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Biomedical subjects

N Basara

Publications and source records attributed to N Basara.

At least 37 records · Page 2Linked to original sources
PubMed2000

Toxoplasmosis, a severe complication in allogeneic hematopoietic stem cell transplantation: successful treatment strategies during a 5-year single-center experience.

Toxoplasmosis is a rare but often fatal complication that occurs after patients undergo allogeneic hematopoietic stem cell transplant. At our institution, toxoplasmosis was diagnosed in 8 of 301 patients who received stem cell transplants. Disseminated toxoplasmosis with a rapid fatal course was observed in 2 patients. Six patients had cerebral toxoplasmosis diagnosed on the basis of neurological signs and observation of the patients' mental confusion, seizures, and typical lesions (which were assessed by computed tomography, magnetic resonance imaging, or both). Seroconversion of antitoxoplasma immunoglobulin and a discovery of toxoplasma deoxyribonucleic acid in the cerebrospinal fluid (confirmed by use of polymerase chain reaction) were documented in all patients. Treatment consisted of clindamycin therapy (for 2 patients) and of pyrimethamine-clindamycin therapy, sulfadiazine therapy, or both (for 5 patients). Patients showed improvement after therapy, as assessed by clinical and radiological means. Three of 8 patients survive-1 without any residual neurological symptoms and 2 with minimal neurological symptoms.

Adult↗
PubMed2000

Mycophenolate mofetil in stem cell transplant patients in relation to plasma level of active metabolite.

OBJECTIVES: To investigate mycophenolate mofetil (MMF) plasma levels and impact on acute graft versus host disease (aGvHD) after stem cell transplantation (SCT). METHODS: SCT patients (n = 14) with aGvHD (>/= II) receiving MMF (1-3 g/d) in addition to cyclosporine, prednisolone, and methotrexate for aGvHD prophylaxis were investigated. Plasma levels of mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) were determined by high-performance liquid chromatography. RESULTS: Overall median steady state pre-dose plasma MPA concentration was 0.47 mg/L and increased within 75 min after administration to 1.64 mg/L. In comparison to patients with skin aGvHD, patients with gut aGvHD had lower MPA concentrations, both pre-dose (p = 0.16) and after 75 min, (p = 0.02). All 7 patients with skin aGvHD but only 2 patients with gut aGvHD responded to MMF. Overall, the pre-dose plasma MPA concentration was significantly (p = 0.007) greater in responders (n = 9) than in non-responders (n = 5). CONCLUSION: MMF seems to be an effective treatment for aGvHD in SCT patients particular in those patients without gut involvement.

Drug Therapy, Combination↗
PubMed2000

Mycophenolate mofetil for the prophylaxis of acute GVHD in HLA-mismatched bone marrow transplant patients.

Mycophenolate mofetil (MMF), a new immunosuppressive drug successfully used in renal and heart transplant recipients, was used in combination with cyclosporin A (CsA), methotrexate (MTX) and prednisolone for the prophylaxis of acute graft-versus-host disease (aGVHD) after bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) from human leukocyte antigen (HLA)-mismatched, unrelated (n = 9) and related donors (n = 4) in an open single-centre phase II study. Thirteen patients, transplanted from HLA-mismatched donors of 18-57 yr of age, received 1 g MMF daily, starting at day 10, in addition to CsA and prednisolone for aGVHD prophylaxis. All patients were engrafted between days 13 and 15. Four of the 13 patients experienced aGVHD grade I/II (n = 2) and grade III (n = 2). All patients except 3 were alive on day 100 post-transplantation. No severe adverse effects of MMF were recorded. In our pilot study, we demonstrated that MMF can be used safely for the prophylaxis of aGVHD.

Acute Disease↗
PubMed2000

Second allogeneic hematopoietic stem cell transplantation as treatment for leukemia relapsing following a first transplant.

We report 27 patients with relapsed acute or chronic leukemia who underwent a second hematopoietic stem cell transplant (HSCT) from a related or unrelated donor. Seventeen patients were diagnosed with acute myelogenous leukemia (AML), six with acute lymphocytic leukemia (ALL) and four with chronic myeloid leukemia (CML). Ages ranged from 22 to 49 years (median 37); 13 patients were female and 14 male. Relapse was diagnosed between 1 and 45 months after the first HSCT. Sixteen patients who relapsed had received an autologous transplant initially and 11 an allogeneic transplant. Ten patients relapsed within 6 months and 17 patients later than 6 months. Chemotherapy was used as reinduction for relapse after HSCT in 16 patients who had received an autologous transplant and in three who had received an allogeneic transplant, since the latter did not respond to reduction of immunosuppression to induce a graft-versus-leukemia (GVL) reaction. Five of these 19 patients (26%) achieved complete remission (CR), seven patients did not respond to chemotherapy and seven achieved a partial remission (PR). The stem cell source for the second HSCT included bone marrow (n = 12) and PBSC (n = 4) from genotypically identical unrelated donors, PBSC (n = 7) and bone marrow (n = 3) from related donors. Currently eight of the 27 patients are alive and disease-free after the second HSCT. One patient is alive and disease-free after two allogeneic transplants (day +1538), eight patients, who relapsed after an autologous transplant followed by an allogeneic transplant (days +248 to +1140), acute myeloid leukaemia (n = 6) and chronic myeloid leukemia (n = 2) are alive and disease-free. The overall disease-free survival is 30% (8/27). The overall disease-free survival of autologous transplant patients subsequently undergoing an allogeneic transplant is 43% (P = 0.049). It is suggested that a second HSCT is possible for patients with leukemia relapse following the first autologous transplant. A second transplant might also be offered to patients relapsing after the first allogeneic HSCT. Bone Marrow Transplantation (2000) 25, 41-45.

Acute Disease↗
PubMed2000

Lenograstim-mobilized peripheral blood progenitor cells in volunteer donors: an open label randomized split dose escalating study.

Mobilization of peripheral blood cell progenitor cells was investigated in 36 healthy sibling donors using three different split doses of glycosylated rhG-CSF (lenograstim). The donors were randomized into three groups: group 1 was given lenograstim at 8, group 2 at 11 and group 3 at 15 micrograms/kg/day in two split doses, subcutaneously for 4 and 5 days, respectively. Leukapheresis was performed on day 4 or 5 depending on the WBC and CD34+ cell count. We were able to demonstrate that there was a significant correlation between circulating CD34+ cells on the day of harvest and CD34+ cells in the apheresis products in all three groups. The number of CD34+ cells pre-apheresis was inversely correlated with age in group 1 and group 2. However, in group 3, the number of CD34+ cells pre-apheresis did not correlate with age. There was also a difference between the number of progenitor cells mobilized in the three dose groups regarding the time of harvest. Apheresis was performed in groups 1 and 2 on day 5 of mobilization in order to obtain a sufficient number of stem cells for allogeneic transplantation. In contrast, with the split dose of 15 micrograms/kg/day, harvest could be routinely performed on day 4 of stimulation. We conclude that lenograstim given twice a day at doses of 8, 11 and 15 micrograms/kg/day provided different CD34+ cell yields in normal donors, in particular, with regard to the time of harvest. The number of CD34+ cells pre-apheresis was not correlated with age in the group of donors mobilized with a split dose of 15 micrograms/kg/day, indicating that this dosage might also be suitable for older donors.

Adjuvants, Immunologic↗
PubMed2000

Faster engraftment of neutrophils and platelets with peripheral blood stem cells from unrelated donors: a comparison with marrow transplantation.

Engraftment was achieved in 43/45 (95%) recipients of peripheral blood stem cells (PBSC) from HLA-compatible unrelated donors (n = 45), compared to all 45 patients in matched controls receiving bone marrow and 14/18 (78%) recipients of CD34-selected PBSC (P < 0.01). The time to reach ANC >0.5 x 10(9)/l was a median of 16 days in the PBSC and CD34 groups, compared to 20 days in the bone marrow controls (P < 0.001 vs PBSC). The time to reach platelets >50 x 10(9)/l was a median of 23 days in the PBSC group and 24 days in the CD34 group, which was significantly faster than 29 days in the bone marrow controls (P < 0.01). Acute GVHD grades II-IV developed in 30% in the PBSC group, 20% in the recipients of bone marrow and 18% in the CD34 group. The corresponding figures for chronic GVHD were 59%, 85% and 0% (P < 0.01) in the three groups, respectively. The probability of non-relapse death was 27% in the recipients of PBSC, 21% in the bone marrow controls and 60% in the CD34 group (NS). The 2-year leukaemia-free survival was 46% in the PBSC group, 41% in the bone marrow group and 25% in the CD34 group (NS).

Adolescent↗
PubMed2000

New strategies in the treatment of graft-versus-host disease.

GVHD continues to be a major complication after allogeneic hematopoietic stem cell transplantation even when the recipient is given immunosuppression for the prophylaxis of this severe disease. There have been many advances in the prevention and treatment of GVHD, using compounds such as cyclosporine, FK506, mycophenolate mofetil or monoclonal IL-2 receptor antagonist. New strategies seem to include sequential therapy involving the blocking of both endogenous cytokines and alloreactive donor cells. However, further clinical and laboratory studies are needed in order to improve the therapy of established GVHD.

Acute Disease↗
PubMed2000

New strategies in GVHD prophylaxis.

Despite immunosuppressive therapy using cyclosporine (CsA) and prednisolone and methotrexate (MTX), the incidence for aGVHD grade II to IV after transplantation from HLA matched unrelated donors (MUD) is 78%, the incidence for grade III and IV 36%. Since GVHD contributes to morbidity and mortality after MUD-BMT, a more effective prophylactic regimen is needed in order to prevent these transplant-associated complications. Recently, we described that mycophenolate mofetil (MMF, CellCept), an immunosuppressive agent successfully used for the prevention of acute rejection in renal allograft recipients, can safely and effectively be used for the treatment of aGVHD in hematopoietic stem cell transplantation. Information on the i.v. formulation of mycophenolic acid (MPA) is not yet available. Here we report on the i.v. formulation of MMF in hematopoietic stem cell recipients. MMF is effective in the prophylaxis of acute GVHD after stem cell transplantation; the optimal dosage needs further investigation. At the present time the relevance of measurement of plasma MPA concentrations on MMF dosage is not yet understood and further evaluation is required.

Acute Disease↗
PubMed2000

A comparative study of peripheral blood stem cell vs bone marrow transplantation from unrelated donors (MUD): a single center study.

Peripheral blood stem cell transplants (PBSCT) from unrelated donors (n = 37) were compared with bone marrow transplants (BM, bone marrow group, n = 37) in a matched pair analysis. Ten patients (2, class 1) in the alloPBSCT group and seven patients (2, class 1) in the BM group had one HLA locus mismatch donor, respectively. The following factors were matched: HLA-compatibility, diagnosis, disease stage, age and gender. The median age in the PBSC group was 37 years (19-56, excluding one 6-year-old child) and in the BM group 37 years (18-53). The BM group consisted of 12 females and 25 males, 17 females and 20 males were in the PBSC group. Twelve patients in the BM and 11 patients in the PBSC group were diagnosed with AMI,; 7/7, ALL; 15/15, CML; 2/3, MDS; 1/1, NHL. Thirty-four (14/20) of the 74 patients (45%) were considered as high risk patients. The conditioning regimen was BU/CY for standard risk patients with myeloid diseases (31 patients) and TBI/CY for ALL and NHL patients (36 patients); six patients received intensified conditioning with VP16 (2 patients), thiotepa (2 patients) or melphalan (1 patient). The GVHD prophylaxis regimen was used according to the Seattle protocol. DFS was 51% (19 patients) with a median of 352 days and 59% (21 patients) with a median of 760 days, in PBSC and BM transplants, respectively. The median time to leukocyte engraftment in PBSC patients was 14 days (range 6-26 days) and in the BM group 19 days (range 9-29 days; P < 0.02). The time of platelet engraftment did not differ significantly between the groups. The incidence of grade II-IV acute GVHD was 40% (four patients died, 13%) in the PBSC group and 20)% (three patients died, 8%) in the BM group, respectively (P < 0.05, log-rank). No signs of aGVHD were found in 19% of the patients in the PBSC and 27% in the BM group. Our results indicate that allogeneic PBSCT does lead to a significantly faster leukocyte engraftment. The significant increase with regard to the incidence and shorter time of onset of severe aGVHD in PBSC patients, compared to marrow transplant patients, need to be confirmed in a randomised trial.

Adolescent↗
PubMed2000

Clinical scale production of an improved retroviral vector expressing the human multidrug resistance 1 gene (MDR1).

Retroviral vectors are currently the most important and best characterized tools for ex vivo genetic modification of hematopoietic progenitor/stem cells. As a prerequisite for clinical applications, large volumes of high-titer vector supernatants have to be generated in compliance with 'GMP' guidelines. This goal can be reached using a carefully selected producer cell clone and a conventional large-scale cell culture system. The retroviral vector SF1m provides efficient expression of the human multidrug resistance 1 (MDR1) gene in hematopoietic progenitor/stem cells in vitro and in NOD/SCID mouse repopulating human cells in vivo. Currently, a clinical phase I/II study is in preparation to test whether intensified consolidation chemotherapy is enabled by autologous transplantation of peripheral blood progenitor/stem cells that have been genetically modified with SF1m. Using multi-tray cell factories >19 l of serum-free vector containing supernatant were generated from cells of a previously established SF1m-producer clone, based on the PG13 packaging cell line. Testing of the final samples revealed sufficient quality (>1.5 x 10(6) infectious particles/ml) for clinical scale transduction of CD34+ cells. Results from the production runs and the applied biosafety concept are described.

Animals↗
PubMed2000

Recurrent venous thrombosis in a patient with chronic lymphocytic leukemia and acquired protein S deficiency.

A patient with chronic lymphocytic leukemia and an undetectable plasma level of protein S (PS), associated with recurrent venous thrombosis, is described. The laboratory investigation revealed the concomitant presence of an inhibitor directed to PS and a monoclonal protein in the patient's plasma. After treatment with prednisone and cyclophosphamide both the inhibitor to PS and the monoclonal component disappeared.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Peripheral blood stem cell transplantation from unrelated donors: a comparison with marrow transplantation.

Peripheral blood stem cell (PBSC) transplants from HLA-A, -B, and -DR compatible unrelated donors (n = 45) were compared with bone marrow (BM; BM group, n = 45). Eighteen patients received CD34-selected PBSC (CD34 group). The PBSCs contained more mononuclear cells, CD34(+), CD3(+), and CD56(+) cells compared with marrow (P <.001). Engraftment was achieved in all 45 patients in the BM group, in 43 of 45 (95%) in the PBSC group, and in 14 of 18 (78%) in the CD34 group (P <.01). In multivariate analysis, a short time to absolute neutrophil count (ANC) equal to 0.5 x 10(9)/L was associated with the PBSC/CD34 groups (P <.001) and granulocyte colony-stimulating factor (G-CSF) treatment (P =.017). A short time to platelets equal to 50 x 10(9)/L was associated with PBSC (P =. 003) and no methotrexate (P =.015). Grades II-IV acute graft-versus-host disease (GVHD) was 20% in the BM controls, 30% in the PBSC group, and 18% in the CD34 group (not significant [NS]). The probability of chronic GVHD was 85% in the BM group, 59% in the PBSC group, and 0% in the CD34 group (P <.01). One-year transplant-related mortality was 21% and 27% and survival was 53% and 54% in the BM and PBSC groups, respectively (NS). The 2-year relapse-free survival was 41% and 46% in the two groups, respectively.

Adult↗
PubMed1999

A second unrelated bone marrow transplant: successful quantitative monitoring of mixed chimerism using a highly discriminative PCR-STR system.

A second bone marrow transplant (BMT) might be considered as an option in patients with leukaemia with graft failure after BMT. We report the successful treatment of a patient with graft failure by a second stem cell transplant from another unrelated donor. We evaluated the usefulness of an unrelated donor as the source of the second BMT in this clinical setting. In addition to this, a penta PCR-STR system was tested and shown to be sensitive for monitoring of marrow engraftment. The conditioning regimen for the first transplantation consisted of busulfan and cyclophosphamide while anti-thymocyte globulin and CY were used for the second BMT. The patient successfully engrafted at day +11 after second BMT.

Adult↗
PubMed1999

Modulatory in vitro effects of interleukin-1 receptor antagonist (IL-1Ra) or antisense oligonucleotide to interleukin-1 beta converting enzyme (ICE) on acute myeloid leukaemia (AML) cell growth.

We investigated the effects of interleukin-1 receptor antagonist (IL-1Ra) on the spontaneous proliferation and AML colony forming unit (CFU-AML) formation of bone marrow and peripheral blood cells in 50 acute myeloid leukaemia (AML) patients. Exposure to IL-1Ra (10 micrograms/ml) caused either decreased, unaltered or increased AML cell proliferation, as well as of CFU-AML colony formation, depending on the individual patient, but the inhibitory effects were dominant. To evaluate the involvement of IL-1 beta converting enzyme (ICE) in the autonomous AML cell growth, the effects of an antisense oligonucleotide on ICE were examined in 19 of these patients. In a majority of patients, antisense ICE suppressed both AML cell proliferation and CFU-AML although a stimulatory effect was sometimes evident. The proportion of AML patients with suppression obtained by antisense ICE was higher than with IL-1Ra, suggesting the involvement of additional ICE-dependent cytokine(s) in AML cell growth besides IL-1. The presence of IL-1Ra or antisense ICE also suppressed the endogenous IL-1 beta production of AML cells, at both the level of pro-IL-1 beta and mature IL-1 beta. Although inhibition by IL-1Ra or antisense ICE on growth parameters of AML cells in vitro prevailed, indicating the importance of IL-1 activity in autonomous AML cell growth, stimulatory effects on the cells of some patients suggest that AML is a heterogenous disorder regarding IL-1 beta regulation.

Acute Disease↗
PubMed1998

A second unrelated bone marrow transplant with an unrelated donor marrow: treatment of a patient with relapsed leukemia.

A second bone marrow transplant might be considered as an option in patients with leukemia relapsing after bone marrow transplantation. We report the successful treatment of a patient with relapsed ALL with a second BMT from the same unrelated donor. We evaluated the usefulness of an unrelated donor as the source of the second BMT in this clinical setting. The conditioning regimen for the first transplantation consisted of BU and CY while fractionated TBI and CY were used for the second BMT. Acute skin GVHD, grade III which developed after second BMT, was successfully treated with the use of a new immunosuppressive drug, mycophenolate mofetil. Hemorrhagic cystitis and a CMV infection developed as complications during the second BMT and were successfully treated. The patient was alive and well after the second BMT with limited chronic skin GVHD up to day +170.

Adult↗