J L Pico

Publications (111)587.63 Total impact

• Article: Tumor marker kinetics predict outcome in patients with relapsed disseminated non-seminomatous germ-cell tumors.

  C Massard, A Kramar, J Beyer, J T Hartmann, A Lorch, J L Pico, G Rosti, J P Droz, K Fizazi
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  ABSTRACT: Background An early serum tumor marker (TM) decline during chemotherapy was shown to independently predict survival in patients with poor-prognosis disseminated non-seminomatous germ-cell tumors (NSGCTs). The aim of this study was to assess whether a TM decline (TMD) also correlates with the outcome in the salvage setting.Patients and methodsData regarding 400 patients with progressive or relapsed disseminated NSGCTs after first-line chemotherapy prospectively accrued onto two phase III clinical trials were obtained. Serum alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (hCG) were assessed at baseline and after 6 weeks of chemotherapy. A total of 297 patients, 185 and 112 in the training and validation sets, with initially abnormal TMs for whom a change from baseline could be established were used for this analysis.ResultsAn unfavorable decline in either AFP or hCG was predictive of progression-free survival (PFS) [hazard ratio, HR = 2.15, (95% CI 1.48-3.11); P < 0.001; 2-year PFS rate: 50% versus 26%] as was the Lorch prognostic score (LPS). In the multivariate analysis, an unfavorable TMD, stratified based on the LPS, was an independent adverse prognostic factor for PFS and OS.Conclusion An unfavorable TMD during the first 6 weeks after chemotherapy is associated with a poorer outcome in patients with relapsed disseminated NSGCTs.
  Annals of Oncology 10/2012; · 6.43 Impact Factor
• Article: Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol.

  M Diviné, P Casassus, S Koscielny, J Bosq, C Sebban, C Le Maignan, A Stamattoulas, B Dupriez, M Raphaël, J-L Pico, V Ribrag
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  ABSTRACT: We conducted a phase II study to evaluate in 72 adult patients the efficacy of the intensive LMB chemotherapy regimen, previously reported by the Société Française d'Oncologie Pédiatrique for children with Burkitt lymphoma and L3 acute lymphoblastic leukemia. Treatment began with a prephase (low-dose steroids, vincristine and cyclophosphamide), except in patients with low tumor burden. Group A (resected stage I and abdominal stage II disease) received three courses of vincristine, cyclophosphamide, doxorubicin and prednisone. Group B (not eligible for groups A or C) received five courses of chemotherapy comprising high-dose methotrexate, infusional cytarabine and intrathecal (IT) methotrexate. Group C (patients with central nervous system and/or bone marrow involvement with < 30% of blast cells) received eight courses containing intensified high-dose methotrexate, high-dose cytarabine, etoposide and triple IT injections. The 2 year event-free survival and overall survival rates for the 72 patients were 65% and 70%, respectively. Age > or = 33 years and high lactate dehydrogenase value were associated with a shorter survival. No response to COP was also associated with a poor outcome in group B. Patients with advanced-stage Burkitt lymphoma, including those with bone marrow and/or central nervous system involvement, can be cured with a short-term intensive chemotherapy regime tailored to the tumor burden.
  Annals of Oncology 12/2005; 16(12):1928-35. · 6.43 Impact Factor
• Article: A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours.

  J-L Pico, G Rosti, A Kramar, H Wandt, V Koza, R Salvioni, C Theodore, G Lelli, W Siegert, A Horwich, M Marangolo, W Linkesch, G Pizzocaro, H-J Schmoll, J Bouzy, J-P Droz, P Biron
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  ABSTRACT: Incomplete remission or relapse from first-line chemotherapy has poor prognosis in male germ cell tumour patients. This phase III randomised trial compares conventional salvage to high-dose-intensification chemotherapy. Between February 1994 and September 2001, 280 patients from 43 institutions in 11 countries, were randomly assigned to receive either four cycles of cisplatin, ifosfamide and etoposide (or vinblastine) (arm A), or three such cycles followed by high-dose carboplatin, etoposide and cyclophosphamide (CarboPEC) with haematopoietic stem cell support (arm B). Similar complete and partial response rates were observed in both treatment arms (56%; 95% CI 50% to 62%). There were 3% and 7% toxic deaths in arms A and B, respectively. No significant improvements with CarboPEC were observed in either 3-year event-free survival (35% versus 42%, P=0.16) or overall survival (53%; 95% CI 46% to 59%). Complete responders with CarboPEC had a significant improvement in disease-free survival (55% versus 75% at 3 years, P <0.04). The single cycle of high-dose salvage chemotherapy after three cycles of standard dose chemotherapy had no effect on treatment outcomes. These results suggest that data from uncontrolled studies should not be used to justify routine use of a toxic and expensive treatment without confirmation in a randomised trial.
  Annals of Oncology 07/2005; 16(7):1152-9. · 6.43 Impact Factor
• Source

  Available from: oxfordjournals.org

  Article: Prevention of mucositis in bone marrow transplantation: a double blind randomised controlled trial of sucralfate.

  L Castagna, E Benhamou, E Pedraza, M Luboinski, M Forni, I Brandes, J L Pico, P Y Dietrich
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  ABSTRACT: Mucositis is still a leading side effect of high dose chemotherapy and irradiation delivered in autologous and allogeneic bone marrow transplantation. In this double blind randomised study, we tested the efficacy of sucralfate for the prevention of mucositis induced by such conditioning treatments. Treatment was started one day before conditioning regimen and patients were prospectively evaluated. The main endpoint was severe mucositis that was more frequent in the placebo group than in the sucralfate group (47% vs. 29%, P = 0.07). This trend was confirmed after adjustment on total body irradiation (TBI) (P = 0.06), the sole stratification parameter. Interestingly, patients receiving sucralfate showed a significant reduction of diarrhoea (25%) vs. 53%, P = 0.005). Overall, the preventive administration of sucralfate appears to be an effective procedure to diminish the occurrence of severe oral and intestinal mucositis in patients treated by high dose chemotherapy alone or combined with TBI before bone marrow transplantation.
  Annals of Oncology 08/2001; 12(7):953-5. · 6.43 Impact Factor
• Article: Thrombotic microangiopathy: a new dose-limiting toxicity of high-dose sequential chemotherapy.

  J M Vantelon, J N Munck, J H Bourhis, J L Pico, C Fadel, A Ulusakarya, P Carde, P Fenaux, V Ribrag
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  ABSTRACT: Ten patients with refractory (n = 8) or early relapsing (n = 2) aggressive non-Hodgkin's lymphoma were enrolled in a pilot study evaluating a high-dose sequential chemotherapy regimen with peripheral blood stem cell (PBSC) support. Five treatment phases were scheduled: phase I (cyclophosphamide + etoposide followed by lenograstim (G-CSF), and a PBSC harvest); phase II (cisplatinum + cytarabine + etoposide followed by lenograstim); phases III and IV (cyclophosphamide + cytarabine + etoposide followed by autologous PBSC infusion and lenograstim); and phase V (carmustine + cytarabine + etoposide + melphalan followed by autologous PBSC infusion and lenograstim). Ten, nine, eight, six and four of the 10 patients received one, two, three, four and five of the five scheduled phases of treatment, respectively. Four patients were withdrawn from the study due to progressive disease and two due to thrombotic microangiopathy (TM). Moreover, in the four patients who completed all treatment phases, an additional case of TM was seen. In all three patients with TM, laboratory studies showed evidence of Coombs negative hemolytic anemia, thrombocytopenia, renal dysfunction and in addition cardiac failure in two patients. TM may be a new dose-limiting toxicity of high-dose sequential chemotherapy followed by repeated PBSC transplantation.
  Bone Marrow Transplantation 04/2001; 27(5):531-6. · 3.75 Impact Factor
• Article: Prospective randomized comparison of single-dose versus hyperfractionated total-body irradiation in patients with hematologic malignancies.

  T Girinsky, E Benhamou, J H Bourhis, F Dhermain, D Guillot-Valls, V Ganansia, M Luboinski, A Perez, J M Cosset, G Socie, D Baume, N Bouaouina, E Briot, A Beaudre, A Bridier, J L Pico
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  ABSTRACT: Fractionated total-body irradiation (HTBI) is considered to induce less toxicity to normal tissues and probably has the same efficacy as single-dose total-body irradiation (STBI) in patients with acute myeloid leukemia. We decided to determine whether this concept can be applied to a large number of patients with various hematologic malignancies using two dissimilar fractionation schedules. Between December 1986 and October 1994, 160 patients with various hematologic malignancies were randomized to receive either a 10-Gy dose of STBI or 14.85-Gy dose of HTBI. One hundred forty-seven patients were assessable. The 8-year overall survival rate and cause-specific survival rate in the STBI group was 38% and 63.5%, respectively. Overall survival rate and cause-specific survival rate in the HTBI group was 45% and 77%, respectively. The incidence of interstitial pneumonitis was similar in both groups. However, the incidence of veno-occlusive disease (VOD) of the liver was significantly higher in the STBI group. In the multivariate analysis with overall survival as the end point, the female sex was an independent favorable prognostic factor. On the other hand, when cause-specific survival was considered as the end point, the multivariate analysis demonstrated that sex and TBI were independent prognostic factors. The efficacy of HTBI is probably higher than that of STBI. Both regimens induce similar toxicity with the exception of VOD of the liver, the incidence of which is significantly more pronounced in the STBI group.
  Journal of Clinical Oncology 04/2000; 18(5):981-6. · 18.37 Impact Factor
• Article: Randomized study of recombinant interleukin-2 after autologous bone marrow transplantation for acute leukemia in first complete remission.

  D Blaise, M Attal, J Reiffers, M Michallet, C Bellanger, J L Pico, A M Stoppa, C Payen, G Marit, R Bouabdallah, J J Sotto, J F Rossi, M Brandely, T Hercend, D Maraninchi
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  ABSTRACT: Immunological control of acute leukemia may be achieved after allogeneic transplant. Despite promising preliminary results, the impact of immunotherapy with interleukin-2 (r-IL-2) on patients with acute leukemia (AL), in first complete remission (CR1) remains unclear. We conducted a prospective multicenter randomized trial to compare outcome in patients with AL in CR1, treated with autologous bone marrow transplantation (BMT) with or without postgraft r-IL-2. One hundred and thirty patients with AL in CR1 (myeloblastic (AML): N = 78; lymphoblastic (ALL): N = 52) were randomized at time of BMT to receive (N = 65) or not (N = 65) r-IL-2. r-IL-2 (RU 49637 from Roussel Uclaf) was started after hematological recovery, as a five cycle regimen (12 M IU/m2/day continuous infusion on day 1-5, 15-17, 29-31,43-45 and 57-59). The two groups were balanced for patient and transplant characteristics. Analysis was based on an intent to treat. Thirty-eight (59%) of the 65 patients randomized into the study group started r-IL-2 at a median of sixty-eight days (23-140) after transplant and received 77% (16-100) of the scheduled dosage. They received a median of 120 x 10(6) IU/m2 (25-156) over 10 (3-13) days during a total median period of 56 (3-78) days. With a median follow-up of 7 years (5.4-8.1 years), 79 patients relapsed (study group: 43 (66%); control group: 36 (55%): p = NS). Survival and leukemia-free survival estimates were 33% (23-45) versus 43% (22-52) and 29% (19-41) versus 36% (24-51) respectively for study and control groups (all p = NS). These results show that leukemic control after autologous BMT is not increased by r-IL-2 therapy. Further studies should investigate more appropriate r-IL-2 schedules and the possibilities offered by better antigen recognition and activated effector cells.
  European cytokine network 04/2000; 11(1):91-8. · 1.73 Impact Factor
• Article: Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Société Française de Greffe de moelle (SFGM).

  M Michallet, M L Tanguy, G Socié, A Thiébaut, A Belhabri, N Milpied, J Reiffers, M Kuentz, J Y Cahn, D Blaise, [......], A Sadoun, D Guyotat, M Attal, H Curé, P Bordigoni, L Sutton, A Buzyn-Veil, M Tilly, N Keoirruer, N Feguex
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  ABSTRACT: Although recurrent malignancy is the most frequent indication for second stem cell transplantation (2nd SCT), there are few reports that include sufficiently large numbers of patients to enable prognostic factor analysis. This retrospective study includes 150 patients who underwent a 2nd SCT for relapsed acute myeloblastic leukaemia (n = 61), acute lymphoblastic leukaemia (n = 47) or chronic myeloid leukaemia (n = 42) after a first allogeneic transplant (including 26 T-cell-depleted). The median interval between the first transplant and relapse, and between relapse and second transplant was 17 months and 5 months respectively. After the 2nd SCT, engraftment occurred in 93% of cases, 32% of patients developed acute graft-vs.-host disease (GVHD) >/= grade II and 38% chronic GVHD. The 5-year overall and disease-free survival were 32 +/- 8% and 30 +/- 8%, respectively, with a risk of relapse of 44 +/- 12% and a transplant-related mortality of 45 +/- 9%. In a multivariate analysis, five factors were associated with a better outcome after 2nd SCT: age < 16 years at second transplant; relapse occurring more than 12 months after the first transplant; transplantation from a female donor; absence of acute GVHD; and the occurrence of chronic GVHD. The best candidates for a second transplant are likely to be patients with acute leukaemia in remission before transplant, in whom the HLA-identical donor was female and who relapsed more than 1 year after the first transplant.
  British Journal of Haematology 03/2000; 108(2):400-7. · 4.94 Impact Factor
• Article: Surveillance of Aspergillus galactomannan antigenemia for invasive aspergillosis by enzyme-linked immunosorbent assay in neutropenic patients treated for hematological malignancies.

  A Ulusakarya, E Chachaty, J M Vantelon, A Youssef, C Tancrède, J L Pico, J H Bourhis, P Fenaux, J N Munck
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  ABSTRACT: The incidence of invasive fungal infections is increasing in patients with hematological malignancies. Invasive aspergillosis is one of the most frequently encountered infections with a high mortality rate. New diagnostic tests for invasive aspergillosis such as the detection of Aspergillus galactomannan antigen by a sandwich enzyme-linked immunosorbent assay (ELISA) have recently been described. The objective of this study was to evaluate this assay as a potential surrogate for invasive procedures used to diagnose IA. We analyzed the performance of a commercially available ELISA test which we routinely use for the surveillance of galactomannan antigenemia in patients with hematological malignancies experiencing chemotherapy-induced prolonged neutropenia (ANC < 500/mm(3) for more than 7 days). Serum samples were collected on a weekly basis. Test positivity was defined in accordance with the manufacturer's recommendations. Over the 2 year study period, we analyzed 507 samples obtained during 193 neutropenic episodes from 135 patients. Ten, six and two patients were considered to have proven, probable or possible invasive aspergillosis, respectively, based on clinical, radiological or microbiological data. Forty-four positive (Index>1.5) and 26 'undetermined' (1.5 > Index > 1.0) test results were observed in 17 and ten patients respectively. All invasive aspergillosis cases had at least a positive or an undetermined test result. Only one positive and one undetermined result were found in two patients before the onset of clinical or radiological signs suggesting invasive aspergillosis. Sensitivity was 69% and specificity 96% if only positive results are considered; when 'undetermined' test results were combined with positive results, sensitivity attained 100% and specificity 92% suggesting that the cutoff value for positivity can be lowered from 1.5 to 1.0. Although the ELISA test did not appear to play a role in the early diagnosis of invasive aspergillosis and in the anticipation of antifungal therapy in our experience, it clarifies the diagnosis of infection in probable or possible invasive aspergillosis especially when the cutoff value is lowered and is useful for monitoring patients receiving specific therapy.
  The Hematology Journal 02/2000; 1(2):111-6. · 1.86 Impact Factor
• Article: Unfractionated peripheral blood stem cell autografts and CD(34+)-enriched autografts have similar long-term culture initiating capacity in multiple myeloma.

  A G Turhan, J H Bourhis, M L Bonnet, S Novault, C Bayle, A Bennaceur, W Vainchenker, J L Pico, F Beaujean
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  ABSTRACT: CD(34+)-enriched peripheral blood stem cells (PBSC) are increasingly being used as an autograft in patients with multiple myeloma (MM). The rationale for the use of the CD34+-enriched fraction in MM is the ability to obtain a graft with a significant reduction of contamination by plasma cells. However, the effect of such a manipulation on the proliferating potential of the engrafted cells is not known. We wished to study, as part of a randomized trial comparing the outcome in MM patients transplanted with either CD(34+)-enriched cells or unfractionated PBSC, the primitive hematopoietic cell content of the autografts using long-term culture initiating cell (LTC-IC) assays in 7 MM patients. In 3 patients CD(34+)cell-enriched fraction was compared to unfractionated PBSC whereas in the remaining 4 patients the LTC-IC assay was performed on total PBSC. The mean percentage of CD34+ cells of the CD34+ selected fraction in three patients was 82% (range 71%-96%) whereas the same percentage in PBSC varied from 0.6% to 10% in 4 patients (mean: 4.2%). Out of three patients transplanted with CD34+ cell fraction, two patients were found to have a very similar LTC-IC generating potential in their CD34+ versus PBSC fractions as this was assessed by the clonogenic cell output at week+5 per 10(4) CD34+ cells initiating the culture (PBSC: 92 and 168 and CD34+ fraction: 102 and 16, respectively) whereas one patient had a slightly different values (PBSC: 51 and CD34+ fraction: 103). When the PBSC fraction was compared in all 7 patients, the LTC-IC generation potential was very heterogenous, varying from 1.4 to 168. To determine if the selection procedure influences the numbers of LTC-IC's in both fractions, we have performed limiting dilution assays to determine both the frequency of distribution of hematopoietic colonies and the frequency of LTC-IC's in two patients. The frequency of distribution of hematopoietic colonies was linear in both CD34+ and PBSC fractions as was the frequency of LTC-IC when the corrections were made with regard to the CD34+ cell-content of the cultures (1/20). Our results indicate that the CD34+ selection procedure used in all three patients (Ceprate) is not deleterious for the generation of LTC-IC's and these findings support the rationale for the use of this procedure in multiple for the purposes of tumor depletion.
  Hematology and Cell Therapy 12/1999; 41(5):197-204.
• Article: Gallium scan in the evaluation of post chemotherapy mediastinal residual masses of aggressive non-Hodgkin's lymphoma.

  A Ulusakarya, J Lumbroso, O Casiraghi, S Koscielny, J M Vantelon, T Girinsky, A Tardivon, J H Bourhis, P Dartevelle, J L Pico, J N Munck
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  ABSTRACT: Optimal evaluation of residual masses of non Hodgkin's lymphomas (NHL) after chemotherapy is of major importance, and gallium scan (GS) is routinely used for this purpose, particularly for mediastinal sites. However, sensitivity and specificity of GS in this setting has been diversely appreciated and needs to be more accurately defined especially if radiotherapy is not planned. A retrospective analysis selected all the patients treated in a single institution for aggressive NHL who presented a residual mass in the mediastinum after chemotherapy and who were evaluated by GS. The value of GS for distinguishing true complete responses (CR) from partial responses (PR) was analyzed in patients who were either submitted to resection of their residual mass or followed up without further treatment after GS. A residual mass with mean perpendicular diameters measuring 4.1 cm x 2.8 cm was found in 42 patients and was GS positive in 8 cases and negative in 34 cases. After GS, radiotherapy was delivered to 10 patients, but 12 patients underwent resection of their residual mass and 20 were followed up without further treatment. In the patients who did not receive radiotherapy, 3 false positive and 6 false negative GS results were disclosed. The specificity and the sensitivity of GS were 88% and 25%, and its positive predictive value and negative predictive value 40% and 78%, respectively. GS was not sufficiently reliable to evaluate post chemotherapy residual masses. Surgical resection of residual masses should be considered particularly in young patients. Patients in true CR should be spared pointless radiotherapy and its late side effects, while patients in PR may benefit from further intensified chemotherapy followed by radiotherapy.
  Leukemia and Lymphoma 11/1999; 35(5-6):579-86. · 2.58 Impact Factor
• Article: Fludarabine alone compared to CHVP plus interferon in elderly patients with follicular lymphoma and adverse prognostic parameters: a GELA study. Groupe d'Etudes des Lymphomes de l'Adulte.

  B Coiffier, E M Neidhardt-Bérard, H Tilly, C Belanger, R Bouabdallah, C Haioun, P Brice, P Y Péaud, J L Pico, M Janvier, P Solal-Celigny, N Brousse
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  ABSTRACT: Fludarabine was associated with a good response and was well tolerated in patients with follicular lymphoma in phase II trials and this treatment may be associated with less adverse events than treatment with CHVP plus interferon in elderly patients. One hundred thirty-one patients older than 59 years with a follicular lymphoma and poor prognosis were randomized between the association of CHVP (12 cycles in 18 months) plus interferon (5 MU TIW for 18 months) or fludarabine alone (25 mg/m2/d x 5 days for 6 cycles, then 20 mg/m2/day for 6 further cycles for 18 months). Poor prognosis was defined by the presence of a large tumor mass, poor performance status, the presence of B symptoms, above normal LDH level, or > or = 3 mg/l beta-microglobulin level. Patients treated with CHVP plus interferon had a higher response to treatment, a longer time to progression and a longer survival than those treated with fludarabine alone (P < 0.05 for all analyses). With a median follow-up of 29 months, the 2-year failure-free survival was 63% for the CHVP-plus-interferon arm compared to 49% for the fludarabine arm and the two-year survival was 77% and 62%, respectively. This benefit was confirmed in a multivariate analysis including initial prognostic parameters. Fludarabine alone was associated with less neutropenia than CHVP plus interferon. Interferon was decreased or stopped in 39% of the patients because of severe fatigue. CHVP plus interferon over 18 months was associated with a better outcome, even though the combination of interferon plus chemotherapy was less well tolerated than fludarabine.
  Annals of Oncology 10/1999; 10(10):1191-7. · 6.43 Impact Factor
• Article: Unfractionated peripheral blood stem cell autografts and CD34+-enriched autografts have similar long-term culture initiating capacity in multiple myeloma

  A.G. Turhan, J.H. Bourhis, M.L. Bonnet, S. Novault, C. Bayle, A. Bennaceur, W. Vainchenker, J.L. Pico, F. Beaujean
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  ABSTRACT: CD34+-enriched peripheral blood stem cells (PBSC) are increasingly being used as an autograft in patients with multiple myeloma (MM). The rationale for the use of the CD34+-enriched fraction in MM is the ability to obtain a graft with a significant reduction of contamination by plasma cells. However, the effect of such a manipulation on the proliferating potential of the engrafted cells is not known. We wished to study, as part of a randomized trial comparing the outcome in MM patients transplanted with either CD34+- enriched cells or unfractionated PBSC, the primitive hematopoietic cell content of the autografts using long-term culture initiating cell (LTC-IC) assays in 7 MM patients. In 3 patients CD34+cell-enriched fraction was compared to unfractionated PBSC whereas in the remaining 4 patients the LTC-IC assay was performed on total PBSC. The mean percentage of CD34+ cells of the CD34+ selected fraction in three patients was 82% (range 71%-96%) whereas the same percentage in PBSC varied from 0.6% to 10% in 4 patients (mean: 4.2%). Out of three patients transplanted with CD34+ cell fraction, two patients were found to have a very similar LTC-IC generating potential in their CD34+ versus PBSC fractions as this was assessed by the clonogenic cell output at week+5 per 104 CD34+ cells initiating the culture (PBSC: 92 and 168 and CD34+ fraction: 102 and 161, respectively) whereas one patient had a slightly different values (PBSC: 51 and CD34+ fraction: 103). When the PBSC fraction was compared in all 7 patients, the LTC-IC generation potential was very heterogenous, varying from 1.4 to 168. To determine if the selection procedure influences the numbers of LTC-IC’s in both fractions, we have performed limiting dilution assays to determine both the frequency of distribution of hematopoietic colonies and the frequency of LTC-IC’s in two patients. The frequency of distribution of hematopoietic colonies was linear in both CD34+ and PBSC fractions as was the frequency of LTC-IC when the corrections were made with regard to the CD34+ cell-content of the cultures (1/20). Our results indicate that the CD34+ selection procedure used in all three patients (Ceprate) is not deleterious for the generation of LTC-IC’s and these findings support the rationale for the use of this procedure in multiple myeloma for the purposes of tumor depletion. Key wordsMyeloma–Autograft–PBSC–CD34+-cells–LTC-IC
  Hematology and Cell Therapy 04/1999; 41(5):197-204.
• Source

  Available from: bvsoncologia.org.uy

  Article: Successful cryopreservation of purified autologous CD34+ cells: influence of freezing parameters on cell recovery and engraftment.

  F Beaujean, J H Bourhis, C Bayle, H Jouault, M Divine, C Rieux, M Janvier, C Le Forestier, J L Pico
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  ABSTRACT: Conventional hematopoietic stem cell cryopreservation methods use a DMSO concentration of 10%. However, cells manipulated ex vivo may require more refined freezing protocols adapted to the specific cell suspension. In this retrospective study, we evaluated the results obtained with CD34+ cells purified from peripheral blood of 39 patients on the CEPRATE SC System and frozen in 7.5% DMSO with a view to transplantation. The post-freezing recovery of progenitor cells was 89.4 +/- 27.87% for CD34+ cells, 59.13 +/- 36.93% for CFU-GM, and 53.49 +/- 40.71 for BFU-E. Neither the purity of the suspension nor the nucleated cell density during freezing was predictive of cell recovery. No difference was observed between cells stored in vials and bags. Thirty-seven patients transplanted with the concentrated CD34+ fraction received 4.46 x 10(6) CD34+ cells/kg and 33.04 x 10(4) CFU-GM/kg. The median time to granulocyte (>0.5 x 10(9)/l) and platelet (>50 x 10(9)/l) engraftment was 11 and 13 days, respectively. Only cell density and the infused number of CD34+ cells and CFU-GM were significantly related to hematological recovery. Our data suggest that purified CD34+ cells can be successfully cryopreserved in 7.5% DMSO and may represent a first step in establishing freezing parameters for selected CD34+ cells.
  Bone Marrow Transplantation 01/1999; 22(11):1091-6. · 3.75 Impact Factor
• Article: 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.

  M André, M Henry-Amar, J L Pico, P Brice, D Blaise, M Kuentz, B Coiffier, P Colombat, J Y Cahn, M Attal, J Fleury, N Milpied, G Nedellec, P Biron, H Tilly, J P Jouet, C Gisselbrecht
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  ABSTRACT: 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. 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. 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). 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.
  Journal of Clinical Oncology 01/1999; 17(1):222-9. · 18.37 Impact Factor
• Article: Successful donor lymphocyte infusion (DLI) in a patient with myelodysplastic syndrome (MDS) after failure of T-cell-depleted bone marrow transplantation (TD-BMT)

  L Castagna, A El Weshi, J H Bourhis, V Ribrag, P Naccache, J M Vantelon, P Brault, J L Pico
  British Journal of Haematology 11/1998; 103(1):284-5. · 4.94 Impact Factor
• Article: Treatment-related deaths and second cancer risk after autologous stem-cell transplantation for Hodgkin's disease.

  M André, M Henry-Amar, D Blaise, P Colombat, J Fleury, N Milpied, J Y Cahn, J L Pico, Y Bastion, M Kuentz, G Nedellec, M Attal, C Fermé, C Gisselbrecht
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  ABSTRACT: Autologous stem-cell transplantation has become a widely used therapy in Hodgkin's disease (HD). To appreciate the early and late risks associated with this procedure, its lethal toxicity and effects on the incidence of secondary cancers were studied. Data related to 467 French patients grafted from 1982 to 1995 for primary sensitive disease (PSD, 22%), primary refractory disease (PRD, 18%), first relapse (R1, 45%), or subsequent relapses (R2, 15%) were analyzed. Grafted patients (PSD, PRD, and R1; n = 393) were matched (3 controls for 1 case) on age, gender, clinical stage, B symptoms, and time at risk with 1179 conventionally treated patients issued from international databases. The proportional hazards (Cox) model was used to assess relative risks (RR). Among grafted patients, 8% died of toxicity related to the procedure, and 18 secondary cancers occurred leading to a 5-year cumulative incidence rate of 8.9%. In this series, risk factors for second cancer were age >/=40 years (RR = 3.73, P = .007) and the use of peripheral blood stem cells as source of graft (RR = 3.10, P = .03). Among grafted and matched ungrafted patients, risk factors for the development of secondary cancer were age >/=40 years (RR = 2.90, P < .001), relapse versus no relapse (RR = 5.22, P = .006), PRD versus other patients (RR = 3.86, P = .033), and grafted versus ungrafted patients (RR = 2.04, P = . 024). Solid tumors were more frequent in grafted than in ungrafted patients (RR = 5.19, P = .001) although the incidence of myelodysplasia and acute myeloid leukemia was similar in the two groups. We conclude that high-dose chemotherapy administered as first-line treatment or after relapse is associated with an acceptable toxic death rate. The risk of secondary myelodysplasia or acute myeloid leukemia is not significantly increased after autologous stem-cell transplantation for HD, whereas an increased risk of solid tumors exists. The peripheral blood stem-cell-associated risk of secondary cancer among grafted patients needs further investigations.
  Blood 09/1998; 92(6):1933-40. · 9.90 Impact Factor
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  Available from: oxfordjournals.org

  Article: Neutropenic infections: a review of the French Febrile Aplasia Study Group trials in 608 febrile neutropenic patients.

  J P Marie, A Vekhoff, J L Pico, H Guy, A Andremont, H Richet
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  ABSTRACT: From 1986 to 1992, the Febrile Aplasia Study Group conducted a series of studies involving severely neutropenic patients. The average duration of neutropenia was 21 days, following chemotherapy for leukaemia, or chemotherapy/radiotherapy as part of a conditioning regimen for autologous or allogeneic bone marrow transplantation. A total of 591 evaluable febrile episodes were randomized to treatment with either ceftazidime 3 g daily + amikacin (the reference regimen; n=246), ceftazidime alone (n=98), ceftazidime + vancomycin (n=77), ceftazidime + ciprofloxacin (n=64) or piperacillin/tazobactam + amikacin (n=106). Only three patients treated with the reference dose of ceftazidime died or suffered serious morbidity from infections caused by Gram-negative bacteria. Piperacillin/tazobactam + amikacin was the only antibiotic regimen to have an effect significantly different from the reference regimen. Piperacillin/tazobactam + amikacin produced a higher rate of defervescence at 72 h (P=0.003), fewer days of fever (P < 0.001), fewer superinfections (P=0.018), a less frequent requirement for addition of vancomycin (P=0.01) and a higher incidence of treatment judged to be a 'complete success' (enduring defervescence without a change in antibiotics) (P=0.04). Despite the improved control of Gram-positive microorganisms, the infection-related death rate remained unchanged from 1987 to 1992. An increase in disseminated aspergillosis compensated for the reduction in lethal Gram-positive septicaemia.
  Journal of Antimicrobial Chemotherapy 06/1998; 41 Suppl D:57-64. · 5.07 Impact Factor
• Source

  Available from: bvsoncologia.org.uy

  Article: VIP (etoposide, ifosfamide and cisplatinum) as a salvage intensification program in relapsed or refractory Hodgkin's disease.

  V Ribrag, F Nasr, J H Bouhris, J Bosq, P Brault, T Girinsky, J M Cosset, J N Munck, C Corti, D Decaudin, J L Pico, M Hayat, P Carde
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  ABSTRACT: Forty-two patients with refractory (15 patients) or relapsed (27 patients) Hodgkin's disease (HD) were included in a prospective single center study evaluating the efficacy of a regimen VIP combining etoposide 75 mg/m2/day days 1-5, ifosfamide 1.2 g/m2/day days 1-5 and cisplatinum 20 mg/m2/day days 1-5, one course every 4 weeks as salvage therapy in patients with refractory or relapsed Hodgkin's disease, potentially eligible for high-dose chemotherapy with reinjection of hematopoietic stem cells (HSC). If patients were considered chemosensitive after two courses of VIP, high-dose chemotherapy followed by the reinjection of HSC was planned. After two courses of VIP, 67% achieved an objective response including 38% complete responses. Overall, 28 patients went on to high-dose therapy with reinjection of HSC, and 46% of grafted patients are in a sustained complete remission. When the overall patient population is considered, 33% are in complete remission (CR) with a median follow-up of 37 months. A CR of less than 12 months and refractory disease were associated with a poor survival. These results showed that the VIP regimen is effective in relapsed or refractory HD and allows high-dose therapy to be given in the case of most responding patients. However, results in patients with refractory disease or a first complete remission of less than 12 months need to be further improved.
  Bone Marrow Transplantation 06/1998; 21(10):969-74. · 3.75 Impact Factor
• Article: Recent progress in the biology of multiple myeloma and future directions in the treatment.

  J L Pico, L Castagna, J H Bourhis
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  ABSTRACT: A great amount of scientific information, accumulated over recent years on the biology of Multiple Myeloma (MM), has fuelled speculation about the origin of malignant plasma cells, about a purported critical role played by the bone marrow stroma, and further still, on cytokine interactions and in particular that of IL-6 and its relationship with the immune system. Among the growth factors secreted by stroma cells, IL-6 is a potent stimulator of myeloma cells in vitro but does not induce a malignant phenotype in normal plasma cells. Many efforts have been produced to identify the stem cell in MM and probably memory B lymphocytes are the best candidates. The demonstration of a Graft vs Myeloma effect in the allogeneic setting strongly supports the immunotherapy in MM. Recent data also suggest that a virus (Kaposi-associated herpes virus, HHV-8) may be significantly associated with the development of MM. In parallel, progress has been achieved in the treatment of this incurable disease with well defined prognostic factors, more efficient supportive care and its corollary, improved quality of life and dose-intensified chemo-radiotherapy followed by autologous hematopoietic stem cell support. Improving the quality of grafts with the selection of CD34 positive cells is another approach aimed at reducing plasma cell contamination without impairing haematological recovery. An EBMT randomized study assessing the role of CD34 selection has been initiated by our group Increasingly efficient first-line therapy, better quality autografts and improved post-remission treatment with, for example, anti-idiopathic vaccination are the most promising future directions.
  Hematology and Cell Therapy 05/1998; 40(2):45-61.