Biomedical subjects

F Morschhauser

Publications and source records attributed to F Morschhauser.

14 recordsLinked to original sources

PubMed2006

Phase II study of gemcitabine-dexamethasone with or without cisplatin in relapsed or refractory mantle cell lymphoma.

Single-agent gemcitabine has shown encouraging results in patients with mantle cell lymphoma (MCL). This phase II study further explored the potential of a gemcitabine-based regimen in patients with relapsed or refractory MCL. Patients <70 years old received the PDG regimen: gemcitabine (1000 mg/m(2), days 1 and 8), dexamethasone (40 mg/m(2), days 1-4), and cisplatin (100 mg/m(2), day 1). Patients >/=70 years of age received dexamethasone and gemcitabine only (DG regimen). Thirty patients (12 in the DG group, 18 in the PDG group) with a median age 66.5 years (range, 47-81) received a median of six cycles in both groups. The overall response rate was 36.4% [95% confidence interval (CI), 15.2% to 64.6%] with the DG regimen and 44.4% (95% CI 24.6% to 66.3%) with the PDG regimen. The median progression-free survival was 3 months (95% CI 0.0-7.9) in the DG group and 8.5 months (95% CI 4.8-12.2) in the PDG group. With a median follow-up of 38.8 months, 13 patients (including 11 given PDG) are still alive. DG was well tolerated, and thrombocytopenia was the most prevalent toxicity in patients receiving PDG. Both regimens deserve to be further investigated as a backbone for combination chemotherapy in patients with MCL.

Adult↗

PubMed2005

Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: To analyze the long-term outcome of patients included in the Lymphome Non Hodgkinien study 98-5 (LNH98-5) comparing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to rituximab plus CHOP (R-CHOP) in elderly patients with diffuse large B-cell lymphoma. PATIENTS AND METHODS: LNH98-5 was a randomized study that included 399 previously untreated patients, age 60 to 80 years, with diffuse large B-cell lymphoma. Patients received eight cycles of classical CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2), and prednisone 40 mg/m(2) for 5 days) every 3 weeks. In R-CHOP, rituximab 375 mg/m(2) was administered the same day as CHOP. Survivals were analyzed using the intent-to-treat principle. RESULTS: Median follow-up is 5 years at present. Event-free survival, progression-free survival, disease-free survival, and overall survival remain statistically significant in favor of the combination of R-CHOP (P = .00002, P < .00001, P < .00031, and P < .0073, respectively, in the log-rank test). Patients with low-risk or high-risk lymphoma according to the age-adjusted International Prognostic Index have longer survivals if treated with the combination. No long-term toxicity appeared to be associated with the R-CHOP combination. CONCLUSION: Using the combination of R-CHOP leads to significant improvement of the outcome of elderly patients with diffuse large B-cell lymphoma, with significant survival benefit maintained during a 5-year follow-up. This combination should become the standard for treating these patients.

Aged↗

PubMed2005

Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21).

Despite the favorable prognosis of patients with acute myeloid leukemia (AML) with t(8;21)(q22;q22) translocation, relapses still occur in about 30% of the cases but no initial factors can strongly predict the risk of relapse. Several recent studies suggest that monitoring minimal residual disease (MRD) may identify patients at risk of relapse. We prospectively monitored AML1-ETO rearrangement by real-time quantitative PCR (RQ-PCR) in 21 patients uniformly treated in our center. Blood (PB) and bone marrow (BM) samples were collected during and after therapy. At diagnosis, levels of AML1-ETO transcript showed large variations and there was a trend for a higher relapse rate in patients with high pretreatment expression levels (P=0.065). After induction therapy, absolute transcript levels (below 10(-3), compared to Kasumi cell line), or a greater than 3 log decrease by comparison to diagnosis levels, were significant predictors of the absence of relapse (P=0.02 and P=0.02, respectively). MRD levels after consolidation therapy were also significant indicators of relapse (P=10(-5)). Comparison of BM and PB samples showed similar sensitivity for detecting AML1-ETO transcript. In conclusion, RQ-PCR appears to be an early predictive factor of the relapse risk in AML with t(8;21). PB samples can be used adequately to evaluate the level of MRD by this technique.

Adolescent↗

PubMed2004

Prognostic factors in patients with aggressive non-Hodgkin's lymphoma treated by front-line autotransplantation after complete remission: a cohort study by the Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: Improved survival has been observed in aggressive non-Hodgkin's lymphoma (NHL) patients with adverse prognostic factors when autotransplantation (ASCT) was performed after complete remission. However, there is no agreement on the prognostic factors for patients treated with ASCT. We aimed to estimate the prognostic effect of clinical and biologic variables on relapse and survival rates by pooling the data from two trials. PATIENTS AND METHODS: Of the patients treated in the LNH87 and LNH93 trials, 330 under age 60 years achieved complete remission after high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone, and received consolidative ASCT; 16% of patients had T-cell NHL. The International Prognostic Index (IPI) score was 0 for 11%, 1 for 23%, 2 for 51%, and 3 for 15%. Univariate and Cox multivariate survival analyses were retrospectively performed on this population. RESULTS: Overall survival was 75 +/- 5% at 5 years and disease-free survival (DFS) 67 +/- 5%. For T-cell NHL, these scores were 54% and 44%, respectively. The IPI score had no prognostic value and only the following parameters adversely affected overall survival and DFS (P <.05): marrow involvement; more than one extranodal site; histology (nonanaplastic T-cell v others); and type of anthracycline (mitoxantrone v doxorubicin, for DFS only). CONCLUSION: These results suggest that ASCT can prevent relapse in patients with adverse IPI factors. However, patients presenting with a nonanaplastic T-cell phenotype, more than one extranodal site, or marrow involvement still have a higher risk of relapse. These factors should be taken into account when designing post-ASCT maintenance studies.

Adolescent↗

PubMed2004

All aggressive lymphoma subtypes do not share similar outcome after front-line autotransplantation: a matched-control analysis by the Groupe d'Etude des Lymphomes de l'Adulte (GELA).

BACKGROUND: Data are still conflicting on the indication of front-line autologous stem-cell transplantation (ASCT) as consolidation for aggressive lymphoma. To assess the therapeutic effect of ASCT among different aggressive lymphoma subtypes, we conducted a matched-control analysis by pooling the data from two Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials. PATIENTS AND METHODS: Between October 1987 and September 1998, 330 patients received ASCT after achieving complete remission with the ACBVP induction regimen. The histological slides showed: B aggressive non-Hodgkin's lymphoma (B-NHL) in 249 patients (75%), T-NHL in 52 patients (15%) (including 23 T anaplastic) and non-classified NHL in 29 patients. The age-adjusted International Prognostic Index (aaIPI) was 2 or 3 in 66%. Patients were matched with controls from the same GELA database but treated with chemotherapy only. RESULTS: ASCT did not benefit non-anaplastic T-NHL patients [5-year overall survival (OS) 44% (chemotherapy) versus 49% (ASCT), P=0.87; disease-free survival (DFS) 38% versus 45%, P=0.89] in comparison with B-NHL [5-year OS 77% (chemotherapy) versus 79% (ASCT), P=0.64; DFS 67% versus 72%, P=0.13]. However, for B-NHL patients with aaIPI score 2 or 3, the benefit of ASCT was significant. CONCLUSIONS: This cohort study confirms the high efficacy of front-line ASCT in responding aggressive B-NHL patients with adverse prognostic factors.

Adolescent↗

PubMed2002

Allogeneic bone marrow transplantation in patients with follicular lymphoma: a single center study.

The role of allogeneic BMT for follicular lymphoma remains to be established. From 1995 to 2000, 16 patients with follicular lymphoma underwent allogeneic BMT at our center. At the time of transplantation, two patients were in complete remission, 11 in partial remission and three had refractory disease. Fourteen patients were transplanted using a standard myeloablative conditioning regimen and two a nonmyeloablative conditioning regimen. With a median follow-up of 1184 days (range 403-1999 days) after BMT, 11 patients were alive, whereas five died of transplant-related mortality. Eight patients remained in CR 284+ to 1022+ days (median 560+ days) after BMT. Two patients relapsed 63 and 1073 days after BMT. They achieved a further complete remission after salvage treatment and remained alive 403 and 1224 days after BMT, respectively. One patient with autologous reconstitution had never been in CR after BMT. He was retreated with salvage chemotherapy but only achieved CR with subsequent rituximab treatment and was still alive, 1999 days after transplantation. The estimated 2-year overall survival and event-free survival rates were 68% and 55%, respectively. Age greater than 37 years at diagnosis, positive recipient CMV serology and ECOG performance status > or =1 at diagnosis were associated with shorter overall survival (P = 0.05, P = 0.009 and P = 0.03, respectively). Ann Arbor III-IV stage at diagnosis was associated with shorter event-free survival (P < 0.04). Allogeneic BMT seems to be effective for patients with follicular lymphoma. However, the relatively high rate of early transplant-related mortality emphasizes the need to define indications and use prospective protocols involving a less toxic transplant procedure.

Adult↗

PubMed2001

Assessing the Cox model assumption as a statistical tool for classifying lymphomas.

INTRODUCTION: The Cox model is widely used in medical research for comparing survival. Lymphomas might exhibit important differences in long-term cure rate despite a similar survival. METHODS: Using log-rank test, we compared event-free survival (EFS), and the survival of 64 patients with mantle cell lymphoma (MCL), 525 patients with follicular lymphoma, and 1136 patients with diffuse centroblastic lymphoma (CB). RESULTS: Although EFS and survival of MCL were significantly shorter than those of follicular lymphoma, checking the validity of the proportional hazards assumption shows that the distribution of rates of events and deaths over time did not differ in MCL and follicular lymphoma. In contrast, the ratios of hazards (events and deaths rates) did not remain constant over time in MCL and CB, because of a decrease in late events and deaths rates in the latter histological type. CONCLUSION: Checking the validity of the Cox model hypothesis might be a useful tool for assessing long-term cure rate in seldom lymphoma subtypes. Despite a short overall survival, MCL should not be considered to be an aggressive lymphoma, in which available chemotherapy may cure a subset of patients.

Adult↗

PubMed2001

Gemcitabine as a single agent in the treatment of relapsed or refractory low-grade non-Hodgkin's lymphoma.

A multicentre phase II trial was conducted to evaluate the efficacy and toxicity of gemcitabine in patients with refractory or relapsed indolent non-Hodgkin's lymphoma. Thirty-six patients were enrolled onto the study, including 11 cases of mantle cell lymphoma (MCL), 10 cases of chronic lymphocytic leukaemia (CLL)/lymphocytic lymphoma, nine cases of follicular lymphoma, four cases of lymphoplasmacytic lymphoma and two cases of T-cell lymphoma. Gemcitabine 1 g/m(2) was administered as a 30-min infusion on d 1, 8 and 15 of a 28-d schedule, up to a maximum of six cycles. Complete responses were observed in two patients with MCL, and partial responses were observed in seven patients, including three patients with CLL/lymphocytic lymphoma, two patients with T-cell lymphoma, one patient with MCL and one patient with follicular lymphoma. Minor responses were observed in three patients, including two patients with MCL and one patient with CLL. The median duration of response was 150 d and the overall progression-free survival was 342 d. Haematological toxicity was observed as grade 3-4 leucopenia in 12 patients (33%) and grade 3-4 thrombocytopenia in 18 patients (50%). Severe non-haematological toxicity included one case of fatal veno-occlusive disease, one case of thrombotic microangiopathy leading to terminal renal failure, one case of capillary leak syndrome, one case of myocardial infarction and drug-induced fever in two patients. These data suggest that gemcitabine displays activity in patients with MCL and CLL/lymphocytic lymphoma. Haematological toxicity was frequent in these heavily treated patients. Severe non-haematological toxicity was significant and should be taken into account in the design of future trials.

Adult↗

PubMed2000

Evaluation of minimal residual disease using reverse-transcription polymerase chain reaction in t(8;21) acute myeloid leukemia: a multicenter study of 51 patients.

PURPOSE: Most studies using various reverse-transcription polymerase chain reaction (RT-PCR) techniques reported that the detection of the AML1-ETO fusion transcript was a common finding in long-term complete remission (CR) in acute myeloid leukemia (AML) with t(8;21) translocation. However, larger prospective studies with interlaboratory quality control may be important to investigate more precisely the clinical usefulness of studying minimal residual disease with RT-PCR in t(8;21) AML. PATIENTS AND METHODS: We collected 223 marrow samples from 51 patients with t(8;21) AML diagnosed in five centers and tested all samples by two different RT-PCR techniques (a nested technique and a one-step technique, with a sensitivity of 10(-6) and 10(-5), respectively) in two different laboratories. RESULTS: Samples from 14 patients in long persistent CR (median follow-up duration, 112 months) were taken at least twice, and all were PCR-negative by both techniques. Samples were prospectively taken from 37 patients after achievement of first CR and/or second CR, before intensive consolidation treatment, and every 3 to 6 months after completion of therapy. Patients who converted to PCR negativity with the one-step technique (60%) or both techniques (48%) after CR achievement had a longer CR duration than those with persistently positive PCR results (two-sided log-rank test, P =.0001). Patients who became PCR-negative with the one-step technique before intensive consolidation (23%) had a lower relapse rate (11% v 72%) and a longer CR duration than those who remained persistently PCR-positive at that point (two-sided log-rank test, P =.0015). CONCLUSION: Patients with AML with t(8;21) in long-term remission were all PCR-negative. In prospectively studied patients, a good correlation was found between negative PCR results and absence of relapse. Early negative results with the one-step RT-PCR technique, before consolidation treatment, seemed to carry an especially good prognosis, suggesting that RT-PCR analysis could help in choosing the type of consolidation therapy in patients with t(8;21) AML.

Acute Disease↗

PubMed1999

Feasibility of tandem autologous stem-cell transplantation (ASCT) in induction failure or very unfavorable (UF) relapse from Hodgkin's disease (HD). SFGM/GELA Study Group.

BACKGROUND: Despite high-dose therapy and ASCT some patients with aggressive HD fail to achieve long-term survival. PATIENTS AND METHODS: Forty-three patients with induction failure (n = 19) or very unfavorable (UF) relapse (n = 24) from HD were included in a multicentric study of tandem ASCT. They planned to receive two course of IVA75 with GCSF and blood stem cell collection. ASCT1 was conditioned with CBV + mitoxantrone (30 mg/m2) and ASCT2 (cytarabine 6 g/m2 melphalan 140 mg/m2 and total body irradiation at 12 Gy or busulfan 16 (n = 4) than 12 mg/kg). After salvage therapy, response > 50% was observed in 63% of the patients (six patients were included for refractory relapse). Four patients had no ASCT for disease progression; seven patients had only ASCT1 (disease progression, n = 3) and thirty-two patients (74%) received the two ASCT. RESULTS: Hematologic recovery was normal after ASCT1 but delayed platelet recovery was observed after ASCT2 with busulfan in the conditioning regimen. Two VOD with one fatal occurred with busulfan at 16 mg/kg and one hemorrhagic cystic, no further grade 4 toxicity was observed with the reduced doses of busulfan (12 mg/kg). After ASCT2, 83% of these UF patients were in remission and 20% relapsed within the first year. On an intent-to-treat analysis, 22 of 43 patients are in continuous CR (including 8 patients with induction failure). For the whole population (n = 43) and for patients receiving the two ASCT (n = 32), the two-year survival from the date of progression were respectively at 65% and at 74%. CONCLUSION: Double ASCT is feasible in very UF relapse from HD and may lead to some prolonged remission.

Adult↗

PubMed1999

Semiquantitative analysis of residual disease in patients treated for adult T-cell leukaemia/lymphoma (ATLL).

Many adult T-cell leukaemia/lymphoma (ATLL) patients who respond to induction treatment, then relapse. Knowing the clonality pattern of residual tumourous clones during treatment could help understand disease evolution and aid therapeutic decisions. We developed a sensitive and semi-quantitative molecular analysis of these clones in ATLL patients. DNA samples from PBMCs derived from eight ATLL patients were studied over time by quadruplicate linker mediated PCR (LMPCR) amplification of HTLV-1 integration sites. Patients were treated with combination chemotherapy, zidovudine-interferon-alpha and/or by peripheral stem cell transplantation or allogeneic bone marrow transplantation. Persistence of tumourous clones at a high frequency (>1/300 PBMCs) was frequently observed, even in complete responders, and was invariably correlated with relapse and/or poor outcome. Fluctuation in the frequency of some tumourous clones was observed with evidence for clonal change under treatment in one patient, indicating that treatment of ATLL can result in the selection of resistant clones. Finally, allogeneic bone marrow transplantation (BMT) using an HTLV-1 infected sibling as donor was found to be associated with long-lasting disappearance of tumourous clones and a possible cure of the disease. Long-term persistent clonal expansion of circulating HTLV-1 bearing T cells which derived from the donor bone marrow was evidenced in this patient. In conclusion, variable success in treatment of ATLL is probably due to the clonal heterogeneity which results in the selection of resistant clones. Semi-quantitative assessment of residual disease (RD) through LMPCR may predict treatment failure. Accordingly, additional therapy may be tailored to the clonality pattern observed after first-line therapy.

Adult↗

PubMed1998

Oligoclonal proliferation of human T-cell leukaemia virus type 1 bearing T cells in adult T-cell leukaemia/lymphoma without deletion of the 3' provirus integration sites.

We report a new case of an asymptomatic carrier with a deletion of a 3' HTLV-1 integration site. We further investigated whether these 3' deletions of flanking sequences may explain the oligoclonal pattern of HTLV-1 replication, evidenced by inverse PCR (IPCR) analysis of tumourous samples from patients with adult T-cell leukaemia (ATLL). 48 HTLV-1 3' integration sites, derived from tumourous DNA of five ATLL patients were sequenced. One dominant flanking sequence was obtained in the four samples harbouring a unique band after Southern-blotting. In one sample, which harboured two signals after Southern-blotting, IPCR amplification of diluted tumourous DNA revealed that these two sequences corresponded to one clone harbouring two integrated proviruses rather than to two distinct cellular clones, a result consistent with superinfection of the tumourous sample. In addition to integration sites corresponding to malignant clones, two to six oligoclonal forms were sequenced in four samples. No flanking sequence homology was found between clones derived from each patient, indicating that integration sites deletion in the vicinity of the provirus is a rare event in ATLL. The oligoclonal pattern of HTLV-1 replication in ATLL may result from clonal expansion of non-malignant HTLV-1-bearing clones within the sample and partly from HTLV-1 superinfection of monoclonal tumour cells.

Base Sequence↗

PubMed1997

Antisense oligodeoxyribonucleotides suppress hematologic cell growth through stepwise release of deoxyribonucleotides.

Antisense oligodeoxyribonucleotides (ODNs) are now being extensively investigated in an attempt to achieve cell growth suppression through specific targeting of genes related to cell proliferation, despite increasing evidence of non-antisense cytotoxic effects. In the context of anti-BCR/ABL antisense strategies in chronic myeloid leukemia, we have reexamined the antiproliferative effect of phosphodiester and phosphorothioate ODNs on the leukemic cell line BV173 and on CD34+ bone marrow cells in liquid culture. The 3' sequences of the ODNs determine their effect. At concentrations of 10 micromol/L (for phosphorothioate ODNs) or 25 micromol/L (for phosphodiester ODNs), all the tested ODNs exert an antiproliferative activity, except those that contain a cytosine residue at either their two most terminal 3' positions. We show that this antiproliferative effect is due to the toxicity of the d-NMPs (5' monophosphate deoxyribonucleosides), the enzymatic hydrolysis products of the ODNs in culture medium. The toxicity of the d-NMPs on hematologic cells depends on their nature (d-CMP [2'deoxycytidine 5'-monophosphate] is not cytotoxic), on their concentration (d-GMP [2'-deoxyguanosine 5'-monophosphate], TMP [thymidine 5'-monophosphate], and d-AMP [2'-deoxyadenosine 5'-monophosphate] are cytotoxic at concentrations between 5 and 10 micromol/L), and on the coincident presence of other d-NMPs in the culture medium (d-CMP neutralizes the toxicity of d-AMP, d-GMP, or TMP). The antiproliferative activity of ODNs is thus restricted to conditions where the 3' hydrolysis process by exonucleases generates significant amounts of d-NMPs with a low proportion of d-CMP. Our results reveal a novel example of a nonantisense effect of ODNs, which should be taken into account when performing any experiment using assumed antisense ODNs.

Cell Division↗

PubMed1995

Glomerular injury in chronic myelomonocytic leukemia.

Among 825 cases of de novo myelodysplastic syndromes (MDS) diagnosed over a period of 13 years in our center, 4 had clinically significant glomerulopathy. All 4 fulfilled diagnostic criteria of chronic myelomonocytic leukemia (CMML), and could be classified in the low or intermediate risk groups according to two scoring systems. Presenting symptoms of renal involvement were edema in 3 cases and acute renal failure in the remaining patient. Three patients had the nephrotic syndrome. Renal biopsy (performed in 2 cases but considered as contraindicated in the other cases) showed AL amyloidosis on one case and extracapillary glomerulonephritis in the other case. The 4 patients were treated with V16 or hydroxyurea and two had renal improvement. Only one previous case of MDS associated with glomerulopathy has been reported before and also very probably had CMML. This, and the response of renal disease to chemotherapy in 2 of our patients suggests a possible relationship between the two disorders. More systematic investigation of glomerular function, in CMML, could possibly disclose a higher incidence of cases of glomerular injury in this type of MDS.

Aged↗