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Biomedical subjects

N Schmitz

Publications and source records attributed to N Schmitz.

At least 199 records · Page 11Linked to original sources

Lymphohaematopoietic chimaerism after bone marrow transplantation for chronic myeloid leukaemia: results of simultaneous cytogenetic analyses on T-cell colonies, myeloid, and erythroid progenitor cells.

Various lymphohaematopoietic compartments represented by cells from T-cell colonies, myeloid progenitor cells (CFU-GM), erythroid progenitor cells (BFU-E), and bone marrow after short-term culture (BM) have simultaneously been analysed in 15 patients receiving 17 bone marrow transplants for Philadelphia chromosome (Ph) positive chronic myeloid leukaemia (CML) or acute lymphoblastic leukaemia (ALL). The marrow grafts were not T-cell depleted. Ten patients without relapse did not show any myeloid cells of host origin until their last follow-up or until death. However, in four of these patients single lymphoid host cells not carrying the Ph chromosome were found after BMT without clinical consequences. In patients with cytogenetic or haematological relapse Ph positive metaphases were first detected in any of the progenitor cell compartments along with residual donor cells in two of three patients. BM became Ph positive after various time intervals. Another patient with CML became Ph positive in all compartments investigated at the same time. The only patient with Ph positive ALL remained completely Ph negative also when haematological and clinical relapse was evident. All patients with relapse exhibited complex clonal and non-clonal chromosomal aberrations at the time of recurrence of the Ph chromosome. Such abnormalities not identical to those usually found with evolution of the disease and preferentially occurring in progenitor cells preceded the reappearance of Ph positive metaphases in one of our patients.

Adolescent↗

High-dose chemotherapy and autologous bone marrow transplantation in relapsing angioimmunoblastic lymphadenopathy with dysproteinemia (AILD).

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) or lymphogranulomatosis X is a lymphoproliferative disorder with a histological picture resembling that of reactive lesions but with frequent cytogenetic and molecular abnormalities characteristic of malignant T cell lymphoma. Clinically, the disease runs a fatal course in the majority of patients although occasional spontaneous remissions have been observed. Median survival approaches only 1 year even with the most effective treatment protocols implemented so far. Fewer than 20% of patients survive 5 years after diagnosis and cure seems exceedingly rare. High-dose chemotherapy (HDCT) followed by autologous bone marrow transplantation (ABMT) represents a promising new treatment modality for patients with advanced lymphoma conceivably including AILD. We report the first patient with relapsed AILD successfully treated by HDCT and ABMT. This 21-year-old male is alive and free of disease 27 months after ABMT with a Karnofsky score of 100%.

Adult↗

Successful stimulation of autologous bone marrow recovery by GM-CSF and IL-3 after an unrelated donor BMT for juvenile CML complicated by graft failure.

We report the case of a boy with juvenile chronic myeloid leukemia (jCML), who after initial treatment with interferon alpha-2 (IFN) and hydroxyurea underwent bone marrow transplantation (BMT) from a matched unrelated donor complicated by graft failure. Subsequent stimulation of hematopoiesis by GM-CSF and IL-3 promoted autologous recovery. In contrast to the course of disease pre-BMT, the boy is now off any therapy remaining in complete remission more than 500 days after BMT.

Bone Marrow↗

Remission of juvenile chronic myeloid leukemia following graft failure of an unrelated marrow transplant and autologous recovery of marrow function promoted by GM-CSF and IL-3.

The unusual course of a boy with juvenile chronic myeloid leukaemia is presented. After bone marrow transplantation (BMT) from an unrelated donor followed by graft failure and subsequent stimulation by rhu GM-CFC and II-3, this patient experienced complete recovery of autologous haematopoiesis. At 17 months post-BMT the patient was off any therapy with completely normal blood counts and no signs of disease.

Bone Marrow Transplantation↗

Treatment of refractory Hodgkin's disease with high-dose cytosine arabinoside and mitoxantrone in combination. Results of a clinical phase II study of the German Hodgkin Study Group.

In the present study, the activity and side effects of high-dose cytosine arabinoside (HD-Ara-C) in combination with mitoxantrone (mitox) (HAM) was evaluated in 32 heavily pretreated patients with refractory Hodgkin's disease. Therapy consisted of HD-Ara-C 3 g/m2 every 12 hours days 1 and 2 and mitox 10 mg/m2/d days 3 to 5. In subsequent steps, HD-Ara-C was escalated to six and eight doses for 3 and 4 days, respectively, and mitox to four doses on days 2 to 5. Thirty-two patients 17 to 55 years of age entered the study. Twenty-five cases presented with extranodal disease and disseminated organ involvement and 21 revealed systemic (B) symptoms. Eighteen patients (56%) responded with five complete and 13 partial remissions, ten patients (31%) had refractory disease, and four patients died from infections during treatment-induced cytopenia. The predominant toxicity was severe myelosuppression in all patients with major infections occurring during 55% of treatment courses. Ten of the responding 18 patients underwent subsequent autologous (n = 9) or allogeneic bone marrow transplant (BMT). Seven of these cases are currently alive at 5+ to 22+ months, six of them without evidence of disease. Among the remaining eight patients not receiving BMT, three are alive at 6+ to 19+ months from the initiation of HAM, two of them in ongoing remissions of 2+ and 5+ months' duration. Two patients died from transplant-related complications and six patients succumbed to progressive disease following relapse. The median survival for all treated patients is 6.2 months. These data indicate that HAM has a significant activity in refractory Hodgkin's disease. However, the substantial side effects and the lack of an obvious superiority to alternative, less intensive regimens limits the further application of the two-drug combination in its present form. Modifications in timing and dosage and the addition of hematopoietic growth factors will be evaluated in subsequent trials.

Adolescent↗

[Allogeneic bone marrow transplantation in chronic myeloid leukemia. The results of HLA-identical transplants in the Federal Republic of Germany].

In a multicenter study (seven University clinics) in the German Federal Republic bone marrow transplants from HLA-identical donors were performed in 177 patients (113 men, 64 women, mean age 32 [1.3-50] years) with Philadelphia chromosome-positive chronic myeloid leukaemia from 1982 to 1988. The survival rate among the 144 patients in whom the transplant had been carried out during the first chronic phase amounted to 58.4 +/- 11.4% after a median observation period of 3 years; survival rate among the 24 patients who underwent transplantation during the acceleration phase was 29.2 +/- 20.4%. All nine patients who received bone marrow transplants in the second chronic phase or during a blast crisis died during the period of observation (after median periods of 4 and 2 months, respectively). The most frequent causes of death among the group as a whole (82/177 patients) were interstitial pneumonia, acute and chronic graft versus host reactions (GVHD), recurrences and the toxic effects of previous treatment. The risk factors which significantly diminished survival rate were moderate to severe acute GVHD, chronic GVHD and age over 30 years.

Bone Transplantation↗

Acute monocytic leukemia with translocation t(1;11) (p31;q23): simultaneous staining of chromosomes and cell surface antigens.

Cytogenetic analysis of leukemic cells from a 76-year-old patient with acute monocytic leukemia revealed the karyotype 47,XY, +8,t(1;11)(p31;q23). To the best of our knowledge this is the first case with involvement of the short arm of chromosome 1 in a t(1;11) in acute nonlymphocytic leukemia. In order to determine which hematopoietic cell lineages are involved in this case, we used a method to demonstrate chromosomes and cell surface antigens of the same cell. To identify mitoses as monocytic, erythrocytic, megakaryocytic, or lymphocytic, cell surface antigens were stained with monoclonal antibodies in an APAAP detection procedure. Subsequently, an R-banding technique was performed. About 80% of the abnormal mitoses expressed monocytic markers. No erythrocytic, megakaryocytic, or lymphocytic mitoses were found. Only an involvement of the monocytic cell lineage was revealed.

Aged↗

Bone marrow transplantation in childhood leukaemia--experience and strategies in the Federal Republic of Germany.

BMT has gained its place in the treatment of childhood leukaemia. Nevertheless, there are still many questions open. In acute lymphoblastic leukaemia children should normally be grafted in 2nd remission (CR). Some high risk cases, however, should probably be grafted in 1st CR. It is not clear whether children with late relapses benefit more from BMT than from renewed chemotherapy. Children with a relapse during maintenance therapy, however, have a better survival rate with BMT. In acute nonlymphoblastic leukaemia certain high risk patients should be grafted in 1st CR but it has still to be shown that BMT is superior to chemotherapy in such cases. It is not clear whether children with a relapse following intensive chemotherapy (such as the BFM-protocols) will benefit from BMT at all. In chronic myelocytic leukaemia, BMT in chronic phase should be performed. Thus, for the first time cure has become possible for this disease. Waiting for acceleration or even the occurrence of a blast crisis decreases the chance of survival after BMT dramatically. Since complications of BMT such as graft-versus-host reaction or severe infections are less frequent in children, relapses remain the main problem after BMT in childhood leukaemia.

Bone Marrow Transplantation↗

Fractionated total body irradiation plus high-dose VP-16 prior to allogeneic bone marrow transplantation in children with poor risk acute leukaemias.

Nineteen children (median age, 13 years; range 4 to 18 years) with acute lymphoblastic leukemia/lymphoma (ALL) (10 patients) or acute nonlymphoblastic leukemia (ANNL) (9 patients) received allogeneic bone marrow transplants (BMT). Marrow was taken from HLA-identical sibling donors (16 patients) (pts), HLA-identical unrelated donor (1 pt), or one-antigen-missmatched sibling donor (1 pt). Preparatory regimen consisted of fractionated total body irradiation and high-dose VP-16 (50-70 mg/kg body weight). At the time of BMT nine of the pts were not in complete remission (CR): seven pts were refractory to aggressive multiagent chemotherapy and two pts were in first relapse. Six pts were in second CR, one pt in third CR; three pts grafted in first CR carried additional risk factors; e.g. induction failure. Ten out of the nineteen pts are alive and free of disease between one and 53 months (median, 28 months) after BMT. The actuarial disease-free survival rate is 37% for pts with ANLL and 54% for pts with ALL. Six pts have died from BMT-related complications. Only three pts (1 pt with ALL, 2 pts with ANLL) have relapsed between day +106 and day +134 after BMT and subsequently died. The four-year actuarial relapse rates of 29% for ANLL and 14% for ALL, respectively, demonstrate that the combination of fractionated total body irradiation and high-dose VP-16 is an effective antileucemic regimen for children with advanced leukemias.

Adolescent↗

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↗

Comparison of cyclophosphamide, cytarabine, and etoposide as immunosuppressive agents before allogeneic bone marrow transplantation.

Etoposide and cytarabine have been shown to exert high antileukemic activity and are currently under study as preparatory agents before allogeneic bone marrow transplantation. However, data concerning their engraftment-promoting potency are scarce. Therefore, we tested these agents in LEW rats receiving a myeloablative dose of busulfan followed by transfer of F1 (CAP X LEW) marrow, which is unable to induce a graft-v-host reaction (GVHR). Since busulfan by itself has only minor immunosuppressive potency, graft rejection ensues unless etoposide, cytarabine, or cyclophosphamide provide additional immunosuppression to facilitate durable engraftment. Before allogeneic bone marrow transplantation in humans, 120 mg/kg of cyclophosphamide, 60 mg/kg of etoposide, or 900 mg/kg of cytarabine are the standard doses given in conjunction with total body irradiation. Seventy-five percent of these doses administered in addition to busulfan resulted in rejection rates of 75% for cytarabine and 58% for etoposide, respectively, whereas no rejections were observed with cyclophosphamide. These data indicate that etoposide and cytarabine are inferior to cyclophosphamide in their rejection-preventing potential. Using either of these agents as substitutes for cyclophosphamide before allogeneic bone marrow transplantation may increase the risk of graft rejection in HLA-mismatched bone marrow transplantation and, in case of HLA identity, if T-depleted marrow is administered.

Animals↗

Application of a microseparation technique allowing for extensive marker studies on small bone marrow specimens.

The characterization of surface and intracellular markers of hematopoietic cells by immunocytochemical methods is widely used. While examination of cells of the peripheral blood can easily be performed, investigations of bone marrow cells can be hampered by technical difficulties in labeling routine marrow smears or by limited size of specimens required for cytocentrifugation. A simple and highly efficient method for isolation of bone marrow cells by a microseparation technique is described. Only two to three drops of a routine bone marrow aspirate are necessary for preparation of up to 100 cytocentrifuge slides thereby exceeding separation efficiency of conventional gradient centrifugation by three- to more than four-fold. The application of the method for marker studies on normal marrow and marrow from patients with hematologic malignancies is exemplified.

Antibodies, Monoclonal↗