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Biomedical subjects

H T Greinix

Publications and source records attributed to H T Greinix.

At least 37 records · Page 2Linked to original sources
PubMed2001

PBPC mobilization with chemotherapy and G-CSF in patients with chronic myeloid leukemia: quantification of bcr/abl-positive cells by interphase fluorescence in situ hybridization and competitive PCR.

BACKGROUND: Autografting of normal stem cells mobilized after chemotherapy is increasingly used in chronic myeloid leukemia (CML). Thus, quantification of possible contamination of progenitor cell apheresis with breakpoint cluster region (bcr)/Abelson murine leukemia (abl)-positive cells is of great clinical interest. STUDY DESIGN AND METHODS: Two molecular methods were compared to quantify bcr/abl positivity in leukapheresis components obtained after mobilizing chemotherapy in six patients with CML. To document the efficacy of in vivo purging, the leukapheresis procedures were monitored with interphase fluorescence in situ hybridization (FISH) and quantitative competitive PCR (QC-PCR) as a ratio of bcr/abl:abl. RESULTS: From the first to the last leukapheresis, bcr/abl positivity in FISH increased from a median of 11 percent to 33 percent. For bcr/abl transcripts, a simultaneous increase in consecutive leukapheresis procedures was seen. The median percentage of bcr cells in a bcr/abl:abl ratio was 3.1 percent in the first apheresis. In the last apheresis after the mobilization with mRNA, the QC-PCR showed a median of 19.5 percent. FISH and QC-PCR showed a statistical significant increase of bcr/abl positivity from the first to the last apheresis. CONCLUSIONS: Both FISH and QC-PCR were reliable methods of quantifying bcr/abl positivity, and they allowed selection of the optimal apheresis component for autologous transplantation. In both methods, a significant increase in bcr/abl positivity was seen from the first to the last leukapheresis. With FISH, results can be obtained within 24 hours. This method may prevent additional contaminated leukapheresis in case of increasing percentages of bcr/abl-positive cells.

Adult↗
PubMed2001

Kinetics of PBPC mobilization by cyclophosphamide, as compared with that by epirubicin/paclitaxel followed by G-CSF support: implications for optimal timing of PBPC harvest.

BACKGROUND: Limited information is available on the mobilization kinetics of autologous PBPCs after induction with various chemotherapy regimens. With PBPC mobilization in patients with breast cancer used as a model for chemotherapy-induced PBPC recruitment, the kinetics of progenitor cells mobilized either with cyclophosphamide (CY) or epirubicin/paclitaxel (EPI-TAX) followed by the administration of G-CSF was compared. STUDY DESIGN AND METHODS: The study included a total of 86 patients with breast cancer (stage II-IV) receiving either CY (n = 39) or EPI-TAX (n = 47), both followed by G-CSF support. The progenitor cell content in peripheral blood and apheresis components was monitored by flow cytometric enumeration of CD34+ cells. PBPC collection was started when the threshold of >20 x 10(6) CD34+ cells per L of peripheral blood was reached. RESULTS: The PBPC collection was begun a median of 9 days after the administration of EPI-TAX followed by G-CSF support, as compared to a median of 13 days after mobilization with CY plus G-CSF. After treatment with CY, the total numbers of PBPCs peaked on Day 1 of apheresis, and they rapidly declined thereafter. In contrast, treatment with EPI-TAX followed by G-CSF administration led to a steady mobilization of CD34+ cells during leukapheresis. The difference in the mobilization patterns with CY and EPI-TAX resulted in a greater yield of CD34+ cells per L of processed blood volume. Compared to EPI-TAX, mobilization with CY required the overall processing of 30 percent less whole-blood volume to reach the target yield of > or = 10 x 10(6) CD34+ cells per kg of body weight. After a median of three apheresis procedures, however, both CY+G-CSF and EPI-TAX+G-CSF were equally effective in obtaining this target yield. CONCLUSION: These results imply that specific PBPC mobilization as part of a given chemotherapy regimen should be taken into consideration before the planning of a PBPC harvest.

Adult↗
PubMed2001

Platelet-reactive HLA antibodies associated with low posttransfusion platelet increments:a comparison between the monoclonal antibody-specific immobilization of platelet antigens assay and the lymphocytotoxicity test.

BACKGROUND: Platelet-reactive HLA antibodies are a major reason for low posttransfusion platelet increments. The clinical importance and value of the test systems for their in vitro determination is still controversial. STUDY DESIGN AND METHODS: A prospective analysis of HLA antibodies was performed in sera obtained once a week for at least 4 consecutive weeks from 55 patients (female/male, 28/27; age: median, 49 years; range, 18-69) undergoing intensive chemotherapy and in need of prophylactic platelet transfusions. All sera (n = 330) were analyzed by the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay and by the standard lymphocytotoxicity test (LCT). RESULTS: In the MAIPA, 24.5 percent of sera (81/330) obtained from 22 patients contained HLA antibodies. These were detected significantly more often by the MAIPA assay than by the LCT (24.5% vs. 8.2%). Fifty-five sera (20 patients) were positive in the MAIPA assay only. In 15 patients, HLA antibodies were transient. In 3 patients, HLA antibodies were detected earlier by the MAIPA assay than by the LCT. Significantly more sera obtained at the time of low posttransfusion platelet increments were positive in MAIPA alone, rather than in both MAIPA and the LCT (44% vs. 17%). CONCLUSION: The MAIPA assay is more sensitive than the standard LCT in detecting platelet-reactive HLA antibodies. These MAIPA-positive/LCT-negative HLA antibodies affect the posttransfusion platelet increment.

Adolescent↗
PubMed2001

Increased serum flt3-ligand in healthy donors undergoing granulocyte colony-stimulating factor-induced peripheral stem cell mobilization.

The effect of granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood progenitor cells (PBPC) on the endogenous serum levels of cytokines stem cell factor (SCF) and flt3-ligand (flt3-L) was studied in 18 healthy subjects undergoing allogeneic PBPC donation. Donors received a standardized mobilization regime consisting of a 4-day course of G-CSF, with leukapheresis on day 5. Endogenous serum flt3-L and SCF were determined prior to G-CSF administration, on the day of leukapheresis, and followed up until day +100 after cessation of G-CSF administration. The administration of G-CSF resulted in a transient elevation of endogenous flt3-L serum levels. At the day of leukapheresis serum flt3-L showed a median increase of 75% compared to serum flt3-L levels obtained before G-CSF treatment. The increase in serum flt3-L levels showed no correlation with the total number of progenitor cells mobilized. Cessation of G-CSF treatment led to normalization of serum flt3-L within 7 days post G-CSF administration. In contrast, serum CSF levels remained unchanged in response to G-CSF administration. Our results demonstrate a transient surge in serum flt3-L in relation to G-CSF-induced PBPC mobilization, although the assessment of endogenous flt3-L give no information regarding the ability for G-CSF-induced PBPC recruitment in healthy individuals.

Adolescent↗
PubMed2000

Extracorporeal photochemotherapy in the treatment of severe steroid-refractory acute graft-versus-host disease: a pilot study.

Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing agent 8-methoxypsoralen and UV-A radiation has been shown to be effective in the treatment of selected diseases mediated by T cells, rejection after solid organ transplantation, and chronic graft-versus-host disease (GVHD). We present 21 patients with a median age of 38 years who developed steroid-refractory acute GVHD grades II to IV after stem cell grafting from sibling or unrelated donors and were referred to extracorporeal photochemotherapy (ECP). Three months after initiation of ECP 60% of patients achieved a complete resolution of GVHD manifestations. Complete responses were obtained in 100% of patients with grade II, 67% of patients with grade III, and 12% of patients with grade IV acute GVHD. Three months after start of ECP complete responses were achieved in 60% of patients with cutaneous, 67% with liver, and none with gut involvement. Adverse events observed during ECP included a decrease in peripheral blood cell counts in the early phase after stem cell transplantation (SCT). Currently, 57% of patients are alive at a median observation time of 25 months after SCT. Probability of survival at 4 years after SCT is 91% in patients with complete response to ECP compared to 11% in patients not responding completely. Our findings suggest that ECP is an effective adjunct therapy for acute steroid-refractory GVHD with cutaneous and liver involvement. However, in patients with acute GVHD grade IV or gut involvement other therapeutic options are warranted.

Acute Disease↗
PubMed2000

Excellent disease eradication by myeloablative therapy and stem-cell transplantation in patients with acute myelogenous leukemia.

Between February 1982 and 1999, 118 consecutive patients (65 male, 53 female) with acute myelogenous leukemia (AML), with a median age of 35 years (range 17-56 years), received stem-cell grafts from a human leukocyte antigen-identical sibling (n = 71), one-antigen-mismatched family member (n=2), matched unrelated donor (n=15), one-antigen-mismatched unrelated donor (n = 4) or an autologous (n = 26) graft. At the time of transplant, 56 patients were in the first complete remission (CR), 27 in the second CR, 6 in untreated relapse, 17 in primary refractory, and 12 in refractory relapse. The French-American-British classification (FAB) subtypes were as follows: M1 (n=25), M2 (n=28), M3 (n=11), M4 (n =32), M5 (n=16), M6 (n = 6). For conditioning, most patients underwent total body irradiation-containing regimens. As of 28 February, 1999, probability of leukemia-free survival (LFS) is 58% for patients after related and 45% after unrelated stem-cell transplantation (SCT). The probability of LFS is 70% for patients given allogeneic transplants in the first CR compared with 33% for those beyond the first CR at SCT. In autologous stem-cell graft recipients, the probability of LFS is 37%. Transplant-related mortality was 28% after related, 20% after unrelated, and 4% after autologous SCT. Probability of relapse for patients given related-donor stem-cell grafts in the first CR and beyond the first CR is 30% and 67%, 55% after unrelated and 63% after autologous stem-cell grafting. Thus, myeloablative therapy followed by allogeneic stem-cell infusion has a high curative potential for patients with AML in remission and offers substantial benefits to patients in advanced disease.

Adolescent↗
PubMed2000

Effect of interleukin-3, stem cell factor and granulocyte-macrophage colony-stimulating factor on committed stem cells, long-term culture initiating cells and bone marrow stroma in a one-step long-term bone marrow culture.

Long-term bone marrow culture (LTBMC) supports both differentiation and conservation of hematopoietic progenitor cells. During the culture period, the frequency and proliferative potential of early repopulating stem cells that give rise to progenitors detectable after 5 weeks in LTBMC--so-called long-term culture-initiating cells (LTC-IC)--can be investigated. The adherent stroma cell layer was modified by interleukin-3 (IL-3) + granulocyte-macrophage colony-stimulating factor (GM-CSF)+ stem-cell factor (SCF) with an increased cellularity and higher percentage of differentiated myeloid cells and a reduced percentage of stroma cells. We have studied the effects of stimulative cytokines, such as GM-CSF, SCF, and IL-3, on proliferation of committed colony-forming unit cells (CFU-C), LTC-IC, and stroma cell formation in LTBMC of unseparated bone-marrow cells. IL-3, GM-CSF, and SCF significantly stimulated the cumulative proliferation of nucleated cells and committed CFU-C. Weekly stimulation of LTBMC during the culture period did not exhaust the proliferative capacity of stem cells as seen in maintenance of LTC-IC after 5 weeks in LTBMC. In contrast, no LTC-IC were seen in limiting dilution analyses from LTBMC cultured 5 weeks without cytokine supplementation. Our data indicate that an increased proliferation of committed stem cells can be achieved by the addition of stimulatory growth factors, and maintenance of LTC-IC is possible over a period of 5 weeks. A net expansion of LTC-IC if compared with the starting bone-marrow suspension could not be obtained after a 5-week LTBMC period.

Bone Marrow↗
PubMed2000

Regeneration of erythropoiesis after related- and unrelated-donor BMT or peripheral blood HPC transplantation: a major ABO mismatch means problems.

BACKGROUND: Blood group incompatibility in allogeneic BMT is common but does not appear to affect the outcome in terms of incidence of graft rejection or delayed engraftment. However, major ABO incompatibility may be associated with prolonged erythroid aplasia. STUDY DESIGN AND METHODS: In a retrospective analysis of 286 allogeneic transplant recipients, the prevalence of prolonged erythroid aplasia, including pure RBC aplasia, was determined. RESULTS: Patients receiving major ABO-incompatible grafts showed a significant delay in reticulocyte engraftment (median, 32 days; range, 12-347) from that in patients receiving ABO-identical (20; 10-152) or minor ABO-incompatible (21; 12-47) grafts. Pure RBC aplasia occurred in 7 (3%) of 240 evaluable recipients and was observed only in the major ABO-incompatible group (7/43, 16%). Treatment of pure RBC aplasia consisted of either plasma exchange, which resulted in a response within 16 to 68 days, or immunoadsorption, in which the response occurred between Days 119 and 204 after initiation of treatment. CONCLUSION: Major ABO incompatibility may lead to delayed reticulocyte engraftment, resulting in prolonged transfusion dependency and increased risks of transmission of infection and iron overload. Therefore, therapeutic strategies should be taken into consideration to allow erythroid reconstitution in these patients.

ABO Blood-Group System↗
PubMed2000

Paclitaxel-containing high-dose chemotherapy in high-risk breast cancer patients.

Despite standard-dose adjuvant chemotherapy, the prognosis for patients with breast cancer and extensive axillary lymph node involvement at diagnosis is poor. The efficacy of a paclitaxel-containing, high-dose chemotherapy protocol in 21 high-risk breast cancer patients is assessed. After standard-dose chemotherapy followed by peripheral blood stem cell (PBSC) mobilization, high-dose therapy with paclitaxel, carboplatin, and cyclophosphamide and CD34-selected PBSC rescue was given. Hematologic reconstitution after high-dose therapy was rapid. Main toxicity included diarrhea grade I or II in about half of the patients and infections were observed in 19%. Five-year probabilities for relapse and failure-free survival were 32% and 62%, respectively. High-dose consolidation with paclitaxel, carboplatin, and cyclophosphamide achieves a high failure-free survival in patients with high-risk breast cancer with acceptable toxicities and stable, long-term hematopoietic reconstitution. Evaluation of the benefit of high-dose therapy in these patients in larger prospective, randomized trials is warranted and currently under way.

Adult↗
PubMed2000

Relapse of chronic myelogenous leukemia 12 years after allogeneic marrow transplantation: successful second transplantation with allogeneic peripheral blood progenitor cells.

We report on a 31-year old female patient who relapsed with CML in blast crisis 12 years after a successful BMT for CML in chronic phase from her HLA-identical sister. Because of her good performance status and the long time elapsed since her first BMT, PBPC transplantation of the originial donor was planned. Therefore, the patient was conditioned with busulfan and cyclophosphamide and then received unmanipulated PBPCs from her sister. GVHD prophylaxis consisted of MTX and CsA. She had early engraftment but considerable hepatotoxicity which resolved after more than six months. Furthermore, she developed acute GVHD of the skin grade 2, which responded to corticosteroids. Fifteen months after second transplantation the patient is alive and well in molecular remission and without signs of chronic GVHD.

Adult↗
PubMed2000

Extracorporeal photochemotherapy in the treatment of severe graft-versus-host disease.

Advances in posttransplant immunosuppression have to the present not been able to prevent the development of graft-versus-host disease (GVHD) in patients given related or unrelated stem cell grafts for cure of hematologic diseases. Patients with GVHD not responding to first line therapy with corticosteroids remain at high risk of death due to severe infections or organ failure. Extracorporeal exposure of peripheral blood mononuclear cells to the photosensitizing agent 8-methoxypsoralen and ultraviolet A radiation has been shown to be effective in treatment of selected T-cell mediated diseases, including cutaneous T-cell lymphoma and rejection after organ transplantation. Extracorporeal photochemotherapy (ECP) is also a safe and efficacious adjunct therapy for both acute and chronic extensive GVHD with skin and visceral involvement and resistance to conventional immunosuppressive therapy. A multicenter randomized study should help define the impact of ECP in the treatment of GVHD and overall survival of these patients.

Graft vs Host Disease↗
PubMed2000

[Autologous stem cell transplantation in lymphomas and Hodgkin's disease].

High-dose therapy and autologous stem-cell transplantation (SCT) have been explored as a therapeutic option for patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) for the past years, in an effort to improve the long-term outcome of these patients. After publication of various phase I/II-studies the results of randomized trials in patients with aggressive NHL and HD have been reported. Based on these the conclusion can be drawn that autologous SCT significantly improves the outcome of patients in chemosensitive relapse of aggressive NHL and HD. In patients with aggressive NHL and a high or high-intermediate risk according to the International Prognostic Score, high-dose consolidation therapy may improve their prognosis. This could also be the case in patients with primary refractory HD and some low grade lymphoma such as mantle-cell lymphoma. However, there is a lack of randomized trials in patients with low grade NHL and, thus, the benefit of autologous SCT in these populations remains to be determined.

Blood Transfusion, Autologous↗
PubMed1999

Effect of high-dose melphalan and peripheral blood stem cell transplantation on renal function in patients with multiple myeloma and renal insufficiency: a case report and review of the literature.

Multiple myeloma with IgG-lambda monoclonal gammopathy and severe renal impairment with light-chain deposit disease was diagnosed in a 51-year-old man. Following conventional therapy with VAD (vincristine, adriamycin, dexamethasone) a partial remission was achieved. Peripheral blood stem cells (PBSC) were then collected following mobilization with cyclophosphamide and recombinant human granulocyte colony-stimulating factor and enriched for CD34-positive cells by immunoaffinity column. Fourteen months after diagnosis high-dose melphalan was given, followed by infusion of CD34-positive PBSC. Aside from mild oral mucositis and trigonitis, high-dose therapy was tolerated well. After he underwent PBSC transplantation his renal function improved, and the patient has been in in continuous complete remission for 1 year. Thus, high-dose chemotherapy can be safely administered to patients with multiple myeloma and severe renal impairment. Our findings confirm previous reports summarized in the current presentation.

Antineoplastic Agents, Alkylating↗
PubMed1999

Hematopoietic donor chimerism and graft-versus-myeloma effect in relapse of multiple myeloma after allogeneic bone marrow transplantation.

A large group of patients relapsing after allogeneic bone marrow transplantation (BMT) have obtained remission after infusion of leukocytes from their original donor, suggesting a graft-versus-myeloma effect. However, side effects such as graft-versus-host disease and myelosuppression are severe, and sometimes fatal, complications of this therapeutic approach. Previously we demonstrated that patients with leukemia who lack donor hematopoiesis in relapse after BMT experience severe and lasting aplasia after infusion of donor leukocytes. In two patients - one with extramedullary and one with marrow relapse after a sex-mismatched transplantation - we analyzed hematopoietic chimerism by cell sorting and bone marrow cultures. CD34-positive cells, CD4-CD8-positive cells, committed progenitors, and LTC-IC were of donor origin, as demonstrated by two-color fluorescence in situ hybridization (FISH). Additionally, in relapse complete donor T-cell chimerism was seen. In contrast, plasma cells were of recipient origin in the patient who had a relapse in the bone marrow. Both patients were treated with infusions of donor leukocytes from their original donor. Neither patient suffered myelosuppression, and one achieved a stable complete remission.

Adult↗
PubMed1999

Long-term follow-up of patients after related- and unrelated-donor bone marrow transplantation for chronic myelogenous leukemia.

Between January 1983 and December 1997, 88 patients (36 female, 52 male, median age 37 years, range 19-57) with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) at the University Hospital of Vienna. Sixty patients were in chronic phase, 18 in accelerated phase, and ten in blast crisis. Marrow donors were HLA-identical siblings for 64 patients (BM 58, PBSC 6), 2-antigen-mismatched related donors (RD) for two, HLA-identical unrelated donors (URD) for 17, and 1-antigen-mismatched URD for five. The median time from diagnosis to BMT was 22 months (range 2-91), and 63 patients had received prior interferon (IFN)-alpha therapy, 46 (73%) for more than 6 months. Conditioning therapy consisted of cyclophosphamide (CY) and total body irradiation (TBI) in 71 patients and CY and busulfan (BU) in 16. One patient received etoposide and TBI. For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) was given to 12 patients, MTX and cyclosporin A (CSA) to 67, CSA alone to four, and CSA and methylprednisolone to five. Durable engraftment was documented in 80 of 82 patients (98%). As of December 31, 1997, 52 patients (59%) were alive, 38 (58%) after sibling transplantation with a median observation time of 73 months and 14 (64%) after URD transplantation with a median observation time of 12 months. Probability of overall survival is 59%, for patients undergoing transplantation in chronic phase and 44% for patients undergoing transplantation in advanced stage CML. Probability of disease-free survival (DFS) after sibling and URD BMT is 55% and 59%, respectively. Ten patients (12%) experienced relapse of CML. Transplant-related mortality was 32% both after RD and after URD transplantation. Acute GVHD occurred in 53 of 80 evaluable patients (66%), consisting of grade III or IV in 14 patients (18%). Chronic GVHD developed in 40 of 63 eligible patients (63%), including extensive disease in 26 patients (41%). Thus, sibling and URD BMT offer high cure rates with acceptable toxicity to patients with CML.

Acute Disease↗