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Biomedical subjects

P Viens

Publications and source records attributed to P Viens.

At least 19 recordsLinked to original sources

Bone marrow and blood cells as alternative sources of hematopoietic progenitors after failure of a first collection. A single institution retrospective study.

From October 1992 through October 1994, we retrospectively identified 12 patients who underwent two collections of hematopoietic progenitors because the first one was considered inadequate. Five patients had bone marrow harvest first and underwent apheresis later. Seven patients underwent apheresis first and had bone marrow harvest later. Most patients had advanced cancer and had been heavily pretreated at time of harvesting. The second harvest yielded an appropriate number of progenitors for a proportion of patients. Nine of 12 patients received both cryopreserved marrow and blood cells. Hematopoietic recovery in these patients was somewhat longer than in patients currently receiving blood cells as a support for high dose chemotherapy at our institution; however, except for 2 patient, neutrophil and platelet recovery was observed within a reasonable delay. We conclude that patients who have poor blood cell collection may benefit from bone marrow harvesting, and vice versa.

Adolescent

Autologous transplantation of blood stem cells mobilized with filgrastim alone in 93 patients with malignancies: the number of CD34+ cells reinfused is the only factor predicting both granulocyte and platelet recovery.

High-dose chemotherapy (HDC) supported by autologous transplantation of blood stem cells (BSC) is used increasingly for patients with poor-risk malignancies. We report our experience with 93 consecutive patients who were mobilized with recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone. They received a fixed dose of G-CSF for 5 or 6 days, and BSC were collected by leukapheresis. Aphereses were evaluated for MNC, CD34+ cells, and CFU-GM counts and cryopreserved. All patients received a conditioning regimen without TBI. Engraftment was assessed as the first of 2 consecutive days on which patients achieved 0.5 and 1 x 10(9)/L neutrophils and an unsupported platelet count of 25 x 10(9)/L. Multivariate analysis was performed to study patients and graft characteristics that could influence reconstitution. The G-CSF priming regimen was well tolerated and allowed collection of BSC for all patients, 66% of them achieving >3 x 10(6)/kg CD34+ cells, and 86% achieving >10 x 10(4) CFU-GM/kg. The numbers of collected CD34 and CFU-GM cells were highly correlated. The number of courses of chemotherapy prior to collection, a diagnosis of breast cancer, the use of rhG-CSF posttransplant, and the numbers of CFU-GM and CD34+ cells reinfused were correlated with hematologic recovery. In a multivariate analysis, however, the number of CD34+ cells was the only factor independently influencing both granulocyte and platelet recovery. Patients who received at least 3 x 10(6)/kg CD34+ cells achieved granulocyte reconstitution on day 11 after reinfusion (range 8-15) and an unsupported platelet count of 25 x 10(9)/l on day 14 (range 12-180), significantly earlier than patients who received fewer cells (p < 0.001). In addition, G-CSF administration postreinfusion independently enhanced granulocyte reconstitution but not platelet recovery. In conclusion, CD34+ cell number appears to be the only factor predicting both granulocyte and platelet reconstitution. Based on this study, the collection of a minimal number of 3 x 10(6)/kg CD34+ cells appears desirable.

Adolescent

High-dose therapy and autologous bone marrow transplantation in first complete or partial remission for poor prognosis Hodgkin's disease.

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

Adolescent

[Contamination of cytapheresis by tumor cells: apropos of 39 breast cancer cases].

The purpose of the present study was the detection of tumor cells in aphereses after mobilization of peripheral blood stem cells (PBSCs) with G-CSF from 39 breast cancer patients. Circulating tumor cells were searched using sensitive immunocytochemical technique (APAAP) with three anticytokeratin monoclonal antibodies. Counting of mononuclear cells and CD34 progenitor cells was also performed. Circulating tumor cells were detected in 35% of the patients. Cytokeratin-positive cells were detected in 45% of the patients of the metastatic group compared with 20% of the non metastatic one. Aphereses contamination was not correlated with lymph node involvement. Numbers of mononuclear cells and CD34 cells were not significantly different in positive and negative PBSCs collections. In our study, presence of tumor cells was associated with advanced clinical stage and could not be related to a higher CD34 cells mobilization by G-CSF.

Adult

Impact of recombinant human granulocyte colony stimulating factor on dose intensity and toxicity of three cycles of methotrexate, vinblastine, doxorubicin and cisplatin in patients with previously untreated urothelial bladder carcinoma.

This single arm, open labeled, non randomized study was aimed to evaluate the toxicity of 3 cycles of MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) with rhG-CSF (5 micrograms/kg/day from day 3 to day 14), on 14 patients with previously untreated infiltrating bladder carcinoma, 42 cycles were administered. Chemotherapy toxicity was very low, with 7% of neutropenia grade 3 or 4.4% of thrombocytopenia grade 2, no mucositis above grade 2 and no nadir sepsis. Bone pain related to rhG-CSF occurred in 14% of cycles. 88% of the cycles were given at full dose without any delay and mean relative dose intensity was 96.4% (RDI was 100% for 9 patients). One patient achieved a complete pathological response (cystectomy: 1) and 6 clinical responses with negative transurethral resection. Addition of rhG-CSF to MVAC chemotherapy allows a high dose intensity of MVAC with very low toxicity over 3 cycles. This association should be compared to standard MVAC or intensified regimens to evaluate efficacy, toxicity, and cost effectiveness.

Adult

[Comparison of anxiety and pain in two procedures of hematopoietic stem cell collection: cytapheresis and bone marrow collection].

The aim of this study was to compare anxiety, pain and discomfort of cancer patients submitted to two procedures of hematopoietic stem cells collection: peripheral blood stem cells collection (PBSCC) or bone marrow collection (BMC). Patients, randomized (July 1993-February 1994), in view of autograft, to receive the first procedure or the second one, completed self-administered questionnaires before, during and after the procedure. Anxiety was evaluated by State-Trait Anxiety Inventory. Pain was assessed using visual analogical scale (VAS) and McGill Pain questionnaire. Before the procedure, in comparison with PBSCC patients (n = 40), BMC patients (n = 25) experienced more State-anxiety due to the procedure approach (p < 0.01) and more trouble or inconvenience for having to come and stay at the hospital (p < 0.0001). During the procedure, pain related to BMC, as assessed by VAS, is significatively higher than pain induced by PBSCC, whichever the access used (p < 0.001). The McGill total score is twice as high for BMC patients than for patients submitted to PBSCC with femoral catheter (n = 19). The latter patients significatively reported more pain than patients without femoral catheter (n = 21). At the discharge from hospital, 32% of BMC patients judged the procedure quite difficult vs 5% of PBSCC patients (p < 0.05). These results explain a higher acceptability of the peripheral blood stem cells collection.

Adult

Comparison of anxiety, pain and discomfort in two procedures of hematopoietic stem cell collection: leukacytapheresis and bone marrow harvest.

The aim of this study was to compare anxiety, pain and discomfort of cancer patients submitted to either peripheral blood progenitor cell collection (PBPCC) or bone marrow harvest (BMH). Patients, randomized (7/1993-2/1994), in view of autograft, to receive the first procedure or the second one, completed self-administered questionnaires. Anxiety was assessed by the State Trait Anxiety Inventory and pain using visual analogical scale (VAS) and McGill Pain questionnaire. Before the procedure, BMH patients (n = 25) experienced more anxiety (P < 0.01) and more trouble or inconvenience for having to come and stay at the hospital (P < 0.0001) than PBPCC patients (n = 40). Pain due to BMH is significantly higher than pain induced by PBPCC (P < 0.001 for VAS and total McGill score). However, patients submitted to PBPCC with a femoral catheter (n = 19) had significantly higher total McGill scores and sensory sub-scores than patients without it (n = 21). At discharge from the hospital, PBPCC patients expressed more positive judgements towards the collection procedure than BMH patients. These results suggest that a better patient acceptability of high-dose chemotherapy followed by autograft may be obtained by substituting PBPCC for BMH for stem cell collection.

Adult

In vivo stimulation of neutrophil function by lenograstim (glycosylated rHuG-CSF) in oncohematologic patients: results of a phase I trial.

The aim of this work was to study the evolution of neutrophil functions in non-neutropenic cancer patients. Thirty non-neutropenic patients, median age 35 years (range 19-52), with solid tumors (n = 21) or lymphomas (n = 9) entered a phase I study of five days of s.c. (n = 24) or i.v. bolus (n = 6) lenograstim, recombinant human glycosylated granulocyte colony-stimulating factor (rHuG-CSF Chugai-Rhône-Poulenc), with dose escalation from 1 to 40 micrograms/kg/day. Neutrophil functions were studied before lenograstim (D1) and 24 h after the last dose (D6). Granulocyte count rose in a significant way, and enzyme release, phagocytosis and bacterial killing were stimulated. All patients had improvement of at least one neutrophil function. Directed migration was depressed, although it was still in the normal range. These findings confirm that lenograstim is a potent activator of neutrophil functions in non-neutropenic cancer patients and may be useful as an adjunct to conventional antimicrobial therapy.

Adult

Concomitant chemoradiation prior to surgery in the treatment of advanced cervical carcinoma.

In patients with locally advanced cervical cancer, most of the treatment failures occur within the pelvis. In an attempt to improve local control, 40 patients with bulky tumors (stage IB > 5 cm, stage IIB with distal parametrial invasion, and stage III-IVA) were treated between 1988 and 1992 with concurrent chemoradiation (CCR). The whole pelvis received a midplane dose of 45 Gy over 33 days. Daily radiation dose was 1.8 Gy, with twice-daily fractionation in the last 20 patients. Chemotherapy was administered on the 1st and 21st days of radiation therapy (RT) consisting of cisplatin (60 mg/m2), followed by 5-fluorouracil (600 mg/m2/day continuous i.v. infusion) over 96 hr (and decreased to 40 and 400 mg/m2, respectively, in the last 23 patients). CCR was first followed by a single intracavitary application and then by a parametrial boost in stage IIB-III patients and in stage IVA patients with disease reaching the pelvis side wall. Then surgery (colpohysterectomy with lymphadenectomy or pelvic exenteration) was performed in 35 patients. Median follow-up time was 2.6 years (0.6-5.6 years). Acute toxicity (WHO grade 3-4 diarrhea) in 13 patients led to 6 RT interruptions and 4 incomplete RTs. One patient died of a septic episode without leukopenia after completion of CCR. Five postexenteration complications required a second surgical procedure, of which one patient died with tumor and small bowel fistula. One patient developed small bowel late complication and another patient developed urinary late complications. No postoperative or late complications were observed in patients treated with twice-daily fractionation. Pelvic control was achieved in 32 of 40 patients (81 and 74% in stage IB-IIB and stage III-IVA, respectively). Sites of failure were the pelvis (6 cases), metastases (7 cases), and both (2 cases). Two-year survival and DFS rates were 61 and 66%, respectively, in stage IB-IIB and 77 and 65% in stage III-IVA. High SCC-TA4 values significantly worsened DFS rates. In patients with stage III-IVA tumors, additional surgery could be an important component of this treatment strategy and may be compatible with CCR using twice-daily fractionation radiotherapy. However, these results must be confirmed by a large-scale prospective study.

Adult

p53 immunohistochemical analysis in breast cancer with four monoclonal antibodies: comparison of staining and PCR-SSCP results.

The expression of p53 protein was examined in a series of 136 primary breast carcinomas, 106 of which were analysed with a panel of four monoclonal antibodies (MAbs 1801, 240, DO7 and DO1). p53 expression was detected with at least one antibody in 40 tumours (38%), whereas only 15 tumours (14%) were positive with all four antibodies. Some variability in the immunostaining could be observed depending on the antibody used. This was noticeable both for the number of positive cells within a section and for the intensity of staining. We therefore selected a panel of 17 tumour sections (nine were highly positive, three with medium to low staining and five with low to negative staining), which we analysed by polymerase chain reaction-single-strand conformation polymorphism analysis (PCR-SSCP) for the presence of a p53 mutation at the molecular level. Mutations were identified in 15 cases. Therefore the proportion of p53-stained cells does not seem to be an exact representation of the number of cancer cells bearing a mutation within a tumour. A statistically significant correlation was observed between p53 expression, regardless of the number of positive antibodies, and grade III disease (P < 0.0001), oestrogen (P < 0.0001) or progesterone receptor negativity (P = 0.0061), increased Ki 67 index (P = 0.0018), epidermal growth factor receptor (EGFR) positivity (P = 0.0076) and aneuploidy (P = 0.037). No correlation was observed with tumour size or lymph node involvement. In univariate analysis p53 expression was not correlated with disease-free survival, in contrast to the classical prognostic parameters, which were statistically correlated. In this series p53 expression was not a marker of early recurrence.

Antibodies, Monoclonal

Phase I study of in vivo lenograstim (rHuG-CSF) for stem cell collection demonstrates improved neutrophil recovery after autologous bone marrow transplantation.

Colony stimulating factors and especially rHuG-GSF, the first available neutrophil growth factor, have led to considerable interest in the field of stem cell transplantation because of their ability to induce stem cell peripheralization either alone or in association with high-dose chemotherapy. Few data exist, however, on the impact of rHuG-CSF on large scale bone marrow collection and autologous bone marrow transplantation (ABMT). This phase I, non-randomized, dose escalation study of rHu-G-CSF (lenograstim) administered to 30 patients at doses ranging from 1 to 40 micrograms/kg/day for 5 days before bone marrow harvesting showed that priming with rHu-G-CSF in vivo increased the number of bone marrow cells and D14 myeloid restricted progenitors (CFU-GM) and led to a better neutrophil recovery after ABMT compared with a contemporary unprimed control population. Otherwise, this study established that 5 days of rHuG-CSF therapy, as a sole stimulus, induced a tenfold increase in the circulating CFU-GM amongst which immature progenitors, estimated by the Delta assay (secondary CFU-GM grown after 7 days of liquid culture/primary CFU-GM), are detected. These conclusions were valid for doses as low as 2 micrograms/kg/day which induced only mild neutrophilia up to the highest dose (40 micrograms/kg/day) and suggest that a short course of rHuG-CSF is beneficial in increasing the stem cell collection.

Adolescent

Delayed administration of granulocyte colony-stimulating factor after autologous bone marrow transplantation: effect on granulocyte recovery.

Recombinant granulocyte colony-stimulating factor (rhG-CSF) has been shown to hasten granulocyte recovery after autologous BMT. In current protocols, rhG-CSF treatment starts 1 day after BM reinfusion. Our study retrospectively examined the effects on haematological recovery of a day 6 delayed administration. Seventy-eight patients receiving autologous BMT for malignant lymphoma (21 non-Hodgkin's lymphoma and 9 Hodgkin's disease) or solid tumors (33 breast carcinoma and 5 ovarian carcinoma) were split up into three study groups. Two groups receiving a 5 micrograms/kg/day of rhG-CSF starting either 1 day (day +1 group, n = 25 patients) or 6 days (day +6 group, n = 24 patients) after BM reinfusion were compared with 29 historical control patients. Granulocyte recovery to 0.5 x 10(9)/l was 12 days in day +6 and day +1 groups versus 16 days in control group (p < 0.005) without any difference in other hematological parameters, infectious complications or length of hospitalisation between the three groups. The day +6 administration allows elimination of a median of 7 days rhG-CSF. It has been concluded that the day +6 administration gives the same clinical benefit as day +1 administration with consequent cost reductions.

Adult

[Why use chemotherapy in cancer of the bladder? What are the initial limitations].

Four chemical agents are active, in isolation, against metastatic bladder cancer: cisplatin (nephrotoxicity) (C or Cis), doxorubicin (cardiac toxicity) or adriamycin (A), vinblastine (V) and methotrexate (M). Combinations of these drugs are more effective, with complete response rates of up to 30 to 40%. The current combinations are: CM; Cis cyclophosphamide, A; CMV; MVAC. This last combination appears to be the most effective. Chemotherapy is essentially prescribed for palliative purposes (improvement of symptoms) in metastatic cancers. It may also constitute adjuvant treatment following total cystectomy, in order to decrease the local or distant recurrence rate. Neoadjuvant chemotherapy, before surgery, can reduce the tumour bulk allowing preservation of the bladder. Haematopoietic growth factors are used to reduce the toxicity of chemotherapy and the action of these drugs can also be potentiated by radiotherapy.

Antineoplastic Combined Chemotherapy Protocols

Detection of circulating antigens in the diagnosis of acute toxoplasmosis.

Using an enzyme-linked immunosorbent assay, we have found circulating antigens of Toxoplasma gondii in three models of murine toxoplasmosis: mice infected with trophozoites of the RH strain (acute toxoplasmosis), the Beverley strain (subacute toxoplasmosis), and the T626 strain (chronic toxoplasmosis). Circulating antigens were detected 48 hr after infection in the mice infected with the RH strain, and all mice had antigenemia by the fourth day. In those infected with the Beverley strain, circulating antigens were detected from the second day after inoculation until the end of the study, with a peak (71% of the infected mice) on day 10. Of those infected with the T626 strain, 40% had antigenemia at 13 days after infection. The detection of circulating antigens in serum is directly related to the presence of toxoplasmosis in the acute phase in the three models studied and, therefore, may prove very useful in the rapid diagnosis of this disease.

Acute Disease

Bone marrow transplantation in 63 adult patients with acute lymphoblastic leukemia in first complete remission.

Over a 10 year period, we transplanted 63 patients with acute lymphoblastic leukaemia (ALL) who had achieved first complete remission (CR). All were > 15 years old and 45 (71%) had at least one poor prognostic factor. Twenty-nine patients with a suitable sibling underwent autologous bone marrow transplantation (BMT). Beginning in 1984, patients without a donor received an allogeneic BMT (34 patients). Preparation consisted of cyclophosphamide (CY)/TBI (78%) or melphalan (Mel)/TBI (22%); marrow was treated in vitro in 31 patients (allogeneic: 7; autologous: 24). Kaplan-Meier estimates of the probability at 6 years of relapse, survival and DFS were 41% (allogeneic: 10%, autologous: 65%, p < 0.05), 44% (allogeneic: 62%, autologous: 26%, p = NS) and 42% (allogeneic: 62%, autologous: 27%, p < 0.06), respectively. This report confirms that allogeneic BMT permits long-term remissions giving high levels of survival when performed shortly after entering first CR while autologous BMT, when performed in the same setting, is less successful at preventing relapse. This study also confirms the high sensitivity of ALL to the graft-versus-leukemia effect provided by allogeneic BMT. Chemoradiotherapy dose intensification delivered at autologous BMT is not sufficient to prevent relapses. Autologous BMT must therefore be augmented by other approaches of which immunotherapy may be one.

Adolescent