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D Maraninchi

Publications and source records attributed to D Maraninchi.

At least 109 records · Page 6Linked to original sources
PubMed1996

Administration of G-CSF can be delayed after transplantation of autologous G-CSF-primed blood stem cells: a randomized study.

Hematopoietic growth factors like G-CSF or GM-CSF have been shown to shorten the period of severe neutropenia after HD chemotherapy and autologous BMT, and are now widely used to mobilize hemopoietic stem cells into peripheral blood. In order to evaluate the possibility of delaying G-CSF administration after transplantation of G-CSF mobilized blood stem cells (BSC), we randomized 35 cancer patients to receive CSF at day 1 (group 1, n = 19) or at day 6 (group 2, n = 16) after transplantation and here we present their hematological reconstitution. BSC collection was performed by apheresis after G-CSF priming for 5 or 6 days (600 micrograms daily subcutaneously). Hematological recovery is comparable between the two groups: a median of 10 (range 7-16) vs 11 (range 9-18) days to reach an ANC > 0.5 x 10(9)/1 in group 1 (G-CSF day 1 after transplant) vs group 2 (G-CSF day 6 after transplant, P = NS). Median time to reach an unsupported platelet count of 25 x 10(9)/1 was 14 days in the two groups (range 8-110 and 10-40 respectively, P = NS); patients received less G-CSF after transplantation in group 2. No difference appeared in terms of transfusion support, number of days of fever of i.v. antibiotic treatment. Patients' hospital stay was the same in the two groups. Our data suggest that delaying G-CSF administration after infusion of mobilized blood cells is not detrimental to hematological recovery, while it lowers the overall cost of the procedure.

Adolescent↗
PubMed1996

Third autologous stem cell transplants for late relapse of multiple myeloma.

Double autologous bone marrow transplantation (ABMT) has been reported as an efficient form of consolidation for patients with multiple myeloma (MM). However, few data are available about feasibility and efficacy of a third ASCT in case of relapse. Here we report two patients with MM who received a third ASCT for late relapse (74 and 52 months) after a double ABMT. Both patients were male with IgG gamma MM (stage IIIA according to the Durie Salmon classification). The two patients were in PR > 50% after a first-line treatment. A double ABMT was performed after relapse and patients remained in PR > 50% after double intensification, lasting 71 and 49 months, respectively. The third ASCT was performed 7 and 10 months, after second relapse. One patient needed 15 months to reach 50 000 platelets, however he did not receive any transfusion after day 14. He was in PR > 50%. The other patient was in PR < 50%, 4 months after ABMT with a full hematological reconstitution. For patients with late relapse of MM after double ABMT, a third ABMT was a feasible treatment and patients seem to remain sensitive to high-dose therapy.

Adult↗
PubMed1996

[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↗
PubMed1996

A pilot study of busulfan and melphalan as preparatory regimen prior to allogeneic bone marrow transplantation in refractory or relapsed hematological malignancies.

In this pilot study; we assessed the immunosuppressive and the antileukemic potential of a combination of busulfan and melphalan prior to allogeneic BMT in 25 adult patients with refractory or relapsed hematological malignancies. Twelve patients were transplanted for acute myeloid leukemia (relapse: five patients; primary refractory: four patients; second remission: two patients), two patients for primary refractory acute lymphoblastic leukemia, nine patients for chronic myelogenous leukemia (accelerated phase: six patients; blastic phase: three patients) and two patients for primary refractory lymphoma. All received an unmanipulated marrow from HLA-identical siblings. All patients but one engrafted (median time to ANC > or = 0.5 x 10(9)/l = 17 days, to platelets > or = 50 x 10(9)/l = 29 days). Full chimerism was documented in the seven evaluable patients. The probability for developing acute GVHD was 58%. Complete remission was obtained in 17/18 measurable patients. With a 42 month median follow-up, eight patients are alive in unmaintained remission. The 4-year probabilities for relapse, survival, and DFS are respectively: 42%, 35%, and 31%. These results show that the combination of busulfan and melphalan ensures an effective immunosuppression allowing long-term engraftment. This regimen can provide long-term disease-free survival in patients with high-risk disease and thus represents an interesting alternative to the CY and/or TBI-containing regimens.

Adult↗
PubMed1996

Cyclophosphamide/mitoxantrone/melphalan (CMA) regimen prior to autologous bone marrow transplantation (ABMT) in metastatic breast cancer.

Dose-intensive treatment followed by ABMT is currently used in different approaches to treat breast cancer patients. An active non cross-resistant regimen combining cyclophosphamide (C), mitoxantrone (M) and melphalan (A) (CMA), was developed as the conditioning regimen before ABMT. The purpose of this phase II study was to evaluate this protocol and the duration of its effect in metastatic patients, who responded to chemotherapy. Criteria for inclusion included histologically documented breast cancer, age < 55 years and the first detection of measurable metastatic lesions. Following first-line chemotherapy in responding patients, histologically negative bone marrow was collected and cryopreserved. Then, intensification with cyclophosphamide (120 mg/kg), mitoxantrone (60 mg/m2), and melphalan (140 mg/m2) was followed by ABMT. Sixty-one metastatic breast cancer patients with a mean age of 40 years were included. Sites of measurable metastases included: liver 24, lung 14, central nervous system four, pleura three, skin six, and chest wall six, nodes eight and bone marrow one. Nineteen patients had lesions in two or more sites, and 22 had bone involvement. The response of 60 patients could be evaluated: before ABMT 31 were in clinical complete response (CR), 22 in partial response > 50% (PR), and seven had new progression. After ABMT, 36 patients were in CR, 16 in PR, one progressed and one was stable. Seven (11.5%) toxic deaths occurred. Mean time for hematological recovery was 32.5 days, without hematopoietic growth factors. Median survival was 33 +/- 9.4 months from the start of therapy, and 25.7 +/- 4.6 months from the date of ABMT. Median event-free survival was 20 months from the start of therapy, and 13 +/- 2 months from ABMT. With a median follow-up of 51 months, probability of actuarial survival, measured from the beginning of initial chemotherapy, was 36%, and event-free survival was 18%. In metastatic breast cancer responding to chemotherapy, high-dose consolidation with CMA and ABMT resulted in a median survival of 33 months. These results lay the ground work for evaluation in a randomized trial in metastatic breast cancer.

Adult↗
PubMed1996

Allogeneic vs autologous stem cell transplantation vs chemotherapy in patients with acute myeloid leukemia in first remission: the BGMT 87 study.

In 204 adult patients with de novo acute myeloid leukemia (AML), we prospectively compared allogeneic bone marrow transplantation (alloBMT), autologous stem cell transplantation (ASCT) and chemotherapy (Chemo). 162 patients (79.4%) achieved a complete remission (CR). Of the 135 patients who were still in CR after consolidation, 96 patients were less than 46 years of age: 36 patients had an HLA-identical sibling donor and were allocated for alloBMT (group I); they were compared to the 60 other patients who did not have an HLA-identical sibling donor and were treated with either ASCT or chemotherapy (group II). The 3-year disease-free survival was higher for group I patients (66.5 +/- 16%) than for the 60 group II patients (42.4 +/- 13%) (P < 0.05). The actuarial risk of relapse at 3 years was significantly lower for group I patients (24 +/- 15%) than for the other 60 group II patients (56 +/- 13%; P < 0.009). By multivariate analysis, the disease-free survival and risk of relapse were influenced by the initial WBC count (P < 0.02 and P < 0.006), the number of chemotherapy courses for CR (P < 0.001 and P < 0.01) and the type of post-induction treatment (alloBMT vs no alloBMT; P < 0.1 and P < 0.02). The 99 patients who did not fulfill the inclusion criteria for alloBMT were given intensive chemotherapy including high-dose aracytine. When they were still in CR (n = 77), these patients were then randomized for either ASCT (n = 39) or Chemo (n = 38). We were unable to detect any statistical difference between ASCT and Chemo for either disease-free survival, risk of relapse or survival. These results indicate that alloBMT seems to produce results which are at least superior to those of other therapeutic modalities. The results of either ASCT or Chemo look similar.

Acute Disease↗
PubMed1996

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↗
PubMed1995

[Lymphoproliferative syndrome induced by Epstein-Barr virus after kidney transplantation: value of genotypic analysis].

Forty-six days after renal transplantation for inborn tubulointerstitial nephropathy, an 18-year-old man was rehospitalized for renal failure with creatinine at 200 mumol/l. There was no sign of infection and ciclosporin level was within therapeutic range. Transplant biopsy showed minor interstitial infiltration with mononucleated cells. Methylprednisolone by 10 mg/kg/d bolus did not improve renal function and OKT3 5 mg/d was substituted for ciclosporin but had to be stopped on day 8 because of a severe infectious syndrome. The patient developed fever (39 degrees C), erythemato-pultaceous pharyngitis followed by major multiple lymph node and spleen enlargement. The diagnosis of primary Epstein-Barr infection was confirmed serologically. Histology of a submaxillary lymph node reported monomorphic immunoblastic lymphoproliferation. Immunologic phenotyping showed CD19, CD20 and CD22 surface antigens characteristic of B cells and in situ Epstein-Barr hybridization was positive in 100% of the cells. Southern Blot showed an oligoclonal pattern. Ciclosporin and azathioprin were stopped and the patient was treated with corticosteroids (15 mg/d) and aciclovir given orally (3.2 g/d) for 3 months. Outcome at six months was favorable with normalization of the renal function and complete regression of the infectious syndrome. This case demonstrated the importance of molecular biology techniques for virologic and genotypic assessment of lymphomatous proliferation allowing positive aetiologic diagnosis.

Acyclovir↗
PubMed1995

Impairment of leukaemia-free survival by addition of interleukin-2-receptor antibody to standard graft-versus-host prophylaxis.

Graft-versus-host disease (GVHD) is the most important adverse effect of HLA-matched allogeneic bone-marrow transplantation. T-cell depletion of the graft eliminates GVHD but also causes an unacceptable increase in rejections and leukaemic relapses. We have attempted to block the activation of resting T cells with a monoclonal antibody against the interleukin-2 receptor (33B3.1). 101 patients with leukaemia (acute lymphocytic 22, acute myelogenous 34, chronic myeloid 45) in first complete remission or first chronic phase were randomly assigned to groups receiving standard post-transplantation immunosuppression (methotrexate plus cyclosporin; n = 50) or the standard treatment plus antibody 33B3.1 (n = 51). There were 2 graft failures in the 33B3.1 group. The antibody did not significantly affect the cumulative frequency of acute GVHD of grade 2 or worse (19 [38%] vs 23 [46%]) but merely delayed its onset (median 36 [IQR 21-70] vs 25 [11-44] days; p < 0.01). At median follow-up of 58 (range 41-71) months, the antibody-treated group had significantly lower leukaemia-free survival (p < 0.05) mainly because of a progressive increase in the rate of late relapses (p = 0.08). Our findings confirm the importance of T cells in transplantation for leukaemia. The fine balance between the early modulation of transplant immunity and leukaemic control suggests that further anti-leukaemic measures may be needed when attempts are made to improve tolerance between the graft and the leukaemic host.

Adolescent↗
PubMed1995

Patient condition affects the collection of peripheral blood progenitors after priming with recombinant granulocyte colony-stimulating factor.

A total of 258 aphereses were performed in 79 patients with nonmyeloid malignancies after mobilization of peripheral blood stem cells (PBSC) with recombinant human granulocyte colony-stimulating factor (rhG-CSF). Apheresis products were examined for viable mononuclear cell (VMC), CD34+ cell, and clonogenic cell contents. The number of progenitors in aphereses differs in subgroups of patients with different diagnoses. However, the number of CD34+ or clonogenic cells is dependent on age and amount of chemotherapy delivered to patients before collection rather than on the nature of the disease itself. In addition, the actual dose of rhG-CSF used to mobilize PBSC and the number of VMC in aphereses influenced the clonogenicity of CD34+ cells, although the daily dose of rhG-CSF seems to play little role on the number of clonogenic cells in each individual apheresis product. CD34+ cell and CFU-C (or CFU-GM) numbers are related parameters, and the relation can be described as linear. However, the linear relation varies in different patient groups, and most of the linearity is induced by the highest sets of values. We conclude that mobilization with low doses of rhG-CSF alone is feasible and that the probability of collecting a high number of peripheral blood progenitors is increased in young patients undergoing apheresis early in the course of the disease. Although the relationship between CD34+ cells and CFUs can be described as linear in well-defined situations, its relevance may be limited because it is not a universal finding.

Adolescent↗
PubMed1995

Direct evidence for dissociated megakaryocytic chimaerism in a Wiskott-Aldrich patient successfully allografted.

We report a Wiskott-Aldrich patient who underwent allogeneic bone marrow transplantation from his HLA-identical sister at the age of 25. Conditioning regimen consisted of cyclophosphamide (180 mg/kg) and thoraco-abdominal irradiation (6 Grays). Cytogenetic follow-up revealed rapid and complete lymphoid chimaerism, but prolonged mixed bone marrow chimaerism. Correlative interphase cytogenetics performed on bone marrow smears using dual-colour fluorescence in situ hybridization with X and Y specific probes showed that the proportion of donor cells was significantly higher within megakaryocytes than in other lineages. This patient therefore presented with dissociated lineage engraftment, which is not exceptional in congenital diseases and aplastic anaemia, but has not previously been described in Wiskott-Aldrich syndrome. Bone marrow transplantation was successful despite this delayed engraftment which ensured adequate production in the involved cell lines.

Adult↗
PubMed1995

Philadelphia chromosome-negative chronic myeloid leukaemia: a report of 14 new cases.

The Philadelphia chromosome (Ph) is the cytogenetic hallmark of chronic myeloid leukaemia (CML) and is used to confirm the diagnosis of CML based on clinical and morphological criteria. We investigated 14 patients with features of CML but without detectable Ph chromosome. In seven patients, referred to as BCR+, M-bcr/abl rearrangement was detected by polymerase chain reaction (PCR). The seven remaining patients did not have M-bcr/abl rearrangement and are described as BCR-. BCR- patients were younger, had lower white blood cell counts (WBC) and lower basophilia. Four BCR- and four BCR+ patients underwent blastic transformation (BT). Response to therapy was fairly similar in both populations. According to French-American-British (FAB) Cooperative Leukaemia Group guidelines, all BCR- patients were classified as having classic form CML or 'chronic granulocytic leukaemia' (CGL) when based only on morphological data. This study further confirms the existence of true CML cases without Ph chromosome or M-bcr/abl rearrangement and shows that this entity differs only slightly from classic form Ph+ CML. The Ph-BCR- subgroup raises two problems. First, the differential diagnosis with atypical CML or CMML, based on morphological data, and secondly, the therapeutic follow-up in the absence of a specific marker. In contrast, the residual disease of Ph-BCR- patients can be monitored by PCR. More advanced molecular and biochemical techniques will be required to understand which molecular mechanisms underlie Ph-BCR- CML, resulting in phenotypes sometimes indistinguishable from Ph+ CML.

Base Sequence↗
PubMed1995

Persistence of BCR/ABL mRNA-expressing bone-marrow cells in patients with chronic myelogenous leukemia in complete cytogenetic remission induced by interferon-alpha therapy.

Complete hematologic and cytogenetic responses can be obtained with interferon-alpha (IFN-alpha) in 15-25% of the patients with chronic myelogenous leukemia (CML). In these patients, reverse-transcription polymerase chain reaction (RT-PCR) can be used to evaluate minimal residual disease. We studied 12 patients who remained Philadelphia-negative for a median period of 21 months on IFN-alpha therapy. Using RT-PCR, the specific transcript was found in all bone marrow (BM) samples. Ten patients still exhibiting a persistent residual clone remained in cytogenetic remission for a median period of 14 months. As we observed a dissociation between bcr-abl expression in BM and peripheral blood (PB) cells, and given the known fluctuations of the bcr-abl PCR results, we suggest that PB negative results should be confirmed on BM specimens. Alternatively, it remains to be demonstrated whether longitudinal monitoring of residual disease would benefit from quantitative PCR or double fluorescence in situ hybridization.

Adult↗
PubMed1995

[Methodology and legitimacy of French clinical trials in primary chemoprevention of cancers. The point of view of the National Federation of French cancer centers].

In connection with the breast cancer prevention trial (BCPT) controversy, the "Fédération nationale des centres de lutte contre le cancer" (FNCLCC) decided to clarify, with the help of various discipline experts, its position on chemoprevention trials. If in terms of inclusion, two approaches can be opposed: high relative risk versus high attributable risk, these trials share in common a considerable importance of the informed consent according to potentially prosecution. A particular attention should be given to the unambiguous definition of end-points and indicators, and to monitoring of the side effects (medical or not). Non medical actors would have to play significant interventions in the schedule, the follow-up and the evaluation of such protocols. Methodological difficulties have been pointed, for example: recruitment, observance, drop out and confounding factors. French specificity has to be taking into account for the choice of pathologies, kind of interventions and global evaluation non limited to the sole dimension of the medical efficiency.

Antineoplastic Agents↗
PubMed1995

[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↗