Search PubMed⌕ Search

Biomedical subjects

M Wiesneth

Publications and source records attributed to M Wiesneth.

At least 55 records · Page 3Linked to original sources
PubMed1993

Interferon-alpha and donor buffy coat transfusions for treatment of relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation.

Eight patients with chronic myeloid leukemia relapse after allogeneic BMT were treated with IFN-alpha and buffy coat transfusions (BC) of the bone marrow donor. The antileukemic effect of this treatment was directly demonstrated in 4 patients by the disappearance of Philadelphia chromosome-positive metaphases or the loss of detectable BCR-ABL transcripts by polymerase chain reaction. In 2 patients in whom cytogenetic or polymerase chain reaction analysis was not performed, a change in hemopoietic chimerism with recurrence of donor-type hemopoiesis was demonstrated. Two patients, both treated in advanced stages of hematological relapse after BMT, did not respond. However, severe side effects of the treatment were observed: graft-versus-host disease (GVHD) occurred in 5 patients. Two of these patients progressed to severe chronic GVHD and 1 patient ultimately died of this complication. GVHD occurred in 5 of the 6 responding patients; one patient responded without developing clinical symptoms of GVHD. Six patients developed bone marrow hypoplasia after IFN/BC treatment, and pancytopenia occurred in 4 patients. None of these 4 patients recovered spontaneously and 2 patients died of complications of pancytopenia (cerebral bleeding, infection). Our results demonstrate that treatment of chronic myeloid leukemia relapse with IFN and BC transfusions is highly effective in patients with relapse in chronic phase. The occurrence of GVHD and pancytopenia, however, resulted in a high treatment-associated morbidity and mortality. Whereas a response to treatment was observed in 1 patient without GVHD, indicating that GVHD and a graft-versus-leukemia effect may be clinically separable, bone marrow hypoplasia occurred in all responding patients.

Adult↗
PubMed1993

[Effect of preparation and preservation modality on thrombocyte quality].

In patients with acute leukemia, chemotherapy leads to subsequent aplasia-associated thrombocytopenia requiring the substitution of platelets to avoid and treat bleeding complications. A multitude of tests to assess the quality of platelet concentrates is available to date. In this study, we investigated the quality of platelet concentrates prepared by two different methods, preparation from platelet-rich plasma versus preparation from buffy coat, and stored under varying conditions, namely horizontal versus vertical rotation, by measuring the binding rate of corresponding antibodies to platelet membrane glycoproteins GPIb, GPIIb-IIIa, GPIa-IIa and GPIV using flow cytometry. Expression of platelet surface antigens was well maintained during platelet preparation and storage for 7 days. Preparation and storage modalities showed no significant effect on the expression of membrane glycoproteins. These results indicate that platelet function as represented by antibody binding is well maintained during platelet preparation and storage leading to sufficient hemostasis following transfusion.

Acute Disease↗
PubMed1993

[Thrombocyte substitution in hematologic patients].

Worldwide, platelet transfusions have increased substantially, especially in hematological patients. The prophylactic and therapeutic indications for platelet substitution as well as the choice of platelet preparation are discussed for patients with acute leukemia or aplastic anemia who need the highest platelet support. Here we present our current strategy, i.e., prophylactic transfusions with random platelets in acute leukemia and therapeutic transfusions with filtered random platelets in aplastic anemia patients only.

Acute Disease↗
PubMed1993

In vitro and in vivo depletion of T cells.

Transplant related mortality and relapse after bmt have a negative influence on the outcome of patients transplanted for acute leukaemia in first remission. Transplant related mortality includes graft-versus-host disease, infections and graft failure. To prevent gvhd and associated infections without increased graft rejection, a protocol of combined in vivo/ex vivo T-cell depletion (Campath IgG 20 mg i.v. for 5 days and Campath IgM T-cell depleted graft) with no further immunosuppression was initiated. Up to now 22 adult patients (median age 39 years, range 21 to 51) have been transplanted. One graft failure most probably due to persistent leukaemia, three acute gvhd (grade I) and no chronic gvhd occurred. Two patients relapsed after bmt and died. Two further patients died due to idiopathic interstitial pneumonitis and acute liver failure, respectively. Eighteen patients are alive in complete remission. With a median follow up of 13 months (1-30) the probability of survival is 78%, disease free survival is 80% and transplant related mortality is 10%. We compared these results with 3 historical control groups with different regimens of gvhd prophylaxis. 1. MTX group (n = 15): With a median follow up of 135 (115-147) months after bmt the probability of survival is 40%, disease free survival is 40% and transplant related mortality is 60% (mainly gvhd and infection). 2. Campath group (only ex vivo T-cell depletion n = 25): With a median follow up of 86 (62-102) months probability of survival is 52%, disease free survival is 43% and transplant related mortality is 36% (mainly rejection and infection).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1993

Graft rejection by a population of primed CDw52- host T cells after in vivo/ex vivo T-depleted bone marrow transplantation.

We investigated a case of graft rejection after in vivo/ex vivo T-depleted BMT in a patient who had received a HVG-matched, GVH one locus-mismatched, MLC-negative graft from his cousin. In vivo/ex vivo T cell depletion was performed with Campath 1G (CP1G) and Campath 1M (CP1M), respectively. We identified a failure of CP1G to eradicate a CDw52- (Campath-negative) host T cell population as the main cause of treatment failure. The analysis also suggests that significant host-versus-donor reactivity prior to transplant, as detected by limiting dilution analysis, also contributed to graft rejection. The rejecting T cells were bifunctional in that they showed cytotoxic activity and were capable of inhibiting haemopoietic progenitor growth by producing inhibitory lymphokines.

Adult↗
PubMed1993

Influence of graft-versus-host disease on the eradication of minimal residual leukemia detected by polymerase chain reaction in chronic myeloid leukemia patients after bone marrow transplantation.

To evaluate the remission quality of Philadelphia chromosome (Ph)-positive, BCR/ABL-positive CML patients after allogeneic bone marrow transplantation (BMT) we used the polymerase chain reaction (PCR) to detect BCR-ABL specific RNA in addition to Southern blotting, cytogenetic, and hematological investigation. Fifty-five bone marrow samples of 27 patients in clinical remission were studied by PCR, 0.5 to 99 months (median 8 months) after BMT. The median clinical follow-up of this cohort of patients is 24 months (1-109) after BMT. BCR-ABL transcripts could be detected in 16 out of 27 patients (59%). Risk factors for minimal residual leukemia (MRD) as defined by PCR were the kind of graft-versus-host disease (GvHD) prophylaxis (patients with T-cell-depleted grafts had a higher rate of MRD in comparison to patients treated with methotrexate/cyclosporin A) and the presence or absence of GvHD after BMT (patients without GvHD had a higher incidence of MRD than patients with GvHD). Moreover, the detection of minimal residual leukemia had prognostic significance. Out of 16 patients with minimal residual leukemia as detected by PCR, four patients relapsed clinically and two further cases relapsed cytogenetically. In contrast none of the patients lacking evidence of minimal residual leukemia relapsed. Serial PCR analysis may prove helpful in deciding about further therapeutic interventions (e.g. interferon therapy or adoptive immunotherapy) before leukaemic relapse becomes manifest after BMT.

Adult↗
PubMed1992

Parvovirus B19 infection and bone marrow transplantation.

Parvovirus B19 lytically infects erythroid progenitor cells and thereby causes cessation of erythropoiesis in infected individuals. Anemia develops only if red cell turnover is increased, as in patients with chronic hemolysis (transient aplastic crisis). In addition to transient marrow failure, B19 can cause chronic anemia and, rarely, pancytopenia in immunodeficient patients who are not able to mount an adequate immune response to clear the virus. Bone marrow transplantation, although causing significant immunosuppression, is rarely complicated by symptomatic B19 infection. This is probably due to effective passive immunotherapy by immunoglobulin infusions immediately after transplantation and early reconstitution of antibody responses after uncomplicated transplantation.

Adult↗
PubMed1992

Cryopreserved autologous platelet transfusions in alloimmunized patients with acute leukemia.

Autologous platelets of 5 alloimmunized patients with acute leukemia in remission were cryopreserved with 5% dimethylsulfoxide in liquid nitrogen and retransfused in the following therapy-induced thrombocytopenic phase. The mean platelet recovery after freezing, thawing and washing was 85 +/- 6%. The mean corrected 1-hour increment in platelet counts was 11 (4-27) x 10(9)/l, i.e. 61% in comparison with fresh platelet transfusions in other patients. In vivo function of frozen platelets was documented by improvement of the posttransfusion bleeding time. Cryopreserved autologous platelets function hemostatically and can be used even for completely refractory patients and thus permit curative antileukemic therapy.

Adult↗
PubMed1992

ABO-incompatible bone marrow transplantation.

In the past 10 years 201 HLA-identical bone marrow transplantations (BMT) were performed with major ABO incompatibility in 41 (20%) and minor ABO incompatibility in 35 (18%) patients. ABO compatibility between donor and recipient showed no influence on granulocyte and platelet recovery after BMT. Erythrocyte reconstitution was significantly (p < 0.01) delayed for about 1 week in major ABO-incompatible BMT. In addition, a pure red cell aplasia lasting for 2-5 months occurred in 6 out of 21 blood group 0 patients who received transplants of group A. The rate of graft rejection, incidence of graft-versus-host disease as well as the leukemic relapse rate were similar in ABO-compatible and ABO-incompatible BMT. The probability of a 10-year survival after BMT is independent of ABO compatibility between donor and recipient.

ABO Blood-Group System↗
PubMed1991

Comparison of plateletpheresis with two different cell separators using 100 identical donors.

Plateletpheresis with the cell separator COBE Spectra and Fenwal CS 3000 was compared in 100 identical donors. The Spectra was significantly superior with regard to collection efficiency (53% vs. 42%, p less than .001) and leukocyte contamination of the platelet products (.1 x 10(8) vs. 1.4 x 10(8), p less than .001). Additionally, it offers a selectable volume of the concentrate and a better control of the ACD infusion. The Spectra standard procedure needs more ACD, resulting in more citrate dependent donor reactions (5% vs. 1%). In conclusion, the Spectra system shows a more efficient and pure platelet separation compared with the CS 3000.

Adolescent↗
PubMed1990

Graft failure after T cell-depleted bone marrow transplantation: clinical and immunological characteristics and response to immunosuppressive therapy.

We have investigated the clinical and immunological features of 10 cases of graft failure after T cell-depleted marrow transplantation. In addition, the hypothesis that the process of graft failure can be reversed by immunosuppressive therapy with cyclosporin + steroids +/- monoclonal antibodies was tested in seven patients. Early graft failures (before day 50) presented a uniform clinical syndrome with a host T lymphocytosis preceding the loss of the graft. In the majority of cases of late graft failure (after day 50) a syndrome comprising delayed granulopoietic regeneration, fever of unknown origin and abdominal symptoms was observed. Surface marker analysis of peripheral blood and bone marrow lymphocytes implicated a population of CD3+, CD8+, DR+ host T lymphocytes with a frequent co-expression of the Leu7+ antigen in the pathogenesis of graft failure. Immunosuppressive therapy reversed graft failure in the three cases of incomplete graft failure (i.e. with residual reticulocytes) and failed in the four cases of complete graft failure (i.e. no residual reticulocytes).

Antibodies, Monoclonal↗
PubMed1989

Evaluation of remission state in chronic myeloid leukemia patients after bone marrow transplantation using cytogenetic and molecular genetic approaches.

The remission state of 13 Philadelphia positive chronic myeloid leukemia patients was studied after bone marrow transplantation (BMT) by cytogenetic and Southern blot analysis of the breakpoint cluster region (BCR) gene. Eight of 13 patients showed neither clinical nor genetic evidence of residual disease. In two patients hematological relapse was confirmed by cytogenetic and molecular analysis. Evidence for residual leukemic cells in otherwise complete remission was obtained genetically in three patients. One of the latter cases revealed BCR rearrangement despite negative cytogenetic findings, while in another patient cytogenetic relapse was observed without demonstrable rearrangement within the major BCR. Our results may indicate that cytogenetic and molecular genetic methods complement rather than replace each other for the detection of residual CML cells after BMT.

Adolescent↗
PubMed1988

[Bone marrow transplantation as therapy in chronic myeloid leukemia].

Between April 1982 and December 1986, HLA-identical bone marrow transplantations were performed on 25 patients with Philadelphia chromosome-positive chronic myelocytic leukaemia (CML), 18 in the chronic phase, 7 in acceleration or blast crisis. Twelve of the 18 patients (67%) in the chronic phase are still alive a median period of 570 days after transplantation, but only two of the seven (29%) in acceleration or blast crisis a median period of 227 days after transplantation (P less than 0.025). The duration of the chronic phase was of great importance for survival after transplantation: 86% of patients in the chronic phase for less than two years survived, but all patients in the chronic phase for over two years died (P less than 0.001). CML relapses occurred in one patient in a late chronic phase and in two in an advanced stage of the disease. These results confirm the unfavorable outcome of bone marrow transplantation in the accelerated phase or blast crisis, as well as in the late chronic phase. Since at present there are no reliable risk factors for the occurrence of acceleration or blast crisis, bone marrow transplantation should be undertaken as early as possible in the chronic phase of CML.

Adolescent↗
PubMed1988

T-cell depletion versus methotrexate as GvHD-prophylaxis in allogeneic bone marrow transplantation for leukaemia.

Graft-versus-host disease (GvHD) prophylaxis using methotrexate (23 patients) and T-cell depletion of the graft (40 patients) was compared in 63 allogeneic bone marrow transplantations (BMT) for leukaemia. T-cell depletion significantly reduced (p = 0.001) the incidence of GvHD from 68% to 11% and the GvHD-associated mortality from 79% to 5%. Actuarial disease-free survival for low-risk patients (57% with T-cell depletion and 47% with MTX) was not significantly improved, due to graft failure and possibly due to a higher leukaemic relapse rate after T-cell depletion. Prevention of graft failure after T cell-depleted BMT is essential and could also reduce the risk of leukaemic relapse by improved engraftment.

Acute Disease↗
PubMed1988

Norfloxacin for prevention of bacterial infections during severe granulocytopenia after bone marrow transplantation.

48 patients treated with bone marrow transplantation (BMT) received the quinolone norfloxacin (NOR) in a total decontamination (TD-NOR, n = 36) or selective decontamination (SD-NOR, n = 12) regimen and were compared with a historical control group of 48 BMT patients receiving oral non-absorbable antibiotics (TD-NAA, n = 31 and SD-NAA, n = 17). 17/36 patients (47%) of group TD-NOR and 16/31 patients (52%) of group TD-NAA remained free of febrile episodes and infections. 4/12 patients (33%) of group SD-NOR and only 1/17 patients (6%) of group SD-NAA remained free of fever and infections. The use of norfloxacin in selective decontamination resulted in a statistically significant lower incidence of fever days than in patients receiving SD-NAA (p less than 0.001). These data suggest that norfloxacin may replace non-absorbable antibiotics in total and in selective decontamination regimens used for infection prophylaxis in BMT recipients.

Adolescent↗
PubMed1988

Concentration of bone marrow mononuclear cells for in vitro treatment and AB0-incompatible transplantation: a rapid and reproducible procedure using the haemonetics V50 cell separator.

Forty-nine allogeneic and 14 autologous bone marrow grafts were processed with the Haemonetics V50 cell separator (Haemonetics Corp., Braintree, USA) for in vitro treatment with antibodies and cryopreservation respectively. The concentration of hemopoietic progenitor cells was performed without any sedimentation or density gradient agents. The recovery is given in percent (mean +/- sd) of the original marrow values: mononuclear cells (MNC) 74 +/- 10%, polymorphonuclear cells (PMC) 48 +/- 17%, red blood cells (RBC) 12 +/- 5%, granulocyte/monocyte progenitors (CFU-GM) 83 +/- 36%, and erythroid progenitors (BFU-E) 78 +/- 38%. The recovery of nucleated cells (NC) was 90 +/- 13% and the viability 82 +/- 11% after cryopreservation. The technique described provides a simple, rapid and efficient preparation of large bone marrow volumes for in vitro treatment and AB0-incompatible transplantation.

Blood Grouping and Crossmatching↗
PubMed1987

Cytomegalovirus (CMV) infections in patients receiving CMV-IgG-hyperimmunoglobulin prophylaxis after bone-marrow transplantation.

Conditioning therapy with aggressive chemotherapy and irradiation induces a state of transient combined immunodeficiency in bone-marrow transplant recipients. This promotes the occurrence of severe cytomegalovirus (CMV) infections, the most frequent lethal complication after bone-marrow transplantation (BMT) at present. Forty-four BMT recipients received CMV-IgG-hyperimmunoglobulin for CMV prophylaxis intravenously. The efficacy of this prophylaxis and possible risk factors for the occurrence of CMV-induced interstitial pneumonia (IP) were analyzed. Risk factors for the promotion of a CMV-IP were: additional immunosuppressive therapy after BMT, CMV-positive serostatus of the recipient, CMV-seropositive granulocyte transfusion, CMV infection immediately prior to BMT, and HLA-haploidentical BMT. In this study the incidence of graft-versus-host disease was low and was not associated with the incidence of CMV infections. The use of T-cell-depleted grafts did not result in increased CMV infections or IP and may possibly have improved the immunological reconstitution.

Adolescent↗