Biomedical subjects

H T Greinix

Publications and source records attributed to H T Greinix.

At least 19 recordsLinked to original sources

PubMed2006

Assessing the potential role of photopheresis in hematopoietic stem cell transplant.

The First International Symposium on Photopheresis in Hematopoietic Stem Cell Transplantation was held in Vienna, Austria with an educational grant from Therakos Inc. from 25 May to 27 May 2005. Three general issues were addressed: (1) pathophysiology of graft-versus-host disease (GvHD), (2) induction of immune tolerance and the immunology of phototherapy and (3) current standard treatment and prevention strategies of acute and chronic GvHD and the use of extracorporeal photopheresis (ECP). The objectives of the meeting were to open a dialogue among leading researchers in photobiology, immunology, and hematopoietic stem cell transplantation; foster discussions and suggestions for future studies of the mechanism of action of ECP in acute and chronic GvHD; and promote collaboration between basic scientists and clinicians. As can be seen from the summaries of the individual presentations, important advances have been made in our understanding of GvHD, including the use of photoimmunology interventions and the development of robust model systems. It is our expectation that data from photoimmunology studies can be used to generate hypotheses in animal models that can further define the mechanism of action of ECP and help translate the findings to clinical trials of ECP for the prophylaxis and treatment of both chronic and acute GvHD.

Graft vs Host Disease↗

PubMed2005

Impact of HLA class I high-resolution mismatches on chronic graft-versus-host disease and survival of patients given hematopoietic stem cell grafts from unrelated donors.

There is consensus that matching of unrelated donors (URD) and patients for HLA class II alleles improves the outcome of hematopoietic stem cell transplantation (HSCT). However, the significance of HLA class I allelic mismatches for transplant outcome is under discussion and reports on long-term effects like chronic graft-versus-host disease (GVHD) are rare. Thus, we investigated the association of human leukocyte antigen (HLA) class I allele mismatches and outcome in 144 patients given HSCT from URD who were matched for HLA-DRB1, DRB3/4/5, and DQB1 alleles. The risk of chronic GVHD was significantly increased in patients with class I mismatched donors, the mismatch either detected by low- or high-resolution typing. A single HLA class I allele mismatch significantly increased the risk of chronic GVHD in multivariate analysis. Overall survival was significantly reduced in patient/donor pairs with more than one-allele class I mismatch. Thus, selection of unrelated donors for transplantation should be based on high-resolution HLA class I typing.

Adolescent↗

PubMed2004

Diffuse large B-cell lymphomas with plasmablastic/plasmacytoid features are associated with TP53 deletions and poor clinical outcome.

To define reproducible criteria for subgroups of diffuse large B-cell lymphomas (DLBCL), including lymphomas with plasmablastic/plasmacytoid features (PB/PC-Fs), we investigated 66 DLBCL; the samples were categorized as either centroblastic (CB), immunoblastic (IB) or PB/PC-F applying standardized morphologic criteria. Blinded specimens were reviewed by three independent pathologists. The final consensus classification included 44 CB (67%), seven IB (10%) and 15 PB/PC-F (23%). The interobserver agreement between two centers (Vienna, Würzburg) was 93.5%. Most PB/PC-F were CD20+, cIgM+, MUM-1+, CD138+/-, bcl-6-, corresponding to an activated B-cell phenotype. Immunoglobulin-V(H) gene mutation analysis was consistent with a germinal or postgerminal center-cell origin. By fluorescence in situ hybridization analysis, 11/13 (85%) PB/PC-F had a monoallelic TP53 deletion. The pretreatment characteristics of patients with PB/PC-F included a tendency for more B symptoms, extranodal disease and a higher IPI. Importantly, PB/PC-F were resistant to standard chemotherapy (complete remission rate 47%, relapse rate 71%) and even autologous stem-cell transplantation. The median overall survival (OS) (14 months, P<0.002) and disease-free survival (6 months, P=0.02) were significantly shorter compared to patients with CB and IB. The OS difference was pronounced within the low and low-intermediate IPI risk group (P<0.001). Our data indicate a strong association of plasmablastic/plasmacytoid morphology with TP53 deletions, poor response to chemotherapy and short survival.

Adult↗

PubMed2004

Impact of cytogenetics on the prognosis of adults with de novo AML in first relapse.

Karyotype is an important prognostic factor in patients with newly diagnosed acute myeloblastic leukaemia (AML). The prognostic value of cytogenetics on the outcome of patients with AML in relapse has not yet been well defined. We analysed the clinical outcome of 152 patients with de novo, chemotherapy-treated AML in first relapse according to the cytogenetic classification of the United Kingdom Medical Research Council. The rate of second complete remission (CR) (88, 64 and 36%) and the probability of survival at 3 years (43, 18 and 0%) were significantly different between the favourable, intermediate and adverse cytogenetic risk groups, respectively. Compared to the favourable group, the relative risk (RR) of death (multivariate analyses) was 2.6 (confidence interval (CI): 1.5-4.4, P<0.001) for the intermediate and 3.7 (CI: 1.7-7.9, P=0.001) for the adverse group. The prognostic value of the duration of first CR was confirmed (RR of death: 2.0 (CI: 1.0-4.0) for each additional year in first CR), whereas the FLT3 mutation obtained at diagnosis did not markedly influence the outcome of patients with AML in relapse. In conclusion, our results indicate that both karyotype and the duration of first CR are independent prognostic factors for patients with de novo AML in first relapse.

Acute Disease↗

PubMed2004

RT-PCR and FISH analysis of acute myeloid leukemia with t(8;16)(p11;p13) and chimeric MOZ and CBP transcripts: breakpoint cluster region and clinical implications.

The translocation t(8;16)(p11;p13) is associated with acute myeloid leukemia displaying monocytic differentiation (AML FAB M4/5) and fuses the MOZ (also named MYST3) gene (8p11) with the CBP (also named CREBBP) gene (16p13). Detection of the chimeric RNA fusions has proven difficult; only three studies have described successful amplification of the chimeric MOZ-CBP and CBP-MOZ fusions by reverse transcriptase-polymerase chain reaction (RT-PCR). We analyzed four cases of AML M4/5 with t(8;16)(p11;p13) by RT-PCR and fluorescence in situ hybridization (FISH) and characterized the reciprocal RNA fusions from three cases. We cloned both genomic translocation breakpoints from one case by long-range PCR and successfully applied RT-PCR to monitor minimal residual disease (MRD) between clinical complete remission and relapse. In three cases, the genomic breakpoints occurred in MOZ intron 16 and CBP intron 2. In one case, no fusion transcript was detected. The available data suggest clustering of t(8;16)(p11;p13) breakpoints in these introns leading to reciprocal in-frame MOZ exon 16/CBP exon 3 and in-frame CBP exon 2/MOZ exon 17 chimeric transcripts in the majority of cases. The described RT-PCR strategy may be valuable both for the routine detection of the t(8;16)(p11;p13) as well as for monitoring of MRD in this prognostically unfavorable patient group.

Acetyltransferases↗

PubMed2003

Early and late gastrointestinal complications after myeloablative and nonmyeloablative allogeneic stem cell transplantation.

Upper and lower gastrointestinal symptoms are major and serious complications after stem cell transplantation. Their main causes are gastrointestinal graft-versus-host disease (GVHD), infections, toxicity, or preexisting gastrointestinal diseases. The clinical presentation of each disease is nonspecific. The diagnostic procedure for this study included physical exam, stool cultures, endoscopy with biopsies, and abdominal computed tomography (CT). The study was designed prospectively with consecutive patients and performed at our institution in a clinical stem cell transplantation setting. Between January 1996 and September 2001, we analyzed 42 consecutive patients who had been admitted at our institution for gastrointestinal complaints after allogeneic stem cell transplantation for hematologic diseases. Diagnostic procedures revealed in decreasing order: GVHD (62%), gastritis/esophagitis (19%), cytomegalovirus (CMV) enteritis (11%), bacterial enteritis (6%), and toxic mucosal damage (2%). CT showed unspecific findings. Gastrointestinal GVHD and infectious colitis accounted for the majority of gastrointestinal complications after allogeneic stem cell transplantation in our patient population. The diagnosis was mainly based on endoscopically obtained biopsies.

Adult↗

PubMed2003

Successful immunotherapy in early relapse of acute myeloid leukemia after nonmyeloablative allogeneic stem cell transplantation.

We report on a 35-year-old woman who underwent allogeneic stem cell transplantation (SCT) in second complete remission (CR) of acute myeloid leukemia (AML) after reduced-intensity conditioning with fludarabine and 2 Gy of total body irradiation. For graft-versus-host disease (GVHD) prophylaxis, cyclosporin A (CsA) and mycophenolate mofetil (MMF) were given. On day 27 after SCT complete hematological remission and donor chimerism was documented. However, in CD34(+) bone marrow cells 28% of recipient hematopoiesis persisted. On day +59 leukemic relapse occurred. After discontinuation of CsA and onset of GVHD, complete donor chimerism and hematological CR were achieved which has been maintained for 14 months.

Acute Disease↗

PubMed2003

Influence of human platelet antigen match on the success of stem cell transplantation after myeloablative conditioning.

Mismatches between donor and recipient for human platelet antigens (HPA) may affect the success of transplantation due to: (a) serving as minor histocompa-tibility antigens and therefore render recipients at risk for graft-versus-host disease (GvHD), (b) inhibition of thrombopoiesis due to platelet antibodies. We therefore evaluated the occurrence of GvHD and need of platelet support by prospective analysis of donor-recipient pairs (n=53) for HPA-1, -2, -3, and -5 allotypes and screening for platelet antibodies prior to transplantation and in weekly intervals until day 100 after transplantation. Neither the incidence of GvHD nor the onset of thrombopoiesis, nor the CCI after platelet transfusions, nor the frequency of platelet transfusions was affected by HPA mismatches. Settings of homozygous donors vs heterozygous recipients or homozygous recipients vs heterozygous donors were not associated with any adverse effects on the outcome of the transplantation. Thus, the HPA-match does not affect the success of transplantation.

Adolescent↗

PubMed2002

Streptococcus pneumoniae mycotic aortic aneurysm after allogeneic bone marrow transplantation.

BACKGROUND: Streptococcus pneumoniae (SP) is a common cause of community-acquired pneumonia and accounts for up to 30% of all cases of pneumonia. Patients with chronic graft-versus-host-disease (GvHD) after allogeneic bone marrow transplantation (BMT) have a high susceptibility to SP infections. So far, mycotic aneurysm resulting from SP has not been reported after BMT. METHODS: We report on a patient with extensive, chronic GvHD who developed low back pain 22 months after allogeneic BMT. RESULTS: Computed tomography of the abdomen displayed mycotic, saccular aneurysmatic enlargement of the infrarenal aorta, with leakage of contrast medium into the aneurysm. The aneurysm was resected, and the defect was closed with an autologous patch from the internal iliac artery. Bacteriologic samples from the abscess grew SP. The patient recovered uneventfully. CONCLUSIONS: This observation confirms the importance of pneumococcal prophylaxis after BMT and suggests that an aggressive diagnostic approach should always be considered in patients with chronic GvHD, even if they present with nonspecific symptoms.

Adult↗

PubMed2002

Autologous blood stem cell transplantation in refractory systemic lupus erythematosus with severe pulmonary impairment: a case report.

For patients with severe forms of autoimmunity, including systemic lupus erythematosus (SLE), purging autoreactive T cells from the immune repertoire by transplanting autologous hematopoietic stem cells (ASCT) is a therapeutic option. We describe an 18-year-old woman with SLE who had been treated with corticosteroids, azathioprine, cyclophosphamide (CYC), and immunopheresis for 4 years, during which time mechanical ventilation for lupus pneumonitis had been repeatedly required. After the patient was conditioned by administration of CYC and antithymocyte globulin, a total of 8.87 x 10(6) purified CD34+ cells per kg of body weight was infused. Hematopoietic regeneration was observed within 9 days. Twenty-one months after ASCT, the patient continues to be in complete clinical remission, with no signs of SLE-related disease activity and without any immunosuppressive medications. Her pulmonary function has returned to normal. Although a longer followup is required for assessment of the durability of response, the patient's course indicates that ASCT may be a way to reinduce tolerance in patients with SLE.

Adolescent↗

PubMed2002

Long-term outcome and quality of life of patients who are alive and in complete remission more than two years after allogeneic and syngeneic stem cell transplantation.

We assessed long-term outcome in 155 patients who had undergone an allogeneic/syngeneic stem cell transplant (SCT) and were in complete remission for more than 2 years after transplant. Probability of late transplant-related mortality was 6%, and affected only patients with chronic graft-versus-host disease (cGVHD). Thirteen percent of patients experienced relapse. Overall survival projected at 10 and 15 years was 83% and 76%, respectively. Secondary malignancies occurred in two patients, 7.5 and 11 years after SCT. Three female and four male patients parented children 19 to 84 months after SCT. Quality of life (QoL) was assessed in a cross-sectional study by the means of a 30-item questionnaire (QLQ-C30) of the EORTC. The questionnaire was sent to 127 patients remaining alive and answered by 106 patients. Seventy-three percent reported a good to very good QoL within 5 years after SCT and 78% after this time point. However, patients with cGVHD had significant impairment of physical, role and social functioning and only 60% of them were fit for work. These results from long-term survivors show that high cure rates with good to very good QoL can be achieved by allogeneic or syngeneic SCT.

Adolescent↗

PubMed2002

Positron emission tomography with [18F]2-fluoro-D-2-deoxyglucose (FDG-PET) predicts relapse of malignant lymphoma after high-dose therapy with stem cell transplantation.

We have determined the predictive value of [18F]2-fluoro-2-deoxy-glucose (FDG-PET) in patients with Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) scheduled for high-dose therapy with stem cell transplantation (HDT/SCT). Inclusion criteria were the presence of an FDG-PET scan after chemotherapy (ChT) within 8 weeks prior to HDT/SCT and available follow-up data. Sixteen patients (10 NHL and six HD) were observed during a follow-up period of 4 to 28 months (median 13 months). Before SCT, five patients had a negative PET, three were weakly positive, two moderately positive, and six strongly positive. None of the five patients with a negative PET before HDT/SCT relapsed and two of three patients with a weakly positive scan are still in remission after HDT/SCT. Of eight patients with a moderate or high positive PET before HDT/SCT, seven relapsed and one died of early HDT/SCT related complications (P< 0.01). Three of eight relapsing patients died of lymphoma 5 to 10 months after SCT and in one additional patient not responding to HDT/SCT, the main cause of death was chronic toxicity 4 months after transplantation. After 12 months, in PET-negative patients the overall and relapse-free survival was 100%, in PET-positive patients 55% and 18%, respectively. In NHL, two patients with negative PET, but with an age-adjusted international prognostic index (AaIPI) of 2 and one with AaIPI = 1 are still in remission. In the seven PET-positive subjects, one patient with AaIPI = 0, three with AaIPI = 1, and two with AaIPI = 2 relapsed. We conclude that FDG-PET is accurate in the prediction of relapse prior to HDT/SCT in patients with lymphoma. It provides additional information when compared with the AaIPI.

Adult↗

PubMed2002

DLI or second transplant.

We analyzed toxicity and efficacy of second allogeneic hematopoietic stem cell transplantation (HSCT) or donor lymphocyte infusions (DLI) in 66 patients relapsing with acute myeloid leukemia (n = 15), acute lymphoblastic leukemia (n = 5), chronic myeloid leukemia (n = 14), non-Hodgkin's lymphoma (n = 14), myeloma (n = 8), myelodysplastic syndrome (n = 8), and metastatic renal cell carcinoma (n = 2). Forty-one patients were given second HSCT and 25 DLI. Sixteen patients (39%) are alive and disease-free after a second HSCT including 13 who had received nonmyeloablative conditioning. Thirteen patients (52%) are alive after DLI with mainly chronic myeloid leukemia patients in continuous complete remission. Relapse after HSCT is still a challenging situation and further studies to improve outcome of these patients are warranted.

Adolescent↗

PubMed2001

Successful lung transplantation for bronchiolitis obliterans after allogeneic marrow transplantation.

BACKGROUND: Bone marrow transplantation (BMT) is an established therapy for a variety of hematological diseases with curative potential. However, despite improvements in supportive care, pulmonary complications remain a significant cause of morbidity and mortality. METHODS: We report on a patient who received a double lung transplantation (LTX) for therapy-refractory bronchiolitis obliterans (BO) associated with extensive chronic graft-versus-host disease (GVHD) after allogeneic BMT. RESULTS: At present, 38 months after BMT and 23 months after LTX, the patient is in complete hematological and cytogenetic remission and without signs of respiratory distress. CONCLUSIONS: This case illustrates that lung transplantation could be a therapeutic option in selected patients with BO after allogeneic BMT that is associated with extensive chronic GVHD and who are refractory to conventional immunosuppressive therapy.

Adult↗

PubMed2001

Energy and substrate metabolism in patients with chronic extensive graft-versus-host disease.

BACKGROUND: Allogeneic stem cell transplantation is frequently complicated by graft-versus-host disease (GVHD). Weight loss is one of the characteristic features of GVHD. The etiology of weight loss in GVHD is not completely understood. METHODS: We measured resting energy expenditure (REE) and substrate oxidation rates by indirect calorimetry in patients with stable chronic extensive GVHD under immunosuppressive therapy (n=13) and sex-, age-, height-, and weight-matched healthy controls (n=13) in order to evaluate metabolic changes in these patients. Measurements were done on day 518+/-261 after allogeneic stem cell transplantation in the postabsorptive state. Serum concentrations of glucagon, norepinephrine, tumor necrosis factor-alpha, interleukin-6, and free fatty acids were determined. RESULTS: Patients showed a maximum weight loss of 22% during their course of GVHD; nevertheless, they regained 15% of total body weight (TBW) during successful treatment of GVHD. Indirect calorimetry showed an increase in REE per kilogram of TBW (patients, 21.8+/-3.1 kcal/kg TBW/day; controls, 19.9+/-2 kcal/kg TBW/day; P<0.05). Respiratory quotient (patients, 0.79+/-0.04, controls, 0.86+/-0.04; P<0.005) and non-protein respiratory quotient (0.78+/-0.05 and 0.87+/-0.05, respectively; P<0.005) were decreased in patients. GVHD patients had elevated serum glucagon and norepinephrine concentrations, whereas tumor necrosis factor-alpha and interleukin-6 were in the normal range. CONCLUSIONS: Patients with chronic extensive GVHD show an increase in REE and alterations in fat and carbohydrate oxidation rates. These changes seem to be the result of increased action of glucagon and norepinephrine.

Adult↗

PubMed2001

CMV monitoring after peripheral blood stem cell and bone marrow transplantation by pp65 antigen and quantitative PCR.

We prospectively monitored 74 consecutive allogeneic and 50 autologous patients after bone marrow/stem cell transplantation from May 1999 to October 2000 at our institution with quantitative CMV PCR and pp65 antigen assay once weekly from conditioning therapy to days 120 and 80 after transplantation, respectively. Written informed consent was obtained from every patient. CMV prophylaxis consisted of acyclovir during transplant. Additionally all patients received only platelet products from CMV-negative donors. In the case of CMV infection preemptive therapy with gancyclovir was applied. In the case of CMV disease high-dose immunoglobulin was given as well. In the allogeneic setting 16 out of 74 (22%) patients developed a positive PCR. Seven episodes of a positive pp65 antigen assay occurred in six allograft recipients. In the autologous setting no positive assay was found during the whole observation period. Additionally, in 6/16 patients a lymphoproliferative assay was performed during CMV infection. Two patients showed a positive (15 and 5.4) and four a negative (2,1.6,1,1.8) stimulation index.

Adolescent↗

PubMed2001

Treatment of leukemic relapse after allogeneic stem cell transplantation with cytotoreductive chemotherapy and/or immunotherapy or second transplants.

We analyzed toxicity and efficacy of chemotherapy (CT) or second stem cell transplantation (SCT) and/or immunotherapy defined as stop of immunosuppression (IS) or donor leukocyte infusion (DLI) in 47 patients relapsing with acute leukemia. Ten patients received no treatment and 14 patients were treated with CT only. In 12 patients IS was stopped and three of them received additional CT. Five patients received DLI after CT as consolidation and one patient as frontline therapy. Five patients received a second SCT. Median overall survival after relapse was 2 months for the untreated patients, 2 months for patients receiving CT only, 2 months in patients after cessation of IS, 17 months in DLI treated patients and three months in patients receiving a second SCT. Fourteen patients achieved remission after relapse. Two with CT (2, 2 months), three with SI (3, 19, 19+ months), six with DLI (3, 8, 9, 14, 20, 36 months) and three with second SCT (2, 4, 6 months). Conventional CT was able do re-establish donor hematopoiesis and patients achieving remission showed a significantly better survival than patients with refractory disease. Patients who were brought into remission by DLI or cessation of IS had a significantly better survival than patients who achieved remission with CT alone or a second SCT. We conclude that a selected group of patients achieving remission with regeneration of donor hematopoiesis following CT might benefit from immunotherapy as consolidation.

Adult↗

PubMed2001

Long-term clinical and molecular remission after allogeneic stem cell transplantation (SCT) in patients with poor prognosis non-Hodgkin's lymphoma.

From 1987 to 1999 35 patients with poor prognosis non-Hodgkin's lymphoma (NHL) underwent allogeneic stem cell transplantation (SCT) at the University Hospitals of Vienna and Graz. Initial biopsy specimens were reclassified according to the Revised European-American Classification of Lymphoid Neoplasms (REAL). All patients surviving 28 days engrafted. Twenty-eight of them (93%) attained clinical remission. At the last follow-up 14 patients were alive and disease-free at a median of 5.0 (range, 2.3-12.9) years after allogeneic SCT. The actuarial overall survival is 35%. Five patients relapsed 1.8 to 27.6 months after transplant, the probability of relapse is 23%. Of the 21 deaths following SCT, seven were due to relapse/refractory disease and 14 due to transplant-related causes. The probability of treatment-related mortality is 48%. After SCT, minimal residual disease (MRD) was monitored by polymerase chain reaction (PCR) in seven patients with a BCL-2/IgH translocation and in 13 with a clonal immunoglobulin heavy chain (IgH) rearrangement. All 20 patients attained clinical remission rapidly and converted to PCR negativity. In the follow-up nine of these patients are in long-term clinical and molecular remission, six PCR-negative patients died of transplant-related causes and five patients relapsed. In summary, allogeneic stem cell transplantation has a curative potential for patients with refractory and recurrent non-Hodgkin's lymphoma. In our series long-term disease-free survival was associated with molecular disease eradication after SCT. Treatment-related mortality rate was high, thus earlier referral of selected patients to allogeneic SCT should be considered.

Adult↗