Biomedical subjects

B Hertenstein

Publications and source records attributed to B Hertenstein.

At least 73 records · Page 4Linked to original sources

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

Single-drug oral antibacterial prophylaxis with ofloxacin in BMT recipients.

We evaluated the efficacy and safety of a new oral fluoroquinolone, ofloxacin (200 mg twice daily), as antibacterial prophylaxis after BMT in a non-comparative prospective study of patients nursed in either LAF plastic isolators or HEPA filtered single rooms. Of the 101 evaluable patients who were neutropenic (< 500 x 10(6)/l) for a median duration of 20 days, 92 (91%) had febrile episodes of varying length and causes. Infections were documented in 34 patients, of whom 14 had proven bacterial infection (13 with bacteremia and one with pneumonia). Mortality rate within 6 weeks after transplant was 6%. Only one patient died from bacterial infection. Univariate analysis using an array of potentially prognostic factors including the type of isolation was not helpful in identifying significant variables for predicting the development of documented infection. Tolerance was excellent. Oral ofloxacin was associated with a relatively low incidence of documented bacterial infection and related mortality, although it did not obviate the need for frequent empiric antimicrobial therapy due to a high incidence of febrile episodes.

Administration, Oral↗

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

Thrombotic thrombocytopenic purpura in early pregnancy with maternal and fetal survival.

Thrombotic thrombocytopenic purpura (TTP) is a hematologic disorder which is clinically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurologic symptoms, and cardiac and renal involvement. The pathogenic mechanisms of this disease are poorly understood. It is well known that TTP is associated with pregnancy and that prognosis for the mother and child is poor. We present the first case of a severe TTP diagnosed in the first trimester of pregnancy (13th week of gestation) with maternal survival and birth of a healthy child which required continuous and intensive treatment with plasma therapy until delivery. During a period of 24 weeks several attempts to discontinue plasma therapy failed because of continuous active disease, and it became evident that plasma infusions were not as effective as plasma exchanges. The fact that the patient entered into remission soon after delivery of a healthy child by cesarean section in the 37th gestational week shows that in this case pregnancy activated an unknown factor which does not cross the placenta and which can be removed by plasmapheresis.

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↗

PubMed1992

[Phases in the rehabilitation of male and female bone marrow transplant patients].

Teamwork is essential when investigating the long-term adoption of such medical intervention that are highly demanding on patients, physicians and nursing staff. Bone marrow transplantation represent such an intervention for a series of well defined hematological diseases. The contribution demonstrates the multiple perspective approach of the Ulm team. A case report illustrates the multiplicity of clinical issues. The state of research allows the sketching of a process model on rehabilitation.

Adaptation, Psychological↗

PubMed1990

Aggressive polychemotherapy for acute myelofibrosis.

Acute myelofibrosis is a rare and still ill-defined disease. Based on morphological observation, immunophenotyping and ultrastructural analysis, we support the assumption that acute myelofibrosis is a malignant disorder mainly of the megakaryocytic lineage and is closely related to acute megakaryocytic/blastic leukaemia. Consequently, the 11 patients reported here were treated with aggressive polychemotherapy with combinations including daunorubicin and cytosine arabinoside and 6-thioguanin or VP16-213. 4 complete remissions, 2 partial remissions and 1 minor response were observed. Duration of aplasia was not significantly prolonged. These findings indicate that the use of aggressive polychemotherapy is feasible in acute myelofibrosis and results in a significant number of remissions.

Acute Disease↗

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↗

PubMed1988

Fractionated total body irradiation and high-dose VP 16-213 followed by allogeneic bone marrow transplantation in advanced leukemias.

Thirty-eight patients (median age, 21 years) with acute nonlymphoblastic leukemia (ANLL) (17 patients), acute lymphoblastic leukemia/lymphoma (ALL) (18 patients), chronic myelogenous leukemia (two patients), and refractory anemia received allogeneic bone marrow transplants from HLA-identical sibling donors or a one-antigen-mismatched brother (one patient) after a preparatory regimen consisting of fractionated total body irradiation and high-dose VP 16-213 (60 to 70 mg/kg body weight). Of the 33 patients with acute leukemia who received grafts from HLA-identical donors, three patients with ANLL received transplants in first remission and one patient with standard-risk ALL received a graft while in second remission. All other patients were in more advanced stages of their disease or exhibited other high-risk features. At the time of analysis, 20 of the 33 patients were alive, with 19 of them remaining in continued complete remission for 6 to 35 months (median, 18 months). The 3-year actuarial disease-free survival rate of 56.6% +/- 9.7% (SE) and the actuarial relapse rate of 11.9% +/- 6.8% (SE) demonstrate that the combination of fractionated total body irradiation and high-dose VP 16 is an effective mode of therapy in patients with advanced leukemias. Preliminary experience cautions against the use of VP 16 instead of cyclophosphamide in any clinical situation carrying an increased risk of graft rejection because the immunosuppressive potency of VP 16 is largely untested but may be inferior to that of cyclophosphamide.

Adolescent↗

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↗

PubMed1987

[Orbital and ocular mucormycosis].

A case of mucormycosis in a 46-year-old woman with acute lymphoblastic leukemia is described. The typical clinical findings, diagnostic procedures, and therapeutic considerations are discussed. Mucormycosis is a rare complication in immunocompromised patients. Early ophthalmological diagnosis and rigorous therapy may improve the course of this otherwise fatal disease.

Endophthalmitis↗

PubMed1984

Natural killer (NK) cells and interferon in Friend-virus-infected susceptible and resistant mice.

Natural killer (NK) cells, as determined by the lysis of YAC-1 and Eveline target cells, were determined in F-MuLV-P susceptible DBA/2 and resistant C57/Bl/6 and in beige mice. No difference was found between DBA/2 and C57/Bl/6 mice. Spleens from beige mice showed, as expected, a much lower lysis. The NK cell activity and interferon levels were also studied in these mice after F-MuLV-P infection. Peak NK activities of spleen cells against both target cell types were found at day 3; peak interferon levels were detected in the serum 24 h after infection in all three strains. At day 12, the splenic NK cell activity remained above control levels only in C57/Bl/6 mice. Beige mice were as resistant to Friend leukemia development as C57/Bl/6 mice. The injection of endotoxin, which makes C57/Bl/6 mice virus-susceptible, was followed by increased NK cell activity. The significance of the NK cell system for the resistance of C57/Bl/6 mice against the development of Friend leukemia is discussed.

Animals↗