFU-GM production with GM-CSF-mobilized PB CD34+ cells was not different from cultures with BMC CD34+ cells. These results suggest that GM-CSF can mobilize CFU-GM in the blood mainly by differentiation at the expense of the primitive stem cell compartment. It appears valuable to define clearly for each mobilizing procedure a particular threshold of CFU-GM which reflects sufficient numbers of primitive stem cells to ensure long-term engraftment.

[North-South cooperation on transfusion and hematology teaching: A Benin experience]. / Coopération Nord-Sud pour le renforcement des capacités du personnel de santé en hématologie et transfusion : expérience du Bénin.

Hematologic diseases are a significant part of health disorders in Benin. As an example, anemia is the second cause of hospitalization, measuring up to 7.9% all over the country (National Plan of Sanitary Development, 2009-2018). By contrast, there is only one active hematologist in the country. Thanks to two partnerships, on one hand between the health sciences faculty in Cotonou (Benin) and the medicine one in Tours (France), and on the other hand between the Beninese Blood Transfusion National Agency and the French Blood Establishment, a first blood transfusion and hematology formation was held in Cotonou on December 2014. Among other benefits, was created an hematology-transfusion network in order to facilitate relations between Beninese hospital doctors, with the support of the two French partner institutions. The article describes this progress.

Treatment of poor prognosis Burkitt's lymphoma in adults with the Société Française d'Oncologie Pédiatrique LMB Protocol--a study of the Federation Nationale des Centres de Lutte Contre le Cancer (FNLCC).

14 adult patients between 16 and 50 years old with small non-cleaved cell lymphoma (Burkitt's lymphoma) were prospectively treated from 1982 to 1990 with the LMB protocols of the Société Française d'Oncologie Pédiatrique (SFOP). No HIV-positive patients were included. All patients had extensive disease with bad prognosis factors, i.e. 10 patients had Murphy stage III and 4 had stage IV with bone marrow involvement. The LMB protocols were characterised by high-dose fractionated cyclophosphamide, high-dose methotrexate (HD-MTX), and cytosine arabinoside. No local or central nervous system irradiation was used. Treatment duration ranged from 5 (LMB 84) to 12 (LMB 81) months. There were no therapy-related deaths. All patients achieved complete remission (CR). 6 patients relapsed between 2 and 30 months following CR. 8 of the 14 patients (57%) are still alive and disease-free after treatment by LMB protocol alone. 2 patients were salvaged with bone marrow transplantation after relapse and a total of 10 out of 14 patients (71%) are disease-free at the time of this report. Our results showed the high curability of advanced Burkitt's lymphoma using a paediatric protocol, even in adult patients. The LMB protocol may be applied to adult patients but requires intensive care during the induction period.

Effect of cell determinant (CD)34+ cell dose on the cost and consequences of peripheral blood stem cell transplantation for non-Hodgkin's lymphoma patients in front-line therapy.

The aim of this study was to assess the effect of cell determinant (CD)34+ cell dose on the cost and consequences of peripheral blood stem cell transplantation for non-Hodgkin's lymphoma (NHL) patients in front-line therapy. Resource utilisation, length of aplasia, overall (OS) and event-free survival (EFS) were assessed for 63 patients. Economic data were calculated taking into account harvest, hospitalisation, blood product requirements and drugs required until discharge. The point of view of the Hospital Institution was chosen. A significantly earlier haematopoietic engraftment was achieved in patients with a count of more than 5 x 10(6) CD34+/kg. There were no differences for OS and EFS. A high CD34+ cell content resulted in a total cost saving of $4210. This was principally related to a significant reduction in the length of hospitalisation (-$3010) and platelet and red blood cell transfusions (-$815), although the latter was not significant. Several sensitivity analyses showed the robustness of our results. A CD34+ cell dose higher than 5 x 10(6)/kg appeared to be optimal for clinical and economic considerations in NHL patients undergoing transplantation in front-line therapy.

Induction of granulocytic maturation in acute myeloid leukemia by G-CSF and retinoic acid.

AML cells were cultured free of serum with G-CSF in combination with all-trans-retinoic acid (RA), prostaglandin E2 or 8-bromocyclic AMP to see whether the maturation blockade of these cells could be overcome. The combination G-CSF + RA was most effective in inducing morphologic maturation, i.e. in 7/10 cases. Morphological alterations in response to G-CSF + RA indicated progression of the cells along the granulocytic pathway towards metamyelocytes and granulocytes. However, morphologically mature AML cells remained negative for myeloperoxidase and Sudan black stainings, indicators of granulocytic maturation. Chloracetate esterase positivity and CD15 membrane antigens became expressed on cultured AML cells, i.e. on unstimulated and G-CSF/RA exposed blasts. Ingestion of latex beads and reduction of nitroblue tetrazolium salt occurred in cultured AML cells regardless of the presence of inducers. In almost all cases clonogenic cells persisted after exposure to G-CSF + RA suggesting that subpopulations of immature cells escaped the action of these inducers. Thus although G-CSF + RA were capable of inducing maturation of AML cells along the granulocytic lineage, maturation was incomplete and the effect was evident in a subfraction of the cells only.

Cytokine production in long-term marrow cultures after autologous bone marrow transplantation.

We compared the release of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor alpha (TNF alpha) in the supernatant of long-term bone marrow cultures (LTBMC) derived from 10 control patients and from 14 patients before and 3 months after autologous bone marrow transplantation (BMT). The three cytokines were spontaneously present in the supernatant of cultures established from patients before and after autologous BMT, while GM-CSF remained undetectable in the supernatants of control patients. The maximal levels of cytokines were produced after the first week and were not statistically different between control, patients before and after grafts although the granulocyte-macrophage colony-forming unit (CFU-GM) production in long-term culture (LTC) was lower in patients after graft compared with control patients (median values at LTC initiation: 32 and 158, respectively, P < 0.001 and median values of the total production: 510 and 12406, respectively, P < 0.002). However, GM-CSF was more frequently detected in patients after graft than in control patients. This study demonstrated that the production of GM-CSF, G-CSF and TNF alpha is not impaired in patients after graft (medians 0, 870.5, 173.5 pg/ml and ranges 0-31.2, 0-10 000 and 0-1426, respectively) compared with control patients (medians 0, 69, 66 pg/ml and ranges 0, 0-13 280 and 0-1318, respectively), although patients after graft were shown to have lower marrow CFU-GM counts. These results suggest that the ability of the accessory cells to produce these cytokines was not reduced after autologous BMT.

Acute hepatitis B after autologous stem cell transplantation in a man previously infected by hepatitis B virus.

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.

Value of autologous stem cell transplantation with purged bone marrow as first-line therapy for follicular lymphoma with high tumor burden: a GOELAMS phase II study.

This prospective phase II study was undertaken to evaluate the efficacy and toxicity of early intensive therapy followed by purged autologous bone marrow transplantation (ABMT) in patients with follicular lymphoma with high tumor burden. All patients received the VCAP regimen (vindesine, cyclophosphamide, doxorubicin and prednisone) as conventional chemotherapy and DHAP as second-line therapy. Twenty-nine consecutive patients were included in the study. Twenty-seven patients were grafted, seven in first complete remission (CR) and 20 in first partial remission (PR). Preparative therapy consisted of cyclophosphamide and total body irradiation (TBI) in all the patients. With a median follow-up of 6 years, the actuarial overall survival is 64% and the actuarial event-free survival is 55%. Two treatment-related early deaths were observed. Eleven patients were informative for serial PCR analysis of minimal residual disease after ABMT: two relapsed, four remained disease-free with PCR positivity and five were disease-free with PCR negativity. These encouraging results lay the basis of future prospective randomized trials comparing autologous stem cell transplantation as front-line treatment with conventional chemotherapy for patients with bad prognostic factors.