Biomedical subjects

P Colombat

Publications and source records attributed to P Colombat.

At least 37 records · Page 2Linked to original sources

PubMed1999

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.

Adolescent↗

PubMed1999

Intensive therapy with autologous stem cell transplantation as first-line therapy in poor-risk Hodgkin's disease and analysis of predictive factors of outcome.

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

Adolescent↗

PubMed1998

Treatment-related deaths and second cancer risk after autologous stem-cell transplantation for Hodgkin's disease.

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.

Adolescent↗

PubMed1998

Early intensive therapy with autologous stem cell transplantation in advanced Hodgkin's disease: retrospective analysis of 158 cases from the French registry.

This retrospective study was undertaken to evaluate cure rates, toxicity and late effects of early intensive therapy followed by autologous stem cell transplantation (ASCT) in patients with advanced Hodgkin's disease (HD). One hundred and fifty-eight cases of ASCT registered in the French database (SFGM) were retrospectively analyzed. Disease status at the time of ASCT was first partial response (PR) in 85, first complete remission (CR1) in 45 or primary refractory in 28 cases. The median time interval between diagnosis and ASCT was 7 months (range 4-13). At the time of analysis in December 1995, 121/158 patients (76.6%) were alive, including 111 (70.2%) in continuous CR with a median follow-up for surviving patients of 46 months (range 8-123). Peri-ASCT toxic death rate was 3%, and the actuarial risk of new malignancies was 4.9% at 5 years. The cumulative probability of 5-year overall survival (OS) was 75.2% for the entire group of patients, 80.6% for the chemosensitive ones, and 33.9% for the primary refractory (chemosensitive vs refractory, P < 0.0001). The cumulative probability of 5-year event-free survival (EFS) was 66.1% for the entire group of patients, 73.7% for the chemosensitive ones, and 26.1% for the primary refractory (chemosensitive vs refractory, P < 0.0001). The only significant prognostic factor for both OS and EFS was disease status at the time of ASCT. Early ASCT in advanced HD is feasible, with a low risk of toxicity and without a higher rate of late effects compared with conventional treatment. Results achieved in chemosensitive patients at the time of transplantation lay the basis of future prospective randomized trials comparing ACST as front-line treatment to conventional treatment in high-risk cases.

Adolescent↗

PubMed1998

Peripheral blood stem cell transplantation as front-line therapy in patients aged 61 to 65 years: a pilot study.

The aim of the present trial was to investigate the feasibility of high-dose therapy followed by autologous peripheral blood stem cell transplantation (PBSCT) as a component of front-line treatment in patients with disseminated intermediate- and high-grade non-Hodgkin's lymphoma (NHL) aged 61-65 years. From October 1993 to June 1996, 14 consecutive patients entered this single-center prospective pilot trial. Patients were five males and nine females, median age 63 (range 61-65). The first-line treatment consisted of three courses of CHOP therapy. Patients achieving either a partial response (PR) or a complete response (CR) after initial therapy were eligible for PBSCT, while those with refractory or progressive disease were not autografted but included in the feasibility study in an intent-to-treat analysis. Of the 14 patients, 11 achieved either a CR (one) or a PR (10) after three courses of CHOP while the three patients with no response were not autografted and subsequently died of progressive disease. PBSC collection was feasible in responding patients after G-CSF priming (10 microg/kg/day for 6 days). Conditioning therapy was the BEAM protocol. All patients engrafted after PBSCT. The median time to granulocyte (>0.5 x 10(9)/l) and platelet recovery (>25 x 10(9)/l) was 12 (range 9-18) and 13 days (range 7-22), respectively. No toxic deaths VOD or IP were observed. Four of the 11 responding patients relapsed 2, 7, 9 and 12 months after PBSCT, respectively, and all died from progressive disease. Overall, 7/14 patients are alive and free from disease, 16-43 months after initial diagnosis (median 28). The actuarial overall survival is 45.7 %, and the actuarial event-free survival is 50% at 3.5 years. This study shows the feasibility of high-dose therapy and PBSCT in patients with intermediate- or high-grade disseminated NHL aged 61-65 years. Such patients should not be excluded from trials evaluating the role of ASCT as part of initial treatment for disseminated and histologically aggressive NHL.

Aged↗

PubMed1998

All-trans-retinoic acid up-regulates CD38 but not c-Kit antigens on human marrow CD34+ cells without recruitment into cell cycle.

Retinoids, especially all-trans-retinoic acid (ATRA), are well known for their differentiating activity on HL-60 cells. Moreover ATRA induces CD38 antigen overexpression on these cells. In this study we examined the effects of ATRA on purified normal CD34+ cells from adult human marrows incubated with ATRA (1 microM) or stem cell factor (SCF) after 7 d liquid cultures in serum-deprived medium. Before and after the incubation, CD34+ cells were studied by flow cytometry to evaluate the cell-surface expression of CD38 and c-Kit antigens and the cycle status of these cells using high-resolution analysis (DNA content v Ki-67 antigen expression) to clarify the functional meaning of antigenic variations. When compared with control cultures, ATRA-treated cells displayed changes in their immunophenotypic profile. Particularly relevant was the up-regulation of CD38 antigen with a mean (+/-SEM) fold increase of 21 +/- 0.1 (P=0.028) for geometric mean fluorescence intensity (GMFI), without modulation of c-Kit expression. SCF only down-regulated expression of c-Kit with a fold decrease of 4.6 +/- 0.9 for GMFI (P=0.043). Unlike SCF, ATRA did not induce CD34+ cells to entry into cell cycle despite increased levels of surface CD38 antigen. Moreover morphological and functional assays did not argue for an ATRA-induced maturation process. Contrary to steady-state cells, CD34+ cells treated with pharmacological doses of ATRA alone displayed CD38 over-expression without change in c-Kit levels and cycle status, suggesting an absence of maturation pressure.

ADP-ribosyl Cyclase↗

PubMed1998

Cytokines released in vitro by stromal cells from autologous bone marrow transplant patients with lymphoid malignancy.

Marrow stromal cells of patients treated by autologous bone marrow transplantation (ABMT) for malignancies have been assessed for their ability to secrete granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), transforming growth factor beta1 (TGFbeta1) and macrophage inflammatory protein-1alpha. (MIP-1alpha). Long-term marrow cultures were established from 10 patients prior to and 3 months after ABMT, from 7 patients 1 yr after ABMT and from 11 controls. Cytokines in culture supernatants of stromal layers (SL) were evaluated by enzyme-linked immunosorbent assay (ELISA). Significant differences between patient groups and controls were apparent in baseline production of GM-CSF, SCF, MIP-1alpha and TGFbeta1. After IL-1beta addition in cultures, G-CSF production was reduced in pretransplant and post-transplant patients compared to controls. The production of TGFbeta1, LIF, IL-6 and more particularly SCF were reduced in post-transplant patients, while elevated levels of GM-CSF and MIP-1alpha were observed in these patients only when the values were corrected for the number of cells growing in the SL. These results indicate a prolonged stromal defect in growth factor production following ABMT for the early-stage acting cytokines IL-6, LIF and SCF as well as for G-CSF, but not for GM-CSF, while the production of the 2 inhibitors shows different pathways.

Adult↗

PubMed1998

In vitro effect of stem cell factor on human clonogenic marrow progenitors after myeloablative treatments.

Abnormal hematopoiesis, including a deficiency of marrow progenitors and particularly of erythroid progenitors, has been described after autologous stem cell transplantation (ASCT), persisting for several years. In order to explain this deficiency, a resistance of marrow progenitors to stem cell factor (SCF) after ASCT was investigated. Marrow samples were harvested from pregraft patients at graft collection prior to ASCT, transplanted patients 6-24 months after high-dose therapy and control patients. CD34+ cells were cultured in a serum-free clonogenic assay with increasing doses of SCF. The clonogenic efficiency without SCF was lower for BFU-E in treated groups than in controls, whereas it was not different for CFU-GM. With increasing doses of SCF a dose-dependent effect was found on the numbers of both CFU-GM and BFU-E in all groups, although the maximal number of BFU-E remained lower in treated groups. However, the SCF dose that induced 50% of maximal BFU-E growth (D50) was similar in all groups. Furthermore, a dose-dependent effect on the size of BFU-E was found in all groups, with no difference in the proportion of large colonies. Thus, clonogenic erythroid progenitors from patients who have received myelotoxic treatments remain sensitive to SCF, with no evidence for a chemotherapy-related resistance.

Adult↗

PubMed1998

Changes in the functional capacity of marrow stromal cells after autologous bone marrow transplantation.

Marrow stromal cells were evaluated several months after autologous BMT for their capacity to support both normal hemopoiesis and secrete the main growth factors involved in its control, G-CSF, GM-CSF, IL-3 and SCF. Stromal layers (SL) were obtained by long-term marrow cultures (LTMC) established from 15 patients (9 with hematologic malignancies and 6 with solid tumors) 3 months after autologous BMT and were compared to pre-graft patients. After irradiation, both post-graft and pre-graft SL were recharged with the same inoculum of normal marrow cells. As compared to pre-graft values, CFU-GM production on post-graft SL was significantly increased during the first 2 weeks of culture whereas it was decreased from week 3 to week 8. These findings were only observed in patients with hematologic malignancies and not in patients with solid tumors. Growth factor secretion was evaluated by ELISA in the supernatants of unstimulated and IL-1-stimulated SL from 10 post-graft patients, 13 pre-graft patients and 5 normal controls. In any group of patients, IL-3 was undetectable either spontaneously or after IL-1-stimulation. As compared to controls, secretion by IL-1-stimulated SL was not different for GM-CSF in pre- and post-graft patients but tended to be decreased for G-CSF in post-graft patients. SCF secretion, which was not induced by IL-1, appeared dramatically decreased in both pre- and post-graft patients. The capacity of post-graft SL to support CFU-GM growth in LTMC was correlated at week 1 with G-CSF secretion and from week 3 to week 8 with SCF secretion. These results suggest that microenvironment remains qualitatively damaged several months after BMT involving a decreased capacity both to support early hemopoiesis and to secrete SCF, particularly in patients grafted for hemopoietic malignancies.

Adult↗

PubMed1998

CD5 negative B-cell chronic lymphocytic leukemia: clinical and biological features of 42 cases.

Chronic lymphocytic leukemia cell (CLL) usually (95%) express B-phenotype and the CD5 antigen which is usually present on the surface of normal T cells. However, among B CLL, 7 to 20% do not express CD5. The significance of the lack of CD5 expression remains unclear. We reviewed 42 consecutive CD5- B CLL seen in three French medical centers from 1985 to 1991 and compared them with 79 CD5+ B CLL. Immunophenotype studies were performed using indirect immunofluorescence under light microscopy as well as flow cytometry after 1988. B CLL was considered to be CD5 negative when less than 5% of mononuclear cells expressed CD5 after subtraction of the number of T-cells. Cases with CD5- B CLL had isolated splenomegaly more frequently (p = 2.10(-7)). They frequently expressed a higher level of surface immunoglobulin (S-Ig) or the switch mu/delta phenotype (p = 4.7 10(-2)). The median survival time was not reached but no significant difference between CD5 negative and positive B CLL was observed at the time of our data analysis (p = 0.97). Clinical presentation of CD5- B CLL seems to be different from other forms of B CLL. Although, no conclusion can be reached in terms of prognosis, CLL with low expression of CD5 should be regarded as a subtype of CLL with a different clinical presentation than CD5+ CLL.

Adult↗

PubMed1998

Mediastinal large-cell lymphoma with sclerosis refractory to conventional chemotherapy can respond after daily oral cyclophosphamide.

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

Administration, Oral↗

PubMed1998

[Dose-effects and chemotherapy dose intensity of aggressive non-Hodgkin's lymphomas in the adult].

The CHOP regimen (cyclophosphamide vincristine, adriamycin, prednisone) is considered since twenty years as the standard treatment of disseminated aggressive non-Hodgkin's lymphomas and cures approximately 30% of patients. More recently, intensive chemo(radio)therapy followed by rescue with bone marrow or blood hematopoietic stem cells has become the standard treatment of chemosensitive relapses of aggressive non-Hodgkin's lymphomas. Consequently, two questions with practical applications have arisen and are discussed in this review: Is it justified to increase the dose intensity of chemotherapy, using either single treatment intensification with stem-cell rescue, or sequential intensified chemotherapies, especially in cases with adverse prognostic factors? On the contrary, is a decrease in treatment intensity compared to CHOP chemotherapy, especially in elderly patients, harmful to the patient?

Adult↗

PubMed1998

[Similarities between pleuropulmonary blastoma and Askin tumor].

Adult pleuropulmonary blastoma is an uncommon mesenchymal tumor of the peripheral lung parenchyma composed of undifferentiated cells. The differential diagnosis with Askin-Rosaï's tumor, an extrapulmonary pleuroparietal neuroectodermal tumor, may be a difficult task. We propose a similar therapeutic approach for these two malignant conditions: surgical excision associated with chemotherapy and autologous bone marrow transplant with adjuvant radiotherapy in case of recurrence. These two entities have many epidemiological, clinical, histological and immunohistochemical similarities.

Adult↗

PubMed1997

A case of veno-occlusive disease complicated by severe hemorrhagic cystitis successfully treated with recombinant plasminogen activator.

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

Adolescent↗

PubMed1997

Prognostic factors for survival after high-dose therapy and autologous stem cell transplantation for patients with relapsing Hodgkin's disease: analysis of 280 patients from the French registry. Société Française de Greffe de Moëlle.

High-dose therapy with autologous stem cell transplantation (ASCT) has been widely proposed for patients with relapsed Hodgkin's disease (HD). From 1982 to 1993, we selected (from the French registry for bone marrow transplantation) 280 patients, who underwent ASCT for relapsed HD after initial treatment including chemotherapy. Patient characteristics at diagnosis were: sex ratio (M/F): 1.5; median age: 30 years (5-59 years), stage I, II: 43%; III, IV: 57%; 32% had chemotherapy, 68% chemo+ radiotherapy. All patients achieved complete remission after first-line therapy and subsequently relapsed. The median interval between diagnosis and high-dose therapy was 34 months. First relapse occurred in 78% of the patients at a median end-of-treatment to relapse time of 18 months. All patients received salvage chemotherapy before high-dose therapy, and the median time between relapse and high-dose therapy was 5 months. After this regimen, 84% of the patients were considered to have chemosensitive relapse. Conditioning regimens were: BEAM: 60%; CBV/BEAC: 26%. Transplant-related mortality was 6%. With a median follow-up of 3 years after high-dose therapy, overall and progression-free survivals at 4 years were 66 and 60%, respectively. Neither the conditioning regimen nor the stem cell source affected survival. Good prognostic factors for survival were: chemosensitivity of relapse (P < 0.01) and first relapse vs further relapse (P < 0.05). For 214 patients in first relapse, other significant factors for survival were: end-of-treatment to relapse interval < 12 months (P < 0.05) and nodal vs extranodal relapse (P < 0.001). These two prognostic factors were used to validate a prognostic model with three significantly different subgroups: 0 (n = 59), 1 (n = 125), or 2 factors (n = 30) with 4-year survival, respectively, at 93, 59 and 43% (P < 0.001). Salvage therapy can be tailored in patients with relapsing HD: conventional treatment in the good prognosis group (0 factor), high-dose therapy after response to second line regimen (1 factor) and more intensive treatments for the bad prognosis group (2 factors).

Adolescent↗

PubMed1997

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.

Adult↗

PubMed1997

Is the International Prognostic Index for aggressive lymphomas useful for low-grade lymphoma patients? Applicability to stage III-IV patients. The GOELAMS Group, France.

BACKGROUND: The International Prognostic Index (IPI) is widely used to predict outcome of patients with aggressive lymphomas. Our goal was to assess the prognostic value of this index for low-grade lymphoma. PATIENTS AND METHODS: One hundred eighty-two patients with disseminated (stage III or IV) low-grade lymphoma were enrolled in a prospective multicenter trial. According to the initial features, treatment either was started immediately or was deferred until indicated by disease progression. Patients received the same polychemotherapy regimen, given monthly for six cycles. They were assigned to one of four risk groups according to the number of presenting risk factors: low-risk (0 or 1), low-intermediate-risk (2), high-intermediate-risk (3), high-risk groups (4). RESULTS: Survival curves (Kaplan-Meier method) demonstrated a high significant difference for the four groups (log-rank: P < 0.0001). Median survival for the low-risk group has yet to be reached, while that for the three other groups are, respectively, 65, 34, and 12 months. CONCLUSIONS: In this study, the IPI has been found to be an important prognostic tool in low-grade lymphoma and may be used in the selection of appropriate therapeutic approaches for individual patients.

Humans↗

PubMed1996

Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study.

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor-risk ALs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗