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Biomedical subjects

A R Zander

Publications and source records attributed to A R Zander.

At least 127 records · Page 7Linked to original sources
PubMed1995

Comparative studies of induction and repair of DNA double-strand breaks in X-irradiated alveolar macrophages and resting peripheral blood lymphocytes using constant-field gel electrophoresis.

Induction and repair of X-ray-induced DNA double-strand breaks (dsbs) was compared for normal broncho-alveolar macrophages and human peripheral blood lymphocytes, using CHO cells as a reference cell model. The cells, upon their separation, were processed in a similar manner. After X-irradiation, cell lysis and proteinase K treatment, the DNA samples were subjected to constant-field gel electrophoresis (CFGE) followed by fluorimetric densitometry for quantification of released DNA. Induction of dsbs after X-ray doses of 5-100 Gy was found to show no gross differences for all cell systems used. Repair of dsbs was studied after X-ray dose of 60 Gy for up to 24 h after irradiation. The repair curves obtained proved to be similar for bronchoalveolar macrophages and CHO cells (97% of all dsbs rejoined after 24 h). However, in blood lymphocytes from normal subjects and from bone marrow recipients, dsb repair proceeded rapidly only for 0.5-1 h post-irradiation, being followed by the gradual degradation of DNA at longer intervals. The kinetics of DNA degradation correlated with cytological features of pyknosis and necrosis.

Animals↗
PubMed1995

Separation and characterization of mobilized and unmobilized peripheral blood progenitor cells by counterflow centrifugal elutriation.

Peripheral blood stem cell (PBSC) harvests are highly contaminated with lymphocytes. In allogeneic transplantations with PBSC, this might lead to an increased risk of graft-vs.-host disease (GVHD). Marrow graft T cells depletion (TCD) by counterflow centrifugal elutriation (CCE) has been performed to decrease the incidence of GVHD, but in some cases, it has also led to a reduction in the PBSC content of the graft due to the distinct elutriation properties of these cells. We studied the ability of CCE to deplete lymphocytes from recombinant human granulocyte colony-stimulating factor (rhG-CSF)-mobilized PB mononuclear cells (PBMNC) and from unmobilized PBMNC from healthy volunteers. We characterized the elutriation properties of circulating mobilized and unmobilized hematopoietic progenitors. With an experimental three-flow rate CCE procedure, originally described for separation of bone marrow, fractions 24, 28, and Rotor Off (RO) were obtained without impairing yield or viability. This CCE procedure can also be used for the separation of PBMNC harvests by reducing the T cell contamination to or below the range seen in bone marrow grafts; CD3+ cell contamination in the RO fractions of mobilized and unmobilized PBMNC was reduced to < 10% of the input. This could bring allogeneic PBSCT within the range of feasibility. In unmobilized PBMNC, 25% of the recovered CD34+ cells were found in fraction 24, where no colonies were detected, and 50% of the recovered CD34+ cells were found in fraction RO, where most of the colonies were detected. In mobilized PBMNC, 80% of the recovered CD34+ cells were found in fraction RO, together with 90% of the colonies, but almost no colonies or CD34+ cells were detected in fraction 24. CD34+ cells in fraction 24 expressed less CD13, and antigen found on more mature myeloid cells. Mobilization with rhG-CSF causes a shift of CD34+ cells from smaller cells (fraction 24) to larger cells (fractions 28 and RO).

Antigens, CD↗
PubMed1995

Results of a randomised, controlled, multicentre study of recombinant human granulocyte colony-stimulating factor (filgrastim) in patients with Hodgkin's disease and non-Hodgkin's lymphoma undergoing autologous bone marrow transplantation.

In 54 patients with malignant lymphoma, haematopoietic recovery after high-dose chemotherapy and autologous bone marrow transplantation (BMT) was compared between patients randomised to receive 10 or 30 micrograms/kg/day of r-metHuG-CSF (filgrastim) or no growth factor. After standard high-dose chemotherapy with cyclophosphamide, etoposide and BCNU (CVB regimen for patients with Hodgkin's disease) or BCNU, etoposide, cytosine arabinoside and melphalan (BEAM regimen for patients suffering from non-Hodgkin's lymphoma) followed by autologous BMT, r-metHuG-CSF was administered by continuous intravenous infusion from the first day after autologous BMT until neutrophil recovery. When the r-metHuG-CSF groups were compared with the control group the major findings were: the median time to reach an absolute neutrophil count (ANC) > or = 0.5 x 10(9)/L was 20 days in the control group and 12 and 14 days, respectively, in the r-metHuG-CSF groups (P = 0.0004). The duration of neutropenia (ANC < 0.5 x 10(9)/L) was reduced from 27 days in the control group to 11 and 13 days in the r-metHuG-CSF groups (P = 0.0001). In addition, fewer days of febrile neutropenia were observed in the r-metHuG-CSF groups (5 and 6 days) than in the control group (10 days; P = 0.036). No significant effects of r-metHuG-CSF administration on the number of days with fever, the use of intravenous antibiotics and hospitalisation were detected. R-metHuG-CSF was well tolerated without any serious side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Infusion of tumor-contaminated bone marrow for autologous rescue after high-dose therapy leading to long-term remission in a patient with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia.

We report a female patient with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia remaining in long-term second remission after high-dose radiochemotherapy followed by autologous stem cell rescue with bone marrow showing evidence of residual disease. The Philadelphia chromosome and a positive signal for the BCR/ABL p185 translocation by the polymerase chain reaction were detected in the harvested marrow. After mafosfamide-purged marrow failed to engraft, her unpurged 'back-up' bone marrow was also infused. Control marrow examinations after recovery were repeatedly positive for the BCR/ABL translocation on PCR analysis turning negative 30 months after high-dose therapy. She remains in unsustained complete clinical remission for 48+ months showing no evidence of leukemia by cytological and cytogenetic analyses.

Adult↗
PubMed1995

Inhibition of CFU-C growth by VP-16 containing plasma samples obtained from patients after conditioning therapy for bone marrow transplantation.

The introduction of VP-16 into high-dose therapy regimens used for conditioning before BMT or PBSCT has resulted in higher remission rates and prolonged disease-free survival, even in high risk patients. VP-16 levels have been measured in plasma at the time of transplantation. The question is, is there a biological activity that corresponds with the risk of delayed engraftment or graft failure? We investigated the inhibitory effects of plasma samples obtained from patients under high-dose VP-16 therapy on the growth of human bone marrow progenitor cells. Bone marrow cells from healthy donors were exposed to the plasma samples and seeded into methylcellulose-culture (CFU-C-assay). We found a dose dependent CFU-C inhibition related to VP-16 plasma levels at the time of transplantation (k = 0.769, P < 0.01). There were signs of a correlation between CFU-C growth inhibition at the time of BMT and haematological recovery (k = 0.656, P < 0.05) between CFU-C inhibition and the time until leucocytes reached 0.2 x 10(9)/l. Patients with CFU-C growth inhibition at the time of BMT may show delayed engraftment of leucocytes and that there might be a correlation with VP-16 levels, but further investigation is necessary to determine the significance of the latter thesis and if VP-16 plasma levels could lead to failure of engraftment. We recommend a minimum time interval between VP-16 infusion and graft transplantation of 72 h.

Adolescent↗
PubMed1995

Increasing the yield of harvested bone marrow cells by raising room temperature during marrow collection.

The time it takes to harvest bone marrow before transplantation could be reduced significantly by increasing the temperature of the operating room by 8-10 degrees C, to about 28-30 degrees C. In healthy donors, the collected volume of marrow was increased from 22.45 to 36.31 mL/min; in patients who received chemotherapy previously, from 21.67 to 29.98 mL/min. The time to collect a volume of 1200 mL marrow could be reduced significantly, from 57.78 to 38.25 minutes in healthy donors and from 71.07 to 43.36 minutes in patients who received chemotherapy previously, without any loss of quality of the sampled marrow. Operation time and thereby time of anesthesia could be reduced significantly by heating the operating room to a temperature of 28-30 degrees C. Harvesting at higher room temperature did not result in any adverse side effects for the patients. The procedure to increase the body temperature could be simplified by using electric blankets and aluminum foils for wrapping to avoid heat emission.

Adolescent↗
PubMed1994

Allogeneic bone marrow transplantation for leukemia following piperazinedione and fractionated total body irradiation.

Between 1980 and 1988, 126 patients with leukemia were treated with piperazinedione and fractionated total body irradiation (TBI) followed by allogeneic bone marrow transplantation from HLA matched siblings. Sixty-one patients had acute myelogenous leukemia, 46 acute lymphoblastic leukemia, and 19 chronic myelogenous leukemia. Patients with acute leukemia in first complete remission were transplanted only if perceived to have a low probability of remaining in remission with conventional therapy. The toxicity from the preparative regimen was similar to that of cyclophosphamide and TBI except that none of the patients in the study had hemorrhagic cystitis or veno-occlusive disease. After a median follow up of 114 months, 29 patients (23%) are still alive without relapse. The survival of patients with acute myelogenous or lymphoblastic leukemia transplanted in their first remission were 35% and 43%, respectively. The survival of patients transplanted in their first chronic phase of chronic myelogenous leukemia was 60%. The results of this preparative regimen are comparable to those of cyclophosphamide and TBI.

Adolescent↗
PubMed1993

Monoclonal gammopathy of unknown significance in a bone marrow donor.

We report on a patient suffering from multiple myeloma, for whom allogeneic bone marrow transplantation was planned. Donor workup revealed monoclonal gammopathy of unknown significance. We discuss this finding and stress the importance of performing complete donor examinations.

Adult↗
PubMed1993

Atypical chronic myelogenous leukemia in a patient with trisomy 8 mosaicism syndrome.

A 17-year-old woman was admitted for bone marrow transplantation with the diagnosis of atypical Philadelphia-negative chronic myelogenous leukemia (aCML), cytogenetically characterized by trisomy 8 as the sole chromosome aberration. A striking feature was a congenital opacity of the right cornea. Chromosomal analysis of skin fibroblasts were performed and revealed a mosaic for trisomy 8. Commonly, a distinct clinical picture leads to the diagnosis of trisomy 8 mosaicism syndrome (T8ms), but an extreme phenotypic variability has been observed. To our knowledge the development of an aCML in a patient with T8ms has not been reported. A review of the literature revealed that an association to other hematological disorders had been described in two cases. The question of whether our patient's aCML was a random event or not is discussed. The patient is now 24 months post transplant and shows no evidence of disease. Her Karnofsky score is 100%. We conclude that it might be worthwhile to look for an associated constitutional trisomy 8 mosaicism in all patients with trisomy 8 leukemia.

Abnormalities, Multiple↗
PubMed1992

Second bone marrow transplants for relapsed leukemia.

Seventeen patients who had a relapse at a median of 9 months after marrow transplant (14 allogeneic and three syngeneic) received second transplants. Eight patients were in remission when transplanted. Of the nine patients with active disease at the time of transplant, six had complete remissions, and one converted from blastic to chronic phase of chronic myelogenous leukemia. The median survival was 9 months (95% confidence interval, 4 to 17 months). Four patients died within 100 days of transplantation, and three were disease-free. Ten patients died after 100 days, all except two of disease relapse. Five patients had remissions that were greater than 12 months and longer than the remission after their first transplant (inversions). Three patients remain alive and disease-free at 37+, 55+, and 61+ months, the former two despite remissions of less than 1 year after their first transplant. Second transplants with a different cytoreductive regimen can eradicate disease resistant to prior myeloablative treatment; some patients may benefit from second transplants, even if the first transplant only achieves a short remission.

Adolescent↗
PubMed1991

Transplantation with blood stem cells.

Peripheral blood stem cell transplantation (PBSCT) offers an alternative to autologous bone marrow transplants (A-BMT), especially in malignant diseases with bone marrow contamination. The presence of hemopoietic precursors in peripheral blood has been documented in several animal models and in humans. While many of these precursors might be committed cells with finite renewal capacity, ample evidence suggests that true pluripotent stem cells are circulating in a number sufficient to enable sustained trilineage engraftment after transplantation. Stem cell mobilization is markedly increased in the early recovery phase after intensive chemotherapy and can be promoted by the administration of various cytokines or polyanionic substances. These effects are used to optimize stem cell harvesting by leukapheresis. Clinical trials of PBSCT have been performed in several hundred patients with various hematological and nonhematological malignancies. Recovery was generally more rapid than after A-BMT. However, the envisioned advantage concerning disease control has not been documented so far.

Hematopoietic Stem Cell Transplantation↗
PubMed1990

High-dose chemotherapy and unpurged autologous bone marrow transplantation for acute leukemia in second or subsequent remission.

The authors administered high-dose chemotherapy with cyclophosphamide, BCNU (carmustine) and VP-16 (etoposide) plus autologous bone marrow transplantation (ABMT) to 22 adult patients with relapsed acute leukemia in second or subsequent remission. The marrow was not treated ex vivo. The long-term, disease-free survival rate was 14%. Comparison of results with other treatments can be difficult because of patient selection biases. The concept of inversion (achievement of a longer remission with salvage therapy than with prior treatments) is proposed to compare treatment results. Three patients remain in complete remission beyond 4 years, with inversions. More intensive cytoreductive regimens will be needed to improve results.

Adult↗
PubMed1990

Double intensification with amsacrine/high dose ara-C and high dose chemotherapy with autologous bone marrow transplantation produces durable remissions in acute myelogenous leukemia.

Eighteen adult patients under 55 years of age with acute myelogenous leukemia (AML) who entered remission with induction chemotherapy (AMSA-OAP) received two remission intensification cycles. The first intensification used amsacrine and high dose ara-C (AMSA-HDAC), and the second intensification utilized high dose cyclophosphamide, BCNU and VP-16 (CBV) plus unpurged autologous bone marrow transplantation. This double intensified program features two highly active, non-cross-resistant intensification regimens. We observed a 56% long-term disease free survival rate in this group of patients followed for a minimum time of 40 months, with very tolerable toxicity and no transplantation-related deaths. The bone marrow collected after AMSA-HDAC probably contained very low numbers of leukemic cell (in vivo purge). A multivariate logistic regression model may better define the patient population that benefits from this regimen. If these promising findings are confirmed with larger, randomized studies, this treatment strategy could be used in newly diagnosed patients with AML.

Adult↗
PubMed1989

Red cell aplasia due to host type isohemagglutinins with exuberant red cell progenitor production of donor type in an ABO-mismatched allogeneic bone marrow transplant recipient.

ABO-mismatched bone marrow transplants have resulted in delayed red cell production in patients who have persistently elevated anti-ABO isohemagglutinin titers. We present a patient with chronic myelogenous leukemia who received an HLA-matched, ABO-incompatible bone marrow transplant from his sister. Post-transplant, he developed pure red cell aplasia with exuberant production of donor red cell precursors by in vitro BFU-E assay. Restriction fragment length polymorphism (RFLP) analysis of bone marrow, peripheral blood and BFU-E colonies demonstrated only donor type DNA post-transplant. However, the patient had persistently elevated isohemagglutinin titer and Ph1 chromosome-positive metaphases on chromosome analysis, indicating the presence of persistent host lymphocytes. With onset of acute graft vs. host disease (GVHD), the isohemagglutinin titer dropped, Ph1 chromosome-positive metaphases disappeared, and full hematopoietic recovery ensued. Longitudinal analysis of RFLP's, isohemagglutinin titers and chromosomes may be helpful in understanding the immunological interplay following allogeneic bone marrow transplantation.

ABO Blood-Group System↗
PubMed1989

Piperazinedione plus total body irradiation: an alternative preparative regimen for allogeneic bone marrow transplantation in advanced phases of chronic myelogenous leukemia.

Twenty-one patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in advanced phases were treated with piperazinedione (PIP), total body irradiation (TBI) and allogeneic bone marrow transplantation. Eleven were in blastic transformation, five were in accelerated phase, and five were in second chronic phase. The median age was 29 years (range, 13-41 years); there were 14 males. All patients but one were rendered aplastic by this regimen. Of these, 17 had hematologic engraftment, recovering granulocytes to 1.0 x 10(9)/l in a median of 28 days (range, 11-52 days). Three patients failed to engraft. Of those who engrafted, five relapsed and died of disease, one relapsed and died of a polymicrobial wound infection, nine patients died of treatment-related complications, including graft-versus-host disease, interstitial pneumonitis and sepsis, and one patient developed large-cell lymphoma 27 months after transplant and died of this 18 months later. One patient relapsed after 31 months died of polymicrobial sepsis at 37 months, and one patient remains disease-free at 54+ months. The 3-year survival rate was 14%. Survival at 1 year was related to having a spleen that did not extend beyond 2 cm below the left costal margin at the time of transplantation, and those with a large spleen at initial presentation relapsed more often. PIP-TBI with allogeneic bone marrow transplantation can induce durable remissions in a small proportion of patients in advanced phases of CML, but it is not superior to cyclophosphamide-TBI in this patient group.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

A comparison of marrow transplantation with chemotherapy for adults with acute leukemia of poor prognosis in first complete remission.

From July 1980 to November 1985, 109 patients with acute myelogenous and lymphoblastic leukemia who had reached a complete remission (CR) following induction treatment were assigned to a study comparing marrow transplantation with chemotherapy as a postremission treatment. Sixty-nine patients did not have a human leukocyte antigen (HLA)-identical donor, and therefore served as chemotherapy controls; 40 patients had HLA-identical donors, and therefore were assigned to the transplant arm. Of these, 23 were transplanted in first remission and 17 were not. Ten of these 17 were subsequently transplanted in relapse. Initially, only patients with poor prognosis determined by a predictive model were entered into the study. Subsequently, patients with moderately poor prognosis were admitted. Comparing the chemotherapy group with the patients transplanted in first CR, significant control of leukemia relapse in transplanted patients was seen in the subgroup with acute myelogenous leukemia (AML) (P less than .1), and acute lymphoblastic leukemia (ALL) (P less than .01), in the poor (P = .01) and intermediate subgroup (P = .01), and in the good-prognostic groups (P = .05). The survival was affected significantly in only the poor and intermediate subgroups. The use of predictive models might help to select patients for whom bone marrow transplantation is appropriate in first remission and those for whom bone marrow transplantation can be left as the initial treatment of relapse. Predictive models could further be helpful in comparing studies performed at different transplant centers.

Adolescent↗