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N Schmitz

Publications and source records attributed to N Schmitz.

At least 109 records · Page 6Linked to original sources
PubMed1999

In childhood acute lymphoblastic leukemia the hypophosphorylated retinoblastoma protein, p110RB, is diminished, as compared with normal CD34+ peripheral blood progenitor cells.

Acute lymphoblastic leukemia (ALL) of childhood arises from dysregulated clonal expansion of immature lymphoid precursor cells that fail to differentiate into functional lymphocytes. The cell-cycling status of ALL cells shares many common features with that of normal CD34+ hematopoietic progenitor cells, such as low number of resting G0 and cycling S phase cells even though the growth fraction is high. Thus, ALL cells should be in a long G1 phase. Phosphorylation of the retinoblastoma protein is a crucial step in cell-cycle progression from G0/early G1 to late G1/S phase. We therefore analyzed the G1 distribution of these two immature cell populations by immunostaining and Western blot. Bone marrow samples from children with ALL at diagnosis as well as purified CD34+ cells, before and after in vitro stimulation with cytokines, were investigated for the expression of hypophosphorylated p110RB (early G1 phase), total retinoblastoma protein, statin (G0 phase), bromo-deoxyuridine (S phase), proliferating cell nuclear antigen, and p120 (cycling cells). Compared with unstimulated CD34+ cells (95.8 +/- 1.2%) the component of ALL cells containing hypophosphorylated p110RB (16.3 +/- 13.2%) was significantly reduced (p = 0.00018), whereas only a minor difference could be detected for the proportion of cycling cells (p = 0.03), and no difference in G0 and S phase cells (p > 0.05). Our results indicate that, as opposed to unstimulated CD34+ cells, the majority of ALL cells are beyond the restriction point and therefore irreversible committed to DNA replication and mitosis.

Antigens, CD34↗
PubMed1999

[Not Available].

Facing the increasing number of single-parent-families we investigated the impact of fathers absence within the first six years of childhood on psychic/psychosomatic impairment in later life. We used data from the Mannheim Cohort Study on the Epidemiology of Psychogenic (neurotic spectrum) Disorders for a comparison of extreme groups with a favourable or bad course of clinical impairment. In adition we performed regression analysis of the long term course of clinical impairment for the total follow-up sample (mean follow-up intervall 11 years, N=301) with psychometric, clinical and childhood variables. The absence of the probands father (> six months within the first six years of life) was a significant independend predictor of clinical impairment in later life, accompanied by clinical and psychometric variables. A significant and increasing impairment existed even in 73 of 125 older probands (birth cohort 1935), who missed their father in early childhood. The sociopolitical implications of these findings are discussed.

Childhood↗
PubMed1999

[Diagnosis and management of patients with psychogenic disorders in family practice. Results of a field study].

The majority of patients with psychological disorders are seen in primary care. The diagnosis of the general practitioner (GP) influences decisively the subsequent treatment. Our study provides an insight into GP's diagnosis and treatment. 18 GP's and a psychotherapist rated 572 patients using a global diagnostic rating scale and the impairment score (BSS). The GPs noted down their treatment. The patients filled in symptom checklists (SCL-90-R, GHQ-12). Agreement between the doctor and the researchers on mental ill health was modest. GPs identified 51.4% of the patients with psychological disorders. Adjustment disorders were often ignored by GPs. They prescribed psychotherapy for 3.3% of their patients, especially patients with somatoform disorders and with high values in the impairment score. A path analysis shows, that psychotherapists' ratings agree much more with patients' self-assessment than GP ratings.

Adult↗
PubMed1999

[The Dusseldorf short-term dynamic psychotherapy project (DKZP)].

Time-limited psychodynamic therapies in the outpatient setting are offered for a broad spectrum of psychogenic disorders. Meta-analyses prove their effectiveness mainly for neurotic disorders. We are interested in the suitability of the here applied CMP/SASB model (Tress et al. 1996) of psychodynamic short-term therapy for patients with psychosomatic and severe personality disorders. We extensively present the concept of Cyclic Mal-adaptive Pattern (CMP) in its clinically relevant parts as the core of psychogenic pathological developments. Particularly the introject, as the patient's attitude towards him- or herself, is of great importance for therapeutic change and its follow-up development. Within the DKZP (Duesseldorf Short-Term Psychotherapy Project), 36 male and female therapists, mostly interns at the local university clinic, treated 82 patients (m: 23/f: 59) with personality disorders (n = 26) and psychosomatic disorders (n = 31) as research groups and, in comparison, neurotic patients (n = 25) in a naturalistic design. 68 treatments have been completed so far, 11 patients have dropped out, the remaining 3 are still in therapy. Relevant research instruments are the Beeinträchtigungsschwere Score (BSS, an impairment score), Global Assessment of Functioning Scale (GAF), Cyclic Maladaptive Pattern (CMP), Symptom Check List (SCL-90-R), and Structural Analysis of Social Behavior (SASB) including process and content ratings, as well as the Intrex questionnaire. The treatments last 25 sessions. We carried out follow-up examinations after 6 months, 1 year, 2, and 5 years. Effect sizes for the whole sample by BSS and GAF are remarkably high, with further increase at follow-up interviews. Psychosomatic patients came off best, but personality disorders in comparison to neurotic patients profited surprisingly well. Effect sizes in self-rating (SCL and Intrex) were less high. However, in self-rating the changes of social functions are not sufficiently addressed. As a result, our form of focal therapy is well suited not only for neuroses, but also for psychosomatic disorders and personality disorders. An enlargement of the indication spectrum for this form of psychodynamic therapy to include these disorders is well founded and promising.

Adult↗
PubMed1998

Moderate dose escalation for advanced stage Hodgkin's disease using the bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone scheme and adjuvant radiotherapy: a study of the German Hodgkin's Lymphoma Study Group.

The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has been shown to be effective and safe in a previous pilot study for advanced stage Hodgkin's disease (HD). The present study aimed to determine a maximum practicable dose of three drugs, ie, etoposide, adriamycin, and cyclophosphamide, for which acute toxicities were acceptable and to assess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study. Radiotherapy was given in 44 patients (73%) after chemotherapy to initial bulk lesions and residual disease. Granulocyte-colony stimulating factor (G-CSF) was given from day 8 to prevent prolonged neutrocytopenia and severe infections. The intended doses of adriamycin, etoposide, and cyclophosphamide in the BEACOPP schedule could be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m2. The major toxicities were leukocytopenia and thrombocytopenia with considerable heterogeneity between individual patients. Of 60 patients, 56 (93%) achieved a complete remission (CR). At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95% confidence interval 83% to 99%) and 90% (82% to 98%). These results show that a moderate dose escalation of adriamycin, cyclophosphamide, and etoposide of the baseline BEACOPP regimen is feasible. The escalated BEACOPP regimen shows very encouraging results in advanced stage HD and is now being compared in a randomized phase III study with BEACOPP at baseline dose level.

Adolescent↗
PubMed1998

[Febrile neutropenia: practical aspects].

BACKGROUND: Infections are a major cause of mortality in neutropenic patients. They require long hospital stays and highly expensive therapeutic measures. In this review we discuss the practical and pharmaco-economic aspects of the management of febrile neutropenia. PREVENTION AND THERAPY: Prevention of fever of unknown origin (FUO) demands hygienic and antimicrobiotic measures. First-line antibiotic therapy consists of an aminoglycoside combined with an ureidopenicillin or a 3rd-generation cephalosporin. Double beta-lactam antibiotic combinations are equally effective and less toxic, but more expensive. Monotherapy with carbapenems, ceftazidime, or cefepime appear to offer comparable efficacy. Lung infiltrates require immediate treatment with amphotericin B. If the initial therapeutic regime fails, a carbapenem plus a glycopeptide antibiotic and a parenteral antimycotic drug should be applied after 3 to 4 days. The prophylactic or interventional administration of hematopoietic growth factors is only indicated in special high-risk situations. CONCLUSIONS: Using the described therapeutic procedure, the response rate exceeds 90%. Consistent, step-wise escalating administration of antibiotics is essential. More evaluation is needed to determine whether selected patients with febrile neutropenia can be treated on an outpatient basis.

Anti-Bacterial Agents↗
PubMed1998

[Therapy of highly malignant non-Hodgkin lymphoma with high-dose chemotherapy and stem cell transplantation].

Patients with intermediate or high-grade non-Hodgkin's lymphoma are rarely cured of their disease after the failure of conventional therapy. High-dose chemotherapy followed by transplantation of either autologous marrow (ABMT) or peripheral stem cells (PBSCT) offers such patients a new possibility of cure. To patients younger than 60 years and without contraindications high-dose chemotherapy should be offered in case of relapse and bad prognosis. The PARMA-study demonstrated, that high-dose chemotherapy with subsequent autologous stem cell transplants is superior to conventional chemotherapy for relapsing patients. However high-dose chemotherapy in first complete or partial remission followed by ABMT and PBSCT as post-remission therapy for adult NHL has yielded only similar results randomized to those achieved with conventional chemotherapy in several prospectively studies. This approach should be limited to patients with bad prognostic factors (high-intermediate or high-risk groups according to the International Prognostic Factor Project). The success of ABMT and PBSCT in treating these diseases mandates exploration of the best high-dose chemotherapy, the use of autologous or allogenic bone marrow resp. peripheral stem cell for haematopoietic reconstitution and technical aspects such as purging of tumor cells, the short- and long-term transplant-related mortality continues to be a major concern.

Adult↗
PubMed1998

A three stage model of awareness: formulation and initial experimental support.

The various components which together make up the complex state of consciousness require neural support involving a connected network of many brain areas at differing levels. At the lowest level is non-aware processing, of which there is not direct awareness. There are also modules involved in processing with awareness but without focussed attention. Finally there must be a set of modules involved in directing attention in a controlled manner. We expect to be able to dissociate the various components of the three-stage network by using different levels of attention. The results of an auditory experiment performed under three different levels of awareness and attention are analysed to show support for the three-stage model of awareness. The relevant auditory areas are delineated.

Acoustic Stimulation↗
PubMed1998

[Bronchopulmonary carcinosarcoma].

INTRODUCTION: Bronchopulmonary carcinosarcoma is an uncommon neoplasm consisting of mixed malignant epithelial and mesenchymal cells. EXEGESIS: We report a case of bronchopulmonary carcinosarcoma in a 62-year-old man illustrating some characteristics of this tumor of poor prognosis and unknown histogenesis. CONCLUSION: Bronchopulmonary carcinosarcoma has clinical and X rays features identical to those of bronchopulmonary epithelial malignant tumors. Most of the authors consider that a totipotential cell might be at the origin of this "mixed" tumor. Although 90% of bronchopulmonary carcinosarcomas are resectable, their prognosis is worse than that of other lung cancers, with a 6-month median survival.

Bronchial Neoplasms↗
PubMed1998

Early stem cell transplantation for chronic lymphocytic leukaemia: a chance for cure?

B-cell chronic lymphocytic leukaemia (CLL) cannot be cured by conventional therapy. To improve the prognosis of patients with CLL, we have designed a sequential treatment strategy that comprises intensive chemotherapy for mobilization of peripheral blood progenitor cells (PBPCs) and induction of minimal disease, followed by high-dose radiochemotherapy with stem cell reinfusion and post-transplant molecular monitoring by polymerase chain reaction (PCR) amplification of the complementary determining region III (CDRIII) gene. In a prospective study, we have evaluated this protocol in 18 patients with CLL, also including early stages of the disease. The median age was 49 (29-61) years; Binet stages were A, six; B, nine; and C, three. Adverse prognostic factors [high lymphocyte count and/or diffuse bone marrow (BM) infiltration] were present in 16 out of 18 patients. All patients showed a clone-specific molecular marker as demonstrated by PCR amplification of CDRIII rearrangements. For stem cell mobilization and reduction of tumour load, one to two cycles of Dexa-BEAM chemotherapy were administered, resulting in minimal disease (circulating lymphoma cells <1 x 10(9) l(-1); BM infiltration <20%; lymphomas <2 cm) in 16 out of 18 patients, including four patients who already had minimal disease before Dexa-BEAM. Stem cell harvesting was successful in 14 patients. All grafts [three BM, 11 peripheral blood (PB)] were purged from leukaemic cells using immunomagnetic methods. Thirteen patients having achieved minimal disease were reinfused with purged autologous stem cells (ASC) after preparation with total body irradiation and cyclophosphamide. Engraftment was delayed in patients receiving BM (n = 3) but prompt [neutrophils >0.5 x 10(9) l(-1) after 10 (9-13) days, platelets >20 x 10(9) l(-1) after 11 (9-214) days] in patients restored with PBPCs (n = 10). Procedure-related deaths did not occur. Although the results of CDRIII PCR suggest persistence or recurrence of the leukaemic clone in at least three cases, to date only one patient has relapsed, whereas all others survive without clinical evidence of disease with a maximum follow-up of 48 months. We conclude that sequential high-dose therapy using Dexa-BEAM and autologous stem cell transplantation is a safe and highly effective treatment for patients with CLL. However, a longer follow-up is needed to assess whether definite cures can be achieved using this strategy.

Adult↗
PubMed1998

Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe in 1998. Accreditation Sub-Committee of the European Group for Blood and Marrow Transplantation.

In 1996, the Accreditation Sub-Committee of the EBMT published a special report summarising current practice in Europe in relation to haemopoietic stem cell transplants for haematological diseases, solid tumours and immune disorders. An updated report is presented here. The major change has been the recognition that transplant practice is appreciably different between children and adults, who should therefore be considered in separate categories. The autoimmune disorders for which autografting may be useful are now specified. Non-CML myeloproliferative disorders and AL amyloidosis have been added to the list of indications for transplant procedures in adults. Other changes have been incorporated into the revised tables.

Adolescent↗
PubMed1998

Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukaemia: first results of a randomised multicentre trial of the European Group for Blood and Marrow Transplantation.

In a multicentre trial involving 20 transplant centres from 10 countries haematopoietic stem cells were obtained either from the bone marrow of 33 sibling donors or from the peripheral blood of 33 such donors after administration of filgrastim (10 microg/kg/day). The haematopoietic stem cells were infused into their HLA-identical recipients suffering from acute leukaemias in remission or chronic myeloid leukaemia in chronic phase. PBPC donors tolerated filgrastim administration and leukapheresis well with the most frequent side-effects being musculoskeletal pain, headache, and mild increases of LDH, AP, Gamma-GT or SGPT. Pain and haematoma at the harvest site and mild anaemia were the most frequent complaints of BM donors. Severe or life-threatening complications were not seen with any type of harvest procedure. Time to platelet recovery greater than 20 x 10(9)/l was 15 days (95% confidence interval (CI) 13-16 days) in the PBPCT group and 19 days (CI 16-25) in the BMT group. Time to neutrophil recovery greater than 0.5 x 10(9)/l was 14 days (CI 12-15 days) in the PBPCT group as compared to 15 days (CI 15-16 days) in the BMT group. The numbers of platelet transfusions administered to PBPCT and BMT patients were 12 (range: 1-28) and 10 (range: 3-39), respectively. Sixteen patients (48%) transplanted with bone marrow and 18 patients (54%) transplanted with PBPC developed acute GVHD of grades II-IV; acute GVHD of grades III or IV developed in six (18%) and seven (21%) patients, respectively. Kaplan-Meier plots for transplant-related mortality until day 100 and leukaemia-free survival at a median of 400 days after BMT or PBPCT showed no significant differences. Administration of filgrastim and leukapheresis in normal donors were feasible and well tolerated. The number of days with restricted activity and of nights spent in hospital was lower in donors of PBPC. Transplantation of PBPC to HLA-identical siblings with early leukaemia resulted in earlier platelet engraftment. The incidence of moderate to severe acute GVHD, transplant-related mortality, and leukaemia-free survival did not show striking differences. Further investigation of allogeneic PBPCT as a substitute for allogeneic BMT is warranted.

Adolescent↗
PubMed1998

Comparison of different strategies of molecular genetic monitoring following autologous stem cell transplantation in patients with follicular lymphoma.

Two different molecular genetic methods were compared for their suitability for monitoring minimal residual disease in patients with follicular lymphoma (FL) treated with high-dose therapy and autologous stem cell transplantation. Fifteen patients were selected because of a specific PCR-amplifiable t(14;18) mbr translocation. PCR amplification of rearrangements of the complementary region III (CDRIII) of the immunoglobulin heavy chain gene was also carried out. After autologous stem cell transplantation, patients were prospectively monitored with both molecular genetic methods. Seven of the 15 patients with detectable t(14;18) prior to transplantation were persistently negative during follow-up to 32 months post transplant. None of these patients relapsed, whereas four of eight patients with positive PCR signals post transplant relapsed. Comparing t(14;18) and PAGE results, we observed six patients showing clonal signals in CDRIII PAGE in spite of persistent negativity of t(14;18) PCR. We concluded that in patients with FL, t(14;18) PCR is superior to CDRIII PCR in terms of sensitivity and specificity. A positive t(14;18) PCR during the first year post transplant is highly predictive for disease recurrence. CDRIII PCR may be used for monitoring in t(14;18) negative lymphomas. However, due to the poor specificity of conventional gel electrophoresis PCR, the use of clone-specific probes is highly desirable.

Adult↗
PubMed1998

Abrogation of graft-vs.-leukemia activity after depletion of CD3+ T cells in a murine model of MHC-matched peripheral blood progenitor cell transplantation (PBPCT).

Using a murine transplantation model, we simulated a clinical situation in which major histocompatibility complex (MHC)-identical allogeneic peripheral blood progenitor cells (PBPCs) are transplanted for the treatment of a malignant disease that is resistant to resting natural killer (NK) cells but sensitive to cytokine-activated NK cells and T cell-mediated antitumor activity. We determined the influence of selective T cell depletion of allogeneic PBPC grafts on graft-vs.-leukemia (GVL) activity and investigated the effectiveness of ex vivo treatment with NK cell-activating cytokines to compensate for the putative loss of T cell-derived factors stimulating natural cytotoxicity. After pretreatment of Balb/c (H-2d) recipients with 7.5 Gy of total body irradiation, 2x10(7) rhG-CSF-mobilized PBPCs of splenectomized syngeneic or MHC-identical DBA (H-2d) mice were transferred. Selective T cell depletion (TCD) was performed by immunomagnetic purging with a mononoclonal antibody directed against CD3. In some experimental groups, T cell-depleted PBPCs were incubated with 200 U/mL interleukin (IL)-2 and 100 U/mL IL-12 for 24 hours. To investigate antileukemic activity in vivo, recipient mice were inoculated with 1x10(5) A20 cells (a B-lymphoblastic leukemia of Balb/c origin) 2 days before PBPC transplantation (PBPCT). After transplantation of unmanipulated allogeneic cells, 25% of the animals died with signs of graft-vs.-host disease (GVHD) but 71% were free from relapse 100 days after PBPCT. After TCD of allogeneic grafts with anti-CD3, the incidence of GVH-related mortality was below 5% but the leukemia-free survival rate was significantly (p < 0.05) decreased to 25% and thus was similar to that observed after syngeneic PBPCT (17%). When CD3-depleted grafts were incubated with IL-2 and IL-12, 45% of the animals remained free from leukemia; however, the difference was not statistically significant. Our results suggest that ex vivo activation of residual NK cells with IL-2 and IL-12 does not fully compensate for the abrogation of GVL activity after depletion of CD3+ T cells from MHC-matched PBPCT.

Animals↗
PubMed1998

Immunotherapeutic aspects of allogeneic peripheral progenitor cells.

In a newly developed murine model of allogeneic peripheral progenitor transplantation (PBPCT) we investigated the immunotherapeutic potential of allogeneic peripheral stem cells. The following topics were addressed by our experiments: (1) comparison of the graft-versus-leukemia effect exerted by allogeneic PBPCT compared to allogeneic BMT; (2) the influence of T-lymphocytes on GVL activity; (3) the possibility to enhance the GVL activity of allogeneic PBPCT grafts by ex vivo cytokine incubation. Balb/c mice received cells of the syngeneic B-lymphatic leukemia A20 2 days prior to TBI (7.5 Gy) and the respective graft. The recipients received allogeneic bone marrow grafts or allogeneic peripheral progenitor cells obtained after mobilization of the donors (DBA/2) with either G-CSF in a dose of 250 microg/kg/day for 5 days. In some experiments T lymphocytes were removed by immunomagnetic depletion with CD3-coated beads. An additional group received T cell-depleted and IL-2/IL12-activated PBPCT grafts. The antileukemic activity of an allogeneic PBPCT graft was significantly greater than the antileukemic activity of an allogeneic BMT graft of the same size. Relapse rates were 80% in syngeneic PBPCT, 60% after allogeneic BMT and 34% after allogeneic PBPCT. This rise in antileukemic activity is not accompanied by a rise in GVHD mortality. Depletion of T lymphocytes by CD3-coated beads resulted in a nearly complete loss of the GVL activity with a relapse rate of 75%. Incubation of the T-depleted graft with IL-2 and IL-12 to enhance NK-based GVL activity has only limited success after MHC-matched transplantation with a relapse rate of 55%. Allogeneic PBPC exert a pronounced antileukemic effect. After MHC-matched PBPCT, this GVL effect resides mostly on the T cells of the graft. Ex vivo activation of T cell-depleted grafts by IL-2 and IL-12 is accompanied by an only limited reduction of relapse rate. PBPC are a valuable modality for primary transplantation in situations with high risk of relapse and for the treatment of relapse after BMT.

Animals↗
PubMed1998

Superior antileukemic activity of murine peripheral blood progenitor cell (PBPC) grafts mobilized by G-CSF and stem cell factor (SCF) as compared to G-CSF alone.

We have established a murine model to compare the antileukemic effect of PBPC grafts obtained after treatment with SCF + G-CSF and G-CSF alone. C57/BL6, DBA and Balb/c mice were splenectomized and injected with optimal doses of rhG-CSF (250 microg/kg/day s.c.) or rrSCF (100 microg/kg/day s.c.) or with a combination thereof. On day 5, we determined the hematopoietic potential (number of CD34+ cells, CFUs, total CFC, CFU-gm), the proportion of lymphoid (T, NK and B cells) and myeloid components and graft-versus-leukemia activity after allogeneic and syngeneic PBPCT and BMT in Balb/c mice bearing a B-lymphoblastic leukemia cell line (A20). The absolute number of progenitor cells increased two-fold after administering a combination of G-CSF and SCF as compared to G-CSF alone (1500 vs 940 CD34+ cells/microl; 190 vs 70 total CFC/microl; 150 vs 50 CFU-gm/microl and 6600 vs 3000 CFUs/ml). Although no differences could be detected in the cellular composition, especially in the number of T cells, PBPC grafts mobilized by the combination of G-CSF + SCF demonstrated significantly higher antileukemic activity compared to G-CSF alone (94% vs 71% freedom from leukemia, P < 0.05). Because the incidence of lethal GVHD was similar in both groups, improved GVL activity resulted in superior overall survival. Our data suggest that the higher number of progenitor cells can be harvested after G-CSF + SCF and that grafts mobilized by G-CSF + SCF exert significantly enhanced antileukemic activity compared to those harvested after treatment with G-CSF alone.

Animals↗
PubMed1998

Eradication of residual disease by administration of leukemia-specific T cells after experimental allogeneic bone marrow transplantation.

It is now well established that allogeneic lymphocytes can mediate a potent graft-vs.-leukemia (GVL) reaction when administered to bone marrow transplant (BMT) recipients. The benefit of allogeneic lymphocyte transfusion is limited because many patients develop graft-vs.-host disease (GVHD) with prolonged pancytopenia, which sometimes proves fatal. The object of the present study was to determine the antileukemic potential and GVHD risk of in vivo-generated tumor-specific allogeneic T cells given shortly after BMT. BALB/C (H-2d) mice were inoculated with different cell doses (10(5) and 5 x 10(5)) of the A20 leukemia (BALB/C origin) 2 days prior to lethal total-body irradiation (TBI) and transplantation of allogeneic, major histocompatibility complex (MHC)-matched DBA marrow grafts (H-2d, minor difference to BALB/C). Donors of BM grafts and T cells were allogeneic, MHC-matched mice (DBA, H-2d, minor difference to BALB/C). Donor-type T cells were generated from mice immunized with irradiated A20 leukemia cells or nonmalignant BALB/C splenocytes and restimulated in vitro. Whereas no significant immunotherapeutic effect was seen in mice with high tumor burden (5 x 10(5)), allogeneic BMT in mice inoculated with 1 x 10(5) A20 cells resulted in a modest antileukemic effect. This survival rate remained unchanged when 10(6) T cells obtained from donors immunized with nonmalignant BALB/C derived cells were given posttransplantation. In contrast, a single injection of 10(6) T cells from leukemia-immunized donors led to potent GVL effects without mediating clinically overt GVHD. Our data provide evidence for the hypothesis that minimal residual disease can be eradicated without inducing GVHD by administering small amounts of specific allogeneic cytotoxic T cells after BMT.

Animals↗